Vascular Age: A narrative review of assessment methods, clinical applications, and future directions.

P1553Differential association between vascular and chronological age with cardiovascular outcomes

Estimating Is Not Measuring: The Lessons About Estimated Pulse Wave Velocity.

Pulse wave velocity is an established marker of early vascular aging but may also help identifying individuals with supernormal vascular aging. We tested the hypothesis that individuals with the largest difference (Δ-age) between chronological and vascular age show the lowest rate of cardiovascular events and may thus be defined as supernormal vascular aging. Vascular age was defined as the predicted age in the best fitting multivariable regression model including classical risk factors and treatment and pulse wave velocity, in a subset of the Reference Values for Arterial Stiffness Collaboration Database (n=3347). Δ-age was then calculated as chronological age minus vascular age, and the 10th and 90th percentiles were used to define early (Δ-age<-5.7 years), normal (Δ-age -5.7 to 6.8 years) and supernormal vascular aging (Δ-age>6.8 years). The risk for fatal and nonfatal cardiovascular events associated with vascular aging categories was investigated in the Malmö Diet and Cancer Study cohort (n=2642). In the Malmö Diet and Cancer Study Cohort (6.6-year follow-up, 286 events), Δ-age was significantly (P<0.01) and inversely associated with cardiovascular events. Compared with normal vascular aging, supernormal vascular aging had lower risk (hazard ratio, 0.59 [95% CI, 0.41-0.85]), whereas early vascular aging had higher risk (hazard ratio, 2.70 [95% CI, 1.55-4.70]) of cardiovascular events, in particular coronary events. There was no significant association with all-cause mortality. This study represents the first validation of the clinical significance of the supernormal vascular aging concept, based on prospective data. Its further characterization may help discovering novel protective molecular pathways and providing preventive strategies for successful vascular aging.

Vascular age (VA) as a surrogate of chronological age can improve cardiovascular risk prediction. This study examines which vascular age calculated by brachial-ankle pulse wave velocity (baPWV) or carotid-femoral pulse wave velocity (cfPWV) has a stronger association with the risk of cardiovascular events. This prospective study included 5723 participants from a community-based atherosclerosis cohort in Beijing, China. VA was defined as the predicted age in a multivariable regression model, including classical cardiovascular risk factors, treatment, and pulse wave velocity (baPWV or cfPWV). Residuals by regressing vascular age on chronological age were defined as ∆-age, and the 10th and 90th percentiles of ∆-age were used as cutoffs to define supernormal vascular aging, normal vascular aging, and early vascular aging, respectively. During the median 3.1-year follow-up period, 173 (3.0%) composite endpoints were observed. After adjusting for age and sex, ∆-age calculated by baPWV was significantly associated with cardiovascular risk (hazard ratio [HR]: 1.05, 95% confidence interval [CI]: 1.01–1.09, p = 0.025). After adjusting for traditional cardiovascular risk factors, early vascular aging group calculated by baPWV had an increased cardiovascular risk (HR: 1.84, 95% CI: 1.25–2.73, p = 0.002), compared with the normal vascular aging group. In contrast, no significant results were observed in the analyses of VA calculated by cfPWV. Since baPWV is a simple and convenient method, VA calculated by baPWV is more valuable for cardiovascular disease risk prediction of large sample population.The association between VA based on baPWV or cfPWV and MACE. EVA early vascular aging, normal VA normal vascular aging, SUPERNOVA supernormal vascular aging.

Early vascular ageing contributes to cardiovascular (CV) morbidity and mortality. There are different possibilities to calculate vascular age including methods based on CV risk scores, but different methods might identify different subjects with early vascular ageing. We aimed to compare SCORE and Framingham Risk Score (FRS)-based vascular age calculation methods on subjects that were involved in a national screening program in Hungary. We also aimed to compare the distribution of subjects identified with early vascular ageing based on estimated pulse wave velocity (ePWV). The Three Generations for Health program focuses on the development of primary health care in Hungary. One of the key elements of the program is the identification of risk factors of CV diseases. Vascular ages based on the SCORE and FRS were calculated based on previous publications and were compared with chronological age and with each other in the total population and in patients with hypertension or diabetes. ePWV was calculated based on a method published previously. Supernormal, normal, and early vascular ageing were defined as <10%, 10-90%, and >90% ePWV values for the participants. In total, 99,231 subjects were involved in the study, and among them, 49,191 patients had hypertension (HT) and 15,921 patients had diabetes (DM). The chronological age of the total population was 54.0 (48.0-60.0) years, while the SCORE and FRS vascular ages were 59.0 (51.0-66.0) and 64.0 (51-80) years, respectively. In the HT patients, the chronological, SCORE, and FRS vascular ages were 57.0 (51.0-62.0), 63.0 (56.0-68.0), and 79.0 (64.0-80.0) years, respectively. In the DM patients, the chronological, SCORE, and FRS vascular ages were 58.0 (52.0-62.0), 63.0 (56.0-68.0), and 80.0 (76.0-80.0) years, respectively. Based on ePWV, the FRS identified patients with an elevated vascular age with high sensitivity (97.3%), while in the case of the SCORE, the sensitivity was much lower (13.3%). In conclusion, different vascular age calculation methods can provide different vascular age results in a population-based cohort. The importance of this finding for the implementation in CV preventive strategies requires further studies.

