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Abstract Aims New tools are needed to identify heart failure (HF) risk earlier in its course. We evaluated the association of multidimensional cardiopulmonary exercise testing (CPET) phenotypes with subclinical risk markers and predicted long‐term HF risk in a large community‐based cohort. Methods and results We studied 2532 Framingham Heart Study participants [age 53 ± 9 years, 52% women, body mass index (BMI) 28.0 ± 5.3 kg/m2, peak oxygen uptake (VO2) 21.1 ± 5.9 kg/m2 in women, 26.4 ± 6.7 kg/m2 in men] who underwent maximum effort CPET and were not taking atrioventricular nodal blocking agents. Higher peak VO2 was associated with a lower estimated HF risk score (Spearman correlation r: −0.60 in men and −0.55 in women, P

Background The association of the American Heart Association's updated cardiovascular health score, the Life's Essential 8 (LE8), with cardiovascular disease (CVD) and death is not described in the FHS (Framingham Heart Study). Methods and Results We evaluated Framingham Offspring participants at examinations 2 and 6 (n=2888 and 1667; and mean age, 44 and 57 years, respectively), free of CVD with information on LE8 components. Using age‐sex–adjusted Cox models, we related LE8 and its change (examination 2 to examination 6) with CVD and death risk and compared associations with those of the Life's Simple 7 score. Mean LE8 score at examination 2 was 67 points (minimum, 26 points; maximum, 100 points). At both examinations, participants were reclassified to a different cardiovascular health status, depending on which method (LE8 versus Life's Simple 7) was used (60% of participants in ideal Life's Simple 7 status were in intermediate LE8 category). On follow‐up after examination 2 (median, 30 and 33 years for CVD and death, respectively), we observed 966 CVD events, and 1195 participants died. Participants having LE8≥68 (sample median) were at lower CVD and death risk compared with those with LE8

Background During exercise, a healthy arterial system facilitates increased blood flow and distributes it effectively to essential organs. Accordingly, we sought to understand how arterial stiffening might impair cardiorespiratory fitness in community‐dwelling individuals. Methods and Results Arterial tonometry and maximum effort cardiopulmonary exercise testing were performed on Framingham Heart Study participants (N=2898, age 54±9 years, 53% women, body mass index 28.1±5.3 kg/m2). We related 5 arterial stiffness measures (carotid‐femoral pulse wave velocity [CFPWV]: a measure of aortic wall stiffness; central pulse pressure, forward wave amplitude, characteristic impedance: measures of pressure pulsatility; and augmentation index: a measure of relative wave reflection) to multidimensional exercise responses using linear models adjusted for age, sex, resting heart rate, habitual physical activity, and clinical risk factors. Greater CFPWV, augmentation index, and characteristic impedance were associated with lower peak oxygen uptake (VO2; all P0.05). However, the CFPWV‐peak oxygen uptake relation was attenuated in individuals with obesity (P=0.002 for obesity*CFPWV interaction). Higher CPFWV, augmentation index, and characteristic impedance were also related to cardiopulmonary exercise testing measures reflecting adverse O2 kinetics and lower stroke volume and peripheral O2 extraction but not to ventilatory efficiency, a prognostic measure of right ventricular‐pulmonary vascular performance. Conclusions Our findings delineate relations of arterial stiffness and cardiorespiratory fitness in community‐dwelling individuals. Future studies are warranted to evaluate whether the physiological measures implicated here may represent potential targets for improving cardiorespiratory fitness in the general population.

Background Systolic blood pressure increases with age after midlife, particularly in women, and contributes to development of wide pulse pressure hypertension in middle‐aged and older adults. Relative contributions of aortic stiffness and premature wave reflection to increases in pulse pressure remain controversial. Methods and Results We evaluated visit‐specific values and change in key correlates of pulse pressure, aortic characteristic impedance, forward and backward wave amplitude, and global reflection coefficient, at 3 sequential examinations of the Framingham Generation 3 (N=4082), Omni‐2 (N=410), and New Offspring Spouse (N=103) cohorts (53% women). Data were analyzed using repeated‐measures linear mixed models adjusted for age, sex, and risk factor exposures. Pulse pressure increased markedly with age after midlife (age and age‐squared terms, P

