Healthy Vascular Aging Research Articles

The Relationship between Healthy Vascular Aging with the Mediterranean Diet and Other Lifestyles in the Spanish Population: The EVA Study.

In this cross-sectional descriptive study, 501 individuals aged 35 to 75 years were recruited from five health centers by random sampling stratified by age and sex (55.90 ± 14.24 years, 49.70% men). HVA was determined in two steps. Step 1: Subjects with vascular damage to the carotid arteries or peripheral arterial disease were classified as non-HVA. Step 2: The study population was classified by age and sex using the percentiles of the vascular aging index (VAI), with VAI ≤p25 considered HVA and >p25 considered non-HVA. The VAI was estimated using the following formula (VAI = (log (1.09) × 10 cIMT + log (1.14) cfPWV) × 39.1 + 4.76. Carotid-femoral pulse wave velocity (cfPWV) was measured with the SphygmoCor® device, and carotid intima-media thickness using Sonosite Micromax® ultrasound. Mediterranean diet (MD) adherence, alcohol and tobacco use were recorded through validated questionnaires. Physical activity was assessed with the ActiGraph-GT3X® accelerometer. The mean VAI value was 61.23 ± 12.86 (men-63.47 ± 13.75 and women-59.04 ± 11.54; p < 0.001). HVA was found in 18.9% (men-19.9% and women-17.8%). In the multiple regression analysis after adjusting for possible confounding factors, the mean VAI value showed a positive association with alcohol use (β = 0.020) and sedentary hours per week (β = 0.109) and a negative association with hours of activity per week (β = -0.102) and with the number of healthy lifestyles (β = -0.640). In the logistic regression analysis, after adjusting for possible confounding factors and compared to those classified as non-HVA, subjects classified as HVA were more likely to show MD adherence (OR = 0.571), do more than 26 h per week of physical activity (OR = 1.735), spend under 142 h per week being sedentary (OR = 1.696), and have more than two healthy lifestyles (OR = 1.877). The results of this study suggest that the more time spent doing physical activity and the less time spent in a sedentary state, the lower the vascular aging index and the greater the likelihood of being classified in the group of subjects with HVA.

The bottlenose dolphin (Tursiops truncatus): A novel model for studying healthy vascular aging

Aging is the primary non-modifiable risk factor for the development of cardiovascular diseases (CVD). CVD are often preceded by arterial dysfunction, including endothelial dysfunction and aortic stiffening. Our preliminary results suggest that the circulating milieu is associated with differences in arterial function in young and mid-life/older (ML/O) adults. Moreover, incubation of mouse arteries with serum from young and ML/O adult humans can directly transfer arterial aging phenotypes for endothelial function and aortic stiffness. These results suggest that age-related changes in the circulating milieu are an underlying mechanism of age-related arterial dysfunction. Dolphins are mammals that have evolutionary adapted to diving, with constant cycles of tissue hypoxia/reoxygenation and disturbed shear stress -- exposures which cause arterial dysfunction in humans. Dolphins also have long lifespans and are relatively free of CVD. Taken together, dolphins may be a unique model of healthy vascular aging, with possible applications to clinical medicine. PURPOSE: To determine if the serum of bottlenose dolphins ( Tursiops truncatus) induces the same arterial aging phenotypes as the serum of age-equivalent humans. Methods: Common carotid arteries and aorta rings from young (Y; 5 mo) and old (O; 25 mo) wildtype female (F) and male (M) C57BL/6N mice were exposed ex vivo for 24 and 48h, respectively, to 5% sex-matched adult dolphin serum. Dolphin serum of Y (17 ± 4 years; n = 16: 5F / 11 M) and ML/O (29 ± 2 years; n = 4: 1F/3M) adults was obtained from the National Marine Mammal Tissue Bank. Endothelial function was assessed as carotid artery endothelium-dependent dilation (EDD) in response to increasing doses of acetylcholine. Aortic stiffness was measured as elastic modulus, a measure of intrinsic mechanical wall stiffness. Dolphin serum-mediated responses in mouse arteries were compared with that of adult human serum data (Y, 24 ± 1 years, n=10: 5F/5M; ML/O, 67 ± 3 years, n=10: 5F/5M). Differences were assessed via 2-way ANOVAs; within species post hoc analyses conducted between age groups. Results: Endothelial Function. Peak EDD in Y mouse carotid arteries was lower following exposure to serum from ML/O adult humans (ML/O, 78 ± 2 v. Y, 92 ± 2%; P &lt; 0.001) and higher in O mouse carotid arteries after exposure to Y adult serum (92 ± 2 vs. 73 ± 5%, P = 0.001). In contrast, EDD was similarly high across all groups following dolphin serum exposure (³ 93% peak EDD), independent of the age of the serum donor or the mouse arteries (Y v. ML/O serum donor in Y arteries, P = 0.773; in O mouse arteries, P = 0.942). Aortic Stiffness. Stiffness in Y aortic rings was ~60% higher following exposure to ML/O adult human serum (P = 0.001 v. Y adult serum). In O mouse aortic rings, stiffness was 25% lower after exposure to Y adult serum (P = 0.044 v. ML/O adult serum). In contrast, stiffness was similar across all groups following dolphin serum exposure, independent of age of the serum donor or the arteries (Y v. ML/O serum donor in Y aortic rings, P = 0.974; in O aortic rings P = 0.157). CONCLUSIONS: The circulating milieu of bottlenose dolphins may be geroprotective, which could serve as a model to investigate mechanisms and potential therapies for preventing adverse vascular aging and promoting CV health and longevity in humans. FUNDING: R21 AG078408 &amp; MSCA-IF-2019:892267. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Validation of an early vascular aging construct model for comprehensive cardiovascular risk assessment using external risk indicators for improved clinical utility: data from the EVasCu study

