Age-related Increases In Arterial Stiffness Research Articles

Impact of arterial stiffness on cerebrovascular function: a review of evidence from humans and preclincal models.

With advancing age, the cerebral vasculature becomes dysfunctional, and this dysfunction is associated with cognitive decline. However, the initiating cause of these age-related cerebrovascular impairments remains incompletely understood. A characteristic feature of the aging vasculature is the increase in stiffness of the large elastic arteries. This increase in arterial stiffness is associated with elevated pulse pressure and blood flow pulsatility in the cerebral vasculature. Evidence from both humans and rodents supports that increases in large elastic artery stiffness are associated with cerebrovascular impairments. These impacts on cerebrovascular function are wide-ranging and include reductions in global and regional cerebral blood flow, cerebral small vessel disease, endothelial cell dysfunction, and impaired perivascular clearance. Furthermore, recent findings suggest that the relationship between arterial stiffness and cerebrovascular function may be influenced by genetics, specifically APOE and NOTCH genotypes. Given the strength of the evidence that age-related increases in arterial stiffness have deleterious impacts on the brain, interventions that target arterial stiffness are needed. The purpose of this review is to summarize the evidence from human and rodent studies, supporting the role of increased arterial stiffness in age-related cerebrovascular impairments.

Abstract 13452: Age-Related Increases in Arterial Stiffness is Attenuated With Long-Term Senolytic Therapy in Mice

Introduction: It has been established that with advancing age, large elastic arteries (i.e. aorta) demonstrate increased stiffening resulting in detrimental CV health outcomes. Cellular senescence, the permanent arrest of the cell cycle, within the vasculature is characterized by a population of cells that are profibrotic and proinflammatory. Profibrotic and proinflammatory environments have been shown to directly lead to increased large artery stiffness (LAS) with aging. We tested the hypothesis that treatment with the senolytic cocktail dasatinib and quercetin (D&Q) will attenuate LAS in aging mice. Methods: 21-month-old C57Bl/6 mice were treated with D&Q or vehicle via oral gavage on a bi-monthly basis for three months. LAS was measured pre, mid and post treatment by quantifying the aortic pulse wave velocity (aPWV) using a combined Doppler and EKG recording system. Expression of inflammatory genes was assessed by quantitative polymerase chain reaction. Aortic tissue histology was assessed by standard histological methods. Results: D&Q treatment attenuated the age-associated increase in LAS in mice. In the vehicle group, we observed that aPWV increased steadily with age in the vehicle group at 21, 22.5 and 24 months of age (338.9 ± 10.84 cm/s, 351.6 ± 11.53 cm/s, and 369.5 ± 18.57 cm/s respectively, intragroup p=0.004). However, in the D&Q group, we observed a blunted response with corresponding aPWVs (339.5 ± 12.96 cm/s, 322.9 ± 13.9 cm/s, and 342.1 ± 5.67 cm/s; intragroup p=0.7729). Intergroup analysis confirms a significant difference with a p<0.001. Inflammatory markers (TGF-β and TNF-α) were significantly reduced in the D&Q compared to the vehicle group (p<0.05). Extracellular matrix collagen content was lower in aortic tissue from D&Q treated compared to vehicle mice (p<0.01). Conclusions: Chronic, intermittent administration of D&Q prevented the progression of aortic stiffening with advancing age as measured in a longitudinal preclinical mouse study. Aortic inflammatory markers were reduced in the treatment group and similarly the treatment group had attenuated fibrosis vs. vehicle controls. Overall, senolytic therapy represents a potential therapy for aortic fibrosis and age-related increases in large artery stiffness.