Background Stiffness of the proximal aorta may play a critical role in adverse left ventricular (LV)–vascular interactions and associated LV diastolic dysfunction. In a community‐based sample, we sought to determine the association between proximal aortic stiffness measured by cardiovascular magnetic resonance (CMR) and several clinical measures of LV diastolic mechanics. Methods and Results Framingham Heart Study Offspring adults (n=1502 participants, mean 67±9 years, 54% women) with available 1.5T CMR and transthoracic echocardiographic measures were included. Measures included proximal descending aortic strain and aortic arch pulse wave velocity by CMR (2002–2006) and diastolic function (mitral Doppler E and A wave velocity, E wave area, and LV tissue Doppler e' velocity) by echocardiography (2005–2008). Multivariable linear regression analysis was used to relate CMR aortic stiffness measures to measures of echocardiographic LV diastolic function. All continuous variables were standardized. In multivariable‐adjusted regression analyses, aortic strain was inversely associated with E wave deceleration time (estimated β=−0.10±0.032, P=0.001), whereas aortic arch pulse wave velocity was inversely associated with E/A ratio (estimated β=−0.094±0.027, P=0.0006), E wave area (estimated β=−0.070±0.027, P=0.010), and e' (estimated β=−0.061±0.027, P=0.022), all indicating associations of higher aortic stiffness by CMR with less favorable LV diastolic function. Compared with men, women had a larger inverse relationship between pulse wave velocity and E/A ratio (interaction β=−0.085±0.031, P=0.0064). There was no significant effect modification by age or a U‐shaped (quadratic) relation between aortic stiffness and LV diastolic function measures. Conclusions Higher proximal aortic stiffness is associated with less favorable LV diastolic function. Future studies may clarify temporal relations of aortic stiffness with varying patterns and progression of LV diastolic dysfunction.

Background Measures of vascular dysfunction are related to adverse cardiovascular disease (CVD) outcomes in non‐Hispanic, White populations; however, data from Black individuals are limited. We aimed to investigate the associations between novel hemodynamic measures and prevalent CVD in a sample of Black individuals. Methods and Results Among older Black participants of the Jackson Heart Study, we assessed noninvasive vascular hemodynamic measures using arterial tonometry and Doppler ultrasound. We assessed 5 measures of aortic stiffness and wave reflection (carotid‐femoral pulse wave velocity, pulse wave velocity ratio, forward pressure wave amplitude, central pulse pressure, and augmentation index), and 2 measures of microvascular function (baseline and hyperemic brachial flow velocity). Using multivariable logistic regression models, we examined the relations between vascular hemodynamic measures and prevalent CVD. In models adjusted for traditional CVD risk factors, higher carotid‐femoral pulse wave velocity (odds ratio [OR],1.25; 95% CI, 1.01–1.55; P=0.04), lower augmentation index (OR, 0.84; 95% CI, 0.70–0.99; P=0.05), and lower hyperemic brachial flow velocity (OR, 0.77; 95% CI, 0.65–0.90; P=0.001) were associated with higher odds of CVD. After further adjustment for hypertension treatment, lower augmentation index (OR, 0.84; 95% CI, 0.70–0.99; P=0.04) and hyperemic brachial flow velocity (OR, 0.79; 95% CI, 0.67–0.94; P=0.006), but not carotid‐femoral pulse wave velocity (OR, 1.23; 95% CI, 0.99–1.051; P=0.06), were associated with higher odds of CVD. Conclusions In a sample of older Black individuals, more severe microvascular damage and aortic stiffness were associated with prevalent CVD. Further research on hemodynamic mechanisms that contribute to cardiovascular risk among older Black individuals is merited.

Background A higher circulating plasma ceramide ratio (C16:0/C24:0) is associated with an increased risk of heart failure, even after accounting for standard risk factors including lipid markers. However, the pathobiological mechanisms that underlie this association are incompletely understood. We tested the hypothesis that plasma ceramide ratio (C16:0/C24:0) is associated with adverse cardiac remodeling in the community. Methods and Results We evaluated 2652 Framingham Offspring Study participants (mean age, 66±9 years; 55% women) who attended their eighth examination cycle and underwent routine echocardiography and liquid chromatography–tandem mass spectrometry–based assays for circulating ceramide concentrations. We used multivariable linear regression models to relate C16:0/C24:0 (independent variable) to the following echocardiographic measures (dependent variables; separate models for each): left ventricular mass, left ventricular ejection fraction, left atrial emptying fraction, left atrial end‐systolic volume, E/e′ (a measure of left ventricular diastolic function), and left ventricular global circumferential and longitudinal strain by speckle‐tracking echocardiography. In multivariable‐adjusted analyses, higher C16:0/C24:0 per standard deviation increment was associated with lower left ventricular ejection fraction (0.991‐fold change in left ventricular ejection fraction; P=0.0004), worse global circumferential strain (β=0.34, P=0.004), higher left atrial end‐systolic volume (β=2.48, p

