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J Am Coll Cardiol. 2019 Jul 9;74(1):70-79. doi: 10.1016/j.jacc.2019.04.047.

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

Author information

Section on Men's Health Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:
Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Framingham Heart Study, Section of Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts; Section of Cardiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts; Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts.
Duke Clinical Research Institute, Durham, North Carolina.
Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada.



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.


This study determined the extent to which lipid levels in young adulthood predict future lipid trajectories and associated long-term CVD risk.


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.


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.


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.


cardiovascular disease prevention; lipids; non-HDL cholesterol


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