Abstract P037: Age Modifies The Inverse Association Between Standing Height And Pulse Pressure

Purpose: While standing height is positively associated with blood pressure in the pediatric population, studies have suggested an inverse association in adults. We sought to therefore determine whether age modified the association between standing height and pulse pressure (PP). Methods: The study included adults ≥20 years from the 1999-2018 National Health and Nutrition Examination Surveys who were not taking antihypertensive medications. Standing height was categorized into gender-specific quintiles (Table). High PP was defined as PP ≥60 mmHg. We estimated odds ratios (OR) using logistic regression, adjusting for covariates, accounting for the complex survey design, and stratifying by 10-year age groups. Results: Among the 26,779 adults (mean [SD] age of 43 [30], 50% female, 70% White), 16% had elevated PP, ranging from 23% in the lowest height quintile (Q1) to 11% in the highest quintile (Q5). Those in Q5 were younger, of higher socioeconomic status, had greater waist circumference, and less likely to have cardiovascular disease or diabetes compared to those in Q1. Those in Q5 had 46% lower adjusted odds of high PP compared to Q1. Race and gender did not modify associations (race: p for interaction = 0.28; gender: p =0.34). When stratifying by 10-year age groups, odds of high PP significantly decreased with increasing age up to 70 years (Table, P-trend <0.001). Conclusion: Standing height was found to be negatively associated high PP, especially in adults 30-69 years. We speculate that augmented pulse wave deflection in shorter individuals may play a role in age-related increases in arterial stiffness.

Influence of age on arterial stiffness responses following a short period of sitting in healthy males

Background: Age-related increases in arterial stiffness including carotid-femoral pulse wave velocity (cf-PWV), aortic wave reflection via augmentation index (AIx) and reflection magnitude (RM) have been associated with future cardiovascular event risk. Chronic or prolonged inactivity has been reported to exacerbate the age-related increases in arterial stiffness. However, little is known about the impact of a short, period of inactivity on arterial stiffness with age potentially an influencing factor.

Exercise, Arterial Stiffness, and Cerebral Vascular Function: Potential Impact on Brain Health.

The purpose is to discuss the epidemiological, observational, and mechanistic evidence regarding the link between age-related changes in vascular health and brain health. We performed a literature review and integrated with our published data. Epidemiological evidence suggests a link between age-related increases in arterial stiffness and lower cognitive function, which may be mediated by cerebral vascular function, including cerebral vasoreactivity and cerebral pulsatility. Age-associated impairments in central arterial stiffness and peripheral vascular function have been attenuated or reversed through lifestyle behaviors such as exercise. Greater volumes of habitual exercise and higher cardiorespiratory fitness are associated with beneficial effects on both peripheral vascular health and cognition. Yet, the extent to which exercise directly influences cerebral vascular function and brain health, as well as the associated mechanisms remains unclear. Although there is evidence that exercise positively impacts cerebral vascular function, more research is necessary in humans to optimize experimental protocols and address methodological limitations and physiological considerations. Understanding the impact of exercise on cerebral vascular function is important for understanding the association between exercise and brain health and may inform future intervention studies that seek to improve cognition.

Physical Activity, Autonomic Function And Cerebral Pulsatility In Young Women

Cerebral pulsatility increases stress on the microvasculature of the brain causing damage. Age-related increases in arterial stiffness augment cerebral pulsatility via effects on large artery buffering capacity. Autonomic nervous system function also affect cerebral pulsatility by altering vascular tone. Physical activity (PA) may have a favorable effect on both vascular and autonomic function, and in turn, cerebral pulsatility. PURPOSE: 1) Determine the relationship between aortic stiffness and autonomic function with cerebral pulsatility index (PI) in young women. 2) Explore the role of PA as a potential correlate. METHODS: Eighty-two women (21±4 years) participated in this study. Moderate-to-vigorous physical activity (MVPA) was measured for 7 days using an accelerometer. Body composition was assessed using air displacement plethysmography. Middle cerebral artery PI was determined via transcranial Doppler. Aortic stiffness was measured via carotid-femoral pulse wave velocity (cf-PWV) using applanation tonometry. Autonomic function was assessed via heart rate variability (HRV). Low frequency (LF) power of HRV was used as a measure of sympathetic activity, while high frequency (HF) power of HRV was used as a measure of parasympathetic activity. RESULTS: PI was not significantly correlated with cf-PWV (r=-0.03, p=0.82) or lnHF (r=0.25, p=0.06). There was a significant, positive association between lnLF and PI (r=0.39, p=0.002). MVPA was not associated with cf-PWV (r=-0.18, p=0.13), lnLF (r=0.01, p=0.95) or PI (r=-0.04, p=0.79). CONCLUSION: Sympathetic activity is a more prominent correlate of cerebral pulsatility than large artery stiffness in young women. Sympathetic tone may increase vasoconstriction of the cerebral vasculature resulting in augmentation of cerebral pulsatility. Physical activity was not associated with vascular or autonomic correlates of cerebral pulsatility in young women. Supported by NIH Grant 1R03MD011306-01A1

Cerebrovascular reactivity: a new frontier for measuring cognitive health in models of accelerated ageing?

