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1
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Vallée A. Added value of arterial stiffness index for the 10-year atherosclerotic cardiovascular disease risk determination in a middle-aged population-based study. Clin Res Cardiol 2023; 112:1679-1689. [PMID: 37650913 DOI: 10.1007/s00392-023-02267-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 07/12/2023] [Indexed: 09/01/2023]
Abstract
OBJECTIVE Atherosclerotic cardiovascular disease (ASCVD) is considered the leading cause of mortality worldwide. Arterial stiffness, measured by arterial stiffness index (ASI), could be a main predictor in target damage of organs. Uncertainty remains regarding the contribution of ASI to estimated ASCVD risk. This study investigates the added value of ASI in ASCVD risk determination using the general UK Biobank middle-aged population. METHODS Among 100,598 participants from the UK Biobank population, ASI was assessed and associations between ASCVD risk were stratified by sex and estimated using multiple linear and logistic regressions adjusted for heart rate, physical activity, alcohol status, smocking pack years, BMI categories and CKD. RESULTS Males presented higher ASCVD risk than females (8.58% vs. 2.82%, p < 0.001) and higher ASI levels (9.50 m/s vs. 7.00 m/s, p < 0.001). The Youden index was determined at 9.70 m/s in males (p < 0.001) and 10.46 m/s in females (p < 0.001). Among females, participants with ASI > 10.46 m/s showed higher ASCVD risk than others (3.64% vs. 2.56%, p < 0.001), similar results were observed for males (9.92% vs. 7.21%, p < 0.001). In males, ASI showed significant added value information when including overall covariates (AUC = 0.695 vs. AUC = 0.663, p < 0.001). Similar results were observed in females (AUC = 0.693 vs. AUC = 0.687, p = 0.001). In both genders, for the association between ASI and ASCVD risk, nonlinear relationships were observed with higher accuracies than linear models. CONCLUSION Further studies should investigate ASCVD risk stratification management depending on ASI measurement.
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Affiliation(s)
- Alexandre Vallée
- Department of Epidemiology and Public Health, Foch Hospital, 92150, Suresnes, France.
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2
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Flow-Mediated Dilatation in the Assessment of Coronary Heart Disease: A Meta-Analysis. Cardiol Res Pract 2022; 2022:7967324. [PMID: 36213460 PMCID: PMC9534706 DOI: 10.1155/2022/7967324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 08/03/2022] [Indexed: 11/23/2022] Open
Abstract
Endothelial dysfunction may contribute to the increased morbidity and mortality associated with coronary heart disease (CHD). Flow-mediated dilatation (FMD) is the most popular noninvasive method for vascular endothelial function evaluation. This meta-analysis aimed to investigate the association between FMD and CHD. We searched the publications listed in the PubMed, Web of Science, Scopus, and Embase databases. Stata 14 software was used to analyze the data. Standardized mean difference (SMD) was used to calculate FMD levels, and the effect sizes were expressed with a 95% confidence interval (CI). I2 statistics were used to evaluate statistical heterogeneity. In this meta-analysis, 9 studies enrolled a total number of 943 participants, including 534 (56.63%) patients with CHD and 409 controls (43.37%). We found that patients with CHD showed a significantly lower FMD than the controls (SMD −0.706%; 95% CI: −0.985, −0.427; P=0.001) with high heterogeneity. In addition, funnel plot analysis suggested asymmetry that could be evidence of publication bias. But sensitivity analyses show that there were no influential studies. This meta-analysis provides evidence that patients with CHD show a significantly lower FMD than controls and highlights the literature on FMD as a hallmark in CHD diseases.
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3
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Gao L, Lu D, Xia G, Zhang H. The relationship between arterial stiffness index and coronary heart disease and its severity. BMC Cardiovasc Disord 2021; 21:527. [PMID: 34743695 PMCID: PMC8573853 DOI: 10.1186/s12872-021-02350-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 10/26/2021] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Arterial stiffness index (ASI) is closely related to coronary atherosclerosis. This study aims to explore whether ASI can predict coronary heart disease (CHD) and its severity. METHODS In this study, a total of 726 patients with suspected CHD were recruited. Based on coronary angiography results, the subjects were assigned into three groups: the control group (without obvious coronary artery disease), single-vessel disease group, and multi-vessel disease group (the number of vessels diseased ≥ 2). At the same time, according to the results of angiography, myocardial enzyme spectrum, electrocardiogram, color Doppler echocardiography and clinical manifestations, these patients were divided into four groups: the control group, stable angina (SA) Group, unstable angina (UA) group, and acute myocardial infarction (AMI) group. We have compared whether there were differences in ASI and related baseline data between groups. Receiver operating curve (ROC) analysis was conducted to determine whether ASI could predict CHD and evaluate the severity. RESULTS ASI was positively correlated with the number of diseased branches of coronary artery. The value of ASI was increased as the number of the diseased branches increased. The ASI value in the SA group was significantly higher compared with the control group. Furthermore, the ASI value in the UA and AMI groups was remarkably increased compared with the control and SA groups. The results of ROC analysis indicated that the sensitivity and specificity of ASI was 71.0% and 85.4% in diagnosing CHD, respectively. While ASI was used in predicting the severity of CHD, the sensitivity was 72.1% and specificity 57.9%. CONCLUSION ASI is of great value in the diagnosis of coronary heart disease and the prediction of its severity.
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Affiliation(s)
- Longjian Gao
- Department of Cardiology, Hebei Medical University, 361# Zhongshan east road, Shijiazhuang, 050017, Hebei Province, China
| | - Dasheng Lu
- Department of Cardiology, The Second Affiliated Hospital of Wannan Medical College, 10# Kangfu road, Wuhu, 241000, Anhui Province, China
| | - Guangwei Xia
- Department of Cardiology, The Affiliated Hospital of Yangzhou University, 41# Taizhou Road, Yangzhou, 225000, Jiangsu Province, China
| | - Hao Zhang
- Department of Cardiology, The Affiliated Hospital of Yangzhou University, 41# Taizhou Road, Yangzhou, 225000, Jiangsu Province, China.
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4
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Maruhashi T, Kajikawa M, Kishimoto S, Takaeko Y, Yamaji T, Harada T, Hashimoto Y, Han Y, Aibara Y, Mohamad Yusoff F, Chayama K, Nakashima A, Goto C, Nakano Y, Higashi Y. Volume Elastic Modulus, Vascular Function, and Vascular Structure in Patients with Cardiovascular Risk Factors. J Atheroscler Thromb 2021; 28:963-973. [PMID: 33100278 PMCID: PMC8532062 DOI: 10.5551/jat.59261] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
Aims:
Volume elastic modulus (V
E
), an index of arterial elasticity, and arterial diameter of the brachial artery can be automatically measured by a newly developed oscillometric device. We investigated the associations of V
E
with flow-mediated vasodilation (FMD), an index of endothelium-dependent vasodilation, nitroglycerine-induced vasodilation (NID), an index of endothelium-independent vasodilation, and intima-media thickness (IMT) of the brachial artery and association of oscillometrically measured brachial artery diameter with ultrasonographically measured brachial artery diameter in patients with cardiovascular risk factors.
Methods:
Oscillometric measurements of V
E
and brachial artery diameter and ultrasound measurements of brachial artery diameter, FMD, NID, and IMT of the brachial artery were performed in 50 patients with cardiovascular risk factors.
Results: The mean values were 2.1±0.4 mmHg/% for V
E
, 0.31±0.05 mm for brachial IMT, 4.48±0.70 mm for oscillometric brachial artery diameter, and 4.30±0.55 mm for ultrasound brachial artery diameter. V
E
significantly correlated with brachial IMT (r=0.51,
P
＜0.001), whereas there was no significant correlation of V
E
with FMD (r=-0.08,
P
=0.58) or NID (r=0.07,
P
=0.61). Multivariate analysis revealed that V
E
was significantly associated with brachial IMT (β=0.33,
P
=0.04). Oscillometric brachial artery diameter significantly correlated with ultrasound brachial artery diameter (r=0.79,
P
＜0.001). The Bland-Altman plot showed good agreement between oscillometric brachial artery diameter and ultrasound brachial artery diameter (mean difference, -0.17 mm; limits of agreement, -1.03 mm to 0.69 mm).
Conclusions:
In patients with cardiovascular risk factors, V
E
may represent atherosclerotic structural alterations of the vascular wall but not vascular function. The accuracy of oscillometric measurement of brachial artery diameter is acceptable.
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Affiliation(s)
- Tatsuya Maruhashi
- Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University
| | - Masato Kajikawa
- Division of Regeneration and Medicine, Hiroshima University Hospital
| | - Shinji Kishimoto
- Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University
| | - Yuji Takaeko
- Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University
| | - Takayuki Yamaji
- Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University
| | - Takahiro Harada
- Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University
| | - Yu Hashimoto
- Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University
| | - Yiming Han
- Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University
| | - Yoshiki Aibara
- Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University
| | - Farina Mohamad Yusoff
- Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University
| | - Kazuaki Chayama
- Department of Medicine and Molecular Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima University
| | - Ayumu Nakashima
- Department of Stem Cell Biology and Medicine, Graduate School of Biomedical and Sciences, Hiroshima University
| | - Chikara Goto
- Department of Rehabilitation, Faculty of General Rehabilitation, Hiroshima International University
| | - Yukiko Nakano
- Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University
| | - Yukihito Higashi
- Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University.,Division of Regeneration and Medicine, Hiroshima University Hospital
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5
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Abstract
UNLABELLED Exercise is associated with higher cognitive function and is a promising intervention to reduce the risk of dementia. With advancing age, there are changes in the vasculature that have important clinical implications for brain health and cognition. Primary aging and vascular risk factors are associated with increases in arterial stiffness and pulse pressure, and reductions in peripheral vascular function. OBJECTIVE The purpose is to discuss the epidemiological, observational, and mechanistic evidence regarding the link between age-related changes in vascular health and brain health. METHODS We performed a literature review and integrated with our published data. RESULTS Epidemiological evidence suggests a link between age-related increases in arterial stiffness and lower cognitive function, which may be mediated by cerebral vascular function, including cerebral vasoreactivity and cerebral pulsatility. Age-associated impairments in central arterial stiffness and peripheral vascular function have been attenuated or reversed through lifestyle behaviors such as exercise. Greater volumes of habitual exercise and higher cardiorespiratory fitness are associated with beneficial effects on both peripheral vascular health and cognition. Yet, the extent to which exercise directly influences cerebral vascular function and brain health, as well as the associated mechanisms remains unclear. CONCLUSION Although there is evidence that exercise positively impacts cerebral vascular function, more research is necessary in humans to optimize experimental protocols and address methodological limitations and physiological considerations. Understanding the impact of exercise on cerebral vascular function is important for understanding the association between exercise and brain health and may inform future intervention studies that seek to improve cognition.
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6
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Rajendran R, Sharma VK, Nandeesha H, Ananthakrishnan R, Vinod KV, Subramanian SK. Assessment of vascular function in complete glycaemic spectrum. Clin Exp Hypertens 2021; 43:436-442. [PMID: 33703968 DOI: 10.1080/10641963.2021.1896729] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Purpose: The present study was conceived to delineate the point of vascular dysfunction along the glycemic spectrum (normoglycemic individuals with no family history of diabetes, normoglycemic individuals with family history of diabetes, prediabetic individuals, and diabetic individuals).Materials and Methods: In this cross-sectional comparative study, we enrolled 252 participants of both gender in the age group of 30-50 years. They were classified based on their family history of diabetes and glycemic status into four groups along the glycemic spectrum as mentioned above. We measured flow-mediated dilation (FMD) from brachial artery and vascular function biomarkers such as enthothelin-1 (ET-1), von Willbrand Factor (vWF), Vascular Endothelial Growth Factor (VEGF) to assess the vascular function. The comparison of data between groups were done using One Way ANOVA/Kruskal-Wallis followed by post-hoc analysis using LSD/Mann-Whitney U Test depending on the normality of the data. Spearman correlation was done between vascular function and plasma glucose levels to identify its relationship. Linear regression was carried out to identify the factors influencing the FMD across the glycemic spectrum.Results: We observed that vascular function negatively correlated with blood glucose levels. However, endothelin-1 and vWF derangement was there even in normoglycemic first degree relatives of diabetes (FDRD) and the derangement increased in prediabetes and diabetes. Physiological dysfunction in terms of decreased flow-mediated dilation starts from prediabetes only. VEGF derangement is found only in diabetic individuals.Conclusion: Vascular dysfunction is found even in normoglycemic FDRD and the derangement increased and compounded with the advancement of disease.
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Affiliation(s)
- Rajathi Rajendran
- Tutor, Department of Physiology, AIIMS, Mangalagiri, Andhra Pradesh, India
| | - Vivek Kumar Sharma
- Department of Physiology, All India Institute of Medical Sciences, Rajkot, India
| | - Hanumanthappa Nandeesha
- Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
| | - Ramesh Ananthakrishnan
- Department Department of Radiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
| | - Kolar Vishwanath Vinod
- Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
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7
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Scudder MR, Jennings JR, DuPont CM, Lockwood KG, Gadagkar SH, Best B, Jasti SP, Gianaros PJ. Dual impedance cardiography: An inexpensive and reliable method to assess arterial stiffness. Psychophysiology 2021; 58:e13772. [PMID: 33496965 DOI: 10.1111/psyp.13772] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 12/17/2020] [Accepted: 12/30/2020] [Indexed: 01/08/2023]
Abstract
Pulse wave velocity (PWV) is a common measure of arterial stiffness. Non-invasive methods to measure PWV are widely used in biomedical studies of aging and cardiovascular disease, but they are rarely used in psychophysiology. Barriers to wider use include the prohibitive costs of specialized equipment and need for trained technicians (e.g., ultrasonographers). Here, we describe an impedance cardiography method to measure PWV. By this method, impedance signals are dually collected from the thorax and calf. Combined with ensemble averaging of vascular signals, this dual impedance cardiography (d-ICG) method allows for the measurement of aortic flow onset and the arrival time of peripheral pulse waveforms to compute PWV. In a community sample of adults (aged 19-78 years), PWV measured with d-ICG exhibited a strong positive correlation with age. Moreover, age-specific mean PWV values were within the normative reference intervals established by large scale studies using other techniques. PWV derived from d-ICG exhibited high test-retest reliability across several days, as well as excellent inter-rater reliability. Last, PWV exhibited expected associations with known cardiovascular disease risk factors and indicators of autonomic cardiovascular control. d-ICG is an inexpensive and reliable method to assess arterial stiffness.
