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Gold ME, Kulkarni S, Yadalam A, Patel KJ, Gold DA, Vatsa N, Jain V, Razavi A, Ko YA, Liu C, Gupta D, Sperling LS, Quyyumi AA. Cardiac Allograft Vasculopathy Mediates the Relationship Between Vitamin D Deficiency and Cardiovascular Mortality Following Heart Transplantation. Am Heart J 2025:S0002-8703(25)00166-8. [PMID: 40383505 DOI: 10.1016/j.ahj.2025.05.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Revised: 05/12/2025] [Accepted: 05/15/2025] [Indexed: 05/20/2025]
Abstract
BACKGROUND Patients undergoing orthotopic heart transplantation (OHT) often have vitamin D deficiency (VDD) and cardiac allograft vasculopathy (CAV). Both VDD and CAV are associated with activation of the renin-angiotensin-aldosterone system. Although VDD is associated with adverse cardiovascular outcomes in multiple cohorts, the impact of VDD in OHT patients remains unknown. We hypothesized that lower VD levels would independently predict the presence of CAV and adverse cardiovascular outcomes. METHODS In 327 participants with OHT recruited prospectively and followed for outcomes, baseline presence of CAV and all-cause and cardiovascular mortality at 5 years were evaluated. Multivariate logistic, cox, and Fine-Gray regression models were used to explore the associations between VDD and outcomes. RESULTS VDD, present in 95 (29.1%) participants at enrollment, was associated with double the risk of 5-year mortality (HR: 2.08, 95% CI: 1.20-3.60), which was driven mostly by cardiovascular death (SHR: 2.21, 95% CI: 1.13-4.31), and also associated with a 3-fold higher likelihood of having CAV (OR: 3.08, 95% CI: 1.39-6.80) after adjustment for demographic and clinical covariates. There was a significant interaction between VDD and CAV on cardiovascular death (p=0.042). Mediation analysis showed that CAV grade accounts for 26.5% of the overall association between VD and cardiovascular mortality. CONCLUSION VDD is an independent predictor of all-cause mortality, cardiovascular mortality, and presence of CAV in patients with OHT. Higher CAV grade appears to mediate, at least in part, the impact of VD levels on cardiovascular mortality, suggesting that VDD may contribute to higher risk of death through development of CAV.
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Affiliation(s)
- Matthew E Gold
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Sarah Kulkarni
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Adithiya Yadalam
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Krishan J Patel
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Daniel A Gold
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Nishant Vatsa
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Vardhmaan Jain
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Alexander Razavi
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Yi-An Ko
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Chang Liu
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Divya Gupta
- Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Laurence S Sperling
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Arshed A Quyyumi
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
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Chin WC, Chu PH, Wu LS, Lee KT, Lin C, Ho CT, Yang WS, Chung IH, Huang YS. The Prognostic Significance of Sleep and Circadian Rhythm for Myocardial Infarction Outcomes: Case-Control Study. J Med Internet Res 2025; 27:e63897. [PMID: 39903495 PMCID: PMC11836589 DOI: 10.2196/63897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 11/19/2024] [Accepted: 12/18/2024] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND Myocardial infarction (MI) is a medical emergency resulting from coronary artery occlusion. Patients with acute MI often experience disturbed sleep and circadian rhythm. Most previous studies assessed the premorbid sleep and circadian rhythm of patients with MI and their correlations with cardiovascular disease. However, little is known about post-MI sleep and circadian rhythm and their impacts on prognosis. The use of actigraphy with different algorithms to evaluate sleep and circadian rhythm after acute MI has the potential for predicting outcomes and preventing future disease progression. OBJECTIVE We aimed to evaluate how sleep patterns and disrupted circadian rhythm affect the prognosis of MI, using actigraphy and heart rate variability (HRV). Nonparametric analysis of actigraphy data was performed to examine the circadian rhythm of patients. METHODS Patients with MI in the intensive care unit (ICU) were enrolled alongside age- and gender-matched healthy controls. Actigraphy was used to evaluate sleep and circadian rhythm, while HRV was monitored for 24 hours to assess autonomic nerve function. Nonparametric indicators were calculated to quantify the active-rest patterns, including interdaily stability, intradaily variability, the most active 10 consecutive hours (M10), the least active 5 consecutive hours (L5), the relative amplitude, and the actigraphic dichotomy index. Follow-ups were conducted at 3 and 6 months after discharge to evaluate prognosis, including the duration of current admission, the number and duration of readmission and ICU admission, and catheterization. Independent sample t tests and analysis of covariance were used to compare group differences. Pearson correlation tests were used to explore the correlations of the parameters of actigraphy and HRV with prognosis. RESULTS The study included 34 patients with MI (mean age 57.65, SD 9.03 years) and 17 age- and gender-matched controls. MI patients had significantly more wake after sleep onset, an increased number of awakenings, and a lower sleep efficiency than controls. Circadian rhythm analysis revealed significantly lower daytime activity in MI patients. Moreover, these patients had a lower relative amplitude and dichotomy index and a higher intradaily variability and midpoint of M10, suggesting less sleep and wake activity changes, more fragmentation of the rest-activity patterns, and a more delayed circadian rhythm. Furthermore, significant correlations were found between the parameters of circadian rhythm analysis, including nighttime activity, time of M10 and L5, and daytime and nighttime activitySD, and patient prognosis. CONCLUSIONS Patients with acute MI experienced significantly worse sleep and disturbed circadian rhythm compared with healthy controls. Our actigraphy-based analysis revealed a disturbed circadian rhythm, including reduced daytime activities, greater fluctuation in hourly activities, and a weak rest-activity rhythm, which were correlated with prognosis. The evaluation of sleep and circadian rhythm in patients with acute MI can serve as a valuable indicator for prognosis and should be further studied.
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Affiliation(s)
- Wei-Chih Chin
- Division of Psychiatry and Sleep Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan
- College of Life Sciences and Medicine, National Tsing Hua University, Hsinchu, Taiwan
| | - Pao-Hsien Chu
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan
- Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Lung-Sheng Wu
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan
- Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Kuang-Tso Lee
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan
- Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chen Lin
- Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan
| | - Chien-Te Ho
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan
- Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Wei-Sheng Yang
- Department of Psychiatry, New Taipei City Tucheng Hospital, New Taipei City, Taiwan
| | - I-Hang Chung
- Division of Psychiatry and Sleep Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Yu-Shu Huang
- Division of Psychiatry and Sleep Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan
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Abu-Zaid A, Saleh SAK, Adly HM, Baradwan S, Alharran AM, Alhatm M, Alzayed MM, Alotaibi MN, Saad AR, Alfayadh HM, Abuzaid M, Alomar O. The Impact of Vitamin D on Androgens and Anabolic Steroids among Adult Males: A Meta-Analytic Review. Diseases 2024; 12:228. [PMID: 39452471 PMCID: PMC11506788 DOI: 10.3390/diseases12100228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 09/18/2024] [Accepted: 09/20/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND Recent studies indicate that vitamin D impacts male reproductive function, with deficiency linked to infertility. This review evaluates the effect of vitamin D supplementation on male fertility, focusing on total testosterone, free testosterone, the free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex-hormone-binding globulin (SHBG), and estradiol. METHODS We systematically searched Medline, Web of Science, Cochrane Library, and Scopus from their inception until July 2024 for randomized controlled trials (RCTs) involving adult males. The primary focus of these studies was on reproductive hormone parameters, analyzed using a random-effects meta-analysis and weighted mean difference (WMD). Evidence quality was assessed using ROB2 and GRADE. Meta-regression and dose-response analyses were performed. RESULTS Seventeen studies met the criteria for quantitative analysis. Vitamin D supplementation significantly increased total testosterone levels (WMD 0.38, 95% CI 0.06-0.70, n = 15, I2 = 67.03). However, it had no significant effect on other hormone parameters: free testosterone (WMD 0.00, 95% CI -0.02-0.03, n = 9, I2 = 48.12), FSH (WMD -0.02, 95% CI -0.57-0.53, n = 7, I2 = 48.72), LH (WMD -0.09, 95% CI -0.30-0.12, n = 8, I2 = 0.00), SHBG (WMD 0.73, 95% CI -1.14-2.61, n = 10, I2 = 69.05), FAI (WMD -0.92, 95% CI -2.12-0.27, n = 6, I2 = 0.00), and estradiol (WMD -0.02, 95% CI -2.95-2.92, n = 5, I2 = 20.63). CONCLUSION This meta-analysis shows that vitamin D supplementation may increase total testosterone levels in men. However, further well-designed RCTs are needed to determine vitamin D's effects on other reproductive hormone parameters.
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Affiliation(s)
- Ahmed Abu-Zaid
- Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
| | - Saleh A. K. Saleh
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah 24382, Saudi Arabia
| | - Heba M. Adly
- Department of Community Medicine and Pilgrims Healthcare, Faculty of Medicine, Umm Al-Qura University, Makkah 24382, Saudi Arabia
| | - Saeed Baradwan
- Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Jeddah 23433, Saudi Arabia
| | - Abdullah M. Alharran
- College of Medicine and Medical Sciences, Arabian Gulf University, Manama 329, Bahrain
| | - Mshal Alhatm
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
| | - Mooza M. Alzayed
- College of Medicine and Medical Sciences, Arabian Gulf University, Manama 329, Bahrain
| | - Muteb N. Alotaibi
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
| | - Abdulbadih Rabih Saad
- College of Medicine and Medical Sciences, Arabian Gulf University, Manama 329, Bahrain
| | | | - Mohammed Abuzaid
- Department of Obstetrics and Gynecology, Al Birk General Hospital, Al Birk 63525, Saudi Arabia
| | - Osama Alomar
- Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh 11564, Saudi Arabia
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Kharel M, Subedi A, Hossain MF. Hypocalcemic cardiomyopathy with heart failure: A rare Case report. Clin Case Rep 2024; 12:e9463. [PMID: 39314906 PMCID: PMC11417007 DOI: 10.1002/ccr3.9463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 08/18/2024] [Accepted: 09/07/2024] [Indexed: 09/25/2024] Open
Abstract
Hypocalcemia is one of the rarest causes of reversible cardiomyopathy. Patients with refractory heart failure need to be explored for hypocalcemia and need prompt correction. Abstract Hypocalcemia is a rare cause of reversible dilated cardiomyopathy. Correction of calcium is crucial to recover left ventricular function and structure. We presented the case of a 55-year-old female who was admitted to the hospital with refractory heart failure due to hypocalcemia induced by primary hypoparathyroidism and complicated by vitamin D deficiency. The patient's cardiac symptoms improved dramatically upon correction of hypocalcemia, and vitamin D. Therefore, the key clinical message of this case report is, that hypocalcemia, although rare, should be considered as one of the differential diagnoses when heart failure is refractory and early diagnosis and treatment is necessary as it is the cause of reversible cardiomyopathy and could reduce morbidity and mortality.
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Affiliation(s)
| | | | - Md Fahad Hossain
- Ministry of Health and Family WelfareKuliarcharKishoreganjBangladesh
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Lee MJ, Jung H, Shin SD, Ro YS, Park JH, Roh YI, Jung WJ, Park JO, Park SM, Kim SC, Shin J, Kim YW, Hong JY, Ryu HH, Kim SJ, Park JH, Kim WY, Lee GT, Oh SB. Vitamin D deficiency as a risk factor for sudden cardiac arrest: A multicenter case-control study. Nutr Metab Cardiovasc Dis 2024; 34:2182-2189. [PMID: 38866622 DOI: 10.1016/j.numecd.2024.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 04/21/2024] [Accepted: 05/07/2024] [Indexed: 06/14/2024]
Abstract
BACKGROUND AND AIMS Vitamin D is known to influence the risk of cardiovascular disease, which is a recognized risk factor for sudden cardiac arrest (SCA). However, the relationship between vitamin D and SCA is not well understood. Therefore, this study aims to investigate the association between vitamin D and SCA in out-of-hospital cardiac arrest (OHCA) patients compared to healthy controls. METHODS AND RESULTS Using the Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance (CAPTURES II) registry, a 1:1 propensity score-matched case-control study was conducted between 2017 and 2020. Serum 25-hydroxyvitamin D (vitamin D) levels in patients with OHCA (454 cases) and healthy controls (454 cases) were compared after matching for age, sex, cardiovascular risk factors, and lifestyle behaviors. The mean vitamin D levels were 14.5 ± 7.6 and 21.3 ± 8.3 ng/mL among SCA cases and controls, respectively. Logistic regression analysis was used adjusting for cardiovascular risk factors, lifestyle behaviors, corrected serum calcium levels, and estimated glomerular filtration rate (eGRF). The adjusted odds ratio (aOR) for vitamin D was 0.89 (95% confidence interval [CI] 0.87-0.91). The dose-response relationship demonstrated that vitamin D deficiency was associated with SCA incidence (severe deficiency, aOR 10.87, 95% CI 4.82-24.54; moderate deficiency, aOR 2.24, 95% CI 1.20-4.20). CONCLUSION Vitamin D deficiency was independently and strongly associated with an increased risk of SCA, irrespective of cardiovascular and lifestyle factors, corrected calcium levels, and eGFR.
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Affiliation(s)
- Mi Jin Lee
- Department of Emergency Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - Haewon Jung
- Department of Emergency Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.
| | - Sang Do Shin
- Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Young Sun Ro
- Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Jeong Ho Park
- Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Young-Il Roh
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Woo Jin Jung
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Ju Ok Park
- Department of Emergency Medicine, Hallym University College of Medicine, Dongtan Sacred Heart Hospital, Hwaseong, South Korea
| | - Seung Min Park
- Department of Emergency Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Sang-Chul Kim
- Department of Emergency Medicine, Chungbuk National University College of Medicine, Cheongju, South Korea
| | - Jonghwan Shin
- Department of Emergency Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, South Korea
| | - Yong Won Kim
- Department of Emergency Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, South Korea
| | - Ju-Young Hong
- Department of Emergency Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Hyun Ho Ryu
- Department of Emergency Medicine, Chonnam National University College of Medicine, Gwangju, South Korea
| | - Su Jin Kim
- Department of Emergency Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Jong-Hak Park
- Department of Emergency Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Won Young Kim
- Department of Emergency Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Gun Tak Lee
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, South Korea
| | - Sung Bum Oh
- Department of Emergency Medicine, Dankook University College of Medicine, Seoul, South Korea
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Theodosis-Nobelos P, Rekka EA. The Antioxidant Potential of Vitamins and Their Implication in Metabolic Abnormalities. Nutrients 2024; 16:2740. [PMID: 39203876 PMCID: PMC11356998 DOI: 10.3390/nu16162740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 08/13/2024] [Accepted: 08/15/2024] [Indexed: 09/03/2024] Open
Abstract
Vitamins are micronutrients necessary for the normal function of the body. Although each vitamin has different physicochemical properties and a specific role in maintaining life, they may also possess a common characteristic, i.e., antioxidant activity. Oxidative stress can harm all the main biological structures leading to protein, DNA and lipid oxidation, with concomitant impairment of the cell. It has been established that oxidative stress is implicated in several pathological conditions such as atherosclerosis, diabetes, obesity, inflammation and metabolic syndrome. In this review we investigate the influence of oxidative stress on the above conditions, examine the interrelation between oxidative stress and inflammation and point out the importance of vitamins in these processes, especially in oxidative load manipulation and metabolic abnormalities.