BackgroundCardiovascular diseases (CVDs) remain a major global health concern, necessitating advanced risk assessment beyond traditional factors. Early vascular aging (EVA), characterized by accelerated vascular changes, has gained importance in cardiovascular risk assessment.MethodsThe EVasCu study in Spain examined 390 healthy participants using noninvasive measurements. A construct of four variables (Pulse Pressure, Pulse Wave Velocity, Glycated Hemoglobin, Advanced Glycation End Products) was used for clustering. K-means clustering with principal component analysis revealed two clusters, healthy vascular aging (HVA) and early vascular aging (EVA). External validation variables included sociodemographic, adiposity, glycemic, inflammatory, lipid profile, vascular, and blood pressure factors.ResultsEVA cluster participants were older and exhibited higher adiposity, poorer glycemic control, dyslipidemia, altered vascular properties, and higher blood pressure. Significant differences were observed for age, smoking status, body mass index, waist circumference, fat percentage, glucose, insulin, C-reactive protein, diabetes prevalence, lipid profiles, arterial stiffness, and blood pressure levels. These findings demonstrate the association between traditional cardiovascular risk factors and EVA.ConclusionsThis study validates a clustering model for EVA and highlights its association with established risk factors. EVA assessment can be integrated into clinical practice, allowing early intervention and personalized cardiovascular risk management.

Vascular aging and cardiovascular disease: pathophysiology and measurement in the coronary arteries

Age is a key risk factor for cardiovascular disease, including atherosclerosis. However, pathophysiological disease processes in the arteries are not an inevitable feature of aging. Large cohort studies with arterial phenotyping along with clinical and demographic data are essential to better understand factors related to the susceptibility or resilience to age-related vascular pathophysiology in humans. This review explores the mechanisms by which vascular structure and function alters with age, and how these changes relate to cardiovascular pathophysiology and disease. Features of vascular aging in the coronary arteries have historically been difficult to quantify pre-mortem due to their size and location. However, non-invasive imaging modalities including CT Coronary Angiogram are now being used to assess coronary vascular age, and further advances in imaging analysis such as the CT Fat Attenuation Index will help provide further measurement of features associated with coronary vascular aging. Currently, markers of vascular aging are not used as therapeutic targets in routine clinical practice, but non-pharmacological interventions including aerobic exercise and low salt diet, as well as anti-hypertensives have been demonstrated to reduce arterial stiffness. Advances in imaging technology, both in acquisition and advanced analysis, as well as harmonisation of measurements for researchers across the globe will be invaluable in understanding what constitutes healthy vascular aging and in identifying features of vascular aging that are associated with coronary artery disease and its adverse outcomes. Assessing such images in large cohorts can facilitate improved definitions of resilient and susceptible phenotypes to vascular aging in the coronary arteries. This is a critical step in identifying further risk factors and biomarkers within these groups and driving forward the development of novel therapies aimed at slowing or stopping age-related vascular changes in the coronary arteries.

Association of Accelerometer-Measured Sedentary Time and Physical Activity with Arterial Stiffness and Vascular Aging in the General Spanish Population, Analyzed by Sex.