Objective: Early vascular ageing contributes to cardiovascular (CV) morbidity and mortality. There are different possibilities to calculate vascular age including methods based on CV risk scores, but different methods might identify different subjects with early vascular ageing. We aimed to compare SCORE and Framingham Risk Score (FRS)-based vascular age calculation methods on subjects that were involved into a national screening program in Hungary. We also aimed to compare the distribution of subjects identified with early vascular ageing based on estimated pulse wave velocity (ePWV). Design and method: The Three Generations for Health program focuses on the development of primary health care in Hungary. One of the key elements of the program is the identification of risk factors of CV diseases. Vascular ages based on SCORE and FRS were calculated based on previous publications and were compared with chronological age and with each other in the total population and in patients with hypertension or diabetes. ePWV was calculated based on a method published previously. Supernormal, normal, and early vascular ageing were defined as &lt;10%, 10-90% and &gt;90% ePWV values of the participants. Results: 99 231 subjects were involved in the study and among them 49 191 patients had hypertension (HT) and 15 921 patients had diabetes (DM). Chronological age of the total population was 54.0 (48.0 – 60-0) years, while SCORE and FRS vascular ages were 59.0 (51.0 – 66.0) and 64.0 (51-80) years, respectively. In HT patients chronological, SCORE and FRS vascular ages were 57.0 (51.0 – 62.0), 63.0 (56.0 – 68.0) and 79.0 (64.0 – 80.0) years, respectively. In DM patients chronological, SCORE and FRS vascular ages were 58.0 (52.0 – 62.0), 63.0 (56.0 – 68.0) and 80.0 (76.0 – 80.0) years, respectively. Based on ePWV, FRS identified patients with elevated vascular age with high sensitivity (97.3%), while in case of SCORE, the sensitivity was much lower (13.3%). Conclusions: In conclusion, different vascular age calculation methods can provide different vascular age results in a population-based cohort. The importance of this finding for the implementation into CV preventive strategies requires further studies.

Comparison of the predicting value for incident cardiovascular events by vascular age based on brachial-ankle pulse wave velocity or carotid-femoral pulse wave velocity

Carotid intima-media thickness stratifies early and supernormal vascular aging phenotypes in the UK Biobank: implications for cardiovascular risk prediction

Advanced vascular aging in patients with paroxysmal atrial fibrillation - Data from RACE V

Objective: Pulse wave velocity (PWV) is an established marker of early vascular aging (EVA), but may also help identifying individuals with supernormal vascular aging (SUPERNOVA). Aim of this study is to test the hypothesis that individuals with the largest difference between chronological and vascular age (Delta-age), calculated from classical CV risk factors and PWV, show the lowest rate of CV events, and may thus be defined SUPERNOVA. Design and method: Vascular age was calculated according to the best fitting model for chronological age prediction, in the cross-sectional Reference Values for Arterial stiffness Collaboration Database (n = 11,406), for different age categories. The risk of fatal and non-fatal CV events associated with Delta-age was investigated in the longitudinal Malmö Diet and Cancer Study cohort (n = 2642). Delta-age deciles were used to define EVA (&lt;3.0 years), normal vascular ageing (VA, 3.0 to 8.8 years) and SUPERNOVA (&gt;8.8 years). Results: In the Reference Values Database, the most significant predictor of vascular age (full model r2 = 0.598) was PWV. In the Malmö Diet and Cancer Study Cohort (6.6-year follow-up, 286 events). Delta-age was significantly and inversely associated with CV events. Compared to normal VA, SUPERNOVA had lower risk [HR 0.55 (95%CI 0.36–0.82)], whereas EVA had higher risk [HR 2.88 (95%CI 1.88–4.40)]. There was no significant association with all-cause mortality. Conclusions: PWV proved to be useful to identify SUPERNOVA individuals. Further characterization of this extreme phenotype may help discovering novel protective molecular pathways and providing preventive strategies for successful vascular aging.