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Affiliation(s)
| | - Eleni A. Rekka
- Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, 54124 Thessaloniki, Greece;
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Gruszka J, Włodarek D. General Dietary Recommendations for People with Down Syndrome. Nutrients 2024; 16:2656. [PMID: 39203792 PMCID: PMC11357503 DOI: 10.3390/nu16162656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 07/24/2024] [Accepted: 08/08/2024] [Indexed: 09/03/2024] Open
Abstract
Down syndrome (DS) is caused by trisomy of chromosome 21 and is associated with characteristic features of appearance, intellectual impairment to varying degrees, organ defects, and health problems typical of this syndrome. Studies on the frequency of consumption of food products in this group show many irregularities, in particular too low consumption of vegetables and fruits, wholegrain cereal products and dairy products, and excessive consumption of meat products and sweets. It is necessary to correct eating habits. The diets of people with trisomy 21 should be consistent with the recommendations of rational nutrition for the general population and take into account specific dietary modifications related to the occurrence of diseases and health problems characteristic of this syndrome.
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Affiliation(s)
- Joanna Gruszka
- Dieta Plus Nutritional and Dietary Counseling, 45-072 Opole, Poland;
| | - Dariusz Włodarek
- Department of Dietetics, Institute of Human Nutrition Science, Warsaw University of Life Science (WULS-SGGW), 159C Nowoursynowska Street, 02-776 Warszawa, Poland
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Chin WC, Huang YS, Wu LS, Lee KT, Ho CT, Lin C, Yang WS, Chung IH, Chu PH. The prognosis of patients with myocardial infarction after light therapy: A preliminary study. Biomed J 2024; 48:100783. [PMID: 39122187 DOI: 10.1016/j.bj.2024.100783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Revised: 07/23/2024] [Accepted: 08/06/2024] [Indexed: 08/12/2024] Open
Abstract
BACKGROUND Patients with myocardial infarction (MI) can have disturbed sleep, but little is known about the efficacy of light therapy on sleep and the prognosis of patients with MI. We conducted a randomized controlled study to investigate its efficacy. MATERIAL AND METHODS This preliminary study included 34 patients with MI. They were randomized into the blue light and the white light groups during their stay in intensive care unit. 17 age and gender-matched healthy controls were also enrolled. Actigraphy was used to evaluate objective sleep since enrollment. Delirium scales were used to screen delirium. Lab work-up, including vitamin D level was performed at the baseline and discharge. We used the Mann-Whitney U test or Wilcoxon signed-rank test to compare the difference between the MI group and the healthy control group, and the group difference after receiving light therapy. RESULTS Patients with MI had significantly lower vitamin D levels than healthy controls (p < 0.001). They also had significantly poorer sleep, as indicated by actigraphy parameters, including sleep onset latency (p = 0.01), sleep efficiency (p = 0.002), wake after sleep onset (p < 0.001), and awake times (p = 0.002). No significant group difference was found by actigraphy after light therapy except a non-significant higher relative amplitude of the blue light group (p = 0.061). Besides, the vitamin D level of the blue light group increased significantly (p1 = 0.047, p2 = 0.045). CONCLUSIONS Patients with MI had poorer sleep, highlighting the need to develop interventions. Significantly increased vitamin D levels and a non-significant better rest-active rhythm after light therapy suggest its potential with sleep and prognosis, which warrants further investigation.
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Affiliation(s)
- Wei-Chih Chin
- Division of Psychiatry and Sleep Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; College of Life Sciences and Medicine, National Tsing Hua University, Hsinchu, Taiwan
| | - Yu-Shu Huang
- Division of Psychiatry and Sleep Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Lung-Sheng Wu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Kuang-Tso Lee
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chien-Te Ho
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chen Lin
- Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan
| | - Wei-Sheng Yang
- Department of Psychiatry, New Taipei City Tucheng Hospital, New Taipei City, Taiwan
| | - I-Hang Chung
- Division of Psychiatry and Sleep Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pao-Hsien Chu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
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Zhao Y, Zhao X, Jiang T, Xi H, Jiang Y, Feng X. A Retrospective Review on Dysregulated Autophagy in Polycystic Ovary Syndrome: From Pathogenesis to Therapeutic Strategies. Horm Metab Res 2024. [PMID: 38565184 DOI: 10.1055/a-2280-7130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
The main purpose of this article is to explore the relationship between autophagy and the pathological mechanism of PCOS, and to find potential therapeutic methods that can alleviate the pathological mechanism of PCOS by targeting autophagy. Relevant literatures were searched in the following databases, including: PubMed, MEDLINE, Web of Science, Scopus. The search terms were "autophagy", "PCOS", "polycystic ovary syndrome", "ovulation", "hyperandrogenemia", "insulin resistance", "inflammatory state", "circadian rhythm" and "treatment", which were combined according to the retrieval methods of different databases. Through analysis, we uncovered that abnormal levels of autophagy were closely related to abnormal ovulation, insulin resistance, hyperandrogenemia, and low-grade inflammation in patients with PCOS. Lifestyle intervention, melatonin, vitamin D, and probiotics, etc. were able to improve the pathological mechanism of PCOS via targeting autophagy. In conclusion, autophagy disorder is a key pathological mechanism in PCOS and is also a potential target for drug development and design.
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Affiliation(s)
- Yan Zhao
- Department of Gynecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xiaoxuan Zhao
- Department of Traditional Chinese Medicine (TCM) Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
| | - Tianyue Jiang
- Department of Gynecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Hongyan Xi
- Department of Gynecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yuepeng Jiang
- College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xiaoling Feng
- Department of Gynecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
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Milazzo V, Cosentino N, Trombara F, Marenzi G. Vitamin D and cardiovascular diseases. ADVANCES IN FOOD AND NUTRITION RESEARCH 2024; 109:68-91. [PMID: 38777418 DOI: 10.1016/bs.afnr.2023.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2024]
Abstract
Vitamin D has an established role in calcium homeostasis but its deficiency is emerging also as a new risk factor for cardiovascular disease (CVD). In particular, several epidemiological and clinical studies have reported a close association between low vitamin D levels and several cardiovascular risk factors and major CVDs, such as coronary artery disease, heart failure, and cardiac arrhythmias. In all these clinical settings, vitamin D deficiency seems to predispose to increased morbidity, mortality, and recurrent cardiovascular events. Despite this growing evidence, interventional trials with supplementation of vitamin D in patients at risk of or with established CVD are still controversial. In this chapter, we summarize the currently available evidence on the links between vitamin D deficiency and major cardiovascular risk factors and CVD, in terms of both clinical relevance and potential therapeutic implications.
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Affiliation(s)
- Valentina Milazzo
- Intensive Cardiac Care Unit, Centro Cardiologico Monzino, I.R.C.C.S., Milan, Italy
| | - Nicola Cosentino
- Intensive Cardiac Care Unit, Centro Cardiologico Monzino, I.R.C.C.S., Milan, Italy
| | - Filippo Trombara
- Intensive Cardiac Care Unit, Centro Cardiologico Monzino, I.R.C.C.S., Milan, Italy; Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Milan, Italy
| | - Giancarlo Marenzi
- Intensive Cardiac Care Unit, Centro Cardiologico Monzino, I.R.C.C.S., Milan, Italy.
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Gerede Uludag DM, Aydogan BI, Tan TS, Acıbuca A, Turan N, Emral R, Dincer I, Erol C. Evaluation of the Relationship Between Vitamin D Deficiency and Subclinical Cardiac Dysfunction Using 2D/3D Strain Echocardiography in Healthy People. KARDIOLOGIIA 2024; 64:73-79. [PMID: 38462807 DOI: 10.18087/cardio.2024.2.n2331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 01/16/2023] [Indexed: 03/12/2024]
Abstract
AIM Vitamin D deficiency has a high prevalence in the population and is highly associated with cardiovascular diseases. The aim of this study was to evaluate subclinical left ventricular (LV) function using strain analysis in healthy individuals with vitamin D deficiency. MATERIAL AND METHODS 113 healthy volunteers were enrolled in the study (age, 44.1±7 yrs, 34 male). All volunteers underwent two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography after conventional echocardiographic evaluation. The subjects were divided into two groups according to their vitamin D concentrations. 61 subjects with vitamin D less than 20 ng / ml were included in the vitamin D deficiency group. The baseline clinical characteristics, laboratory measurements, echocardiographic data, including 2D and 3D global longitudinal strain (GLS) values, were compared between the groups. RESULTS The 2D GLS values of the subjects with vitamin D deficiency were lower (mathematically less negative) than subjects with normal vitamin D (-16.1±3.4 vs -19.3±4.2, p<0.001). Similarly, the 3D GLS results were lower in subjects with vitamin D deficiency (-18.3±5.2 vs -24.1±6.9, p<0.001). A significant correlation was detected between the vitamin D concentrations and the 2D and 3D GLS measurements. (r=0.765 and r=0.628, respectively, p<0.001). Vitamin D was found to be an independent predictor of impaired 2D and 3D LV GLS (p=0.031, p=0.023, respectively). CONCLUSION Subclinical LV dysfunction in healthy individuals with vitamin D deficiency was demonstrated by 3D and 2D strain analysis. Due to potential negative effects of vitamin D deficiency on cardiac function, more attention should be paid to healthy individuals with vitamin D deficiency.
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Affiliation(s)
| | | | - Türkan Seda Tan
- Ankara University, Faculty of Medicine, Department of Cardiology
| | - Aynur Acıbuca
- Ankara University, Faculty of Medicine, Department of Cardiology
| | - Nazlı Turan
- Ankara University, Faculty of Medicine, Department of Cardiology
| | - Rıfat Emral
- Ankara University, Faculty of Medicine, Department of Endocrinology
| | - Irem Dincer
- Ankara University, Faculty of Medicine, Department of Cardiology
| | - Cetin Erol
- Ankara University, Faculty of Medicine, Department of Cardiology
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12
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Di Molfetta IV, Bordoni L, Gabbianelli R, Sagratini G, Alessandroni L. Vitamin D and Its Role on the Fatigue Mitigation: A Narrative Review. Nutrients 2024; 16:221. [PMID: 38257114 PMCID: PMC10818509 DOI: 10.3390/nu16020221] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 01/02/2024] [Accepted: 01/04/2024] [Indexed: 01/24/2024] Open
Abstract
Vitamin D has historically been associated with bone metabolism. However, over the years, a growing body of evidence has emerged indicating its involvement in various physiological processes that may influence the onset of numerous pathologies (cardiovascular and neurodegenerative diseases, rheumatological diseases, fertility, cancer, diabetes, or a condition of fatigue). This narrative review investigates the current knowledge of the pathophysiological mechanisms underlying fatigue and the ways in which vitamin D is implicated in these processes. Scientific studies in the databases of PubMed, Scopus, and Web of Science were reviewed with a focus on factors that play a role in the genesis of fatigue, where the influence of vitamin D has been clearly demonstrated. The pathogenic factors of fatigue influenced by vitamin D are related to biochemical factors connected to oxidative stress and inflammatory cytokines. A role in the control of the neurotransmitters dopamine and serotonin has also been demonstrated: an imbalance in the relationship between these two neurotransmitters is linked to the genesis of fatigue. Furthermore, vitamin D is implicated in the control of voltage-gated calcium and chloride channels. Although it has been demonstrated that hypovitaminosis D is associated with numerous pathological conditions, current data on the outcomes of correcting hypovitaminosis D are conflicting. This suggests that, despite the significant involvement of vitamin D in regulating mechanisms governing fatigue, other factors could also play a role.
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Affiliation(s)
- Ippolita Valentina Di Molfetta
- Chemistry Interdisciplinary Project, School of Pharmacy, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy; (I.V.D.M.); (L.A.)
| | - Laura Bordoni
- Unit of Molecular Biology and Nutrigenomics, School of Pharmacy, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy; (L.B.); (R.G.)
| | - Rosita Gabbianelli
- Unit of Molecular Biology and Nutrigenomics, School of Pharmacy, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy; (L.B.); (R.G.)
| | - Gianni Sagratini
- Chemistry Interdisciplinary Project, School of Pharmacy, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy; (I.V.D.M.); (L.A.)
| | - Laura Alessandroni
- Chemistry Interdisciplinary Project, School of Pharmacy, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy; (I.V.D.M.); (L.A.)
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13
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Rasouli MA, Darvishzadehdaledari S, Alizadeh Z, Moradi G, Gholami F, Mahmoudian A. Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 134000 Individuals in 29 Randomized Clinical Trials and 157000 Individuals in 30 Prospective Cohort Studies: An Updated Systematic Review and Meta-analysis. J Res Health Sci 2023; 23:e00594. [PMID: 38315909 PMCID: PMC10843321 DOI: 10.34172/jrhs.2023.129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 10/09/2023] [Accepted: 11/02/2023] [Indexed: 02/07/2024] Open
Abstract
BACKGROUND According to the findings from observational studies and clinical trials assessing the effect of vitamin D supplements on cardiovascular diseases (CVDs), there are still contradictory results. This systematic review aimed to assess the effect of vitamin D supplements on CVDs considering cohort studies and clinical trials. Study Design: A systematic review. METHODS MEDLINE/PubMed, Science Direct, Embase, and Cochrane Library databases were reviewed by two reviewers independently until 2022. The study effect is risk ratio (RR) and 95% confidence interval (CI) according to Mantel Haenszel's random-effects model. Then, Stata version 14 was used for statistical analysis. RESULTS In clinical trial studies, the incidence of CVDs among the vitamin D-consuming group was not significantly different from that in the placebo group (RR: 0.99, 95% CI: 0.95-1.03; P=0.77; I 2=0%). CVD mortality was also not significantly different between the two groups (RR: 0.97, 95% CI: 0.90-1.05; P=0.72; I2=0%). In cohort studies, circulating 25 (OH) D increased the risk of CVD incidence by 31% (RR: 1.31, 95% CI: 1.19-1.45) and CVD mortality by 37% (RR: 1.37, 95% CI: 1.17-1.61). CONCLUSION According to current evidence from clinical trials, vitamin D supplementation should not be recommended for CVD prevention. However, there is a direct association between vitamin D deficiency and the incidence of CVDs as well as its mortality. According to the results of clinical trial studies carrying higher levels of scientific evidence, it can be concluded that vitamin D supplementation does not exert a significant effect on the incidence, mortality, and reduction of CVDs.
