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Background: Elastic arteries stiffen via 2 main mechanisms: (1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to changes in the vessel wall. It is unknown how these different mechanisms contribute to incident cardiovascular disease (CVD) events. Methods: The MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6814 men and women without CVD at enrollment, from 6 communities in the United States. MESA participants with B-mode carotid ultrasound and brachial blood pressure at baseline Exam in (2000–2002) and CVD surveillance (mean follow-up 14.3 years through 2018) were included (n=5873). Peterson’s elastic modulus was calculated to represent total arterial stiffness. Structural stiffness was calculated by adjusting Peterson’s elastic modulus to a standard blood pressure of 120/80 mm Hg with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. Results: In Cox models adjusted for traditional risk factors, load-dependent stiffness was significantly associated with higher incidence of CVD events (hazard ratio/100 mm Hg, 1.21 [95% CI, 1.09–1.34] P P =0.10). Analysis of participants who were normotensive (blood pressure P P =0.16). Conclusions: These results provide valuable new insights into mechanisms underlying the association between arterial stiffness and CVD. Load-dependent stiffness was significantly associated with CVD events but structural stiffness was not.

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.

Introduction: Elevated high-sensitive cardiac troponin T (hs-cTnT>14 ng/L) and low ankle-brachial index (ABI < 0.9) are known to be associated with cardiovascular diseases (CVD) but their joint effect on the risk of CVD events is unknown. Methods: We used data from the MESA and CHS among 10,900 participants free of CVD events at baseline (mean age 66.3 years, 44.7% males). Incident coronary heart disease (CHD) was defined as fatal or non-fatal myocardial infarction or revascularization and incident CVD was defined as CHD, transient ischemic attack, stroke, or atrial fibrillation. Hazard ratio (HR) and 95% CI was calculated from a Cox regression model. Interaction on the additive scale was assessed using relative excess risk due to interaction (RERI) and interaction on the multiplicative scale was assessed by Likelihood ratio (LR) test. Results: At baseline (2000-2002 for MESA and 1989-1990 for CHS), 10.2% of participants had elevated hs-cTnT and 7.5% had low ABI. During 26.1 years of total follow-up (median follow-up 18.4 years), there were 3,911 incident CVD events. The risk of CHD and CVD was higher in participants with both elevated hs-cTnT and low ABI [CHD HR: 2.1 (1.5, 2.9), CVD HR: 2.1 (1.7, 2.5)], only elevated hs-cTnT [CHD HR: 1.7 (1.4, 2.0), CVD HR: 1.6 (1.5, 1.8)], and only low ABI [CHD HR: 1.8 (1.5, 2.2), CVD HR: 1.5 (1.3, 1.7)] than those with unelevated hs-cTnT and normal ABI. Interaction on the multiplicative scale was observe in both adjusted and unadjusted models for CHD (unadjusted LR test p-value=0.002, adjusted LR test p-value=0.042) and only in unadjusted model for CVD (LR test p-value=0.001). No significant additive interaction was detected for both CHD and CVD (RERI p-value≥0.25 for unadjusted and adjusted models). Conclusion: Having both elevated cTnT and low ABI was associated more strongly with CVD events than only elevated cTnT or low ABI. Antagonistic multiplicative interaction was found indicating the observed joint effect of elevated cTnT and low ABI was smaller than the expected combined individual effects.

Introduction: Long-term blood pressure variability (BPV) refers to fluctuation in BP that occur over weeks, months and years. BPV has been identified as a risk factor for the development of subclinical and clinical cardiovascular events independent of mean BP. However, little is known about the factors associated with long-term BPV. We hypothesized that long-term BPV will vary by demographic, behavioral, anthropometric, lab, and clinical factors. Methods: Using data from the CARDIA study – a longitudinal population based cohort study, we investigated whether baseline demographics (age, sex, race, education); behavioral factors (smoking, alcohol intake, physical activity); anthropometric measures (height, weight, body mass index - BMI); lab markers (total cholesterol, high density lipoprotein cholesterol - HDL-C, low density lipoprotein cholesterol – LDL-C, triglycerides, fasting blood glucose, glomerular filtration rate - GFR); and history of asthma are associated with different indictors of long-term BPV. Variability independent of the mean (VIM) and coefficient of variation (CV) of BP were calculated to quantify within-individual long-term BPV from baseline to visit 9 across 30 years. A least absolute shrinkage and selection operator (lasso) linear regression was used to identify variables that may be associated with long-term BPV and multivariate linear regression models were used to assess magnitude of association. Results: Participants were 3,095 individuals who were not taking antihypertensive medication (mean age 24.6 years, 45.5% male and 56.9% white). Mean VIM was 8.5 mmHg (SD=3.7) for systolic and 7.1 mmHg (SD=3.2) for diastolic BP. Age, sex, race, education, physical activity, alcohol intake, pack-years of smoking, height, weight, triglyceride, LDL-C and asthma were potential correlates of VIM or CV of diastolic BP by the lasso model. In addition to those variables, total cholesterol, HDL-C, fasting glucose, and GFR were potential correlates of VIM or CV of systolic BP. Variables that significantly associated with VIM of systolic BP were: age (years) (β=0.11, p Conclusion: Identifying factors associated with long-term BPV can be useful to detect individuals who may be at a greater risk for future higher long-term BPV, which in turn is associated with greater cardiovascular risk.