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Affiliation(s)
- Mark R Scudder
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
| | - J Richard Jennings
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.,Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
| | - Caitlin M DuPont
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Kimberly G Lockwood
- Center for Health and Community, University of California San Francisco, San Francisco, CA, USA
| | | | - Belen Best
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Swetha P Jasti
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Peter J Gianaros
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
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8
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McCallinhart PE, Scandling BW, Trask AJ. Coronary remodeling and biomechanics: Are we going with the flow in 2020? Am J Physiol Heart Circ Physiol 2020; 320:H584-H592. [PMID: 33185115 DOI: 10.1152/ajpheart.00634.2020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Under normal conditions, coronary blood flow (CBF) provides critical blood supply to the myocardium so that it can appropriately meet the metabolic demands of the body. Dogmatically, there exist several known regulators and modulators of CBF that include local metabolites and neurohormonal factors that can influence the function of the coronary circulation. In disease states such as diabetes and myocardial ischemia, these regulators are impaired or shifted such that CBF is reduced. Although functional considerations have been and continued to be well studied, more recent evidence builds upon established studies that collectively suggest that the relative roles of coronary structure, biomechanics, and the influence of cardiac biomechanics via extravascular compression may also play a significant role in dictating CBF. In this mini review, we discuss these regulators of CBF under normal and pathophysiological conditions and their potential influence on the control of CBF.
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Affiliation(s)
- Patricia E McCallinhart
- Center for Cardiovascular Research, The Heart Center, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio
| | - Benjamin W Scandling
- Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, Ohio.,Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Aaron J Trask
- Center for Cardiovascular Research, The Heart Center, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio.,Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio
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9
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Galvão RDV, Pereira CDS, Freitas EGB, Lima DRART, Santos WAM, Souza DF, Nomelini QSS, Ferreira-Filho SR. Association between diabetes mellitus and central arterial stiffness in elderly patients with systemic arterial hypertension. Clin Exp Hypertens 2020; 42:728-732. [DOI: 10.1080/10641963.2020.1783547] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Affiliation(s)
| | - Cristiane de Sousa Pereira
- Internal Medicine Department, Federal University of Uberlândia (Universidade Federal De Uberlândia), Uberlândia, Brazil
| | | | | | | | - Denis Fabiano Souza
- Internal Medicine Department, Federal University of Uberlândia (Universidade Federal De Uberlândia), Uberlândia, Brazil
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10
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Zekavat SM, Aragam K, Emdin C, Khera AV, Klarin D, Zhao H, Natarajan P. Genetic Association of Finger Photoplethysmography-Derived Arterial Stiffness Index With Blood Pressure and Coronary Artery Disease. Arterioscler Thromb Vasc Biol 2020; 39:1253-1261. [PMID: 31070453 DOI: 10.1161/atvbaha.119.312626] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Objective- Arterial stiffness index (ASI) is independently associated with blood pressure (BP) and coronary artery disease (CAD) epidemiologically. However, it is unknown whether these associations represent causal relationships. Here, we assess whether genetic predisposition to increased ASI is associated with elevated BP and CAD risk. Approach and Results- We first performed a large-scale epidemiological association of finger photoplethysmography-derived ASI in the UK Biobank, finding significant associations with systolic BP (β=0.55 mm Hg; [95% CI, 0.45-0.65]; P=5.77×10-24; N=137 858), diastolic BP (β=1.05 mm Hg; [95% CI, 0.99-1.11]; P=7.27×10-272; N=137 862), and incident CAD (hazard ratio, 1.08; [95% CI, 1.04-1.11]; P=1.5×10-6; N=3692 cases, 126 615 controls) in multivariable models. We then performed an ASI genome-wide association study analysis in 131 686 participants from the UK Biobank. Across participants not in the ASI genome-wide association study, a 6-variant ASI polygenic risk score was calculated. Each SD increase in genetic ASI was associated with systolic BP (β=4.63 mm Hg; [95% CI, 2.1-7.2]; P=3.37×10-4; N=208 897), and diastolic BP (β=2.61 mm Hg; [95% CI, 1.2-4.0]; P=2.85×10-4; N=208 897); however, no association was observed with incident CAD (hazard ratio, 1.12; [95% CI, 0.55-2.3]; P=0.75; N=223 061; 7534 cases). The lack of CAD association observed was replicated among 184 305 participants (60 810 cases) from the CARDIOGRAMplusC4D (Coronary Artery Disease Genetics Consortium; odds ratio, 0.56; [95% CI, 0.26-1.24]; P=0.15). Conclusions- Our data support the conclusion that finger photoplethysmography-derived ASI is an independent, genetically causal risk factor for BP, but do not support the notion that ASI is a suitable surrogate for CAD risk.
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Affiliation(s)
- Seyedeh M Zekavat
- From the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (S.M.Z., K.A., C.E., A.V.K., D.K., P.N.).,Yale School of Medicine, New Haven, CT (S.M.Z.).,Computational Biology and Bioinformatics Program, Yale University, New Haven, CT (S.M.Z., H.Z.).,Center for Genomic Medicine (S.M.Z., K.A., A.V.K., D.K., P.N.), Massachusetts General Hospital, Boston.,Cardiovascular Research Center (S.M.Z., K.A., P.N.), Massachusetts General Hospital, Boston
| | - Krishna Aragam
- From the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (S.M.Z., K.A., C.E., A.V.K., D.K., P.N.).,Center for Genomic Medicine (S.M.Z., K.A., A.V.K., D.K., P.N.), Massachusetts General Hospital, Boston.,Cardiovascular Research Center (S.M.Z., K.A., P.N.), Massachusetts General Hospital, Boston.,Harvard Medical School, Boston, MA (K.A., C.E., A.V.K., D.K., P.N.)
| | - Connor Emdin
- From the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (S.M.Z., K.A., C.E., A.V.K., D.K., P.N.).,Harvard Medical School, Boston, MA (K.A., C.E., A.V.K., D.K., P.N.)
| | - Amit V Khera
- From the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (S.M.Z., K.A., C.E., A.V.K., D.K., P.N.).,Center for Genomic Medicine (S.M.Z., K.A., A.V.K., D.K., P.N.), Massachusetts General Hospital, Boston.,Harvard Medical School, Boston, MA (K.A., C.E., A.V.K., D.K., P.N.)
| | - Derek Klarin
- From the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (S.M.Z., K.A., C.E., A.V.K., D.K., P.N.).,Center for Genomic Medicine (S.M.Z., K.A., A.V.K., D.K., P.N.), Massachusetts General Hospital, Boston.,Harvard Medical School, Boston, MA (K.A., C.E., A.V.K., D.K., P.N.)
| | - Hongyu Zhao
- Computational Biology and Bioinformatics Program, Yale University, New Haven, CT (S.M.Z., H.Z.).,Department of Biostatistics, Yale School of Public Health, New Haven, CT (H.Z.)
| | - Pradeep Natarajan
- From the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (S.M.Z., K.A., C.E., A.V.K., D.K., P.N.).,Center for Genomic Medicine (S.M.Z., K.A., A.V.K., D.K., P.N.), Massachusetts General Hospital, Boston.,Cardiovascular Research Center (S.M.Z., K.A., P.N.), Massachusetts General Hospital, Boston.,Harvard Medical School, Boston, MA (K.A., C.E., A.V.K., D.K., P.N.)
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11
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Ballak DB, Brunt VE, Sapinsley ZJ, Ziemba BP, Richey JJ, Zigler MC, Johnson LC, Gioscia‐Ryan RA, Culp‐Hill R, Eisenmesser EZ, D'Alessandro A, Dinarello CA, Seals DR. Short-term interleukin-37 treatment improves vascular endothelial function, endurance exercise capacity, and whole-body glucose metabolism in old mice. Aging Cell 2020; 19:e13074. [PMID: 31755162 PMCID: PMC6974720 DOI: 10.1111/acel.13074] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 10/23/2019] [Accepted: 10/25/2019] [Indexed: 12/31/2022] Open
Abstract
Aging is associated with vascular endothelial dysfunction, reduced exercise tolerance, and impaired whole-body glucose metabolism. Interleukin-37 (IL-37), an anti-inflammatory cytokine of the interleukin-1 family, exerts salutary physiological effects in young mice independent of its inflammation-suppressing properties. Here, we assess the efficacy of IL-37 treatment for improving physiological function in older age. Old mice (26-28 months) received daily intraperitoneal injections of recombinant human IL-37 (recIL-37; 1 µg/200 ml PBS) or vehicle (200 ml PBS) for 10-14 days. Vascular endothelial function (ex vivo carotid artery dilation to increasing doses of acetylcholine, ACh) was enhanced in recIL-37 vs. vehicle-treated mice via increased nitric oxide (NO) bioavailability (all p < .05); this effect was accompanied by enhanced ACh-stimulated NO production and reduced levels of reactive oxygen species in endothelial cells cultured with plasma from IL-37-treated animals (p < .05 vs. vehicle plasma). RecIL-37 treatment increased endurance exercise capacity by 2.4-fold, which was accompanied by a 2.9-fold increase in the phosphorylated AMP-activated kinase (AMPK) to AMPK ratio (i.e., AMPK activation) in quadriceps muscle. RecIL-37 treatment also improved whole-body insulin sensitivity and glucose tolerance (p < .05 vs. vehicle). Improvements in physiological function occurred without significant changes in plasma, aortic, and skeletal muscle pro-inflammatory proteins (under resting conditions), whereas pro-/anti-inflammatory IL-6 was greater in recIL-37-treated animals. Plasma metabolomics analysis revealed that recIL-37 treatment altered metabolites related to pathways involved in NO synthesis (e.g., increased L-arginine and citrulline/arginine ratio) and fatty acid metabolism (e.g., increased pantothenol and free fatty acids). Our findings provide experimental support for IL-37 therapy as a novel strategy to improve diverse physiological functions in old age.
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Affiliation(s)
- Dov B. Ballak
- Department of Integrative PhysiologyUniversity of Colorado BoulderBoulderCOUSA
- Department of MedicineUniversity of Colorado DenverAuroraCOUSA
| | - Vienna E. Brunt
- Department of Integrative PhysiologyUniversity of Colorado BoulderBoulderCOUSA
| | | | - Brian P. Ziemba
- Department of Integrative PhysiologyUniversity of Colorado BoulderBoulderCOUSA
| | - James J. Richey
- Department of Integrative PhysiologyUniversity of Colorado BoulderBoulderCOUSA
| | - Melanie C. Zigler
- Department of Integrative PhysiologyUniversity of Colorado BoulderBoulderCOUSA
| | - Lawrence C. Johnson
- Department of Integrative PhysiologyUniversity of Colorado BoulderBoulderCOUSA
| | | | | | | | | | - Charles A. Dinarello
- Department of MedicineUniversity of Colorado DenverAuroraCOUSA
- Department of Internal MedicineRadboud University Medical CenterNijmegenThe Netherlands
| | - Douglas R. Seals
- Department of Integrative PhysiologyUniversity of Colorado BoulderBoulderCOUSA
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12
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Resende LAPR, Silva MAV, Resende JAM, Resende EAMR, Silva VJD, Correia D. Comparison of pulse wave analysis parameters by oscillometry in hypertensive diabetic and nondiabetic patients in a Brazilian outpatient care. Medicine (Baltimore) 2019; 98:e18100. [PMID: 31852069 PMCID: PMC6922585 DOI: 10.1097/md.0000000000018100] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 10/29/2019] [Indexed: 01/13/2023] Open
Abstract
INTRODUCTION Pulse wave analysis is an emerging approach that analyzes parameters comprising strong predictors of cardiovascular (CV) events and all-cause mortality, especially in patients with high CV risk based on established risk factors. This study used the oscillometric method, provided by the Mobil-o-Graph (PWA-EMI GmbH, Stolberg, Germany) device, to compare data regarding the pulse wave analysis parameters in hypertensive nondiabetic and diabetic patients. MATERIAL AND METHODS In this cross-sectional study, 276 individuals were examined in the academic hypertension outpatient care unit of the Federal University of the Triângulo, in Mineiro, Brazil, from January to December 2016. The pulse wave analysis was performed by oscillometry, and its parameters were acquired from all patients. RESULTS Of the 276 patients, 99 were diabetic and 177 nondiabetic. The mean systolic and pulse central blood pressure were significantly higher in diabetic patients than in nondiabetic patients (P = .008 and.0003, respectively). The mean peripheral systolic blood pressure and pulse pressure were also significantly higher in the diabetic group (P = .001 and P < .0001, respectively). The average pulse wave velocity (PWV, m/s) was 9.4 ± 1.6 and 8.8 ± 1.6 in the diabetic and nondiabetic groups, respectively (P = .003). CONCLUSION The group of hypertensive diabetic patients had significantly higher central blood pressure, peripheral blood pressure, and PWV than the hypertensive nondiabetic patients. The patients with overlapping established CV risk factors presented values of the pulse wave analysis parameters consistent with higher central pressure and greater arterial stiffness.
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Affiliation(s)
| | | | | | | | | | - Dalmo Correia
- Department of Internal Medicine
- Department of Tropical Medicine and Infectiology, Federal University of the Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
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13
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Ghiadoni L, Bruno RM. Is Central Blood Pressure a Determinant of Flow-Mediated Dilation in Patients With Coronary Artery Disease? Am J Hypertens 2019; 32:930-931. [PMID: 31504128 DOI: 10.1093/ajh/hpz126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 07/25/2019] [Accepted: 07/29/2019] [Indexed: 11/12/2022] Open
Affiliation(s)
- Lorenzo Ghiadoni
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Rosa Maria Bruno
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
- INSERM U970 Equipe 7, Paris Cardiovascular Research Center—PARCC, Paris, France
- Institute of Clinical Physiology—CNR, Pisa, Italy
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14
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Park KH, Park WJ, Han SJ, Kim HS, Jo SH, Kim SA, Suh SW. Association Between Intra-arterial Invasive Central and Peripheral Blood Pressure and Endothelial Function (Assessed by Flow-Mediated Dilatation) in Stable Coronary Artery Disease. Am J Hypertens 2019; 32:953-959. [PMID: 31233098 DOI: 10.1093/ajh/hpz100] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Revised: 05/14/2019] [Accepted: 06/18/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Endothelial function is an independent predictor of coronary artery disease (CAD) and is regulated by a number of factors, including blood pressure. OBJECTIVES The current study was designed to test the hypothesis that intra-arterial invasive central blood pressure is strongly associated with endothelial function in patients with CAD. METHODS In patient with CAD (diameter stenosis ≥30%), invasive central (aortic) and left peripheral (brachial) blood pressures were determined during transradial coronary angiography. The endothelial function was evaluated by way of flow-mediated dilatation (FMD) of the brachial artery. RESULTS We enrolled 413 consecutive patients. There were 260 patients with significant CAD (sCAD, diameter stenosis ≥50%) and 153 patients with nonsignificant CAD (nsCAD, diameter stenosis <50% and ≤30%). FMD was significantly and inversely correlated with central and peripheral parameters in terms of systolic blood pressure, mean arterial pressure, and pulse pressure (PP) (r = -0.332, r = -0.184, and r = -0.407, respectively, all P < 0.001) and (r = -0.303, r = -0.190, and r = -0.319, respectively, all P < 0.001). Compared with sCAD, there was closer correlation between central PP with FMD in nsCAD (r = -0.548 vs. r = -0.345, both P < 0.001). After adjusting potential confounders such as age, body mass index and high-sensitivity C-reactive protein, multivariate analysis showed that FMD remained independently associated with central PP, degree of coronary artery stenosis, and brachial-ankle pulse wave velocity in all patients. In patients with nsCAD, the multivariate analysis showed that only central PP was independently correlated with FMD. CONCLUSIONS In patients with stable CAD, a decline in endothelial function is most closely associated with invasive central pulse pressure.
