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Kennelly JP, Xiao X, Gao Y, Kim S, Hong SG, Villanueva M, Ferrari A, Vanharanta L, Nguyen A, Nagari RT, Burton NR, Tol MJ, Becker AP, Lee MJ, Ikonen E, Backus KM, Mack JJ, Tontonoz P. Cholesterol binding to VCAM-1 promotes vascular inflammation. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.09.17.613543. [PMID: 39345495 PMCID: PMC11429921 DOI: 10.1101/2024.09.17.613543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/01/2024]
Abstract
Hypercholesterolemia has long been implicated in endothelial cell (EC) dysfunction, but the mechanisms by which excess cholesterol causes vascular pathology are incompletely understood. Here we used a cholesterol-mimetic probe to map cholesterol-protein interactions in primary human ECs and discovered that cholesterol binds to and stabilizes the adhesion molecule VCAM-1. We show that accessible plasma membrane (PM) cholesterol in ECs is acutely responsive to inflammatory stimuli and that the nonvesicular cholesterol transporter Aster-A regulates VCAM-1 stability in activated ECs by controlling the size of this pool. Deletion of Aster-A in ECs increases VCAM-1 protein, promotes immune cell recruitment to vessels, and impairs pulmonary immune homeostasis. Conversely, depleting cholesterol from the endothelium in vivo dampens VCAM-1 induction in response to inflammatory stimuli. These findings identify cholesterol binding to VCAM-1 as a key step during EC activation and provide a biochemical explanation for the ability of excess membrane cholesterol to promote immune cell recruitment to the endothelium.
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Affiliation(s)
- John P. Kennelly
- Department of Pathology and Laboratory Medicine, University of California, Los Angeles (UCLA); Los Angeles, CA 90095, USA
- Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA
- These authors contributed equally
| | - Xu Xiao
- Department of Pathology and Laboratory Medicine, University of California, Los Angeles (UCLA); Los Angeles, CA 90095, USA
- Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA
- These authors contributed equally
| | - Yajing Gao
- Department of Pathology and Laboratory Medicine, University of California, Los Angeles (UCLA); Los Angeles, CA 90095, USA
- Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA
| | - Sumin Kim
- Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, 03080, Korea
| | - Soon-Gook Hong
- Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA
- Department of Medicine, Division of Cardiology, UCLA, Los Angeles, CA, USA
| | | | - Alessandra Ferrari
- Department of Pathology and Laboratory Medicine, University of California, Los Angeles (UCLA); Los Angeles, CA 90095, USA
- Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA
| | - Lauri Vanharanta
- Department of Anatomy and Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland
- Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland
| | - Alexander Nguyen
- Department of Pathology and Laboratory Medicine, University of California, Los Angeles (UCLA); Los Angeles, CA 90095, USA
- Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Rohith T. Nagari
- Department of Pathology and Laboratory Medicine, University of California, Los Angeles (UCLA); Los Angeles, CA 90095, USA
- Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA
| | - Nikolas R. Burton
- Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA
- Department of Chemistry and Biochemistry, UCLA, Los Angeles, California 90095, United States
| | - Marcus J. Tol
- Department of Pathology and Laboratory Medicine, University of California, Los Angeles (UCLA); Los Angeles, CA 90095, USA
- Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA
| | - Andrew P. Becker
- Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA
| | - Min Jae Lee
- Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, 03080, Korea
| | - Elina Ikonen
- Department of Anatomy and Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland
- Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland
| | - Keriann M. Backus
- Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA
- Department of Chemistry and Biochemistry, UCLA, Los Angeles, California 90095, United States
- DOE Institute for Genomics and Proteomics, UCLA, Los Angeles, California 90095, United States
- Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095, United States
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, California 90095, United States
| | - Julia J. Mack
- Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA
- Department of Medicine, Division of Cardiology, UCLA, Los Angeles, CA, USA
| | - Peter Tontonoz
- Department of Pathology and Laboratory Medicine, University of California, Los Angeles (UCLA); Los Angeles, CA 90095, USA
- Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA
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Yu MH, Zhang RJZ, Yu XY, Shi JW, Liu ZG. Association of LDL to HDL ratio with new-onset atrial fibrillation after on-pump coronary artery bypass graft surgery. BMC Cardiovasc Disord 2022; 22:564. [PMID: 36564701 PMCID: PMC9783402 DOI: 10.1186/s12872-022-03016-7] [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: 06/18/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE This study aims to analyze the association between preoperative LDL/HDL ratio and new-onset atrial fibrillation (AF) after on-pump coronary artery bypass grafting (on-pump CABG), evaluate the clinic value of preoperative LDL/HDL ratio to identify postoperative rhythm. METHODS A retrospective study of consecutive patients (n = 2052) who underwent on-pump CABG at TEDA International Cardiovascular Hospital (Tianjin, China), from June 1, 2020, to December 30, 2021, was conducted. The association between preoperative LDL/HDL and new-onset POAF was analyzed by Lowess curve and univariate logistic regression. The receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the identification capacity of preoperative LDL/HDL level for new-onset POAF. RESULTS In studied populations, the incidence of new-onset POAF was about 29.24%. The lowess curve showed that the association between preoperative LDL/HDL ratio and POAF after on-pump CABG was similar to a linear relationship. With the increasement of preoperative LDL/HDL ratio, the incidence of POAF increased simultaneously. ROC analysis showed that preoperative LDL/HDL ratio could identify postoperative arrhythmia after on-pump CABG (AUC = 0.569,95% CI = 0.529-0.608, P = 0.006) among female patients, the best preoperative LDL/HDL ratio cutoff of 2.11, which was considered a predictive factor of incident POAF, showed a sensitivity of 83.60% (95% CI = 0.775-0.886) and a specificity of 30.02% (95% CI = 0.257-0.346). CONCLUSION Preoperative LDL/HDL ratio is associated with new-onset POAF, but there is a difference in different sex. Preoperative LDL/HDL level can help to identify postoperative rhythm in females.
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Affiliation(s)
- Ming-Huan Yu
- grid.478012.8Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Graduate School of Peking Union Medical College, 61, Third Avenue, TEDA, Tianjin, China
| | - Ren-Jian-Zhi Zhang
- grid.478012.8Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Graduate School of Peking Union Medical College, 61, Third Avenue, TEDA, Tianjin, China
| | - Xin-Yi Yu
- grid.478012.8Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Graduate School of Peking Union Medical College, 61, Third Avenue, TEDA, Tianjin, China
| | - Jian-Wei Shi
- grid.478012.8Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Graduate School of Peking Union Medical College, 61, Third Avenue, TEDA, Tianjin, China
| | - Zhi-Gang Liu
- grid.478012.8Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences and Graduate School of Peking Union Medical College, 61, Third Avenue, TEDA, Tianjin, China
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3
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Yoshimura H, Yoshikawa Y, Noguchi Y, Totani T, Kusuta R, Shimazu K, Tanaka A, Komura K. The fluctuation of skin perfusion pressure in hemodialysis patients treated with
LDL
apheresis therapy: A comparison of
LDL
adsorption and double filtration plasmapheresis. J Clin Apher 2022. [DOI: 10.1002/jca.22029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 10/01/2022] [Accepted: 10/27/2022] [Indexed: 11/13/2022]
Affiliation(s)
- Hitoshi Yoshimura
- Department of Clinical Engineering Osaka Saiseikai Nakatsu Hospital Osaka Japan
| | - Yuki Yoshikawa
- Department of Urology Osaka Medical and Pharmaceutical University Osaka Japan
| | - Yuki Noguchi
- Department of Clinical Engineering Osaka Saiseikai Nakatsu Hospital Osaka Japan
| | - Teruhiko Totani
- Department of Clinical Engineering Osaka Saiseikai Nakatsu Hospital Osaka Japan
| | - Risa Kusuta
- Department of Nephrology Osaka Saiseikai Nakatsu Hospital Osaka Japan
| | - Keiji Shimazu
- Department of Nephrology Osaka Saiseikai Nakatsu Hospital Osaka Japan
| | - Atsuo Tanaka
- Department of Nephrology Osaka Saiseikai Nakatsu Hospital Osaka Japan
| | - Kazumasa Komura
- Department of Urology Osaka Medical and Pharmaceutical University Osaka Japan
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Kuno T, So M, Iwagami M, Takahashi M, Egorova NN. The association of statins use with survival of patients with COVID-19. J Cardiol 2021; 79:494-500. [PMID: 34974938 PMCID: PMC8692086 DOI: 10.1016/j.jjcc.2021.12.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 11/16/2021] [Accepted: 12/02/2021] [Indexed: 12/19/2022]
Abstract
Background Statins are frequently prescribed for patients with dyslipidemia and diabetes mellitus. These comorbidities are highly prevalent in coronavirus disease 2019 (COVID-19) patients. Statin's beneficial effect on mortality in COVID-19 infection has been reported in several studies. However, these findings are still inconclusive. Methods We conducted a retrospective observational study among 6,095 patients with laboratory confirmed COVID-19 hospitalized in Mount Sinai Health System between March 1st 2020 and May 7th 2020. Patients were stratified into two groups: statin use prior to or during hospitalization (N = 2,423) versus no statins (N = 3,672). We evaluated in-hospital mortality as a primary outcome using propensity score matching and inverse probability treatment weighted (IPTW) analysis. In additional analysis, we compared continuous use of statins (N = 1,108) with no statins, continuous use of statins with discontinuation of statins (N = 644), and discontinuation of statins with no statins. Results Among 6,095 COVID-19 patients, statin use prior to or during hospitalization group were older (70.8 ± 12.7 years versus 59.2 ± 18.2 years, p<0.001) and had more comorbidities compared to no statins group. After matching by propensity score (1,790 pairs), there were no significant differences in-hospital mortality between patients with statins and those without [28.9% versus 31.0%, p = 0.19, odds ratio (OR) 95% confidence interval (CI): 0.91 (0.79–1.05)]. This result was confirmed by IPTW analysis [OR (95% CI): 0.96 (0.81–1.12), p = 0.53]. In the additional analysis comparing continuous use of statins with no statins group, in-hospital mortality was significantly lower in continuous use of statins compared to no statins group [26.3% versus 34.5%, p<0.001, OR (95% CI): 0.68 (0.55–0.82)] after matching by propensity score (944 pairs), as well as IPTW analysis [OR (95% CI): 0.77 (0.64–0.94), p = 0.009]. Finally, comparison of continuous use of statins with discontinuation of statins showed lower in-hospital mortality in continuous use of statins group [27.9% versus 42.1%, p<0.001, OR (95% CI): 0.53 (0.41–0.68)]. Conclusions Use of statins prior to or during hospitalization was not associated with a decreased risk of in-hospital mortality, however, continuous use of statins was associated with lower in-hospital mortality compared to no statin use and discontinuation of statins.
