Abstract
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 HRdeath=2.47, 95% CI 1.28–4.76] [LDL-C HRASCVD=5.09, 95% CI 1.54–16.85; LDL-C HRdeath=4.04, 95% CI 1.84–8.89] [non-HDL-C HRASCVD=4.60, 95% CI 1.98–10.70; LDL-C HRdeath=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 (HRASCVD=3.81, 95% CI 2.04–7.15; HRdeath=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.
Original language | English |
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Article number | e011433 |
Journal | Journal of the American Heart Association |
Volume | 8 |
Issue number | 11 |
DOIs | |
State | Published - Jun 4 2019 |
Bibliographical note
Funding Information:This work was supported by the National Heart, Lung, and Blood Institute contracts N01-HC-25195 and HHSN268201500001I. Dr Vasan was also funded by the Evans Foundation and Jay and Louise Coffman Endowment at Boston University.
Publisher Copyright:
© 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
Keywords
- cardiovascular disease
- life-course
- lipids
- longitudinal
- trajectories
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine