Disorders in mineral metabolism are associated with risk for cardiovascular disease (CVD) events in patients with kidney disease as well as in the general population. This risk is thought to be mediated, in part, through the mechanism of stiffening of the arteries.
The objective of this study was to evaluate the relationships between serum calcium, phosphorus, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D levels and arterial pulse wave velocity (aPWV) among 2,229 community-dwelling elderly persons participating in the Health Aging and Body Composition (Health ABC) study.
The mean age of the participants was 72 years; 52% were woman, 39% were black, and 17% had chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2). In parallel unadjusted analyses, the following associations were observed: 2.86% greater aPWV per 12 ng/ml (s.d.) lower 25-hydroxyvitamin D (95% confidence interval −4.38%, −1.31%), 3.04% greater aPWV per 28 pg/ml (s.d.) higher iPTH (95% confidence interval 1.42–4.68%), and 2.37% lower aPWV per 0.5 mg/dl (s.d.) higher phosphorus (95% confidence interval −3.90% to − 0.81%). Except for phosphorus, these associations were attenuated and rendered no longer statistically significant after adjustment for demographic risk factors, clinical site, season, medications and other CVD risk factors. The results were similar in men and women and were not dependent on the presence of CKD.
Among well-functioning community-dwelling elderly persons, only serum phosphorus was associated with aPWV; and this association was in the opposite direction of the one hypothesized. Factors other than vascular stiffening may mediate the relationship between disordered mineral metabolism and CVD events in community-living elders.
arterial stiffness; blood pressure; cardiovascular disease; hypertension; kidney disease; mineral metabolism; PWV
Accelerated central arterial stiffening as represented by progression of aortic pulse-wave velocity (PWV) may be influenced by cardiovascular disease (CVD) risk factors. Little is known about the relationships between CVD risk factors and PWV progression among women transitioning through the menopause, or whether these relationships vary by ethnicity. To address this knowledge gap, we conducted a subgroup analysis of 303 African American and Caucasian participants in the Study of Women's Health Across the Nation (SWAN) Heart Study received PWV scans at baseline examination and at a follow-up examination an average of 2.3 years later. CVD risk factors were also assessed at baseline.
Methods and Results
Systolic blood pressure (SBP) and waist circumference were the strongest predictors of PWV progression, after adjustment for age, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), diastolic blood pressure (DBP), glucose, and triglyceride levels. The magnitude of the influence of SBP, DBP, LDL-C, and glucose on PWV progression varied by ethnicity (difference in slopes: p=0.02 for SBP, p=0.0009 for DBP, p=0.005 for LDL-C, and p=0.02 for glucose). The positive relationship between SBP and PWV progression was significant among women of both ethnicities. LDL-C, DBP, and, to a lesser extent, glucose levels were positively associated with PWV progression only among African Americans.
Blood pressure, LDL-C, glucose, and excess body size may be important targets for improving vascular health and preventing clinical outcomes related to arterial stiffening, particularly among African American women.
arteriosclerosis; risk factors; aging; ethnicity; pulse wave velocity; atherosclerosis
Evidence of premature atherosclerosis and systemic arterial stiffening in patients after Kawasaki disease is accumulating.
To test the hypothesis that carotid intima‐media thickness (IMT), a surrogate marker of atherosclerosis, is associated with systemic arterial stiffness in children after Kawasaki disease.
A cohort of 72 patients was studied, comprising 26 patients with Kawasaki disease and coronary aneurysms (group I), 24 patients with Kawasaki disease and normal coronary arteries (group II) and 22 healthy age‐matched children (group III). The carotid IMT, carotid artery stiffness index, brachioradial pulse wave velocity (PWV), fasting total cholesterol, high‐density lipoprotein (HDL) cholesterol and low‐density lipoprotein (LDL) cholesterol were determined and compared among the three groups.
The carotid IMT was related to indices of arterial stiffness, and significant determinants of carotid IMT were identified by multivariate analysis. The mean (standard deviation (SD)) carotid IMT of both group I (0.41 (0.04) mm) and group II (0.39 (0.04) mm) was significantly greater than that of group III (0.36 (0.04) mm; p<0.001 and p = 0.008, respectively). For the entire cohort, carotid IMT correlated positively with LDL cholesterol (r = 0.31, p = 0.009), carotid artery stiffness index (r = 0.40, p = 0.001) and brachioradial PWV (r = 0.28, p = 0.016), but not with age, body mass index, systemic blood pressure, and HDL and total cholesterol. Multiple linear regression analysis identified carotid artery stiffness index (β = 0.25, p = 0.028) and subject grouping (β = −0.39, p = 0.001; model R2 = 0.29) as significant correlates of carotid IMT.