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Affiliation(s)
- Toshiki Kuno
- Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, NY, USA; Department of Cardiology, Montefiore Medical Center, Albert Einstein Medical College, New York, NY, USA.
| | - Matsuo So
- Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, NY, USA
| | - Masao Iwagami
- Department of Health Services Research, University of Tsukuba, Ibaraki, Japan
| | - Mai Takahashi
- Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, NY, USA
| | - Natalia N Egorova
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, NY, USA
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5
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Izar MCDO, Giraldez VZR, Bertolami A, Santos Filho RDD, Lottenberg AM, Assad MHV, Saraiva JFK, Chacra APM, Martinez TLR, Bahia LR, Fonseca FAH, Faludi AA, Sposito AC, Chagas ACP, Jannes CE, Amaral CK, Araújo DBD, Cintra DE, Coutinho EDR, Cesena F, Xavier HT, Mota ICP, Giuliano IDCB, Faria Neto JR, Kato JT, Bertolami MC, Miname MH, Castelo MHCG, Lavrador MSF, Machado RM, Souza PGD, Alves RJ, Machado VA, Salgado Filho W. Update of the Brazilian Guideline for Familial Hypercholesterolemia - 2021. Arq Bras Cardiol 2021; 117:782-844. [PMID: 34709306 PMCID: PMC8528358 DOI: 10.36660/abc.20210788] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
| | - Viviane Zorzanelli Rocha Giraldez
- Instituto do Coração (InCor) da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP - Brasil
- Grupo Fleury, São Paulo, SP - Brasil
| | | | | | - Ana Maria Lottenberg
- Hospital Israelita Albert Einstein (HIAE) - Faculdade Israelita de Ciências da Saúde Albert Einstein (FICSAE), São Paulo, SP - Brasil
- Faculdade de Medicina da Universidade de São Paulo, Laboratório de Lípides (LIM10), São Paulo, São Paulo, SP - Brasil
| | | | | | - Ana Paula M Chacra
- Instituto do Coração (InCor) da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP - Brasil
| | | | | | | | | | - Andrei C Sposito
- Universidade Estadual de Campinas (UNICAMP), Campinas, SP - Brasil
| | | | - Cinthia Elim Jannes
- Instituto do Coração (InCor) da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP - Brasil
| | | | | | | | | | - Fernando Cesena
- Hospital Israelita Albert Einstein (HIAE), São Paulo, SP - Brasil
| | | | | | | | | | | | | | - Marcio Hiroshi Miname
- Instituto do Coração (InCor) da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP - Brasil
| | - Maria Helane Costa Gurgel Castelo
- Universidade Federal do Ceará (UFC), Fortaleza, CE - Brasil
- Hospital do Coração de Messejana, Fortaleza, CE - Brasil
- Professora da Faculdade Unichristus, Fortaleza, CE - Brasil
| | - Maria Sílvia Ferrari Lavrador
- Hospital Israelita Albert Einstein (HIAE) - Faculdade Israelita de Ciências da Saúde Albert Einstein (FICSAE), São Paulo, SP - Brasil
| | - Roberta Marcondes Machado
- Faculdade de Medicina da Universidade de São Paulo, Laboratório de Lípides (LIM10), São Paulo, São Paulo, SP - Brasil
| | - Patrícia Guedes de Souza
- Hospital Universitário Professor Edgard Santos da Universidade Federal da Bahia (UFBA), Salvador, BA - Brasil
| | | | | | - Wilson Salgado Filho
- Instituto do Coração (InCor) da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP - Brasil
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Ishiyama K, Sato T. Efficacy of LDL apheresis for the treatment of cholesterol crystal embolism: A prospective, controlled study. Ther Apher Dial 2021; 26:456-464. [PMID: 34216189 DOI: 10.1111/1744-9987.13706] [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: 02/21/2021] [Revised: 06/24/2021] [Accepted: 07/01/2021] [Indexed: 11/29/2022]
Abstract
This study was performed to evaluate the efficacy and safety of LDL apheresis (LDL-A) for the treatment of cholesterol crystal embolism (CCE) after cardiovascular procedures. We conducted a prospective multicenter study of 34 patients with CCE and 15 historical control patients. The present participants underwent six sessions of LDL-A for 4 weeks and underwent medical therapy with corticosteroids and statins. The mean creatinine concentration and estimated glomerular filtration rate at baseline were 3.82 ± 2.29 mg/dL and 17.8 ± 9.9 mL/min/1.73 m2 , respectively. The prevalence of maintenance dialysis at 24 weeks was significantly lower in the present participants than in the historical controls (3.1% vs. 40.0%, respectively; p < 0.0001), but the mortality rate at 24 weeks was comparable (19% vs. 33%, respectively). Although 45 adverse events occurred in 23 participants, there were no unexpected adverse events. LDL-A for CCE reduces the prevalence of maintenance dialysis 24 weeks later and is well tolerated. This study was registered in the Japan Registry of Clinical Trials (jRCTs022180029) and clinicaltrials.gov (NCT01726868).
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Affiliation(s)
- Katsuya Ishiyama
- Department of Nephrology, Japan Community Health Care Organization Sendai Hospital, Sendai, Miyagi, Japan.,Department of Comprehensive Medicine for Kidney Disease-related Disorders, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.,Faculty of Medicines, Division of Nephrology and Endocrinology, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan
| | - Toshinobu Sato
- Department of Nephrology, Japan Community Health Care Organization Sendai Hospital, Sendai, Miyagi, Japan.,Department of Comprehensive Medicine for Kidney Disease-related Disorders, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
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Management Considerations for Lipid Disorders During Pregnancy. CURRENT TREATMENT OPTIONS IN CARDIOVASCULAR MEDICINE 2021. [DOI: 10.1007/s11936-021-00926-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Seo WW, Jo SH, Kim SE, Han SH, Lee KY, Her SH, Lee MH, Cho SS, Baek SH. Clinical impact of statin therapy on vasospastic angina: data from a Korea nation-wide cohort study. Heart Vessels 2020; 35:1051-1059. [PMID: 32152732 DOI: 10.1007/s00380-020-01579-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Accepted: 02/28/2020] [Indexed: 12/18/2022]
Abstract
The effect of statin therapy on reducing adverse cardiovascular events in vasospastic angina (VSA) has been inconsistent. Therefore, we investigated the association between statin therapy and adverse cardiovascular events in a large, prospective VSA cohort. The Variant Angina Korea registry consecutively enrolled 2960 patients suspected VSA. Among them, we included 1713 patients who were diagnosed with VSA based on coronary provocation test. We divided the patients into the statin (n = 744) and no-statin group (n = 914) according to the medication prescribed at discharge. The primary outcome was a composite of cardiac death, acute coronary syndrome, and new-onset life-threatening arrhythmia during a 3-year follow-up period. The primary outcome occurred in 32 patients (4.3%) in the statin and 28 patients (3.1%) in the no-statin group. In Kaplan-Meier analysis before and after propensity score matching, there was no significant difference in the cumulative incidence of primary outcomes between both groups. Multivariate Cox regression analysis demonstrated that the focal type of VSA was independent predictor of primary outcomes, but statin therapy was not. Furthermore, the lack of benefit of statin therapy for primary outcomes was consistently observed across the statin intensity and spasm characteristics. In conclusion, the present study demonstrated that statin therapy did not reduce adverse cardiovascular events in patients with VSA.
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Affiliation(s)
- Won-Woo Seo
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
| | - Sang-Ho Jo
- Division of Cardiology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, 896, Pyeongchon-dong, Dongan-gu, Anyang-si, Gyeonggi-do, 431-070, South Korea.
| | - Sung Eun Kim
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
| | - Seung Hwan Han
- Department of Cardiovascular Medicine, Gil Medical Center, Gachon University, Incheon, South Korea
| | - Kwan Yong Lee
- Department of Cardiovascular Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, South Korea
| | - Sung Ho Her
- Department of Cardiovascular Medicine, Daejeon St. Mary's Hospital, The Catholic University of Korea, Daejeon, South Korea
| | - Min-Ho Lee
- Department of Cardiovascular Medicine, Soon Chun Hyang Seoul Hospital, Seoul, South Korea
| | - Sung Seek Cho
- Department of Epidemiology and Occupational Medicine, College of Medicine, Dong-A University, Busan, South Korea
| | - Sang Hong Baek
- Department of Cardiovascular Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
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Park JW, Matschke K, Mrowietz C, Krüger-Genge A, Jung F. HELP-(Heparin-induced Extracorporeal LDL Precipitation)-apheresis in heart recipients with cardiac allograft vasculopathy and concomitant hypercholesterolemia: Influence of long-term treatment on the microcirculation. Clin Hemorheol Microcirc 2020; 73:19-27. [PMID: 31561344 DOI: 10.3233/ch-199216] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Hyperlipidemic heart transplant patients who develop cardiac allograft vasculopathy (CAV) benefit from HELP-apheresis (Heparin-induced Extracorporeal LDL Precipitation) which enables drastic lowering of plasma low-density lipoprotein, lipoprotein (a), and fibrinogen. There is evidence that HELP-apheresis also improves microcirculation by an immediate improvement of impaired endothelial-dependent vasodilatation and additive hemorheological effects.Therefore, cutaneous microcirculation was examined before, during, and after the first HELP-apheresis in eight hyperlipidemic cardiac transplant recipients with CAV. To study the long-term effect the intravital microscopy was repeated after three and 12 months of weekly apheresis treatment.In CAV patients the baseline mean erythrocyte velocity was pathologically reduced with 0.13±0.07 mm/s. During the first HELP-apheresis the erythrocyte velocity increased significantly (p = 0.0001) and remained increased until the end of the HELP procedure (p < 0.05). After three months of weekly apheresis treatment a decrease of temporary flow stops in the capillaries with a progressive homogenization (concordance) of the cutaneous microcirculation was observed. After one year of weekly treatment a markedly increase in mean erythrocyte velocity under resting conditions occurred. In addition, a reactive post-ischemic hyperemia could be established for the first time.Even the first single HELP-apheresis resulted in a significant improvement of the cutaneous microcirculation. The long-term treatment of these patients resulted in a marked improvement of the cutaneous microcirculation with the tendency to a normalization of the regulation of the capillary perfusion.
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Affiliation(s)
- J W Park
- Division of Cardiology, Dietrich Bonhoeffer Hospital, Academic Teaching Hospital of University of Greifswald, Germany
| | - K Matschke
- Heart Center Dresden, Technical University Dresden, Dresden, Germany
| | - C Mrowietz
- Institute for Animal Hygiene, Animal Welfare and Farm Animal Behavior, Virtual Center for Replacement - Complementary Methods to Animal Testing, University of Veterinary Medicine Hannover, Hannover, Germany
| | - A Krüger-Genge
- Fraunhofer Institute for Applied Polymer Research (IAP), Germany
| | - F Jung
- Institute of Biotechnology, Brandenburgische Technische Universität Cottbus-Senftenberg, Senftenberg, Germany
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10
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Contini C, Pütz G, Pecks U, Winkler K. Apheresis as emerging treatment option in severe early onset preeclampsia. ATHEROSCLEROSIS SUPP 2019; 40:61-67. [PMID: 31818451 DOI: 10.1016/j.atherosclerosissup.2019.08.028] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Based on an early suggestion by Winkler et al. 2003 and a subsequent successful study by Wang et al. 2006 using lipid apheresis (LA) in 9 patients with preeclampsia to prolong pregnancies, the use of apheresis as therapeutic option in severe early onset preeclampsia has received increasing attention. Further studies using different LA systems also prolonged pregnancy and have been published in the last few years. Albeit using different LA systems and relying on different working hypothesis, all studies demonstrated a promising stabilisation against the disease's progression. Overall time from hospitalisation to the need for mandatory delivery was longer for those patients receiving apheresis compared to historical or matched control patients not receiving apheresis. These data will be reviewed and different hypotheses about the beneficial mechanism of action of apheresis will be discussed. Since up to now there is no curative treatment for preeclampsia other than observation and delivery, future work shall be encouraged.