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Affiliation(s)
- Kyoung-Ha Park
- Division of Cardiovacular Disease, Hallym University Medical Center, Anyang, Korea
| | - Woo Jung Park
- Division of Cardiovacular Disease, Hallym University Medical Center, Anyang, Korea
| | - Sang Jin Han
- Division of Cardiovacular Disease, Hallym University Medical Center, Anyang, Korea
| | - Hyun-Sook Kim
- Division of Cardiovacular Disease, Hallym University Medical Center, Anyang, Korea
| | - Sang Ho Jo
- Division of Cardiovacular Disease, Hallym University Medical Center, Anyang, Korea
| | - Sung-Ai Kim
- Division of Cardiovacular Disease, Hallym University Medical Center, Anyang, Korea
| | - Sang Won Suh
- Department of Physiology, College of Medicine, Hallym University, Chuncheon, Korea
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15
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Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C Activation. Appl Bionics Biomech 2019; 2019:6578492. [PMID: 31110559 PMCID: PMC6487160 DOI: 10.1155/2019/6578492] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 01/28/2019] [Accepted: 02/19/2019] [Indexed: 02/07/2023] Open
Abstract
Arterial stiffness, which increases with aging and hypertension, is an independent cardiovascular risk factor. While stiffer substrates are known to affect single endothelial cell morphology and migration, the effect of substrate stiffness on endothelial monolayer function is less understood. The objective of this study was to determine if substrate stiffness increased endothelial monolayer reactive oxygen species (ROS) in response to protein kinase C (PKC) activation and if this oxidative stress then impacted adherens junction integrity. Porcine aortic endothelial cells were cultured on varied stiffness polyacrylamide gels and treated with phorbol 12-myristate 13-acetate (PMA), which stimulates PKC and ROS without increasing actinomyosin contractility. PMA-treated endothelial cells on stiffer substrates increased ROS and adherens junction loss without increased contractility. ROS scavengers abrogated PMA effects on cell-cell junctions, with a more profound effect in cells on stiffer substrates. Finally, endothelial cells in aortae from elastin haploinsufficient mice (Eln+/-), which were stiffer than aortae from wild-type mice, showed decreased VE-cadherin colocalization with peripheral actin following PMA treatment. These data suggest that oxidative stress may be enhanced in endothelial cells in stiffer vessels, which could contribute to the association between arterial stiffness and cardiovascular disease.
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16
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Dai X, Yang Y, Cheng GL, Jia J, Fan FF, Li JP, Huo Y, Liu Z, Chen D, Zhang Y. Higher blood pressure increases arterial stiffness modified by blood glucose levels in a Chinese community-based study. Diabetes Metab Syndr Obes 2019; 12:901-911. [PMID: 31417293 PMCID: PMC6599895 DOI: 10.2147/dmso.s195405] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Accepted: 05/10/2019] [Indexed: 12/12/2022] Open
Abstract
Background: Increased arterial stiffness measured by brachial-ankle pulse wave velocity is associated with cardiovascular disease. However, the rates at which brachial-ankle pulse wave velocity and blood glucose accelerate within individuals who differ in blood pressure levels are largely unknown. Methods: This study was based on the baseline data of a Chinese community-based atherosclerosis cohort which included 7402 individuals. Using generalized linear regression models, the relationship between blood glucose levels and brachial-ankle pulse wave velocity, and the relationship between blood pressure levels and brachial-ankle pulse wave velocity were examined. Results: A marked interaction between hypertensive state and diabetic state was seen for brachial-ankle pulse wave velocity (P for interaction <0.001). The adjusted coefficient for subjects stratified by hypertensive groups and diabetic states showed that the highest brachial-ankle pulse wave velocity risk subjects were those who had both diabetes and hypertension (B=403.24; 95% CI: 372.43-434.05; P<0.001). Conclusions: The participants with increased arterial stiffness demonstrate a high prevalence of higher blood pressure. When high blood glucose levels co-occur with high blood pressure levels, there is a remarkable increase in arterial stiffness.
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Affiliation(s)
- Xiaotong Dai
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, People’s Republic of China
| | - Ying Yang
- Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of China
| | - Guan-Liang Cheng
- Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of China
| | - Jia Jia
- Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of China
| | - Fang-Fang Fan
- Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of China
| | - Jian-Ping Li
- Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of China
| | - Yong Huo
- Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of China
| | - Zhike Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, People’s Republic of China
| | - Dafang Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, People’s Republic of China
- Correspondence: Dafang ChenDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University, No.38, Xueyuan Road, Haidian District, Beijing100191, People’s Republic of ChinaTel +86 108 280 2644Fax +86 108 280 2644 Email
| | - Yan Zhang
- Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of China
- Yan ZhangDepartment of Cardiology, Peking University First Hospital, No.8 Xishiku St, Xicheng District, Beijing, People’s Republic of ChinaTel +86 108 357 5728 Email
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Jekell A, Kalani M, Kahan T. The interrelation of endothelial function and microvascular reactivity in different vascular beds, and risk assessment in hypertension: results from the Doxazosin-ramipril study. Heart Vessels 2018; 34:484-495. [PMID: 30244381 PMCID: PMC6373355 DOI: 10.1007/s00380-018-1265-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 09/14/2018] [Indexed: 12/14/2022]
Abstract
There are several non-invasive methods to study endothelial function, but their interrelation and association to cardiovascular risk have not been well evaluated. We studied macrovascular and microvascular endothelial function simultaneously in different vascular beds in relation to cardiovascular mortality risk (Systematic Coronary Risk Evaluation, SCORE) and hypertension induced cardiac organ damage, and their interrelationship. The study investigated 71 hypertensive patients by forearm post-ischemic flow-mediated vasodilation, pulse wave analysis (applanation tonometry) and beta 2-adrenoceptor agonist stimulation for changes in reflection index, skin microvascular reactivity by laser Doppler fluxmetry with iontophoresis and heat-induced hyperaemia, and coronary microvascular function by subendocardial viability ratio (derived from pulse wave analysis). Flow mediated vasodilation related inversely to SCORE (r = 0.34, P = 0.011). Adding microalbuminuria and pulse wave velocity strengthened the associations. Pulse wave reflection changes did not relate to SCORE. Skin microvascular reactivity related inversely to SCORE (peak flux change to sodium nitroprusside r = 0.29, P = 0.033, and to heating r = 0.31, P = 0.018). Subendocardial viability ratio did not relate to SCORE. Endothelial function indices showed no consistent relation to cardiac target organ damage. The agreement between the different methods for evaluating indices of macrovascular and microvascular endothelial function was weak. In conclusion, indices of macrovascular and microvascular endothelial function relate to cardiovascular mortality risk. Their use may improve cardiovascular risk prediction in hypertension. However, methods representing different vascular beds show little interrelationship and are not interchangeable, which may depend on different pathogenetic mechanisms representing different aspects of future cardiovascular risk. Trial registry: NCT02901977
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Affiliation(s)
- Andreas Jekell
- Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, 182 88, Stockholm, Sweden. .,Department of Cardiology, Danderyd University Hospital Corp, Stockholm, Sweden.
| | - Majid Kalani
- Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, 182 88, Stockholm, Sweden
| | - Thomas Kahan
- Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, 182 88, Stockholm, Sweden.,Department of Cardiology, Danderyd University Hospital Corp, Stockholm, Sweden
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18
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Vaes AW, Spruit MA, Theunis J, Wouters EF, De Boever P. Peripheral endothelial function is positively associated with maximal aerobic capacity in patients with chronic obstructive pulmonary disease. Respir Med 2018; 142:41-47. [DOI: 10.1016/j.rmed.2018.07.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 07/19/2018] [Accepted: 07/20/2018] [Indexed: 01/16/2023]
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Rodriguez-Miguelez P, Gregg J, Seigler N, Bass L, Thomas J, Pollock JS, Sullivan JC, Dillard TA, Harris RA. Acute Tetrahydrobiopterin Improves Endothelial Function in Patients With COPD. Chest 2018; 154:597-606. [PMID: 29705218 DOI: 10.1016/j.chest.2018.04.028] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 02/27/2018] [Accepted: 04/02/2018] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Cardiovascular diseases represent a hallmark characteristic in COPD, and endothelial dysfunction has been observed in these patients. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthesis and a regulator of endothelial function. The goal of this study was to test the hypothesis that a single dose of BH4 would improve endothelial function in patients with COPD via an increase in NO bioavailability. METHODS Seventeen patients with COPD completed a randomized, double-blind, placebo (PLC)-controlled, crossover trial with an acute dose of either BH4 (Kuvan; BioMarin Pharmaceutical Inc) or PLC. Flow-mediated dilation (FMD), a bioassay of endothelial function, was completed prior to and 3 h following each treatment. Phospho- and total endothelial NO synthase (NOS3) protein was evaluated after incubating endothelial cells with plasma from the patients prior to and following treatment. Fifteen demographically matched control subjects were tested at baseline for case control comparisons. RESULTS Treatment with BH4 significantly (P ≤ .004) increased FMD, improving endothelial function in patients compared to control values (P ≥ .327). BH4 increased (P = .013) the ratio of phospho-NOS3 to total NOS3 protein. No changes in FMD (P ≥ .776) or the protein ratio (P = .536) were observed following PLC. CONCLUSIONS An acute dose of BH4 was able to improve endothelial function in patients with COPD to values similar to control subjects. The improvement in endothelial function was accompanied by an increase in NOS3 phosphorylation. BH4 may represent a potential novel therapy to improve endothelial function and reduce cardiovascular disease risk in patients with COPD. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01398943; URL: www.clinicaltrials.gov.
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Affiliation(s)
| | - Justin Gregg
- Pulmonary and Critical Care Medicine Department, Greenville Memorial Hospital, Greenville, SC
| | - Nichole Seigler
- Georgia Prevention Institute, Department of Pediatrics, Augusta University, Augusta, GA
| | - Leon Bass
- Pulmonology Department, Holston Medical Group, Kingsport, TN
| | - Jeffrey Thomas
- Georgia Prevention Institute, Department of Pediatrics, Augusta University, Augusta, GA
| | - Jennifer S Pollock
- Cardio-Renal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, AL
| | | | - Thomas A Dillard
- Pulmonary and Critical Care, Department of Medicine, Augusta University, Augusta, GA
| | - Ryan A Harris
- Georgia Prevention Institute, Department of Pediatrics, Augusta University, Augusta, GA; Sport and Exercise Science Research Institute, Ulster University, Jordanstown, Northern Ireland.
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20
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Alem MM, Alshehri AM, Cahusac PMB, Walters MR. Effect of Xanthine Oxidase Inhibition on Arterial Stiffness in Patients With Chronic Heart Failure. CLINICAL MEDICINE INSIGHTS-CARDIOLOGY 2018; 12:1179546818779584. [PMID: 29899669 PMCID: PMC5992797 DOI: 10.1177/1179546818779584] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 04/30/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND The xanthine oxidase inhibitor allopurinol improves endothelial function in different populations, including patients with chronic heart failure (CHF). Its effect on arterial stiffness parameters is less clear. We investigated the effect of short-term low-dose allopurinol therapy on arterial stiffness in Saudi patients with stable mild-moderate CHF. METHODS A prospective, randomized, double-blind, placebo-controlled study was performed on 73 patients with mild-moderate CHF. In all, 36 patients were randomized to allopurinol 300 mg daily for 3 months, while 37 patients were randomized to placebo. Arterial stiffness parameters, aortic pulse wave velocity (Ao-PWV) and heart rate corrected augmentation index (c-AIx), were assessed before and after treatment along with serum uric acid. RESULTS A total of 66 patients completed the study. Both groups were matched for age, sex, severity of heart failure, and arterial stiffness. Compared with placebo, allopurinol recipients had a significant fall in uric acid concentration from 6.31 ± 1.4 (SD) mg/dL to 3.81 ± 1.2 (P < .001). Despite that, there was no significant change in arterial stiffness parameters between allopurinol and placebo groups. Post-treatment Ao-PWV was 9.79 ± 2.6 m/s in the allopurinol group and 10.07 ± 3.4 m/s in the placebo group, P = .723. Post-treatment c-AIx was 24.0% ± 9.1% and 22.0% ± 9.9%, respectively, P = .403. CONCLUSIONS We have shown that allopurinol significantly reduced uric acid concentration in Saudi patients with CHF but was not associated with a change in arterial stiffness. Our cohort of patients had worse arterial stiffness values at baseline, which might make them more resistant to change using our study regimen.The study has been registered with the International Standard Randomized Controlled Trial Number registry with an identifier number of ISRCTN58980230.
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Affiliation(s)
- Manal M Alem
- Department of Pharmacology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Abdullah M Alshehri
- Internal Medicine Department, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Peter MB Cahusac
- Department of Pharmacology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- Department of Comparative Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Matthew R Walters
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK
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Zahner GJ, Spaulding KA, Ramirez JL, Schaller MS, Walker SC, Hills NK, Gasper WJ, Grenon SM. Characterizing the relationship between flow-mediated vasodilation and radial artery tonometry in peripheral artery disease. J Surg Res 2018; 224:121-131. [PMID: 29506827 PMCID: PMC5844355 DOI: 10.1016/j.jss.2017.11.062] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Revised: 11/18/2017] [Accepted: 11/22/2017] [Indexed: 01/22/2023]
Abstract
BACKGROUND Arterial stiffness, measured by the augmentation index (AIX) from radial artery tonometry, and endothelial dysfunction, measured by brachial-artery flow-mediated vasodilation (FMD), have each been associated with increased risk of cardiovascular events. However, their interrelationship in peripheral artery disease (PAD) patients is poorly understood. MATERIALS AND METHODS In a cross-sectional analysis of 123 vascular surgery outpatients, the association between FMD and AIX was examined in controls with atherosclerotic risk factors (n = 32) and patients with PAD (n = 91). PAD was defined as claudication symptoms with an ankle-brachial index of <0.9 or a history of revascularization for symptomatic PAD. Controls had an ankle-brachial index ≥0.9 and no history of atherosclerotic vascular disease. RESULTS Compared to controls, patients with PAD had lower FMD (6.3 ± 3.8 versus 8.4 ± 3.7, P = 0.008), while central AIX normalized to 75 beats per minute (25.5 ± 9.0 versus 19.3 ± 8.6, P = 0.001) and peripheral AIX (91.3 ± 14.5 versus 81.3 ± 11.4, P = 0.001) were higher. FMD was not significantly correlated with either central or peripheral AIX (central AIX: P = 0.58; peripheral AIX: P = 0.89) across the entire cohort, or in either the patients with PAD (central AIX: P = 0.48; peripheral AIX: P = 0.23) or controls (central AIX: P = 0.43; peripheral AIX: P = 0.92). In a multivariate model including FMD, higher AIX remained independently associated with PAD. CONCLUSIONS In an analysis of vascular surgery outpatients, no correlation between FMD and AIX was detected. Larger prospective studies are needed to determine whether the inclusion of both parameters improves predictive models for the early identification and potential risk stratification of PAD patients.