The increased carotid IMT in children after Kawasaki disease is associated with systemic arterial stiffening.
To investigate the relationship between arterial stiffness and low-grade inflammation in subjects with type 1 diabetes without clinical cardiovascular disease.
RESEARCH DESIGN AND METHODS
Sixty-eight patients with type 1 diabetes and 68 age- and sex-matched healthy subjects were evaluated. Arterial stiffness was assessed by aortic pulse wave velocity (aPWV). Serum concentrations of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and soluble fractions of tumor necrosis factor-α receptors 1 and 2 (sTNFαR1 and sTNFαR2, respectively) were measured. All statistical analyses were stratified by sex.
Subjects with diabetes had a higher aPWV compared with healthy control subjects (men: 6.9 vs. 6.3 m/s, P < 0.001; women: 6.4 vs. 6.0 m/s, P = 0.023). These differences remained significant after adjusting for cardiovascular risk factors. Men with diabetes had higher concentrations of hsCRP (1.2 vs. 0.6 mg/L; P = 0.036), IL-6 (0.6 vs. 0.3 pg/mL; P = 0.002), sTNFαR1 (2,739 vs. 1,410 pg/mL; P < 0.001), and sTNFαR2 (2,774 vs. 2,060 pg/mL; P < 0.001). Women with diabetes only had higher concentrations of IL-6 (0.6 vs. 0.4 pg/mL; P = 0.039). In men with diabetes, aPWV correlated positively with hsCRP (r = 0.389; P = 0.031) and IL-6 (r = 0.447; P = 0.008), whereas in women with diabetes no significant correlation was found. In men, multiple linear regression analysis showed that the following variables were associated independently with aPWV: age, BMI, type 1 diabetes, and low-grade inflammation (R2 = 0.543). In women, these variables were age, BMI, mean arterial pressure, and type 1 diabetes (R2 = 0.550).
Arterial stiffness assessed as aPWV is increased in patients with type 1 diabetes without clinical cardiovascular disease, independently of classical cardiovascular risk factors. In men with type 1 diabetes, low-grade inflammation is independently associated with arterial stiffness.
Vascular reactivity may affect the stiffness characteristics of the arterial wall. We investigated the association between forearm microcirculatory and conduit artery function and measures of arterial stiffness in 527 asymptomatic non-Hispanic white adults without known cardiovascular disease. High-resolution ultrasonography of the brachial artery (ba) was performed to assess forearm microcirculatory function (ba blood flow velocity, local shear stress, and forearm vascular resistance at rest and during reactive hyperemia) and conduit artery function (ba flow-mediated dilatation baFMD and ba nitroglycerin-mediated dilatation baNMD). Arterial stiffness was assessed by cuff-derived brachial pulse pressure and aortic pulse wave velocity (aPWV) measured by applanation tonometry. In regression analyses that adjusted for heart rate, mean arterial pressure, height, cardiovascular risk factors, and hypertension medication and statin use, higher baseline ba systolic velocity and systolic shear stress were associated with greater pulse pressure (P=0.0002 and P=0.006, respectively) and higher aPWV (each P<0.0001). During hyperemia, lower ba mean velocity and lower mean shear stress were associated with higher pulse pressure (P=0.045 and P=0.036, respectively) while both systolic and mean velocity (P<0.0001 and P=0.002, respectively) and systolic and mean shear stress (P<0.0001 and P=0.003, respectively) were inversely associated with aPWV. baFMD was not associated with pulse pressure but was inversely associated with aPWV (P=0.011). baNMD was inversely associated with pulse pressure (P=0.0002) and aPWV (P=0.008). Our findings demonstrate that impaired forearm microvascular function (in the form of elevated resting blood flow velocity and impaired flow reserve) and impaired brachial artery reactivity are associated with increased arterial stiffness.