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Affiliation(s)
- Christine Contini
- Institute of Clinical Chemistry and Laboratory Medicine, Medical Center - University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Germany.
| | - Gerhard Pütz
- Institute of Clinical Chemistry and Laboratory Medicine, Medical Center - University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Germany
| | - Ulrich Pecks
- Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Arnold-Heller-Straße 3, 24105, Kiel, Germany
| | - Karl Winkler
- Institute of Clinical Chemistry and Laboratory Medicine, Medical Center - University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Germany
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11
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Li L, Wang S, Huang H, Cai Y, Xi Y, Bai Y, Ma C. Effects of Rosuvastatin and Aspirin on Retinal Vascular Structures in Hypercholesterolemic Patients with Low-to-Moderate Risk of Coronary Artery Disease. Am J Cardiovasc Drugs 2019; 19:415-420. [PMID: 30793259 DOI: 10.1007/s40256-019-00330-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
INTRODUCTION Atherosclerosis erodes large elastic arteries and damages peripheral small vessels. Evaluating retinal vessel caliber enables exploration of the effect of improving microcirculation with statins. OBJECTIVE We investigated whether rosuvastatin therapy improves retinal vasculature in hypercholesterolemic patients with a low-to-moderate risk of coronary artery disease (CAD). METHODS This was a prospective, open-label, randomized study in which 127 patients were enrolled and randomized (ratio 1:1) into rosuvastatin and control groups. RESULTS Rosuvastatin increased retinal arteriolar calibers by 3.560 µm at 12 months, decreased retinal venular calibers by 3.110 µm at 6 months and by 5.860 µm at 12 months, and increased the artery-vein ratio (AVR) by 2.68% at 6 months and by 5.90% at 12 months. Meanwhile, in the control group, retinal arteriolar calibers decreased by 1.110 µm at 12 months, retinal venular calibers increased by 1.020 µm at 6 months and by 1.04 µm at 12 months, and AVR decreased by 1.12% at 6 months and by 1.73% at 12 months. All the above parameters were statistically significant between groups, but there was no significant change in retinal arteriolar calibers at 6 months. The increased AVR correlated significantly with decreased C-reactive protein (CRP) at 6 months and decreased low-density lipoprotein and CRP at 12 months. DISCUSSION For patients with a low-to-moderate risk of CAD, we found a significant effect of rosuvastatin on retinal microvasculature, including AVR increase, venular constriction, and arteriolar dilation after 6-12 months of treatment. CLINICAL TRIAL REGISTRATION Chinese Clinical Trial Registry identifier number ChiCTR-IOR-15006664.
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Affiliation(s)
- Li Li
- Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University, No.1, Dong Jiao Min Xiang, Dong Cheng District, Beijing, 100730, China.
| | - Shuang Wang
- Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Key Laboratory of Ophthalmology and Visual Scienses, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Huilian Huang
- Department of Diagnostic Ultrasound, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Yi Cai
- Department of Ophthalmology, People's Eye Institute, Peking University People's Hospital, Beijing, China
| | - Yutao Xi
- Texas Heart Institute, Texas Medical Center, Houston, TX, USA
| | - Ying Bai
- Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University, No.1, Dong Jiao Min Xiang, Dong Cheng District, Beijing, 100730, China
| | - Changsheng Ma
- Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University, No.1, Dong Jiao Min Xiang, Dong Cheng District, Beijing, 100730, China.
- Cardiology Department, Atrial Fibrillation Center, Beijing An Zhen Hospital, Capital Medical University, An Ding Men Wai, An Zhen Li, Chao Yang District, Beijing, 100029, China.
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Caiati C. Contrast-Enhanced Ultrasound Reveals That Lipoprotein Apheresis Improves Myocardial But Not Skeletal Muscle Perfusion. JACC Cardiovasc Imaging 2019; 12:1441-1443. [PMID: 30553683 DOI: 10.1016/j.jcmg.2018.06.029] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 06/12/2018] [Accepted: 06/21/2018] [Indexed: 11/28/2022]
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Cozma A, Fodor A, Orasan OH, Vulturar R, Samplelean D, Negrean V, Muresan C, Suharoschi R, Sitar-Taut A. Pharmacogenetic Implications of eNOS Polymorphisms ( Glu298Asp, T786C, 4b/4a) in Cardiovascular Drug Therapy. In Vivo 2019; 33:1051-1058. [PMID: 31280192 PMCID: PMC6689342 DOI: 10.21873/invivo.11573] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 06/09/2019] [Accepted: 06/19/2019] [Indexed: 12/17/2022]
Abstract
Endothelial nitric oxide synthase (NOS3 or eNOS) is the enzyme responsible for the highest production of nitric oxide, with the greatest impact on the cardiovascular system, encoded by the eNOS gene, which presents various polymorphisms. ENOS gene polymorphisms play an important role in the response to drugs affecting nitric oxide (NO) signaling. This review discusses the pharmacogenetic impact of eNOS polymorphisms on the response to drugs affecting NO activity: angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, calcium blockers, beta-blockers, diuretics, phosphodiesterase inhibitors, and statins. The identification of biomarkers that accurately predict particular phenotypes is a challenge that needs additional large studies, in different populations. Efforts should be oriented towards a more accurate evaluation of the effects of eNOS genetic variants on biochemical parameters reflecting eNOS gene expression and enzymatic activity, in different diseases, as well as following drug treatment. This approach will allow for a better understanding of the role of eNOS genetic variants in cardiovascular disease progression and for cardiovascular drug therapy optimization.
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Affiliation(s)
- Angela Cozma
- University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
- 4th Internal Medicine Department, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
| | - Adriana Fodor
- University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
- Clinical Center of Diabetes, Nutrition and Metabolic Disease, Cluj-Napoca, Romania
| | - Olga Hilda Orasan
- University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
- 4th Internal Medicine Department, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
| | - Romana Vulturar
- University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
- Department of Cell Biology, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
| | - Dorel Samplelean
- University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
- 4th Internal Medicine Department, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
| | - Vasile Negrean
- University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
- 4th Internal Medicine Department, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
| | - Crina Muresan
- University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, Faculty of Food Science &Technology, Cluj-Napoca, Romania
| | - Ramona Suharoschi
- University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, Faculty of Food Science &Technology, Cluj-Napoca, Romania
| | - Adela Sitar-Taut
- University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
- 4th Internal Medicine Department, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
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Makino H, Koezuka R, Tamanaha T, Ogura M, Matsuki K, Hosoda K, Harada-Shiba M. Familial Hypercholesterolemia and Lipoprotein Apheresis. J Atheroscler Thromb 2019; 26:679-687. [PMID: 31231083 PMCID: PMC6711846 DOI: 10.5551/jat.rv17033] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Lipoprotein apheresis has been developed as the treatment for refractory familial hypercholesterolemia (FH) to remove low-density lipoprotein (LDL), which is the main pathogenic factor. Currently, three procedures are available in Japan, including the plasma exchange, double-membrane filtration, and selective LDL adsorption. Selective LDL adsorption, which was developed in Japan, has been one of the most common treatment methods in the world. Lipoprotein apheresis enabled the prevention of atherosclerosis progression even in homozygous FH (HoFH) patients. However, in our observational study, HoFH patients who started lipoprotein apheresis in adulthood had a poorer prognosis than those who started in childhood. Therefore, HoFH patients need to start lipoprotein apheresis as early as possible. Although the indication for lipoprotein apheresis in heterozygous FH (HeFH) patients has been decreasing with the advent of strong statins, our observational study showed that HeFH patients who discontinued lipoprotein apheresis had a poorer prognosis than patients who continued apheresis therapy. These results suggest that it is beneficial for very-high-risk HeFH patients to be treated by lipoprotein apheresis even if their LDL cholesterol is controlled well by lipid-lowering agents. Since launching a new class of lipid-lowering agents, proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody and microsome triglyceride transfer protein inhibitors, the indication for lipoprotein apheresis in FH has been changing. However, despite the development of these drugs, lipoprotein apheresis is still an option with a high therapeutic effect for FH patients with severe atherosclerotic cardiovascular disease.
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Affiliation(s)
- Hisashi Makino
- Department of Diabetes and Lipid Metabolism, National Cerebral and Cardiovascular Center
| | - Ryo Koezuka
- Department of Diabetes and Lipid Metabolism, National Cerebral and Cardiovascular Center
| | - Tamiko Tamanaha
- Department of Diabetes and Lipid Metabolism, National Cerebral and Cardiovascular Center
| | - Masatsune Ogura
- Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute
| | - Kota Matsuki
- Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute
| | - Kiminori Hosoda
- Department of Diabetes and Lipid Metabolism, National Cerebral and Cardiovascular Center
| | - Mariko Harada-Shiba
- Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute
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Scicchitano P, Cortese F, Gesualdo M, De Palo M, Massari F, Giordano P, Ciccone MM. The role of endothelial dysfunction and oxidative stress in cerebrovascular diseases. Free Radic Res 2019; 53:579-595. [PMID: 31106620 DOI: 10.1080/10715762.2019.1620939] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 05/11/2019] [Accepted: 05/13/2019] [Indexed: 01/02/2023]
Abstract
Cerebrovascular diseases (CBD) are one of the most dangerous complications of atherosclerosis. The clinical consequences of CBD deeply impact quality of life and the prognosis of patients. Atherosclerosis is the main cause of CBD development. Hypertension, dyslipidemia, diabetes, smoking, obesity, and other risk factors explain the higher CBD incidence in the general population, as they are able to anticipate the clinical expression of atherosclerosis. These risk factors are effectively able to promote endothelial dysfunction which is the premise for the early, clinical expression of atherosclerosis. The mechanisms by which risk factors can influence the occurrence of CBD are different and not fully understood. The inflammatory background of atherosclerosis can explain a great part of it. In particular, the oxidative stress may promote the development of vascular lesions by negatively influencing biochemical cellular processes of the endothelium, thus predisposing the vascular tree to morphological and functional damages. The aim of this narrative review is to evaluate the role of endothelial dysfunction and oxidative stress in CBD development.
