Marker Of Vascular Aging Research Articles

Amyloid beta, a marker of vascular aging and cardiovascular disease, is associated with accelerated progression of renal dysfunction

Abstract Background Amyloid-beta (1-40) (Αb1-40), a proinflammatory and pro-atherosclerotic peptide, is involved in Alzheimmer’s disease and vascular aging and is considered an emerging prognostic marker of atherosclerotic cardiovascular disease (ASCVD) and heart failure. Because Ab1-40 clearance is largely dependent on renal function while clinical data consistently associate this peptide with renal function, we hypothesized that Ab1-40 circulating levels would serve as a predictor of progression of renal dysfunction. Purpose To examine the potential cross-sectional and prospective bidirectional association of Ab1-40 levels with renal function in a population with a wide range of ASCVD risk. Methods In the settings of the Athens Cardiometabolic registry, data from consecutively recruited subjects with (n=137) and without clinically overt ASCVD (n=674) with available both Ab1-40 plasma levels and GFR values (total n=811) were analyzed. Αb1-40 was measured by enzyme-linked immunosorbent assay and renal function was assessed by estimation of glomerular filtration rate (GFR). Of these subjects, 182 individuals consented to be followed up and re-assessed after a minimum period of 12 months in order to examine a potential bidirectional link between changes in Ab1-40 levels and GFR. Results Patients with increased Ab1-40 levels at baseline had significantly worse renal function, reflected as lower GFR values, compared with their counterparts with lower Ab1-40 levels (GFR= 74.8 vs 93.3 vs 100.2 ml/min/1.73m2 for high, middle and low tertile of Ab1-40 levels, p<0.001). Elevated Ab1-40 levels were associated with chronic kidney disease (CKD) stage 2 [odds ratio (OR)=2.29, 95% confidence intervals (CI)= 1.58-3.31, p<0.001] and CKD stage 3 (OR=3.67, 95% CI=2.37-5.70, p<0.001) at baseline. Furthermore, increased Ab1-40 at baseline was prospectively associated with accelerated progression of renal dysfunction as assessed by changes in GFR values between baseline and follow-up [mean adjusted rate of decrease=-7.20 (95% CI=-1.33, -13.07) for higher vs lowest tertiles of Ab1-40 levels across a follow-up period of 12 months, p=0.017 for interaction). On the contrary, baseline GFR values were not prospectively associated with Ab1-40 levels at follow-up visits (p>0.05). Conclusion In a population with a wide range of ASCVD risk, high Αb1-40 levels at baseline were associated both with renal function at baseline and with accelerated rate of progression of GFR deterioration at follow-up irrespective of its baseline levels. These findings suggest a mechanistic background for the established association of Ab1-40 with renal function and warrant further research to clarify the clinical value of monitoring its circulating levels as a novel biomarker which could reflect enhanced risk for renal dysfunction.

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.

Abstract 13220: Independent Effects of Baseline Pulse Wave Velocity versus Advancing Age on Changes in Arterial Stiffness Over Time

Introduction: While arterial stiffness (AS) is a known marker of vascular ageing that prognosticates cardiovascular disease (CVD), prospective analyses of AS evolution alongside chronological age are necessary to understand factors that drive progressive AS. Using pulse wave velocity (PWV) we investigated the impact of baseline factors in predicting PWV changes over a 5-year period. Hypothesis: We hypothesized that certain baseline factors in older Asian adults are predictive of PWV trajectories later in life independent of chronological age. Methods: Participants without CVD from a community-based cohort had their clinical risk factors collected prospectively, and PWV (m/s) measured using a cuff-based oscillometric pulse wave analysis machine at baseline and 5-year timepoint. Results: This analysis included 159 participants (41.5% women, mean age 67.7 ± 10.2 years). ΔPWV (2.19 ± 2.25), the 5-year change in PWV, was associated with baseline PWV (β = -0.687, p < 0.001), age (β = 0.084, p < 0.001), hypertension (β=0.763, p = 0.033), weight (β = -0.042, p = 0.018) and waist circumference (β = -0.045, p = 0.018). Gender, body mass index, dyslipidemia, diabetes mellitus and lifetime smoking status were not significantly associated with ΔPWV. ΔPWV was independently associated with baseline PWV (β = -1.17, 95% CI -1.65 - -0.70, p < 0.001) and age (β = 0.144, 95% CI 0.09 - 0.20, p < 0.001) adjusting for weight, waist circumference and hypertension, with insignificant interaction between baseline PWV and age (p = 0.431). Participants with increases in PWV after 5 years, compared to those without PWV increase, had lower PWV (8.52 ± 1.81 vs 11.10 ± 2.44) at baseline. Conclusions: Baseline PWV was associated with changes in AS over a 5-year period independent of age and clinical risk factors. The inverse relationship between baseline PWV and ΔPWV may suggest plateauing of PWV increases at higher baseline PWV levels. In addition, high baseline PWV may not predict worsening of AS later in life.

