Relationship between clinical, 24-hour, average day-time and night-time blood pressure and measures of arterial stiffness in essential hypertension

Arterial wall stiffness is considered an independent cardiovascular risk factor. Aim of this study was to evaluate relationship between clinical, 24-hour, average day-time and night-time blood pressure (BP) and measures of arterial stiffness assessed by pulse wave velocity (PWV) (using SphygmoCor applanation tonometer) in essential hypertension (severe-resistant (RH, n=29) and moderate hypertension (EH, n=35)) and in normotensive control subjects (n-29) (NCS) matched by age. After multiple regression analysis, PWV remains significantly correlated mainly with night-time pulse pressure and to a lesser extent with age. PWV was significantly higher in RH compared to moderate EH and NCS.     

Determinants of arterial stiffness in COPD

Background

Cardiovascular morbidity and mortality is high in patients with chronic obstructive pulmonary disease (COPD) and arterial stiffness is a potentially modifiable risk factor with added predictive value beyond that obtained from traditional risk factors. Arterial stiffness has been the target of pharmacologic and exercise interventions in patients with COPD, but the effects appear limited to those patients with more significant elevations in arterial stiffness. We aimed to identify predictors of increased arterial stiffness in a cohort with moderate to severe COPD.

Methods

Aortic pulse wave velocity (aPWV) was measured in subjects with moderate to severe COPD enrolled in a multicenter randomized controlled trial. Subjects were categorized into quartiles based on aPWV values and factors affecting high arterial stiffness were assessed. Multivariate models were created to identify independent predictors of high aPWV, and cardiovascular disease (CVD).

Results

153 patients were included. Mean age was 63.2 (SD 8.2) years and mean FEV₁ was 55.4 (SD 15.2) % predicted. Compared to the quartile with the lowest aPWV, subjects in the highest quartile were older, had higher systolic blood pressure (SBP), were more likely to be current smokers, and had greater burden of thoracic aortic calcification. On multivariate analyses, age (adjusted OR 1.14, 95%CI 1.05 to 1.25, p?=?0.003) and SBP (adjusted OR 1.06, 95% CI 1.02 to 1.09, p?=?0.001) were independent predictors of elevated aPWV. Body mass index, therapy with cholesterol lowering medications and coronary calcification were independent predictors of CVD.

Conclusions

Elevated arterial stiffness in patients with COPD can be predicted using age, blood pressure and thoracic aortic calcification. This will help identify subjects for enrollment in clinical trials using aPWV for assessing the impact of COPD therapies on CV outcomes.

Trial registration

Clinicaltrials.gov NCT00857766     

Aortic stiffness and pulse pressure amplification in Wistar-Kyoto and spontaneously hypertensive rats

In humans, increased body weight and arterial stiffness are significantly associated, independently of blood pressure (BP) level. The finding was never investigated in rodents devoid of metabolic disorders as spontaneously hypertensive rats (SHR). Using simultaneous catheterization of proximal and distal aorta, we measured body weight, intra-arterial BP, heart rate and their variability (spectral analysis), aortic pulse wave velocity (PWV), and systolic and pulse pressure (PP) amplifications in unrestrained conscious Wistar-Kyoto (WKY) rats and SHR between 6 and 24 wk of age. Aortic proximal systolic and diastolic pressure, PP, and mean BP were significantly higher in SHR than in WKY rats and increased significantly with age (with the exception of PP). PP amplification increased with age but did not differ between strains. PWV was significantly associated with heart rate variability. PWV was significantly higher (via two-way variance analysis) in SHR than in WKY rats (strain effect) and increased markedly with age in both strains (age effect). Adjustment of PWV to mean BP attenuated markedly both the age and the strain effects. After adjustment for body weight, either alone or associated with mean BP, the age effect was not more significant, but the strain effect was markedly enhanced. In conscious unanesthetized SHR and WKY rats, aortic stiffness is consistently associated with body weight independent of age and mean BP. An intervention study should consider in the objectives systolic BP and PP amplifications measured in conscious animals, central control of body weight, and autonomic nervous system.     