microvascular function; flow-mediated dilatation; nitroglycerin-mediated dilatation; arterial stiffness; pulse pressure; pulse wave velocity
We tested the hypothesis that sodium nitrite treatment reverses large elastic artery stiffening in old mice via reductions in collagen I, increases in elastin and/or decreases in advanced glycation endproducts (AGEs) mediated by reduced oxidative stress. Aortic pulse wave velocity (aPWV), a measure of large elastic artery stiffness, was greater in old (26–28 mo) compared with young (4–6 mo) control animals (520 ± 9 vs. 405 ± 6 cm/s, p<0.05), and this was reversed by 3 weeks of sodium nitrite treatment (50 mg/L) (435 ± 17 cm/s). Age-related increases (p<0.05) in aortic superoxide production were associated with greater total and adventitial nitrotyrosine staining, all of which were reversed by nitrite treatment. Total and adventitial transforming growth factor β and collagen I were increased, and total and medial elastin were reduced with aging (p<0.05), but were unaffected by sodium nitrite. Aorta from old mice had increased total, adventitial and medial AGEs (p<0.05 vs. young), which were normalized by sodium nitrite treatment. In aortic segments from young mice in vitro, pyrogallol (10 µM), a superoxide generator, induced an “aging-like” increase in AGEs, and direct treatment with AGEs induced vascular stiffening; these effects were prevented by incubation with sodium nitrite. De-stiffening of aged large elastic arteries by short-term sodium nitrite therapy is mediated in part by normalization of AGEs secondary to amelioration of oxidative stress.
arterial stiffness; collagen; elastin; nitrotyrosine; superoxide
Metabolically benign obese individuals have a 10-year cardiovascular disease (CVD) risk comparable to healthy normal weight individuals. However, the burden of subclinical CVD among metabolically benign obese is not well known.
In cross-sectional analyses of 475 mid-life women, we compared common carotid artery intima media thickness (CCA-IMT), aortic pulse wave velocity (aPWV) and coronary (CAC) and aortic calcification (AC) among three groups: healthy normal weight, metabolically benign overweight/obese (<3 metabolic syndrome components/elevated CRP), and at-risk overweight/obese (≥3 metabolic syndrome components/elevated CRP).
The mean (SD) CCA-IMT and aPWV were lowest in the normal weight group (n=145), followed by the benign overweight/obese (n=260) and at-risk overweight/obese (n=70) groups [CCA-IMT: 0.64 (0.08) vs. 0.68 (0.09) vs. 0.73 (0.13) mm, p<0.001; aPWV: 731.0 (176.4) vs. 809.9 (182.3) vs. 875.7 (228.8) cm/s, p<0.001]. Similar results were found for the frequency (%) of women with increased CAC and AC [CAC: 13 (9%) vs. 53(20%) vs. 28(40%), p<0.001; AC: 47(32%) vs. 130 (50%) vs. 55(79%), p<0.001]. These differences remained significant after multivariable adjustment. Further adjustment for BMI attenuated the statistical significance of differences in aPWV and calcification between benign and at-risk overweight/obese women, but had little effect on the magnitude of these differences.
Metabolically benign overweight/obese women have a significantly greater subclinical CVD burden than normal weight women, despite published data finding similar CVD event rates between the two groups. Prospective studies tracking the progression of subclinical atherosclerosis to clinical CVD in these women are needed.
Obesity phenotypes; subclinical atherosclerosis; carotid intima media thickness; pulse wave velocity; coronary calcification; aortic calcification
Pulse wave velocity (PWV) and ankle-brachial pressure index (ABI) are non-invasive tools to measure atherosclerosis and arterial stiffness. Heart rate variability (HRV) has proven to be a non-invasive powerful tool in the investigation of the autonomic cardiovascular control. Therefore, the purpose of this study was to determine the relationship among PWV, ABI, and HRV parameters in adult males.
The study was carried out with 117 males who visited a health care center from April, 2009 to May, 2010. We conducted blood sampling (total cholesterol, triglyceride, high density lipoprotein, cholesterol, fasting glucose) and physical examination. We studied brachial-ankle PWV (baPWV) and ABI. We examined HRV parameters including standard deviation of NN interval (SDNN), low frequency (LF), high frequency (HF), LF/HF ratio. We analyzed the relationship among baPWV, ABI, and HRV parameters.
SDNN had a significant negative correlation with age, systolic blood pressure and heart rate. LF and HF had a significant negative correlation with age, and age and heart rate, respectively. baPWV was significantly and positively associated with age, systolic and diastolic blood pressures, total cholesterol, fasting glucose and heart rate. ABI was negative correlated significantly with systolic and diastolic blood pressures and heart rate. After adjusting for all associated variables, baPWV was not correlated with HRV parameters, but there was a significant positive association between SDNN and ABI (r = 0.195, P = 0.014).
SDNN of HRV parameters had a significant positive correlation with ABI.
Heart Rate Variability; Pulse Wave Velocity; Ankle-Brachial Pressure Index
Central arterial stiffness is increasingly recognized as an important predictor of cardiovascular events and mortality in older adults; however, few studies have evaluated the association of arterial stiffness with mobility decline, a common consequence of vascular disease.