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Affiliation(s)
- Mohammad Aziz Rasouli
- Department of Epidemiology and Biostatistics, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | | | - Zeynab Alizadeh
- Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Ghobad Moradi
- Department of Epidemiology and Biostatistics, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Fatemeh Gholami
- Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Ako Mahmoudian
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
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14
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Haider F, Ghafoor H, Hassan OF, Farooqui K, Bel Khair AOM, Shoaib F. Vitamin D and Cardiovascular Diseases: An Update. Cureus 2023; 15:e49734. [PMID: 38161941 PMCID: PMC10757591 DOI: 10.7759/cureus.49734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/30/2023] [Indexed: 01/03/2024] Open
Abstract
Vitamin D is a vital nutrient that plays a significant part in several physiological processes within the human body, including calcium metabolism, bone health, immune function, and cell growth and differentiation. It is obtained mainly through exposure to sunlight but can be acquired from certain foods and supplements as well. Vitamin D deficiency (VDD) could be the risk factor for cardiovascular diseases (CVDs), such as heart disease and stroke. In blood vitamin D low levels have been linked with an enhanced risk of developing CVDs. However, it is unclear whether vitamin D levels are the leading cause or consequence of these conditions. While some studies highlight that taking vitamin D supplements could decrease the risk of CVD; however, more research is required to better understand the association between vitamin D and cardiovascular health. In this review, we aimed to summarize the currently available evidence supporting the association between vitamin D and CVDs and anesthesia considerations.
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Affiliation(s)
- Farrookh Haider
- Department of Internal Medicine, Section of Cardiology Al Khor Hospital, Hamad Medical Corporation, Al Khor, QAT
- Department of Internal Medicine, College of Medicine/Qatar University, Doha, QAT
| | - Hashsaam Ghafoor
- Department of Anesthesia, Al Khor Hospital, Hamad Medical Corporation, Al Khor, QAT
- Department of Anesthesiology, Qatar University, Doha, QAT
| | - Omar F Hassan
- Department of Internal Medicine, Section of Cardiology Al Khor Hospital, Hamad Medical Corporation, Al Khor, QAT
| | - Khalid Farooqui
- Department of Internal Medicine, Al Khor Hospital, Hamad Medical Corporation, Al Khor, QAT
| | | | - Faryal Shoaib
- Department of Internal Medicine, Shifa International Hospitals, Islamabad, PAK
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15
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Asghari G, Yuzbashian E, Najd-Hassan-Bonab L, Mirmiran P, Daneshpour MS, Azizi F. Association of rs2282679 polymorphism in vitamin D binding protein gene (GC) with the risk of vitamin D deficiency in an iranian population: season-specific vitamin D status. BMC Endocr Disord 2023; 23:217. [PMID: 37814286 PMCID: PMC10563356 DOI: 10.1186/s12902-023-01463-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 09/18/2023] [Indexed: 10/11/2023] Open
Abstract
BACKGROUND Genome-wide association studies in Western countries indicate a considerable impact of variations in vitamin D binding protein (GC) genes on serum concentrations of 25-hydroxyvitamin D (25(OH)D). We aimed to investigate an association between rs2282679 polymorphism in GC and vitamin D deficiency. METHODS A cross-sectional study conducted in the framework of the Tehran Cardio-Metabolic Genetic Study (TCGS) cohort. A total of 1568 participants aged > 18 years were randomly selected, and their 25(OH) D concentration was measured. Vitamin D deficiency was assessed concerning rs2282679 by descriptive and multivariate analysis, odds ratio (OR), and 95% confidence intervals (95%CI) calculated. Since the interaction term between rs2282679 and recruitment season was significant, we performed regression analysis separately for individuals whose blood was taken in high sunny and those whose blood was drawn in the low sunny season. RESULTS The rs2282679 polymorphism was in Hardy-Weinberg equilibrium (P > 0.05) in the studied population. The serum concentration of 25(OH) D median was 15.0 ng/mL, and the prevalence of VDD was 27.8%. The presence of the G allele in rs2282679 increases the risk of VDD in additive (OR = 1.35, 95% CI: 1.06-1.73) and dominant (OR = 1.33, 95% CI: 1.06-1.68) genetic models. After separating participants based on the recruitment season, the unfavorable association was observed in the additive and dominant only in the low sunny season. CONCLUSION The finding of the current study indicates that the GC rs2282679 SNP is associated with vitamin D deficiency. It seems that the impact of risk allele increased in the low sunny season when UV exposure has been declined.
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Affiliation(s)
- Golaleh Asghari
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Emad Yuzbashian
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Leila Najd-Hassan-Bonab
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, 19195-4763, Iran
| | - Parvin Mirmiran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam S Daneshpour
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, 19195-4763, Iran.
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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16
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Kong SY, Jung E, Hwang SS, Ro YS, Shin SD, Cha KC, Hwang SO. Circulating Vitamin D Level and Risk of Sudden Cardiac Death and Cardiovascular Mortality: A Dose-Response Meta-Analysis of Prospective Studies. J Korean Med Sci 2023; 38:e260. [PMID: 37605499 PMCID: PMC10442497 DOI: 10.3346/jkms.2023.38.e260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 04/13/2023] [Indexed: 08/23/2023] Open
Abstract
BACKGROUND We conducted a comprehensive meta-analysis of prospective cohort studies to analyze the effect of circulating vitamin D level on the risk of sudden cardiac death (SCD) and cardiovascular disease (CVD) mortality. METHODS Prospective cohort studies evaluating the association between circulating vitamin D and risk of SCD and CVD mortality were systematically searched in the PubMed and Embase. Extracted data were analyzed using a random effects model and results were expressed in terms of hazard ratio (HR) and 95% confidence interval (CI). Restricted cubic spline analysis was used to estimate the dose-response relationships. RESULTS Of the 1,321 records identified using the search strategy, a total of 19 cohort studies were included in the final meta-analysis. The pooled estimate of HR (95% CI) for low vs. high circulating vitamin D level was 1.75 (1.49-2.06) with I² value of 30.4%. In subgroup analysis, strong effects of circulating vitamin D were observed in healthy general population (pooled HR, 1.84; 95% CI, 1.43-2.38) and the clinical endpoint of SCD (pooled HRs, 2.68; 95% CI, 1.48-4.83). The dose-response analysis at the reference level of < 50 nmol/L showed a significant negative association between circulating vitamin D and risk of SCD and CVD mortality. CONCLUSION Our meta-analysis of prospective cohort studies showed that lower circulating vitamin D level significantly increased the risk of SCD and CVD mortality.
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Affiliation(s)
- So Yeon Kong
- Laboratory of Emergency Medical Services, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea
| | - Eujene Jung
- Laboratory of Emergency Medical Services, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea
- Department of Emergency Medicine, Chonnam National University Hospital, Gwangju, Korea.
| | - Seung-Sik Hwang
- Department of Public Health Sciences, Seoul National University Graduate School of Public Health, Seoul, Korea
| | - Young Sun Ro
- Laboratory of Emergency Medical Services, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea
| | - Sang Do Shin
- Laboratory of Emergency Medical Services, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea
| | - Kyoung-Chul Cha
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Kangwon, Korea
| | - Sung Oh Hwang
- Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Kangwon, Korea
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17
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Stančáková Yaluri A, Tkáč I, Tokarčíková K, Kozelová Z, Rašiová M, Javorský M, Kozárová M. Decreased 25-Hydroxy Vitamin D Level Is Associated with All-Cause Mortality in Patients with Type 2 Diabetes at High Cardiovascular Risk. Metabolites 2023; 13:887. [PMID: 37623831 PMCID: PMC10456820 DOI: 10.3390/metabo13080887] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 07/21/2023] [Accepted: 07/25/2023] [Indexed: 08/26/2023] Open
Abstract
Cardiovascular diseases are among the leading causes of morbidity and mortality, particularly in individuals with type 2 diabetes. There is a need for new biomarkers to improve the prediction of cardiovascular events and overall mortality. We investigated the association of selected atherosclerosis related biomarkers, specifically osteoprotegerin (OPG), 25-hydroxy-vitamin D (25(OH)D), C-reactive protein (CRP), lipopolysaccharide-binding protein (LBP), and asymmetric dimethylarginine (ADMA), with the occurrence of any cardiovascular event or all-cause mortality (primary outcome) during a 5.6-year follow-up of 190 patients with type 2 diabetes. Data were analyzed using logistic regression to adjust for baseline cardiovascular status and cardiovascular risk factors. The primary outcome occurred in 89 participants (46.8%) during the study. When analyzed individually, 25(OH)D, CRP, and LBP significantly predicted the primary outcome in multivariable models. However, in a model that included all biomarkers, only a decreased level of 25(OH)D remained a significant predictor of the primary outcome. Moreover, the level of 25(OH)D significantly predicted all-cause mortality: a reduction of 10 ng/mL was associated with a two-fold increase in all-cause mortality. Our study thus demonstrates that vitamin D deficiency was the strongest factor associated with the primary outcome and all-cause mortality after a 5.6-year follow-up in patients with type 2 diabetes at high cardiovascular risk.
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Affiliation(s)
- Alena Stančáková Yaluri
- Department of Internal Medicine 4, Faculty of Medicine, P. J. Šafárik University and L. Pasteur University Hospital, 04190 Košice, Slovakia; (A.S.Y.); (K.T.); (Z.K.); (M.J.)
| | - Ivan Tkáč
- Department of Internal Medicine 4, Faculty of Medicine, P. J. Šafárik University and L. Pasteur University Hospital, 04190 Košice, Slovakia; (A.S.Y.); (K.T.); (Z.K.); (M.J.)
| | - Katarína Tokarčíková
- Department of Internal Medicine 4, Faculty of Medicine, P. J. Šafárik University and L. Pasteur University Hospital, 04190 Košice, Slovakia; (A.S.Y.); (K.T.); (Z.K.); (M.J.)
| | - Zuzana Kozelová
- Department of Internal Medicine 4, Faculty of Medicine, P. J. Šafárik University and L. Pasteur University Hospital, 04190 Košice, Slovakia; (A.S.Y.); (K.T.); (Z.K.); (M.J.)
| | - Mária Rašiová
- Department of Angiology, Faculty of Medicine, P. J. Šafárik University and East Slovak Institute of Cardiovascular Disease, 04011 Košice, Slovakia;
| | - Martin Javorský
- Department of Internal Medicine 4, Faculty of Medicine, P. J. Šafárik University and L. Pasteur University Hospital, 04190 Košice, Slovakia; (A.S.Y.); (K.T.); (Z.K.); (M.J.)
| | - Miriam Kozárová
- Department of Internal Medicine 4, Faculty of Medicine, P. J. Šafárik University and L. Pasteur University Hospital, 04190 Košice, Slovakia; (A.S.Y.); (K.T.); (Z.K.); (M.J.)
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18
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Tikkanen JT, Soliman EZ, Pester J, Danik JS, Gomelskya N, Copeland T, Lee IM, Buring JE, Manson JE, Cook NR, Albert CM. A randomized clinical trial of omega-3 fatty acid and vitamin D supplementation on electrocardiographic risk profiles. Sci Rep 2023; 13:11454. [PMID: 37454148 PMCID: PMC10349832 DOI: 10.1038/s41598-023-38344-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 07/06/2023] [Indexed: 07/18/2023] Open
Abstract
Beneficial and adverse associations with arrhythmias have been reported for omega-3 fatty acids (omega-3 FA) and Vitamin D. The 12 lead electrocardiogram (ECG) contains quantitative measures reflecting diverse aspects of electrophysiology that might provide insights into mechanisms underlying these associations. In a pre-specified ancillary study of the VITaminD and omegA-3 (VITAL) trial, we examined the effect of 1 g of marine omega-3 FA per day, comprised of 460 mg eicosapentanoic acid and 380 mg of docosahexaenoic acid, and 2000 IU VitaminD3 per day on ECG characteristics associated with atrial and ventricular arrhythmias among individuals age 50 years or greater. A total of 911 study participants underwent ECGs at baseline and again at 2 years after the randomization. Individuals randomized to active omega-3 FA demonstrated significant net increase in PR-interval duration (p = 0.005) and P-wave duration (p = 0.03) as well significant net decrease in P-wave amplitude (p = 0.037) as compared to placebo. RMSSD increased to a greater extent in the omega-3 FA arm compared to placebo (p = 0.040). For Vitamin D3, the Cornell voltage increased to a lesser extent in the participants assigned to active treatment as compared to placebo (p = 0.044). There were no other significant differences in QRS, QTc, Cornell voltage or heart rate. Thus, randomized treatment with omega-3 FA supplements resulted in changes on the ECG that are potentially reflective of heightened vagal tone and/or slowing of intraatrial and AV conduction. Vitamin D3 supplementation resulted in modest reductions in progressive LV voltage suggestive of a potential antihypertrophic effect.Trial registration ClinicalTrials.gov Identifiers: NCT01169259, NCT02178410 (06/26/2010 and 06/30/2014).
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Affiliation(s)
- Jani T Tikkanen
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Elsayed Z Soliman
- Department of Internal Medicine, Epidemiological Cardiology Research Center, Section On Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Julie Pester
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, 127 South San Vincente Blvd., AHSP 3100, Los Angeles, CA, 90048, USA
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Jacqueline S Danik
- Division of Cardiovascular Medicine, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Natalia Gomelskya
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Trisha Copeland
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - I-Min Lee
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Julie E Buring
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - JoAnn E Manson
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Nancy R Cook
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Christine M Albert
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, 127 South San Vincente Blvd., AHSP 3100, Los Angeles, CA, 90048, USA.