Dehydroepiandrosterone replacement therapy in older adults improves indices of arterial stiffness

Serum dehydroepiandrosterone (DHEA) concentrations decrease approximately 80% between ages 25 and 75 year. 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 whether 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 day^?1 DHEA replacement on AI (n = 92) and PWV (n = 51) in women and men aged 65–75 year. 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). Pulse wave velocity also decreased (difference between groups, ?3.5 ± 1.0 m s^?1, P = 0.001); however, after adjusting for baseline values, the between‐group comparison became nonsignificant (P = 0.20). The reductions in AI and PWV were accompanied by decreases in inflammatory cytokines (tumor necrosis factor α 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). In conclusion, 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 this study suggest that DHEA replacement might partly reverse arterial aging and reduce CVD risk.     

The prostacyclin analogue beraprost sodium prevents development of arterial stiffness in elderly patients with cerebral infarction

Prostacyclin (PGI(2)) inhibits platelet aggregation, smooth muscle cell proliferation, and vasoconstriction. Arterial stiffness assessed by pulse wave velocity (PWV) predicts mortality in various cardiovascular diseases. To study the preventive effects of a prostacyclin analogue, beraprost sodium, on arterial PWV values in elderly patients with cerebral infarction. Forty-four patients with a history of cerebral infarction received beraprost sodium (120 microg/day p.o.) or no beraprost sodium (control) for 3 months. Arterial PWV and ankle brachial indices (ABI) were determined prior to starting the medication and after 3 months of medication. Initially, there were no differences in age, blood pressure, and body mass index. Further, PWV or ABI did not differ between the beraprost sodium group (n = 22) and the control group (n = 22). After 3 months, PWV in beraprost sodium group was significantly reduced (-123 +/- 282) when compared with the control group (147 +/- 274)(P = 0.006). ABI was not significantly different when comparing the two groups at 3 months. Long-term administration of beraprost sodium prevents the decline in arterial biomechanics in elderly patients with cerebral infarction.     

Relationship between sleep duration and arterial stiffness in a multi-ethnic population: The HELIUS study

We examined the relationship between sleep duration and arterial stiffness among a multi-ethnic cohort, and whether the associations differed among ethnic minority groups in the Netherlands. Data were derived from 10 994 participants (aged 18–71 years) of the Healthy Life in an Urban Setting (HELIUS) study. Self-reported sleep duration was categorized into: short (<7 h/night), healthy (7–8 h/night) and long (≥9 h/night). Arterial stiffness was assessed by duplicate pulse-wave velocity (PWV in m/s) measurements using the Arteriograph system. The association of sleep duration with PWV was analysed using linear regression (β) with 95% confidence interval (CI). Results showed that neither short nor long sleep was related to PWV in all ethnic groups, except for long sleep in Dutch men which was associated with higher PWV (indicating stiffer arteries) after adjustment for potential confounders (β = 0.67, 95%CI, 0.23–1.11). Our study showed no convincing evidence that sleep duration was related to arterial stiffness among various ethnic groups. The link between sleep duration and cardiovascular outcomes does not seem to operate through arterial stiffness. Further research is needed to consolidate these findings.     