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Affiliation(s)
- Pietro Scicchitano
- a Department of Cardiology , Hospital "F. Perinei" , Altamura , Italy
- b Section of Cardiovascular Diseases, Department of Emergency and Organ Transplantation, School of Medicine , University of Bari , Bari , Italy
| | - Francesca Cortese
- b Section of Cardiovascular Diseases, Department of Emergency and Organ Transplantation, School of Medicine , University of Bari , Bari , Italy
| | - Michele Gesualdo
- c Department of Cardiology , Castellaneta Hospital , Taranto , Italy
| | - Micaela De Palo
- d Department of Cardiac Surgery , Mater Dei Hospital , Bari , Italy
| | - Francesco Massari
- a Department of Cardiology , Hospital "F. Perinei" , Altamura , Italy
| | - Paola Giordano
- e Department of Biomedical Sciences and Human Oncology - Paediatric Unit , Policlinico Hospital , Bari , Italy
| | - Marco Matteo Ciccone
- b Section of Cardiovascular Diseases, Department of Emergency and Organ Transplantation, School of Medicine , University of Bari , Bari , Italy
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16
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Jones PJH, Shamloo M, MacKay DS, Rideout TC, Myrie SB, Plat J, Roullet JB, Baer DJ, Calkins KL, Davis HR, Barton Duell P, Ginsberg H, Gylling H, Jenkins D, Lütjohann D, Moghadasian M, Moreau RA, Mymin D, Ostlund RE, Ras RT, Ochoa Reparaz J, Trautwein EA, Turley S, Vanmierlo T, Weingärtner O. Progress and perspectives in plant sterol and plant stanol research. Nutr Rev 2018; 76:725-746. [PMID: 30101294 PMCID: PMC6130982 DOI: 10.1093/nutrit/nuy032] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Current evidence indicates that foods with added plant sterols or stanols can lower serum levels of low-density lipoprotein cholesterol. This review summarizes the recent findings and deliberations of 31 experts in the field who participated in a scientific meeting in Winnipeg, Canada, on the health effects of plant sterols and stanols. Participants discussed issues including, but not limited to, the health benefits of plant sterols and stanols beyond cholesterol lowering, the role of plant sterols and stanols as adjuncts to diet and drugs, and the challenges involved in measuring plant sterols and stanols in biological samples. Variations in interindividual responses to plant sterols and stanols, as well as the personalization of lipid-lowering therapies, were addressed. Finally, the clinical aspects and treatment of sitosterolemia were reviewed. Although plant sterols and stanols continue to offer an efficacious and convenient dietary approach to cholesterol management, long-term clinical trials investigating the endpoints of cardiovascular disease are still lacking.
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Affiliation(s)
- Peter J H Jones
- Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Maryam Shamloo
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- George and Fay Yee Centre for Healthcare Innovation, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Dylan S MacKay
- George and Fay Yee Centre for Healthcare Innovation, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Todd C Rideout
- Department of Exercise and Nutrition Sciences, University of Buffalo, Buffalo, New York, USA
| | - Semone B Myrie
- Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Jogchum Plat
- Department of Human Biology, Maastricht University, Maastricht, the Netherlands
| | - Jean-Baptiste Roullet
- Division of Metabolism, Child Development and Rehabilitation Center—Portland, Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, USA
| | - David J Baer
- US Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Beltsville, Maryland, USA
| | - Kara L Calkins
- Department of Pediatrics, Division of Neonatology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; and the UCLA Mattel’s Children’s Hospital, Los Angeles, California, USA
| | | | - P Barton Duell
- Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA
| | - Henry Ginsberg
- Institute of Human Nutrition, Columbia University Irving Medical Center, New York, New York, USA
| | - Helena Gylling
- University of Helsinki and the Helsinki University Central Hospital, Helsinki, Finland
| | - David Jenkins
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada; and the Clinical Nutrition and Risk Factor Modification Centre, St. Michael’s Hospital, Toronto, Ontario, Canada
| | - Dieter Lütjohann
- Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany
| | - Mohammad Moghadasian
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Robert A Moreau
- Eastern Regional Research Center, US Department of Agriculture, Agricultural Research Service, Wyndmoor, Pennsylvania, USA
| | - David Mymin
- Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Richard E Ostlund
- Division of Endocrinology, Metabolism and Lipid Research, Washington University, St Louis, USA
| | - Rouyanne T Ras
- Unilever Research & Development Vlaardingen, Vlaardingen, the Netherlands
| | | | - Elke A Trautwein
- Unilever Research & Development Vlaardingen, Vlaardingen, the Netherlands
| | | | - Tim Vanmierlo
- Department of Immunology and Biochemistry, Biomedical Research Institute, Hasselt University, Hasselt, Belgium
| | - Oliver Weingärtner
- Klinik für Innere Medizin I, Universitätsklinikum Jena, Friedrich-Schiller-Universität Jena, Jena, Germany; Abteilung für Kardiologie, Klinikum Oldenburg, European Medical School Oldenburg-Groningen, Oldenburg, Germany
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17
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Mickiewicz A, Borowiec-Wolna J, Bachorski W, Gilis-Malinowska N, Gałąska R, Raczak G, Chmara M, Wasąg B, Jaguszewski MJ, Fijałkowski M, Gruchała M. Long-term lipoprotein apheresis in the treatment of severe familial hypercholesterolemia refractory to high intensity statin therapy: Three year experience at a lipoprotein apheresis centre. Cardiol J 2018; 26:669-679. [PMID: 30234904 DOI: 10.5603/cj.a2018.0100] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 08/22/2018] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Severe familial hypercholesterolemia (FH) individuals, refractory to conventional lipidlowering medications are at exceptionally high risk of cardiovascular events. The established therapeutic option of last choice is lipoprotein apheresis (LA). Herein, it was sought to investigate the clinical usefulness of LA in a highly selected group of severe heterozygous FH (HeFH), as recently described by the International Atherosclerosis Society (IAS), for their efficacy in lipid reduction and safety. METHODS Efficacy and safety of LA were investigated in 318 sessions of 7 severe HeFH females with cardiovascular disease, over a mean period of 26.9 ± 6.5 months. Relative reduction of low density lipoprotein cholesterol (LDL-C) ≥ 60%, clinical complications and vascular access problems were evaluated and compared between the direct adsorption of lipoproteins (DALI) and lipoprotein filtration (Membrane Filtration Optimized Novel Extracorporeal Treatment [MONET]). Additionally, lipoprotein (a) [Lp(a)], total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and fibrinogen concentrations were investigated. RESULTS The relative reduction of LDL-C, TC, TG and Lp(a) were 69.4 ± 12.9%, 59.7 ± 9.1, 51.5 ± ± 14.2% and 71.3 ± 14.4%, respectively. A similar efficacy was found in both systems in LDL-C removal. DALI system led to larger depletions of Lp(a) (80.0 [76-83]% vs. 73.0 [64.7-78.8]%; p < 0.001). The frequency of clinical side effects and vascular access problems were low (8.5%). CONCLUSIONS Long-term LA in severe HeFH individuals is safe and efficiently reduces LDL-C and Lp(a). Higher efficacy of the DALI system than MONET in Lp(a) removal may indicate the need for individualized application of the LA system in severe HeFH individuals.
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Affiliation(s)
| | | | | | | | - Rafał Gałąska
- Department of Cardiology, Medical University of Gdansk, Poland
| | - Grzegorz Raczak
- Department of Cardiology and Electrotherapy Medical University of Gdansk
| | - Magdalena Chmara
- Department of Biology and Genetics, Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, Poland.,Laboratory of Clinical Genetics, University Clinical Centre, Gdansk, Dębinki 7, 80-211 Gdańsk, Poland
| | - Bartosz Wasąg
- Department of Biology and Genetics, Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, Poland
| | | | | | - Marcin Gruchała
- Department of Cardiology, Medical University of Gdansk, Poland
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Sachais BS, Shaz BH. Apheresis to Mitigate Atherosclerotic Vascular Disease. Am J Hypertens 2018; 31:945-949. [PMID: 30016414 DOI: 10.1093/ajh/hpy068] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Accepted: 04/19/2018] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Therapeutic apheresis is a term used to describe a group of treatments where blood components are separated in real time, and one component is removed, exchanged, and/or treated to remove pathogenic substances from the circulation. Plasma exchange, which removed all plasma components, and lipid apheresis which selectively removes lipoproteins from circulation, have both been used to treat atherosclerotic vascular diseases. METHODS To review the literature regarding the application of therapeutic apheresis for atherosclerotic vascular diseases. RESULTS Primarily lipid apheresis is used to treat atherosclerotic vascular diseases, particularly familial hypercholesterolemia, lipoprotein (a) hyperlipoproteinemia and peripheral vascular diseases. Lipid apheresis can be used as first line or second line treatment with a strong evidenced-based recommendation. Its use has decreased atherosclerotic events. CONCLUSION Lipid apheresis is an important therapy for the treatment of familial hypercholesterolemia, lipoprotein (a) hyperlipoproteinemia and peripheral vascular diseases. Lipid apheresis does more than remove low-density lipoproteins and other lipoproteins but also decreases inflammatory markers and improves blood flow.
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Affiliation(s)
| | - Beth H Shaz
- New York Blood Center, New York, New York, USA
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Karadeniz M, Kandemir H, Sarak T, Alp Ç. The prevalence of contrast nephropathy in patients undergoing percutaneous coronary intervention in acute coronary syndrome. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2018. [DOI: 10.32322/jhsm.410522] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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Lipoprotein Apheresis Acutely Reverses Coronary Microvascular Dysfunction in Patients With Severe Hypercholesterolemia. JACC Cardiovasc Imaging 2018; 12:1430-1440. [PMID: 29909101 DOI: 10.1016/j.jcmg.2018.05.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 04/23/2018] [Accepted: 05/01/2018] [Indexed: 01/18/2023]
Abstract
OBJECTIVES This study evaluated whether lipoprotein apheresis produces immediate changes in resting perfusion in subjects with severe hypercholesterolemia, and whether there is a difference in the response between peripheral and coronary microcirculations. BACKGROUND Lipoprotein apheresis is used in patients with severe hypercholesterolemia to reduce plasma levels of low-density lipoprotein cholesterol. METHODS Quantitative contrast-enhanced ultrasound perfusion imaging of the myocardium at rest and skeletal muscle at rest and during calibrated contractile exercise was performed before and immediately after lipoprotein apheresis in 8 subjects with severe hypercholesterolemia, 7 of whom had a diagnosis of familial hypercholesterolemia. Myocardial perfusion imaging was also performed in 14 normal control subjects. Changes in myocardial work and left ventricular function were assessed by echocardiography. Ex vivo ovine coronary and femoral artery ring tension assays were assessed in the presence of pre- and post-apheresis plasma. RESULTS Apheresis acutely decreased low-density lipoprotein cholesterol (234.9 ± 103.2 mg/dl vs. 67.1 ± 49.5 mg/dl; p < 0.01) and oxidized phospholipid on apolipoprotein B-100 (60.2 ± 55.2 nmol/l vs. 47.0 ± 24.5 nmol/l; p = 0.01), and acutely increased resting myocardial perfusion (55.1 [95% confidence interval: 77.2 to 73.1] IU/s vs. 135 [95% confidence interval: 81.2 to 189.6] IU/s; p = 0.01), without changes in myocardial work. Myocardial longitudinal strain improved in those subjects with reduced pre-apheresis function. Skeletal muscle perfusion at rest and during contractile exercise was unchanged by apheresis. Acetylcholine-mediated dilation of ex vivo ovine coronary but not femoral arteries was impaired in pre-apheresis plasma and was completely reversed in post-apheresis plasma. CONCLUSIONS Lipoprotein apheresis produces an immediate improvement in coronary microvascular function, which increases myocardial perfusion and normalizes endothelial-dependent vasodilation. These changes are not observed in the periphery. (Acute Microvascular Changes With LDL Apheresis; NCT02388633).
