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1.  Reductions in arterial stiffness with weight loss in overweight and obese young adults: potential mechanisms 
Atherosclerosis  2012;223(2):485-490.
Arterial stiffness decreases with weight loss in overweight/obese young adults. We aimed to determine the mechanisms by which this occurs.
We evaluated carotid-femoral pulse wave velocity (cfPWV) and brachial-ankle pulse wave velocity (baPWV) in 344 young adults (23% male, BMI 25–40 kg/m2) at baseline, 6, and 12 months in a behavioral weight loss intervention. Linear mixed models were used to evaluate associations between weight loss and arterial stiffness and to examine whether improvements in obesity-related factors explained these associations.
At 6 months (7% mean weight loss), there was a significant median decrease of 47.5 cm/s in cfPWV (p<0.0001) and a mean decrease of 11.7 cm/s in baPWV (p=0.049). At 12 months (6% mean weight loss), only cfPWV remained reduced. In models adjusting for changes in mean arterial pressure and obesity-related factors, changes in BMI (p=0.01) and common carotid artery diameter (p=0.003) were positively associated with change in cfPWV. Reductions in heart rate (p<0.0001) and C-reactive protein (p=0.02) were associated with reduced baPWV and accounted for the association between weight loss and reduced baPWV.
Weight loss is associated with reduced cfPWV independently of changes in established hemodynamic and cardiometabolic risk factors, but its association with reduced baPWV is explained by concurrent reductions in heart rate and inflammation.
PMCID: PMC3411893  PMID: 22703865
arterial stiffness; obesity; lifestyle modification
2.  Regional pulse wave velocities and their cardiovascular risk factors among healthy middle-aged men: a cross-sectional population-based study 
Both carotid-femoral (cf) pulse wave velocity (PWV) and brachial-ankle (ba) PWV employ arterial sites that are not consistent with the path of blood flow. Few previous studies have reported the differential characteristics between cfPWV and baPWV by simultaneously comparing these with measures of pure central (aorta) and peripheral (leg) arterial stiffness, i.e., heart-femoral (hf) PWV and femoral-ankle (fa) PWV in healthy populations. We aimed to identify the degree to which these commonly used measures of cfPWV and baPWV correlate with hfPWV and faPWV, respectively, and to evaluate whether both cfPWV and baPWV are consistent with either hfPWV or faPWV in their associations with cardiovascular (CV) risk factors.
A population-based sample of healthy 784 men aged 40–49 (202 white Americans, 68 African Americans, 202 Japanese-Americans, and 282 Koreans) was examined in this cross-sectional study. Four regional PWVs were simultaneously measured by an automated tonometry/plethysmography system.
cfPWV correlated strongly with hfPWV (r = .81, P < .001), but weakly with faPWV (r = .12, P = .001). baPWV correlated moderately with both hfPWV (r = .47, P < .001) and faPWV (r = .62, P < .001). After stepwise regression analyses with adjustments for race, cfPWV shared common significant correlates with both hfPWV and faPWV: systolic blood pressure (BP) and body mass index (BMI). However, BMI was positively associated with hfPWV and cfPWV, and negatively associated with faPWV. baPWV shared common significant correlates with hfPWV: age and systolic BP. baPWV also shared the following correlates with faPWV: systolic BP, triglycerides, and current smoking.
Among healthy men aged 40 – 49, cfPWV correlated strongly with central PWV, and baPWV correlated with both central and peripheral PWVs. Of the CV risk factors, systolic BP was uniformly associated with all the regional PWVs. In the associations with factors other than systolic BP, cfPWV was consistent with central PWV, while baPWV was consistent with both central and peripheral PWVs.
PMCID: PMC3893368  PMID: 24410766
Arterial stiffness; Aorta; Carotid arteries; Brachial artery; Femoral artery
3.  Associations between arterial stiffness and platelet activation in normotensive overweight and obese young adults 
Obese individuals have elevated platelet activation and arterial stiffness, but the strength and temporality of the relationship between these factors remain unclear. We aimed to determine the effect of increased arterial stiffness on circulating platelet activity in overweight/obese young adults. This analysis included 92 participants (mean age 40 years, 60 women) in the Slow Adverse Vascular Effects of excess weight (SAVE) trial, a clinical trial examining the effects of a lifestyle intervention with or without sodium restriction on vascular health in normotensive overweight/obese young adults. Carotid-femoral (cf), brachial-ankle (ba), and femoral-ankle (fa) pulse wave velocity (PWV) served as measures of arterial stiffness and were measured at baseline and 6, 12, and 24 months follow-up. Platelet activity was measured as plasma beta-thromboglobulin (β-TG) at 24 months. Higher plasma β-TG was correlated with greater exposure to elevated cfPWV (p=0.02) and baPWV (p=0.04) during the preceding two years. After adjustment for serum leptin, greater exposure to elevated baPWV remained significant (p=0.03) and exposure to elevated cfPWV marginally significant (p=0.054) in predicting greater plasma β-TG. Greater arterial stiffness, particularly central arterial stiffness, predicts greater platelet activation in overweight/obese individuals. This relationship might partly explain the association between increased arterial stiffness and incident atherothrombotic events.
