Cumulative exposure to risk factors and subsequent cardiovascular disease events: The Jackson Heart Study

Background: Cumulative exposure to risk factor levels may capture cardiovascular disease (CVD) risk independent of a single measurement. We examined the association between cumulative exposure to systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and fasting plasma glucose (FPG) with CVD events among African American participants in the Jackson Heart Study (JHS). Methods: We included all JHS participants with SBP, LDL-C, and FPG measurements at Exams 1 (2000-2004) and 3 (2009-2013) who were alive at 8 years of follow-up after Exam 1. We calculated 8-year cumulative exposures as the area under the trajectory of each risk factor using all available measurements from Exams 1, 2, and 3. Adjudicated coronary heart disease (CHD), stroke, and heart failure (HF) events after the 8-year exposure period and through December 31, 2016 were evaluated separately using conditional Cox regression models with each cumulative exposure, respective values at 8 years, and Exam 1 covariates as independent variables. Models were conducted separately for each risk factor, and exposures were centered and scaled for comparability. Results: Among 3188 eligible JHS participants, mean age was 54 years, and 64% were women. Higher cumulative exposures to SBP and LDL-C were associated with CHD events after adjustment for covariates and the 8-year values [adjusted hazard ratios (aHR) per SD: 1.37 per 136 mmHg-years of SBP (95% CI: 1.09, 1.71), and 1.56 per 309 mg/dL-years of LDL-C (95% CI: 1.02, 2.37)]. Higher cumulative exposure to SBP and FPG were associated with HF events after adjustment [aHR: 1.15 per 136 mmHg-years of SBP (95% CI: 1.04, 1.27) and 1.10 per 262 mg/dL-years of FPG (95% CI: 1.02, 1.18)]. Only the 8-year values, but not cumulative exposures, were associated with stroke risk after full adjustment. Conclusions: Cumulative exposure to risk factors may provide additional information on CVD risk compared with single measurements later in life, particularly for CHD and HF events.