Activation of DNA demethylases attenuates aging‐associated arterial stiffening and hypertension

DNA methylation increases with age. The objective of this study was to investigate whether compound H, a potential activator of DNA demethylases, attenuates aging‐related arterial stiffness and hypertension. Aged mice (24–27 months) and adult mice (12 months) were used. Pulse wave velocity (PWV), a direct measure of arterial stiffness, and blood pressure (BP) were increased significantly in aged mice. Notably, daily treatments with compound H (15 mg/kg, IP) for 2 weeks significantly attenuated the aging‐related increases in PWV and BP. Compound H abolished aging‐associated downregulation of secreted Klotho (SKL) levels in both kidneys and serum likely by enhancing DNA demethylase activity and decreasing DNA methylation. Aging‐related arterial stiffness was associated with accumulation of stiffer collagen and degradation of compliant elastin which are accompanied by increased expression of MMP2, MMP9, TGF‐β1, and TGF‐β3. These changes were effectively attenuated by compound H, suggesting rejuvenation of aged arteries. Compound H also rescued downregulation of Sirt1 deacetylase, AMPKα, and eNOS activities in aortas of aged mice. In cultured smooth muscle cells (SMCc) Klotho‐deficient serum upregulated expression of MMPs and TGFβ which, however, was not affected by compound H. In conclusion, compound H attenuates aging‐associated arterial stiffness and hypertension by activation of DNA demethylase which increases renal SKL expression and consequently circulating SKL levels leading to activation of the Sirt1‐AMPK‐eNOS pathway in aortas of aged mice.     

Aortic and Carotid Arterial Stiffness and Epigenetic Regulator Gene Expression Changes Precede Blood Pressure Rise in Stroke-Prone Dahl Salt-Sensitive Hypertensive Rats

Multiple clinical studies show that arterial stiffness, measured as pulse wave velocity (PWV), precedes hypertension and is an independent predictor of hypertension end organ diseases including stroke, cardiovascular disease and chronic kidney disease. Risk factor studies for arterial stiffness implicate age, hypertension and sodium. However, causal mechanisms linking risk factor to arterial stiffness remain to be elucidated. Here, we studied the causal relationship of arterial stiffness and hypertension in the Na-induced, stroke-prone Dahl salt-sensitive (S) hypertensive rat model, and analyzed putative molecular mechanisms. Stroke-prone and non-stroke-prone male and female rats were studied at 3- and 6-weeks of age for arterial stiffness (PWV, strain), blood pressure, vessel wall histology, and gene expression changes. Studies showed that increased left carotid and aortic arterial stiffness preceded hypertension, pulse pressure widening, and structural wall changes at the 6-week time-point. Instead, differential gene induction was detected implicating molecular-functional changes in extracellular matrix (ECM) structural constituents, modifiers, cell adhesion, and matricellular proteins, as well as in endothelial function, apoptosis balance, and epigenetic regulators. Immunostaining testing histone modifiers Ep300, HDAC3, and PRMT5 levels confirmed carotid artery-upregulation in all three layers: endothelial, smooth muscle and adventitial cells. Our study recapitulates observations in humans that given salt-sensitivity, increased Na-intake induced arterial stiffness before hypertension, increased pulse pressure, and structural vessel wall changes. Differential gene expression changes associated with arterial stiffness suggest a molecular mechanism linking sodium to full-vessel wall response affecting gene-networks involved in vascular ECM structure-function, apoptosis balance, and epigenetic regulation.     

The Association between Pulse Wave Velocity and Cognitive Function: The Sydney Memory and Ageing Study

Objectives

Pulse wave velocity (PWV) is a measure of arterial stiffness and its increase with ageing has been associated with damage to cerebral microvessels and cognitive impairment. This study examined the relationship between carotid-femoral PWV and specific domains of cognitive function in a non-demented elderly sample.

Method

Data were drawn from the Sydney Memory and Ageing Study, a cohort study of non-demented community-dwelling individuals aged 70–90 years, assessed in successive waves two years apart. In Wave 2, PWV and cognitive function were measured in 319 participants. Linear regression was used to analyse the cross-sectional relationship between arterial stiffness and cognitive function in the whole sample, and separately for men and women. Analysis of covariance was used to assess potential differences in cognition between subjects with PWV measurements in the top and bottom tertiles of the cohort. Covariates were age, education, body mass index, pulse rate, systolic blood pressure, cholesterol, depression, alcohol, smoking, hormone replacement therapy, apolipoprotein E ε4 genotype, use of anti-hypertensive medications, history of stroke, transient ischemic attack, myocardial infarction, angina, diabetes, and also sex for the whole sample analyses.