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
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19
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Majid MA, Hassan WN, Ridha AF. Prevalence of 25-Hydroxyvitamin D (Vitamin D) Deficiency in a Group of Infertile Women from Baghdad City. Biochem Res Int 2023; 2023:6597730. [PMID: 37350868 PMCID: PMC10284658 DOI: 10.1155/2023/6597730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 04/24/2023] [Accepted: 06/05/2023] [Indexed: 06/24/2023] Open
Abstract
Background Infertility is a common issue affecting a large number of Iraqi women of reproductive age. The relationship between vitamin D deficiency and infertility has previously drawn the attention of gynecologists, and an increasing number of vitamin D testing has been requested. Methods 120 women were enrolled in this study between April 2019 and April 2020. Patients were divided into two groups comprising sixty women complaining of infertility, with the other 60 women being fertile and enrolled as controls. All patients were assessed for vitamin D level. Results In the fertile study group, patients with deficient, insufficient, and sufficient level of vitamin were 28%, 23%, and 48%, respectively (these numbers were rounded to the nearest whole digit, as the numbers for the infertile group were given with that level of precision), whereas the infertile study group showed a statistically significant (p value = 0.002) distribution of vitamin levels with 50%, 35%, and 15% of women being deficient, insufficient, and sufficient, respectively. Conclusions Vitamin D is significantly deficient in infertile patients which suggests a possible, positive impact if vitamin D is considered in the management of female infertility. Further study with more participants is highly recommended.
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Affiliation(s)
- Muthana Anad Majid
- Department of Basic Sciences, College of Dentistry, Mustansiryiah University, Palestine Street, Baghdad, Iraq
| | - Wafaa Nasser Hassan
- Department of Basic Sciences, College of Medicine, Ibn Sina University for Medical and Pharmaceutical Sciences, Qadisya District, Baghdad, Iraq
| | - Amna Fadhil Ridha
- Department of Obstetrics and Gynecology, College of Medicine, Mustansiryah University, Yarmouk Hospital, Baghdad, Iraq
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20
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GUAN B, CHEN XQ, LIU Y, ZHOU H, YANG MY, ZHENG HW, LI SJ, CAO J. Causal effects of circulating vitamin levels on the risk of heart failure: a Mendelian randomization study. J Geriatr Cardiol 2023; 20:195-204. [PMID: 37091260 PMCID: PMC10114193 DOI: 10.26599/1671-5411.2023.03.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/25/2023] Open
Abstract
BACKGROUND Observational studies suggest inverse associations between serum vitamin levels and the risk of heart failure (HF). However, the causal effects of vitamins on HF have not been fully elucidated. Here, we conducted a Mendelian randomization (MR) study to investigate the causal associations between genetically determined vitamin levels and HF. METHODS Genetic instrumental variables for circulating vitamin levels, including vitamins A, B, C, D, and E, which were assessed as either absolute or metabolite levels were obtained from public genome-wide association studies. Summary statistics for single-nucleotide-polymorphisms and HF associations were retrieved from the HERMES Consortium (47,309 cases and 930,014 controls) and FinnGen Study (30,098 cases and 229,612 controls). Two-sample MR analyses were implemented to assess the causality between vitamin levels and HF per outcome database, and the results were subsequently combined by meta-analysis. RESULTS Our MR study did not find significant associations between genetically determined circulating vitamin levels and HF risk. For absolute vitamin levels, the odds ratio for HF ranged from 0.97 (95% confidence interval [CI]: 0.85-1.09, P = 0.41) for vitamin C to 1.05 (95% CI: 0.61-1.82, P = 0.85) for vitamin A. For vitamin metabolites, the odds ratio ranged between 0.94 (95% CI: 0.75-1.19, P = 0.62) for α-tocopherol and 1.11 (95% CI: 0.98-1.26, P = 0.09) for γ-tocopherol. CONCLUSION Evidence from our study does not support the causal effects of circulating vitamin levels on HF. Therefore, there may be no direct beneficial effects of vitamin intake on the prevention of primary HF.
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Affiliation(s)
- Bo GUAN
- Medical School of Chinese PLA General Hospital, Beijing, China
| | - Xiao-Qiang CHEN
- Department of Cardiology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yan LIU
- Department of Cardiology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hui ZHOU
- Xiangya School of Nursing, Central South University, Changsha, Hunan, China
| | - Ming-Yan YANG
- Medical School of Chinese PLA General Hospital, Beijing, China
| | - Hong-Wei ZHENG
- Department of Cardiology, Tangshan Gongren Hospital Affiliated to Hebei Medical University, Tangshan, China
| | - Shi-Jun LI
- Geriatric Cardiology Department of the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
- (CAO J)
| | - Jian CAO
- Geriatric Cardiology Department of the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
- (LI SJ)
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Chow SL, Bozkurt B, Baker WL, Bleske BE, Breathett K, Fonarow GC, Greenberg B, Khazanie P, Leclerc J, Morris AA, Reza N, Yancy CW. Complementary and Alternative Medicines in the Management of Heart Failure: A Scientific Statement From the American Heart Association. Circulation 2023; 147:e4-e30. [PMID: 36475715 DOI: 10.1161/cir.0000000000001110] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Complementary and alternative medicines (CAM) are commonly used across the world by diverse populations and ethnicities but remain largely unregulated. Although many CAM agents are purported to be efficacious and safe by the public, clinical evidence supporting the use of CAM in heart failure remains limited and controversial. Furthermore, health care professionals rarely inquire or document use of CAM as part of the medical record, and patients infrequently disclose their use without further prompting. The goal of this scientific statement is to summarize published efficacy and safety data for CAM and adjunctive interventional wellness approaches in heart failure. Furthermore, other important considerations such as adverse effects and drug interactions that could influence the safety of patients with heart failure are reviewed and discussed.
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22
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Manolis AA, Manolis TA, Melita H, Manolis AS. Role of Vitamins in Cardiovascular Health: Know Your Facts-Part 2. Curr Vasc Pharmacol 2023; 21:399-423. [PMID: 37694779 DOI: 10.2174/1570161121666230911115725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 08/11/2023] [Accepted: 08/23/2023] [Indexed: 09/12/2023]
Abstract
Cardiovascular disease (CVD) is a major cause of morbidity/mortality world-wide, hence preventive interventions are crucial. Observational data showing beneficial CV effects of vitamin supplements, promoted by self-proclaimed experts, have led to ~50% of Americans using multivitamins; this practice has culminated into a multi-billion-dollar business. However, robust evidence is lacking, and certain vitamins might incur harm. This two-part review focuses on the attributes or concerns about specific vitamin consumption on CVD. The evidence for indiscriminate use of multivitamins indicates no consistent CVD benefit. Specific vitamins and/or combinations are suggested, but further supportive evidence is needed. Data presented in Part 1 indicated that folic acid and certain B-vitamins may decrease stroke, whereas niacin might raise mortality; beta-carotene mediates pro-oxidant effects, which may abate the benefits from other vitamins. In Part 2, data favor the anti-oxidant effects of vitamin C and the anti-atherogenic effects of vitamins C and E, but clinical evidence is inconsistent. Vitamin D may provide CV protection, but data are conflicting. Vitamin K appears neutral. Thus, there are favorable CV effects of individual vitamins (C/D), but randomized/controlled data are lacking. An important caveat regards the potential toxicity of increased doses of fat-soluble vitamins (A/D/E/K). As emphasized in Part 1, vitamins might benefit subjects who are antioxidant-deficient or exposed to high levels of oxidative-stress (e.g., diabetics, smokers, and elderly), stressing the importance of targeting certain subgroups for optimal results. Finally, by promoting CV-healthy balanced-diets, we could acquire essential vitamins and nutrients and use supplements only for specific indications.
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Turk AC, Ozdemir YB, Karavelioglu Y, Yetim M, Sahin F. The effect of vitamin D level on cardiac rehabilitation in patients with Coronary Artery Disease. J Back Musculoskelet Rehabil 2022; 35:1373-1380. [PMID: 35723087 DOI: 10.3233/bmr-210355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND 25-hydroxy vitamin D (25OHD) deficiency is associated with cardiovascular disease and poor physical performance. OBJECTIVE To assign the effect of 25OHD level on cardiac rehabilitation (CR) in patients with coronary artery disease (CAD). METHODS One-hundred-thirty-five patients with CAD who underwent a CR programme were enrolled in this retrospective study. Patients were divided into two-group according to 25OHD level (Group 1: < 20 ng/dl; Group 2: ⩾ 20 ng/dl). All patients received CR for 30 sessions. Each participant performed 40 minutes of aerobic exercise with a cycloergometer followed by muscle strengthening exercises. The patients were evaluated before and after CR by a pulmonary function test (PFT) and a cardiopulmonary exercise test (CPET). RESULTS There were 77 (57%) patients in Group 1 and 58 patients (43%) in Group 2. Demographic characteristics between the groups were similar. Pre- and post-rehabilitation CPET parameters were lower in Group 1 (p< 0.05). Both groups had significant improvement in CPET (p< 0.05). Post-rehabilitation PFT parameters (FEV1, FVC) were higher in Group 2 (p< 0.05). There was a positive correlation between the 25OHD-level and the CPET-PFT parameters (p< 0.05). CONCLUSION 25OHD deficiency in patients with CAD reduces the response to CR. It also affects respiratory function according to the FEV1, FVC parameters. In patients scheduled for CR, 25OHD-levels should be evaluated, and any deficiency corrected.
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Affiliation(s)
- Ayla Cagliyan Turk
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Hitit University, Corum, Turkey
| | - Yeliz Bahar Ozdemir
- Department of Physical Medicine and Rehabilitation, Abdulhamid Han Training and Research Hospital, Health Sciences University Sultan 2, Istanbul, Turkey
| | - Yusuf Karavelioglu
- Department of Cardiology, Faculty of Medicine, Hitit University, Corum, Turkey
| | - Mucahit Yetim
- Department of Cardiology, Faculty of Medicine, Hitit University, Corum, Turkey
| | - Fusun Sahin
- Physical Medicine and Rehabilitation Physician, Denizli, Turkey
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Nägele MP, Barthelmes J, Kreysing L, Haider T, Nebunu D, Ruschitzka F, Sudano I, Flammer AJ. Endocrine hormone imbalance in heart failure with reduced ejection fraction: A cross-sectional study. Health Sci Rep 2022; 5:e880. [PMID: 36320653 PMCID: PMC9616169 DOI: 10.1002/hsr2.880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 09/04/2022] [Accepted: 09/20/2022] [Indexed: 11/16/2022] Open
Abstract
Background and Aims Sustained neurohormonal activation plays a central role in the progression of heart failure (HF). Other endocrine axes may also be affected. It was the aim of this study to examine the endocrine profile (thyroid, parathyroid, glucocorticoid, and sex hormones) in a contemporary sample of patients with HF and reduced ejection fraction (EF) on established disease-modifying therapy. Methods This study prospectively measured morning fasting hormones in 52 ambulatory and stable HF patients with EF < 50% on disease-modifying therapy (mean age 63 ± 11 years, 29% female, mean LVEF 32 ± 9.6%) and compared them to 54 patients at elevated risk for HF (61 ± 12 years, 28% female) and 62 healthy controls (HC; 61 ± 13 years, 27% female). Main comparisons were performed using one-way analysis of variance. Associations with biomarkers were studied with linear regression. Results HF patients showed a reduced free triiodothyronine (fT3)/free thyroxine (fT4) ratio compared to HC (0.30 ± 0.06 vs. 0.33 ± 0.05, p = 0.046). Parathyroid hormone (PTH) and cortisol were increased in HF compared to both HC (median [IQR] 59 [50-84] vs. 46 [37-52] ng/L, p < 0.001 and 497 ± 150 vs. 436 ± 108 nmol/L, p = 0.03, respectively) and patients at risk (both p < 0.001). Total testosterone was reduced in male HF compared to HC (14.4 ± 6.6 vs. 18.6 ± 5.3 nmol/L; p = 0.01). No differences in TSH, estradiol, progesterone, and prolactin were found. Lower fT3 levels were found in HF with EF < 40% versus EF 40%-49% (4.6 ± 0.3 vs. 5.2 ± 0.7 pmol/L, p = 0.009). In HF patients, fT3 was an independent predictor of NT-proBNP and high-sensitivity troponin T in multiple regression analysis. PTH was positively associated with NT-proBNP. Conclusion There is evidence of endocrine hormonal imbalance in HF with reduced EF beyond principal neurohormones and despite the use of disease-modifying therapy.
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Affiliation(s)
- Matthias P. Nägele
- CardiologyUniversity Heart Center Zurich, University Hospital ZurichZurichSwitzerland
| | - Jens Barthelmes
- CardiologyUniversity Heart Center Zurich, University Hospital ZurichZurichSwitzerland
| | - Leonie Kreysing
- CardiologyUniversity Heart Center Zurich, University Hospital ZurichZurichSwitzerland
| | - Thomas Haider
- CardiologyUniversity Heart Center Zurich, University Hospital ZurichZurichSwitzerland
| | - Delia Nebunu
- CardiologyUniversity Heart Center Zurich, University Hospital ZurichZurichSwitzerland
| | - Frank Ruschitzka
- CardiologyUniversity Heart Center Zurich, University Hospital ZurichZurichSwitzerland
| | - Isabella Sudano
- CardiologyUniversity Heart Center Zurich, University Hospital ZurichZurichSwitzerland
| | - Andreas J. Flammer
- CardiologyUniversity Heart Center Zurich, University Hospital ZurichZurichSwitzerland
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Yin WW, Huang CC, Chen YR, Yu DQ, Jin M, Feng C. The effect of medication on serum anti-müllerian hormone (AMH) levels in women of reproductive age: a meta-analysis. BMC Endocr Disord 2022; 22:158. [PMID: 35698127 PMCID: PMC9195431 DOI: 10.1186/s12902-022-01065-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 05/30/2022] [Indexed: 12/03/2022] Open
Abstract
OBJECTIVE The study aims to address whether serum anti-müllerian hormone (AMH) levels fluctuate in the short term after medication application, including oral contraceptives (OCs), metformin (MET), Gonadotropin-releasing hormone agonist (GnRH-a), dehydroepiandrosterone (DHEA), vitamin D (VD), clomiphene citrate (CC), and letrozole (LET). METHODS Published literature from PubMed, Embase, and Cochrane central was retrieved up until 19 September 2021. A total of 51 self-control studies with an average Newcastle-Ottawa quality assessment scale (NOS) score of 6.90 were analyzed. The extracted data were entered into Stata software, and the weighted mean difference/standardized mean difference (WMD/SMD) and 95% confidence interval (CI) were used for data analysis. RESULTS After OCs treatment the AMH level showed a significant decline in women with normal ovarian function, which was significant within 3 months (WMD = -1.43, 95% CI: -2.05 to -0.80, P < 0.00001). After MET treatment, the serum AMH decreased in polycystic ovary syndrome (PCOS) patients (WMD = -1.79, 95% CI: -2.32 to -1.26, P < 0.00001), in both obese and non-obese patients. GnRH-a treatment in endometriosis patients led to dynamic changes in the serum AMH levels, that is, ascent at 1 month (P = 0.05), and descent at 3 months (P = 0.02). After DHEA treatment the serum AMH increased in diminished ovarian reserve (DOR) / poor ovarian response (POR) patients (WMD = 0.18, 95% CI: 0.09 to 0.27, P < 0.0001). After VD treatment the serum AMH increased, and it was obvious in non-PCOS patients (WMD = 0.78, 95% CI: 0.34 to 1.21, P = 0.0004). After CC treatment the serum AMH decreased significantly in PCOS patients, specifically in non-obese patients (WMD = -1.24, 95% CI: -1.87 to -0.61, P = 0.0001). CONCLUSIONS Serum AMH levels may be affected in the short term after drug application. Specifically, OC, MET and CC lead to decreased AMH level, DHEA and VD lead to increased AMH level, and GnRH-a leads to dynamic variation, which is correlated with PCOS, obesity, age, and duration of medication. The impacts of these medications should be taken into consideration when AMH is used as a marker of ovarian reserve.