In this study we analyzed the association between physical activity and sedentary lifestyle with vascular aging in Spanish populations aged 35-75 years. A cross-sectional study was developed, in which 501 subjects aged 35-75 years were recruited. Physical activity and sedentary time were measured with an accelerometer (Actigraph GTX3) for a week. We measured carotid-femoral pulse wave velocity (cfPWV) by a Sphygmo Cor® device and carotid intima-media thickness (cIMT) by ultrasound (Sonosite Micromax®). The vascular aging index (VAI) was calculated as described in the literature. Vascular aging was defined considering the 25th and 75th percentiles by age and sex of cfPWV and VAI, presence of vascular injury, type-2 diabetes mellitus or arterial hypertension. Individuals were classified into three groups: healthy, normal, and early vascular aging. The mean age of the sample was 55.90 14.24 years, 50% being women. Total physical activity was negatively associated with cfPWV ( = -0.454) and VAI ( = -1.845). Similarly, the number of steps per day obtained a negative association with cfPWV ( = -0.052) and VAI ( = -0.216), while sedentary time showed a positive association with cfPWV ( = 0.028) and VAI ( = 0.117). In the analysis by sex, the results showed similar values. The odds ratio (OR) of total physical activity of subjects classified as early vascular aging (EVA) with regarding those classified as healthy vascular aging (HVA) was 0.521 (95% confidence interval [CI] 0.317 to 0.856) for cfPWV, and 0.565 (95% CI 0.324 to 0.986) for VAI. In terms of the number of steps per day, the OR was 0.931 (95% CI 0.875 to 0.992) for cfPWV and 0.916 (95% CI 0.847 to 0.990) for VAI and for sedentary time the OR was 1.042 (95% CI 1.011 to 1.073) for cfPWV and 1.037 (95% CI 1.003 to 1.072) for VAI. The OR of subjects classified as vigorous physical activity was 0.196 (95% CI 0.041 to 0.941) using cfPWV and 0.161 (95% CI 0.032 to 0.820) using VAI. In the analysis by sex, the results showed an association in men when cfPWV was used and an association in women when VAI was used to define vascular aging. The results of this study indicate that the more time spent performing physical activity and the less sedentary time, the lower the arterial stiffness and the probability of developing early vascular aging. The study was registered in ClinicalTrials.gov (number: NCT02623894).

Clustering of vascular aging manifestations and incident cardiovascular events. The Paris Prospective Study III

Abstract Background Vascular aging is a key contributor to cardiovascular disease (CVD). Manifestations of vascular aging are heterogeneous and include atherosclerosis, arterial stiffening, increased arterial wall stress and arterial diameter enlargement. These manifestations have different pathophysiological mechanisms and likely require different prevention strategies. How the different vascular aging manifestations co-exist, or cluster, at the individual level and the association of any such clusters with incident CVD is unknown. Purpose To examine how vascular aging manifestations cluster and whether any such clusters are associated with incident CVD. Methods In the Paris Prospective Study III, a French community-based prospective study on novel determinants of CVD, 10,157 participants underwent a high-resolution carotid echotracking (Artlab, Esaote) between 2008 and 2012, and were thereafter monitored every two years for CVD events up to end 2020 . Hospitalized stroke and coronary heart disease (CHD) events were validated after the review of all medical records. Hierarchical clustering analysis was employed to identify patterns of vascular aging. Hazard ratios (HRs) were quantified in Cox models. Results The study sample included 8,360 participants (39% women, mean age 59.6 years) without prevalent CVD. Three clusters of vascular aging manifestations were identified: - Cluster 1 included 3,995 (47.8%) participants and was characterized by low prevalence of carotid plaques, low carotid intima-media thickness (IMT), low carotid artery stiffness, small carotid diameter and low carotid circumferential wall stress (healthy vascular aging cluster). - Cluster 2 included 2,109 (25.2%) participants and was characterized by high carotid artery stiffness and high carotid circumferential wall stress (arterial stiffness vascular aging cluster). - Cluster 3 included 2,256 (27.0%) participants, and was characterized by high prevalence of carotid plaques and high carotid IMT(atherosclerosis vascular aging cluster). After a median follow-up of 8.5 years, 108 incident stroke events, 218 CHD events and 192 deaths occurred. Compared with cluster 1, cluster 2 (HR 1.76, [95%CI, 1.06-2.94]), but not cluster 3 (HR 1.57, [0.94-2.62]), was associated with a higher risk of stroke. In addition, compared to cluster 1, cluster 3 (HR 1.53, [1.08-2.16]), but not cluster 2 (HR 1.38, [95% CI, 0.96-1.98]), was associated with higher risk of CHD. Both cluster 2 and 3 were associated with higher all-cause mortality (HR for cluster 2: 1.50, [1.02-2.21]; HR for cluster 3: 1.48, [1.01-2.17]). Internal validation using bootstrapping methods (n=1000 samples) provided consistent findings. Conclusion The simultaneous analysis of carotid-echotracking vascular aging parameters identified three patterns of vascular aging that are differentially associated with CHD and stroke in the community.Carotid properties by clustersKM survival curves by clusters

Vascular stiffness and healthy arterial aging in older patients with optimal blood pressure.