Background Excess transmission of pressure pulsatility caused by increased arterial stiffness may incur microcirculatory damage in end organs (target organ damage [TOD]) and, in turn, elevate risk for cardiovascular disease (CVD) events. Methods and Results We related arterial stiffness measures (carotid‐femoral pulse wave velocity, mean arterial pressure, central pulse pressure) to the prevalence and incidence of TOD (defined as albuminuria and/or echocardiographic left ventricular hypertrophy) in up to 6203 Framingham Study participants (mean age 50±15 years, 54% women). We then related presence of TOD to incident CVD in multivariable Cox regression models without and with adjustment for arterial stiffness measures. Cross‐sectionally, greater arterial stiffness was associated with a higher prevalence of TOD (adjusted odds ratios ranging from 1.23 to 1.54 per SD increment in arterial stiffness measure, P

Background Waveform parameters derived from pressure‐only Windkessel models are related to cardiovascular disease risk and could be useful for understanding arterial system function. However, prior reports varied in their adjustment for potential confounders. Methods and Results Carotid tonometry waveform data from 2539 participants (mean age 63±11 years, 58% women) of the Framingham Heart Study were used to derive Windkessel measures using pressure and assuming a linear model with fixed diastolic time constant (τdias) and variable asymptotic pressure (Pinf, median 54.5; 25th, 75th percentiles: 38.4, 64.9 mm Hg) or nonlinear model with inverse pressure‐dependent τdias and fixed Pinf (20 mm Hg). During follow‐up (median 15.1 years), 459 (18%) participants had a first cardiovascular disease event. In proportional hazards models adjusted for age, sex, total cholesterol, high‐density lipoprotein cholesterol, smoking, antihypertensive medication use, diabetes mellitus, and physician‐acquired systolic blood pressure, only the systolic time constant (τsys) derived from the nonlinear model was related to risk for cardiovascular disease events (hazard ratio=0.91 per 1 SD, 95% CI=0.84–0.99, P=0.04). When heart rate was added to the model, τsys (hazard ratio=0.92, CI=0.84–1.00, P=0.04) and reservoir pressure amplitude (hazard ratio=1.14, CI=1.01–1.28, P=0.04) were related to events. In contrast, measures derived from the linear model were not related to events in models that adjusted for risk factors including systolic blood pressure (P>0.31) and heart rate (P>0.19). Conclusions Our results suggest that pressure‐only Windkessel measures derived by using a nonlinear model may provide incremental risk stratification, although associations were modest and further validation is required.

Background Black individuals have greater risk for cardiovascular disease (CVD) than whites. Identifying CVD risk factors associated with abnormal aortic hemodynamics in blacks may optimize CVD prevention and treatment strategies. Methods and Results Jackson Heart Study participants underwent applanation tonometry (2011–2016) with assessment of carotid‐femoral pulse wave velocity (CFPWV) and forward wave amplitude (FWA). CVD risk factors were assessed during examination 3 (2009–2012). We examined the association of risk factors with binary and continuous CFPWV and FWA in multivariable stepwise models. We evaluated for effect modification by sex to determine differential associations of risk factors with aortic hemodynamics in men and women. We examined 1322 individuals (mean age 66±11 years, 66% women). Age was strongly associated with elevated CFPWV (odds ratio, 4.76; 95% confidence interval, 3.84–5.89 [P

Background Blacks have more severe endothelial dysfunction and aortic stiffening as compared with whites. We aimed to investigate the association between aortic stiffness and microvascular function in the black community. Methods and Results We assessed the association between forearm vascular reactive hyperemia (an indicator of microvascular function) and aortic stiffness in 1458 black participants (N=965 [66% women]; mean age: 66±11 years) in the Jackson Heart Study. We evaluated 2 measures of aortic stiffness: brachial pulse pressure and carotid‐femoral pulse wave velocity. Using high‐resolution ultrasound and Doppler, we evaluated brachial blood flow at baseline and during reactive hyperemia after 5 minutes of forearm ischemia. Multiple cardiovascular risk factors were significantly related to baseline and hyperemic brachial flow velocity. Women had lower baseline flow across the entire age spectrum. During hyperemia, we observed a significant age‐sex interaction for flow velocity (P=0.02). Female sex was protective against microvascular dysfunction among younger participants, but older women exhibited a greater attenuation of the hyperemic flow reserve. In multivariable models that adjusted for cardiovascular disease risk factors and mean arterial pressure, higher carotid‐femoral pulse wave velocity (β=−0.106±0.033; P=0.001 was related to lower baseline flow. However, during reactive hyperemia, elevated brachial pulse pressure (β=−0.070±0.031; P=0.03) and carotid‐femoral pulse wave velocity (β=−0.128±0.030; P