Vascular Aging Is Accelerated in Hematological Cancer Survivors Who Undergo Allogeneic Stem Cell Transplant.

Survivors of allogeneic stem cell transplant (SCT) receive intensive cancer treatments that are associated with cardiovascular dysfunction. Markers of vascular age can indicate early signs of adverse (cardio)vascular changes; however, the impact of SCT on these makers is unknown. We aimed to determine the short (3 months) and longer-term (≥2 years) effect of SCT on markers of vascular age in hematologic cancer survivors compared with an age-matched noncancer control group. The short-term effects of SCT, markers of vascular age (aortic compliance, arterial elastance, and ventricular-vascular coupling) were assessed via cardiac magnetic resonance imaging (cardiac and aortic volumes) before and ≈3 months post-SCT in 13 short-term survivors and compared with 11 controls. The longer-term impact was assessed by comparing 14 long-term survivors (6.5 [2-20] years post-SCT) to the short-term survivors (post-SCT) and controls (n=16). The groups were similar for age and body mass index. In the short-term survivors, no significant group-by-time interactions were observed for any markers of vascular aging from pretransplant to posttransplant (net difference for change in compliance between groups -0.07 [95% CI, -1.49 to 1.35]). For the time-course analysis, aortic compliance was significantly lower in both SCT groups (overall P=0.007) compared with controls, whereas ventricular-vascular coupling was higher in both survivor groups as was arterial elastance in long-term SCT survivors (ie, worse; P<0.01 for all). This study provides evidence of an accelerated vascular aging phenotype in allogeneic SCT survivors and provides insight into the increased burden of cardiovascular disease among hematologic cancer survivors.

Global distributions of age- and sex-related arterial stiffness: systematic review and meta-analysis of 167 studies with 509,743 participants.

Arterial stiffening is central to the vascular ageing process and a powerful predictor and cause of diverse vascular pathologies and mortality. We investigated age and sex trajectories, regional differences, and global reference values of arterial stiffness as assessed by pulse wave velocity (PWV). Measurements of brachial-ankle or carotid-femoral PWV (baPWV or cfPWV) in generally healthy participants published in three electronic databases between database inception and August 24th, 2020 were included, either as individual participant-level or summary data received from collaborators (n=248,196) or by extraction from published reports (n=274,629). Quality was appraised using the Joanna Briggs Instrument. Variation in PWV was estimated using mixed-effects meta-regression and Generalized Additive Models for Location, Scale, and Shape. The search yielded 8920 studies, and 167 studies with 509,743 participants from 34 countries were included. PWV depended on age, sex, and country. Global age-standardised means were 12.5m/s (95% confidence interval: 12.1-12.8m/s) for baPWV and 7.45m/s (95% CI: 7.11-7.79m/s) for cfPWV. Males had higher global levels than females of 0.77m/s for baPWV (95% CI: 0.75-0.78m/s) and 0.35m/s for cfPWV (95% CI: 0.33-0.37m/s), but sex differences in baPWV diminished with advancing age. Compared to Europe, baPWV was substantially higher in the Asian region (+1.83m/s, P=0.0014), whereas cfPWV was higher in the African region (+0.41m/s, P<0.0001) and differed more by country (highest in Poland, Russia, Iceland, France, and China; lowest in Spain, Belgium, Canada, Finland, and Argentina). High vs. other country income was associated with lower baPWV (-0.55m/s, P=0.048) and cfPWV (-0.41m/s, P<0.0001). China and other Asian countries featured high PWV, which by known associations with central blood pressure and pulse pressure may partly explain higher Asian risk for intracerebral haemorrhage and small vessel stroke. Reference values provided may facilitate use of PWV as a marker of vascular ageing, for prediction of vascular risk and death, and for designing future therapeutic interventions. This study was supported by the excellence initiative VASCage funded by the Austrian Research Promotion Agency, by the National Science Foundation of China, and the Science and Technology Planning Project of Hunan Province. Detailed funding information is provided as part of the Acknowledgments after the main text.