PMCID: PMC3742736  PMID: 23654212
platelet activation; arterial stiffness; pulse wave velocity; obesity; weight loss
4.  Acute exercise with whole-body vibration decreases wave reflection and leg arterial stiffness 
Aim: Whole-body vibration exercise (WBV) acutely decreases brachial-ankle pulse wave velocity (baPWV), an index of systemic arterial stiffness. However, the effect of WBV on segmental PWV and aortic hemodynamics is unknown. We examined the acute effects of WBV on arterial function. Methods: Fifteen young men performed ten 1-min sets of static squat with WBV (40 Hz, 1 mm, 5.37 G) and without WBV (no-WBV). Brachial and aortic blood pressure (BP), heart rate (HR), augmentation index (AIx), baPWV, carotid-femoral PWV (cfPWV), and femoral-ankle (faPWV), were recorded before and 5, 15, and 30 min after both trials. Results: Brachial and aortic SBP (P < 0.01), and HR (P < 0.01) were increased only at 5 min after both exercise trials. AIx was elevated through the recovery after no-WBV while decreased at 15 and 30 min after WBV exercise. FaPWV was decreased (P < 0.01) at 5 min after both trials, but returned to baseline at 15 min after no-WBV exercise and was maintained decreased at 15 and 30 min after WBV exercise. There were no significant changes in brachial and aortic diastolic BP, cfPWV and baPWV after both trials. Conclusions: Our findings indicate that regardless of WBV, static squat causes a small transient increase in hemodynamic responses during early recovery. WBV counteracts the increase in AIx induced by static squat and reduces wave reflection magnitude through a local effect on arterial stiffness.
PMCID: PMC3253511  PMID: 22254186
Aortic hemodynamics; pulse wave velocity; wave reflection; static exercise
5.  Particle Numbers of Lipoprotein Subclasses and Arterial Stiffness among Middle-aged men from the ERA JUMP study 
Journal of human hypertension  2013;28(2):111-117.
We examined the association between serum lipoprotein subclasses and the three measures of arterial stiffness i.e. (i) carotid-femoral pulse wave velocity (cfPWV) which is a gold standard measure of central arterial stiffness, (ii) brachial-ankle PWV (baPWV) which is emerging as a combined measure of central and peripheral arterial stiffness, and (iii) femoral-ankle PWV (faPWV) which is a measure of peripheral arterial stiffness. Among a population-based sample of 701 apparently healthy Caucasian, Japanese American and Korean men aged 40–49 years, concentrations of lipoprotein particles were assessed by nuclear magnetic resonance (NMR) spectroscopy, and PWV was assessed with an automated waveform analyzer (VP2000, Omron, Japan). Multiple linear regressions were performed to analyze the association between each NMR lipoprotein subclasses and PWV measures, after adjusting for cardiovascular risk factors and other confounders. A cut-off of p<0.01 was used for determining significance. All PWV measures had significant correlations with total and small low-density lipoprotein particle number (LDL-P) (all p<0.0001) but not LDL-cholesterol (LDL-C) (all p>0.1), independent of race and age. In multivariate regression analysis, no NMR lipoprotein subclass was significantly associated with cfPWV (all p>0.01). However, most NMR lipoprotein subclasses had significant associations with both baPWV and faPWV (p<0.01). In this study of healthy middle-aged men, as compared to cfPWV, both baPWV and faPWV had stronger associations with particle numbers of lipoprotein subclasses. Our results may suggest that both baPWV and faPWV are related to arterial stiffness and atherosclerosis, whereas cfPWV may represent arterial stiffness alone.
PMCID: PMC3800263  PMID: 23823580
lipoproteins; lipoprotein fractions; pulse wave velocity; atherosclerosis
6.  Non-invasive assessment of arterial stiffness using oscillometric blood pressure measurement 
Arterial stiffness is a major contributor to cardiovascular diseases. Because current methods of measuring arterial stiffness are technically demanding, the purpose of this study was to develop a simple method of evaluating arterial stiffness using oscillometric blood pressure measurement.
Blood pressure was conventionally measured in the left upper arm of 173 individuals using an inflatable cuff. Using the time series of occlusive cuff pressure and the amplitudes of pulse oscillations, we calculated local slopes of the curve between the decreasing cuff pressure and corresponding arterial volume. Whole pressure-volume curve was derived from numerical integration of the local slopes. The curve was fitted using an equation and we identified a numerical coefficient of the equation as an index of arterial stiffness (Arterial Pressure-volume Index, API). We also measured brachial-ankle (baPWV) PWV and carotid-femoral (cfPWV) PWV using a vascular testing device and compared the values with API. Furthermore, we assessed carotid arterial compliance using ultrasound images to compare with API.
The slope of the calculated pressure-volume curve was steeper for compliant (low baPWV or cfPWV) than stiff (high baPWV or cfPWV) arteries. API was related to baPWV (r = -0.53, P < 0.05), cfPWV (r = -0.49, P < 0.05), and carotid arterial compliance (r = 0.32, P < 0.05). A stepwise multiple regression analysis demonstrated that baPWV and carotid arterial compliance were the independent determinants of API, and that API was the independent determinant of baPWV and carotid arterial compliance.
These results suggest that our method can simply and simultaneously evaluate arterial stiffness and blood pressure based on oscillometric measurements of blood pressure.
PMCID: PMC3359259  PMID: 22325084
arterial stiffness; blood pressure measurement; pulse wave velocity
7.  Pulse Wave Velocity Involving Proximal Portions of the Aorta Correlates with the Degree of Aortic Dilatation at the Sinuses of Valsalva in Ascending Thoracic Aortic Aneurysms 
Annals of Vascular Diseases  2014;7(4):404-409.
Objective: To determine the relationship between arterial stiffness measured in different aortic segments and the presence and extent of ascending thoracic aortic aneurysm (ATAA).
Methods: Patients at a Thoracic Aortic Diseases clinic at a University teaching hospital were compared to patients attending a Cardiology outpatient Clinic at the same institution. A non-invasive measure of vascular stiffness was performed using pulse wave velocity (PWV) measurement of several vascular segments—carotid-femoral pulse wave velocity (cfPWV), heart-femoral pulse wave velocity (hfPWV) and brachial-ankle pulse wave velocity (baPWV). Aortic dimensions were measured on echocardiogram.