We analyzed the association of pulse wave velocity (PWV), a measure of aortic stiffness, with longitudinal gait speed over seven years in 2,172 participants in the Health, Aging and Body Composition (Health ABC) Study (mean age ± SD 73.6 ± 2.9 years, 48% men, 39% black).
In mixed-effects models adjusted for demographics, each SD (396 cm/s) higher PWV was associated with 0.015 (SE 0.004) m/s slower gait at baseline and throughout the study period in the full cohort (p < 0.001); this relationship was largely explained by hypertension and other vascular risk factors. Among participants with peripheral arterial disease (PAD) (n = 261; 12.7%) each SD higher PWV was independently associated with 0.028 (SE 0.010) m/s slower gait speed at baseline and throughout the study period (p < 0.01).
These findings suggest that aortic stiffness may be especially detrimental to mobility in older adults with already compromised arterial function.
Arterial stiffness; peripheral arterial disease; physical function; aging
Safflower seed extract (SSE) contains characteristic polyphenols and serotonin derivatives (N-( p-coumaroyl) serotonin and N-feruloylserotonin), which are reported to inhibit oxidation of low-density lipoprotein (LDL), formation of atherosclerotic plaques, and improve arterial stiffness as assessed by pulse wave analysis in animal models. The effects of long-term supplementation with SSE on arterial stiffness in human subjects were evaluated. This doubleblind, placebo-controlled study was conducted in 77 males (35–65 years) and 15 postmenopausal females (55–65 years) with high-normal blood pressure or mild hypertension who were not undergoing treatment. Subjects received SSE (70 mg/day as serotonin derivatives) or placebo for 12 weeks, and pulse wave measurements, ie, second derivative of photoplethysmogram (SDPTG), augmentation index, and brachial-ankle pulse wave velocity (baPWV) were conducted at baseline, and at weeks 4, 8, and 12. Vascular age estimated by SDPTG aging index improved in the SSE-supplemented group when compared with the placebo group at four (P = 0.0368) and 12 weeks (P = 0.0927). The trend of augmentation index reduction (P = 0.072 versus baseline) was observed in the SSE-supplemented group, but reduction of baPWV by SSE supplementation was not observed. The SSE-supplemented group also showed a trend towards a lower malondialdehyde-modified-LDL autoantibody titer at 12 weeks from baseline. These results suggest long-term ingestion of SSE in humans could help to improve arterial stiffness.
safflower; serotonin derivatives; antioxidants; augmentation index; pulse wave velocity
Circulating aldosterone is increased in obesity and is associated with arterial stiffening in hypertensives and older adults. We aimed to determine whether serum aldosterone is associated with pulse wave velocity (PWV), a measure of arterial stiffness, in normotensive overweight and obese adults aged 20–45 years (n=344). We measured heart-femoral, femoral-ankle and brachial-ankle PWV. The sample was 77% female with mean BMI 32.9 kg/m2 (SD 3.9), median serum aldosterone 106.5 pg/mL (IQR 79.9, 155.5), and mean 24-hour urinary sodium excretion 185.9 mEq/day (SD 69.6). Higher serum aldosterone was not significantly correlated with any PWV measure in bivariate analysis. However, in multiple linear regression, adjusting for age, sex, race, height, heart rate, mean arterial pressure, and waist circumference, higher log aldosterone was associated with greater log heart-femoral PWV (β(se)=0.042(0.021), p=0.049). After adjusting for C-reactive protein, this association was no longer significant (β(se)=0.035(0.021), p=0.10). Circulating aldosterone may play an important role in vascular inflammation and aortic stiffening in normotensive overweight and obese adults.
aldosterone; arterial stiffness; inflammation; obesity; RAAS
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.
Gender difference; Metabolic syndrome; Brachial-ankle pulse wave velocity; Subclinical arterial stiffness.