Background Adipokines mediate cardiometabolic risk associated with obesity but their role in the pathogenesis of obesity‐associated heart failure remains uncertain. We investigated the associations between circulating adipokine concentrations and echocardiographic measures in a community‐based sample. Methods and Results We evaluated 3514 Framingham Heart Study participants (mean age 40 years, 53.8% women) who underwent routine echocardiography and had select circulating adipokines measured, ie, leptin, soluble leptin receptor, fatty acid–binding protein 4, retinol‐binding protein 4, fetuin‐A, and adiponectin. We used multivariable linear regression, adjusting for known correlates (including weight), to relate adipokine concentrations (independent variables) to the following echocardiographic measures (dependent variables): left ventricular mass index, left atrial diameter in end systole, fractional shortening, and E/e′. In multivariable‐adjusted analysis, left ventricular mass index was inversely related to circulating leptin and fatty acid–binding protein 4 concentrations but positively related to retinol‐binding protein 4 and leptin receptor levels (P≤0.002 for all). Left atrial end‐systolic dimension was inversely related to leptin but positively related to retinol‐binding protein 4 concentrations (P≤0.0001). E/e′ was inversely related to leptin receptor levels (P=0.0002). We observed effect modification by body weight for select associations (leptin receptor and fatty acid–binding protein 4 with left ventricular mass index, and leptin with left atrial diameter in end systole; P

BackgroundLeft ventricular diastolic dysfunction (DD) is common, particularly in women and older individuals, and it is associated with adverse cardiovascular outcomes. We evaluated the impact of age‐ and sex‐specific diagnostic criteria on the assessment of DD in the community‐based Framingham Heart Study. Methods and ResultsWe estimated age‐ and sex‐specific reference limits for echocardiographic measures of DD in a healthy reference subsample (N=2355, mean age 44 years, 66% women). The prevalence, correlates, and association with future cardiovascular disease were compared for DD using age‐ and sex‐specific versus single cut point reference limits in a broad sample (N=6102, mean age 50 years, 56% women). Using age‐ and sex‐specific criteria, DD was present in ≈25% to 30% of individuals across age groups, and it was directly associated with a number of modifiable risk factors. In contrast, with single cut point criteria, age was the primary determinant of DD. During follow‐up (mean 7.9±2.2 years), incident cardiovascular disease occurred in 213 of 5770 individuals. Using age‐ and sex‐specific criteria, mild and moderate‐severe DD were associated with 50% (95% confidence interval, 1.09–2.05) and 65% (95% confidence interval, 1.14–2.38) higher incidences of cardiovascular disease, respectively, in age‐ and sex‐adjusted analyses. With single cut point criteria, moderate‐severe DD (hazard ratio, 1.66; 95% confidence interval, 1.05–2.61), but not mild DD (hazard ratio, 0.94; 95% confidence interval, 0.63–1.40), was associated with incident cardiovascular disease. ConclusionsAge‐ and sex‐specific reference limits may result in DD assessments that are less dependent on age, more robustly related to modifiable risk factors, and are more closely associated with incident cardiovascular disease.