Results: Patients with ATAA (N = 32) were 66 years and the same age as those without ATAA (N = 46). There was no significant difference between those with or without aortic aneurysm with respect to cfPWV, hfPWV or baPWV. In ATAA, there was a significant (p <0.05) inverse correlation between aortic diameter at the sinuses of Valsalva and cfPWV, as well as hfPWV, but not with baPWV. This relationship was not evident in persons without ATAA.
Conclusion: Reduced aortic stiffness (increased compliance), assessed by cfPWV or hfPWV, correlates with larger aortic size of ATAA at the level of the sinuses of Valsalva but not at the ascending aorta, suggesting cfPWV may be a useful method to assess the size of ATAA at the level of the sinuses of Valsalva. Overall aortic stiffness assessed by PWV did not differentiate persons with or without an ATAA, in individuals who do not have a genetic or inheritable cause of their ATAA.
PMCID: PMC4293191  PMID: 25593626
Thoracic aortic aneurysm; aortic compliance; aortic stiffness
8.  Determinants of Brachial-Ankle Pulse Wave Velocity and Carotid-Femoral Pulse Wave Velocity in Healthy Koreans 
Journal of Korean Medical Science  2014;29(6):798-804.
The aim of this study was to determine the normal value of brachial-ankle pulse wave velocity (baPWV) and carotid-femoral pulse wave velocity (cfPWV) according to age group, gender, and the presence of cardiovascular risk factors in healthy Koreans, and to investigate the association between PWV and risk factors such as prehypertension, dyslipidemia, smoking, and obesity. We measured an arterial stiffness in 110 normal subjects who were 20 to 69 yr-old with no evidence of cardiovascular disease, cerebrovascular accident or diabetes mellitus. The mean values of baPWV and cfPWV were 12.6 (±2.27) m/sec (13.1±1.85 in men, 12.1±2.51 in women; P=0.019) and 8.70 (±1.99) m/sec (9.34±2.13 in men, 8.15±1.69 in women; P=0.001), respectively. The distribution of baPWV (P<0.001) and cfPWV (P=0.006) by age group and gender showed an increase in the mean value with age. Men had higher baPWV and cfPWV than women (P<0.001). There was a difference in baPWV and cfPWV by age group on prehypertension, dyslipidemia, current smoking, or obesity (P<0.001). In multiple linear regression, age and prehypertension were highly associated with baPWV and cfPWV after adjustment for confounding factors (P<0.001). The present study showed that baPWV and cfPWV are associated with age, gender, and prehypertension in healthy Koreans.
Graphical Abstract
PMCID: PMC4055813  PMID: 24932081
Prehypertension; Gender Identity; Age Groups; Ankle Brachial Index; Carotid-Femoral; Pulse Wave Analysis
9.  Clinical Factors Associated with Brachial-Ankle Pulse Wave Velocity in Patients on Maintenance Hemodialysis 
Pulse wave velocity (PWV) is a main parameter for arterial stiffness. In patients with end-stage renal disease (ESRD), PWV is known to be associated with increased mortality. But factors related to the increased PWV in ESRD patients are not well defined. In addition, the carotid-femoral PWV (cfPWV) measurement, which traditionally has been used to evaluate arterial stiffness, has low reproducibility. Recently, brachial-ankle PWV (baPWV) measurement, which can be performed more easily than cfPWV measurement, has become available as a means of measuring PWV. The aim of this study is to investigate the clinical factors associated with increased baPWV in ESRD patients. BaPWV was examined for 65 ESRD patients on maintenance hemodialysis during the period between the 7th to the 11th of February in 2005 using VP-1000. The clinical factors included age, sex, smoking history, blood pressure, diabetes, body mass index, interdialytic weight gain, duration of dialysis, lipid profile, uric acid, albumin, creatinine, C-reactive protein, calcium, phosphate, intact parathyroid hormone, and hematocrit were analyzed regarding associations (or to determine associations) with baPWV. The median age was 53.8±12.0, 31 males and 34 females. BaPWV was 18.9±5.2 m/s and there was no significant difference between gender (18.1±4.4 m/s vs 19.4±5.9 m/s, p=NS). In multiple regression models, age, predialysis systolic blood pressure, and diabetes were independent variables. In conclusion, age, systolic blood pressure, and diabetes were correlated with baPWV in ESRD patients. Thus baPWV measured by simple, noninvasive methods may become available for screening high risk groups in ESRD patients, although further longitudinal studies are necessary.
PMCID: PMC3894478  PMID: 24459524
atherosclerosis; renal dialysis; blood pressure
10.  Impact of the Metabolic Syndrome and Its Components on Pulse Wave Velocity 
Pulse wave velocity (PWV) reflects arterial stiffness and may provide an integrated index of vascular status and cardiovascular disease (CVD) risk. Although the individual components of the metabolic syndrome (MS) are well established cardiovascular risk factors, the impact of the MS and its components on PWV has not been well defined.
Using an automatic wave form analyzer, heart-femoral (hf) and brachial-ankle (ba) PWVs were measured simultaneously in 364 subjects (age, 44.8±9.3 years). None of the subjects had clinical atherosclerotic CVD, diabetes, or systemic disease. The association between PWVs and the features of the MS, individual and clustered, were analyzed.
By univariate analysis, the individual components of the MS, except for a low HDL-cholesterol level, were associated with increased hfPWV and baPWV. Hypercholesterolemia was also associated with increase in both PWVs. A low HDL-cholesterol level was associated with an increased baPWV. However, by multivariate analysis, none of the components of the MS, except for an elevated blood pressure (BP), was an independent factor affecting hfPWV and baPWV. After controlling for age and gender, hfPWV and baPWV were increased according to the number of MS components present (p<0.001 for both). After controlling for age, gender and BP, the MS was associated with an increased baPWV (p<0.05).
The clustering of MS components may interact to synergistically affect arterial stiffness, even though the individual MS components, except for an elevated BP, do not affect arterial stiffness independently.