To test the hypothesis that the antioxidant enzyme superoxide dismutase (SOD) mimetic TEMPOL improves arterial aging, young (Y, 4–6 mo) and old (O, 26–28 mo) male C57BL6 mice received regular or TEMPOL-supplemented (1mM) drinking water for 3 weeks (n=8/group). Aortic superoxide was 65% greater in O (p<0.05 vs. Y), which was normalized by TEMPOL. O had large elastic artery stiffening, as indicated by greater aortic pulse wave velocity (aPWV, 508 ± 22 vs. 418 ± 22 AU), which was associated with increased adventitial collagen I expression (p<0.05 vs. Y). TEMPOL reversed the age-associated increases in aPWV (434 ± 21 AU) and collagen in vivo, and SOD reversed increases in collagen I in adventitial fibroblasts from older rats in vitro. Isolated carotid arteries of O had impaired endothelial function as indicated by reduced acetylcholine-stimulated endothelium-dependent dilation (EDD) (75.6 ± 3.2 vs. 94.5 ± 2.0%) mediated by reduced nitric oxide (NO) bioavailability (L-NAME) associated with decreased endothelial NO synthase (eNOS) expression (p<0.05 vs. Y). TEMPOL restored EDD (94.5 ± 1.4%), NO bioavailability and eNOS in O. Nitrotyrosine and expression of NADPH oxidase were ~100–200% greater, and MnSOD was ~75% lower in O (p<0.05 vs. Y). TEMPOL normalized nitrotyrosine and NADPH oxidase in O, without affecting MnSOD. Aortic pro-inflammatory cytokines were greater in O (p<0.05 vs. Y) and normalized by TEMPOL. Short-term treatment of excessive superoxide with TEMPOL ameliorates large elastic artery stiffening and endothelial dysfunction with aging, and this is associated with normalization of arterial collagen I, eNOS, oxidative stress and inflammation.
superoxide dismutase; inflammation; collagen; nitric oxide; glycation endproducts
It is currently unclear whether reductions in adiposity mediate the improvements in vascular health that occur with aerobic exercise. The purpose of this longitudinal study of 13 healthy women (33 ± 4 years old) was to determine whether 14 weeks of aerobic exercise would alter functional measures of vascular health, namely resting aortic pulse wave velocity (aPWV, an index of arterial stiffness), femoral artery diameter (DFA), and femoral artery blood flow (BFFA) independent of changes in adiposity.
Aerobic fitness was assessed as VO2peak normalized to fat-free mass, and adiposity (percent body fat) was determined by dual energy x-ray absorptiometry. Serum concentrations of proteins associated with risk for cardiovascular disease, including C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and leptin, were also measured. Subjects cycled for 50 minutes, 3 times per week.
Aerobic fitness normalized to fat-free mass increased 6% (P = 0.03) whereas adiposity did not change. Resting DFA increased 12% (P < 0.001) and resting shear rate decreased 28% (P = 0.007). Aortic PWV, and serum sICAM-1, CRP and leptin did not change with training.
Significant reductions in adiposity were not necessary for aerobic exercise training to bring about improvements in aerobic fitness and arterial remodeling. Peripheral arterial remodeling occurred without changes in central arterial stiffness or markers of inflammation.
To examine the association between depressive symptoms and subclinical markers of cardiovascular disease (CVD), specifically arterial stiffness, as indexed by pulse wave velocity (PWV), and carotid artery intima thickening (IMT), in a sample of healthy adolescents, and to explore adolescent hostility as a potential moderator of depression on subclinical markers of CVD.
One hundred and fifty-seven (n = 157) black and white adolescents between the ages of 16-21 completed a follow-up study of psychosocial stress and cardiovascular risk factors that included measures of PWV and carotid IMT. Psychosocial measures included the Center for Epidemiologic Studies Depression Scale (CES-D; divided into tertiles), and the Cook-Medley Hostility Inventory subscales. Linear regression models controlled for sociodemographic variables, health behaviors, blood pressure, body mass index, and heart rate.
Results show that more severe depressive symptoms were associated with higher levels of PWV (B = 0.17, R2 = 0.30, ΔR2 = 0.03, CI = 2.2 – 47.0, p = .03) but not with higher IMT. Adolescent depression remained a significant predictor of PWV when controlling for adolescent hostility; hostility did not moderate the relationship between adolescent depression and PWV.
Depression may be important in the development of arterial stiffness in adolescence. Further research is needed to delineate the relationship in adolescence and young adulthood between depressive symptoms and the pathogenesis of CVD.
depression; adolescents; hostility; pulse wave velocity; cardiovascular disease
To examine the risk factors related to the incidence of aortic stiffness, 1,045 Japanese men aged 40 to 54 years with aortic pulse wave velocity (PWV) of less than 8.0 m/sec were followed up for seven years with annual examinations, with an average period of observation of 6.3 years with standard deviation of 1.56 years. Subjects who showed 8.0 m/sec and over of PWV during follow-up surveys were defined as incidental cases of aortic stiffness. Kaplan-Meier analysis showed that die incidence of aortic stiffness increased significantly with increases in age, body mass index, and total cholesterol and low-density lipoprotein (LDL) cholesterol levels. The incidence of aortic stiffness was significantly higher among those who had or currently smoked than among those who never smoked. From multivariate analysis using Cox proportional hazards model, the incidence of aortic stiffness showed a significant dose-response relationship for age, PWV, total cholesterol and LDL cholesterol levels and smoking habits. These results indicate that increased levels of total cholesterol and LDL cholesterol and smoking habits may constitute contributing factors for the development of aortic stiffness in middle-aged Japanese men.
