LDL cholesterol (LDL-C) exposure in younger adulthood predicted later cardiovascular events independent of cholesterol in middle age, large observational cohorts showed.
Coronary heart disease significantly correlated with cumulative LDL-C (HR 1.57, P=0.01 for trend) as well as time-weighted average LDL (HR 1.69, P<0.001 for trend) across four studies and a median of 16 years of follow-up.
Risk was seen as low as 100 mg/dL, far below current treatment thresholds, Yiyi Zhang, PhD, of Columbia University Medical Center in New York City, and colleagues reported in JAMA Cardiology.
“The findings suggest that maintaining an optimal level of LDL-C throughout young adulthood and middle age can minimize the lifetime risk for atherosclerotic cardiovascular disease,” the researchers concluded.
Cholesterol guidelines recommend statins for young adults ages 20 to 39 years below an LDL of 190 mg/dL only when there is family history of premature atherosclerotic cardiovascular disease, long-standing diabetes, or multiple risk factors.
The findings “suggest that the current guideline-endorsed paradigm of deferring the treatment of mild and moderate elevations of LDL-C levels in young adults not only misses a critical opportunity for prevention but also unnecessarily allows lipid-related risk to accumulate for decades,” wrote Ann Marie Navar, MD, PhD, of the University of Texas Southwestern Medical Center in Dallas, and Gregg Fonarow, MD, of the University of California Los Angeles.
The concept is similar to pack-years of smoking, they noted in an editorial accompanying the paper. That’s no surprise, “yet exactly when to begin lipid-lowering therapy has not been well demarcated. Atherosclerotic lesions develop slowly over many years, if not decades.”
Navar and Fonarow concluded that “if the clinical community can support treating hypertension early in life to prevent the long-term risks of elevated blood pressure, the findings in the study by Zhang et al. suggest that a similar paradigm should be considered for LDL-C.”
The study included 18,288 participants from four studies: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Framingham Heart Study Offspring Cohort, and the Multi-Ethnic Study of Atherosclerosis.
The slope of LDL-C wasn’t associated with coronary heart disease after adjusting for midlife LDL levels, the researchers wrote, “likely because at a given LDL-C level during middle age, individuals who reached a steeper slope may have a smaller area under the curve or cumulative LDL-C exposure compared with those with a shallower slope.”
No associations were seen with the risk of ischemic stroke or heart failure, although those outcomes are less frequent than coronary heart disease endpoints, which were significantly linked to risk.
Included patients had two or more LDL-C measures at least 2 years apart between ages 18 and 60 years, with at least one in middle age at 40 to 60 years. Participants were followed for a median of 16 years from their index visit at a median age of 56.
Limitations of the study included use of multiple imputation to estimate long-term LDL-C exposures because the cohort studies had restricted enrollment age ranges without direct measurement of LDL-C levels during both young adulthood and middle age.
The study was funded by the NIH.
Zhang disclosed no relevant relationships with industry.
Navar reported receiving grants from Bristol Myers Squibb, Esperion, Amgen, and Janssen; receiving personal fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, CSL, Esperion, Janssen, Lilly, Sanofi, Regeneron, Novo Nordisk, Novartis, The Medicines Company, New Amsterdam, Cerner, 89Bio, and Pfizer outside the submitted work; and being the associate editor of JAMA Cardiology.
Fonarow reported receiving personal fees from Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis outside the submitted work, and being the section editor of JAMA Cardiology.