Introduction: Optimal cardiovascular health (CVH), based on lifestyle and clinical factors, is associated with lower risk of CV events and this may occur partly by preventing progression of arterial stiffness. We assessed the association of optimal lifestyle and clinical factors with changes in arterial stiffness in the Multi-Ethnic Study of Atherosclerosis. Methods: Among 2,729 participants (aged 44-84 years, 46.5% male), number of optimal lifestyle factors (BMI 500 METS minutes/week) and optimal clinical factors (systolic BP Results: On average, DC decreased by 5.3% and YEM increased by 24.4% over ten years. Mean optimal lifestyle score was 10.2 (range: 0-19) and optimal clinical score was 9.1 (range: 0-15) across 5 visits. There was no difference in arterial stiffness progression between individuals in the upper quartiles of optimal lifestyle score and those in the lowest quartile. A higher score on optimal clinical factors was inversely associated with progression in arterial stiffness. Linear trends in the increase of DC (P-trend Conclusion: Optimal CVH was associated with less arterial stiffening, but only the clinical factors were predicting arterial stiffness and lifestyle factors had no influence on arterial stiffness.

Introduction: Diastolic blood pressure (DBP) instead of systolic BP (SBP) or pulse pressure (PP) has been suggested as an important predictor for cardiovascular disease (CVD) events in those Methods: Using data from the Coronary Artery Risk Development in Young Adults (CARDIA), which recruited healthy black and white young adults ages 18 to 30 years (n=4880) in 1985-1986, we assessed the associations between distinct BP components (SBP, DBP, mean arterial pressure [MAP], and PP) and incident CVD, defined as a composite endpoint of CVD deaths, myocardial infarction, angina, stroke, and heart failure. Results: The mean SBP, DBP, and PP at baseline (mean age 25 years) were 112, 69, and 43 mmHg in blacks (n=2473) and 109, 68, and 41 mmHg in whites (n=2407), respectively. Over 25 years of follow-up (100,291 person-years), 210 CVD events (140 events in blacks) occurred before the age of 55. Results from Cox proportional hazards models suggest that SBP was superior to DBP for predicting incident CVD in blacks, while DBP was superior to SBP in whites (Table). In blacks, CVD risk associated with higher PP was significant in models including MAP. Significant interactions were found between race and PP (P=0.02) but not SBP (P=0.14) and DBP (P=0.38) in association with incident CVD risk. Conclusions: In this long-term follow-up study, SBP outperformed DBP for predicting incident CVD in young blacks, while DBP outperformed SBP in young whites. In blacks, higher PP, representing large arterial stiffness, was associated with CVD risk. These racial differences may be attributable to earlier development of arterial stiffness in blacks compared with whites.

Introduction: In addition to average blood pressure (BP) values, BP variability has been suggested to be associated with lower cognitive function. It is unclear how long-term BP variability throughout young adulthood is associated with cerebrovascular structure (e.g., hippocampus) and function in midlife. Methods: Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, which recruited healthy young adults ages 18 to 30 years (mean age 25 years) in 1985-1986, we assessed average BP over visits and visit-to visit BP variability (average real variability [ARV], defined as the absolute differences of BP between successive BP measurements) during 25-year follow-up (8 visits). Normal brain volume, abnormal brain volume, brain integrity assessed by fractional anisotropy, and cerebral blood flow were calculated by 3-Tesla MRI at the Year 25 follow-up (n=557, 52.2 % women, and 34.5 % African Americans). Results: For the 557 participants, mean ARV of SBP was 7.8±3.1 mm Hg. Higher ARV of SBP was associated with lower normal total brain volume, gray matter, and hippocampus after adjustment for covariates including intracranial volume and average BP during follow-up (Table). Higher average SBP during follow-up was associated with higher abnormal brain volume and lower integrity in the whole brain and the white matter, and lower blood flow in the hippocampus. Conclusions: Long-term visit-to-visit BP variability for 25 years beginning in young adulthood was associated with midlife cerebrovascular structural and functional alterations, independent of average BP during follow-up. Focusing not only on BP values alone but also on visit-to-visit BPV may be important to identify younger adults who may be at risk for developing lower cognitive function later.