Non-HDL Cholesterol a CV-Risk Crystal Ball for Young Adults

Megan Brooks

July 10, 2019

New data from the Framingham Offspring cohort support obtaining at least two lipid panels from adults ages 25 to 40 as a means of gauging risk for cardiovascular disease (CVD) over the next decades.

People with elevated non-high-density lipoprotein cholesterol (non-HDL-C) levels in young adulthood were apt to also show high non-HDL-C throughout their lives, suggests an analysis published July 1 in the Journal of the American College of Cardiology.

"Our study demonstrated that measurements of non-HDL taken in young adults between age 25 and 40 with reasonable certainty characterize subsequent levels of non-HDL over the next 25 to 30 years," lead author Karol Pencina, PhD, Brigham and Women's Hospital, Boston, Massachusetts, told theheart.org | Medscape Cardiology.

The findings are based on lipid data from 2516 people aged 25 to 40 years when they entered the Framingham Offspring study. The researchers modeled the life-course of non-HDL-C levels over about 30 years to gauge how reliably elevations in cholesterol in early adulthood persist. 

Lipid-level trajectories were "generally stable" over the decades. Two non-HDL-C measurements obtained between ages 25 and 40, averaged, were seen to reliably categorize people into high (≥160 mg/dL) and low (<130 mg/dL) non-HDL-C groups over the next 25 to 30 years.

Two high non-HDL-C readings in young adulthood worked out to an 80% chance that they would remain elevated over the next 3 decades. If the first two values are low, there is an 88% chance that they will remain below 160 mg/dL during the next 30 years, the analysis suggested.

There were "dramatic" between-group differences in outcomes, the report says. For example, the authors state, people with high non-HDL-C at baseline had a 22.6% risk of CVD over the next 25 years, compared with a 6.4% risk in their peers with low levels.

"These event rates are particularly striking given the young age of our cohort at the beginning of the follow-up, an age at which the 10-year risk of cardiovascular events determined by conventional algorithms is generally low," the researchers write.

The findings, write the investigators, are said to highlight the importance of measuring non-HDL-C levels before age 40, which will help "facilitate informed patient–provider discussion about the potential benefits of preventive lipid-lowering efforts during the early midlife period."

"In the algorithms currently used for calculation of CVD risk, very few people would be at high enough risk to qualify for statin therapy, because age is a dominant factor in these calculators," Pencina said.

"Nevertheless, we estimated that statin therapy in the high non-HDL group (>160 mg/dL) would result in a number needed to treat of 8. That is, for every 8 individuals treated, 1 event would be prevented," she noted.

"These results demonstrate that CVD prevention could be advanced by identifying a subgroup of young individuals with elevated lipid levels who are at high long-term risk who could benefit from statin therapy," Pencina said.

This study "adds valuable insight into the role of non-HDL-C as both a stable biomarker and robust predictor of future CVD events extending from young adulthood," Michael Miller, MD, Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, writes in an accompanying editorial.

Intensive lifestyle changes can appreciably reduce triglycerides (TG) and LDL cholesterol in most young adults with elevated non-HDL-C, translating into reduced CVD risk, Miller notes.

These include weight loss for people who are overweight or obese, replacing saturated fat for mono- or polyunsaturated fat, increasing intake of marine-derived omega-3 fatty acids, soluble fiber, cutting intake of "trans" fats, and increasing aerobic activity, he says. 

"Young adults with persistent elevation in non-HDL-C may be candidates for statins, icosapent ethyl [Vascepa, Amarin], or other therapies, despite the lack of outcome data supporting such primary prevention measures."

Thus, the current findings "justify future proposals aimed at reducing CVD in young and middle-aged individuals, such as the ECAD (Eliminate Coronary Artery Disease) study. The ultimate goal is to turn back the atherosclerotic clock, one tick at a time," Miller says.

Because age is the major determinant of CVD risk, "few young patients are eligible for primary prevention until after 60 years of age, despite perhaps having very high-risk lipid profiles," the journal's editor-in-chief Valentin Fuster, MD, notes in an accompanying podcast commentary.

Much of the atherosclerotic disease that produces CV events after age 60 begins and matures in those younger than age 60, Fuster notes, "so it is reasonable to address preventive strategies and to identify individuals who have risk for cardiovascular disease early in life and to intervene."

Pencina discloses receiving data safety monitoring board member fees from Ironwood Pharmaceuticals and consulting fees from HunterRockhold; conflict of interest statements for the other authors are in the report. Miller discloses serving on the steering committee for the REDUCE-IT trial and consulting for Amarin and Akcea Therapeutics. Fuster has disclosed no relevant financial relationships.

J Am Coll Cardiol. Published online July 1, 2019. Abstract, Editorial

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