Results

There was no association between PWV and cognition after Bonferroni correction for multiple testing. When examining this association for males and females separately, an association was found in males, with higher PWV being associated with lower global cognition and memory, however, a significant difference between PWV and cognition between males and females was not found.

Conclusion

A higher level of PWV was not associated with lower cognitive function in the whole sample.     

Sex Differences in Flexibility-Arterial Stiffness Relationship and Its Application for Diagnosis of Arterial Stiffening: A Cross-Sectional Observational Study

Purpose

Arterial stiffness might be related to trunk flexibility in middle-aged and older participants, but it is also affected by age, sex, and blood pressure. This cross-sectional observational study investigated whether trunk flexibility is related to arterial stiffness after considering the major confounding factors of age, sex, and blood pressure. We further investigated whether a simple diagnostic test of flexibility could be helpful to screen for increased arterial stiffening.

Methods

According to age and sex, we assigned 1150 adults (male, n = 536; female, n = 614; age, 18–89 y) to groups with either high- or poor-flexibility based on the sit-and-reach test. Arterial stiffness was assessed by cardio-ankle vascular index.

Results

In all categories of men and in older women, arterial stiffness was higher in poor-flexibility than in high-flexibility (P<0.05). This difference remained significant after normalizing arterial stiffness for confounding factors such as blood pressure, but it was not found among young and middle-aged women. Stepwise multiple-regression analysis also supported the notion of the sex differences in flexibility-arterial stiffness relationship. Receiver operating characteristic curve analysis revealed that cut-off values for sit-and-reach among men and women were 33.2 (area under the curve [AUC], 0.711; 95% confidence interval [CI], 0.666–0.756; sensitivity, 61.7%; specificity, 69.7%) and 39.2 (AUC, 0.639; 95% CI, 0.592–0.686; sensitivity, 61.1%; specificity, 62.0%) cm, respectively.

Conclusion

Our results indicate that flexibility-arterial stiffness relationship is not affected by BP, which is a major confounding factor. In addition, sex differences are observed in this relationship; poor trunk flexibility increases arterial stiffness in young, middle-aged, and older men, whereas the relationship in women is found only in the elderly. Also, the sit-and-reach test can offer a simple method of predicting arterial stiffness at home or elsewhere.     

Beneficial effect of beraprost sodium plus telmisartan in the prevention of arterial stiffness development in elderly patients with hypertension and cerebral infarction

Beraprost sodium (BPS, an analogue of prostacyclin) and telmisartan (TS, an angiotensin receptor blocker) have been reported to have a preventive effect on arterial stiffness in patients with cardiovascular diseases. The purpose of this study was to estimate the effects of a combined therapy using BPS and TS on arterial pulse wave velocity (PWV) values in elderly patients with hypertension and cerebral infarction. Over a 3-month period, 80 subjects with hypertension and histories of cerebral infarction received BPS only (120 microg/day p.o.), TS only (40 mg/day p.o.), both BPS and TS, or no medication at all (control). Arterial PWV and ankle brachial indices (ABI) were determined prior to and after 3 months of drug administration. During the follow-up, there were no significant changes in any of the parameters monitored with the exception of a significant decrease in systolic blood pressure in the BPS only, TS only, and BPS plus TS groups when compared to controls. The difference values for PWV in the control group, BPS only group, TS only group, and BPS plus TS group were +232.5, -114.6, -151.5, and -248.1 cm/s, respectively. The reduction values were significantly more pronounced in the BPS plus TS group than in the BPS only (P=0.037) and the TS only (P=0.022) groups. When BPS is combined with TS, an overall additive effect is seen in the improvement of PWV in Japanese patients with hypertension and cerebral infarction. This combination therapy is more beneficial than the corresponding monotherapies.     