PMCID: PMC3890732  PMID: 16913440
Blood flow velocity; Metabolic syndrome
11.  Association between arterial stiffness and risk of coronary artery disease 
Pakistan Journal of Medical Sciences  2014;30(6):1314-1318.
Objective: To investigate the role of Brachial ankle Pulse Wave Relocity (baPWV) and cfPWV on the risk of Coronary artery disease and the interaction between baPWV and risk factors of Coronary artery disease (CAD).
Methods: A case-control study was conducted at Department of Emergency, SunYat-Sen memorial Hospital, China. We collected 332 cases with coronary artery disease and 328 subjects without CAD between February 2012 and October 2013. A multivariate logistic regression analysis was performed to analyze the risk factors of CAD.
Results: CAD subjects were more likely to be old age, and have higher BMI, waist-hip ratio, hypertension, fasting glucose, TG, carotid-femoral PWV (cfPWV) and baPWV, and CAD subjects had a lower TC, HDL–C and LDL-C. We found that older age, smoking, higher hypertension, TC, TG, HDL-C, LDL-C, carotid-femoral PWV (CfPWV) and baPWV were associated with risk of CAD. baPWV had significant interaction with age, TC, TG, HDL-C and LDL-C, carotid-femoral PWV (cfWV) was correlated with age, HDL-C and LDL-C.
Conclusion: This study showed that baPWV and cfPWV are two independent factors for the risk of Coronary artery disease, and baPWV and cfPWV have interaction with age, TC, TG, HDL-C and LDL-C.
PMCID: PMC4320722
Arterial stiffness; baPWV; cfPWV; Coronary Artery Disease
12.  Brachial-Ankle Pulse Wave Velocity Is the Only Index of Arterial Stiffness That Correlates with a Mitral Valve Indices of Diastolic Dysfunction, but No Index Correlates with Left Atrial Size 
The objective of this study was to determine the optimal assessment of arterial stiffness that relates to diastolic dysfunction. Forty-one patients had measurements of brachial-ankle pulse wave velocity (baPWV), carotid-femoral pulse wave velocity (cfPWV), ankle brachial index (ABI), pulse pressure (PP), and augmentation index (AIx). Diastolic dysfunction was evaluated by echocardiographic indices of the ratio of the peak early diastolic mitral valve velocity and the peak late diastolic velocity (E/A ratio), left atrial diameter, and left atrial volume indexes. There was a significant (P < 0.05) correlation between baPWV and E/A ratio with an inverse relationship indicating that higher arterial stiffness was associated with greater diastolic dysfunction. In contrast, there was no significant correlation between E/A ratio and cfPWV, PP, ABI, or AIx. After multivariate analysis, the relationship between baPWV and E/A ratio remained significant (P < 0.05), independent of age and systolic blood pressure (BP). There were no correlations between any index of vascular stiffness and left atrial dimension or volume. In summary, baPWV correlates with diastolic dysfunction, independent of a patient's age and BP and is a better indicator of diastolic dysfunction than other indicators of arterial stiffness. baPWV has the utility of infering the presence of left ventricular diastolic dysfunction.
PMCID: PMC3606736  PMID: 23533943
13.  Age- and Gender Dependent Association between Components of Metabolic Syndrome and Subclinical Arterial Stiffness in a Chinese Population 
Background: The aim of this study was to estimate the relationship between arterial stiffness and components of metabolic syndrome (MetS) in different age- and gender groups.
Methods: A total of 12,900 Chinese adults aged 20-79 years were recruited and stratified on the basis of gender and age. All participants underwent the measurement of waist circumference, blood pressure (BP), brachial-ankle pulse wave velocity (baPWV; an indicator of arterial stiffness), and blood chemistry. Multiple linear regression analysis was performed to evaluate the relationship between baPWV and above variables, to determine the relative influence of each component of MetS on baPWV.
Results: The prevalence of metabolic disorders except for low high-density lipoprotein cholesterol (HDL-C) was much higher in men than in women. All participants with MetS or any component of MetS except for low HDL-C had higher baPWV. BP was positively correlated with baPWV in all groups, while HDL-C was not correlated with baPWV in any groups. In addition, fasting glucose was related to baPWV in middle-aged adults and the elderly. Waist circumference had a positive association with baPWV in middle-aged adults and young men, triglyceride levels showed a significant correlation with baPWV in middle-aged women and young men. Of the MetS components, elevated BP was the strongest predictor of baPWV.
Conclusion: The prevalence of metabolic disorders and the association between baPWV and metabolic variables are dependent on age and gender. Different components of MetS exert distinct impacts on the baPWV in different age- and gender groups, with BP being the strongest predictor. It is suggested that age and gender should be taken into accounted in the management of MetS aiming to reduce subsequent complications.
PMCID: PMC3477683  PMID: 23091411
Gender difference; Metabolic syndrome; Brachial-ankle pulse wave velocity; Subclinical arterial stiffness.
14.  The Effect of Telmisartan on Endothelial Function and Arterial Stiffness in Patients With Essential Hypertension 
Korean Circulation Journal  2009;39(5):180-184.
Background and Objectives
Several studies have shown that angiotensin II receptor blockers (ARBs) improve endothelial function and arterial stiffness. Telmisartan is a highly selective ARB that activates peroxisome proliferator-activated receptor γ (PPARγ). The purpose of this study was to evaluate the effects of telmisartan, such as endothelial function, arterial stiffness, and insulin sensitivity, in patients with essential hypertension.
Subjects and Methods
Thirty-nine patients with essential hypertension were administered telmisartan (80 mg once daily) using an open-labeled and prospective protocol. The patients were examined before and 8 weeks after treatment to assess changes in flow mediated-vasodilation (FMD), pulse wave velocity (PWV), quantitative insulin-sensitivity check index (QUICKI), homeostasis model assessment (HOMA), and adiponection.