Abstract P664: Proteomic Profiling of African-Ancestry Adults Identifies Potential Novel Biomarkers of Vascular Aging

During the aging process, the vasculature undergoes pathologic changes which are strongly associated with hypertension and future cardiovascular disease (CVD) risk. Previous work to identify protein biomarkers of these subclinical vascular changes, which have largely focused on single proteins, has observed many associations in different populations. However, research in African-ancestry populations, who are at high risk for hypertensive CVD, is limited and may be biased by the existing research in Whites. Therefore, we used a proteomic approach to identify biomarkers of vascular aging as assessed by pulse-wave velocity (PWV) and abdominal aortic calcification (AAC). We included 346 African-ancestry men from the Tobago Health Study, a prospective cohort study of community-dwelling men aged ≥40 years residing on the Caribbean island of Tobago. These men were aged from 53-89 years old (mean ± SD = 63.4 ± 8.1 years) and were overweight on average (mean ± SD BMI = 27.7 ± 4.3kg/m2). 79.2% of men had hypertension, 24.6% had diabetes, and 5.9% were current smokers. We quantified protein expression using the Olink® Target 96 Cardiovascular III proteomics panel which includes 92 proteins with known association to human cardiovascular processes (CVDIII; Olink®, Waltham, MA). Brachial-ankle PWV (cm/s) was measured using an automated waveform analyzer. AAC was measured in the aorta at the iliac bifurcation via CT and scored using the Agatston method. Partial Spearman correlations were calculated to assess the relationship between each protein biomarker and both vascular aging outcomes adjusting for age, Olink® assay batch, height, weight, diabetes status, hypertension status, and current smoking. There were 13 and 5 proteins correlated with PWV and AAC, respectively (at P&lt;0.05). All correlations were in the direct direction of effect. Only one protein, cystatin B, was correlated with both PWV and AAC (r= 0.17 and 0.12, P=0.002 and 0.03; respectively). After applying false discovery rate adjustment for multiple comparisons, only fatty acid binding protein 4 (FABP4) and PWV remained significant (r=0.18, P=0.046). In general, proteins categorized by Olink® as belonging to the inflammatory pathway were most likely to be correlated with PWV; whereas, those in the hormone response pathway were most frequently correlated with AAC. Our results highlight that FABP4, a protein related to atherosclerosis via inflammation, may also be an important marker of arterial stiffening in these African-ancestry men. Additionally, we identified cystatin B, a member of the cathepsin protease pathway, as a strong correlate of both PWV and AAC, which may warrant further research into it as a novel biomarker of vascular aging and CVD in this high-risk population. In conclusion, proteomics may be an effective tool for evaluating and identifying novel markers of vascular aging and CVD in underrepresented populations.

Blood Pressure Complexity Discriminates Pathological Beat-to-Beat Variability as a Marker of Vascular Aging.