Cerebrovascular reactivity: a new frontier for measuring cognitive health in models of accelerated ageing?

Longitudinal interaction between APOA5 -1131T>C and overweight in the acceleration of age-related increase in arterial stiffness through the regulation of circulating triglycerides.

We aimed to evaluate whether the longitudinal interaction between APOA5-1131C variants and overweight could accelerate age-related increases in arterial stiffness and circulating triglycerides in healthy subjects. This 3-year prospective cohort study included 503 healthy subjects. Brachial-ankle pulse wave velocity (baPWV), triglycerides, APOA5 -1131T > C, apolipoprotein (apo) A-V level, and low-density lipoprotein (LDL) particle size were measured at baseline and within a mean follow-up period of 3 years. At the 3-year follow-up, in the overweight group, subjects with the C allele showed increases in triglycerides and baPWV relative to baseline. Additionally, in the overweight group, there was a genotype effect on changes in triglycerides: subjects with the C allele had greater increases in triglyceride concentrations than subjects with the TT genotype. Furthermore, overweight subjects with the C allele had greater increases in triglyceride concentrations than normal-weight subjects with the C allele (P-interaction = 0.013). Overweight subjects with the C allele had greater increases in baPWV than normal-weight subjects with the C allele (P-interaction = 0.047). Changes in baPWV were affected by age, baseline baPWV, and changes in systolic blood pressure (BP) and triglycerides. Changes in triglycerides were affected by APOA5 -1131T > C genotype, age, baseline triglyceride level, and changes in BMI and apo A-V. In the overweight group, changes in baPWV were affected by changes in systolic BP, LDL particle size, and triglycerides. This prospective study shows that the interactive effect between APOA5 -1131C variants and overweight can accelerate age-related increase in arterial stiffness via the regulation of circulating triglycerides in healthy subjects.

Cardiorespiratory fitness, exercise, and blood pressure.

Findings from well-designed large epidemiological studies and diverse populations support a robust, inverse, and independent association between physical activity, cardiorespiratory fitness, and cardiovascular and overall mortality risk. The association is independent of age, race, sex, documented cardiovascular disease, or comorbidities, including hypertension.1,2 In prehypertension and hypertension, cardiorespiratory fitness exhibits preventive, prognostic, and therapeutic properties.1–4 Thus, appropriate lifestyle interventions, including increased physical activity designed to enhance cardiorespiratory fitness, are recommended by the Eight Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8) and the European Society of Hypertension/European Society of Hypertension of Cardiology recent guidelines as initial therapy to prevent, treat, and control hypertension.5,6 This review presents evidence on the preventive, prognostic, and therapeutic aspects of exercise and fitness status of the individual on blood pressure (BP). The age-related progressive increase in BP is accompanied by an incremental increase in cardiovascular risk evident beyond BP levels of 115/75 mm Hg.7 Evidence suggests that this increase in BP is preceded by arterial stiffness, an important and independent contributor to hypertension.8–12 To some extent, the age-related increase in arterial stiffness and BP is inevitable (biological aging). However, a substantial portion of the pronounced increase observed in industrialized societies is pathological and more likely a consequence of lifestyle characterized by high-fat and salt diets and physical inactivity than an inevitable outcome of aging.13–19 Indigenous populations living a relatively traditional hunter-gatherer lifestyle exhibit only a modest and substantially lower increase in arterial stiffness and BP compared with individuals living in westernized environments.14,15 Additionally, vascular health is improved by habitual physical activity and exercise intervention programs implemented in westernized populations16–19 and diminished by inactivity and …