The systolic and diastolic blood pressure (BP) decreased from 153±15 mmHg and 90±13 mmHg to 137±16 mmHg and 84±10 mmHg after telmisartan treatment, respectively (p<0.01). Telmisartan therapy increased the FMD from 7.6±3.5 to 9.0±2.8% (p<0.01). The following parameters of arterial stiffness were significantly improved after telmisartan therapy: brachial-ankle pulse wave velocity (baPWV), from 17.2±3.1 to 15.9±2.6 m/sec; heart-carotid PWV (hcPWV), from 9.7±1.8 to 9.0±1.9 m/sec; and heart-femoral PWV (hfPWV), from 11.3±1.9 to 10.7±1.9 m/sec (p<0.01). There were no changes in QUICKI, the HOMA level, and plasma adiponectin (p=NS).
These results suggest that telmisartan is effective in improving endothelial function and arterial stiffness in patients with essential hypertension.
PMCID: PMC2771788  PMID: 19949576
Angiotensin II type 1 receptor blockers; Endothelium, vascular; Arteriosclerosis
15.  The Product of Resting Heart Rate Times Blood Pressure Is Associated with High Brachial-Ankle Pulse Wave Velocity 
PLoS ONE  2014;9(9):e107852.
To investigate potential associations between resting heart rate, blood pressure and the product of both, and the brachial-ankle pulse wave velocity (baPWV) as a maker of arterial stiffness.
The community-based “Asymptomatic Polyvascular Abnormalities in Community (APAC) Study” examined asymptomatic polyvascular abnormalities in a general Chinese population and included participants with an age of 40+ years without history of stroke and coronary heart disease. Arterial stiffness was defined as baPWV≥1400 cm/s. We measured and calculated the product of resting heart rate and systolic blood pressure (RHR-SBP) and the product of resting heart rate and mean arterial pressure (RHR-MAP).
The study included 5153 participants with a mean age of 55.1±11.8 years. Mean baPWV was 1586±400 cm/s. Significant (P<0.0001) linear relationships were found between higher baPWV and higher resting heart rate or higher arterial blood pressure, with the highest baPWV observed in individuals from the highest quartiles of resting heart rate and blood pressure. After adjusting for confounding parameters such as age, sex, educational level, body mass index, fasting blood concentrations of glucose, blood lipids and high-sensitive C-reactive protein, smoking status and alcohol consumption, prevalence of arterial stiffness increased significantly (P<0.0001) with increasing RHR-SBP quartile (Odds Ratio (OR): 2.72;95%Confidence interval (CI):1.46,5.08) and increasing RHR-MAP (OR:2.10;95%CI:1.18,3.72). Similar results were obtained in multivariate linear regression analyses with baPWV as continuous variable.
Higher baPWV as a marker of arterial stiffness was associated with a higher product of RHR-SBP and RHR-MAP in multivariate analysis. In addition to other vascular risk factors, higher resting heart rate in combination with higher blood pressure are risk factors for arterial stiffness.
PMCID: PMC4166598  PMID: 25225895
16.  Visceral Adiposity Index May Be a Surrogate Marker for the Assessment of the Effects of Obesity on Arterial Stiffness 
PLoS ONE  2014;9(8):e104365.
The relationship between obesity and cardiovascular disease (CVD) remains unclear. This study aims to describe the relationship between arterial stiffness and obesity in order to investigate the effects of obesity on CVD.
We collected data from 5,158 individuals over 40 years of age from a cross-sectional study in Nanjing, China. Anthropometric, demographic, hemodynamic measurements and arterial stiffness measured through brachial-ankle pulse wave velocity (baPWV) were obtained. Subjects were grouped by body mass index (BMI), waist circumference (WC) and visceral adiposity index (VAI), a sex-specific index based on BMI, WC, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C).
The multivariate regression analysis revealed a negative but weak effect of BMI (β = −0.047, P<0.001) on baPWV, but failed to demonstrate any significant effect of WC on baPWV while VAI was a positive independent indicator of baPWV (β = 0.023, P = 0.022). The unadjusted baPWV significantly increased across groups with higher obesity categories (P<0.01). Although the positive association was lost after adjustments for confounding factors in the BMI or WC categories (P>0.05), it was still obtained between baPWV and VAI quartile (P<0.01). No differences were observed among the metabolically healthy groups or the metabolically abnormal groups in the BMI and WC categories (P>0.05). However, baPWV significantly increased across groups with higher VAI categories even in the same metabolic category (P<0.01).
This study supports the concept of heterogeneity of metabolic status among individuals within the same obesity range. Obese individuals are at an increased risk of arterial stiffness regardless of their metabolic conditions. VAI may be a surrogate marker for the assessment of obesity and the effects of obesity on arterial stiffness.
PMCID: PMC4126713  PMID: 25105797
17.  Association between non-alcoholic fatty liver disease and arterial stiffness in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population 
Background and objective: Non-alcoholic fatty liver disease (NAFLD) is associated with arterial stiffness in the general population. Age, obesity, hypertension, and diabetics are risk factors for arterial stiffness. In this study, we aimed to investigate the association between NAFLD and arterial stiffness as measured by brachial-ankle pulse wave velocity (baPWV) in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population. Methods: A cross-sectional study with 1296 non-obese, non-hypertensive, and non-diabetic young and middle-aged (20–65 years) subjects undergoing routine medical check-ups in the International Health Care Center of the Second Affiliated Hospital of School of Medicine of Zhejiang University was carried out. Fatty liver was diagnosed by ultrasonography, and baPWV was measured using an automatic waveform analyzer. The subjects were classified into two groups according to the presence of NAFLD, and divided into a further two groups according to their baPWV. Results: The overall incidence of NAFLD was 19.0%, and NAFLD patients had a significantly higher level of baPWV than the controls ((1321±158) cm/s vs. (1244±154) cm/s; P<0.001). The incidence of NAFLD was clearly higher in the increased baPWV group than in the normal baPWV group (29.3% vs. 16.9%; P<0.001), and the incidence increased in line with the increase of baPWV quartiles in the normal range as well as with the severity of arterial stiffness (both P for trend <0.001). Multiple linear logistic regression analysis showed that the presence of NAFLD was positively and independently associated with baPWV. Conclusions: Our results suggest that the presence of NAFLD is associated with arterial stiffness as measured by baPWV in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population.