BackgroundBeat‐to‐beat blood pressure variability (BPV) is associated with an increased risk of stroke but can be driven by both healthy physiological processes and failure of compensatory mechanisms. Blood pressure (BP) complexity measures structured, organized variations in BP, as opposed to random fluctuations, and its reduction may therefore identify pathological beat‐to‐beat BPV.Methods and ResultsIn the prospective, population‐based OXVASC (Oxford Vascular Study) Phenotyped Cohort with transient ischemic attack or minor stroke, patients underwent at least 5 minutes of noninvasive beat‐to‐beat monitoring of BP (Finometer) and ECG to derive the following: BPV (coefficient of variation) and complexity (modified multiscale entropy) of systolic BP and diastolic BP, heart rate variability (SD of R‐R intervals), and baroreflex sensitivity (BRS; Welch's method), in low‐ (0.04–0.15 Hz) and high‐frequency (0.15–0.4 Hz) bands. Associations between BPV or BP complexity with autonomic indexes and arterial stiffness were determined (linear regression), unadjusted, and adjusted for age, sex, and cardiovascular risk factors. In 908 consecutive, consenting patients, BP complexity was inversely correlated with BPV coefficient of variation (P<0.001) and was similarly reduced in patients with hypertension or diabetes (P<0.001). However, although BPV coefficient of variation had a U‐shaped relationship with age, BP complexity fell systematically across age quintiles (quintile 1: 15.1 [14.0–16.1] versus quintile 5: 13.8 [12.4–15.1]) and was correlated with markers of autonomic dysfunction (heart rate variability SD of R‐R intervals: r = 0.20; BRS low frequency: 0.19; BRS high frequency: 0.26) and arterial stiffness (pulse wave velocity: −0.21; all P<0.001), even after adjustment for clinical variables (heart rate variability SD of R‐R intervals: 0.12; BRS low frequency and BRS high frequency: 0.13 and 0.17; and pulse wave velocity: −0.07; all P<0.05).ConclusionsLoss of BP complexity discriminates BPV because of pathological failure of compensatory mechanisms and may represent a less confounded and potentially modifiable risk factor for stroke.

Arterial Stiffness in Type 1 Diabetes: The Case for the Arterial Wall Itself as a Target Organ.

Arterial stiffness (AS) integrates the cumulative burden of known and unknown cardiovascular risk factors on the elastic wall of large arteries along the lifespan of an individual. As a marker of vascular aging, AS is an independent predictor of cardiovascular events and improves cardiovascular risk prediction when added to the Framingham Risk Score. In addition, AS may affect the microvasculature and promote the development of microvascular complications. Its impact on both the macro- and microvasculature has led to the concept that the arterial wall itself should be considered as a target organ. Here, we review the biological and clinical consequences of AS on the macro- and microvasculature and the measurement of AS in routine clinical practice. We also discuss the pathophysiological mechanisms underpinning AS development using diabetes and, in particular, type 1 diabetes, as a disease model with a high risk of cardiovascular events and microvascular complications that are accelerated by AS.

Arterial Stiffness and Vascular Aging: Effects of Hypertension

This review highlights the relationship of age and arterial hypertension observed in the aging process. The main structural and functional changes underlying the increase in vascular stiffness are analyzed. The similarity of vascular changes in aging and arterial hypertension was noted. The negative effect of increased central blood pressure on target organs is considered. Attention is paid to the analysis of arterial stiffness as a marker of vascular aging. The parameters of the carotid-femoral pulse wave propagation velocity, the cardio-ankle vascular index (CAVI), the ankle-brachial index, the finger-brachial index, and the augmentation index were examined separately. The prognostic and clinical value of the parameters of vascular stiffness is considered. In particular, the clinical guidelines for arterial hypertension report the need to use arterial stiffness indicators to improve the accuracy of cardiovascular risk stratification, especially in medium-risk patients. Measurement of vascular stiffness and central aortic pressure should be recommended as one of the methods for stratifying cardiovascular risk in patients with intermediate SCORE risk, as well as in those whose target organ damage was not detected by routine methods. The article also notes the independent diagnostic and prognostic value of the CAVI.