Circulating Bacterial-Derived DNA Fragment Level Is a Strong Predictor of Cardiovascular Disease in Peritoneal Dialysis Patients

BackgroundCirculating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that plasma bacterial DNA level predicts cardiovascular events in new PD patients.MethodsWe measured plasma bacterial DNA level in 191 new PD patients, who were then followed for at least a year for the development of cardiovascular event, hospitalization, and patient survival.ResultsThe average age was 59.3 ± 11.8 years; plasma bacterial DNA level 34.9 ± 1.5 cycles; average follow up 23.2 ± 9.7 months. At 24 months, the event-free survival was 86.1%, 69.8%, 55.4% and 30.8% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (p < 0.0001). After adjusting for confounders, plasma bacterial DNA level, baseline residual renal function and malnutrition-inflammation score were independent predictors of composite cardiovascular end-point; each doubling in plasma bacterial DNA level confers a 26.9% (95% confidence interval, 13.0 – 42.5%) excess in risk. Plasma bacterial DNA also correlated with the number of hospital admission (r = -0.379, p < 0.0001) and duration of hospitalization for cardiovascular reasons (r = -0.386, p < 0.0001). Plasma bacterial DNA level did not correlate with baseline arterial pulse wave velocity (PWV), but with the change in carotid-radial PWV in one year (r = -0.238, p = 0.005).ConclusionsCirculating bacterial DNA fragment level is a strong predictor of cardiovascular event, need of hospitalization, as well as the progressive change in arterial stiffness in new PD patients.     

Aortic Stiffness and Cardiovascular Risk in Women with Previous Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is a significant risk factor for cardiovascular disease (CVD) in later life, but the mechanism remains unclear. The aim of the study was to investigate indices of glucose metabolism, dyslipidemia, and arterial stiffness (as measured by pulse wave velocity (PWV)), in women with and without a history of GDM, using both the old WHO and new IADPSG diagnostic criteria, at 5 years after the index pregnancy. Dyslipidemia and PWV were used as surrogate markers for CVD risk. The population-based prospective cohort included 300 women from the original STORK study. All participants had an oral glucose tolerance test (OGTT) during pregnancy. Five years later, the OGTT was repeated along with dual-energy x-ray absorptiometry, lipid analysis, and PWV analysis. Measurements were compared between those women who did and did not have GDM based on both the WHO and IADPSG criteria. We found that women with GDM based on the old WHO criteria had higher CVD risk at 5 years than those without GDM, with markedly elevated PWV and more severe dyslipidemia (higher triglycerides (TG)/HDL cholesterol ratio). After adjusting for known risk factors, the most important predictors for elevated PWV and TG/HDL-C ratio at 5-year follow-up were maternal age, BMI, GDM, systolic blood pressure, and indices of glucose metabolism in the index pregnancy. In conclusion, we found a higher risk for CVD, based on the surrogate markers PWV and TG/HDL-C ratio, at 5-year follow-up in women diagnosed with GDM in the index pregnancy when using the old WHO diagnostic criteria.     

Increased Arterial Stiffness in Systemic Lupus Erythematosus (SLE) Patients at Low Risk for Cardiovascular Disease: A Cross-Sectional Controlled Study