Introduction: Vascular aging (VA) refers to the progressive deterioration of vascular structure and function with age. Vascular age exceeding chronological age indicates higher cardiovascular risk. Indices such as brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness (cIMT), carotid plaque, and ankle-brachial index (ABI) are often used to assess VA. Research questions: The comparative performance of VA models constructed using these different indicators has not yet been evaluated. This study aimed to compare the cardiovascular risk predictive value of VA models based on baPWV, cIMT, carotid plaque, and ABI. Methods: This study included participants from a Chinese community-based prospective cohort, excluding those with baseline stroke or myocardial infarction. Vascular age was calculated from multivariable regression models incorporating traditional cardiovascular risk factors, medications, and a vascular index (baPWV, cIMT, carotid plaque, or ABI). Residuals between vascular age and chronological age were defined as ΔAge. VA phenotypes were classified as supernormal VA, normal VA (NVA), or early VA (EVA) based on the 10th and 90th percentiles of ΔAge. The endpoint was major adverse cardiovascular events (MACE), including cardiovascular mortality, nonfatal stroke, and nonfatal myocardial infarction. Restricted cubic spline analyses and Cox proportional hazards models were used to examine the association of ΔAge and VA phenotypes with MACE. Results: A total of 3,561 participants (mean chronological age: 58.7±8.5 years) were included. During a mean follow-up of 7.2±1.3 years, 294 (8.26%) participants experienced MACE. The VA model based on baPWV showed the highest explanatory power (R 2 = 0.505) (Table 1).ΔAge based on baPWV showed a backwards L-shape association with MACE (Figure 1A). After adjustment, each standard deviation increase in ΔAge based on baPWV was associated with a 14% higher risk of MACE (HR 1.14, 95% CI 1.01–1.27, P=0.027; Table 2). EVA group based on baPWV had a significantly higher risk of MACE compared with NVA group (HR 1.44, 95% CI 1.05–1.97, P=0.023; Table 3). In contrast, VA phenotypes by other indices were not significantly associated with MACE (Table 3). Conclusions: Vascular age based on baPWV demonstrated superior cardiovascular risk prediction versus models using cIMT, plaque, or ABI. baPWV may serve as the preferred method for vascular aging assessment in cardiovascular risk stratification.

Disentangling Arterial Stiffness and Blood Pressure

Primary hypertension may lead to early vascular ageing. We aimed to evaluate differences between expected vascular age based on pulse wave velocity (PWV)/carotid intima-media thickness (cIMT) and actual chronological age (CHA) in adolescents with primary hypertension. Three hundred and fifty-two children (median age of 15.5 years) with office hypertension and 64 normotensive healthy children of the same age underwent anthropometry, office and ambulatory blood pressure (BP), left ventricular mass index, cIMT, PWV, pulse wave analysis and biochemistry measurements. Vascular age was calculated using pooled pediatric and adult normative PWV and cIMT data. The difference between vascular age and CHA was calculated in relation to the 90th percentile for PWV (PWVAgeDiff90) and the 95th percentile for cIMT (cIMTAgeDiff95). One hundred and sixty-six patients had white-coat hypertension (WCH), 32 had ambulatory prehypertension (AmbPreHT), 55 had isolated systolic hypertension with normal central SBP (ISH+cSBPn), 99 had elevated office, ambulatory and cSBP (true hypertension, tHT). The differences between vascular age (both PWV and cIMT based) and CHA were significantly higher in AmbPreHT and tHT compared with normotension, WCH and ISH+cSBPn. Median PWVAgeDidff90 was -3.2, -1.2, -2.1, +0.8 and +0.3 years in normotension, WCH, ISH+cSBPn, AmbPreHT and tHT, respectively. Median cIMTAgeDiff95 was -8.0, -6.3, -6.8, -3.8 and -4.3 years in normotension, WCH, ISH+cSBPn, AmbPreHT and tHT, respectively. Significant predictors of PWVAge90Diff were the DBP and serum cholesterol, whereas cSBP and augmentation index were significant predictors of cIMTAgeDiff95. Children with AmbPreHT and tHT show accelerated vascular age compared with their normotensive peers.

Whether chronological age affects the ability of vascular aging indicators to predict cardiovascular events risk remains unknown. This study sought to examine whether the predictability of vascular aging indicators is better in middle-aged participants than older participants. This prospective cohort study included 8163 participants from a community-based atherosclerosis cohort in Beijing, China. Vascular age (VA) was defined as the predicted age in a multivariable regression model including cardiovascular risk factors and pulse wave velocity. Residuals by regressing VA on chronological age were defined as ∆-age, reflecting vascular aging. We used Cox proportional hazard regression model to examine the association between ∆-age and the risk of cardiovascular events in different chronological age groups. Of all participants, 5691 (69.7%) were between 40 and 60 years old, and 2472 (30.3%) were over 60 years old. During a median 9.9-year follow-up period, 818 (10%) endpoints were observed. After adjusting for confounders, ∆-age was positively associated with the risk of cardiovascular events in middle-aged participants (HR: 1.13, 95% CI: 1.07-1.21; p < 0.001), whereas no significant association was observed in older participants (HR: 1.03, 95% CI: 0.99-1.06; p = 0.148). Interaction analysis in total participants showed that chronological age significantly modified the relationship between ∆-age and the risk of cardiovascular events (p = 0.017). Our findings indicate that the predictive ability of residuals between VA and chronological age for the risk of cardiovascular events is better in middle-aged people than that in older people. The VA assessment may be more valuable to the middle-aged population. The modifying effect of chronological age showed that vascular aging categories in middle-aged participants have stronger predictive ability for the risk of cardiovascular events than that in older participants. MACE, a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular mortality; normal VA, normal vascular aging; EVA, early vascular aging; SUPERNOVA, supernormal vascular aging.

Transforming growth factor, arterial stiffness and vascular aging in patients with uncontrolled arterial hypertension