AGE-SPECIFIC ACUTE CHANGES IN CAROTID-FEMORAL PULSE WAVE VELOCITY DURING HEAD-UP TILTING

Objective: Hydrostatic blood pressure (BP) gradient following changes in body posture may generate concomitant, age-dependent, increases in aortic stiffness. We analyzed the relationship between BP gradient, measured during head-up body tilting, and related changes in carotid-femoral pulse wave velocity (cf-PWV) at different age ranges, with the aim to separate the BP-dependent and BP-independent components of cf-PWV. Design and method: cf-PWV and other hemodynamic parameters were measured in 30 healthy individuals during head-up tilting at 0°, 30° and 60°. BP was taken at the upper arm, constantly kept at heart level. Aortic BP was reconstructed from radial tonometry (SphygmoCor). Stiffness index β0 was estimated at 0° (Spronck et al, J Hypertens 2017;35:98–104). We assumed that: from MRI studies (Sugawara et al, Am J Hypertens. 2016;29:1237–1244), the effective cf-PWV travel distance (ETD, 80% of straight carotid-to-femoral distance) begins at heart level; the change in DBP along the aorta is predictable from the hydrostatic pressure gradient (0.73 mmHg/cm, Gavish et al, J Hypertens. 2011;29:2099–2104); cf-PWV and hydrostatic pressure relate linearly, hence predicted cf-PWV can be calculated as the average of aortic (using β0 and aortic DBP) and femoral (using β0 and femoral DBP, corresponding to aortic DBP + (ETD x sin(α)∗0.73)) PWVs. Results: cf-PWV and peripheral SBP increases during head-up body tilting were different between age groups, being more pronounced in the “old” (&gt;45 years) vs “young” group (both p for interaction &lt;0.05), whereas both central and peripheral DBP changes were not influenced by age (Figure, panel left). Central SBP was not affected by tilt angles. When cf-PWV gradient measured by applanation tonometry (observed), was compared with that predicted from estimated DBP gradient (predicted), the difference in observed-vs-predicted PWV gradient increased non-linearly as a function of age (R2 for quadratic trend=0.38, p &lt; 0.01, p vs linear=0.04, Figure panel right). Conclusions: Under a hydrostatic pressor gradient, the pulse wave travelling along the aorta undergoes positive acceleration which, for any given pressor change, increases non-linearly as a function of age. The evaluation of aortic pulse wave acceleration induced by pressor gradient may be of clinical relevance as a marker of vascular ageing.

Abstract 17467: Early Vascular Aging Predicts the Incidence of Diabetes in Hypertensives

Introduction: Diabetes is associated with vascular aging. Arterial stiffness, a marker of vascular aging, is an independent predictor of cardiovascular events and mortality. However, the role of arterial stiffness in the incidence of diabetes has not been investigated. Hypothesis: We sought to investigate the role of carotid-femoral pulse wave velocity (PWV) in the prediction of incident diabetes in hypertensives and hypertensives under treatment with statins. Methods: 376 never-treated hypertensives (mean age 53±13 years, 175 females) without a known history of diabetes or cardiovascular disease at baseline, were included in the study. Markers of target organ damage [carotid-femoral PWV, aortic augmentation index corrected for heart rate (AIx@75) and estimated glomerular filtration rate (eGFR)] were evaluated at baseline in all patients. eGFR was estimated using the Cockcroft-Gault formula. Hemoglobin A1c (HbA1c) and blood glucose were measured in venous blood samples. Patients were followed-up prospectively for the incidence of diabetes as defined by the American Diabetes Association criteria. 139 patients received statins during follow-up. Results: During a median of 13.6 years follow-up, 55 patients (13.4%) patients were diagnosed with diabetes. In multivariable logistic regression analysis, higher PWV (Odds Ratio [OR] = 1.29, 95% Confidence intervals [CI]: 1.02-1.63, P = 0.034) was associated with a higher risk of incident diabetes, which was independent of relevant confounders. In further analysis, receiver operating characteristic (ROC) curves were generated to evaluate the ability of PWV to discriminate subjects with diabetes. The area under the curve (AUC) and 95% CIs of the ROC curve was AUC=0.67 (95% CI: 0.59-0.74, P&lt;0.001) for PWV. In the subgroup of patients under treatment with statins, higher PWV (OR = 1.69, 95% CI: 1.19-2.40, P = 0.004) was also independently associated with a higher risk of incident diabetes. AIx@75 was not associated with the incidence of diabetes. Conclusions: Higher arterial stiffness, a marker of early vascular aging, is associated with the incidence of diabetes and also can identify subjects under treatment with statins that are more likely to present with diabetes in the future.