Pulse wave velocity is used to diagnose central arterial stiffness (CAS) and quantify healthy vascular aging (HVA). To evaluate the CAS and HVA in elderly patients with systemic blood pressure levels classified as optimal/normal. A total of 102 patients without comorbidities and with systolic pressure (SP) < 120 mmHg and diastolic pressure (DP) < 80 mmHg were selected from the EVOPIU database (Pulse Wave Velocity of Elderly Individuals in an Urban area of Brazil). The carotid-femoral pulse wave velocity (c-fPWV) and the central and peripheral pressures were evaluated in all patients. The patients were divided into four groups: G1: (n = 19, with c-fPWV < 7.6 m/s, without medication), G2 (n = 26, c-fPWV ≥ 7.6 m/s; without medication), G3 (n = 25, c-fPWV < 7.6 m/s with antihypertensive medication), and G4 (n = 32, c-fPWV ≥ 7.6 m/s with antihypertensive medication). In our sample, 56.7% of patients had c-fPWV ≥ 7.6 m/s. The central systolic pressure in G1 [99 (10) mmHg] was lower than that found in the other three groups [vs. 112 (14) mmHg, 111 (15), 112 (20) mmHg; P < 0.05)]. Older people with optimal arterial blood pressure do not necessarily have HVA and could have c-fPWV values close to the limits established for CAS diagnosis.

Early vascular aging as an index of cardiovascular risk in healthy adults: confirmatory factor analysis from the EVasCu study

BackgroundThe concept of early vascular aging (EVA) represents a potentially beneficial model for future research into the pathophysiological mechanisms underlying the early manifestations of cardiovascular disease. For this reason, the aims of this study were to verify by confirmatory factor analysis the concept of EVA on a single factor based on vascular, clinical and biochemical parameters in a healthy adult population and to develop a statistical model to estimate the EVA index from variables collected in a dataset to classify patients into different cardiovascular risk groups: healthy vascular aging (HVA) and EVA.MethodsThe EVasCu study, a cross-sectional study, was based on data obtained from 390 healthy adults. To examine the construct validity of a single-factor model to measure accelerated vascular aging, different models including vascular, clinical and biochemical parameters were examined. In addition, unsupervised clustering techniques (using both K-means and hierarchical methods) were used to identify groups of patients sharing similar characteristics in terms of the analysed variables to classify patients into different cardiovascular risk groups: HVA and EVA.ResultsOur data show that a single-factor model including pulse pressure, glycated hemoglobin A1c, pulse wave velocity and advanced glycation end products shows the best construct validity for the EVA index. The optimal value of the risk groups to separate patients is K = 2 (HVA and EVA).ConclusionsThe EVA index proved to be an adequate model to classify patients into different cardiovascular risk groups, which could be valuable in guiding future preventive and therapeutic interventions.

PS-C04-2: LONGITUDINAL CONSTANCY OF VASCULAR AGEING PHENOTYPES AND FACTORS ASSOCIATED WITH THE PHENOTYPE CONSTANCY OVER TIME

Background: The concept of two phenotypes of vascular aging, healthy vascular aging (HVA) and early vascular aging (EVA) has been proposed. Objectives: To examine the: (1) constancy of these phenotypes over time; (2) validity of assuming that a constantly maintained phenotype reflects the rate of structural arterial stiffening; and (3) longitudinal associations between the vascular phenotypes and cardiovascular risk factors/heart rate (HR). Methods: The brachial-ankle pulse wave velocity (baPWV) was measured annually over a 16-year period in 4682 middle-aged Japanese subjects. The vascular phenotypes of 4682 middle-aged Japanese subjects were measured at the start and end of a 16-year study period, by measuring the arterial stiffness as a function of the age and blood pressure. Results: Of 4682 subjects, 158 (3.4%) showed constancy of the HVA phenotype, and 192 (4.1%) subjects showed constancy of the EVA phenotype throughout the study periods. The baPWV adjusted for the mean blood pressure differed significantly between the two groups. Elevated mean blood pressure, serum HbA1c levels and HR were significantly associated with constancy of the EVA phenotype, whereas only a low HR was significantly associated with constancy of the HVA phenotype. Conclusions: In middle-aged Japanese subjects with the HVA/EVA phenotype at the study baseline, while the phenotype changed during the study period in many subjects, phenotype constancy appeared to reflect the rate of structural arterial stiffening. Elevated blood pressure and abnormal glucose metabolism were associated with constancy of the EVA phenotype. On the other hand, HR was a robust marker of the presence/constancy of the HVA/EVA phenotype.