O174 Accelerated Age-Related Increases In Arterial Stiffness In American Vs Japanese Women

O174 Accelerated Age-Related Increases In Arterial Stiffness In American Vs Japanese Women

Follow-Ups of Metabolic, Inflammatory and Oxidative Stress Markers, and Brachial–Ankle Pulse Wave Velocity in Middle-Aged Subjects without Metabolic Syndrome

This study investigates the association among metabolic risk factors, inflammatory and oxidative stress markers, and brachial–ankle pulse wave velocity (ba-PWV). We conducted a 3-year longitudinal, observational study of 288 middle-aged adults not meeting the criteria for metabolic syndrome (MetS) at the initial screening. We measured metabolic risk factors, inflammatory and oxidative stress markers, and ba-PWV. Within the 3-year study period, 15.6% (45 out of 288) of participants developed MetS. At the 3-year follow-up, patients were categorized as those with MetS (n = 45) and those without MetS (n = 243). Patients with MetS had significantly unfavorable initial measurements of baseline body mass index (BMI), waist circumference (WC), blood pressure (BP), triglyceride (TG), high-density lipoprotein (HDL)-cholesterol, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index, and ba-PWV. After 3 years, participants without MetS showed significant increases in WC, diastolic BP (DBP), total- and low-density lipoprotein (LDL)-cholesterol, malondialdehyde (MDA), oxidized-LDL (ox-LDL), and ba-PWV and a significant decrease in HDL-cholesterol and free fatty acids (FFA). Subjects who developed MetS showed significant increases in BMI, WC, BP, TG, glucose, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), MDA, ox-LDL, and ba-PWV and a significant decrease in HDL-cholesterol. Changes in BMI, WC, BP, TG, HDL-cholesterol, glucose, HOMA-IR index, FFA, C-reactive protein (P = .022), IL-6 (P = .004), leukocyte count (P < .001), MDA (P = .002), ox-LDL (P = .015), and ba-PWV (P = .001) differed significantly between the two groups after adjustment for baseline values. Changes in ba-PWV were positively correlated with the changes in systolic and DBP, total-cholesterol, glucose, leukocyte count, and MDA. The age-related increase in arterial stiffness is greater in the presence of MetS with higher levels of inflammatory and oxidative stress markers.

Abstract 270: Arginase I Deletion Blocks Age-Related Enhancement of Vascular Stiffness and Endothelial Dysfunction

Vascular stiffening, decreased nitric oxide (NO) bioavailability and vascular endothelial dysfunction (ED) are markers of the aging cardiovascular system. Increased vascular stiffness and ED are predictors for adverse cardiovascular outcomes. Increased vascular arginase activity has been noted to accompany aging-induced endothelial dysfunction (ED). Therefore, we hypothesized that enhanced arginase activity is involved in age-related increases in arterial stiffness and ED and that limiting the activity of arginase I (Arg I) would reduce this pathology. We tested this hypothesis by analysis of vascular stiffness and ED in aortas from old (12-month) and young (3-month) male wild type (WT) mice and mice lacking one copy of arginase I (Arg I +/- KO). In vivo studies measured vascular stiffness by pulse wave velocity (PWV) and systolic blood pressure (SBP) by tail cuff. Vascular endothelial function studies also were performed ex vivo using myography. Arginase activity assay showed that activity in the aged WT mice was 1.47-fold greater than that in the young WT mice. PWV was markedly increased in old WT mice (1.96±0.28 m/s) compared to young WT mice (1.08±0.10 m/s). By contrast, PWV remained normal in old Arg I +/- KO mice (1.15±0.08 m/s). Endothelium (NO)-dependent vasorelaxation to acetylcholine (ACh) was significantly reduced in the old WT mice as compared with young WT mice (maximum relaxation (MR) of 60±3% vs 78±4%, respectively). This age-induced impairment was markedly blunted in aged Arg I +/- KO mice (MR: 71±3%). The arginase inhibitor BEC (100 μM) also reversed the impairment in ACh-induced vasorelaxation in old WT mice (P&lt;0.05). No differences were observed in endothelial-independent relaxation to SNP among the groups. SBP was also unchanged. In conclusion, deletion of one copy of Arg I prevents ED and reduces vascular stiffness in aging. Thus, reduction of arginase I function may serve as a therapeutic target for normalizing arterial stiffness and preventing vascular dysfunction in aging.

