Trajectories of Blood Lipid Concentrations Over the Adult Life Course and Risk of Cardiovascular Disease and All‐Cause Mortality: Observations From the Framingham Study Over 35 Years

BACKGROUND: Elevated total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), triglycerides, and non‐high‐density lipoprotein cholesterol (non‐HDL‐C) and low high‐density lipoprotein cholesterol (HDL‐C) concentrations correlate with atherosclerotic cardiovascular disease (ASCVD) and mortality. Therefore, understanding how lipid trajectories throughout adulthood impact ASCVD and mortality risk is essential. METHODS AND RESULTS: We investigated 3875 Framingham Offspring participants (54% women, mean age 48 years) attending ≥1 examination between 1979 and 2014. We evaluated longitudinal correlates of each lipid subtype using mixed‐effects models. Next, we clustered individuals into trajectories through group‐based modeling. Thereafter, we assessed the prospective association of lipid trajectories with ASCVD and mortality. Male sex, greater body mass index, and smoking correlated with higher TC, LDL‐C, triglycerides, non‐HDL‐C, and lower HDL‐C concentrations. We identified 5 TC, HDL‐C, and LDL‐C trajectories, and 4 triglycerides and non‐HDL‐C trajectories. Upon follow‐up (median 8.2 years; 199 ASCVD events; 256 deaths), elevated TC (>240 mg/dL), LDL‐C (>155 mg/dL), or non‐HDL‐C (>180 mg/dL) concentrations conferred >2.25‐fold ASCVD and mortality risk compared with concentrations <165 mg/dL, <90 mg/dL, and <115 mg/dL, respectively ([TC hazard ratio (HR)(ASCVD)=4.17, 95% CI 1.94–8.99; TC HR (death)=2.47, 95% CI 1.28–4.76] [LDL‐C HR(ASCVD)=5.09, 95% CI 1.54–16.85; LDL‐C HR (death)=4.04, 95% CI 1.84–8.89] [non‐HDL‐C HR(ASCVD)=4.60, 95% CI 1.98–10.70; LDL‐C HR (death)=3.74, 95% CI 2.03–6.88]). Consistent HDL‐C concentrations <40 mg/dL were associated with greater ASCVD and mortality risk than concentrations >70 mg/dL (HR(ASCVD)=3.81, 95% CI 2.04–7.15; HR (death)=2.88, 95% CI 1.70–4.89). Triglycerides trajectories were unassociated with outcomes. CONCLUSIONS: Using a longitudinal modeling technique, we demonstrated that unfavorable lipid trajectories over 35 years confer higher ASCVD and mortality risk later in life.