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Affiliation(s)
- Greg J Zahner
- Department of Surgery, University of California, San Francisco, San Francisco, California
| | - Kimberly A Spaulding
- Department of Surgery, University of California, San Francisco, San Francisco, California; Vascular Surgery Section, Veterans Affairs Medical Center, San Francisco, California
| | - Joel L Ramirez
- Department of Surgery, University of California, San Francisco, San Francisco, California
| | - Melinda S Schaller
- Department of Surgery, University of California, San Francisco, San Francisco, California
| | - Shane C Walker
- Department of Surgery, University of California, San Francisco, San Francisco, California
| | - Nancy K Hills
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California
| | - Warren J Gasper
- Department of Surgery, University of California, San Francisco, San Francisco, California; Vascular Surgery Section, Veterans Affairs Medical Center, San Francisco, California
| | - S Marlene Grenon
- Department of Surgery, University of California, San Francisco, San Francisco, California; Vascular Surgery Section, Veterans Affairs Medical Center, San Francisco, California.
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Badhwar S, Chandran DS, Jaryal AK, Narang R, Deepak KK. Regional arterial stiffness in central and peripheral arteries is differentially related to endothelial dysfunction assessed by brachial flow-mediated dilation in metabolic syndrome. Diab Vasc Dis Res 2018; 15:106-113. [PMID: 29283006 DOI: 10.1177/1479164117748840] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The interrelationship between endothelial function and arterial stiffness may be different for central and peripheral arteries due to their structural and functional differences. The study aims to assess the interrelationship between central and peripheral vascular function and haemodynamics in metabolic syndrome. Thirty-seven patients [63.0 (57.5-66.0) years, 68.4% males] of metabolic syndrome (National Cholesterol Education Program - Adult Treatment Panel-III criteria) were studied. Carotid-femoral, carotid-radial pulse wave velocity and augmentation index (AIx@75) were assessed using applanation tonometry. Endothelial function was evaluated by brachial flow-mediated dilation using B-mode ultrasonography. Central and peripheral pressures were measured by radial tonometry and sphygmomanometer, respectively. Carotid-radial pulse wave velocity correlated significantly with peripheral diastolic blood pressure ( r = 0.33, p = 0.04) and inversely with flow-mediated dilation ( r = -0.61, p = 0.0001). AIx@75 correlated significantly with carotid-femoral pulse wave velocity ( r = 0.35, p = 0.03) and with aortic pulse pressure ( r = 0.43, p = 0.01). In principal component analysis, an inverse relationship was observed between flow-mediated dilation and carotid-radial pulse wave velocity but not with carotid-femoral pulse wave velocity. Regional arterial stiffness assessed by pulse wave velocity in central-elastic and peripheral-muscular arteries differentially relates to endothelial dysfunction. The central arteries might be predominantly influenced by endothelial dysfunction-induced structural changes, while the peripheral arteries are majorly affected by functional alterations.
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Affiliation(s)
- Smriti Badhwar
- 1 Autonomic and Vascular Function Lab, Department of Physiology, All India Institute of Medical Sciences, New Delhi, India
| | - Dinu S Chandran
- 1 Autonomic and Vascular Function Lab, Department of Physiology, All India Institute of Medical Sciences, New Delhi, India
| | - Ashok Kumar Jaryal
- 1 Autonomic and Vascular Function Lab, Department of Physiology, All India Institute of Medical Sciences, New Delhi, India
| | - Rajiv Narang
- 2 Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | - Kishore Kumar Deepak
- 1 Autonomic and Vascular Function Lab, Department of Physiology, All India Institute of Medical Sciences, New Delhi, India
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Sciatti E, Vizzardi E, Castiello A, Valentini F, Bonadei I, Gelsomino S, Lorusso R, Metra M. The role of type 2 diabetes mellitus on hypertensive-related aortic stiffness. Echocardiography 2018; 35:798-803. [PMID: 29457265 DOI: 10.1111/echo.13841] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
BACKGROUND Hypertension is strongly related to arterial stiffness in a cause-effect fashion. Diabetes mellitus is also thought to determine vascular damage, mostly by means of advanced glycosylation end-products (AGEs). Aim of our study was to study the role of type 2 diabetes mellitus (T2DM) as regard ascending aortic elastic properties in hypertensive patients. METHODS We prospectively enrolled outpatients with hypertension (n = 99) and type 2 diabetes mellitus plus hypertension (n = 42) without cardiovascular events. They underwent a transthoracic echocardiography to measure aortic diameters, aortic elastic properties (ie, compliance, distensibility, stiffness index, Peterson's elastic modulus, pulse wave velocity, M-mode strain), tissue Doppler imaging (TDI) to calculate diastolic (E' and A') and systolic (S') velocities, and tissue strain. Multivariable analysis was run to assess the association between T2DM and these variables after correcting for possible confounders (age, sex, body mass index [BMI], dyslipidemia). RESULTS The two groups did not differ as regards age, sex, BMI, and blood pressure. However, T2DM patients were more likely to be dyslipidemic (43% vs 71%, P = .003). Aortic diameters were similar in the two groups, but the aortic elastic properties significantly more impaired in T2DM group. At multivariable analysis, stiffness index, Peterson's elastic modulus, the TDI waves, and the tissue strain remained associated with the co-presence of T2DM and hypertension. CONCLUSION Our data suggest that people suffering from both T2DM and hypertension have more impaired aortic elastic properties than those hypertensive alone. Considering the prognostic role of aortic stiffness, these patients may benefit from a closer follow-up.
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Affiliation(s)
- Edoardo Sciatti
- Cardiology Unit, University and ASST Spedali Civili, Brescia, Italy
| | - Enrico Vizzardi
- Cardiology Unit, University and ASST Spedali Civili, Brescia, Italy
| | | | | | - Ivano Bonadei
- Cardiology Unit, University and ASST Spedali Civili, Brescia, Italy
| | - Sandro Gelsomino
- Department of Cardio-Thoracic Surgery, Cardiovascular Research Institute Maastricht-CARIM, Heart & Vascular Center, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
| | - Roberto Lorusso
- Department of Cardio-Thoracic Surgery, Cardiovascular Research Institute Maastricht-CARIM, Heart & Vascular Center, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
| | - Marco Metra
- Cardiology Unit, University and ASST Spedali Civili, Brescia, Italy
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24
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Yasuda T, Fukumura K, Tomaru T, Nakajima T. Thigh muscle size and vascular function after blood flow-restricted elastic band training in older women. Oncotarget 2018; 7:33595-607. [PMID: 27244884 PMCID: PMC5085105 DOI: 10.18632/oncotarget.9564] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Accepted: 05/12/2016] [Indexed: 12/20/2022] Open
Abstract
We examined the effect of elastic band training with blood flow restriction (BFR) on thigh muscle size and vascular function in older women. Older women were divided into three groups: low-intensity elastic band BFR training (BFR-Tr, n = 10), middleto high-intensity elastic band training (MH-Tr, n = 10), and no training (Ctrl, n = 10) groups. BFR-Tr and MH-Tr groups performed squat and knee extension exercises using elastic band, 2 days/week for 12 weeks. During BFR-Tr exercise session, subjects wore pressure cuffs around the most proximal region of both thighs. The following measurements were taken before (pre) and 3-5 days after (post) the final training session: MRI-measured muscle cross-sectional area (CSA) at mid-thigh, maximum voluntary isometric contraction (MVIC) of knee extension, central systolic blood pressure (c-SBP), central-augmentation index (c-AIx), cardio-ankle vascular index testing (CAVI), ankle-brachial pressure index (ABI). Quadriceps muscle CSA (6.9%) and knee extension MVIC (13.7%) were increased (p < 0.05) in the BFR-Tr group, but not in the MH-Tr and the Ctrl groups. Regarding c-SBP, c-AIx, CAVI and ABI, there were no changes between pre- and post- results among the three groups. Elastic band BFR training increases thigh muscle CSA as well as maximal muscle strength, but does not decrease vascular function in older women.
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Affiliation(s)
- Tomohiro Yasuda
- Graduate School of Medicine, University of Tokyo, Tokyo, Japan.,School of Nursing, Seirei Christopher University, Shizuoka, Japan.,Faculty of Medicine, Toho University, Chiba, Japan
| | - Kazuya Fukumura
- Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | | | - Toshiaki Nakajima
- Graduate School of Medicine, University of Tokyo, Tokyo, Japan.,Heart Center, Dokkyo Medical University Hospital, Tochigi, Japan
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25
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Vilmi-Kerälä T, Koivistoinen T, Palomäki O, Uotila J, Palomäki A. Arterial stiffness in fertile women with metabolic syndrome. Ann Med 2017; 49:636-643. [PMID: 28590772 DOI: 10.1080/07853890.2017.1339907] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
INTRODUCTION Although metabolic syndrome (MetS) is evidently associated with the risk of cardiovascular disease (CVD), recently its use has been questioned. We studied the utility of MetS diagnosis when estimating individual CVD risk. METHODS We compared 27 fertile women with MetS and 27 counterparts without the syndrome, matched pairwise according to well-known risk factors of CVD. Pulse wave velocity (PWV) and central blood pressure (cBP) were determined noninvasively via a SphygmoCor device. Arterial compliance was measured noninvasively with an HDI/PulseWaveTMCR-2000 arterial tonometer. RESULTS PWV (7.1 ± 2.5 versus 6.5 ± 1.1 m/s, p = .037), and both systolic (120.9 ± 12.2 versus 111.5 ± 16.0 mmHg, p = .031) and diastolic cBP (81.3 ± 8.5 versus 74.1 ± 11.2 mmHg, p = .035) were higher in the MetS group. Systemic arterial compliance values were lower in both large (15.1 ± 8.0 versus 16.1 ± 4.4 mL/mmHg × 10, p = .034) and small arteries (7.1 ± 2.5 versus 9.3 ± 3.2 mL/mmHg ×100, p = .010) in women with MetS. CONCLUSIONS Fertile women with MetS had increased arterial stiffness, as measured by three different methods. Our results highlight the utility of MetS when revealing increased individual CVD risks in fertile-aged women. Key messages Women with MetS have increased arterial stiffness when measured by different methods. MetS is a useful clinical tool to assess increased cardiovascular risk, particularly among fertile-aged women.
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Affiliation(s)
- Tiina Vilmi-Kerälä
- a Faculty of Medicine and Life Sciences , University of Tampere , Tampere , Finland.,b Department of Obstetrics and Gynecology , Tampere University Hospital , Tampere , Finland
| | - Teemu Koivistoinen
- c Department of Emergency Medicine , Kanta-Häme Central Hospital , Hämeenlinna , Finland
| | - Outi Palomäki
- b Department of Obstetrics and Gynecology , Tampere University Hospital , Tampere , Finland
| | - Jukka Uotila
- a Faculty of Medicine and Life Sciences , University of Tampere , Tampere , Finland.,b Department of Obstetrics and Gynecology , Tampere University Hospital , Tampere , Finland
| | - Ari Palomäki
- a Faculty of Medicine and Life Sciences , University of Tampere , Tampere , Finland.,c Department of Emergency Medicine , Kanta-Häme Central Hospital , Hämeenlinna , Finland.,d Cardiometabolic Unit , Linnan Klinikka , Hämeenlinna , Finland
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26
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Okada Y, Shibata S, Fujimoto N, Best SA, Levine BD, Fu Q. Long-term effects of a renin inhibitor versus a thiazide diuretic on arterial stiffness and left ventricular diastolic function in elderly hypertensive patients. Am J Physiol Regul Integr Comp Physiol 2017; 313:R400-R409. [PMID: 28724547 DOI: 10.1152/ajpregu.00125.2017] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Revised: 07/12/2017] [Accepted: 07/13/2017] [Indexed: 01/15/2023]
Abstract
Arterial stiffness and cardiac function are important predictors of cardiovascular events in patients with hypertension, even with adequate blood pressure (BP) control. We evaluated whether a direct renin inhibitor, aliskiren, reduces arterial stiffness and modulates left ventricular function compared with a diuretic, hydrochlorothiazide, in elderly hypertensive patients. Twenty-one hypertensive patients [67 ± 14 (SD) yr] were randomly assigned to receive 6-mo aliskiren (n = 11) or hydrochlorothiazide (n = 10)-based therapy. We assessed β-stiffness of the local arteries, arterial elastance (Ea), and echocardiographic variables, including early (E) and late (A) mitral inflow velocity, deceleration time of E, early (E') and late (A') diastolic mitral annular velocity, and left ventricular end-systolic elastance (Ees) before and after treatment. BP decreased similarly (P < 0.001) after both therapies. β-Stiffness of the carotid artery decreased after aliskiren but increased after hydrochlorothiazide treatment (aliskiren: 6.42 ± 2.34 pre vs. 5.07 ± 1.29 post; hydrochlorothiazide: 5.05 ± 1.78 vs. 7.25 ± 2.68, P = 0.001 for interaction). β-Stiffness of the femoral and radial arteries were not different after either treatment. Different from aliskiren, E decreased (73 ± 16 vs. 67 ± 14 cm/s, P = 0.026), and the deceleration time was prolonged (218 ± 40 vs. 236 ± 35 ms, P = 0.032) after hydrochlorothiazide therapy, whereas the E/A, and E' remained unchanged after both treatments. Ea and Ees decreased after aliskiren therapy (both P < 0.05), whereas the Ea/Ees (ventricular-arterial coupling) was maintained after both treatments. Thus, aliskiren decreased the stiffness of carotid artery and left ventricular end-systolic elastance with maintenance of ventricular-arterial coupling without any effects on diastolic filling, while hydrochlorothiazide increased carotid arterial stiffness and slowed early diastolic filling in elderly hypertensive patients.