PMCID: PMC4201316  PMID: 25294377
Non-alcoholic fatty liver disease; Arterial stiffness; Brachial-ankle pulse wave velocity; Risk factor
18.  Arterial Stiffness and β-Amyloid Progression in Nondemented Elderly Adults 
JAMA neurology  2014;71(5):562-568.
Recent studies show that cerebral β-amyloid (Aβ) deposition is associated with blood pressure and measures of arterial stiffness in nondemented individuals.
To examine the association between measures of arterial stiffness and change in Aβ deposition over time.
Deposition of Aβ was determined in a longitudinal observational study of aging by positron emission tomography using the Pittsburgh compound B twice 2 years apart in 81 nondemented individuals 83 years and older. Arterial stiffness was measured with a noninvasive and automated waveform analyzer at the time closest to the second positron emission tomography scan. All measures were performed under standardized conditions. Pulse wave velocity (PWV) was measured in the central (carotid-femoral and heart-femoral PWV), peripheral (femoral-ankle PWV), and mixed (brachial-ankle PWV) vascular beds.
The change in Aβ deposition over 2 years was calculated from the 81 individuals with repeat Aβ-positron emission tomography.
The proportion of Aβ-positive individuals increased from 48% at baseline to 75% at follow-up. Brachial-ankle PWV was significantly higher among Aβ-positive participants at baseline and follow-up. Femoral-ankle PWV was only higher among Aβ-positive participants at follow-up. Measures of central stiffness and blood pressure were not associated with Aβ status at baseline or follow-up, but central stiffness was associated with a change in Aβ deposition over time. Each standard deviation increase in central stiffness (carotid-femoral PWV, P = .001; heart-femoral PWV, P = .004) was linked with increases in Aβ deposition over 2 years.
This study showed that Aβ deposition increases with age in nondemented individuals and that arterial stiffness is strongly associated with the progressive deposition of Aβ in the brain, especially in this age group. The association between Aβ deposition changes over time and generalized arterial stiffness indicated a relationship between the severity of subclinical vascular disease and progressive cerebral Aβ deposition.
PMCID: PMC4267249  PMID: 24687165
19.  Clinical utility of brachial-ankle pulse wave velocity in the prediction of cardiovascular events in diabetic patients 
Cardiovascular Diabetology  2014;13(1):128.
Brachial-ankle pulse wave velocity (baPWV) is a method to estimate arterial stiffness, which reflects the stiffness of both the aorta and peripheral artery; it would be applicable to general practice, since its measurementis automated. The aim of this study was to evaluate whether baPWV can be predictors of future cardiovascular events (CVE) in diabetic patients.
We prospectively evaluated the association between baPWV or carotid intima-media thickness (carotid IMT) at baseline and new onset of CVE in 1040 type 2 diabetic patients without CVE. The predictability of baPWV and/or carotid IMT for identifying patients at high risk for CVE was evaluated by time-dependent receiver-operating-characteristic (ROC) curve analysis.
During a median follow-up of 7.5 years, 113 had new CVD events. The cumulative incidence rates of CVE were significantly higher in patients with high baPWV values (≥1550 cm/s) as compared to those with low baPWV values (<1550 cm/s) (p < 0.001, log-rank test). Similarly, the cumulative incidence rate of CVE was significantly higher in patients with higher maximum carotid IMT (maxIMT) values (≥1.0 mm) as compared to those with lower maxIMT values (<1.0 mm) (p < 0.001, log-rank test). Subjects with both “high PWV” and “high IMT” had a significantly higher risk of developing CVE as compared to those with either “high PWV” or “high IMT,” as well as those with neither. A multivariate Cox proportional hazards regression model revealed that both baPWV (HR = 1.30, [95%CI: 1.07-1.57]; p = 0.009) and maxIMT (HR = 1.20, [95%CI: 1.01-1.41]; p = 0.033) were independent predictors for CVE, even after adjustment for the conventional risk factors. Time-dependent ROC curve analyses revealed that the addition of maxIMT to the Framingham risk score resulted in significant increase in AUC (from 0.60 [95%CI: 0.54-0.67] to 0.63 [95%CI: 0.60-0.82]; p = 0.01). Notably, the addition of baPWV to the Framingham risk score and maxIMT resulted in further and significant (p = 0.02) increase in AUC (0.72 [95%CI: 0.67-0.78]).
Evaluation of baPWV, in addition to carotid IMT and conventional risk factors, improved the ability to identify the diabetic individuals with high risk for CVE.
Electronic supplementary material
The online version of this article (doi:10.1186/s12933-014-0128-5) contains supplementary material, which is available to authorized users.
PMCID: PMC4172854  PMID: 25186287
Brachial-ankle pulse wave velocity (baPWV); Carotid intima-media thickness (carotid IMT); Cardiovascular risk; Diabetes mellitus
20.  Arterial Stiffness and Functional Outcome in Acute Ischemic Stroke 
Arterial stiffness is a common change associated with aging and can be evaluated by measuring pulse wave velocity (PWV) between sites in the arterial tree, with the stiffer artery having the higher PWV. Arterial stiffness is associated with the risk of stroke in the general population and of fatal stroke in hypertensive patients. This study is to clarify whether PWV value predicts functional outcome of acute ischemic stroke.