Cardiovascular disease (CVD) is a major cause of death in systemic lupus erythematosus (SLE) patients. Although the risk for cardiovascular events in patients with SLE is significant, the absolute number of events per year in any given cohort remains small. Thus, CVD risks stratification in patients with SLE focuses on surrogate markers for atherosclerosis at an early stage, such as reduced elasticity of arteries. Our study was designed to determine whether arterial stiffness is increased in SLE patients at low risk for CVD and analyze the role for traditional and non-traditional CVD risk factors on arterial stiffness in SLE. Carotid-femoral pulse wave velocity (PWV) was prospectively assessed as a measure of arterial stiffness in 41 SLE patients and 35 controls (CTL). Adjustment on age or Framingham score was performed using a logistic regression model. Factors associated with PWV were identified separately in SLE patients and in controls using Pearson''s correlation coefficient for univariate analysis and multiple linear regression for multivariate analysis. SLE patients and controls displayed a low 10-year risk for CVD according to Framingham score (1.8±3.6% in SLE vs 1.6±2.8% in CTL, p = 0.46). Pulse wave velocity was, however, higher in SLE patients (7.1±1.6 m/s) as compared to controls (6.3±0.8 m/s; p = 0.01, after Framingham score adjustment) and correlated with internal carotid wall thickness (p = 0.0017). In multivariable analysis, only systolic blood pressure (p = 0.0005) and cumulative dose of glucocorticoids (p = 0.01) were associated with PWV in SLE patients. Interestingly, the link between systolic blood pressure (SBP) and arterial stiffness was also confirmed in SLE patients with normal systolic blood pressure. In conclusion, arterial stiffness is increased in SLE patients despite a low risk for CVD according to Framingham score and is associated with systolic blood pressure and glucocorticoid therapy.     

Arterial Stiffness,Carotid Intima-Media Thickness,Endocan, and A Disintegrin and Metalloproteinase With Thrombospondin Type I Motif 9 Levels and Their Relationship With Disease Activity in Patients With Acromegaly With and Without Cardiovascular Risk Factors

ObjectiveCardiovascular complications such as cardiomyopathy and endothelial dysfunction, which are frequently seen in patients with acromegaly, are among the most important causes of morbidity and mortality. In this study, we aimed to investigate arterial stiffness, carotid intima-media thickness, endocan level, and A disintegrin and metalloproteinase with thrombospondin type I motif 9 level and their relationship with disease activity in patients with acromegaly with and without cardiovascular risk factors.MethodsA total of 60 patients with acromegaly—25 with active disease, 26 with well-controlled disease, and 9 with newly diagnosed disease—and 60 age-, sex-, and body mass index (BMI)-matched healthy control subjects were enrolled in this study. All the subjects’ height, weight, BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG) level, insulin, hemoglobin A1C (HbA1C), C-reactive protein , lipid, endocan, A disintegrin and metalloproteinase with thrombospondin type I motif 9 levels, pulse wave velocity (PWV), and carotid intima-media thickness were measured.ResultsThe SBP, DBP, FPG level, HbA1C level, and PWV of the acromegaly group were higher than those of the control group. In patients with acromegaly with cardiovascular disease (CVD) risk factors, the PWV was higher than that in the control group, and in patients with acromegaly without CVD risk factors, the PWV was similar to that in the control group. In a correlation analysis, a positive correlation was found between PWV and age, BMI, SBP, DBP, FPG level, and HbA1C level in the acromegaly group.ConclusionIn our study, we found that arterial stiffness increased in patients with acromegaly with CVD risk factors and that increased arterial stiffness was associated with hemodynamic (SBP and DBP) and metabolic (BMI, FPG level, and HbA1C level) parameters.     

老年原发性高血压患者脉搏波传导速度与心脑血管危险因素关系的研究

目的:探讨老年原发性高血压患者脉搏波传导速度与心脑血管危险因素关系。方法:随机选取2012年5月至2012年8月在我院体检的160例新诊老年原发性高血压患者及120例健康个体,所有个体均未接受治疗,采用动脉硬化检测仪测定患者肱踝脉搏波传导速度(baPWV),同时测量身高、腰围、体重、血压、总胆固醇(TC)、甘油三酯(TG)、空腹血糖(FBS)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、尿酸(UA)、肌酐(Cr)等指标,探讨老年原发性高血压患者高脂血症、吸烟、肥胖、糖尿病等危险因素与baPWV指标变化的关系。结果:不同血压分级的老年原发性高血压患者之间肱踝脉搏波传导速度值存在显著差异(P0.01)。合并冠心病、肥胖、糖尿病、吸烟、高脂血症等危险因素的高血压患者baPWV值显著高于单纯性原发性高血压患者(P0.01)。多元回归分析表明:吸烟史(P0.01)、冠心病史(P0.01)、糖尿病史(P0.01)、年龄(P0.01)、腰围(P0.01)、血压(P0.01)、HDL-C(P0.01)、TC(P0.01)、FBS(P0.01)、LDL-C(P0.01)、Cr(P0.01)是baPWV升高的独立风险因素。结论:老年原发性高血压患者存在不同程度的的动脉僵硬增高,常见心脑血管风险因素同样影响老年原发性高血压患者僵硬度。     

