What is the clinical evidence from this study?

Study design: Cohort. Population: Atherosclerotic cardiovascular disease (ASCVD) and mortality (n=3875). Intervention: Lipid trajectories vs. Favorable lipid trajectories. Primary outcome: Atherosclerotic cardiovascular disease (ASCVD) (HR 4.17, 95% CI 1.94-8.99).

May 29, 2019Open Access

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

Key Result

Elevated total cholesterol (>240 mg/dL) trajectories over 35 years conferred a higher risk of ASCVD (HR 4.17; 95% CI 1.94-8.99) compared with concentrations <165 mg/dL.

Study Design

Type

Cohort (n=3,875)

Structured PICO

Do unfavorable blood lipid trajectories over the adult life course increase the risk of ASCVD and all-cause mortality?

Population

3875 Framingham Offspring participants (54% women, mean age 48 years) attending ≥1 examination between 1979 and 2014.

Intervention

Trajectories of blood lipid concentrations (total cholesterol, LDL-C, triglycerides, non-HDL-C, and HDL-C) over 35 years.

Comparator

Lower concentration trajectories (e.g., TC <165 mg/dL, LDL-C <90 mg/dL, non-HDL-C <115 mg/dL, HDL-C >70 mg/dL).

Outcome

Atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality at median 8.2 years follow-up.hard clinical

Unfavorable lipid trajectories over a 35-year period are strongly associated with increased risk of ASCVD and all-cause mortality later in life.

Main Result

Effect estimate: HR 4.17 (95% CI 1.94-8.99)

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 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.