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Background Although there is research on the impact of social determinants of health (SDOHs) on cardiovascular health, most existing evidence is based on individual SDOH components. We evaluated the impact of cumulative SDOH burden on cardiovascular risk factors, subclinical atherosclerosis, and incident cardiovascular disease events. Methods and Results We included 6479 participants from the MESA (Multi‐Ethnic Study of Atherosclerosis). A weighted aggregate SDOH score representing the cumulative number of unfavorable SDOHs, identified from 14 components across 5 domains (economic stability, neighborhood and physical environment, community and social context, education, and health care system access) was calculated and divided into quartiles (quartile 4 being the least favorable). The impact of cumulative SDOH burden on cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking, and obesity), systemic inflammation, subclinical atherosclerosis, and incident cardiovascular disease was evaluated. Increasing social disadvantage was associated with increased odds of all cardiovascular risk factors except dyslipidemia. Smoking was the risk factor most strongly associated with worse SDOH (odds ratio [OR], 2.67 for quartile 4 versus quartile 1 [95% CI, 2.13–3.34]). Participants within SDOH quartile 4 had 33% higher odds of increased high‐sensitivity C‐reactive protein (OR, 1.33 [95% CI, 1.11–1.60]) and 31% higher risk of all cardiovascular disease (hazard ratio, 1.31 [95% CI, 1.03–1.67]), yet no greater burden of subclinical atherosclerosis (OR, 1.01 [95% CI, 0.79–1.29]), when compared with those in quartile 1. Conclusions Increasing social disadvantage was associated with more prevalent cardiovascular risk factors, inflammation, and incident cardiovascular disease. These findings call for better identification of SDOHs in clinical practice and stronger measures to mitigate the higher SDOH burden among the socially disadvantaged to improve cardiovascular outcomes.

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Introduction: The Universal Definition of Heart Failure (HF) has incorporated N-terminal proB-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin (hs-cTnT) as markers to identify “stage B” HF (asymptomatic left ventricular dysfunction). Plasma ketone bodies (KB) have demonstrated an association with disease severity in HF patients. A multi-biomarker risk score may improve risk stratification of incident HF in the community. Methods: Participants free of CVD from the Multiethnic Study of Atherosclerosis (MESA) at the baseline visit were included. A multi-biomarker score was developed incorporating NT-proBNP ≥ 125 pg/mL, hs-cTnT ≥ 14 ng/L, and total KB ≥ 75 th percentile (316 μmol/L), with 1 point allocated for each abnormal marker. A multivariable Cox model was used to assess the association between multi-biomarker risk score categories and the risk of incident HF. The 5- year Kaplan Meier estimates for incident HF was determined for each biomarker score. Results: Among 6748 participants there were 383 incident HF events over a median follow-up of 15.7 yrs. Total KB displayed a poor correlation with other biomarkers (r<0.06 for all). The addition of KB to the current standard of care to identify pre-HF (either elevation in NT-proBNP and/or hs-cTnT) improved risk prediction (C-statistic 0.70 vs. 0.73). The 3-biomarker score demonstrated good discrimination for predicting 5-year HF risk [C-statistic 0.74 (95%CI 0.70-0.78)]. A graded association was observed between biomarker score groups and the risk of HF independent of established clinical factors ( Figure ). 8% of participants with biomarker score ≥2 developed HF within 5 yrs, while those with biomarker scores≤1 faced very low risk (≤2% over 5 yrs). Conclusions: The addition of plasma KB to a clinical risk score using routinely collected biomarkers of cardiac injury and stress may further personalize risk estimation and reduce misclassification of those at risk of incident HF.

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