BackgroundLeft atrial (LA) size, a marker of atrial structural remodeling, is associated with increased risk for atrial fibrillation (AF) and cardiovascular disease (CVD). LA function may also relate to AF and CVD, irrespective of LA structure. We tested the hypothesis that LA function index (LAFI), an echocardiographic index of LA structure and function, may better characterize adverse LA remodeling and predict incident AF and CVD than existing measures. Methods and ResultsIn 1786 Framingham Offspring Study eighth examination participants (mean age, 66±9 years; 53% women), we related LA diameter and LAFI (derived from the LA emptying fraction, left ventricular outflow tract velocity time integral, and indexed maximal LA volume) to incidence of AF and CVD on follow‐up. Over a median follow‐up of 8.3 years (range, 7.5–9.1 years), 145 participants developed AF and 139 developed CVD. Mean LAFI was 34.5±12.7. In adjusted Cox regression models, lower LAFI was associated with higher risk of incident AF (hazard ratio=3.83, 95% confidence interval=2.23–6.59, lowest [Q1] compared with highest [Q4] LAFI quartile) and over 2‐fold higher risk of incident CVD (hazard ratio=2.20, 95% confidence interval=1.32–3.68, Q1 versus Q4). Addition of LAFI, indexed maximum LA volume, or LA diameter to prediction models for AF or CVD did not significantly improve model discrimination for either outcome. ConclusionsIn our prospective investigation of a moderate‐sized community‐based sample, LAFI, a composite measure of LA size and function, was associated with incident AF and CVD. Addition of LAFI to the risk prediction models for AF or CVD, however, did not significantly improve their performance.

BackgroundRelations of orthostatic change in blood pressure with brain structure and function have not been studied thoroughly, particularly in younger, healthier individuals. Elucidation of factors that contribute to early changes in brain integrity may lead to development of interventions that delay or prevent cognitive impairment. Methods and ResultsIn a sample of the Framingham Heart Study Third Generation (N=2119; 53% women; mean age±SD, 47±8 years), we assessed orthostatic change in mean arterial pressure (MAP), aortic stiffness (carotid‐femoral pulse wave velocity), neuropsychological function, and markers of subclinical brain injury on magnetic resonance imaging. Multivariable regression analyses were used to assess relations between orthostatic change in MAP and brain structural and neuropsychological outcomes. Greater orthostatic increase in MAP on standing was related to better Trails B‐A performance among participants aged

Background Microvascular dysfunction is a marker of early vascular disease that predicts cardiovascular events. Whether metabolically healthy obese individuals have impaired microvascular function remains unclear. The aim of this study was to evaluate the relation of obesity phenotypes stratified by metabolic status to microvascular function. Methods and Results We meta‐analyzed aggregate data from 3 large cohorts (Brazilian Longitudinal Study of Adult Health, the Framingham Heart Study, and the Gutenberg Heart Study; n=16 830 participants, age range 19–90, 51.3% men). Regression slopes between cardiovascular risk factors and microvascular function, measured by peripheral arterial tonometry (PAT), were calculated. Individuals were classified as normal‐weight, overweight, or obese by body mass index (BMI) and stratified by healthy or unhealthy metabolic status based on metabolic syndrome using the ATP‐III criteria. Male sex, BMI, and metabolic risk factors were associated with higher baseline pulse amplitude and lower PAT ratio. There was stepwise impairment of vascular measures from normal weight to obesity in both metabolic status strata. Metabolically healthy obese individuals had more impaired vascular function than metabolically healthy normal‐weight individuals (baseline pulse amplitude 6.12±0.02 versus 5.61±0.01; PAT ratio 0.58±0.01 versus 0.76±0.01, all P

BackgroundAortic stiffness impairs optimal ventricular–vascular coupling and left ventricular systolic function, particularly in the long axis. Left ventricular global longitudinal strain (GLS) has recently emerged as a sensitive measure of early cardiac dysfunction. In this study, we investigated the relation between aortic stiffness and GLS in a large community‐based sample. Methods and ResultsIn 2495 participants (age 39–90 years, 57% women) of the Framingham Offspring and Omni cohorts, free of cardiovascular disease, we performed tonometry to measure arterial hemodynamics and echocardiography to assess cardiac function. Aortic stiffness was evaluated as carotid–femoral pulse wave velocity and as characteristic impedance, and GLS was calculated using speckle tracking–based measurements. In multivariable analyses adjusting for age, sex, height, systolic blood pressure, augmentation index, left ventricular structure, and additional cardiovascular risk factors, increased carotid–femoral pulse wave velocity (B±SE: 0.122±0.030% strain per SD, P