Orthostatic hypotension: a marker of blood pressure variability and arterial stiffness: a cross-sectional study on an elderly population: the 3-City study.

Orthostatic hypotension, blood pressure (BP) variability, and arterial stiffness are three markers of cardiovascular risk beyond the average BP. However, the relationships between these three parameters are not well known. To examine the relationships between orthostatic hypotension, BP variability, and arterial stiffness. In the Three-City study, a sample of 1151 elderly participants (mean age = 80 ± 3 years) was screened for orthostatic hypotension, undertook home BP and pulse wave velocity (PWV) measurements. We performed logistic regression analyses to look at the associations between orthostatic hypotension and both day-to-day (D-to-D) BP variability quartiles and PWV quartiles. Orthostatic hypotension was detected in 210 participants who were more likely to be hypertensive, exhibit higher BP variability and have increased arterial stiffness. In the multivariate logistic regression analysis, the frequency of orthostatic hypotension increased by 20% with every quartile of D-to-D SBP variability and by 20% with every quartile of PWV. PWV and D-to-D BP variability were not associated. In stratified analysis, the use of beta-blocker changes these relationships: orthostatic hypotension was not associated to PWV anymore but its association with D-to-D SBP variability was apparently stronger. In this large sample of elderly individuals, orthostatic hypotension was independently associated with both BP variability and PWV. BP variability being more indicative of a baroreflex dysfunction and PWV being a marker of vascular ageing, these two components would participate to the orthostatic hypotension mechanisms.

Awareness of major cardiovascular risk factors and its relationship with markers of vascular aging: Data from the Brisighella Heart Study

Background and aimGeneral population awareness about cardiovascular risk factors is usually low. The aim of the present study was to evaluate the vascular aging of subjects aware and not aware to be hypertensive, hypercholesterolemic, hypertriglyceridemic or diabetics in a general population sample. Methods and resultsWe interviewed 1652 subjects without atherosclerotic cardiovascular diseases (M: 46.6%, F: 53.4%) about their awareness of hypertension, hypercholesterolemia, hypertriglyceridemia or type 2 diabetes. Then we compared the augmentation index and pulse wave velocity of subjects aware and not aware of the investigated cardiovascular risk factors. 1049 participants declared not to be hypertensive, while 32 were not sure. Among them, respectively, 23.5% and 50% were hypertensive. Subjects not aware of their hypertension had significantly higher aortic blood pressure than aware ones (p < 0.001). 841 participants declared not to be hypercholesterolemic, while 60 were not sure. Among them, respectively, 18.1% and 40% were hypercholesterolemic. Subjects not aware of their hypercholesterolemia had significantly higher augmentation index than the aware ones (p < 0.05). 1226 participants declared not to be hypertriglyceridemic, while 200 were not sure. Among them, respectively, 19.2% and 44% were hypertriglyceridemic. Subjects not aware of their hypertriglyceridemia had significantly higher TG levels aware ones (p < 0.05), although this seemed to not related to increased arterial stiffness. 1472 participants declared not to be diabetic, while 20 were not sure. Among them, respectively, 2.0% and 25.0% were diabetics. Subjects not aware of their diabetes had significantly higher augmentation index than the aware ones (p < 0.05). ConclusionsIn conclusion, the lack of awareness of hypertension and hypercholesterolemia is relatively frequent in the general population and is associated to significantly higher arterial stiffness.