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Affiliation(s)
- Yoshiyuki Okada
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,University of Texas Southwestern Medical Center, Dallas, Texas; and.,Department of Special Care Dentistry, Matsumoto Dental University, Nagano, Japan
| | - Shigeki Shibata
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,University of Texas Southwestern Medical Center, Dallas, Texas; and
| | - Naoki Fujimoto
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,University of Texas Southwestern Medical Center, Dallas, Texas; and
| | - Stuart A Best
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,University of Texas Southwestern Medical Center, Dallas, Texas; and
| | - Benjamin D Levine
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,University of Texas Southwestern Medical Center, Dallas, Texas; and
| | - Qi Fu
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; .,University of Texas Southwestern Medical Center, Dallas, Texas; and
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27
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Mikael LDR, Paiva AMGD, Gomes MM, Sousa ALL, Jardim PCBV, Vitorino PVDO, Euzébio MB, Sousa WDM, Barroso WKS. Vascular Aging and Arterial Stiffness. Arq Bras Cardiol 2017; 109:253-258. [PMID: 28678931 PMCID: PMC5586233 DOI: 10.5935/abc.20170091] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 05/04/2017] [Indexed: 01/03/2023] Open
Abstract
Cardiovascular diseases (CVD) account annually for almost one third of all deaths
worldwide. Among the CVD, systemic arterial hypertension (SAH) is related to
more than half of those outcomes. Type 2 diabetes mellitus is an independent
risk factor for SAH because it causes functional and structural damage to the
arterial wall, leading to stiffness. Several studies have related oxidative
stress, production of free radicals, and neuroendocrine and genetic changes to
the physiopathogenesis of vascular aging. Indirect ways to analyze that aging
process have been widely studied, pulse wave velocity (PWV) being considered
gold standard to assess arterial stiffness, because there is large
epidemiological evidence of its predictive value for cardiovascular events, and
it requires little technical knowledge to be performed. A pulse wave is
generated during each cardiac contraction and travels along the arterial bed
until finding peripheral resistance or any bifurcation point, determining the
appearance of a reflected wave. In young individuals, arteries tend to be more
elastic, therefore, the reflected wave occurs later in the cardiac cycle,
reaching the heart during diastole. In older individuals, however, the reflected
wave occurs earlier, reaching the heart during systole. Because PWV is an
important biomarker of vascular damage, highly valuable in determining the
patient’s global cardiovascular risk, we chose to review the articles on
vascular aging in the context of cardiovascular risk factors and the tools
available to the early identification of that damage.
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Affiliation(s)
| | | | | | - Ana Luiza Lima Sousa
- Liga de Hipertensão Arterial - Faculdade de Medicina - UFG, Goiânia, GO - Brazil
| | | | | | - Maicon Borges Euzébio
- Liga de Hipertensão Arterial - Faculdade de Medicina - UFG, Goiânia, GO - Brazil.,Pontifícia Universidade Católica de Goiás, Goiânia, GO - Brazil
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Vilmi-Kerälä T, Lauhio A, Tervahartiala T, Palomäki O, Uotila J, Sorsa T, Palomäki A. Subclinical inflammation associated with prolonged TIMP-1 upregulation and arterial stiffness after gestational diabetes mellitus: a hospital-based cohort study. Cardiovasc Diabetol 2017; 16:49. [PMID: 28407807 PMCID: PMC5390403 DOI: 10.1186/s12933-017-0530-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Accepted: 04/04/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) has significant implications for the future health of the mother. Some clinical studies have suggested subclinical inflammation and vascular dysfunction after GDM. We aimed to study whether concentrations of high-sensitivity C-reactive protein (hsCRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-8 (MMP-8) and -9, as well as values of arterial stiffness differ between women with and without a history of GDM a few years after delivery. We also investigated possible effects of obesity on the results. METHODS We studied two cohorts-120 women with a history of GDM and 120 controls-on average 3.7 years after delivery. Serum concentrations of hsCRP were determined by immunonephelometric and immunoturbidimetric methods, MMP-8 by immunofluorometric assay, and MMP-9 and TIMP-1 by enzyme-linked immunosorbent assays. Pulse wave velocity (PWV) was determined using the foot-to-foot velocity method from carotid and femoral waveforms by using a SphygmoCor device. Arterial compliance was measured non-invasively by an HDI/PulseWave™CR-2000 arterial tonometer. All 240 women were also included in subgroup analyses to study the effect of obesity on the results. Multiple linear regression analyses were performed with adjustment for confounding factors. RESULTS PWV after pregnancy complicated by GDM was significantly higher than after normal pregnancy, 6.44 ± 0.83 (SD) vs. 6.17 ± 0.74 m/s (p = 0.009). Previous GDM was also one of the significant determinants of PWV in multiple linear regression analyses. On the other hand, compliance indices of both large (p = 0.092) and small (p = 0.681) arteries did not differ between the study cohorts. Serum TIMP-1 levels were significantly increased after previous GDM (p = 0.020). However, no differences were found in the serum levels of MMP-8, MMP-9 or hsCRP. In subgroup analyses, there were significantly higher concentrations of hsCRP (p = 0.015) and higher PWV (p < 0.001) among obese women compared with non-obese ones. CONCLUSIONS PWV values were significantly higher after GDM compared with normoglycemic pregnancies and were associated with prolonged TIMP-1 upregulation. Cardiovascular risk factors were more common in participants with high BMI than in those with previous GDM.
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Affiliation(s)
- Tiina Vilmi-Kerälä
- School of Medicine, University of Tampere, Tampere, Finland. .,Department of Obstetrics and Gynecology, Tampere University Hospital, Box 2000, 33521, Tampere, Finland.
| | - Anneli Lauhio
- Department of Infectious Diseases, Inflammation Center, Helsinki University Hospital, Helsinki, Finland.,Clinicum, University of Helsinki, Helsinki, Finland.,The Social Insurance Institution of Finland, Benefit Services, Helsinki, Finland
| | - Taina Tervahartiala
- Department of Oral and Maxillofacial Diseases, Helsinki University and University Hospital, Helsinki, Finland
| | - Outi Palomäki
- Department of Obstetrics and Gynecology, Tampere University Hospital, Box 2000, 33521, Tampere, Finland
| | - Jukka Uotila
- School of Medicine, University of Tampere, Tampere, Finland.,Department of Obstetrics and Gynecology, Tampere University Hospital, Box 2000, 33521, Tampere, Finland
| | - Timo Sorsa
- Department of Oral and Maxillofacial Diseases, Helsinki University and University Hospital, Helsinki, Finland.,Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden
| | - Ari Palomäki
- School of Medicine, University of Tampere, Tampere, Finland.,Department of Emergency Medicine, Kanta-Häme Central Hospital, Hämeenlinna, Finland
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Peyster E, Chen J, Feldman HI, Go AS, Gupta J, Mitra N, Pan Q, Porter A, Rahman M, Raj D, Reilly M, Wing MR, Yang W, Townsend RR. Inflammation and Arterial Stiffness in Chronic Kidney Disease: Findings From the CRIC Study. Am J Hypertens 2017; 30:400-408. [PMID: 28391349 PMCID: PMC5861572 DOI: 10.1093/ajh/hpw164] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Revised: 11/30/2016] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) and arterial stiffness are associated with increased cardiovascular morbidity and mortality. Inflammation is proposed to have a role in the development of arterial stiffness, and CKD is recognized as a proinflammatory state. Arterial stiffness is increased in CKD, and cross-sectional data has suggested a link between increased inflammatory markers in CKD and higher measures of arterial stiffness. However, no large scale investigations have examined the impact of inflammation on the progression of arterial stiffness in CKD. METHODS We performed baseline assessments of 5 inflammatory markers in 3,939 participants from the chronic renal insufficiency cohort (CRIC), along with serial measurements of arterial stiffness at 0, 2, and 4 years of follow-up. RESULTS A total of 2,933 participants completed each of the follow-up stiffness measures. In cross-sectional analysis at enrollment, significant associations with at least 2 measures of stiffness were observed for fibrinogen, interleukin-6, high-sensitivity C-reactive protein, proteinuria, and composite inflammation score after adjustment for confounders. In longitudinal analyses, there were few meaningful correlations between baseline levels of inflammation and changes in metrics of arterial stiffness over time. CONCLUSION In a large cohort of CKD participants, we observed multiple significant correlations between initial markers of inflammation and metrics of arterial stiffness, but baseline inflammation did not predict changes in arterial stiffness over time. While well-described biologic mechanisms provide the basis for our understanding of the cross-sectional results, continued efforts to design longitudinal studies are necessary to fully elucidate the relationship between chronic inflammation and arterial stiffening.
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Affiliation(s)
- Eliot Peyster
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Jing Chen
- Tulane University Schools of Medicine and Public Health and Tropical Medicine, New Orleans, Louisiana, USA
| | - Harold I Feldman
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Center for Clinical Epidemiology & Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Alan S Go
- Division of Research, Kaiser Permanente of Northern California, Oakland, California, USA
| | - Jayanta Gupta
- Department of Health Sciences, College of Health Professions and Social Work, Florida Gulf Coast University, Fort Myers, Florida, USA
| | - Nandita Mitra
- Center for Clinical Epidemiology & Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Qiang Pan
- Center for Clinical Epidemiology & Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Anna Porter
- Department of Medicine, University of Illinois, Chicago, Illinois, USA
| | - Mahboob Rahman
- Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA
| | - Dominic Raj
- Division of Renal Diseases & Hypertension, MFA-George Washington University, Washington, DC, USA
| | - Muredach Reilly
- Irving Institute for Clinical and Translational Research, Columbia University, New York, New York, USA
| | - Maria R Wing
- Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA
| | - Wei Yang
- Center for Clinical Epidemiology & Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Raymond R Townsend
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Jekell A, Kalani M, Kahan T. The effects of alpha 1-adrenoceptor blockade and angiotensin converting enzyme inhibition on central and brachial blood pressure and vascular reactivity: the doxazosin-ramipril study. Heart Vessels 2016; 32:674-684. [PMID: 27885499 PMCID: PMC5446849 DOI: 10.1007/s00380-016-0924-9] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Accepted: 11/18/2016] [Indexed: 12/24/2022]
Abstract
We aimed to study whether inhibition of the renin–angiotensin–aldosterone system has effects on vascular structure and function beyond the effects on blood pressure reduction alone. Patients with mild-to-moderate hypertension (n = 61, age 54 ± 12 years, 34% women) received the angiotensin converting enzyme inhibitor ramipril 10 mg or the alpha 1-adrenoceptor blocker doxazosin 8 mg double-blind for 12 weeks. Aortic blood pressure, pulse wave velocity, and augmentation index were assessed by applanation tonometry. Endothelial function was studied by forearm post-ischemic flow mediated vasodilatation and by pulse wave analysis with beta 2-adrenoceptor agonist stimulation. Skin microvascular reactivity was assessed by laser Doppler fluxmetry and iontophoresis. Treatment with doxazosin or ramipril reduced aortic and brachial blood pressures (all P < 0.001), with greater reductions in aortic than brachial systolic blood pressures (P = 0.021) and aortic/brachial pulse pressure ratio (P = 0.005). Compared to doxazosin, ramipril reduced carotid-femoral and carotid-radial pulse wave velocity (both P < 0.05). Forearm endothelial dependent and independent vasodilatation, assessed by post-ischemic flow mediated vasodilatation and glyceryl trinitrate, and by pulse wave analysis remained unchanged by both doxazosin and ramipril. In addition, skin microvascular endothelial dependent (acetylcholine) and independent vasodilatation (sodium nitroprusside) remained unchanged. In conclusion, ramipril reduced indices of aortic stiffness, suggesting that angiotensin converting enzyme inhibitor therapy may have effects beyond blood pressure reduction. However, treatment did not appear to influence endothelial function. Evidence of endothelial dysfunction and its possible improvement by antihypertensive treatment might require more advanced hypertension. This study is registered at ClinicalTrials.gov (NCT02901977) and at EudraCT (# 2007-000631-25).
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Affiliation(s)
- Andreas Jekell
- Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.,Department of Cardiology, Danderyd University Hospital Corp, Stockholm, Sweden
| | - Majid Kalani
- Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Thomas Kahan
- Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. .,Department of Cardiology, Danderyd University Hospital Corp, Stockholm, Sweden.
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Kao YT, Wang ST, Shih CM, Lin FY, Tsao NW, Chiang KH, Chan CS, Lin YC, Hung MY, Hsieh MH, Shyu KG, Chen JW, Chang NC, Yeh JS, Huang CY. Arterial Stiffness Index and Coronary Artery Plaques in Patients with Subclinical Coronary Atherosclerosis. ACTA CARDIOLOGICA SINICA 2016; 31:59-65. [PMID: 27122847 DOI: 10.6515/acs20140630b] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND Arterial stiffness is a physiologic quantitative value used to measure arterial compliance. It is predictive of coronary atherosclerosis in patients with intermediate to high cardiovascular risk. However, a correlation between arterial stiffness and subclinical coronary atherosclerosis has yet to be established. Therefore, the purpose of this study was to evaluate arterial stiffness using an arterial stiffness index (ASI) and investigate its association with coronary artery plaque in patients with subclinical coronary atherosclerosis. METHODS Our study enrolled 156 consecutive subjects who underwent health screening using a 64-slice cardiac computed tomography angiography (CCTA). Their arterial stiffness index was assessed noninvasively by CardioVision(®) MS-2000. The atheroma on the coronary vessel walls was analyzed. RESULTS Of the 156 patients, 53 displayed at least one > 50% stenotic lesion over the coronary arteries in CCTA images. The patients with at least one > 50% coronary stenotic plaque were older and had higher systolic blood pressure and ASI values than patients without > 50% coronary stenotic plaque. After dividing the study population into 2 groups by those patients over and under 50 years of age, the ASI positively correlated with the presentation of at least one > 50% coronary stenotic plaque in patients aged ≥ 50 years (odds ratio = 1.02, 95% confidence interval: 1.00-1.04, p = 0.03). CONCLUSIONS The ASI could play a role in risk stratification systems for coronary artery disease in patients with subclinical coronary atherosclerosis, and is a useful clinical marker for the correlation of early coronary plaque. KEY WORDS Arterial stiffness; Arterial stiffness index; Atherosclerosis; Coronary artery plaque.
