Trajectories of Non–HDL Cholesterol Across Midlife: Implications for Cardiovascular Prevention

Background: Extended elevations of non–high-density lipoprotein cholesterol (non–HDL-C) across a lifespan are associated with increased risk of cardiovascular disease (CVD). However, optimal testing intervals to identify individuals with high lipid-related CVD risk are unknown. Objectives: This study determined the extent to which lipid levels in young adulthood predict future lipid trajectories and associated long-term CVD risk. Methods: A sample of 2,516 Framingham Offspring study participants 25 to 40 years of age free of CVD and diabetes had their non–HDL-C progression modeled over 8 study examinations (mean follow-up 32.6 years) using group-based methods. CVD risk based on 25 to 30 years of follow-up was evaluated using Kaplan-Meier analyses for those with mean non–HDL-C ≥160 mg/dl (“high”) and <130 mg/dl (“low”) at the first 2 examinations. Levels of non–HDL-C for participants on lipid treatment were adjusted by nonparametric algorithm. Results: The trajectories of the lipid levels were generally stable over the 30-year life course; mean non–HDL-C measured in young adulthood were highly predictive of levels later in life. Individuals could be reliably assigned to high and low non–HDL-C groups based on 2 measurements collected between 25 to 40 years of age. Overall, 80% of those with non–HDL-C ≥160 mg/dl at the first 2 exams remained in the high group on subsequent 25-year testing, whereas 88% of those with non–HDL-C <130 mg/dl remained below 160 mg/dl. Those with high non–HDL-C in young adulthood had a 22.6% risk of CVD in the next 25 years as compared with a 6.4% risk in those with low non–HDL-C. Conclusions: Most adults with elevated non–HDL-C early in life continue to have high non–HDL-C over their life course, leading to significantly increased risk of CVD. The results demonstrate that early lipid monitoring before 40 years of age would identify a majority of those with a high likelihood for lifetime elevated lipid levels who also have a high long-term risk for CVD. This information could facilitate informed patient–provider discussion about the potential benefits of preventive lipid-lowering efforts during the early midlife period.