Irisin: A Potentially Fresh Insight into the Molecular Mechanisms Underlying Vascular Aging.

Aging is a natural process that affects all living organisms, including humans. Aging is a complex process that involves the gradual deterioration of various biological processes and systems, including the cardiovascular system. Vascular aging refers to age-related changes in blood vessels. These changes can increase the risk of developing cardiovascular diseases, such as hypertension, atherosclerosis, and stroke. Recently, an exercise-induced muscle factor, irisin, was found to directly improve metabolism and regulate the balance of glucolipid metabolism, thereby counteracting obesity and insulin resistance. Based on a growing body of evidence, irisin modulates vascular aging. Adenosine monophosphate-activated protein kinase (AMPK) serves as a pivotal cellular energy sensor and metabolic modulator, acting as a central signaling cascade to coordinate various cellular processes necessary for maintaining vascular homeostasis. The vascular regulatory effects of irisin are closely intertwined with its interaction with the AMPK pathway. In conclusion, understanding the molecular processes used by irisin to regulate changes in vascular diseases caused by aging may inspire the development of techniques that promote healthy vascular aging. This review sought to describe the impact of irisin on the molecular mechanisms of vascular aging, including inflammation, oxidative stress, and epigenetics, from the perspective of endothelial cell function and vascular macroregulation, and summarize the multiple signaling pathways used by irisin to regulate vascular aging.

Molecular Mechanisms of Vascular Health: Insights From Vascular Aging and Calcification.

Cardiovascular disease is the most common cause of death worldwide, especially beyond the age of 65 years, with the vast majority of morbidity and mortality due to myocardial infarction and stroke. Vascular pathology stems from a combination of genetic risk, environmental factors, and the biologic changes associated with aging. The pathogenesis underlying the development of vascular aging, and vascular calcification with aging, in particular, is still not fully understood. Accumulating data suggests that genetic risk, likely compounded by epigenetic modifications, environmental factors, including diabetes and chronic kidney disease, and the plasticity of vascular smooth muscle cells to acquire an osteogenic phenotype are major determinants of age-associated vascular calcification. Understanding the molecular mechanisms underlying genetic and modifiable risk factors in regulating age-associated vascular pathology may inspire strategies to promote healthy vascular aging. This article summarizes current knowledge of concepts and mechanisms of age-associated vascular disease, with an emphasis on vascular calcification.

Longitudinal constancy of vascular ageing phenotypes in middle-aged Japanese employees

Abstract Background Recently, the concept of healthy vascular aging (HVA) and early vascular aging (EVA) phenotypes was proposed. Purpose We examined following issues; constancy of the vascular phenotypes over time; validity of assuming that constancy of the vascular phenotypes reflects the progression rate of structural arterial stiffening; and associations of vascular phenotype constancy with cardiovascular risk factors/their treatment, and the heart rate (HR). Methods Data on the brachial-ankle pulse wave velocity (baPWV) measured annually over a 16-year period in 4682 middle-aged Japanese employees were analyzed. Results Of all subjects, 30% showed constancy of the vascular phenotype during the study period. The estimated marginal mean of baPWV values and the slope of the annual increase of the baPWV were higher in the constant EVA group (EVA-EVA) than in the constant HVA group (HVA-HVA) (Figure 1). Elevated serum HbA1c levels, medication for hypertension, and high HR were significantly associated with constancy of the EVA phenotype, whereas a low HR was significantly associated with constancy of the HVA phenotype. Conclusions In middle-aged Japanese employees with the HVA/EVA phenotype at the study baseline, while the phenotype changed over time in most subjects, HVA/EVA phenotype constancy in the remaining subjects reliably reflected a low/high rate of progression of structural arterial stiffening. Hypertension and abnormal glucose metabolism were associated with constancy of the EVA phenotype, but treatment for these conditions failed to improve the phenotype. Low/high HR was a robust marker of the presence/constancy of the HVA/EVA phenotype. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Omron Health CareTeijin Pharma

Abstract P340: Associations Of Life’S Simple 7 And 10-year Change In Load-dependent Arterial Stiffness: The Multi-ethnic Study Of Atherosclerosis (mesa)