Effects of nitric oxide synthase inhibitor on decrease in peripheral arterial stiffness with acute low-intensity aerobic exercise

We previously reported that even low-intensity, short-duration acute aerobic exercise decreases arterial stiffness. We aimed to test the hypothesis that the exercise-induced decrease in arterial stiffness is caused by the increased production of NO in vascular endothelium with exercise. Nine healthy men (age: approximately 22-28 yr) performed a 5-min single-leg cycling exercise (30 W) in the supine position under an intravenous infusion of NG-monomethyl-L-arginine (L-NMMA; 3 mg/kg during the initial 5 min and subsequent continuous infusion of 50 mug.kg(-1).min(-1) in saline) or vehicle (saline) in random order on separate days. The pulse wave velocity (PWV) from the femoral to posterior tibial artery was measured on both legs before and after the infusion at rest and 2 min after exercise. Under the control condition, exercised leg PWV significantly decreased after exercise (P <0.05), whereas nonexercised leg PWV did not show a significant change throughout the experiment. Under L-NMMA administration, exercised leg PWV was increased significantly by the infusion (P <0.05) but decreased significantly after the exercise (P <0.05). Nonexercised leg PWV increased with L-NMMA administration and maintained a significantly higher level during the administration compared with baseline (before the infusion, all P <0.05). The NO synthase blockade x time interaction on exercised leg PWV was not significant (P=0.706). These results suggest that increased production of NO is not a major factor in the decrease of regional arterial stiffness with low-intensity, short-duration aerobic exercise.     

Sex-specific outcomes of diabetic patients with acute myocardial infarction who have undergone percutaneous coronary intervention: a register linkage study

Background

Chronic arterial stiffness contributes to the negative health effects of obesity and insulin resistance, which include hypertension, stroke, and increased cardiovascular and all-cause mortality. Weight loss and improved insulin sensitivity are individually associated with improved central arterial stiffness; however, their combined effects on arterial stiffness are poorly understood. The purpose of this study was to determine how insulin levels modify the improvements in arterial stiffness seen with weight loss in overweight and obese young adults.

Methods

To assess the effects of weight loss and decreased fasting insulin on vascular stiffness, we studied 339 participants in the Slow the Adverse Effects of Vascular Aging (SAVE) trial. At study entry, the participants were aged 20?C45, normotensive, non-diabetic, and had a body-mass index of 25?C39.9?kg/m². Measures of pulse wave velocity (PWV) in the central (carotid-femoral (cfPWV)), peripheral (femoral-ankle (faPWV)), and mixed (brachial-ankle (baPWV)) vascular beds were collected at baseline and 6?months. The effects of 6-month change in weight and insulin on measures of PWV were estimated using multivariate regression.

Results

After adjustment for baseline risk factors and change in systolic blood pressure, 6-month weight loss and 6-month change in fasting insulin independently predicted improvement in baPWV but not faPWV or cfPWV. There was a significant interaction between 6-month weight change and change in fasting insulin when predicting changes in baPWV (p?<?0.001). Individuals experiencing both weight loss and insulin reductions showed the greatest improvement in baPWV.