pulse wave velocity; aortic stiffness; risk factors; follow-up study
Aging is associated with reduced endothelium-dependent dilation (EDD) and increased risk for cardiovascular disease (cVD), but the mechanisms are incompletely understood. clinically elevated plasma low-density lipoprotein cholesterol (LDL-C) is associated with impaired EDD. The purpose of this study was to determine whether circulating LDL-C within the “normal” range modulates EDD in healthy older adults and whether young age or habitual aerobic exercise protects against this adverse effect.
In 83 healthy men with optimal/near optimal LDL-C (<130 mg/dl) or borderline high LDL-C (130–159 mg/dl), EDD (brachial artery flow-mediated dilation, FMD), and endothelium-independent dilation (sublingual glyceryl trinitrate, GTN) were assessed.
FMD was 35% lower in older nonexercising men with borderline high LDL-C vs. optimal/near optimal LDL-C (3.1 ± 0.5 vs. 4.8 ± 0.4%Δ, P < 0.05), whereas the GTN response did not differ (P = 0.86). In contrast, FMD was similar between groups of young nonexercising men and between groups of older exercising men differing in LDL-C (P = 0.89–0.95). FMD was inversely related to LDL-C among the older nonexercising men (r = −0.43, P < 0.001), whereas there was no relation in the other groups (P > 0.05).
Borderline high plasma LDL-C is associated with impaired EDD in older sedentary men, but not in young sedentary or older exercising men. Thus, modest elevations in plasma LDL-C within the normal range may contribute to the increased risk of cVD in sedentary older men by exacerbating vascular endothelial dysfunction, whereas resistance to this adverse influence may help explain the enhanced endothelial function and reduced CVD risk associated with young age and regular aerobic exercise.
Background and aims
Carotid sinus hypersensitivity (CSH) is a common cause of fainting and falls in the older adult population and is diagnosed by carotid sinus massage (CSM). Previous work has suggested that age-related stiffening of blood vessels reduces afferent input from the carotid sinus leading to central upregulation of the overall arterial baroreflex response. We examined the differences in arterial stiffness and baroreflex function in older adults at high cardiovascular risk (advanced age, Type 2 diabetes, hypertension and hyperlipidemia) with and without CSH.
Forty-three older adults (mean age 71.4±0.7) with Type 2 diabetes, hyperlipidemia and hypertension were recruited. After resting supine for 45 minutes prior to the start of data collection, each subject had arterial stiffness measured by pulse wave velocity (PWV, Complior SD), followed by spontaneous baroreflex measures (Baroreflex sensitivity, BRS) and CSM.
Of the 43 subjects tested, 10 subjects met the criteria for CSH (8 pure vasodepressor and 2 mixed CSH). CSH subjects had higher measures of arterial stiffness when compared to normal subjects for both radial PWV (11.5±0.6 vs 9.6±0.4 m/s, p=0.043) and femoral PWV (13.4±0.9 vs 11.0±0.5 m/s, p=0.036). The CSH group demonstrated significantly lower BRS as compared to the normal group (BRS, 6.73±0.58 vs 10.41±0.85 ms/mmHg, p=0.038). These results were unchanged when the analysis was repeated with only the VD subjects.
Older adults with CSH have higher arterial stiffness and reduced arterial baroreflex sensitivity. There was no evidence to support upregulation of the arterial baroreflex in patients with CSH.
PMID: 20142630 CAMSID: cams3236
Arterial baroreflex function; arterial stiffness; carotid sinus hypersensitivity; carotid sinus massage; geriatric medicine
Cardiovascular disease is the leading cause of mortality among peritoneal dialysis (PD) patients in Macao. Increased arterial stiffness determined by pulse wave velocity (PWV) has been established as an independent predictor of cardiovascular mortality in end-stage renal disease patients. The present study aims to investigate the relationship between arterial stiffness and its associated risk factors in chronic PD patients.
A total of 96 chronic PD patients (48 males/48 females) were included in the cross-sectional study. Arterial stiffness was assessed by brachial-ankle PWV (baPWV). Patients were divided into two subgroups according to mean baPWV value. On enrollment, clinical characteristics and biochemical parameters were collected.