Association between different lipid parameters and aortic stiffness: clinical and therapeutic implication perspectives.

Recommendations about lipid parameters varied from different guidelines. Aortic stiffness is a marker of vascular aging and may reflect occurrence of cardiovascular diseases. Aortic pulse wave velocity (PWV), a marker of aortic stiffness, can be measured by applanation tonometry. The purpose of our study was to test the associations between lipid parameters and aortic stiffness. A cross-sectional study was conducted from 2012 to 2017, 603 participants were included: 517 patients and 86 'healthy' individuals used to calculate the theoretical PWV. Lipid parameters, including total cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL, total cholesterol/HDL ratio, triglycerides/HDL ratio and LDL/HDL ratio were measured. Theoretical PWV can be calculated according to age, sex, mean blood pressure and heart rate, allowing to form an individual PWV index [(measured PWV - theoretical PWV)/theoretical PWV]. PWV index [(measured PWV - theoretical PWV)/theoretical PWV] greater than 0 defined aortic stiffness. In multiple linear regression analyses, total cholesterol (P = 0.03), LDL (P = 0.04), non-HDL (P = 0.03), total cholesterol/HDL (P = 0.01) and LDL/HDL (P = 0.03) were significantly correlated with PWV. In multiple logistic regression analyses, non-HDL [OR = 1.12 (1.04-1.20), P = 0.01, R value: 0.224], total cholesterol/HDL [OR = 1.12 (1.02-1.22), P = 0.03, R value: 0.219] and total cholesterol [OR = 1.11 (1.01-1.23), P = 0.03, R value: 0.209] were significantly associated with aortic stiffness. Non-HDL, total cholesterol and total cholesterol/HDL were significantly associated with aortic stiffness than others and especially individually lipid parameters. This result should be considered in future clinical lipid-lowering trials.

Application of a decision tree to establish factors associated with a nomogram of aortic stiffness.

Aortic stiffness is a marker of vascular aging and may reflect occurrence of cardiovascular (CV) diseases. Aortic pulse wave velocity (PWV), a marker of aortic stiffness, can be measured by applanation tonometry. A nomogram of aortic stiffness was evaluated by the calculation of PWV index. Theoretical PWV can be calculated according to age, gender, mean blood pressure, and heart rate, allowing to form an individual PWV index [(measured PWV - theoretical PWV)/theoretical PWV]. The purpose of the present cross-sectional study was to investigate the determinants of the PWV index, by applying a decision tree. A cross-sectional study was conducted from 2012 to 2017, and 597 individuals were included. A training decision tree was constructed based on seventy percent of these subjects (N=428). The remaining 30% (N=169) were used as the testing dataset to evaluate the performance of the decision trees. The input variables for the models were clinical and biochemical parameters. The different input variables remained in the model were diabetes, tobacco status, carotid plaque, albuminuria, C-reactive protein, total cholesterol, BMI, and previous CV diseases. For the validation decision model, the sensitivity, specificity, and accuracy values for identifying the related risk factors of PWV index were 70%, 78%, and 0.73. Since determinants of PWV index were all well-accepted CV risk factors, a nomogram of aortic stiffness could be considered as an integrator of CV risk factors on their duration of exposure and could be utilized to develop future programs for CV risk assessment and reduction strategies.

Age-associated features of oxidative stress as marker of vascular aging in comorbid course of hypertension and type 2 diabetes mellitus

Age-associated features of oxidative stress as marker of vascular aging in comorbid course of hypertension and type 2 diabetes mellitus

Telomere uncapping and vascular aging.

Although most telomere biology research continues to focus on telomere shortening, there is increasing evidence that telomere deprotection, or "uncapping," is more biologically and possibly clinically important. Telomeres form t-loops to prevent the chromosome ends from appearing as a double-stranded DNA break and initiating a DNA damage response. Breakdown of the t-loop structure, referred to as uncapping, can lead to cellular senescence, increased oxidative stress, and inflammation in tissues. In this review, we describe how telomere uncapping potentially leads to age-related vascular dysfunction and increased cellular senescence, oxidative stress, and inflammation. Importantly, we present evidence to argue that telomere uncapping is more biologically relevant than telomere shortening and a better marker of vascular aging and target for antiaging interventions.