The menopausal transition does not appear to accelerate age-related increases in arterial stiffness

ABSTRACTObjective Arterial stiffness is an independent marker of cardiovascular risk that increases with age, hypertension, diabetes and hyperlipidemia, both for men and women (although more pronounced in women). This study was designed to establish whether menopause augments the age-dependent change.Methods The study evaluated pulse wave analysis and pulse wave velocity using applanation tonometry in 468 women (aged 40–80 years) sampled from the general population. In multiple linear regression models, age was the predominant correlate of increasing aortic augmentation pressure (p < 0.0001), augmentation index (p < 0.0001), augmentation index adjusted to a heart rate of 75 beats/min (p < 0.0001) and carotid-femoral pulse wave velocity (p < 0.0001).Results Analysis of covariance showed no significant difference in adjusted mean of augmentation pressure, augmentation index or pulse wave velocity between menopause groups (pre-, peri-, postmenopause). Adjusted means of augmentation pressure and pulse wave velocity were comparable between women on hormone therapy (n = 130) and non-users (n = 338).Conclusions The results of the present study challenge the assertion by some researchers that menopause accelerates age-dependent changes in arterial stiffness.

Comment on: Cherney and Sochett. Evolution of Renal Hyperfiltration and Arterial Stiffness From Adolescence Into Early Adulthood in Type 1 Diabetes. Diabetes Care 2011;34:1821–1826

We read the insightful article by Cherney and Sochett (1) with interest. The authors carefully compared changes in kidney hemodynamic function and arterial stiffness in young subjects with type 1 diabetes with and without renal hyperfiltration. During the transition from adolescence to early adulthood, hyperfiltration was not sustained, whereas glomerular filtration rate remained stable in normofiltering subjects. In contrast, arterial stiffness decreased in all patients regardless of filtration status, suggesting that age-related increases in arterial stiffness occur at older ages. It was also mentioned that a variety of factors influence hyperfiltration including the renin-angiotensin system (measured in the study by Cherney and Sochett), cyclo-oxygenase 2, reduced bioavailability of nitric oxide, etc. However, it was unclear why only …

Evolution of Renal Hyperfiltration and Arterial Stiffness From Adolescence Into Early Adulthood in Type 1 Diabetes

OBJECTIVETo determine, in a small but carefully physiologically characterized cohort of subjects with uncomplicated type 1 diabetes, the changes in renal hemodynamic function and arterial stiffness that occur over time as the participants transitioned from adolescence into early adulthood. The classical paradigm for type 1 diabetes suggests that glomerular filtration rate (GFR) declines in patients with renal hyperfiltration, but the natural history of peripheral vascular function abnormalities in uncomplicated type 1 diabetes is less well understood, particularly as patients transition from adolescence to early adulthood.RESEARCH DESIGN AND METHODSRenal hemodynamic function (inulin and p-aminohippuric acid clearance), blood pressure, arterial stiffness (radial augmentation index), albumin excretion, and circulating renin-angiotensin system measures were obtained during clamped euglycemia at baseline and at follow-up 6.8 ± 2.5 years later in 10 patients with hyperfiltration (GFR ≥135 mL/min/1.73 m2) and in 8 with normofiltration.RESULTSCompared with baseline values, GFR (171 ± 20 to 120 ± 15 mL/min/1.73 m2) and filtration fraction (FF, 0.24 ± 0.06 to 0.18 ± 0.03) declined in hyperfilterers (ANOVA P ≤ 0.033), and renal vascular resistance increased (0.0678 ± 0.0135 to 0.0783 ± 0.0121 mmHg/L/min, P = 0.017). GFR and FF did not change in normofiltering subjects. In contrast, the radial augmentation index decreased in hyperfiltering (1.2 ± 11.7 to −11.0 ± 7.8%) and normofiltering (14.3 ± 14.0 to 2.5 ± 14.6%) subjects (within-group changes, ANOVA P ≤ 0.030). The decline in circulating aldosterone levels was similar in both groups.CONCLUSIONSDuring the transition from adolescence to early adulthood, hyperfiltration is not sustained in subjects with type 1 diabetes, whereas GFR remains stable in normofiltering subjects. Our findings suggest early normofiltration may predict stable renal function. In contrast, arterial stiffness decreased in all patients regardless of filtration status, suggesting that age-related increases in arterial stiffness occur at older ages.