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Affiliation(s)
- Wei-Wei Yin
- Department of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Chang-Chang Huang
- Department of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Yi-Ru Chen
- Department of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Dan-Qing Yu
- Department of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Min Jin
- Department of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Chun Feng
- Department of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
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Coskun G, Sencar L, Tuli A, Dundar Yenilmez E, Polat S. The effect of Vitamin D on testosterone and uncarboxylated osteocalcin levels in aged male rats. Ultrastruct Pathol 2022; 46:368-376. [PMID: 35675386 DOI: 10.1080/01913123.2022.2083280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
There is a well-established complex interaction between vitamin D metabolism and bone and gonad functions. In this study, we aimed to investigate the potential effects of vitamin D therapy on testosterone and osteocalcin (OC) levels in aged male rats. Forty-five adult male rats were divided into three groups in this study. Unlike the control group, the two experimental groups received 50 IU/kg/day and 100 IU/kg/day of vitamin D3 (cholecalciferol), respectively, for a 4-week period using the gavage method. Testicular tissue and blood samples from rats were collected under general anesthesia at the end of the 4-week period. Testicular tissue samples were examined using light and electron microscopy. Additionally, serum testosterone and OC levels were measured in blood samples. The 50 IU/kg dose of cholecalciferol increased testosterone and OC levels, which were lower than normal due to aging, and regulated the organization of the seminiferous tubule epithelium and interstitium more effectively than the 100 IU/kg dose of cholecalciferol. Male fertility functions and bone health, which degrade due to aging, were increased due to the use of exogenous vitamin D, although the higher dose was not associated with more effective results.
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Affiliation(s)
- Gulfidan Coskun
- Department of Histology and Embryology, Faculty of Medicine, Cukurova University, Adana, Turkey
| | - Leman Sencar
- Department of Histology and Embryology, Faculty of Medicine, Cukurova University, Adana, Turkey
| | - Abdullah Tuli
- Department of Biochemistry, Faculty of Medicine, Cukurova University, Adana, Turkey
| | - Ebru Dundar Yenilmez
- Department of Biochemistry, Faculty of Medicine, Cukurova University, Adana, Turkey
| | - Sait Polat
- Department of Histology and Embryology, Faculty of Medicine, Cukurova University, Adana, Turkey
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27
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Wu Z, Sluyter J, Liew OW, Chong JPC, Waayer D, Camargo CA, Richards AM, Scragg R. Effect of monthly vitamin D supplementation on cardiac biomarkers: A post-hoc analysis of a randomized controlled trial. J Steroid Biochem Mol Biol 2022; 220:106093. [PMID: 35272017 DOI: 10.1016/j.jsbmb.2022.106093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 02/24/2022] [Accepted: 03/03/2022] [Indexed: 11/29/2022]
Abstract
The effects of vitamin D supplementation on cardiovascular diseases are controversial. Data on effects of vitamin D upon cardiac biomarkers, as surrogate endpoints of cardiovascular diseases, are limited and inconclusive. Therefore, we carried out a post-hoc analysis of sub-samples of a randomized, double-blinded, placebo-controlled trial with community-based older adults who were randomized to receive monthly 100,000-IU vitamin D or placebo, to determine effect of monthly vitamin D supplementation on high-sensitivity cardiac troponin I (hs-cTnI), troponin T (hs-cTnT) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP). Adjusted relative difference (aRD) of follow-up geometric mean of biomarkers and adjusted relative risk (aRR) of elevated biomarkers between two groups were calculated. A total of 779 participants aged 50-84 y, randomized to vitamin D (n = 395) or placebo (n = 384) groups underwent sampling for measurement of plasma biomarkers at baseline and after one or two years treatment. Over a mean follow-up of 1.6 years, we did not find significant relative difference of geometric mean levels of three biomarkers at follow-up between vitamin D and placebo groups: hs-cTnI (aRD=1.03, 95%CI=0.97-1.09), hs-cTnT (aRD=0.99, 95%CI=0.95-1.04), and NT-proBNP (aRD=1.01, 95%CI=0.92-1.10). No significant differences were found in likelihood of clinically elevated biomarkers between two groups: hs-cTnI (aRR=0.92, 95%CI=0.51-1.69), hs-cTnT (aRR=1.11, 95%CI=0.86-1.42), and NT-proBNP (aRR=1.03,95%CI=0.89-1.20). However, among participants with initial low vitamin D status (<50 nmol/L, n = 200), follow-up NT-proBNP were significantly lower in the vitamin D group compared to placebo (geometric mean 75.9 vs 94.5 pg/mL, respectively; aRD=0.84, 95%CI=0.71-<1.00). The same results were observed for the NT-proBNP levels change from baseline between two groups. Overall, in older adults, monthly vitamin D supplementation did not reduce concentrations of hs-cTnI, hs-cTnT, and NT-proBNP. In those with low vitamin D status, vitamin D treatment was associated, on follow up and change from baseline, with lower plasma NT-proBNP compared with placebo. This potentially signals reduced risk of subsequent heart failure within this sub-group. However, we acknowledge that these findings need to be considered exploratory. Further research is required to replicate them.
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Affiliation(s)
- Zhenqiang Wu
- School of Population Health, University of Auckland, Auckland, New Zealand; Department of Geriatric Medicine, University of Auckland, Auckland, New Zealand.
| | - John Sluyter
- School of Population Health, University of Auckland, Auckland, New Zealand
| | - Oi Wah Liew
- Cardiovascular Research Institute, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore
| | - Jenny Pek Ching Chong
- Cardiovascular Research Institute, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore
| | - Debbie Waayer
- School of Population Health, University of Auckland, Auckland, New Zealand
| | - Carlos A Camargo
- Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - A Mark Richards
- Cardiovascular Research Institute, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore; Christchurch Heart Institute, Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Robert Scragg
- School of Population Health, University of Auckland, Auckland, New Zealand
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Thiele K, Cornelissen A, Florescu R, Kneizeh K, Brandenburg VM, Witte K, Marx N, Schuh A, Stöhr R. The Role of Vitamin D 3 as an Independent Predicting Marker for One-Year Mortality in Patients with Acute Heart Failure. J Clin Med 2022; 11:2733. [PMID: 35628860 PMCID: PMC9145950 DOI: 10.3390/jcm11102733] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 04/29/2022] [Accepted: 05/09/2022] [Indexed: 12/19/2022] Open
Abstract
Background: Deficiency in vitamin D3 and its metabolites has been linked to dismal outcomes in patients with chronic diseases, including cardiovascular disease and heart failure (HF). It remains unclear if a vitamin D3 status is a prognostic feature in patients with acute decompensated HF. Methods: We assessed serum levels of 25-OH-vitamin D3 and 1,25-(OH)2-vitamin D3 in 139 patients with acute HF who had been admitted to the intermediate care unit of a maximum care hospital. The follow-up period was one year. After exclusion of patients with sampling errors and those who were lost to follow-up, 118 patients remained in the final study cohort. Outcome estimates by 25-OH-vitamin D3 and 1,25-(OH)2-vitamin D3 levels were compared to the Seattle Heart Failure (SHF) Model. Results: More than two-thirds (79.7%) of the patients showed inadequate 25-OH-vitamin D3 levels (i.e., <30 ng/mL) upon admission. Low levels of 1,25-(OH)2-vitamin D3 (i.e., <19.9 pg/mL) were observed in 16.1% of patients. Of the 118 HF patients, 22 (19%) died during the following 12 months. There were no differences in vitamin D3 levels between patients who died and those who survived, neither in 25-OH-vitamin D3 (23.37 ± 19.14 ng/mL vs. 19.11 ± 12.25 ng/mL; p = 0.19) nor in 1,25-(OH)2-vitamin D3 levels (31.10 ± 19.75 ng/mL vs. 38.25 ± 15.73 ng/mL; p = 0.02); therefore, vitamin D3 levels alone did not predict one-year survival (AUC [25-OH-vitamin D3] 0.50; 95% CI 0.34−0.65; AUC [1,25-(OH)2-vitamin D3] 0.62; 95% CI 0.48−0.76). Moreover, whilst the SHF model exhibited acceptable discriminatory ability for predicting one-year mortality (AUC 0.79; 95% CI 0.66−0.91), adding vitamin D levels on admission to the SHF score did not improve its discriminatory value. Conclusion: Our data do not support the use of vitamin D3 screening in patients admitted with acute decompensated HF to aid prognostication.
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Affiliation(s)
- Kirsten Thiele
- Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany; (A.C.); (R.F.); (K.K.); (K.W.); (N.M.); (A.S.); (R.S.)
| | - Anne Cornelissen
- Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany; (A.C.); (R.F.); (K.K.); (K.W.); (N.M.); (A.S.); (R.S.)
| | - Roberta Florescu
- Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany; (A.C.); (R.F.); (K.K.); (K.W.); (N.M.); (A.S.); (R.S.)
| | - Kinan Kneizeh
- Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany; (A.C.); (R.F.); (K.K.); (K.W.); (N.M.); (A.S.); (R.S.)
| | | | - Klaus Witte
- Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany; (A.C.); (R.F.); (K.K.); (K.W.); (N.M.); (A.S.); (R.S.)
| | - Nikolaus Marx
- Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany; (A.C.); (R.F.); (K.K.); (K.W.); (N.M.); (A.S.); (R.S.)
| | - Alexander Schuh
- Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany; (A.C.); (R.F.); (K.K.); (K.W.); (N.M.); (A.S.); (R.S.)
- Department of Internal Medicine I, St. Katharinen Hospital Frechen, 50226 Frechen, Germany
| | - Robert Stöhr
- Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany; (A.C.); (R.F.); (K.K.); (K.W.); (N.M.); (A.S.); (R.S.)
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Putz Z, Tordai D, Hajdú N, Vági OE, Kempler M, Békeffy M, Körei AE, Istenes I, Horváth V, Stoian AP, Rizzo M, Papanas N, Kempler P. Vitamin D in the Prevention and Treatment of Diabetic Neuropathy. Clin Ther 2022; 44:813-823. [DOI: 10.1016/j.clinthera.2022.03.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 03/22/2022] [Accepted: 03/23/2022] [Indexed: 12/17/2022]
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Abstract
Patients with pre-existing cardiovascular disease (CVD) are at high risk for adverse outcomes with coronavirus disease 2019 (COVID-19). Further, COVID-19 infection is associated with numerous cardiovascular (CV) complications including arrhythmia, myocardial injury, cardiomyopathy, and thrombotic events. Increased susceptibility to COVID-19 and CV complications related to COVID-19 may be in part related to immune dysregulation and inflammation associated with CV disease which is exacerbated with viral infection. Vitamin D plays a major role in immune function and exerts anti-inflammatory effects, which may prove important in the context of CVD and COVID-19. To date, studies have shown minimal benefit for vitamin D supplementation in patients with COVID-19, though there are no studies specific to patients with CVD and related complications. Further, given that vitamin D has important protective effects on the CV system, including augmentation of myocardial contractility and anti-thrombotic effects, it is unknown if supplementation with vitamin D can mitigate CVD complications associated with COVID-19.
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Affiliation(s)
- Elissa Driggin
- New York-Presbyterian Hospital and the Columbia University Irving Medical Center, New York, NY, USA
| | - Mahesh V Madhavan
- New York-Presbyterian Hospital and the Columbia University Irving Medical Center, New York, NY, USA
- Clinical Trial Center, Cardiovascular Research Foundation, New York, NY, USA
| | - Aakriti Gupta
- New York-Presbyterian Hospital and the Columbia University Irving Medical Center, New York, NY, USA.
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Trimarco V, Manzi MV, Mancusi C, Strisciuglio T, Fucile I, Fiordelisi A, Pilato E, Izzo R, Barbato E, Lembo M, Morisco C. Insulin Resistance and Vitamin D Deficiency: A Link Beyond the Appearances. Front Cardiovasc Med 2022; 9:859793. [PMID: 35369303 PMCID: PMC8968037 DOI: 10.3389/fcvm.2022.859793] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 02/17/2022] [Indexed: 12/23/2022] Open
Abstract
Vitamin D is a steroid hormone that plays a key role in the regulation of body homeostasis, including cardiovascular function. Although the chronic deficiency of vitamin D is associated with cardiovascular risk factors, as well as with an adverse prognosis, randomized controlled trials have failed in demonstrating that dietary vitamin D supplementation could ameliorate the prognosis of patients with cardiovascular diseases, and suggested that vitamin D deficiency is the expression of the effects of other determinants of cardiovascular risk. Thus, the supplementation of vitamin D is not sufficient to improve the cardiovascular risk profile and prognosis. Insulin resistance is a complex phenomenon that plays a key role in the pathogenesis of conventional cardiovascular risk factors. Interestingly, defects of vitamin D and insulin resistance have a superimposable epidemiological distribution. According to the common view, Insulin resistance is considered the direct or indirect consequence of vitamin D deficiency. However, it is also reasonable to speculate that the deficit or the impaired action of vitamin D, in some circumstances, could be the result of the same pathogenic mechanisms responsible of insulin resistance development. In this case, vitamin D deficiency could be considered an epiphenomenon of insulin resistance. Insulin resistance is a reversible condition, being possibly ameliorated by physical activity and hypocaloric diets. Notably, both physical exercise and energy-restricted dietary regimens are associated with an increase of vitamin D levels. These findings indicate that improving insulin resistance condition is a necessary step to ameliorate vitamin D supplementation-based strategies in cardiovascular prevention.