BackgroundThe presence and implications of abnormal arterial stiffness, a potential independent predictor of outcomes, in community‐dwelling treated hypertensives is unknown. Furthermore, limited data exist regarding the risk of cardiovascular disease (CVD) associated with arterial stiffness across the entire range of blood pressure. Methods and ResultsWe measured carotid‐femoral pulse wave velocity (PWV) and classical CVD risk factors in 2127 community‐dwelling participants (mean age 60 years, 57% women) of The Framingham Offspring Cohort. The participants were divided into 4 groups according to hypertension (yes/no, defined as blood pressure ≥140/90 mm Hg or use of antihypertensive treatment) and PWV status (high/low based on age‐ and sex‐specific median values) and followed up for CVD events (CVD death, myocardial infarction, unstable angina, heart failure, and stroke). Sixty percent (233 of 390) of controlled and 90% (232 of 258) of uncontrolled treated hypertensives had high PWV. The multivariable‐adjusted risk for CVD events (n=248, median follow‐up 12.6 years) rose from normotension with low PWV (reference) to normotension with high PWV (hazard ratio 1.29, 95% CI 0.83–2.00) and from hypertension with low PWV (hazard ratio 1.54, 95% CI 1.01–2.36) to hypertension with high PWV (hazard ratio 2.25, 95% CI 1.54–3.29). ConclusionsA substantial proportion of treated hypertensives have high arterial stiffness, a finding that may explain some of the notable residual CVD risk associated with even well‐controlled hypertension. High PWV is associated with a trend towards increasing CVD risk in both nonhypertensives and hypertensives, a finding that may support the use of arterial stiffness measurements in both populations.

BackgroundFibroblast growth factor 23 (FGF23) is emerging as a novel biomarker of bone metabolism, chronic kidney disease, and cardiovascular disease (CVD). However, its clinical correlates and potential predictive role in a community‐based setting are incompletely understood. Methods and ResultsWe evaluated participants of the Framingham Heart Study (seventh examination cycle of the Offspring cohort plus second examination cycle of the multiethnic Omni cohort) to identify clinical correlates of plasma FGF23 (N=3236) and examine its cross‐sectional association with vascular function (N=2209), and longitudinal association with 10‐year incidence of CVD (N=2823), and all‐cause mortality (N=3223).Circulating FGF23 concentrations were positively related to African‐American and Asian ethnicity, waist circumference, current smoking, serum glucose, history of CVD, and antihypertensive medication use; and negatively related to male sex, hormone replacement therapy, and estimated glomerular filtration rate. Multivariable‐adjusted cross‐sectional analyses showed no consistent association of FGF23 with vascular function measures. During a median follow‐up time of 10.8 years, 347 incident CVD events and 412 deaths occurred. Multivariable‐adjusted Cox regression models revealed a positive association of FGF23 with all‐cause mortality (hazard ratio [HR] per SD increase, 1.31; 95% CI, 1.20–1.42), but not with incident CVD (HR per SD increase, 1.05; 95% CI, 0.94–1.17). ConclusionsIn our large, community‐based sample, FGF23 was associated with mortality risk, but not with vascular function or incident CVD.

BackgroundThe differing relations of steady and pulsatile components of central hemodynamics and aortic stiffness with cardiac dimensions and function have not been fully elucidated. Methods and ResultsCentral hemodynamics and carotid‐femoral pulse wave velocity (CFPWV, a measure of aortic stiffness) were measured by arterial tonometry in 5799 participants of the Framingham Heart Study (mean age 51 years, 54% women) and related to echocardiographic left ventricular (LV) dimensions and systolic and diastolic function using multivariable‐adjusted partial Pearson correlations. Mean arterial pressure (MAP, steady component of central blood pressure) was associated positively with LV wall thickness (r=0.168; P

Background Aortic stiffening begins in youth and antedates future hypertension. In adults, excess weight, systemic inflammation, dyslipidemia, insulin resistance, neurohormonal activation, and altered adipokines are implicated in the pathogenesis of increased aortic stiffness. In adolescents, we assessed the relations of comprehensive measures of aortic stiffness with body mass index (BMI) and related but distinct circulating biomarkers. Methods and Results A convenience sample of 246 adolescents (mean age, 16±2 years; 45% female, 24% Black, and 43% Hispanic) attending primary care or preventive cardiology clinics at 2 tertiary hospitals was grouped as normal weight (N=98) or excess weight (N=148, defined as BMI ≥age‐ and sex‐referenced 85th percentile). After an overnight fast, participants underwent anthropometry, noninvasive arterial tonometry, and assays for serum lipids, CRP (C‐reactive protein), glucose, insulin, renin, aldosterone, and leptin. We used multivariable linear regression to relate arterial stiffness markers (including carotid‐femoral pulse wave velocity) to BMI z score and a biomarker panel. Carotid‐femoral pulse wave velocity was higher in excess weight compared with normal weight group (5.0±0.7 versus 4.6±0.6 m/s; P