Conclusions

Young adults with excess weight who both lower their insulin levels and lose weight see the greatest improvement in vascular stiffness. This improvement in vascular stiffness with weight loss and insulin declines may occur throughout the vasculature and may not be limited to individual vascular beds.

Trial registration

NCT00366990     

Restoring mitochondrial DNA copy number preserves mitochondrial function and delays vascular aging in mice

Aging is the largest risk factor for cardiovascular disease, yet the molecular mechanisms underlying vascular aging remain unclear. Mitochondrial DNA (mtDNA) damage is linked to aging, but whether mtDNA damage or mitochondrial dysfunction is present and directly promotes vascular aging is unknown. Furthermore, mechanistic studies in mice are severely hampered by long study times and lack of sensitive, repeatable and reproducible parameters of arterial aging at standardized early time points. We examined the time course of multiple invasive and noninvasive arterial physiological parameters and structural changes of arterial aging in mice, how aging affects vessel mitochondrial function, and the effects of gain or loss of mitochondrial function on vascular aging. Vascular aging was first detected by 44 weeks (wk) of age, with reduced carotid compliance and distensibility, increased β‐stiffness index and increased aortic pulse wave velocity (PWV). Aortic collagen content and elastin breaks also increased at 44 wk. Arterial mtDNA copy number (mtCN) and the mtCN‐regulatory proteins TFAM, PGC1α and Twinkle were reduced by 44 wk, associated with reduced mitochondrial respiration. Overexpression of the mitochondrial helicase Twinkle (Tw⁺) increased mtCN and improved mitochondrial respiration in arteries, and delayed physiological and structural aging in all parameters studied. Conversely, mice with defective mitochondrial polymerase‐gamma (PolG) and reduced mtDNA integrity demonstrated accelerated vascular aging. Our study identifies multiple early and reproducible parameters for assessing vascular aging in mice. Arterial mitochondrial respiration reduces markedly with age, and reduced mtDNA integrity and mitochondrial function directly promote vascular aging.     

Digital Photoplethysmography for Assessment of Arterial Stiffness: Repeatability and Comparison with Applanation Tonometry

Introduction

Arterial stiffness is an independent risk factor for cardiovascular morbidity and can be assessed by applanation tonometry by measuring pulse wave velocity (PWV) and augmentation index (AIX) by pressure pulse wave analysis (PWA). As an inexpensive and operator independent alternative, photoelectric plethysmography (PPG) has been introduced with analysis of the digital volume pulse wave (DPA) and its second derivatives of wave reflections.

Objective

The objective was to investigate the repeatability of arterial stiffness parameters measured by digital pulse wave analysis (DPA) and the associations to applanation tonometry parameters.

Methods and Results

112 pregnant and non-pregnant individuals of different ages and genders were examined with SphygmoCor arterial wall tonometry and Meridian DPA finger photoplethysmography. Coefficients of repeatability, Bland-Altman plots, intraclass correlation coefficients and correlations to heart rate (HR) and body height were calculated for DPA variables, and the DPA variables were compared to tonometry variables left ventricular ejection time (LVET), PWV and AIX. No DPA variable showed any systematic measurement error or excellent repeatability, but dicrotic index (DI), dicrotic dilatation index (DDI), cardiac ejection elasticity index (EEI), aging index (AI) and second derivatives of the crude pulse wave curve, b/a and e/a, showed good repeatability. Overall, the correlations to AIX were better than to PWV, with correlations coefficients >0.70 for EEI, AI and b/a. Considering the level of repeatability and the correlations to tonometry, the overall best DPA parameters were EEI, AI and b/a. The two pansystolic time parameters, ejection time compensated (ETc) by DPA and LVET by tonometry, showed a significant but weak correlation.

Conclusion

For estimation of the LV function, ETc, EEI and b/a are suitable, for large artery stiffness EEI, and for small arteries DI and DDI. The only global parameter, AI, showed a high repeatability and the overall best correlations with AIX and PWV.