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Affiliation(s)
- Valentina Trimarco
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Maria Virginia Manzi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Costantino Mancusi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Teresa Strisciuglio
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Ilaria Fucile
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Antonella Fiordelisi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Emanuele Pilato
- Department of Cardiac Surgery, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Raffaele Izzo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Emanuele Barbato
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Maria Lembo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
- *Correspondence: Maria Lembo
| | - Carmine Morisco
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
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32
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Mueller M, Siegenthaler J, Fäh D, Schuetz P. [Nutrition in Case of Heart Failure]. PRAXIS 2022; 111:375-380. [PMID: 35611481 DOI: 10.1024/1661-8157/a003860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Nutrition in Case of Heart Failure Abstract. Despite the complexity of the subject, nutritional medicine has made important advances in recent years, especially regarding cardiovascular health and for patients with heart failure. There is quite good evidence on specific diets, such as the Mediterranean and plant-based diets, but also on individual micronutrients, such as intravenous iron supplementation of iron deficiency in heart failure. No precise quantities can yet be named when dealing with the recommended amount of salt in heart failure patients, but the intake of high amounts of salt (>12 g/day) should be avoided. Considering the risk of malnutrition in this vulnerable patient population, an individualized nutritional therapy is advisable for some patients. This requires targeted screening for malnutrition. Nutritional medicine research still lacks many answers to further questions regarding heart failure patients. More randomized controlled trials and their meta-analyses are therefore required. Studies available so far have - among other shortcomings - paid too little attention to differences in nutrition in the different types and stages of heart failure. Interdisciplinary collaboration between cardiologists, hospital internists, general practitioners and nutritional therapists is in any case crucial for optimal treatment of patients with heart failure.
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Affiliation(s)
- Marlena Mueller
- Abteilung Endokrinologie, Diabetologie und Metabolismus, Medizinischen Universitätsklinik, Kantonsspital Aarau AG, Aarau, Schweiz
- Abteilung für Allgemeine- und Notfallmedizin, Medizinische Universitätsklinik, Kantonsspital Aarau AG, Aarau, Schweiz
| | - Jolanda Siegenthaler
- Abteilung Endokrinologie, Diabetologie und Metabolismus, Medizinischen Universitätsklinik, Kantonsspital Aarau AG, Aarau, Schweiz
- Abteilung für Allgemeine- und Notfallmedizin, Medizinische Universitätsklinik, Kantonsspital Aarau AG, Aarau, Schweiz
| | - David Fäh
- Abteilung für Epidemiologie chronischer Krankheiten, Institut für Epidemiologie, Biostatistik und Prävention, Universität Zürich, Zürich, Schweiz
- Fachbereich Gesundheit - Ernährung und Diätetik, Berner Fachhochschule, Bern, Schweiz
| | - Philipp Schuetz
- Abteilung Endokrinologie, Diabetologie und Metabolismus, Medizinischen Universitätsklinik, Kantonsspital Aarau AG, Aarau, Schweiz
- Abteilung für Allgemeine- und Notfallmedizin, Medizinische Universitätsklinik, Kantonsspital Aarau AG, Aarau, Schweiz
- Medizinische Fakultät, Universitätsspital Basel, Basel, Schweiz
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Sen A, Vincent V, Thakkar H, Abraham R, Ramakrishnan L. Beneficial Role of Vitamin D on Endothelial Progenitor Cells (EPCs) in Cardiovascular Diseases. J Lipid Atheroscler 2022; 11:229-249. [PMID: 36212746 PMCID: PMC9515729 DOI: 10.12997/jla.2022.11.3.229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 03/23/2022] [Accepted: 04/04/2022] [Indexed: 11/23/2022] Open
Abstract
Cardiovascular diseases (CVDs) are the leading cause of death in the world. Endothelial progenitor cells (EPCs) are currently being explored in the context of CVD risk. EPCs are bone marrow derived progenitor cells involved in postnatal endothelial repair and neovascularization. A large body of evidence from clinical, animal, and in vitro studies have shown that EPC numbers in circulation and their functionality reflect endogenous vascular regenerative capacity. Traditionally vitamin D is known to be beneficial for bone health and calcium metabolism and in the last two decades, its role in influencing CVD and cancer risk has generated significant interest. Observational studies have shown that low vitamin D levels are associated with an adverse cardiovascular risk profile. Still, Mendelian randomization studies and randomized control trials (RCTs) have not shown significant effects of vitamin D on cardiovascular events. The criticism regarding the RCTs on vitamin D and CVD is that they were not designed to investigate cardiovascular outcomes in vitamin D-deficient individuals. Overall, the association between vitamin D and CVD remains inconclusive. Recent clinical and experimental studies have demonstrated the beneficial role of vitamin D in increasing the circulatory level of EPC as well as their functionality. In this review we present evidence supporting the beneficial role of vitamin D in CVD through its modulation of EPC homeostasis.
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Affiliation(s)
- Atanu Sen
- Department of Cardiac Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Vinnyfred Vincent
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Himani Thakkar
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Ransi Abraham
- Department of Cardiac Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Lakshmy Ramakrishnan
- Department of Cardiac Biochemistry, All India Institute of Medical Sciences, New Delhi, India
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Robert P, Alina M, Sylwia D, Jolanta MB, Marta B, Anna GG, Jacek N, Bartosz H, Mariusz G, Piotr R. Higher Serum Phosphorus Is Not an Independent Risk Factor of Mortality in Heart Failure with Reduced Ejection Fraction. Nutrients 2021; 13:4004. [PMID: 34836258 PMCID: PMC8618855 DOI: 10.3390/nu13114004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 11/04/2021] [Accepted: 11/06/2021] [Indexed: 11/22/2022] Open
Abstract
Higher serum phosphorus has detrimental health effects. Even high-normal rage sP is associated with worse outcomes. The relationship of serum phosphorus with prognostic markers in heart failure remains unclear. We investigated the association of serum phosphorus with heart failure prognostic factors and risk of mortality related to serum phosphorus. In 1029 stable heart failure patients, we investigated the distribution of markers of more advanced heart failure stage across quintiles of serum phosphorus and estimated the relative risk of mortality in comparison to reference. Higher serum phosphorus levels sP were associated with markers of a worse outcome. The best survival was observed in low-normal serum levels. The unadjusted hazard ratio for mortality increased toward higher phosphorus quintiles but not to lower levels of sP. The correction for age, sex, BMI, percent weight loss, inflammation, kidney function, and LVEF did not modify the risk profile substantially. The adjustment for NYHA, natriuretic peptides, serum sodium, and treatment characteristics broke down the risk relationship completely. A higher serum phosphorus is associated with markers of a more risky profile of heart failure. Elevated serum levels of phosphorus sP does not provide independent prognostic information beyond the strongest markers of the severity of the syndrome. The potential involvement of higher serum phosphorus as a mediator in the pathophysiology of heart failure warrants further study.
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Affiliation(s)
- Partyka Robert
- Clinical Division of Anesthesiology and Intensive Therapy of the Department of Anesthesiology, Intensive Treatment and Emergency Medicine, Medical University of Silesia, 41-800 Zabrze, Poland;
| | - Mroczek Alina
- Department of Toxicology and Health Protection, Faculty of Health Sciences in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland; (M.A.); (D.S.); (M.-B.J.); (B.M.); (G.-G.A.)
| | - Duda Sylwia
- Department of Toxicology and Health Protection, Faculty of Health Sciences in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland; (M.A.); (D.S.); (M.-B.J.); (B.M.); (G.-G.A.)
| | - Malinowska-Borowska Jolanta
- Department of Toxicology and Health Protection, Faculty of Health Sciences in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland; (M.A.); (D.S.); (M.-B.J.); (B.M.); (G.-G.A.)
| | - Buczkowska Marta
- Department of Toxicology and Health Protection, Faculty of Health Sciences in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland; (M.A.); (D.S.); (M.-B.J.); (B.M.); (G.-G.A.)
| | - Głogowska-Gruszka Anna
- Department of Toxicology and Health Protection, Faculty of Health Sciences in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland; (M.A.); (D.S.); (M.-B.J.); (B.M.); (G.-G.A.)
| | - Niedziela Jacek
- Third Department of Cardiology, SMDZ in Zabrze, Medical University of Silesia in Katowice, Silesian Centre for Heart Disease, 41-800 Zabrze, Poland; (N.J.); (H.B.); (G.M.)
| | - Hudzik Bartosz
- Third Department of Cardiology, SMDZ in Zabrze, Medical University of Silesia in Katowice, Silesian Centre for Heart Disease, 41-800 Zabrze, Poland; (N.J.); (H.B.); (G.M.)
- Department of Cardiovascular Disease Prevention, Faculty of Health Sciences in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland
| | - Gąsior Mariusz
- Third Department of Cardiology, SMDZ in Zabrze, Medical University of Silesia in Katowice, Silesian Centre for Heart Disease, 41-800 Zabrze, Poland; (N.J.); (H.B.); (G.M.)
| | - Rozentryt Piotr
- Department of Toxicology and Health Protection, Faculty of Health Sciences in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland; (M.A.); (D.S.); (M.-B.J.); (B.M.); (G.-G.A.)
- Third Department of Cardiology, SMDZ in Zabrze, Medical University of Silesia in Katowice, Silesian Centre for Heart Disease, 41-800 Zabrze, Poland; (N.J.); (H.B.); (G.M.)
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Bahrami A, Farjami Z, Ferns GA, Hanachi P, Mobarhan MG. Evaluation of the knowledge regarding vitamin D, and sunscreen use of female adolescents in Iran. BMC Public Health 2021; 21:2059. [PMID: 34758788 PMCID: PMC8579675 DOI: 10.1186/s12889-021-12133-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Accepted: 10/29/2021] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Vitamin D (Vit D) deficiency/insufficiency is an important risk factor for several chronic conditions. We aimed to evaluate the knowledge and behavior of female adolescents with respect to the association between sunlight exposure, sunscreen use, and Vit D status. METHODS This cross-sectional survey was performed in northeastern Iran, among 940 female adolescents in January 2015. Each subject completed a questionnaire containing items about demographic characteristics, knowledge about Vit D and their use of sunscreen. Serum Vit D levels were measured using an electrochemiluminescence method and dietary intake of Vit D was assessed using a Food Frequency Questionnaire. Statistical analyses were conducted using SPSS software. A P value < 0.05 was considered statistically significant. RESULTS Few of the participants were aware of the biological functions of Vit D (8.8%), the causes of Vit D deficiency (16.7%), and the sources of Vit D (9.3%). Less than half of the participants used sunscreen during the day. The serum levels of Vit D in subjects who used sunscreen were significantly lower than those who did not (p = 0.004). However, there was no significant association between their knowledge about Vit D and serum Vit D, or dietary intake of Vit D. CONCLUSION There appears to be a lack of coherence between lifestyle, behavior and knowledge that may affect the Vit D status of adolescent girls in northeastern Iran. This information provides a basis for developing public health planning (workshops or training at the college level) for the prevention of Vit D deficiency especially in adolescent girls.
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Affiliation(s)
- Afsane Bahrami
- Clinical Research Development Unit of Akbar Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Clinical Research Development Unit, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Farjami
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex, BN1 9PH, UK
| | - Parichehr Hanachi
- Department of Biotechnology, Faculty of Biological Science, Alzahra University, Tehran, Iran.
| | - Majid Ghayour Mobarhan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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36
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Association of Vitamin D Supplementation in Cardiorespiratory Fitness and Muscle Strength in Adult Twins: A Randomized Controlled Trial. Int J Sport Nutr Exerc Metab 2021; 32:2-7. [PMID: 34689128 DOI: 10.1123/ijsnem.2021-0060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 07/29/2021] [Accepted: 09/06/2021] [Indexed: 11/18/2022]
Abstract
Although vitamin D is related to cardiorespiratory fitness and muscle strength, there is no evidence in the literature about the genetic influence of the response to vitamin D supplementation and improvements in these parameters. Therefore, we evaluate the effect of longitudinal supplementation of vitamin D on parameters of physical fitness in monozygotic twins. In total, 74 participants were included, with a mean age of 25 years, divided into two groups, one group received supplementation with cholecalciferol for 60 days and the other group did not. Cardiorespiratory fitness and muscle strength were measured before and after supplementation through maximal treadmill tests and dynamometry, respectively. Wilcoxon tests were used to compare intragroup results and the Mann-Whitney test to examine intergroup differences. There was an increase in the serum concentration of vitamin D in participants who ingested the supplementation. Cardiorespiratory fitness improved after supplementation through increases in the values of maximum oxygen consumption of 28% (p < .001). Muscle strength in left hand grip increased 18% in participants who received the supplement (p = .007). Sixty days of cholecalciferol supplementation improved cardiorespiratory fitness and upper limb muscle strength.
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Cosentino N, Campodonico J, Milazzo V, De Metrio M, Brambilla M, Camera M, Marenzi G. Vitamin D and Cardiovascular Disease: Current Evidence and Future Perspectives. Nutrients 2021; 13:nu13103603. [PMID: 34684604 PMCID: PMC8541123 DOI: 10.3390/nu13103603] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/28/2021] [Accepted: 10/11/2021] [Indexed: 12/14/2022] Open
Abstract
Vitamin D deficiency is a prevalent condition, occurring in about 30–50% of the population, observed across all ethnicities and among all age groups. Besides the established role of vitamin D in calcium homeostasis, its deficiency is emerging as a new risk factor for cardiovascular disease (CVD). In particular, several epidemiological and clinical studies have reported a close association between low vitamin D levels and major CVDs, such as coronary artery disease, heart failure, and atrial fibrillation. Moreover, in all these clinical settings, vitamin deficiency seems to predispose to increased morbidity, mortality, and recurrent cardiovascular events. Despite this growing evidence, interventional trials with supplementation of vitamin D in patients at risk of or with established CVD are still controversial. In this review, we aimed to summarize the currently available evidence supporting the link between vitamin D deficiency and major CVDs in terms of its prevalence, clinical relevance, prognostic impact, and potential therapeutic implications.
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Affiliation(s)
- Nicola Cosentino
- Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy; (N.C.); (J.C.); (V.M.); (M.D.M.); (M.B.); (M.C.)
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
| | - Jeness Campodonico
- Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy; (N.C.); (J.C.); (V.M.); (M.D.M.); (M.B.); (M.C.)
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
| | - Valentina Milazzo
- Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy; (N.C.); (J.C.); (V.M.); (M.D.M.); (M.B.); (M.C.)
| | - Monica De Metrio
- Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy; (N.C.); (J.C.); (V.M.); (M.D.M.); (M.B.); (M.C.)
| | - Marta Brambilla
- Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy; (N.C.); (J.C.); (V.M.); (M.D.M.); (M.B.); (M.C.)
| | - Marina Camera
- Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy; (N.C.); (J.C.); (V.M.); (M.D.M.); (M.B.); (M.C.)
- Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy
| | - Giancarlo Marenzi
- Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy; (N.C.); (J.C.); (V.M.); (M.D.M.); (M.B.); (M.C.)
- Correspondence: ; Tel.: +39-02-580-021
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Walters GWM, Redman E, Gulsin GS, Henson J, Argyridou S, Yates T, Davies MJ, Parke K, McCann GP, Brady EM. Interrelationship between micronutrients and cardiovascular structure and function in type 2 diabetes. J Nutr Sci 2021; 10:e88. [PMID: 34733500 PMCID: PMC8532075 DOI: 10.1017/jns.2021.82] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 09/08/2021] [Indexed: 11/30/2022] Open
Abstract
Micronutrients are important for normal cardiovascular function. They may play a role in the increased risk of cardiovascular disease observed in people with type 2 diabetes (T2D) and T2D-related heart failure. The aims of this study were to (1) examine micronutrient status in people with T2D v. healthy controls; (2) assess any changes following a nutritionally complete meal replacement plan (MRP) compared with routine care; (3) determine if any changes were associated with changes in cardiovascular structure/function. This was a secondary analysis of data from a prospective, randomised, open-label, blinded end-point trial of people with T2D, with a nested case-control [NCT02590822]. Anthropometrics, cardiac resonance imaging and fasting blood samples (to quantify vitamins B1, B6, B12, D and C; and iron and ferritin) were collected at baseline and 12 weeks following the MRP or routine care. Comparative data in healthy controls were collected at baseline. A total of eighty-three people with T2D and thirty-six healthy controls were compared at baseline; all had micronutrient status within reference ranges. Vitamin B1 was higher (148⋅9 v. 131⋅7; P 0⋅01) and B6 lower (37⋅3 v. 52⋅9; P 0⋅01) in T2D v. controls. All thirty participants randomised to routine care and twenty-four to the MRP completed the study. There was an increase in vitamins B1, B6, D and C following the MRP, which were not associated with changes in cardiovascular structure/function. In conclusion, changes in micronutrient status following the MRP were not independently associated with improvements in cardiovascular structure/function in people with T2D.
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Key Words
- BMI, body mass index
- CMR
- CMR, cardiac magnetic resonance imaging
- CVD, cardiovascular disease
- Cardiovascular function
- EF, ejection fraction
- HF, heart failure
- LV, left ventricular
- Low calorie
- Low-energy meal replacement plan
- MRP, meal replacement plan
- Micronutrients
- PLP, pyridoxal 5-phosphate
- RCT, randomised control trial
- T2D, type 2 diabetes
- Type 2 diabetes
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Affiliation(s)
- Grace W. M. Walters
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
- National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK
| | - Emma Redman
- National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK
- Diabetes Research Centre, University of Leicester, Leicester, UK
| | - Gaurav S. Gulsin
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
- National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK
| | - Joseph Henson
- National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK
- Diabetes Research Centre, University of Leicester, Leicester, UK
| | | | - Thomas Yates
- National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK
- Diabetes Research Centre, University of Leicester, Leicester, UK
| | - Melanie J. Davies
- National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK
- Diabetes Research Centre, University of Leicester, Leicester, UK
| | - Kelly Parke
- University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Gerry P. McCann
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
- National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK
| | - Emer M. Brady
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
- National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK
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Ismail HM, Algrafi AS, Amoudi O, Ahmed S, Al-Thagfan SS, Shora H, Aljohani M, Almutairi M, Alharbi F, Alhejaili A, Alamri M, Muhawish A, Abdallah A. Vitamin D and Its Metabolites Deficiency in Acute Coronary Syndrome Patients Undergoing Coronary Angiography: A Case-Control Study. Vasc Health Risk Manag 2021; 17:471-480. [PMID: 34408425 PMCID: PMC8364363 DOI: 10.2147/vhrm.s312376] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 07/15/2021] [Indexed: 12/26/2022] Open
Abstract
Background Vitamin D deficiency is considered an emerging health problem that affects at least one billion patients worldwide. Calcitriol 1,25(OH)2D3 has several systemic effects, including anti-inflammatory, anti-thrombotic and anti-atherosclerotic impacts that explain its cardioprotective effects. The precise association between vitamin D and its metabolites and the value of supplements in acute coronary syndrome (ACS) is still controversial. This study aims to search the association between vitamin D2, D3, and metabolites and ACS in patients undergoing coronary angiography. Materials and Methods This was a case–control study on 73 consecutive adult patients with ACS undergoing coronary angiography compared to 50 controls without coronary artery disease and matched for age and sex from June 2019 till July 2019. Echocardiography and coronary angiography were done for all cases. Plasma vitamin D and its metabolites were measured at admission for all participants along with chemistry profiles. Results Vitamin D and its metabolites were statistically significantly lower in ACS patients than the controls. Multivariate regression analysis revealed that low levels of 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) significantly predicted ACS occurrence; the other significant predictors were high systolic blood pressure (BP), high total cholesterol, and low high-density lipoprotein-cholesterol. Interestingly, vitamin D2 and D3 did not significantly predict ACS (p>0.05). We did not find a statistically significant association between the number of affected coronary vessels and vitamin D metabolites. Moreover, there was no statistically significant correlation between vitamin D and its metabolites and left ventricular ejection fraction measured by echocardiography. Conclusion There was a strong association between vitamin D and all its metabolites with ACS. Significantly, low 25(OH)D and 1,25(OH)2D predicted ACS, but vitamin D2 and D3 did not. Large randomized controlled trials are needed to verify the beneficial values of vitamin D supplementation in ACS patients.
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Affiliation(s)
- Hussein M Ismail
- Department of cardiology, College of Medicine, Suez Canal University, Ismailia, Egypt.,Department of medicine, College of Medicine, Taibah University, Al-Madinah Al-Munawara, Saudi Arabia
| | - Abeer S Algrafi
- Department of medicine, College of Medicine, Taibah University, Al-Madinah Al-Munawara, Saudi Arabia
| | - Osama Amoudi
- Madinah Cardiac Center, Adult cardiology, Al-Madinah Al-Munawara, Saudi Arabia
| | - Sameh Ahmed
- Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al-Madinah Al-Munawara, Saudi Arabia
| | - Sultan S Al-Thagfan
- Department of Clinical and Hospital Pharmacy, College of Pharmacy, Taibah University, Al-Madinah Al-Munawara, Saudi Arabia
| | - Hassan Shora
- Department of molecular biology/biochemistry, Port Said University, Port Said, Egypt
| | - Mohammed Aljohani
- Medical intern, Taibah University, Al-Madinah Al-Munawara, Saudi Arabia
| | | | - Fahad Alharbi
- Medical intern, Taibah University, Al-Madinah Al-Munawara, Saudi Arabia
| | | | - Majed Alamri
- Medical intern, Taibah University, Al-Madinah Al-Munawara, Saudi Arabia
| | - Abdullah Muhawish
- Medical intern, Taibah University, Al-Madinah Al-Munawara, Saudi Arabia
| | - Ayat Abdallah
- Epidemiology and Preventive Medicine Department, National Liver Institute, Shebin El-Kom, Egypt.,Department of Family and Community Medicine, Taibah University, Al-Madinah Al-Munawara, Saudi Arabia
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Kweder H, Eidi H. Vitamin D deficiency in elderly: Risk factors and drugs impact on vitamin D status. Avicenna J Med 2021; 8:139-146. [PMID: 30319955 PMCID: PMC6178567 DOI: 10.4103/ajm.ajm_20_18] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Introduction: Vitamin D (VD) deficiency is a major public health problem worldwide. In spite of its high prevalence, particularly among elderly people, VD deficiency is still underestimated by many physicians. Increasingly, VD deficiency is associated with several known geriatric syndromes. Methods: The study sample consisted of 125 patients, aged 75 years and older, admitted to the acute geriatric unit. The plausible association between the serum 25-hydroxyvitamin D [25(OH)D] level and patient age, sex, body mass index, renal function, cholecystectomy history, and the prescribed drugs had been investigated. The Fisher's exact test was used to conduct the statistical analysis of data. Results: Surprisingly, furosemide treatment was correlated with normal 25(OH)D levels and an increased incidence of secondary hyperparathyroidism. Unlike the other four parameters mentioned above, our data showed that only the patient sex exhibited a significant association with 25(OH)D level as elderly males suffered from a serious VD deficiency as compared to elderly females. Conclusion: Old age is an independent risk factor for VD deficiency. The supplementary dose of VD should be precisely defined to achieve the optimal serum 25(OH)D level in elderly people. The definition of the normal serum 25(OH)D threshold in elderly furosemide-treated patients is worth of further studies.
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Affiliation(s)
- Hasan Kweder
- Department of Geriatric Medicine, Hospital of Pierre Oudot, Bourgoin-Jallieu City, Isère Department, Region of Auvergne-Rhône-Alpes, France
| | - Housam Eidi
- Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada
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Abstract
Coexisting dysfunction of heart and kidney, the cardiorenal syndrome, is a common condition and is associated with worsening of outcomes and complexities of diagnostic, preventive, and therapeutic approaches. The knowledge of the physiology of heart and kidney and their interaction with each other and with other organ systems has progressed significantly in recent years, resulting in a better understanding of the pathogenesis of cardiorenal syndrome. A robust knowledge of the pathophysiology and of the latest practical advancements about cardiorenal syndrome is necessary for cardiologists, nephrologists, and other practitioners who provide medical care to the patients with heart and kidney diseases.
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Affiliation(s)
- Parta Hatamizadeh
- Department of Medicine, Division of Nephrology, Hypertension & Renal Transplantation, University of Florida, 1600 SW Archer Road, CG-98, PO Box 100224, Gainesville, FL 32610, USA.
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Gouni-Berthold I, Berthold HK. Vitamin D and Vascular Disease. Curr Vasc Pharmacol 2021; 19:250-268. [PMID: 32183681 DOI: 10.2174/1570161118666200317151955] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 02/24/2020] [Accepted: 03/01/2020] [Indexed: 12/20/2022]
Abstract
Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Vitamin D deficiency has been identified as a potential risk factor for a number of diseases unrelated to the classical skeletal pathophysiology, such as cancer and CVD, but the effects of vitamin D supplementation are less clear. Purpose of this narrative review is to discuss the evidence suggesting an association between vitamin D status and CVD as well as the results of supplementation studies. Vitamin D deficiency has been associated with CVD risk factors such as hypertension, dyslipidemia and diabetes mellitus as well as with cardiovascular events such as myocardial infarction, stroke and heart failure. While vitamin D deficiency might contribute to the development of CVD through its association with risk factors, direct effects of vitamin D on the cardiovascular system may also be involved. Vitamin D receptors are expressed in a variety of tissues, including cardiomyocytes, vascular smooth muscle cells and endothelial cells. Moreover, vitamin D has been shown to affect inflammation, cell proliferation and differentiation. While observational studies support an association between low plasma vitamin D levels and increased risk of CVD, Mendelian randomization studies do not support a causal association between the two. At present, high quality randomized trials do not find evidence of significant effects on CVD endpoints and do not support supplementation of vitamin D to decrease CVD events.
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Affiliation(s)
- Ioanna Gouni-Berthold
- Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany
| | - Heiner K Berthold
- Department of Internal Medicine and Geriatrics, Bethel Clinic (EvKB), Bielefeld, Germany
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He M, Cao T, Wang J, Wang C, Wang Z, Abdelrahim MEA. Vitamin D deficiency relation to sepsis, paediatric risk of mortality III score, need for ventilation support, length of hospital stay, and duration of mechanical ventilation in critically ill children: A meta-analysis. Int J Clin Pract 2021; 75:e13908. [PMID: 33280208 DOI: 10.1111/ijcp.13908] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 12/01/2020] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION Vitamin D deficiency in children is related to the augmented risk of bone illnesses, but its effect on critically ill children is still conflicting. This meta-analysis study was performed to assess the relationship between vitamin D deficiency in children and sepsis, paediatric risk of mortality III score, need for ventilation support, length of hospital stay, and duration of mechanical ventilation in critically ill children. METHODS Through a systematic literature search up to June 2020, 16 studies with 2382 children, 1229 children of them with vitamin D deficiency, were found recording relationships between vitamin D deficiency and sepsis, paediatric risk of mortality III score, need for ventilation support, length of hospital stay, and/or duration of mechanical ventilation. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated between vitamin D deficiency children to non-vitamin D deficiency children on the different outcomes in critically ill children using the dichotomous or continuous methods with a random or fixed-effect model. RESULTS The vitamin D deficiency children category had significantly higher sepsis (OR, 2.35; 95% CI, 1.19-4.63, P = .01); paediatric risk of mortality III score (OR, 2.19; 95% CI, 1.13-4.25, P = .02); higher length of hospital stay (OR, 4.26; 95% CI, 0.81-7.70, P = .02); higher duration of mechanical ventilation (OR, 1.89; 95% CI, 0.22-3.56, P = .03) compared with that in the non-vitamin D deficiency children. However, the need for ventilation support in vitamin D deficiency children did not significantly differ from non-vitamin D deficiency children (OR, 2.00; 95% CI, 0.98-4.07, P = .06) with relatively higher results in vitamin D deficiency children. CONCLUSIONS Vitamin D deficiency in children might have an independent relationship with higher sepsis, paediatric risk of mortality III score, length of hospital stay, and duration of mechanical ventilation. The relation was relative with a higher risk in need for ventilation support with vitamin D deficiency children. This relationship encouraged us to recommend testing vitamin D levels in all critically ill children and providing them with supplemental vitamin D as prophylaxis.
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Affiliation(s)
- Mingyi He
- Emergency Department, Xuanwu Hospital Capital Medical University, Beijing, Beijing, China
| | - Tao Cao
- Emergency Department, Xuanwu Hospital Capital Medical University, Beijing, Beijing, China
| | - Jing Wang
- Emergency Department, Xuanwu Hospital Capital Medical University, Beijing, Beijing, China
| | - Changyuan Wang
- Emergency Department, Xuanwu Hospital Capital Medical University, Beijing, Beijing, China
| | - Zheng Wang
- Emergency Department, Xuanwu Hospital Capital Medical University, Beijing, Beijing, China
| | - Mohamed E A Abdelrahim
- Clinical Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
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Scharla SH. Pleiotrope Wirkung von Vitamin D mit Berücksichtigung von COVID-19. JOURNAL FÜR MINERALSTOFFWECHSEL & MUSKULOSKELETTALE ERKRANKUNGEN 2021. [PMCID: PMC7968561 DOI: 10.1007/s41970-021-00146-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Vitamin D wird aus der Nahrung aufgenommen oder in der Haut unter Einwirkung von UV-Licht gebildet. In der Leber wird 25(OH)-Vitamin D gebildet und in der Niere 1,25(OH)2-Vitamin D, welches als Hormon den Knochen- und Mineralstoffwechsel reguliert. Außerhalb der Niere besitzen viele Organe Enzyme, um 1,25(OH)2-Vitamin D zu bilden für autokrine und parakrine Wirkungen. Für diese pleiotropen Effekte erscheint eine gleichmäßige Vitamin-D-Versorgung (tägliche Vitamin-D-Supplementation) mit mäßiger Dosierung besser wirksam als hoch dosierte Bolusapplikationen. Neben der klassischen Wirkung von 1,25(OH)2-Vitamin D auf das muskuloskelettale System sind unter den extraskelettalen Wirkungen insbesondere die immunregulatorischen Effekte mittlerweile sehr gut belegt. So kann durch eine gute Vitamin-D-Versorgung das Risiko für respiratorische Infekte vermindert werden, was gerade im Hinblick auf die aktuelle COVID-19(Coronavirus-Erkrankung-19)-Pandemie von Bedeutung erscheint.