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Balzan S, Lubrano V. LOX-1 receptor: A potential link in atherosclerosis and cancer. Life Sci 2018; 198:79-86. [PMID: 29462603 DOI: 10.1016/j.lfs.2018.02.024] [Citation(s) in RCA: 103] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 02/07/2018] [Accepted: 02/16/2018] [Indexed: 12/19/2022]
Abstract
Altered production of reactive oxygen species (ROS), causing lipid peroxidation and DNA damage, contributes to the progression of atherosclerosis and cancer. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a lectin-like receptor for oxidized low-density lipoproteins (ox-LDL) primarily expressed in endothelial cells and vasculature-rich organs. LOX-1 receptors is a marker for atherosclerosis, and once activated by ox-LDL or other ligands, stimulates the expression of adhesion molecules, pro-inflammatory signaling pathways and proangiogenic proteins, including NF-kB and VEGF, in vascular endothelial cells and macrophages. Several different types of cancer reported LOX-1 gene upregulation, and numerous interplays exist concerning LOX-1 in atherosclerosis, metabolic diseases and cancer. One of them involves NF-kB, an oncogenic protein that regulates the transcription of several inflammatory genes response. In a model of cellular transformation, the MCF10A ER-Src, inhibition of LOX-1 gene reduces NF-kB activation and the inflammatory and hypoxia pathways, suggesting a mechanistic connection between cellular transformation and atherosclerosis. The remodeling proteins MMP-2 and MMP-9 have been found increased in angiogenesis in atherosclerotic plaque and also in human prostate cancer cells. In this review, we outlined the role of LOX-1 in atherogenesis and tumorigenesis as a potential link in these diseases, suggesting that LOX-1 inhibition could represent a promising strategy in the treatment of atherosclerosis and tumors.
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Affiliation(s)
- Silvana Balzan
- Institute of Clinical Physiology, CNR, Via Moruzzi 1, Pisa 56124, Italy.
| | - Valter Lubrano
- Fondazione CNR/Regione Toscana G. Monasterio, Via Moruzzi 1, Pisa 56124, Italy
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Ramunni A, Giancipoli G, Saracino A, Guerriero S, Saliani MT, Gentile MC, Sborgia C, Coratelli P. LDL-apheresis in Acute Anterior Ischemic Optic Neuropathy. Int J Artif Organs 2018; 27:337-41. [PMID: 15163068 DOI: 10.1177/039139880402700410] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Acute anterior ischemic optic neuropathy (AION) is a disabling disease which impairs visual function. Standard treatment is unable to affect the outcome and the visual damage persists. We describe the case of a 64-year-old patient affected by AION, whose only known risk factor was hypercholesterolemia. After a first onset of involvement of the right eye (RE), the patient presented four weeks later with an analogous episode affecting the left eye (LE). Since standard treatment, started at involvement of the RE, had not yielded any beneficial effect, the patient underwent three sessions of LDL apheresis. The scotomatous portion of the visual field reduced even after the first session, there was further improvement after the third, and after six months the condition remained stable. Corrected vision improved from 2/10 to 6/10 after the third session. LDL cholesterol and fibrinogen decresade after the third session from 239 mg/dL to 31 mg/dL and from 289 mg/dL to 92 mg/dL, respectively. In conclusion, thanks to its effect of antagonizing hemorheologic disorders of the ocular microcirculation, LDL apheresis seems to be an efficacious treatment of AION, especially in patients suffering from hypercholesterolemia.
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Affiliation(s)
- A Ramunni
- Division of Nephrology, Department of Internal and Public Medicine, University of Bari, Bari, Italy.
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Abstract
BACKGROUND Lipoprotein(LP)-apheresis is the treatment of choice in patients suffering from severe familial hypercholesterolemia. A wide range of mechanisms has been claimed to be responsible for the known clinical benefit. METHODS Patients suffering from heterozygous familial hypercholesterolemia undergoing LP-apheresis either with direct adsorption of lipoproteins (DALI) or dextran sulfate (DS) were examined. A total volume of 10 l blood was exchanged. Non-lipid effects, mainly concerning endothelial function (circulating endothelial cells, circulating endothelial progenitor cells, flow-mediated vasodilation, microalbuminuria) as well as left ventricular ejection fraction and homocysteine were assessed. RESULTS A single LP-apheresis session improves paradox contractile response in statin intolerant patients, but not in those on regular statin therapy. In contrast, over a 6-months follow-up after treatment initiation, all the examined parameters (circulating endothelial cells, circulating endothelial progenitor cells, flow mediated vasodilatation, homocysteine, microalbuminuria and left ventricular ejection fraction) improved. When available, a comparison between DS vs. DALI was performed. In none of the subgroups a significant difference was noted. DISCUSSION These findings indicate that beyond the well known lipid/lipoprotein lowering action the broad spectrum of functional tests examined reflecting mainly endothelial function is significantly improved by LP-apheresis treatment on the long-term and seems to be a key underlying reason for the clinical improvement seen in these patients.
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Affiliation(s)
- Helmut Sinzinger
- Institute for Diagnosis and Treatment of Lipid Disorders and Atherosclerosis (ATHOS), Vienna, Austria.
| | - Sabine Steiner
- University of Leipzig, Dept. of Interventional Angiology, Leipzig, Germany
| | - Kurt Derfler
- Medical University of Vienna, Dept. of Internal Medicine III, Nephrology, Vienna, Austria
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25
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Heigl F, Hettich R, Mauch E, Klingel R, Fassbender C. Lipoprotein(a)-hyperlipoproteinemia as cause of chronic spinal cord ischemia resulting in progressive myelopathy - successful treatment with lipoprotein apheresis. Clin Res Cardiol Suppl 2017; 12:50-54. [PMID: 28160245 PMCID: PMC5352773 DOI: 10.1007/s11789-017-0081-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
High concentrations of lipoprotein(a) (Lp(a)) represent an important independent and causal risk factor associated with adverse outcome in atherosclerotic cardiovascular disease (CVD). Effective Lp(a) lowering drug treatment is not available. Lipoprotein apheresis (LA) has been proven to prevent cardiovascular events in patients with Lp(a)-hyperlipoproteinemia (Lp(a)-HLP) and progressive CVD. Here we present the course of a male patient with established peripheral arterial occlusive disease (PAOD) at the early age of 41 and coronary artery disease (CAD), who during follow-up developed over 2 years a progressive syndrome of cerebellar and spinal cord deficits against the background of multifactorial cardiovascular risk including positive family history of CVD. Spastic tetraplegia and dependency on wheel chair and nursing care represented the nadir of neurological deficits. All conventional risk factors including LDL-cholesterol had already been treated and after exclusion of other causes, genetically determined Lp(a)-HLP was considered as the major underlying etiologic factor of ischemic vascular disease in this patient including spinal cord ischemia with vascular myelopathy. Treatment with an intensive regimen of chronic LA over 4.5 years now was successful to stabilize PAOD and CAD and led to very impressive neurologic and overall physical rehabilitation and improvement of quality of life. Measurement of Lp(a) concentration must be recommended to assess individual cardiovascular risk. Extracorporeal clearance of Lp(a) by LA should be considered as treatment option for select patients with progressive Lp(a)-associated ischemic syndromes.
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Affiliation(s)
- Franz Heigl
- Medical Care Center Kempten-Allgäu, Kempten, Germany.
| | | | - Erich Mauch
- Clinic for Neurology Dietenbronn, Academic Hospital of the University of Ulm, Schwendi, Germany
| | - Reinhard Klingel
- Apheresis Research Institute, Cologne, Germany
- 1st Department Internal Medicine, University of Mainz, Mainz, Germany
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26
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Sandhu K, Mamas M, Butler R. Endothelial progenitor cells: Exploring the pleiotropic effects of statins. World J Cardiol 2017; 9:1-13. [PMID: 28163831 PMCID: PMC5253189 DOI: 10.4330/wjc.v9.i1.1] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Revised: 08/29/2016] [Accepted: 11/02/2016] [Indexed: 02/07/2023] Open
Abstract
Statins have become a cornerstone of risk modification for ischaemic heart disease patients. A number of studies have shown that they are effective and safe. However studies have observed an early benefit in terms of a reduction in recurrent infarct and or death after a myocardial infarction, prior to any significant change in lipid profile. Therefore, pleiotropic mechanisms, other than lowering lipid profile alone, must account for this effect. One such proposed pleiotropic mechanism is the ability of statins to augment both number and function of endothelial progenitor cells. The ability to augment repair and maintenance of a functioning endothelium may have profound beneficial effect on vascular repair and potentially a positive impact on clinical outcomes in patients with cardiovascular disease. The following literature review will discuss issues surrounding endothelial progenitor cell (EPC) identification, role in vascular repair, factors affecting EPC numbers, the role of statins in current medical practice and their effects on EPC number.
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27
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Vogt A. The Italian Consensus Conferences on low density lipoprotein-cholesterol apheresis. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2017; 15:1-3. [PMID: 27416572 PMCID: PMC5269421 DOI: 10.2450/2016.0058-16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Anja Vogt
- Medizinische Klinik und Poliklinik IV, Klinikum der Unversitat Munchen, Germany
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28
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Tanaka A, Inaguma D, Watanabe Y, Ito E, Kamegai N, Shimogushi H, Shinjo H, Koike K, Otsuka Y, Takeda A. Two Patients with Familial Hypercholesterolemia Who Were Successfully Weaned from Low-density Lipoprotein Apheresis after Treatment with Evolocumab. Intern Med 2017. [PMID: 28626179 PMCID: PMC5505909 DOI: 10.2169/internalmedicine.56.7958] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Two elderly patients (a 76-year-old man and a 75-year-old woman), who had been previously diagnosed with familial hypercholesterolemia (at 58 and 48 years of age, respectively) underwent long-term treatment with oral therapy and low-density lipoprotein (LDL) apheresis. As their LDL cholesterol levels remained high (>150 mg/dL and >120 mg/dL, respectively) and their familial hypercholesterolemia was complicated with angina pectoris, we added evolocumab to their prescription. Thereafter, their LDL cholesterol levels decreased rapidly, and the patients were successfully weaned from LDL apheresis. Evolocumab therapy should thus be considered when LDL apheresis cannot achieve the target LDL cholesterol levels, though the prognosis of such treatment remains unclear.