Fish oil supplementation improves large arterial elasticity in overweight hypertensive patients

To observe the effect of fish oil supplementation on arterial elasticity and blood pressure (BP) in overweight hypertensive patients. This was a double-blind, randomized and placebo-controlled clinical study, in which 52 overweight hypertensive patients from a community were selected and randomly allocated to two groups (26 in the fish oil group (3 g day(-1), fish oil capsules) and 26 in the placebo group (only capsules). All the subjects were follow-up for 8 weeks. The arterial elasticity was determined by CVProfilor DO-2020 and expressed as elasticity indexes (C(1)-large artery and C(2)-small artery). During the follow-up, totally nine cases were dropped out (three cases from the fish oil group and six cases from the placebo group). After 8 weeks follow-up, the large artery elasticity in the fish oil group, compared with its baseline, was significantly improved (C(1): 15.5+/-1.5 vs 12.8+/-3.7 ml mm Hg(-1) x 10), whereas no effects were found in the placebo group (C(1): 13.0+/-3.4 vs 13.4+/-3.8 ml mm Hg(-1) x 10), P=0.027, RM-ANOVA across the two groups. The small artery elasticity (C(2)), BP and pulse pressure were not found any changes, either in the fish oil group or in the placebo group. At same time, the serum soluble vascular cell adhesion molecule-1(sVCAM-1) and leptin levels, the lipid profile and insulin sensitivity index (ISI) as well, did not show significant differences between two groups. Fish oil supplementation certainly would improve large arterial elasticity but no effect on BP in overweight hypertensive patients. Further study is needed to confirm the benefits of fish oil supplementation on age-related increases in arterial stiffness.

Habitual Physical Activity and Vascular Aging in a Young to Middle-Age Population at Low Cardiovascular Risk

Regular endurance exercise has been shown to reduce the age-related increase in arterial stiffness that is thought to contribute to cardiovascular risk. The aim of this study was to evaluate the influence of age and habitual physical activity on carotid artery wall thickness and stiffness in a population of young to middle-age subjects at low cardiovascular risk. The study population consisted of 432 healthy subjects (166 men; mean+/-SD age, 43+/-8 years; range, 30 to 60 years) free of carotid atherosclerosis and with low coronary heart disease risk, as determined by the Framingham prediction score sheet. All subjects underwent B-mode ultrasonography of the extracranial carotid arteries and physical activity assessment by actigraph, an accelerometer capable of monitoring the intensity and duration of body movements. The intima-media thickness of the common carotid artery was measured on ultrasound images, along with systodiastolic changes in luminal diameter, and indices of carotid stiffness were calculated. Intima-media thickness and carotid stiffness increased with age in both men and women (r=0.24 to 0.52, P<0.001). The magnitude of objectively assessed daily physical activity was negatively related to indices of carotid stiffness (r from -0.20 to -0.25, P<0.001) but not to intima-media thickness. In multivariate regression analyses that included several cardiovascular risk factors such as obesity, blood pressure, plasma lipids, and smoking habits, age and physical activity were independently related to carotid stiffness. This study provides cross-sectional evidence that habitual physical activity is inversely related to the age-dependent increase in carotid wall stiffness in a young to middle-age population at low risk.