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Affiliation(s)
- Yung-Ta Kao
- Division of Cardiology, Department of Internal Medicine
| | - Sen-Te Wang
- Health Management Center, Taipei Medical University Hospital
| | - Chun-Ming Shih
- Division of Cardiology, Department of Internal Medicine; ; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University
| | - Feng-Yen Lin
- Division of Cardiology, Department of Internal Medicine; ; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University
| | - Nai-Wen Tsao
- Division of Cardiovascular Surgery, Department of Surgery
| | | | | | - Yen-Chung Lin
- Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital
| | - Ming-Yow Hung
- Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University
| | - Ming-Hsiung Hsieh
- Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University; ; Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University
| | - Kuo-Gi Shyu
- Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital; ; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University
| | - Jaw-Wen Chen
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Nen-Chung Chang
- Division of Cardiology, Department of Internal Medicine; ; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University
| | - Jong-Shiuan Yeh
- Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University; ; Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University; ; Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, Orangeburg, NY, USA
| | - Chun-Yao Huang
- Division of Cardiology, Department of Internal Medicine; ; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University
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Triantafyllias K, De Blasi M, Hoffmann I, Thomaidis T, Drees P, Schwarting A. The count of tender rather than swollen joints correlates with aortic stiffness in patients with rheumatoid arthritis. SPRINGERPLUS 2016; 5:428. [PMID: 27104116 PMCID: PMC4828367 DOI: 10.1186/s40064-016-2066-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Accepted: 03/29/2016] [Indexed: 01/21/2023]
Abstract
BACKGROUND Patients with rheumatoid arthritis (RA) are at a higher cardiovascular (CV) risk in comparison to the general population. CV risk associates closely with aortic stiffness. Aim of this exploration was therefore to evaluate aortic stiffness in patients with RA and to examine its association with various RA associated parameters as well as with traditional CV risk factors. METHODS Measurements of carotid-femoral pulse wave velocity (cfPWV) were analyzed retrospectively in 38 RA patients and 25 controls. We investigated the statistical difference between cfPWV values in the two groups. Furthermore, we analyzed the associations of cfPWV with laboratory and clinical RA parameters including Disease Activity Score 28 and its components, rheumatoid factor, cyclic citrullinated peptide antibodies, antinuclear antibodies and RA duration. Finally, we explored the relationship of cfPWV with traditional CV risk factors in the RA group. RESULTS cfPWV was not significantly higher in RA patients in comparison to controls in an adjusted statistical model for confounding factors [-0.587 95 % CI (-1.38 to 0.201), p = 0.144]. Among RA patients there was a statistically significant correlation of cfPWV with age (rho = 0.544, p = 0.001) and the count of tender joints [0.051 95 % CI (0.008-0.207), p = 0.034]. Finally, C-reactive protein associated only marginally with cfPWV [0.105 95 % CI (-0.410 to 0.003), p = 0.053]. CONCLUSIONS In RA patients the number of tender, rather than swollen joints correlates with stiffness of the aorta, as measured through cfPWV. Therefore, RA associated joint pain might play a role in the development of aortic stiffness and thus increase CV risk.
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Affiliation(s)
| | - Michele De Blasi
- />ACURA Rheumatology Clinics, Kaiser-Wilhelm-Str. 9-11, 55543 Bad Kreuznach, Germany
| | - Isabell Hoffmann
- />Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), Johannes Gutenberg University, Mainz, Germany
| | - Thomas Thomaidis
- />First Department of Medicine, Johannes Gutenberg University, Mainz, Germany
| | - Philipp Drees
- />Department of Orthopaedics and Trauma Surgery, Johannes Gutenberg University, Mainz, Germany
| | - Andreas Schwarting
- />ACURA Rheumatology Clinics, Kaiser-Wilhelm-Str. 9-11, 55543 Bad Kreuznach, Germany
- />First Department of Medicine, Johannes Gutenberg University, Mainz, Germany
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Lacroix S, Des Rosiers C, Gayda M, Nozza A, Thorin É, Tardif JC, Nigam A. A single Mediterranean meal does not impair postprandial flow-mediated dilatation in healthy men with subclinical metabolic dysregulations. Appl Physiol Nutr Metab 2016; 41:888-94. [PMID: 27454855 DOI: 10.1139/apnm-2015-0490] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Cardiovascular risk factors are known to exacerbate high-saturated fatty acid meal (HSFAM)-induced endothelial dysfunction, but the influence of subclinical metabolic dysregulations and the acute impact of a single mixed Mediterranean-type meal (MMM) remains unknown. Thus, this study has the objective to evaluate the metabolic and vascular effect of such meals in healthy subjects with or without subclinical fasting metabolic dysregulations. Twenty-eight healthy males without overt cardiovascular risk factors randomly ingested 1 of 2 isocaloric meals on separate days. Plasma metabolic markers, fatty acid (FA) profile, and endothelial function (flow-mediated dilatation; FMD) were assessed at baseline and 2 and 4 h after meal ingestion. Unsupervised hierarchical clustering identified 2 subgroups of participants (n = 11 and 17) differing by their baseline metabolic profiles. The MMM did not significantly alter postprandial endothelial function in all subjects, irrespective of baseline metabolic parameters. In contrast, the HSFAM induced postprandial endothelial dysfunction (Δ%FMDabsolute = -5.28 ± 2.54, p < 0.01 vs. MMM) in a subgroup of individuals with significantly greater body mass index, fasting insulinemia, and lipid parameters (n = 11). Finally, the postprandial plasma FA profiles were differentially enriched by the HSFAM and MMM, notably with saturated FAs and omega-3 polyunsaturated FAs, respectively. Collectively, our results highlight the detrimental impact of a single HSFAM on endothelial function in healthy individuals displaying subclinical fasting metabolic dysregulations. Such individuals could benefit from MMM, demonstrated herein to be without any acute detriment to endothelial function.
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Affiliation(s)
- Sébastien Lacroix
- a Cardiovascular Prevention and Rehabilitation Centre, Montreal Heart Institute, 5055 St-Zotique Street East, Montreal, QC H1T 1N6, Canada.,b Montreal Heart Institute Research Center, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada.,c Department of Nutrition, Faculty of Medicine, Université de Montréal, 2405, Côte-Sainte-Catherine Road, Montréal, QC H3T 1A8, Canada
| | - Christine Des Rosiers
- a Cardiovascular Prevention and Rehabilitation Centre, Montreal Heart Institute, 5055 St-Zotique Street East, Montreal, QC H1T 1N6, Canada.,b Montreal Heart Institute Research Center, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada.,c Department of Nutrition, Faculty of Medicine, Université de Montréal, 2405, Côte-Sainte-Catherine Road, Montréal, QC H3T 1A8, Canada
| | - Mathieu Gayda
- a Cardiovascular Prevention and Rehabilitation Centre, Montreal Heart Institute, 5055 St-Zotique Street East, Montreal, QC H1T 1N6, Canada.,b Montreal Heart Institute Research Center, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada.,d Department of Medicine, Université de Montréal, 2900, Édouard-Montpetit Blvd., Montréal, QC H3T 1J4, Canada
| | - Anna Nozza
- e Montreal Heart Institute Coordinating Center, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada
| | - Éric Thorin
- b Montreal Heart Institute Research Center, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada.,f Department of Surgery, Université de Montréal, 2900, Édouard-Montpetit Blvd., Montréal, QC H3T 1J4, Canada
| | - Jean-Claude Tardif
- b Montreal Heart Institute Research Center, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada.,d Department of Medicine, Université de Montréal, 2900, Édouard-Montpetit Blvd., Montréal, QC H3T 1J4, Canada
| | - Anil Nigam
- a Cardiovascular Prevention and Rehabilitation Centre, Montreal Heart Institute, 5055 St-Zotique Street East, Montreal, QC H1T 1N6, Canada.,b Montreal Heart Institute Research Center, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada.,c Department of Nutrition, Faculty of Medicine, Université de Montréal, 2405, Côte-Sainte-Catherine Road, Montréal, QC H3T 1A8, Canada.,d Department of Medicine, Université de Montréal, 2900, Édouard-Montpetit Blvd., Montréal, QC H3T 1J4, Canada
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Tritakis V, Tzortzis S, Ikonomidis I, Dima K, Pavlidis G, Trivilou P, Paraskevaidis I, Katsimaglis G, Parissis J, Lekakis J. Association of arterial stiffness with coronary flow reserve in revascularized coronary artery disease patients. World J Cardiol 2016; 8:231-239. [PMID: 26981218 PMCID: PMC4766273 DOI: 10.4330/wjc.v8.i2.231] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Revised: 10/09/2015] [Accepted: 12/11/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the association of arterial wave reflection with coronary flow reserve (CFR) in coronary artery disease (CAD) patients after successful revascularization.
METHODS: We assessed 70 patients with angiographically documented CAD who had undergone recent successful revascularization. We measured (1) reactive hyperemia index (RHI) using fingertip peripheral arterial tonometry (RH-PAT Endo-PAT); (2) carotid to femoral pulse wave velocity (PWVc-Complior); (3) augmentation index (AIx), the diastolic area (DAI%) and diastolic reflection area (DRA) of the central aortic pulse wave (Arteriograph); (4) CFR using Doppler echocardiography; and (5) blood levels of lipoprotein-phospholipase A2 (Lp-PLA2).
RESULTS: After adjustment for age, sex, blood pressure parameter, lipidemic, diabetic and smoking status, we found that coronary flow reserve was independently related to AIx (b = -0.38, r = 0.009), DAI (b = 0.36, P = 0.014), DRA (b = 0.39, P = 0.005) and RT (b = -0.29, P = 0.026). Additionally, patients with CFR < 2.5 had higher PWVc (11.6 ± 2.3 vs 10.2 ± 1.4 m/s, P = 0.019), SBPc (139.1 ± 17.8 vs 125.2 ± 19.1 mmHg, P = 0.026), AIx (38.2% ± 14.8% vs 29.4% ± 15.1%, P = 0.011) and lower RHI (1.26 ± 0.28 vs 1.50 ± 0.46, P = 0.012), DAI (44.3% ± 7.9% vs 53.9% ± 6.7%, P = 0.008), DRA (42.2 ± 9.6 vs 51.6 ± 11.4, P = 0.012) and LpPLA2 (268.1 ± 91.9 vs 199.5 ± 78.4 ng/mL, P = 0.002) compared with those with CFR ≥ 2.5. Elevated LpPLA2 was related with reduced CFR (r = -0.33, P = 0.001), RHI (r = -0.37, P < 0.001) and DRA (r = -0.35, P = 0.001) as well as increased PWVc (r = 0.34, P = 0.012) and AIx (r = 0.34, P = 0.001).
CONCLUSION: Abnormal arterial wave reflections are related with impaired coronary flow reserve despite successful revascularization in CAD patients. There is a common inflammatory link between impaired aortic wall properties, endothelial dysfunction and coronary flow impairment in CAD.
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Gkaliagkousi E, Gavriilaki E, Triantafyllou A, Douma S. Clinical Significance of Endothelial Dysfunction in Essential Hypertension. Curr Hypertens Rep 2016; 17:85. [PMID: 26371063 DOI: 10.1007/s11906-015-0596-3] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The endothelium is recognized as a major determinant of vascular physiology and pathophysiology. Over the last few decades, a plethora of studies have implicated endothelial dysfunction in the progression of atherosclerosis and the subclinical target organ damage observed in essential hypertension. However, the clinical significance of diagnosing endothelial dysfunction in patients with essential hypertension remains under investigation. Although a number of vascular and non-vascular markers of endothelial dysfunction have been proposed, there is an ongoing quest for a marker in the clinical setting that is optimal, inexpensive, and reproducible. In addition, endothelial dysfunction emerges as a promising therapeutic target of agents that are readily available in clinical practice. In this context, a better understanding of its role in essential hypertension becomes of great importance. Here, we aim to investigate the clinical significance of endothelial dysfunction in essential hypertension by accumulating novel data on (a) early diagnosis using robust markers with prognostic value in cardiovascular risk prediction, (b) the association of endothelial dysfunction with subclinical vascular organ damage, and (c) potential therapeutic targets.
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Affiliation(s)
- Eugenia Gkaliagkousi
- 3rd Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, Ring Road Nea Eukarpia, 564 03, Thessaloniki, Greece.
| | - Eleni Gavriilaki
- 3rd Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, Ring Road Nea Eukarpia, 564 03, Thessaloniki, Greece
| | - Areti Triantafyllou
- 3rd Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, Ring Road Nea Eukarpia, 564 03, Thessaloniki, Greece
| | - Stella Douma
- 3rd Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, Ring Road Nea Eukarpia, 564 03, Thessaloniki, Greece
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Ajala O, Jensen LA, Ryan E, Chik C. Women with a history of gestational diabetes on long-term follow up have normal vascular function despite more dysglycemia, dyslipidemia and adiposity. Diabetes Res Clin Pract 2015; 110:309-14. [PMID: 26489823 DOI: 10.1016/j.diabres.2015.10.004] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Revised: 09/17/2015] [Accepted: 10/01/2015] [Indexed: 12/26/2022]
Abstract
AIMS Previous gestational diabetes (GDM) is a risk factor for type 2 diabetes and increased metabolic risk, but the link with vascular dysfunction is not clear. This study examined vascular function in women 4-10 years after a diagnosis of GDM who had a normal oral glucose tolerance test (OGTT) in the first postpartum year. METHODS We studied 90 women with a history of GDM and 59 age-matched controls, examining differences in insulin resistance as measured by the Homeostatic Model Assessment (HOMA-IR) and glucose responses during an OGTT, adiposity, lipid profile and C-reactive protein (CRP). Using pulse wave analysis, we also measured cardiac function, vascular compliance, and systemic vascular resistance. RESULTS Women with a history of GDM had higher measures of adiposity (body mass index 28.9 ± 6.5 vs. 26.6 ± 6.9 kg/m(2), P=0.04, waist-hip ratio 0.85 ± 0.06 vs. 0.79 ± 0.07, P<0.001), dyslipidemia (LDL cholesterol 2.78 ± 0.64 vs. 2.41 ± 0.56 mmol/L, P<0.001, total cholesterol: HDL cholesterol 3.93 ± 1.2 vs. 3.21 ± 0.82 mmol/L, P<0.001) and abnormal glucose metabolism (50% vs. 12%, P<0.001). However, there was no difference in CRP, HOMA-IR, or measures of cardiovascular function including pulse rate, pulse pressure, mean arterial pressure, cardiac output, systemic vascular resistance, small and large artery elasticity index. After controlling for adiposity, blood pressure, lipids and CRP, glycemic status did not contribute to vascular function. CONCLUSION Despite a higher incidence of adiposity, dyslipidemia, and impaired glycemia, women with a history of GDM who had a normal postpartum OGTT did not have impaired vascular function 4-10 years postpartum, when compared to healthy controls.
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Affiliation(s)
- Olubukola Ajala
- Division of Endocrinology and Metabolism, Department of Medicine, 9th Floor, Clinical Sciences Building, University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
| | - Louise A Jensen
- Faculty of Nursing Level 3 Edmonton Clinic Health Academy, University of Alberta, Edmonton, Alberta T6G 1C9, Canada
| | - Edmond Ryan
- Division of Endocrinology and Metabolism, Department of Medicine, 9th Floor, Clinical Sciences Building, University of Alberta, Edmonton, Alberta T6G 2G3, Canada
| | - Constance Chik
- Division of Endocrinology and Metabolism, Department of Medicine, 9th Floor, Clinical Sciences Building, University of Alberta, Edmonton, Alberta T6G 2G3, Canada
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Palombo C, Kozakova M. Arterial stiffness, atherosclerosis and cardiovascular risk: Pathophysiologic mechanisms and emerging clinical indications. Vascul Pharmacol 2015; 77:1-7. [PMID: 26643779 DOI: 10.1016/j.vph.2015.11.083] [Citation(s) in RCA: 329] [Impact Index Per Article: 32.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2015] [Revised: 08/25/2015] [Accepted: 11/26/2015] [Indexed: 12/14/2022]
Abstract
Arterial stiffness results from a degenerative process affecting mainly the extracellular matrix of elastic arteries under the effect of aging and risk factors. Changes in extracellular matrix proteins and in the mechanical properties of the vessel wall related to arterial stiffening may activate number of mechanisms involved also in the process of atherosclerosis. Several noninvasive methods are now available to estimate large artery stiffness in the clinical setting, including carotid-femoral pulse wave velocity, the reference for aortic stiffness estimate, and local distensibility measures of superficial arteries, namely carotid and femoral. An independent predictive value of arterial stiffness for cardiovascular events has been demonstrated in general as well as in selected populations, and reference values adjusted for age and blood pressure have been established. Thus, arterial stiffness is emerging as an interesting tissue biomarker for cardiovascular risk stratification and estimation of the individual "biological age". This paper overviews the mechanisms accounting for development and progression of arterial stiffness and for associations between arterial stiffness, atherosclerotic burden and incident cardiovascular events, summarizes the evidence and caveat for clinical use of stiffness as surrogate marker of cardiovascular risk, and briefly outlines some emerging methods for large artery stiffness characterization.
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Affiliation(s)
- Carlo Palombo
- Department of Surgical, Medical and Molecular Pathology and Critical Area Medicine, University of Pisa, Italy.
| | - Michaela Kozakova
- Department of Clinical and Experimental Medicine, University of Pisa, Italy
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Zhang Y, Zhan WW, Wu YJ, Zhao B, Zhou WG, Chen DR, Zhou W, Liu ZH, Jiang WM, Zheng L. Correlation between Echo-Tracking Parameters and In Vitro Measurements of Arterial Contraction and Relaxation in Rats Fed a High-Cholesterol Diet. Med Sci Monit 2015; 21:2933-42. [PMID: 26420461 PMCID: PMC4596455 DOI: 10.12659/msm.894032] [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] [Received: 03/06/2015] [Accepted: 06/10/2015] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Echo-tracking (ET) is a new technique that allows the assessment of arterial function and stiffness. This study aimed to ascertain the utility of the echo-tracking (ET) technique to assess vascular stiffness in rats with hypercholesterolemia and atherosclerosis. MATERIAL AND METHODS ET was used to measure the arterial stiffness of the aorta in cholesterol-fed Sprague-Dawley rats (group T1, n=10, for 4 weeks; group T2, n=10, for 12 weeks) and normal control rats (group C1, n=10; group C2, n=10). In vitro isometric tension experiments were used to measure the maximum contractile tension (MCT) and maximum relaxation percentage (MRR%) of aortic rings. Indicators of arterial stiffness and aortic MCT and MRR% were compared between groups using linear regression analysis. Light microscopic evaluation was used to demonstrate atherosclerotic changes in the aorta. RESULTS The rat models were successfully induced; pathological examination of the aortas showed significant atherosclerosis in group T2, but not in groups C1, C2, or T1. The arterial stiffness parameters obtained using ET and aortic rings in vitro showed significant impairments in T1 and T2 rats compared with C1 and C2 controls (all P<0.05 vs. controls). In addition, these impairments were greater in the T2 group than in the T1 group (all P<0.05). Finally, MRR% correlated with the distensibility coefficient (r=0.396, P=0.012), arterial compliance (r=0.317, P=0.047), stiffness parameter b (r=-0.406, P=0.009) and one-point pulse wave β (r=-0.434, P=0.005). CONCLUSIONS These results suggest that ET could be used to evaluate the changes in arterial wall elasticity associated with atherosclerosis and hypercholesterolemia.
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Affiliation(s)
- Yi Zhang
- Department of Ultrasound, Rui Jin Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, P.R. China
| | - Wei-Wei Zhan
- Department of Ultrasound, Rui Jin Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, P.R. China
| | - Yong-Jie Wu
- Shanghai Institute of Hypertension, Ruijin Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, P.R. China
| | - Bo Zhao
- Department of Ultrasound, Rui Jin Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, P.R. China
| | - Wu-Gang Zhou
- Shanghai Institute of Hypertension, Ruijin Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, P.R. China
| | - Dong-Rui Chen
- Shanghai Institute of Hypertension, Ruijin Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, P.R. China
| | - Wei Zhou
- Department of Ultrasound, Rui Jin Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, P.R. China
| | - Zhen-Hua Liu
- Department of Ultrasound, Rui Jin Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, P.R. China
| | - Wei-Min Jiang
- Department of Pathology, School of Medicine, Shanghai JiaoTong University, Shanghai, P.R. China
| | - Lin Zheng
- Department of Pathology, School of Medicine, Shanghai JiaoTong University, Shanghai, P.R. China
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Chung CM, Tseng YH, Lin YS, Hsu JT, Wang PC. Association of brachial-ankle pulse wave velocity with atherosclerosis and presence of coronary artery disease in older patients. Clin Interv Aging 2015; 10:1369-75. [PMID: 26316732 PMCID: PMC4548723 DOI: 10.2147/cia.s89568] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
OBJECTIVE Brachial-ankle pulse wave velocity (baPWV) is a simple and reproducible measure of arterial stiffness and is extensively used to assess risk of cardiovascular disease in Asia. We examined whether baPWV was associated with coronary atherosclerosis and presence and extent of coronary artery disease (CAD) in older patients with chest pain. METHODS This cross-sectional study enrolled 370 consecutive patients >65 years old who underwent baPWV measurement and elective coronary angiogram for suspected CAD at a single cardiovascular center, between June 2013 and July 2014. RESULTS In addition to diabetes mellitus and body mass index, baPWV was one of the statistically meaningful predictors of significant CAD (diameter of stenosis >50%) in a multivariate analysis. When the extent of CAD was classified as nonsignificant or significant CAD (ie, one-, two-, and three-vessel disease), there was a significant difference in baPWV between the significant and nonsignificant CAD groups, but not between the three significant CAD groups. Multivariate linear regression analyses showed that the number of diseased vessels and baPWV were both significantly associated with the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) score. The cutoff value of baPWV at 1,874 cm/s had a sensitivity of 60.1%, specificity of 70.8%, and area under receiver operating characteristic curve of 0.639 in predicting CAD. CONCLUSION Arterial stiffness determined by baPWV was associated independently with CAD severity, as assessed by angiography and the SYNTAX score in older patients with chest pain. As a result, increased arterial stiffness assessed by baPWV is associated with the severity and presence of CAD in older patients.
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Affiliation(s)
- Chang-Min Chung
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan County, Taiwan ; Chang Gung University of Science and Technology, Chiayi County, Taiwan
| | - Yu-Hsiang Tseng
- Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yu-Sheng Lin
- Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Jen-Te Hsu
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan County, Taiwan
| | - Po-Chang Wang
- Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
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Vizzardi E, Cavazzana I, Sciatti E, Bonadei I, D'Aloia A, Tincani A, Franceschini F, Metra M. Evaluation of ascending aorta wall in rheumatoid arthritis by tissue and strain Doppler imaging during anti-tumor necrosis factor-α therapy. Clin Cardiol 2014; 37:738-43. [PMID: 25236839 PMCID: PMC6647713 DOI: 10.1002/clc.22332] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2014] [Revised: 06/07/2014] [Accepted: 08/04/2014] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Patients with rheumatoid arthritis (RA) are at increased risk of vascular events. Data on the effects of tumor necrosis factor-α (TNF-α) blocking agents on aortic vascular function are still debated. HYPOTHESIS To evaluate the effects of anti-TNF-α treatment on elastic properties of the ascending aorta (distensibility, stiffness, and tissue Doppler imaging [TDI] strain) in RA patients. METHODS We prospectively followed 13 patients affected by RA without cardiovascular risk factors for 1 year during anti-TNF-α treatment. Every subject received an echocardiographic examination before starting anti-TNF-α drugs and after 1 year. Aortic elastic properties were calculated from the echocardiographically derived thoracic aortic diameters, and TDI strain was measured on the wall of the ascending aorta 3 cm above the aortic valve. RESULTS We found lower distensibility (12.9 ± 3.5 vs 21.5 ± 7.5 mm Hg(-1); P <0.001) and a higher stiffness index (21.3 ± 3.6 vs 11.7 ± 1.4; P <0.001) in RA cases at baseline compared with values after 1 year of treatment. Peak systolic (S') and diastolic (E' and A') waves of the aortic wall TDI were similar at baseline and at 1 year follow-up (S' wave: 5.6 ± 2.2 cm/s vs 6.5 ± 2.6 cm/s, E' wave: -4.6 ± 2.9 vs -5.0 ± 1.2 cm/s, A' wave: -5.6 ± 0.19 vs -5.9 ± 2.05 cm/s), whereas TDI strain of the aortic wall was improved after anti-TNF-α treatment (-23.7 ± 1.4% vs -31.6 ± 2.8%, P < 0.001). CONCLUSIONS Anti-TNF-α treatment after 12 months significantly modifies the elastic properties of the aorta. This may reflect the favorable changes in its elastic tissue after anti-TNF-α treatment in RA patients without cardiovascular risk factors. This suggests a potential cardiovascular risk benefit.
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Affiliation(s)
- Enrico Vizzardi
- Section of Cardiovascular Diseases, Department of Medical and Surgical Specialties, Radiological Sciences and Public HealthUniversity of Study of BresciaBresciaItaly
| | - Ilaria Cavazzana
- Rheumatology and Clinical Immunology UnitSpedali Civili and University of Study of BresciaBresciaItaly
| | - Edoardo Sciatti
- Section of Cardiovascular Diseases, Department of Medical and Surgical Specialties, Radiological Sciences and Public HealthUniversity of Study of BresciaBresciaItaly
| | - Ivano Bonadei
- Section of Cardiovascular Diseases, Department of Medical and Surgical Specialties, Radiological Sciences and Public HealthUniversity of Study of BresciaBresciaItaly
| | - Antonio D'Aloia
- Section of Cardiovascular Diseases, Department of Medical and Surgical Specialties, Radiological Sciences and Public HealthUniversity of Study of BresciaBresciaItaly
| | - Angela Tincani
- Rheumatology and Clinical Immunology UnitSpedali Civili and University of Study of BresciaBresciaItaly
| | - Franco Franceschini
- Rheumatology and Clinical Immunology UnitSpedali Civili and University of Study of BresciaBresciaItaly
| | - Marco Metra
- Section of Cardiovascular Diseases, Department of Medical and Surgical Specialties, Radiological Sciences and Public HealthUniversity of Study of BresciaBresciaItaly
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Chung CM, Yang TY, Lin YS, Chang ST, Hsiao JF, Pan KL, Jang SJ, Hsu JT. Relation of arterial stiffness assessed by brachial-ankle pulse wave velocity to complexity of coronary artery disease. Am J Med Sci 2014; 348:294-299. [PMID: 24845468 DOI: 10.1097/maj.0000000000000285] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The progression of atherosclerosis leads to increased arterial stiffness. The present study used brachial-ankle pulse wave velocity (baPWV) to evaluate the connection between arterial stiffness in patients with chest pain and the presence and extent of coronary artery disease (CAD). METHODS On a retrospective basis, we analyzed the data of 703 consecutive patients who had undergone baPWV and an elective coronary angiogram for suspected CAD, between June 2010 and July 2012, at a single cardiovascular center. RESULTS The baPWV was one of the statistically meaningful predictors of significant CAD (diameter of stenosis >50%) in addition to diabetes and dyslipidemia in a multivariate analysis. When the extent of CAD was classified into nonsignificant or significant CAD (ie, 1-, 2- and 3-vessel disease), there was a significant difference in baPWV between the significant and nonsignificant CAD groups, but there was no difference in baPWV among the 3 significant CAD groups. Linear regression analyses showed that baPWV was significantly associated with the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) score. The cutoff value of baPWV at 1735 cm/s had a sensitivity of 55.6%, specificity of 62.4%, and area under receiver operating characteristic curve of 0.612 in predicting CAD. CONCLUSIONS Arterial stiffness as determined by baPWV is associated independently with significant CAD in patients with angina. Arterial stiffness is related to CAD severity as assessed by the SYNTAX score. As a result, increased arterial stiffness assessed by baPWV is associated with the severity and presence of CAD.
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Affiliation(s)
- Chang-Min Chung
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi; Department of Internal Medicine, Chang Gung University of Science and Technology, Chiayi County; Department of Internal Medicine, Chang Gung University, Taoyuan County, Taiwan
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Silswal N, Touchberry CD, Daniel DR, McCarthy DL, Zhang S, Andresen J, Stubbs JR, Wacker MJ. FGF23 directly impairs endothelium-dependent vasorelaxation by increasing superoxide levels and reducing nitric oxide bioavailability. Am J Physiol Endocrinol Metab 2014; 307:E426-36. [PMID: 25053401 PMCID: PMC4154070 DOI: 10.1152/ajpendo.00264.2014] [Citation(s) in RCA: 138] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Accepted: 07/15/2014] [Indexed: 12/17/2022]
Abstract
Fibroblast growth factor 23 (FGF23) is secreted primarily by osteocytes and regulates phosphate and vitamin D metabolism. Elevated levels of FGF23 are clinically associated with endothelial dysfunction and arterial stiffness in chronic kidney disease (CKD) patients; however, the direct effects of FGF23 on endothelial function are unknown. We hypothesized that FGF23 directly impairs endothelial vasorelaxation by hindering nitric oxide (NO) bioavailability. We detected expression of all four subtypes of FGF receptors (Fgfr1-4) in male mouse aortas. Exogenous FGF23 (90-9,000 pg/ml) did not induce contraction of aortic rings and did not relax rings precontracted with PGF2α. However, preincubation with FGF23 (9,000 pg/ml) caused a ∼36% inhibition of endothelium-dependent relaxation elicited by acetylcholine (ACh) in precontracted aortic rings, which was prevented by the FGFR antagonist PD166866 (50 nM). Furthermore, in FGF23-pretreated (9,000 pg/ml) aortic rings, we found reductions in NO levels. We also investigated an animal model of CKD (Col4a3(-/-) mice) that displays highly elevated serum FGF23 levels and found they had impaired endothelium-dependent vascular relaxation and reduced nitrate production compared with age-matched wild types. To elucidate a mechanism for the FGF23-induced impairment, we measured superoxide levels in endothelial cells and aortic rings and found that they were increased following FGF23 treatment. Crucially, treatment with the superoxide scavenger tiron reduced superoxide levels and also restored aortic relaxation to ACh. Therefore, our data suggest that FGF23 increases superoxide, inhibits NO bioavailability, and causes endothelial dysfunction in mouse aorta. Together, these data provide evidence that high levels of FGF23 contribute to cardiovascular dysfunction.