Compared with low baPWV group patients, high baPWV group patients were significant older (p<0.001) and more likely to have a high proportion of female gender (p=0.004) as well as previous CVD history (p=0.008). Serum albumin, pre-albumin levels and residual renal creatinine clearance (CCr) were significantly lower but the serum ferritin level was significantly higher in high baPWV group patients than in low baPWV group patients (all p<0.01). BaPWV was positively associated with age (r=0.534, p<0.001), Charlson comorbidity index (r=0.350, p<0.001) and serum ferritin level (r=0.340, p=0.001). Meanwhile, baPWV negatively correlated with serum albumin (r=−0.479, p<0.001), pre-albumin levels (r=−0.320, p=0.003) and residual renal CCr (r=−0.177, p=0.048). Age-adjusted partial correlation test found a significant correlation between baPWV and CRP (r=0.462, p<0.001). Multivariate regression analysis showed that baPWV was independently associated with age (p<0.001), serum albumin level (p=0.015), CRP (p=0.019) and residual renal CCr (p=0.045).
Arterial stiffness, assessed by baPWV, had an independent correlation with age, serum albumin level, CRP level and residual renal CCr among PD patients in Macao.
Arterial stiffness; Pulse wave velocity; Cardiovascular disease; Peritoneal dialysis
Serum dehydroepiandrosterone (DHEA) concentrations decrease ~80% between ages 25 and 75 yr. Aging also results in an increase in arterial stiffness, which is an independent predictor of cardiovascular disease (CVD) risk and mortality. Therefore, it is conceivable that DHEA replacement in older adults could reduce arterial stiffness. We sought to determine if DHEA replacement therapy in older adults reduces carotid augmentation index (AI) and carotid-femoral pulse wave velocity (PWV) as indices of arterial stiffness.
A randomized, double-blind trial was conducted to study the effects of 50 mg/d DHEA replacement on AI (n=92) and PWV (n=51) in women and men aged 65–75 yr. Inflammatory cytokines and sex hormones were measured in fasting serum.
AI decreased in the DHEA group but not in the placebo group (difference between groups, −6±2 AI units, p=0.002). PWV also decreased (difference between groups, −3.5±1.0 m/sec, p=0.001); however, after adjusting for baseline values, the between-group comparison became non-significant (p=0.20). The reductions in AI and PWV were accompanied by decreases in inflammatory cytokines (TNFα and IL-6, p<0.05) and correlated with increases in serum DHEAS (r = −0.31 and −0.37, respectively, p<0.05). The reductions in AI also correlated with free testosterone index (r = −0.23, p=0.03).
DHEA replacement in elderly men and women improves indices of arterial stiffness. Arterial stiffness increases with age and is an independent risk factor for CVD. Therefore the improvements observed in the present study suggest that DHEA replacement might partly reverse arterial aging and reduce CVD risk.
vasculature; augmentation index; aging
Complement 1 (C1) inhibitor is an acute phase protein with anti-inflammatory properties. The aim of the present study was to elucidate the relationship between brachial ankle pulse wave velocity (baPWV), the parameter of arterial stiffness, and C1 inhibitor. One hundred subjects were randomly enrolled in this study. Data about baPWV, age, gender, hypertension, smoking, and body mass index (BMI) were measured. Blood tests for total cholesterol, low density lipoprotein, high density lipoprotein, triglycerides, hemoglobin A1c, erythrocyte sedimentation rate, C-reactive protein, complement 3, and C1 inhibitor were performed. Based on the Pearson correlation, the C1 inhibitor showed a positive relation to the baPWV (P<0.001). Multiple regression analysis revealed the significant predictors of baPWV were not only the conventional risk factors of arteriosclerosis and/or atherosclerosis, such as age (P<0.001), gender (P<0.001), hypertension (P<0.001), and BMI (P=0.006), but also the acute phase protein, C1 inhibitor (P=0.025). In conclusion, C1 inhibitor is associated with arterial stiffness through its association with increased inflammation.
Complement 1 Inhibitor; Pulse Wave Velocity; Stiffness
The oxidative modification of low-density lipoprotein (LDL) in the intima of
arteries contributes to the initiation and progression of atherosclerotic lesions.
We have previously reported that oxidized LDL (oxLDL) interacts with
an endogenous plasma protein, β2-glycoprotein I (β2GPI), to form
complexes and that the interaction is mediated by oxLDL specific ligands. We have also
demonstrated the presence of oxLDL/β2GPI complexes in the blood stream
of patients with systemic inflammatory and autoimmune diseases. These findings
implicate that oxLDL/β2GPI complexes are possible atherogenic autoantigens.