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Affiliation(s)
- Akihito Tanaka
- Kidney Disease Center, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Daijo Inaguma
- Kidney Disease Center, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Yu Watanabe
- Kidney Disease Center, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Eri Ito
- Kidney Disease Center, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Naoki Kamegai
- Kidney Disease Center, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Hiroya Shimogushi
- Kidney Disease Center, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Hibiki Shinjo
- Kidney Disease Center, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Kiyomi Koike
- Kidney Disease Center, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Yasuhiro Otsuka
- Kidney Disease Center, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Asami Takeda
- Kidney Disease Center, Japanese Red Cross Nagoya Daini Hospital, Japan
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29
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Chen C, Wei J, AlBadri A, Zarrini P, Bairey Merz CN. Coronary Microvascular Dysfunction - Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy. Circ J 2016; 81:3-11. [PMID: 27904032 PMCID: PMC8607842 DOI: 10.1253/circj.cj-16-1002] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/20/2023]
Abstract
Angina has traditionally been thought to be caused by obstructive coronary artery disease (CAD). However, a substantial number of patients with angina are found to not have obstructive CAD when undergoing coronary angiography. A significant proportion of these patients have coronary microvascular dysfunction (CMD), characterized by heightened sensitivity to vasoconstrictor stimuli and limited microvascular vasodilator capacity. With the advent of non-invasive and invasive techniques, the coronary microvasculature has been more extensively studied in the past 2 decades. CMD has been identified as a cause of cardiac ischemia, in addition to traditional atherosclerotic disease and vasospastic disease. CMD can occur alone or in the presence obstructive CAD. CMD shares many similar risk factors with macrovascular CAD. Diagnosis is achieved through detection of an attenuated response of coronary blood flow in response to vasodilatory agents. Imaging modalities such as cardiovascular magnetic resonance, positron emission tomography, and transthoracic Doppler echocardiography have become more widely used, but have not yet completely replaced the traditional intracoronary vasoreactivity testing. Treatment of CMD starts with lifestyle modification and risk factor control. The use of traditional antianginal, antiatherosclerotic medications and some novel agents may be beneficial; however, clinical trials are needed to assess the efficacy of the pharmacologic and non-pharmacologic therapeutic modalities. In addition, studies with longer-term follow-up are needed to determine the prognostic benefits of these agents. We review the epidemiology, prognosis, pathogenesis, diagnosis, risk factors and current therapies for CMD.
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Affiliation(s)
- Cheng Chen
- Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center
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30
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Fogarty TJ, Arko FR, Zarins CK. Ten Years of Advancements in Interventional Cardiology. J Endovasc Ther 2016; 11 Suppl 2:II192-9. [PMID: 15760266 DOI: 10.1177/15266028040110s604] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The past decade has seen the evolution of an exciting technology that has changed forever the treatment of aortic aneurysmal disease. From rather crude homemade stent-grafts constructed in the surgical suite to elegant commercially manufactured devices in a variety of configurations and sizes, the aortic endograft has experienced a meteoric rise in popularity to become a beneficial, minimally invasive therapy that can obviate the risk of rupture and death. There are now 3 approved endovascular devices on the market for infrarenal abdominal aortic aneurysm repair, and it is likely that additional and improved devices will become available in the future. This review revisits the developmental history of the aortic endograft, noting the ongoing refinements that have arisen from our experiences with the growing population of stent-graft patients. Although research continues to search for solutions to the problems of endoleak and migration, long-term results even with the earlier second and third-generation devices are better than has been achieved with open surgical repair.
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Affiliation(s)
- Thomas J Fogarty
- Division of Vascular Surgery, Stanford University Medical Center, Stanford, California 94305, USA
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31
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Lipoprotein apheresis is essential for managing pregnancies in patients with homozygous familial hypercholesterolemia: Seven case series and discussion. Atherosclerosis 2016; 254:179-183. [DOI: 10.1016/j.atherosclerosis.2016.10.018] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Revised: 10/06/2016] [Accepted: 10/07/2016] [Indexed: 11/21/2022]
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Julius U. Lipoprotein apheresis in the management of severe hypercholesterolemia and of elevation of lipoprotein(a): current perspectives and patient selection. MEDICAL DEVICES-EVIDENCE AND RESEARCH 2016; 9:349-360. [PMID: 27785114 PMCID: PMC5067066 DOI: 10.2147/mder.s98889] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
This review reports the current situation with respect to therapeutic options (lifestyle and drugs) reducing the concentrations of atherogenic low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]). Three lipoprotein apheresis (LA) principles have been realized: precipitation, filtration, and adsorption. Available LA methods are herein described in detail - major components, pumps, extracorporeal volume, treated volume, and anticoagulation. General features of all LA methods as well as pleotropic effects are elaborated. Indications for LA therapy are quoted: homozygous familial hypercholesterolemia (HCH), severe HCH, and isolated elevation of Lp(a) and progress of atherosclerotic disease. A major focus is on the evidence of the effect of LA on cardiovascular outcome data, and the most important publications are cited in this context. The best studies have been performed in patients with elevated Lp(a) in whom cardiovascular events were reduced by more than 80%. Major adverse effects and contraindications are listed. The impact of an LA therapy on patient quality of life and the requirements they have to fulfill are also highlighted. Finally, the future role of LA in treating high-risk patients with high LDL-C and/or high Lp(a) is discussed. It is probable that the significance of LA for treating patients with elevated LDL-C will decrease (with the exception of homozygous familial HCH) due to the application of PCSK9 inhibitors. The antisense oligonucleotide against apolipoprotein(a) could replace LA in patients with high Lp(a), provided positive outcome data are generated.
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Affiliation(s)
- Ulrich Julius
- Lipidology and Center for Extracorporeal Therapy, Department for Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany
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Dementia Improvement after Plasma Exchange for Familial Hypercholesterolemia. Case Rep Neurol Med 2016; 2016:6121878. [PMID: 27672461 PMCID: PMC5031882 DOI: 10.1155/2016/6121878] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 08/21/2016] [Accepted: 08/23/2016] [Indexed: 11/17/2022] Open
Abstract
Worldwide dementia related memory issues affect a great number of patients and families. In this case, a "senior moment" was noted at age fifty and issues with memory and mind progressed resulting in early retirement from work. The patient described here was given a diagnosis of "Pre-Alzheimer's disease" and presented for further accurate evaluation, diagnosis, and management. The medical management resulted in an improvement in the patients memory and cognitive ability.
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34
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Marketou ME, Zacharis EA, Nikitovic D, Ganotakis ES, Parthenakis FI, Maliaraki N, Vardas PE. Early Effects of Simvastatin versus Atorvastatin on Oxidative Stress and Proinflammatory Cytokines in Hyperlipidemic Subjects. Angiology 2016; 57:211-8. [PMID: 16518530 DOI: 10.1177/000331970605700212] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The authors investigated the time-dependent action of atorvastatin and simvastatin on oxidative stress and cytokine levels immediately after the start of treatment. These factors play a role in endothelial dysfunction. Hyperlipidemic patients (n=132) were assigned to treatment with 40 mg atorvastatin, 40 mg simvastatin, or placebo. Blood samples were taken before, 2 hours, 24 hours, 7 days, and 3 weeks after the administration of the statin or placebo to evaluate serum concentrations of total peroxides (TP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and soluble intercellular vascular adhesion molecule 1 (sICAM 1). In the atorvastatin group the TP changes were significantly different at 2 hours and 24 hours (p=0.005), whereas in the simvastatin group there was a gradual, more or less linear decline in TP until 7 days (p=0.006) and then a plateau. Simvastatin exhibited a faster statistically significant decrease over time in IL-6 and sICAM 1 levels (at 7 days, p=0.014 and p=0.001, respectively). TNF-a demonstrated a faster linear trend in the simvastatin group, but the significant effect appeared late (p=0.006). Both simvastatin and atorvastatin exerted early beneficial effects on oxidative stress, proinflammatory cytokines, and endothelial activation in hyperlipidemic subjects. These effects became significant 2 hours following the initiation of therapy.
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Affiliation(s)
- Mary E Marketou
- Department of Cardiology, Heraklion University Hospital, Heraklion, Crete, Greece
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35
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Sanai T, Matsui R, Hirano T. LDL Apheresis for Cholesterol Embolism Following Coronary Artery Bypass Graft Surgery. Angiology 2016; 57:379-82. [PMID: 16703200 DOI: 10.1177/000331970605700316] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
A 76-year-old man without any prior history of abnormal urinalysis findings or renal insufficiency demonstrated mild renal dysfunction after coronary bypass graft surgery (CABG). Two months after CABG, pain and blueness in the toes (blue toe syndrome) appeared and, the serum creatinine level (S-Cr) increased from 1.2 to 2.0 mg/dL. On admission (3 months later), the urinary protein level was 0.5 g/day, white blood cell count 8,300/μL with eosinophils (Eo) 10.5%, S-Cr 2.1 mg/dL, and low-density lipoprotein (LDL) 106 mg/dL. Acute renal failure and blue toe syndrome due to a cholesterol embolism (CE) were diagnosed. Alprostadil 40 μg/day orally for 2 weeks and alprostadil 40 μg/day intravenously were used for 5 weeks, and Eo were 250/μL, S-Cr 2.5 mg/dL; however, blue toe syndrome gradually developed. At 8 weeks after admission, limaprost alfadex 30 μg/day orally was used for 3 weeks. However, the Eo gradually rose to 1,520/μL, S-Cr to 3.0 mg/dL, and LDL to 135 mg/dL, and LDL apheresis was therefore performed 20 times for CE. The data just after LDL apheresis was performed 10 times were as follows: Eo 1,120/μL, S-Cr 4.0 mg/dL, and LDL 89 mg/dL, and blue toe syndrome had disappeared. At 10 months after the first LDL apheresis, the Eo were 630/μL, S-Cr 2.9 mg/dL, and LDL 109 mg/dL. As a result, LDL apheresis was found to be beneficial for the treatment of CE with acute renal failure and blue toe syndrome after CABG.
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Affiliation(s)
- Toru Sanai
- Division of Nephrology, Department of Internal Medicine and Clinical Research Institute, National Kyushu Medical Center, Fukuoka, Japan.
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36
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Abstract
Atheromatous embolization is a multisystem disease complicating advanced atherosclerosis. It occurs most often as a complication of angiography, an endovascular procedure or cardiovascular surgery. Atheromatous embolization can present in a subtle manner where it is often under-recognized, or with catastrophic results including myocardial infarction, strake or acute renal failure. It may mimic other disease processes and often goes underdiagnosed and undertreated. A high clinical suspicion is the key to diagnosis. Atheromatous embolization results in significant morbidity and mortality; therefore, early recognition followed by aggressive management may help to prevent end-organ damage and improve overall clinical outcomes. Management strategies should include risk factor modification, prevention of further insults by discontinuing or avoiding predisposing factors, supportive treatment and interventional or surgical approaches to remove the atheroembolic source. Atheromatous embolization is expected to increase as our population ages and the epidemics of diabetes mellitus and obesity increase.