Noninvasive (Input) Impedance, Pulse Wave Velocity, and Wave Reflection in Healthy Middle-Aged Men and Women

The relation between arterial function indices, such as pulse wave velocity and augmentation index with parameters derived from input impedance analysis, is still incompletely understood. Carotid pressure, central flow waveforms, and pulse wave velocity were noninvasively acquired in 2026 apparently healthy, middle-aged subjects (1052 women and 974 men) 35 to 55 years old at inclusion. Input and characteristic impedance, reflection coefficient, the ratio of backward-to-forward pressure amplitude (reflection magnitude), and augmentation index were derived. Pulse wave velocity increased by 15% (from 6.1 to 7.0 m/s) both in men and women. In qualitative terms, input impedance evolved from a pattern indicative of wave transmission and reflection to a pattern more compatible with a windkessel-like system. In women, a decrease in total arterial compliance led to an increased input impedance in the low frequency range, whereas few changes were observed in men. Characteristic impedance did not change with age in women and even decreased in men (P<0.001) and could not be identified as the primary determinant of central pulse pressure. Augmentation index increased with age, as was expected, and was systematically higher in women (P<0.001). Reflection coefficient and reflection magnitude increased with age (P<0.001) without gender differences. We conclude that, in healthy middle-aged subjects, the age-related increase in arterial stiffness (pulse wave velocity) is not fully paralleled by an increase in arterial impedance, suggesting a role for age-dependent modulation of aortic cross-sectional area. Wave reflection increases with age and is not higher in women than in men.

Temocapril, an Angiotensin Converting Enzyme Inhibitor, Ameliorates Age-Related Increase in Carotid Arterial Stiffness in Normotensive Subjects

Background/Aims: Oxidative stress plays an important role in vascular ageing. The close relationship of the renin-angiotensin system with mechanisms of oxidative stress suggests its possible involvement in the deleterious effects of ageing. The present study was designed to investigate whether inhibition of the renin-angiotensin system improves the age-related increase in arterial stiffness. Methods: Normotensive elderly subjects in a geriatric nursing home (n = 24; male/female = 7/17; 86 ± 9 years, mean ± SD) were randomly assigned to receive either an angiotensin converting enzyme inhibitor, temocapril (n = 12, 1 mg daily) or nothing (n = 12). Carot id arterial stiffness parameter β and circulating levels of malondialdehyde-modified low-density lipoprotein were measured before and 6 months after randomization. Results: Temocapril decreased β (from 7.0 ± 1.0 to 4.9 ± 0.9, p < 0.05) and malondialdehyde-modified low-density lipoprotein levels (from 73.2 ± 19.9 to 61.3 ± 18.4 U/l, p < 0.05) without changing the blood pressure. The changes in β and malondialdehyde-modified low-density lipoprotein levels were significantly correlated (ρ = 0.600, p < 0.05). Conclusion: These results suggest that temocapril ameliorates the age-related increase in carotid arterial stiffness in healthy, normotensive elderly subjects.

Menopause is an independent factor augmenting the age-related increase in arterial stiffness in the early postmenopausal phase

The present study examined whether the menopause augments the age-related increase in brachial-ankle pulse-wave velocity (PWV). In total, 3149 women (ranging in age from 21 to 94 years) undergoing an annual health screening examination were enrolled in a cross-sectional study. Conventional atherosclerotic risk factors were examined, and the brachial-ankle PWV of each subject was determined. The relationship between age and the brachial-ankle PWV assumed the form of a quadratic curve, and the slope of the curve was relatively steeper after the menopause (brachial-ankle PWV = 0.17 × age 2 − 0.58 × age + 812) than before (brachial-ankle PWV = 0.23 × age 2 − 8.92 × age + 1058). A logistic regression analysis conducted for subjects between the ages of 45 and 56 years (mean age of menopause ± 2 standard deviations) demonstrated that women who had experienced the menopause at least 6 years previously demonstrated a significant risk of belonging to the highest PWV tertile {adjusted odds ratio: 2.08 (95% confidential interval: 1.04–4.17)}, independent of age and other atherosclerotic risk factors (hypertension, hypercholesterolemia, diabetes mellitus, obesity, and smoking). Thus, this study suggested that the menopause augments the age-related increase in arterial stiffness during the early postmenopausal phase and that this augmentation is probably related, at least in part, to estrogen deficiency. The contribution of this menopause-related increase in arterial stiffness to the risk of cardiovascular disease in postmenopausal women should be further evaluated.