Introduction: Arterial stiffness can be separated into two main mechanisms: 1) load-dependent (LD) stiffening from higher blood pressure (BP) and (2) structural stiffening due to changes in the vessel wall. Structural stiffening is strongly associated with advancing age. LD stiffening is highly variable and is more strongly associated with CVD. Hypothesis: Optimal Life’s Simple 7 factors will be associated with a slower rate of increase in LD stiffness. Methods: MESA participants with carotid ultrasound at Exam 1 and Exam 5 (year 10) were included (n=2557). Peterson’s elastic modulus (PEM) was calculated to represent total stiffness. Structural stiffness was PEM adjusted to a standard BP of 120/80 mmHg using participant-specific models. LD stiffness was the difference between total and structural stiffness. Changes in stiffness mechanisms over 10 years for poor versus optimal Life’s Simple 7 (LSF) factors were compared with linear models adjusted for age, sex, race/ethnicity, study site, education, BP and lipid medication, C-reactive protein, Interleukin-6, and baseline stiffness. Results: No LS7 factors was associated with increased LD stiffening for the whole cohort. For the bottom quartile of baseline LD stiffness, smoking (2.55±1.23 kPa, p=0.039) was associated with increased LD stiffening. For the highest quartile of baseline LD stiffness, no LS7 factors were significantly associated with stiffening. Conclusion: Smoking was associated with increased LD stiffening in those with low baseline stiffness. Smoking cessation and prevention may be especially important in these individuals to promote healthy vascular aging.

Association of physical activity with vascular aging in a population with intermediate cardiovascular risk, analysis by sex: MARK study

BackgroundThe aim of this study was to analyze the association of physical activity and its intensity with arterial stiffness and vascular aging and differences by sex in a Spanish population with intermediate cardiovascular risk.MethodsCross-sectional study. A total of 2475 individuals aged 35–75 years participated in the study. Brachial–ankle pulse wave velocity (baPWV) was measured using a VaSera VS-1500® device. Based on the age and sex percentile presented by the participants, the latter were classified as follows: those with a percentile above 90 and presenting established cardiovascular disease were classified as early vascular aging (EVA); those with a percentile between 10 and 90 were classified as normal vascular aging (NVA) and those with a percentile below 10 were classified as healthy vascular aging (HVA). Physical activity was analyzed through the short version of the Minnesota Leisure Time Physical Activity Questionnaire (MLTPAQ).ResultsThe mean age of the participants was 61.34 ± 7.70 years, with 61.60% men. Of the total sample, 86% were sedentary (83% men vs 90% women). The total physical activity showed a negative association with baPWV (β = − 0.045; 95% CI − 0.080 to − 0.009). Intense physical activity showed a negative relationship with baPWV (β = − 0.084; 95% CI − 0.136 to − 0.032). The OR of the total physical activity and the intense physical activity carried out by the subjects classified as NVA with respect to those classified as HVA was OR = 0.946; (95% CI 0.898 to 0.997) and OR = 0.903; (95% CI 0.840 to 0.971), and of those classified as EVA it was OR = 0.916; (95% CI 0.852 to 0.986) and OR = 0.905; (95% CI 0.818 to 1.000). No association was found with moderate- or low-intensity physical activity.ConclusionsThe results of this study suggest that, when intense physical activity is performed, the probability of presenting vascular aging is lower. In the analysis by sex, this association is only observed in men.

Separate and Joint Associations of Cardiorespiratory Fitness and Healthy Vascular Aging With Subclinical Atherosclerosis in Men.

Achieving healthy vascular aging (HVA) is important for decelerating age-related cardiovascular disease risk. We evaluated the interplay between HVA, cardiorespiratory fitness (CRF), and subclinical atherosclerosis. We analyzed data on 3722 men who underwent cardiopulmonary exercise testing in a health examination program. HVA was defined as blood pressure <140/90 mm Hg without hypertension and brachial-ankle pulse wave velocity <1266 cm/s. CRF was directly measured by peak oxygen uptake. Subclinical atherosclerosis was defined as coronary artery calcification scores of >0 and ≥100 and a mean carotid artery intima-media thickness (CIMT) >75th percentile for each age group as well as >0.8 mm of CIMT. Separate and joint associations of HVA and CRF with subclinical atherosclerosis were evaluated. Each 1 metabolic equivalent increment in CRF was associated with 23% higher odds for having HVA. HVA was associated with lower odds of coronary artery calcification but not CIMT. CRF modified the association between HVA and CIMT>0.8 mm (interaction: P=0.01); HVA was associated with lower odds of CIMT>0.8 mm in fit men with no significant association between HVA and CIMT>0.8 mm in unfit men. Compared with no HVA and being unfit, HVA and being fit was associated with lower odds of subclinical atherosclerosis, but there was no significant association between HVA and being unfit with subclinical atherosclerosis. HVA and higher CRF are each associated with a lower risk of subclinical atherosclerosis in men. Higher CRF is associated with a higher prevalence of HVA and may modify the association between HVA and subclinical atherosclerosis.