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Affiliation(s)
- Yin Ping Liew
- Department of Cardiovascular Medicine, Section of Vascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
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37
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Taylan C, Schlune A, Meissner T, Ažukaitis K, Udink Ten Cate FEA, Weber LT. Disease control via intensified lipoprotein apheresis in three siblings with familial hypercholesterolemia. J Clin Lipidol 2016; 10:1303-1310. [PMID: 27919346 DOI: 10.1016/j.jacl.2016.08.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Revised: 06/13/2016] [Accepted: 08/10/2016] [Indexed: 11/25/2022]
Abstract
BACKGROUND Familial hypercholesterolemia (FH), the prevalent monogenic form of hypercholesterolemia, carries the risk of premature coronary heart disease. Lipoprotein-apheresis is established in children with severe dyslipidemia. We present 3 siblings with a negative/negative residual low-density lipoprotein (LDL) receptor mutation (p.Trp577Arg), unresponsive to drug treatment. OBJECTIVE Intensified lipoprotein-apheresis is well tolerated and results in permanently low lipid values without harming the health-related quality of life in children. METHODS Three homozygous FH siblings, aged 7-13 years, had been treated with statins and ezetimibe for 12 months but still showed highly elevated low-density lipoprotein cholesterol (LDL-C) plasma concentrations. They were started on double-filtration plasmapheresis that was subsequently intensified according to plasma lipid levels. RESULTS Each lipoprotein apheresis session reduced LDL-C concentration by 66% to 70%. Treated plasma volume was doubled after 6 months due to a sustained rebound of LDL-C between sessions. However, the rebound remained unchanged. Only an increase in frequency of sessions to every 3 to 4 days resulted in acceptable pre-treatment LDL-C concentrations (Cmax). Neither cessation of statins nor reduction of plasma exchange volume to 1.5 fold in follow-up influenced Cmax. Intensified therapy did not harm health-related quality of life as assessed by PedsQL and was well tolerated. CONCLUSIONS In pediatric FH patients unresponsive to drug treatment, intensified lipoprotein apheresis can normalize plasma lipid levels. Apparently, treatment frequency rather than volume has greater influence on its efficacy. The potential burden of intensified therapy to daily life has to be regarded. Serum lipid levels in FH should be normalized to minimize cardiovascular risk.
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Affiliation(s)
- Christina Taylan
- Pediatric Nephrology, Children's and Adolescents' Hospital, University Hospital of Cologne, Cologne, Germany.
| | - Andrea Schlune
- Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Düsseldorf, Germany
| | - Thomas Meissner
- Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Düsseldorf, Germany
| | - Karolis Ažukaitis
- Pediatric Nephrology, Vilnius University-Hospital, Vilnius, Lithuania
| | - Floris E A Udink Ten Cate
- Department of Pediatric Cardiology, Heart Center Cologne, University Hospital of Cologne, Cologne, Germany
| | - Lutz T Weber
- Pediatric Nephrology, Children's and Adolescents' Hospital, University Hospital of Cologne, Cologne, Germany
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Abstract
Nitric oxide has been implicated in numerous biological processes, particularly those involved with the cardiovascular system. Nitric oxide production is closely regulated and influenced by a number of factors in both health and disease. Nitric oxide is involved in maintaining the vascular system in its healthy, nondiseased state by producing vasorelaxation which enhances blood flow and prevents both leukocyte and platelet adhesion to the vascular wall. Dysfunctional endothelial cell nitric oxide production has been implicated in a number of disease states, including hypertension and atherosclerosis, and has been associated with adverse cardiac events. Various recent therapies may exert their beneficial effects in part by enhancing endothelial nitric oxide bloavallability. Nitric oxide has been used therapeutically in a number of cardiorespiratory disease states. An improved understanding of the pathologic processes underlying these diseases has resulted in several alternative agents being investigated and used clinically.
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Affiliation(s)
- Stuart M. Lowson
- Department of Anesthesiology and Surgical-Trauma ICU Co-Director, University of Virginia, Charlottesville, Virginia
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39
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Habon T, Toth K. Pre-Treatment with Statins for Coronary Intervention: Pleiotropy of Statins or Effect of LDL-cholesterol Reduction? Korean Circ J 2016; 46:468-71. [PMID: 27482254 PMCID: PMC4965424 DOI: 10.4070/kcj.2016.46.4.468] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Accepted: 07/01/2016] [Indexed: 11/11/2022] Open
Affiliation(s)
- Tamas Habon
- 1st Department of Medicine, Division of Cardiology, University of Pecs, Medical Center, Pecs, Hungary
| | - Kalman Toth
- 1st Department of Medicine, Division of Cardiology, University of Pecs, Medical Center, Pecs, Hungary
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40
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Bae JH, Bassenge E, Kim KY, Synn YC, Park KR, Schwemmer M. Effects of Low-Dose Atorvastatin on Vascular Responses in Patients Undergoing Percutaneous Coronary Intervention With Stenting. J Cardiovasc Pharmacol Ther 2016; 9:185-92. [PMID: 15378139 DOI: 10.1177/107424840400900306] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background: The primary endpoint of this study was to evaluate the effects of low-dose atorvastatin on carotid intima-media thickness (IMT) and endothelial function, and the secondary endpoint comprised restenosis and target lesion revascularization (TLR) in patients undergoing percutaneous coronary intervention (PCI) with stenting for the treatment of coronary artery disease. Methods: Two hundred five consecutive patients (mean age, 60 years) undergoing PCI were prospectively randomized to usual therapy (control group, n = 100) or to 10 mg of atorvastatin daily plus usual therapy (statin group, n = 105). Carotid IMT, endothelial function (flow-mediated dilatation [FMD] of the brachial artery), and coronary angiograms were taken before the study and 6 months after randomization. The 6-month follow-up measurements of the above factors were obtained in 83 patients (83%) of the control group and in 97 patients (92%) of the statin group. Results: No significant differences were noted in the baseline clinical and angiographic findings in either group. FMD was significantly improved during the 6 months in the statin group (4.38% ± 1.7% vs 4.85% ± 1.6%, P = .003), but did not change in the control group. Carotid IMT did not show any significant changes at 6 months in either group. There was a trend in favor of statin in terms of restenosis rate (26.8% vs 36.1%, P = .177) and TLR rate (18.6% vs 25.3%, P = .274). The changes of FMD were significantly correlated with the changes of total cholesterol and the changes of low-density lipoprotein, respectively ( r= -0.336, P = .009, and r = -0.310, P = .046). Conclusion: Low-dose atorvastatin reduces endothelial dysfunction as measured by FMD, which coincides with the beneficial effects on lipid profiles, and can decrease restenosis and TLR rate in patients undergoing PCI with stenting.
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Affiliation(s)
- Jang-Ho Bae
- Division of Cardiology, College of Medicine, Konyang University Hospital, Daejeon, South Korea.
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41
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Efficacy of low-density lipoprotein apheresis combined with corticosteroids for cholesterol crystal embolism. Clin Exp Nephrol 2016; 21:228-235. [DOI: 10.1007/s10157-016-1272-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2015] [Accepted: 04/12/2016] [Indexed: 10/21/2022]
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Single Low-Density Lipoprotein Apheresis Does Not Improve Vascular Endothelial Function in Chronically Treated Hypercholesterolemic Patients. Int J Vasc Med 2016; 2016:4613202. [PMID: 26998360 PMCID: PMC4779839 DOI: 10.1155/2016/4613202] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Accepted: 01/28/2016] [Indexed: 11/18/2022] Open
Abstract
Objective. To investigate vascular endothelial function (VEF) responses to a single low-density lipoprotein (LDL) apheresis session in hypercholesterolemic patients undergoing chronic treatment. Methods. We measured brachial artery flow-mediated dilation (FMD), plasma lipids, vitamin E (α- and γ-tocopherol), markers of oxidative/nitrative stress (malondialdehyde (MDA) and nitro-γ-tocopherol (NGT)), and regulators of NO metabolism (arginine (ARG) and asymmetric dimethylarginine (ADMA)) prior to (Pre) and immediately following (Post) LDL apheresis and at 1, 3, 7, and 14 d Post in 5 hypercholesterolemic patients (52 ± 11 y). Results. Relative to Pre, total cholesterol (7.8 ± 1.5 mmol/L) and LDL-cholesterol (6.2 ± 1.2 mmol/L) were 61% and 70% lower (P < 0.01), respectively, at Post and returned to Pre levels at 14 d. Brachial FMD responses (6.9 ± 3.6%) and plasma MDA, ARG, and ADMA concentrations were unaffected by LDL apheresis. Plasma α-tocopherol, γ-tocopherol, and NGT concentrations were 52-69% lower at Post (P < 0.01), and α-tocopherol remained 36% lower at 1 d whereas NGT remained 41% lower at d 3. Conclusions. Acute cholesterol reduction by LDL apheresis does not alter VEF, oxidative stress, or NO homeostasis in patients treated chronically for hypercholesterolemia.
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Ellins EA, New KJ, Datta DBN, Watkins S, Haralambos K, Rees A, Aled Rees D, Halcox JPJ. Validation of a new method for non-invasive assessment of vasomotor function. Eur J Prev Cardiol 2015. [DOI: 10.1177/2047487315597210] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Elizabeth A Ellins
- Institute of Molecular and Experimental Medicine, Cardiff University, UK
- Institute of Life Sciences, Swansea University, UK
| | - Karl J New
- Neurovascular Research Laboratory, University of South Wales, Pontypridd, UK
| | - Dev BN Datta
- Lipid Unit, University Hospital Llandough, Cardiff, UK
| | | | - Kate Haralambos
- Institute of Molecular and Experimental Medicine, Cardiff University, UK
| | - Alan Rees
- University Hospital of Wales, Cardiff, UK
| | - D Aled Rees
- Institute of Molecular and Experimental Medicine, Cardiff University, UK
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Seshadri S, Mroczkowska S, Qin L, Patel S, Ekart A, Gherghel D. Systemic circulatory influences on retinal microvascular function in middle-age individuals with low to moderate cardiovascular risk. Acta Ophthalmol 2015; 93:e266-74. [PMID: 25487686 DOI: 10.1111/aos.12594] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Accepted: 10/06/2014] [Indexed: 12/21/2022]
Abstract
PURPOSE To investigate the relationship between retinal microvascular reactivity, circulatory markers for CVD risk and systemic antioxidative defence capacity in healthy middle-aged individuals with low to moderate risk of CVD. METHODS Retinal vascular reactivity to flickering light was assessed in 102 healthy participants (46-60 years) by means of dynamic retinal vessel analysis (DVA). Other vascular assessments included carotid intima-media thickness (C-IMT) and blood pressure (BP) measurements. Total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and blood glutathione levels in its reduced (GSH) and oxidized (GSSG) forms were also determined for each participant, along with Framingham risk scores (FRS). RESULTS Retinal arterial baseline diameter fluctuation (BDF) was independently, significantly and negatively influenced by LDL-C levels (β = -0.53, p = 0.027). Moreover, the arterial dilation slope (SlopeAD ) was independently, significantly and positively associated with redox index (GSH: GSSG ratio, β = 0.28, p = 0.016), while the arterial constriction slope (SlopeAC ) was significantly and negatively influenced by blood GSH levels (β = -0.20, p = 0.042), and positively associated with FRS (β = 0.25, p = 0.009). Venous BDF and dilation amplitude (DA) were also negatively influenced by plasma LDL-C levels (β = -0.83, p = 0.013; and β = -0.22, p = 0.028, respectively). CONCLUSIONS In otherwise healthy individuals with low to moderate cardiovascular risk, retinal microvascular dilation and constriction responses to stress levels are influenced by systemic antioxidant capacity, and circulating markers for cardiovascular risk.
