Young Adult Exposure to Cardiovascular Risk Factors and Risk of Events Later in Life: The Framingham Offspring Study

Abstract

Background: It is unclear whether coronary heart disease (CHD) risk factor exposure during early adulthood contributes to CHD risk later in life. Our objective was to analyze whether extent of early adult exposures to systolic and diastolic blood pressure (SBP, DBP) and low-and high-density lipoprotein cholesterol (LDL, HDL) are independent predictors of CHD events later in life.

Methods and findings: We used all available measurements of SBP, DBP, LDL, and HDL collected over 40 years in the Framingham Offspring Study to estimate risk factor trajectories, starting at age 20 years, for all participants. Average early adult (age 20-39) exposure to each risk factor was then estimated, and used to predict CHD events (myocardial infarction or CHD death) after age 40, with adjustment for risk factor exposures later in life (age 40+). 4860 participants contributed an average of 6.3 risk factor measurements from in-person examinations and 24.5 years of follow-up after age 40, and 510 had a first CHD event. Early adult exposures to high SBP, DBP, LDL or low HDL were associated with 8- to 30-fold increases in later life CHD event rates, but were also strongly correlated with risk factor levels later in life. After adjustment for later life levels and other risk factors, early adult DBP and LDL remained strongly associated with later life risk. Compared with DBP≤70 mmHg, adjusted hazard ratios (HRs) were 2.1 (95% confidence interval: 0.8-5.7) for DBP = 71-80, 2.6 (0.9-7.2) for DBP = 81-90, and 3.6 (1.2-11) for DBP>90 (p-trend = 0.019). Compared with LDL≤100 mg/dl, adjusted HRs were 1.5 (0.9-2.6) for LDL = 101-130, 2.2 (1.2-4.0) for LDL = 131-160, and 2.4 (1.2-4.7) for LDL>160 (p-trend = 0.009). While current levels of SBP and HDL were also associated with CHD events, we did not detect an independent association with early adult exposure to either of these risk factors.

Conclusions: Using a mixed modeling approach to estimation of young adult exposures with trajectory analysis, we detected independent associations between estimated early adult exposures to non-optimal DBP and LDL and CHD events later in life.

Fig 1. Adjusted associations between SBP, DBP, LDL and HDL levels at different ages and CHD events.

Hazard ratios (95% confidence intervals) are adjusted for age (via Cox model), sex, calendar year (via spline), body mass index, diabetes, years with diabetes, smoking status (current/past/never), pack-years of tobacco exposure (via spline), and use of blood pressure and lipid medications. The first column of results (for age 20–39) corresponds to the right-hand column of Table 2. Categories for systolic blood pressure (SBP) are ≤120 (reference), 121–140, 141–160 and >160 mmHg; for diastolic blood pressure (DBP) are ≤80, 81–90, 91–100, and >100; for low-density lipoprotein cholesterol (LDL) are ≤100 (reference), 101–130, 131–160 and >160 mg/dl; and for high-density lipoprotein cholesterol (HDL) are >65 (reference), 51–65, 36–50, and ≤35 mg/dl. “P Overall” refers to a test of the overall contribution of the risk factor (including early, later, and current exposures) to the model. No participants had an average SBP>160 mmHg from age 20–39. The * indicates a truncated confidence interval.