Sedentary Behaviour and Its Relationship with Early Vascular Ageing in the General Spanish Population: A Cross-Sectional Study.

Sedentary behaviour is associated with a greater predisposition to developing cardiovascular diseases. The aim of the study was to analyse the relationship between sedentary time and early vascular ageing. A total of 501 participants (49.70% men) were recruited through random sampling stratified by age group and sex. Vascular ageing was evaluated considering three criteria: (1) the vascular ageing index (VAI); (2) the carotid–femoral pulse wave velocity (cfPWV) 10th and 90th percentiles of the reference values in the European population by age; and (3) the Framingham’s heart age. The carotid intima–media thickness was measured using a Sonosite Micromaxx ultrasound, the presence of peripheral artery disease was assessed by calculating the ankle–brachial index using a VaSera VS-1500, and the cfPWV was measured with a SphygmoCor® device. Weekly sedentary hours were evaluated through a sitting time questionnaire. The average age of the population was 55.90 ± 14.24 years. The men spent more hours sitting per week (47.6 ± 16.6 vs. 36.8 ± 17.3 h/W), at work (16.7 ± 16.2 vs. 9.73 ± 14.9 h/W), and watching TV (21.6 ± 12.5 vs. 18.7 ± 11.9 h/W). In the logistic regression analysis, the individuals with early vascular aging (EVA), with respect to those with healthy vascular aging (HVA), spent more hours sitting per week (OR = 1.03 vs. OR = 1.02; p < 0.05) and watching TV (OR = 1.03 vs. OR = 1.03; p < 0.05), using the criteria of the European guideline and VAI, and more hours sitting when commuting (OR = 1.04; p < 0.05), using Framingham’s heart age to define EVA. The results of this study indicate that sedentary time is associated with early vascular ageing. Therefore, reducing sedentary time would improve vascular health.

Preventive Screening of Young People from the Perspective of Vascular Aging Phenotypes: the Role of Body Weight

Aim. To study the cardiovascular stiffness index CAVI in relation to main risk factors (RF) in young people from the point of their vascular aging phenotype and gender.Material and methods. 264 young people (93 boys and 171 girls) at age of 18 to 25 years were examined. Vascular screening was performed with evaluating of CAVI. All subjects were divided into tertile groups for this indicator, taking into account gender. Such interval analysis of gender- and age- homogeneous sample allows to identify carriers of the phenotypes of premature (upper CAVI-tercile), normal (middle CAVI-tercile), and favorable or healthy (low CAVI-tercile) vascular aging. The first of them is also called EVA (early vascular aging) syndrome. In these groups, the incidence of carriers of insufficient, normal body mass (BM) and overweight were estimated. In three groups formed by BM indicator, the parameters of CAVI, hemodynamic and metabolic status in response to changes in BM were determined.Results. Among of the presented RF, the correlation was significant for CAVI with a weight -0.428 (p&lt;0.001) for R-CAVI, -0.453 (p&lt;0.001) for L- CAVI, and even more significant with the BM index - at the level of -0.410 (p&lt;0.001) for R-CAVI and -0.462 (p&lt;0.001) for L-CAVI. This connection is found in boys. Among boys and girls with excessive BM, the most favorable vascular aging phenotype is observed 2.7 and 2.2 times more often than the EVA syndrome. In contrast, among girls with insufficient BM, a favorable vascular phenotype is detected almost twice rarely as compared with EVA syndrome. In similar group of boys, a healthy vascular phenotype is not observed at all. Among normal-weight boys and girls, the occurrence of the two extreme vascular phenotypes is almost identical. The arterial rigidity decrease on the background of BM increase occurs despite the сhanges of hemo- dynamic and metabolic indicators. This changes are especially pronounced in girls. The difference between the extreme weight categories in terms of R- CAVI and L-CAVI for boys was 1.4, while for girls it was only 0.3 for R-CAVI and 0.4 for L-CAVI.Conclusion. When carrying out preventive measures among young people, one should not limit oneself to evaluating only traditional RF. Based on the concept of vascular aging, angiological screening should be more widely implemented. It will allow for more individualized preventive interventions among young people in the future.