One hundred patients were enrolled with a diagnosis of acute ischemic stroke and categorized into two groups: large-artery atherosclerosis (LAAS) or small vessel disease (SVD) subtype of Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Each group was divided into two sub-groups based on the functional outcome of acute ischemic stroke, indicated by modified Rankin Scale (mRS) at discharge. Poor functional outcome group was defined as a mRS ≥ 3 at discharge. Student's t-test or Mann-Whitney U-test were used to compare maximal brachial-ankle PWV (baPWV) values.
Twenty-four patients whose state was inadequate to assess baPWV or mRS were excluded. There were 38 patients with good functional outcome (mRS < 3) and 38 patients with poor functional outcome (mRS ≥ 3). The baPWV values were significantly higher in patients with poor outcome (2,070.05 ± 518.37 cm/s) compared with those with good outcome (1,838.63 ± 436.65) (p = 0.039). In patients with SVD subtype, there was a significant difference of baPWV values between groups (2,163.18 ± 412.71 vs. 1,789.80 ± 421.91, p = 0.022), while there was no significant difference of baPWV among patients with LAAS subtype (2,071.76 ± 618.42 vs. 1,878.00 ± 365.35, p = 0.579).
Arterial stiffness indicated by baPWV is associated with the functional outcome of acute ischemic stroke. This finding suggests that measurement of baPWV predicts functional outcome in patients with stroke especially those whose TOAST classification was confirmed as SVD subtype.
PMCID: PMC3997922  PMID: 24765608
Stroke; Arterial stiffness; Pulse wave velocity; Functional outcome; Large-artery atherosclerosis; Small vessel disease
21.  Determinants of Brachial-Ankle Pulse Wave Velocity in Normotensive Young Adults with Type 2 Diabetes Mellitus 
Journal of Korean Medical Science  2012;27(11):1359-1363.
Brachial-ankle pulse wave velocity (baPWV) is simple, noninvasive method which correlates well with arterial stiffness. Herein, we assessed the determinants of baPWV in normotensive young adults with type 2 diabetes. We retrospectively enrolled 103 consecutive type 2 diabetic patients aged between 30 and 39 yr who measured baPWV with noninvasive pulse wave analyzer. The anthropometric parameters, blood pressure, pulse rate, fasting plasma glucose, fasting insulin, fasting C-peptide, HbA1c, lipid profile, hs-CRP, albuminuria status, AST/ALT, γ-GTP were checked concurrently. Also, we investigated history of smoking, alcohol drinking and medications by questionnaire. We found that maximal baPWV was positively correlated with mean blood pressure (r = 0.404, P < 0.001), heart rate (r = 0.285, P = 0.004), AST (r = 0.409, P < 0.001), ALT (r = 0.329, P = 0.001), γ-GTP (r = 0.273, P = 0.006), Urine albumin/creatinine ratio (r = 0.321, P = 0.003). By multiple linear regression, mean blood pressure and heart rate were significantly associated with maximal baPWV in male and total group. In female group, mean blood pressure was the only variable associated with maximal baPWV. These factors can be surrogate markers of arterial stiffness in this population.
PMCID: PMC3492671  PMID: 23166418
Pulse Wave Velocity; Type 2 Diabetes; Normotension
22.  Pulse wave velocity is associated with β-amyloid deposition in the brains of very elderly adults 
Neurology  2013;81(19):1711-1718.
To determine arterial stiffness and β-amyloid (Aβ) deposition in the brain of dementia-free older adults.
We studied a cohort of 91 dementia-free participants aged 83–96 years. In 2009, participants completed brain MRI and PET imaging using Pittsburgh compound B (PiB; a marker of amyloid plaques in human brain). In 2011, we measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed (e.g., brachial ankle PWV [baPWV]) vascular beds, using a noninvasive and automated waveform analyzer.
A total of 44/91 subjects were Aβ-positive on PET scan. Aβ deposition was associated with mixed PWV, systolic BP, and MAP. One SD increase in baPWV resulted in a 2-fold increase in the odds of being Aβ-positive (p = 0.007). High white matter hyperintensity (WMH) burden was associated with increased central PWV, systolic BP, and MAP. Compared to Aβ-negative individuals with low WMH burden, each SD increase in PWV was associated with a 2-fold to 4-fold increase in the odds of being Aβ-positive and having high WMH.
Arterial stiffness was associated with Aβ plaque deposition in the brain, independent of BP and APOE ε4 allele. The associations differed by type of brain abnormality and vascular bed measured (e.g., WMH with central stiffness and Aβ deposition and mixed stiffness). Arterial stiffness was highest in individuals with both high Aβ deposition and WMH, which has been suggested to be a “double hit” contributing to the development of symptomatic dementia.
PMCID: PMC3812104  PMID: 24132374
23.  Elevated Brachial-Ankle Pulse Wave Velocity Is Independently Associated with Microalbuminuria in a Rural Population 
Journal of Korean Medical Science  2014;29(7):941-949.
Microalbuminuria is a marker of generalized endothelial dysfunction resulting from arterial stiffness or insulin resistance, and brachial-ankle pulse wave velocity (baPWV) is a good measure of arterial stiffness. We aimed to investigate whether elevated baPWV is independently associated with microalbuminuria. This study included 1,648 individuals aged over 40 who participated in the baseline Multi-Rural Cohort Study conducted in Korean rural communities between 2005 and 2006. Participants were classified into less than 30 mg/g as normoalbuminuria or 30-300 mg/g as microalbuminuriausing urinary albumin creatinine ratio (UACR). The median and Q1-Q3 baPWV values were significantly higher in the microalbuminuric group both in men (1,538, 1,370-1,777 cm/s vs. 1,776, 1,552-2,027 cm/s, P < 0.001) and women (1,461, 1,271-1,687 cm/s vs. 1,645, 1,473-1,915 cm/s, P < 0.001). BaPWV was independently associated with microalbuminuria in both genders after adjusting for pulse rate; fasting blood glucose; triglyceride; homeostatic model assessment insulin resistance (HOMAIR) and, history of hypertension and diabetes. Fasting blood sugar and HOMAIR were judged as having nothing to do with multicolinearity (r = 0.532, P < 0.001). Elevated baPWV was independently associated with microalbuminuria regardless of insulin resistance among rural subjects over 40 yr.