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Affiliation(s)
- Stephan H. Scharla
- Praxis für Innere Medizin und Endokrinologie/Diabetologie, Salinenstraße 8, 83435 Bad Reichenhall, Deutschland
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Otaal PS, Pachipala S, Uppal L, Bootla D. Correlation of Vitamin D Deficiency With Severity of Chronic Heart Failure as Assessed by Functional Class and N-Terminal Pro-Brain Natriuretic Peptide Levels. Cureus 2021; 13:e13522. [PMID: 33786229 PMCID: PMC7996472 DOI: 10.7759/cureus.13522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Introduction Chronic heart failure (CHF) is a major cause of mortality and morbidity in spite of tremendous advances in medical therapies. Vitamin D deficiency has been increasingly recognised in heart failure and its therapeutic as well as prognostic implications are debated. This study was carried out to examine the relationship of Vitamin D levels with severity of heart failure as assessed by NYHA functional class and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels in vitamin D deficient patients with CHF. Methodology and results In this cross-sectional analysis, 119 patients of symptomatic CHF presenting to the outpatient/inpatient department of cardiology in a tertiary care institute in North India were screened. Patients were categorised according to their functional class as New York Heart Association (NYHA) class II, III, IV and their serum levels of vitamin D and NT-pro-BNP were measured. Out of 119 patients, 107 (90%) were found to have low vitamin D levels which were classified as insufficient (20-30 ng/ml) (n=25, 23%) or deficient (<20 ng/ml) (n=82,77%). The mean NT-pro-BNP levels increased significantly across functional class as 3783±6132 pg/ml, 7866±4383 pg/ml, 21115±11905 pg/ml in NYHA class II, III and IV respectively (p=0.000). The respective mean serum Vitamin D3 levels of 11.6±5.8ng/ml, 12.2±7.9 ng/ml, 14.4±8.9 ng/ml were not significantly different between classes (p=0.234). We found no correlation between serum NT-pro-BNP and serum vitamin D levels in the study cohort across various NYHA classes. In multivariate regression model, after adjusting for various co-variates, vitamin D levels were not significantly associated with NT-pro-BNP or functional class in patients with CHF. Conclusion Patients with CHF have a high prevalence (90%) of vitamin D deficiency. Although NT-pro-BNP levels increase significantly, vitamin D levels do not vary significantly with worsening NYHA classes. Further, no consistent significant correlation of vitamin D deficiency with NT-pro-BNP across different NYHA classes was observed. Thus, low levels of vitamin D didn't predict the severity and prognosis of patients with heart failure. .
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Affiliation(s)
- Parminder S Otaal
- Department of Cardiology, Post Graduate Institute of Medical Education and Research, Chandigarh, IND
| | - Sudheer Pachipala
- Department of Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, IND
| | - Lipi Uppal
- Department of Cardiology, Post Graduate Institute of Medical Education and Research, Chandigarh, IND
| | - Dinakar Bootla
- Department of Cardiology, Post Graduate Institute of Medical Education and Research, Chandigarh, IND
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Vitamin D: Mechanism of Action and Biological Effects in Uterine Fibroids. Nutrients 2021; 13:nu13020597. [PMID: 33670322 PMCID: PMC7917888 DOI: 10.3390/nu13020597] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 02/07/2021] [Accepted: 02/08/2021] [Indexed: 12/15/2022] Open
Abstract
Uterine fibroids (UFs) are the most common benign gynecological tumors. It was estimated that fifty percent of women presenting with UFs has symptomatology that negatively influences their quality of life. Pharmacological and/or surgical treatments are frequently required, depending on the woman's desire to preserve fertility, with a high impact on healthcare costs. Generally, the use of currently available pharmacological treatments may lead to side effects. Therefore, there is a growing interest in a natural and safe approach for UFs. In recent years, epidemiological studies reported a vitamin D deficiency in patients with UFs raised interest in the potential biological effects of vitamin D supplementation. In vitro studies proved vitamin D efficacy in inhibiting UFs growth by targeting pathways involved in the regulation of various biological processes, including proliferation, extracellular matrix (ECM) remodeling, DNA repair, signaling and apoptosis. However, clinical studies supported only in part the beneficial effects of vitamin D supplementation in reducing UFs growth and tumor volume. Randomized controlled trials and large population studies are mandatory as the potential clinical benefits are likely to be substantial.
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Effects of Vitamin D Supplementation on Surrogate Markers of Fertility in PCOS Women: A Randomized Controlled Trial. Nutrients 2021; 13:nu13020547. [PMID: 33562394 PMCID: PMC7914670 DOI: 10.3390/nu13020547] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/29/2021] [Accepted: 02/02/2021] [Indexed: 12/25/2022] Open
Abstract
Vitamin D (VD) might play an important role in polycystic ovary syndrome (PCOS) and female fertility. However, evidence from randomized controlled trials (RCT) is sparse. We examined VD effects on anti-Müllerian hormone (AMH) and other endocrine markers in PCOS and non-PCOS women. This is a post hoc analysis of a single-center, double-blind RCT conducted between December 2011 and October 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. We included 180 PCOS women and 150 non-PCOS women with serum 25-hydroxyvitamin D (25(OH)D) concentrations <75 nmol/L in the trial. We randomized subjects to receive 20,000 IU of VD3/week (119 PCOS, 99 non-PCOS women) or placebo (61 PCOS, 51 non-PCOS women) for 24 weeks. Outcome measures were AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, dehydroepiandrosterone sulfate, and androstenedione. In PCOS women, we observed a significant treatment effect on FSH (mean treatment effect 0.94, 95% confidence interval [CI] 0.087 to 1.799, p = 0.031) and LH/FSH ratio (mean treatment effect −0.335, 95% CI −0.621 to 0.050, p = 0.022), whereas no significant effect was observed in non-PCOS women. In PCOS women, VD treatment for 24 weeks had a significant effect on FSH and LH/FSH ratio but no effect on AMH levels.
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Tanaka K, Okada Y, Hajime M, Tanaka Y. Low Vitamin D Levels are Associated with Vascular Endothelial Dysfunction in Patients with Poorly Controlled Type 2 Diabetes: A Retrospective Study. J Atheroscler Thromb 2021; 29:242-251. [PMID: 33518614 PMCID: PMC8803557 DOI: 10.5551/jat.59113] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
AIM This study aimed to determine the association between serum 25-hydroxyvitamin D (25(OH)D) levels and vascular endothelial function in patients with type 2 diabetes (T2D). METHODS This retrospective study included 113 patients with poorly controlled T2D who were admitted for in-hospital diabetes educational program and underwent measurements of serum 25(OH)D levels and reactive hyperemia index (RHI). RESULTS Serum 25(OH)D levels significantly correlated with RHI in T2D patients. Receiver operating characteristic (ROC) curve analysis showed that serum 25(OH)D level of 16.5 ng/mL is the optimal cutoff level for predicting vascular endothelial dysfunction (RHI＜1.67), with a sensitivity of 68.5%, specificity of 67.9%, and area under the ROC curve of 0.668 (95% confidence interval [CI]: 0.566-0.770, p=0.002). The mean RHI was significantly lower (1.70±0.54) in patients with low 25(OH)D levels (n=56, 25(OH)D levels ＜16.5 ng/mL) than that (1.99±0.58; p＜0.001) in patients with high 25(OH)D levels (n=57, 25(OH)D level ≥ 16.5 ng/mL). The proportion of patients with RHI＜1.67 was higher in the low 25(OH)D group than in the high 25(OH)D group (38% vs. 18%; p＜0.001). Multivariate logistic regression analysis identified that serum 25(OH)D level ＜16.5 ng/mL was associated with increased odds of RHI ＜1.67 (odds ratio 4.598, 95% CI 1.961-10.783, p＜0.001). CONCLUSION The results demonstrated the association of serum 25(OH)D levels with endothelial function in poorly controlled T2D patients and identified serum 25(OH)D level of ＜16.5 ng/mL as a predictor of RHI ＜1.67. Serum 25(OH)D level is a potentially useful marker of vascular endothelial dysfunction in poorly controlled T2D patients.
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Affiliation(s)
- Kenichi Tanaka
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan
| | - Yosuke Okada
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan
| | - Maiko Hajime
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan
| | - Yoshiya Tanaka
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan
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Vitamin D status and predictors of 25-hydroxyvitamin D levels in patients with heart failure living in a sunny region. NUTR HOSP 2021; 38:349-357. [PMID: 33615819 DOI: 10.20960/nh.03291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Introduction Aims: hypovitaminosis D has frequently been identified in patients with heart failure (HF). However, few studies have been conducted in regions with high solar incidence. Therefore, this study aimed to evaluate vitamin D status and predictors of 25-hydroxyvitamin D (25(OH)D) levels in patients with HF living in a sunny region (5 °- 6 °S). Methods: this cross-sectional study enrolled 70 patients with HF. Biodemographic, clinical, biochemical, dietary, and sun exposure data were collected, and 25(OH)D levels were measured. Results: the mean 25(OH)D level was 40.1 (12.4) ng/mL, and 24.3 % (95 % CI: 14.2-33.8) of patients with HF had hypovitaminosis D (25(OH)D < 30 ng/mL). Female patients (p = 0.001), those with ischemic etiology (p = 0.03) and those with high parathyroid hormone levels (> 67 pg/mL) (p = 0.034) were more likely to present hypovitaminosis D. Higher 25(OH)D levels were observed in men than in women (β = 7.78, p = 0.005) and in patients with HF in New York Heart Association (NHYA) functional class I when compared to those in class III/IV (β = 8.23, p = 0.032). Conclusions: the majority of patients with HF had sufficient 25(OH)D levels. Sex and functional classification were identified as independent predictors of 25(OH)D levels. These results highlight the need for increased monitoring of vitamin D status among female patients with heart failure and those with more severe symptoms.
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Verdoia M, Nardin M, Rolla R, Negro F, Gioscia R, Afifeh AMS, Viglione F, Suryapranata H, Marcolongo M, De Luca G. Prognostic impact of Vitamin D deficiency in patients with coronary artery disease undergoing percutaneous coronary intervention. Eur J Intern Med 2021; 83:62-67. [PMID: 32830035 DOI: 10.1016/j.ejim.2020.08.016] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 08/03/2020] [Accepted: 08/16/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Whether Vitamin D deficiency represents an independent predictor of mortality and major cardiovascular events or rather the mirror of a more advanced clinical condition with increased comorbidities is still debated. We aimed at assessing the impact of vitamin D levels on the long-term outcomes among patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention. METHODS Consecutive patients from a single centre were included. Vitamin D levels were measured at admission by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc). Severe deficiency was defined for 25(OH)D < 10 ng/ml. The primary study endpoint was overall mortality. Secondary endpoints were cardiovascular mortality, recurrent acute coronary syndrome or major cardiovascular events (a composite of death, recurrent MI and target vessel revascularization) at the longest available follow-up. RESULTS We included a total of 705 patients, that were divided according to vitamin D tertiles (<12.7; 12.7-21.59; ≥21.6 ng/ml). Lower levels of Vitamin D were associated with renal failure (p=0.03), more severe coronary disease (p=0.001), diabetes mellitus and previous CABG (p<0.001), lower ejection fraction (p=0.02), acute presentation (p=0.04), use of statins (p=0.02), diuretics, nitrates and clopidogrel (p<0.001) and RASI (p=0.008). An inverse association was documented with BMI, glycemia, total cholesterol (p<0.001), creatinine and WBC (p=0.001). At a median follow-up of 996.5 [377-1552] days, 3.8% of the patients died. Vitamin D deficiency was significantly associated with overall mortality (7.6% vs 2.9% vs 0.4%, adjusted HR[95%CI]=3.6[1.43-8.9], p=0.006), MACE (adjusted HR[95%CI]=1.32[1.07-1.63], p=0.01) and the composite of death and MI (adjusted HR[95%CI]=1.3[1.03-1.65], p=0.03). A similarly increased risk was confirmed for all major higher-risk subsets of patients, with no significant interaction according to age, gender, diabetes mellitus or chronic kidney disease. CONCLUSION Among patients undergoing percutaneous coronary interventions, lower levels of vitamin D are associated with an over 3-fold increased risk of mortality and major cardiovascular events. Future larger studies are certainly warranted in order to define the prognostic implications of cholecalciferol supplementation among high-risk patients with established coronary artery disease.
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Affiliation(s)
- Monica Verdoia
- Division of Cardiology, Ospedale degli Infermi, ASL, Biella, Italy; Department of Translational Medicine, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, C.so Mazzini, 18, 28100 Novara, Italy
| | - Matteo Nardin
- Department of Translational Medicine, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, C.so Mazzini, 18, 28100 Novara, Italy
| | - Roberta Rolla
- Department of Translational Medicine, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, C.so Mazzini, 18, 28100 Novara, Italy
| | - Federica Negro
- Department of Translational Medicine, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, C.so Mazzini, 18, 28100 Novara, Italy
| | - Rocco Gioscia
- Department of Translational Medicine, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, C.so Mazzini, 18, 28100 Novara, Italy
| | - Arraa Maddalena Saghir Afifeh
- Department of Translational Medicine, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, C.so Mazzini, 18, 28100 Novara, Italy
| | - Filippo Viglione
- Department of Translational Medicine, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, C.so Mazzini, 18, 28100 Novara, Italy
| | | | - Marco Marcolongo
- Division of Cardiology, Ospedale degli Infermi, ASL, Biella, Italy
| | - Giuseppe De Luca
- Department of Translational Medicine, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, C.so Mazzini, 18, 28100 Novara, Italy.
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