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Affiliation(s)
- Neerupma Silswal
- Muscle Biology Group, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri; and
| | - Chad D Touchberry
- Muscle Biology Group, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri; and
| | - Dorothy R Daniel
- Muscle Biology Group, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri; and
| | - Darla L McCarthy
- Muscle Biology Group, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri; and
| | - Shiqin Zhang
- The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas
| | - Jon Andresen
- Muscle Biology Group, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri; and
| | - Jason R Stubbs
- The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas
| | - Michael J Wacker
- Muscle Biology Group, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri; and
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The use of pulse wave velocity in predicting pre-eclampsia in high-risk women. Hypertens Res 2014; 37:733-40. [DOI: 10.1038/hr.2014.62] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Revised: 11/11/2013] [Accepted: 12/16/2013] [Indexed: 11/08/2022]
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Shan Y, Lin J, Xu P, Zeng M, Lin H, Yan H. The combined effect of hypertension and type 2 diabetes mellitus on aortic stiffness and endothelial dysfunction: an integrated study with high-resolution MRI. Magn Reson Imaging 2013; 32:211-6. [PMID: 24462301 DOI: 10.1016/j.mri.2013.12.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2013] [Revised: 10/26/2013] [Accepted: 12/23/2013] [Indexed: 02/08/2023]
Abstract
PURPOSE The purpose of this study was to investigate the combined effect of hypertension and type 2 diabetes mellitus (DM2) on aortic stiffness and endothelial dysfunction by using an integrated MRI approach. MATERIALS AND METHODS A total of 31 non-hypertensive DM2 patients and 31 hypertensive DM2 patients underwent 3.0-T MRI. Aortic distensibility (AD), pulse wave velocity (PWV) and brachial artery flow-mediated dilation (FMD) were assessed. Student's t-test, Mann-Whitney U test, chi-squared test, Pearson correlation analysis, and univariable and multiple linear regression analyses were used for statistical analyses. RESULTS The hypertensive patients showed lower AD at multiple levels (ascending aorta [AA]: 2.07±0.98×10(-3)mm Hg(-1) vs. 3.21±1.70×10(-3)mm Hg(-1), p<0.01; proximal thoracic descending aorta [PDA]: 2.58±0.72×10(-3)mm Hg(-1) vs. 3.58±1.47×10(-3)mm Hg(-1), p<0.01; distal descending aorta [DDA]: 3.11±1.84×10(-3)mm Hg(-1) vs. 4.27±1.75×10(-3)mm Hg(-1), p<0.01); faster PWV (7.46±2.28m/s vs. 5.82±1.12m/s, p<0.05) and lower FMD (12.67%±6.49% vs. 20.66%±9.7%; p<0.01). Systolic blood pressure was an independent predictor of PWV, AA-AD, DDA-AD and FMD. FMD was statistically significantly associated with PWV (r=-0.37, p<0.01) and AD (p<0.01). CONCLUSIONS Hypertension has a contributive effect on aortic stiffness and endothelial dysfunction in DM2 patients.
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Affiliation(s)
- Yan Shan
- Department of Radiology, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032, China
| | - Jiang Lin
- Department of Radiology, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032, China.
| | - Pengju Xu
- Department of Radiology, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032, China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032, China
| | - Huandong Lin
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Hongmei Yan
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies. Nutr Res Rev 2013; 26:210-22. [PMID: 24134873 DOI: 10.1017/s0954422413000188] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Evidence has accumulated in recent years that suggests that nitrate from the diet, particularly vegetables, is capable of producing bioactive NO in the vasculature, following bioconversion to nitrite by oral bacteria. The aim of the present review was to consider the current body of evidence for potential beneficial effects of dietary nitrate on blood pressure and endothelial function, with emphasis on evidence from acute and chronic human intervention studies. The studies to date suggest that dietary nitrate acutely lowers blood pressure in healthy humans. An inverse relationship was seen between dose of nitrate consumed and corresponding systolic blood pressure reduction, with doses of nitrate as low as 3 mmol of nitrate reducing systolic blood pressure by 3 mmHg. Moreover, the current studies provide some promising evidence on the beneficial effects of dietary nitrate on endothelial function. In vitro studies suggest a number of potential mechanisms by which dietary nitrate and its sequential reduction to NO may reduce blood pressure and improve endothelial function, such as: acting as a substrate for endothelial NO synthase; increasing vasodilation; inhibiting mitochondrial reactive oxygen species production and platelet aggregation. In conclusion, the evidence for beneficial effects of dietary nitrate on blood pressure and endothelial function is promising. Further long-term randomised controlled human intervention studies assessing the potential effects of dietary nitrate on blood pressure and endothelial function are needed, particularly in individuals with hypertension and at risk of CVD.
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Beck DT, Martin JS, Casey DP, Braith RW. Exercise training reduces peripheral arterial stiffness and myocardial oxygen demand in young prehypertensive subjects. Am J Hypertens 2013; 26:1093-102. [PMID: 23736111 DOI: 10.1093/ajh/hpt080] [Citation(s) in RCA: 95] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Large artery stiffness is a major risk factor for the development of hypertension and cardiovascular disease. Persistent prehypertension accelerates the progression of arterial stiffness. METHODS Forty-three unmedicated prehypertensive (systolic blood pressure (SBP) = 120-139 mm Hg or diastolic blood pressure (DBP) = 80-89 mm Hg) men and women and 15 normotensive time-matched control subjects (NMTCs; n = 15) aged 18-35 years of age met screening requirements and participated in the study. Prehypertensive subjects were randomly assigned to a resistance exercise training (PHRT; n = 15), endurance exercise training (PHET; n = 13) or time-control group (PHTC; n = 15). Treatment groups performed exercise training 3 days per week for 8 weeks. Pulse wave analysis, pulse wave velocity (PWV), and central and peripheral blood pressures were evaluated before and after exercise intervention or time-matched control. RESULTS PHRT and PHET reduced resting SBP by 9.6±3.6mm Hg and 11.9±3.4mm Hg, respectively, and DBP by 8.0±5.1mm Hg and 7.2±3.4mm Hg, respectively (P < 0.05). PHRT and PHET decreased augmentation index (AIx) by 7.5% ± 2.8% and 8.1% ± 3.2% (P < 0.05), AIx@75 by 8.0% ± 3.2% and 9.2% ± 3.8% (P < 0.05), and left ventricular wasted pressure energy, an index of extra left ventricular myocardial oxygen requirement due to early systolic wave reflection, by 573±161 dynes s/cm(2) and 612±167 dynes s/cm(2) (P < 0.05), respectively. PHRT and PHET reduced carotid-radial PWV by 1.02±0.32 m/sec and 0.92±0.36 m/sec (P < 0.05) and femoral-distal PWV by 1.04±0.31 m/sec and 1.34±0.33 m/sec (P < 0.05), respectively. No significant changes were observed in the time-control groups. CONCLUSIONS This study suggests that both resistance and endurance exercise alone effectively reduce peripheral arterial stiffness, central blood pressures, augmentation index, and myocardial oxygen demand in young prehypertensive subjects.
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Affiliation(s)
- Darren T Beck
- Malcom Randall VA Medical Center, Geriatric Research Education and Clinical Center, Gainesville, Florida
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Tsao CW, Seshadri S, Beiser AS, Westwood AJ, Decarli C, Au R, Himali JJ, Hamburg NM, Vita JA, Levy D, Larson MG, Benjamin EJ, Wolf PA, Vasan RS, Mitchell GF. Relations of arterial stiffness and endothelial function to brain aging in the community. Neurology 2013; 81:984-91. [PMID: 23935179 DOI: 10.1212/wnl.0b013e3182a43e1c] [Citation(s) in RCA: 200] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE To determine the association of arterial stiffness and pressure pulsatility, which can damage small vessels in the brain, with vascular and Alzheimer-type brain aging. METHODS Stroke- and dementia-free Framingham Offspring Study participants (n = 1,587, 61 ± 9 years, 45% male) underwent study of tonometric arterial stiffness and endothelial function (1998-2001) and brain MRI and cognition (1999-2002). We related carotid-femoral pulse wave velocity (CFPWV), mean arterial and central pulse pressure, and endothelial function to vascular brain aging by MRI (total cerebral brain volume [TCBV], white matter hyperintensity volume, silent cerebral infarcts) and vascular and Alzheimer-type cognitive aging (Trails B minus Trails A and logical memory-delayed recall, respectively). RESULTS Higher CFPWV was associated with lower TCBV, greater white matter hyperintensity volume, and greater prevalence of silent cerebral infarcts (all p < 0.05). Each SD greater CFPWV was associated with lower TCBV equivalent to 1.2 years of brain aging. Mean arterial and central pulse pressure were associated with greater white matter hyperintensity volume (p = 0.005) and lower TCBV (p = 0.02), respectively, and worse verbal memory (both p < 0.05). Associations of tonometry variables with TCBV and white matter hyperintensity volume were stronger among those aged 65 years and older vs those younger than 65 years (p < 0.10 for interaction). Brachial artery endothelial function was unrelated to MRI measures (all p > 0.05). CONCLUSIONS Greater arterial stiffness and pressure pulsatility are associated with brain aging, MRI vascular insults, and memory deficits typically seen in Alzheimer dementia. Future investigations are warranted to evaluate the potential impact of prevention and treatment of unfavorable arterial hemodynamics on neurocognitive outcomes.
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Affiliation(s)
- Connie W Tsao
- From the Department of Medicine (C.W.T.), Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston; Departments of Neurology (S.S., A.S.B., A.J.W., R.A., J.J.H., P.A.W.), Medicine (N.M.H., J.A.V., D.L., E.J.B., R.S.V.), and Biostatistics (A.S.B., J.J.H., M.G.L.), School of Public Health, School of Medicine and the Department of Mathematics (M.G.L.), Boston University, MA; Department of Neurology (C.D.), Center for Neuroscience and Division of Biostatistics, Department of Public Health Sciences, School of Medicine, University of California, Davis; National Heart Lung and Blood Institute (D.L.), NHLBI's Framingham Heart Study (C.W.T., S.S., A.S.B., R.A., D.L., M.G.L., E.J.B., P.A.W., R.S.V.), Framingham; and Cardiovascular Engineering Inc. (G.F.M.), Norwood, MA
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Progression of arterial stiffness and coronary atherosclerosis: longitudinal evaluation by cardiac CT. AJR Am J Roentgenol 2013; 200:798-804. [PMID: 23521451 DOI: 10.2214/ajr.12.8653] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVE We sought to use cardiac CT angiography (CTA) to longitudinally examine the relationship between changes in aortic stiffness and of the atherosclerotic burden over time. MATERIALS AND METHODS One hundred sixty-four patients with suspected coronary artery disease underwent two retrospectively ECG-gated cardiac CTA studies an average of 12 ± 10 months apart. Arterial stiffness was represented by the aortic distensibility index (ADI) and atherosclerosis by segment involvement score (SIS) (defined as the number of coronary artery segments per patient displaying atherosclerotic plaque). Changes in ADI and SIS between the studies were compared using linear and logistic regression accounting for differences in clinical and demographic baseline characteristics. RESULTS Age (p = 0.004), time between studies (p = 0.02), and increase in SIS (p < 0.001) were associated with a decrease in ADI on univariate analysis. Increase in SIS remained a significant independent predictor of decreased ADI on both multivariate logistic regression (with change in ADI represented categorically) and multivariate linear regression (both p < 0.001). CONCLUSION On longitudinal evaluation with cardiac CTA, the progression of aortic stiffness is associated with the progression of coronary atherosclerosis. Although outcome studies are needed, a comprehensive assessment of vascular health with cardiac CTA, including both indexes of arterial stiffness and atherosclerotic burden, may improve risk stratification and therapy monitoring.
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Pal S, Radavelli-Bagatini S. Association of arterial stiffness with obesity in Australian women: a pilot study. J Clin Hypertens (Greenwich) 2013; 15:118-23. [PMID: 23339730 PMCID: PMC8108253 DOI: 10.1111/jch.12038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2012] [Revised: 09/24/2012] [Accepted: 09/26/2012] [Indexed: 11/28/2022]
Abstract
This study investigated the arterial stiffness status in overweight/obese Australian women compared with their lean counterparts. Twenty-six Caucasian women were designated into one of two groups: overweight/obese (body mass index [BMI] 25-34.9 kg/m2 [ n=12]) and lean (BMI 18.5-24.9 kg/m2 [n=14]) groups. Participants were assessed for clinical, anthropometric, metabolic, and augmentation index (AIx) measurements. Age was similar between groups (P=.482). BMI was significantly higher in overweight/obese compared with lean participants (30.26±1.09 vs 21.62±0.52 kg/m2, P=.001) as well as the percentage of body fat (40.60±2.43 vs 21.57±1.13, P=.001), waist circumference (91.47±2.77 vs 70.67±1.60, P=.001), and waist/hip ratio (0.81±0.04 vs 0.71±0.03, P=.036). Overweight/obese group showed higher total cholesterol, triglyceride, low-density lipoprotein cholesterol, and fasting glucose levels compared with the lean group (all P<.05). Both systolic (122.92±3.18 mm Hg vs 108.14±2.42 mm Hg, P=.001) and diastolic (83.58±2.43 mm Hg vs 72.43±1.29 mm Hg, P=.0001) blood pressures, as well as AIx (50.08±4.7 vs 120.79±2.17, P=.001) were significantly higher in the overweight/obese group compared with the lean group. AIx was positively associated with measurements of body composition (P<.05), triglycerides (r=0.361, P=.035) and glucose levels (r=0.371, P=.031), and systolic and diastolic blood pressure (r=0.793 and r=0.718, respectively; P=.0001). This data suggests that arterial stiffness is associated with obesity, along with other metabolic abnormalities in Australian women.
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Affiliation(s)
- Sebely Pal
- School of Public Health, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.
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