P742 Arterial stiffness as a marker of vascular aging in IBD patients – a pilot study

P742 Arterial stiffness as a marker of vascular aging in IBD patients – a pilot study

Abstract P197: Structural and Functional Arterial Changes in Healthy Women Following Pregnancy

Background: Parity is associated with future maternal cardiovascular disease (CVD) risk in a J-shaped fashion. Markers of vascular aging and future CVD risk, such as common carotid artery intima-media thickness (CCA IMT) and inter-adventitial diameter (IAD), increase acutely during pregnancy. As reported previously, increased CCA IMT did not recede in the early postpartum period. This study aims to determine whether vascular changes during pregnancy persist beyond the initial postpartum period. Methods: This study is a follow-up to a prospective study that assessed vascular health in a cohort of 43 healthy women during a first pregnancy and at 6-8 weeks postpartum. Data on physical measures, biomarker assays, pregnancy outcomes, health history and CCA IMT and IAD via B-mode ultrasound were collected at a second post-partum visit 1-5 years following the index birth. Paired t-tests and multivariable linear regression were used to assess changes in vascular measures. Results: Sixteen participants with mean±SD age 32.4±4.4 years, BMI 25.6±3.1 kg/m 2 , cumulative breastfeeding time of 19.7±11.2 months and time from index delivery of 2.7±0.8 years completed the second postpartum visit. Eight of these women had ≥ 1 subsequent births. Compared to the third trimester, the decrease in IAD and increase in IMT observed early postpartum, persisted further out postpartum (figure). At the second postpartum visit, larger IAD was associated with higher blood pressure whereas thicker IMT was associated with less time since index birth, greater weight gain, shorter duration of breastfeeding, and lower insulin resistance (all p&lt;0.05). Conclusions: Markers of vascular aging did not consistently improve 1 to 5 years after delivery. Persistence of pregnancy related vascular effects suggest a possible mechanism linking increased CVD risk with parity. Prolonged breastfeeding and weight management following pregnancy may be modifiable lifestyle factors affecting future maternal CVD risk.

The role of retinal vessels caliber as a marker of vascular aging in large arteries.

To analyze the relationship between retinal vessel caliber and large arterial structure and function in a sample of the general population. A cross-sectional study was conducted among 229 participants from the EVIDENT trial (mean age 55.6±12.1 years, 61.1% women). Retinal photographs were digitized, temporal vessels were measured in an area of 0.5 to 1 disc diameter from the optic disc and the arterio-venous ratio (AVR) was estimated. Vascular structure and function were assessed by evaluating carotid intima-media thickness (IMT), pulse wave velocity (PWV), augmentation index (AIx), ankle brachial index and ambulatory arterial stiffness index. The mean AVR was 0.792 ± 0.082, calculated from an arterial caliber of 109.1 ± 12.5 μm and a venous caliber of 138.7 ± 15.4 μm. A total of 13.1% of the patients presented vascular damage. The AVR was inversely correlated with carotid IMT (r = -0.190, P < 0.01), PWV (r = -0.178, P < 0.01) and AIx (r = -0.187, P < 0.01). In a multiple linear regression analysis, the associations with IMT and with AIx remained after adjusting for possible confounders (β = -0.152, P = 0.026; and β = -18.1, P = 0.037, respectively), but the association with PWV was lost when blood pressure was added (β = -1.520, P = 0.215). In a logistic regression analysis, the odds ratio of the first tertile of mean AVR (<0.76) of having a vascular injury was 7.09 (95% confidence interval 1.78-28.17, P = 0.011) after adjusting for possible confounders. In the general population, lower AVR values are associated with increases in carotid IMT, AIx and PWV. AVR may be a good predictor of asymptomatic vascular damage in large arteries.