Graphical Abstract
PMCID: PMC4101782  PMID: 25045226
Albuminuria; Insulin Resistance; Risk Factors; Vascular Stiffness
24.  Effects of amlodipine and candesartan on arterial stiffness estimated by cardio-ankle vascular index in patients with essential hypertension: A 24-week study 
Background: Aortic stiffness assessed by brachio-ankle pulse wave velocity (baPWV) can be used to predict cardiovascular events. However, baPWV is dependent on blood pressure. Antihypertensive drugs have been reported to reduce baPWV; but it is difficult to determine if this effect is associated with lowered blood pressure or reduced arterial stiffness.
Objectives: The primary end point of this study was to assess whether antihypertensive drugs reduce arterial stiffness as estimated by cardio-ankle vascular index (CAVI). The secondary end point was to compare the effects of 2 widely used drugs, the calcium-channel blocker amlodipine and the angiotensin II receptor blocker candesartan, on arterial stiffness.
Methods: Between October 2005 and September 2006, consecutive Japanese outpatients with essential hypertension (EHT) (defined as using antihypertensive drugs at screening, systolic blood pressure [SBP] > 140 mm Hg, or diastolic BP [DBP] >90 mm Hg) were assigned to treatment for 24 weeks with either amlodipine (5–10 mg/d) or candesartan (8–12 mg/d). Arterial stiffness was evaluated with CAVI before and after 24 weeks of treatment. Relative change in arterial stiffness from baseline was also compared. The evaluator was blinded to treatment.
Results: Twenty patients (11 men, 9 women; mean [SD] age, 62 [10] years) were included in the study. There were no significant differences in clinical characteristics between the 2 groups. At baseline, mean (SD) CAVI was not significantly different in the amlodipine group compared with the candesartan group (8.93 [0.93] vs 8.46 [1.34], respectively). During the 24-week treatment period, mean SBP and DBP decreased significantly in both the amlodipine (14/10 mm Hg; P = 0.006 and P = 0.005) and the candesartan groups (13/11 mm Hg; P = 0.033 and P = 0.005). Amlodipine was associated with a significant change in CAVI from baseline (8.93 [0.93] vs 8.60 [1.50]; P = 0.017), whereas candesartan was not (8.46 [1.34] vs 8.81 [1.20]). The percentage change in CAVI was significantly different in the amlodipine group compared with the candesartan group (−7.14 [8.83] vs 5.85 [16.0], respectively; P = 0.038). After 24 weeks of treatment, the CAVI of the amlodipine group was still numerically larger than baseline CAVI of the candesartan group, although the difference was not statistically significant. Furthermore, there was no significant difference in absolute CAVI between the 2 groups after 24 weeks, but the relative change from baseline was significant in favor of amlodipine. Logistic regression analysis revealed that amlodipine improved CAVI independent of its antihypertensive effect.
Conclusion: These data suggest that amlodipine and candesartan had different effects on aortic stiffness estimated by CAVI, despite similar effects on brachial blood pressure after 24 weeks of treatment in these Japanese patients with EHT.
PMCID: PMC3969957  PMID: 24692816
arterial stiffness; amlodipne; candesartan; cardio-ankle vascular index
25.  Overall and abdominal obesity indicators had different association with central arterial stiffness and hemodynamics independent of age, sex, blood pressure, glucose, and lipids in Chinese community-dwelling adults 
Limited large sample studies have specially compared overall and abdominal obesity in relation to central arterial stiffness and hemodynamics in community-dwelling adults, especially in the People’s Republic of China. This study aimed to compare the relationship between an overall obesity indicator (body mass index [BMI]), an abdominal obesity index (waist circumference [WC]), and central arterial stiffness and hemodynamics, independent of age, sex, blood pressure, glucose, and lipids, in Chinese community-dwelling adults.
For 2,624 adults in this study, anthropometric indices, such as BMI and WC, were measured. Central arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV). Central hemodynamics was represented by central pulse pressure (cPP).
Both overall and abdominally obese adults were older, with significantly higher cfPWV, cPP, peripheral pulse pressure (pPP), fasting blood glucose (FBG), and low-density lipoprotein-cholesterol (LDL-C), and significantly lower high-density lipoprotein-cholesterol (HDL-C). After adjusting for age and sex, both the overall and abdominally obese individuals had independently higher pPP, FBG, and LDL-C levels, and lower HDL-C level. The overall obese individuals had independently higher cPP, but not cfPWV, after adjusting for age and sex, while the abdominally obese individuals had independently higher cfPWV, but not cPP. After adjusting for age, sex, pPP, FBG, LDL-C, and HDL-C, WC, but not BMI, was independently correlated with cfPWV, and BMI, but not WC, was independently associated with cPP. Age, sex, pPP, FBG, and HDL-C levels have independent association with cfPWV. Age, sex, pPP, but not FBG and HDL-C levels, have independent association with cPP.
The abdominal obesity index (WC), rather than the overall obesity indicator (BMI), was related to central arterial stiffness, independent of age, sex, blood pressure, glucose and lipids, while the overall obesity indicator (BMI), rather than the abdominal obesity indicator (WC), was independently correlated with central hemodynamics. Age, sex, and blood pressure were independently associated with central arterial stiffness and hemodynamics, but blood glucose and lipids were independently associated with central arterial stiffness, rather than hemodynamics.
PMCID: PMC3848376  PMID: 24348027
carotid-femoral pulse wave velocity; central pulse pressure; body mass index; waist circumference

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