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Affiliation(s)
- Swathi Seshadri
- Vascular Research Laboratory; Ophthalmic Research Group; School of Life and Health Sciences; Aston University; Birmingham UK
| | - Stephanie Mroczkowska
- Vascular Research Laboratory; Ophthalmic Research Group; School of Life and Health Sciences; Aston University; Birmingham UK
| | - Lu Qin
- Vascular Research Laboratory; Ophthalmic Research Group; School of Life and Health Sciences; Aston University; Birmingham UK
| | - Sunni Patel
- Vascular Research Laboratory; Ophthalmic Research Group; School of Life and Health Sciences; Aston University; Birmingham UK
| | - Aniko Ekart
- School of Engineering and Applied Sciences; Aston University; Birmingham UK
| | - Doina Gherghel
- Vascular Research Laboratory; Ophthalmic Research Group; School of Life and Health Sciences; Aston University; Birmingham UK
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Ras RT, Fuchs D, Koppenol WP, Garczarek U, Greyling A, Keicher C, Verhoeven C, Bouzamondo H, Wagner F, Trautwein EA. The effect of a low-fat spread with added plant sterols on vascular function markers: results of the Investigating Vascular Function Effects of Plant Sterols (INVEST) study. Am J Clin Nutr 2015; 101:733-41. [PMID: 25809853 PMCID: PMC4381780 DOI: 10.3945/ajcn.114.102053] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Plant sterols (PSs) lower LDL cholesterol, an established risk factor for coronary artery disease (CAD). No direct evidence is available supporting a reduced risk of CAD for foods with added PSs. Endothelial dysfunction is seen as an early indicator of atherosclerotic damage. OBJECTIVES This study was primarily designed to investigate the effect of a low-fat spread with added PSs on brachial artery endothelial function as measured by flow-mediated dilation (FMD). Second, effects on arterial stiffness, blood pressure, serum lipids, and plasma PS concentrations were investigated. We hypothesized that PSs would not worsen FMD but would rather modestly improve FMD. DESIGN This study had a double-blind, randomized, placebo-controlled, parallel design. After a 4-wk run-in period, 240 hypercholesterolemic but otherwise healthy men and women consumed 20 g/d of low-fat spread without (control) or with added PSs (3 g/d) during 12 wk. Pre- and postintervention, vascular function measurements and blood sampling were performed. RESULTS In total, 232 participants completed the study period. For the primary endpoint FMD, 199 participants were included in the statistical analysis. PS intake did not affect FMD (+0.01 percentage points; 95% CI: -0.73, 0.75) compared with control. Measures of arterial stiffness (pulse wave velocity and augmentation index) and blood pressure were also not significantly changed compared with control. After PS intervention, LDL cholesterol significantly decreased on average by 0.26 mmol/L (95% CI: -0.40, -0.12) or 6.7% compared with control. Plasma sitosterol and campesterol concentrations significantly increased in the PS group up to on average 11.5 μmol/L and 13.9 μmol/L (expressed as geometric means), respectively. CONCLUSIONS The intake of a low-fat spread with added PSs neither improved nor worsened FMD or other vascular function markers in hypercholesterolemic men and women. As expected, serum LDL cholesterol decreased, whereas plasma PSs increased after PS intake. This study was registered at clinicaltrials.gov as NCT01803178.
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Affiliation(s)
- Rouyanne T Ras
- From Unilever Research and Development Vlaardingen, Vlaardingen, The Netherlands (RTR, DF, WPK, UG, AG, CV, HB, and EAT), and Charité Research Organisation, Berlin, Germany (CK and FW)
| | - Dagmar Fuchs
- From Unilever Research and Development Vlaardingen, Vlaardingen, The Netherlands (RTR, DF, WPK, UG, AG, CV, HB, and EAT), and Charité Research Organisation, Berlin, Germany (CK and FW)
| | - Wieneke P Koppenol
- From Unilever Research and Development Vlaardingen, Vlaardingen, The Netherlands (RTR, DF, WPK, UG, AG, CV, HB, and EAT), and Charité Research Organisation, Berlin, Germany (CK and FW)
| | - Ursula Garczarek
- From Unilever Research and Development Vlaardingen, Vlaardingen, The Netherlands (RTR, DF, WPK, UG, AG, CV, HB, and EAT), and Charité Research Organisation, Berlin, Germany (CK and FW)
| | - Arno Greyling
- From Unilever Research and Development Vlaardingen, Vlaardingen, The Netherlands (RTR, DF, WPK, UG, AG, CV, HB, and EAT), and Charité Research Organisation, Berlin, Germany (CK and FW)
| | - Christian Keicher
- From Unilever Research and Development Vlaardingen, Vlaardingen, The Netherlands (RTR, DF, WPK, UG, AG, CV, HB, and EAT), and Charité Research Organisation, Berlin, Germany (CK and FW)
| | - Carole Verhoeven
- From Unilever Research and Development Vlaardingen, Vlaardingen, The Netherlands (RTR, DF, WPK, UG, AG, CV, HB, and EAT), and Charité Research Organisation, Berlin, Germany (CK and FW)
| | - Hakim Bouzamondo
- From Unilever Research and Development Vlaardingen, Vlaardingen, The Netherlands (RTR, DF, WPK, UG, AG, CV, HB, and EAT), and Charité Research Organisation, Berlin, Germany (CK and FW)
| | - Frank Wagner
- From Unilever Research and Development Vlaardingen, Vlaardingen, The Netherlands (RTR, DF, WPK, UG, AG, CV, HB, and EAT), and Charité Research Organisation, Berlin, Germany (CK and FW)
| | - Elke A Trautwein
- From Unilever Research and Development Vlaardingen, Vlaardingen, The Netherlands (RTR, DF, WPK, UG, AG, CV, HB, and EAT), and Charité Research Organisation, Berlin, Germany (CK and FW)
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Kobayashi H, Abe M, Murata Y, Maruyama T, Furukawa T, Oikawa O, Okada K. Low-density lipoprotein apheresis for corticosteroid-resistant skin lesions caused by cholesterol crystal embolism: a case report and review of the literature. J Artif Organs 2015; 18:285-9. [PMID: 25821197 DOI: 10.1007/s10047-015-0830-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Accepted: 03/08/2015] [Indexed: 11/25/2022]
Abstract
Cholesterol crystal embolism (CCE) is an arterio-arterial embolism originating from the breakdown of atherosclerotic plaques in the aortic wall. The embolism affects the skin and kidney particularly, as well as frequently affects the gastrointestinal tract and other organs. Although there are no clearly effective direct therapies for CCE, corticosteroid therapy and combination therapy with low-density lipoprotein apheresis (LDL-A) followed by corticosteroids were recently reported to be effective for renal manifestations in some cases. However, few cases offer suggestions for the treatment of skin lesions caused by CCE. We report here a case of a 58-year-old man diagnosed with CCE with skin manifestations and kidney dysfunction who achieved complete remission after LDL-A. LDL-A may be a useful treatment for CCE, particularly in cases with skin manifestations.
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Affiliation(s)
- Hiroki Kobayashi
- Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-chou, Itabashi-ku, Tokyo, 173-8610, Japan
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Tousoulis D, Simopoulou C, Papageorgiou N, Oikonomou E, Hatzis G, Siasos G, Tsiamis E, Stefanadis C. Endothelial dysfunction in conduit arteries and in microcirculation. Novel therapeutic approaches. Pharmacol Ther 2014; 144:253-267. [PMID: 24928320 DOI: 10.1016/j.pharmthera.2014.06.003] [Citation(s) in RCA: 83] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Accepted: 05/28/2014] [Indexed: 11/22/2022]
Abstract
The vascular endothelium not only is a single monolayer of cells between the vessel lumen and the intimal wall, but also plays an important role by controlling vascular function and structure mainly via the production of nitric oxide (NO). The so called "cardiovascular risk factors" are associated with endothelial dysfunction, that reduces NO bioavailability, increases oxidative stress, and promotes inflammation contributing therefore to the development of atherosclerosis. The significant role of endothelial dysfunction in the development of atherosclerosis emphasizes the need for efficient therapeutic interventions. During the last years statins, angiotensin-converting enzyme inhibitors, angiotensin-receptor antagonists, antioxidants, beta-blockers and insulin sensitizers have been evaluated for their ability to restore endothelial function (Briasoulis et al., 2012). As there is not a straightforward relationship between therapeutic interventions and improvement of endothelial function but rather a complicated interrelationship between multiple cellular and sub-cellular targets, research has been focused on the understanding of the underlying mechanisms. Moreover, the development of novel diagnostic invasive and non-invasive methods has allowed the early detection of endothelial dysfunction expanding the role of therapeutic interventions and our knowledge. In the current review we present the available data concerning the contribution of endothelial dysfunction to atherogenesis and review the methods that assess endothelial function with a view to understand the multiple targets of therapeutic interventions. Finally we focus on the classic and novel therapeutic approaches aiming to improve endothelial dysfunction and the underlying mechanisms.
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Affiliation(s)
- Dimitris Tousoulis
- 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Greece.
| | - Chryssa Simopoulou
- 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Greece
| | - Nikos Papageorgiou
- 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Greece
| | - Evangelos Oikonomou
- 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Greece
| | - George Hatzis
- 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Greece
| | - Gerasimos Siasos
- 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Greece
| | - Eleftherios Tsiamis
- 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Greece
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Usefulness of lipid apheresis in the treatment of familial hypercholesterolemia. J Lipids 2014; 2014:864317. [PMID: 25386364 PMCID: PMC4217354 DOI: 10.1155/2014/864317] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2014] [Revised: 08/06/2014] [Accepted: 10/07/2014] [Indexed: 11/17/2022] Open
Abstract
Lipid apheresis is used to treat patients with severe hyperlipidemia by reducing low-density lipoprotein cholesterol (LDL-C). This study examines the effect of apheresis on the lipid panel and cardiac event rates before and after apheresis. An electronic health record screen of ambulatory patients identified 11 active patients undergoing lipid apheresis with 10/11 carrying a diagnosis of FH. Baseline demographics, pre- and postapheresis lipid levels, highest recorded LDL-C, cardiac events, current medications, and first apheresis treatment were recorded. Patients completed a questionnaire and self-reported risk factors and interest in alternative treatment. There were significant reductions in mean total cholesterol (−58.4%), LDL-C (−71.9%), triglycerides (−51%), high-density lipoprotein (HDL) cholesterol (−9.3%), and non-HDL (−68.2%) values. Thirty-four cardiac events were documented in 8 patients before apheresis, compared with 9 events in 5 patients after apheresis. Our survey showed a high prevalence of statin intolerance (64%), with the majority (90%) of participants indicating an interest in alternative treatment options. Our results have shown that lipid apheresis primary effect is a marked reduction in LDL-C cholesterol levels and may reduce the recurrence of cardiac events. Apheresis should be compared to the newer alternative treatment modalities in a randomized fashion due to patient interest in alternative options.
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Lipoprotein apheresis and acute reduction of arterial inflammation: FDG-PET as an imaging biomarker of nonpharmacological effects on the vessel wall. J Am Coll Cardiol 2014; 64:1427-9. [PMID: 25277611 DOI: 10.1016/j.jacc.2014.06.1197] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Accepted: 06/24/2014] [Indexed: 11/23/2022]
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