Autoantibodies to oxLDL/β2GPI complexes have been associated with arterial
thrombosis. Further, circulating IgG immune complexes containing oxLDL and
2GPI were also detected in patients with systemic lupus erythematosus (SLE)
and/or antiphospholipid syndrome (APS). Although many unanswered questions
remain about the exact pathogenic mechanism(s) involved, oxLDL/β2GPI
complexes may be described as metabolic products relevant in atherogenesis and as
significant participants in autoimmune-mediated atherosclerosis.
The relationship between advanced glycation end products and arterial stiffness has previously been examined in highly selected groups of patients with diabetes or hypertension. Our aim was to determine whether elevated serum advanced glycation end products are associated with increased arterial stiffness in relatively healthy, community-dwelling adults.
Aortic pulse wave velocity (PWV), an index of aortic stiffness, and serum AGEs, as represented by the specific AGE, serum carboxymethyl-lysine (CML), were measured in 493 adults, aged 26-93 years, who participated in the Baltimore Longitudinal Study of Aging.
Mean (SD) PWV (m/sec) was 6.6 (1.8) m/sec. Mean CML was 0.47 (0.13) μg/mL. Serum CML (per 1 Standard Deviation [S.D.]) was associated with PWV (beta = 0.16, standard error [S.E.] = 0.07, P = 0.02), adjusting for age, sex, body mass index, mean arterial pressure, fasting plasma glucose, high density lipoprotein cholesterol, smoking, and other covariates. After excluding all diabetic patients, serum CML (per 1 S.D.) was associated with PWV (beta = 0.18, S.E. = 0.07, P = 0.009), adjusting for the same covariates.
Elevated AGEs are associated with increased arterial stiffness, a known predictor of adverse cardiovascular outcomes, among relatively healthy community-dwelling adults. Interventions to lower levels of AGEs, such as altering the pattern of dietary intake, warrant examination as putative novel strategies to lower arterial stiffness in adults.
advanced glycation end products; aging; arterial stiffness; cardiovascular disease; pulse wave velocity
Aortic PWV is a measure of arterial stiffness and has proved useful in predicting cardiovascular morbidity and mortality in several populations of patients, including the healthy elderly, hypertensives and those with end stage renal disease receiving hemodialysis. Little data exist characterizing aortic stiffness in patients with chronic kidney disease who are not receiving dialysis, and in particular the effect of reduced kidney function on aortic PWV.
We performed measurements of aortic PWV in a cross-sectional cohort of participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study to determine factors which predict increased aortic PWV in chronic kidney disease.
PWV measurements were obtained in 2564 participants. The tertiles of aortic PWV (adjusted for waist circumference) were < 7.7 m/sec, 7.7–10.2 m/sec and > 10.2 m/sec with an overall mean (± S.D.) value of 9.48 ± 3.03 m/sec [95% CI = 9.35–9.61 m/sec]. Multivariable regression identified significant independent positive associations of age, blood glucose concentrations, race, waist circumference, mean arterial blood pressure, gender, and presence of diabetes with aortic PWV and a significant negative association with the level of kidney function.
The large size of this unique cohort, and the targeted enrollment of chronic kidney disease participants provides an ideal situation to study the role of reduced kidney function as a determinant of arterial stiffness. Arterial stiffness may be a significant component of the enhanced cardiovascular risk associated with kidney failure.
Statin- and exercise-therapy are both clinically beneficial by preventing cardiovascular events in patients with coronary artery disease (CAD). However, there is no information on the vascular effects of the combination of statins and exercise on arterial wall stiffness in CAD patients.
The present study is a sub-analysis of PRESET study that determined the effects of 20-week treatment with statins (rosuvastatin, n = 14, atorvastatin, n = 14) combined with regular exercise on arterial wall stiffness assessed by measurement of brachial and ankle pulse wave velocity (baPWV) in CAD patients.
The combination of statins and regular exercise significantly improved exercise capacity, lipid profile, including low- and high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein (hs-CRP), baPWV (baseline: 1747±355, at 20 weeks of treatment: 1627±271 cm/s, p = 0.008), and basophil count (baseline: 42±32, 20 weeks: 26±15 cells/µL, p = 0.007), but had no effect on blood pressure (baseline: 125±22, 20 weeks: 121±16 mmHg). Changes in baPWV correlated significantly with changes in basophil count (r = 0.488, p = 0.008), but not with age, lipids profile, exercise capacity, or hs-CRP.
In CAD patients, the combination treatment with statins and exercise resulted in significant amelioration of arterial wall stiffness, at least in part, through reduction of circulating basophils.