Abstract 13428: Mid-Life and Late-Life Exposure to Traditional Cardiovascular Risk Factors and Zero Coronary Artery Calcium: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Our understanding of traditional atherosclerotic risk factors is largely based on their contributions to adverse atherosclerotic events. However, the relative contributions of mid-life and late-life risk factor exposures to persistent zero coronary artery calcium (CAC=0) in older adulthood, a representative healthy vascular aging phenotype, have not been fully examined. Hypothesis: Both mid-life and late-life risk factors are associated with CAC=0, with stronger results for the former. Methods: Using data from 2,035 community-dwelling participants free of coronary heart disease in the ARIC study, we evaluated traditional modifiable risk factors (i.e., lipids, systolic blood pressure, obesity, smoking, and diabetes) at mid-life (median age 49, visit 1 from 1987-1989) and late-life (median age 73, visit 5 from 2011-2013) and their associations with CAC=0 at visit 7 (median age 80, from 2018-2019), using multivariable logistic regression models adjusted for within-visit factors. Results: There were 204 participants (10.0%) with CAC=0. Compared with participants with any CAC, those with CAC=0 had more favorable values for most traditional risk factors (lower cholesterol, BMI, and systolic blood pressure, higher HDL-C, and not smoking) in both mid-life and late-life, with the exception of fasting glucose ( Table ). The results were similar when we modeled diabetes instead of fasting glucose. Lower total cholesterol in mid-life, but not late-life, was associated with CAC=0. Conclusions: Having favorable modifiable risk factors both at mid-life and late-life were independently associated with CAC=0 in older adults free of clinical coronary heart disease. These results highlight the importance of maintaining a healthy risk factor profile from mid-life, with implications on public health promotion and strategy.

Inhibitors of the sodium-glucose transporter type 2 and new possibilities for managing vascular age in patients with type 2 diabetes mellitus

The article discusses the pathophysiological mechanisms of the development of vascular aging as a combination of the influence on the body of genetic, environmental, regulatory, metabolic and other factors causing biochemical, enzymatic and cellular changes in the arterial vascular bed. The concept of “early vascular aging” and “healthy vascular aging” is defined depending on the ratio of the biological and chronological age of the vessels. The role of diabetes mellitus in increasing vascular stiffness, early vascular aging, as well as the progression of atherosclerotic cardiovascular diseases and their complications is considered in detail. Approaches to multifactorial management of vascular age in patients with type 2 diabetes (lifestyle modification with strategy of aggressive treatment of modifiers of atherosclerosis, rejection of bad habits, adherence to dietary recommendations and the use of modern organo- and vasoprotective antidiabetic drugs) are revealed. The mechanism of realization of vasoprotective effects of inhibitors of sodium-glucose transporter-2 (iNGLT-2) is described in detail. The results of completed large random ized trials EMPA-REG Outcome and EMPA-REG BP of the most studied representative of the IGLT-2 group, empagliflozin, are presented. It has been shown that due to their glucose and natriuretic effects, the ability to reduce body weight and blood pressure, improve myocardial metabolism and bioenergetics, decrease the activity of the sympathetic nervous system, as well as positive effects on vascular stiffness, NGLT-2 inhibitors are the drugs of choice in patients with type 2 diabetes mellitus (T2DM) and cardiovascular diseases. This makes it possible to widely use this group of drugs for managing the vascular age of patients and represents a new opportunity in the prevention of vascular aging in T2DM.

P.38 Comparison of Arterial Hemodynamics in Early Vascular Aging (EVA), Average Vascular Aging (AVA) and Healthy Vascular Aging (HVA)

BackgroundLarge artery stiffening, as indexed by carotid-femoral pulse wave velocity (cfPWV), may vary substantially among individuals. The present study aimed to characterize the arterial mechanical properties of the macro- and microvasculature in subjects with early or healthy vascular aging (EVA, HVA).MethodsCarotid and femoral pressure and central flow waveforms were noninvasively acquired in a total of 873 community residents (aged ≥50 years, mean age 66.9 years, 69.2% female). They were classified as EVA and HVA, according to the highest and lowest 10% of the cfPWV stratified by 5-year intervals. The remaining 80% were defined as average vascular aging (AVA). Macrovascular and microvascular functions were characterized by aortic input impedance, systemic vascular resistance and wave reflection indices.ResultsEVA subjects had significantly higher prevalence of hypertension and diabetes. In multivariable analysis adjusting for sex, height, weight and mean arterial pressure (MAP), EVA had significantly increased characteristic impedance and reduced arterial compliance. By contrast, for the microvascular functions, systemic vascular resistance (not adjusted for MAP), amplitude of the reflected wave (Pb) and excess pressure integral (XSPI) derived from the reservoir-wave analysis were significantly increased in EVA when compared with HVA or AVA (all p < 0.05). Primary determinants of HVA included female, lower value of XSPI and SVR, whereas determinants of EVA included male, elevated BP, metabolic syndrome, increased Pb and SVR.ConclusionsSystemic microvasculature play an important role in interacting with macrovasculature, as evidenced from increased or reduced systemic resistance and wave reflection, in subjects with HVA and EVA.