Exposure to LDL-C in Young Adults Linked to Risk of Incident Coronary Heart Disease

September 24, 2021
Connor Iapoce

Connor Iapoce is an associate editor for HCPLive and joined the MJH Life Sciences team in April 2021. He graduated from The College of New Jersey with a degree in Journalism and Professional Writing. He enjoys listening to records, going to concerts, and playing with his cat Squish. You can reach him at ciapoce@mjhlifesciences.com.

Hazard ratios for CHD included 1.57 for cumulative LDL-C level, 1.69 for TWA LDL-C level, and 0.88 for LDL-C slope.

Despite being a major risk factor for cardiovascular disease (CVD), most studies on associations between high low-density lipoprotein cholesterol (LDL-C) levels and CVD are only measured at one time point in life, leaving a lack of data on long-term exposure to LDL-C.

In a recent cohort study, investigators, led by Yiyi Zhang, PhD, Division of General Medicine, Columbia University Medical Center, looked to evaluate the association of cumulative exposure to LDL-C, time-weighted average (TWA) LDL-C, and the LDL-C slope change during young adulthood and middle age, with incident CVD in later life.

Results from the study showed cumulative LDL-C and TWA LDL-C during these time periods were associated with the risk of incident CVD, regardless of LDL-C level at midlife.


The study conducted an analysis of 4 large, community-based prospective cohort studies in the United states, including the Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Framingham Heart Study Offspring Cohort, and Multi-Ethnic Study of Atherosclerosis.

For inclusion criteria, participants were included with ≥2 LDL-C measures that were at least 2 years apart between ages 18 - 60 years, with 1 of the LDL-measures taking place in middle age (40 - 60 years).

The team defined the index visit as the last visit during the middle-age period with an observed LDL-C measurement.

Further, the defined primary exposures of interest as cumulative exposure to LDL-C, TWA LDL-C, and LDL-C scope from ages 18 - 60 years. Then, primary outcomes of interest for the present analysis were incident Exposure to LDL-C in Young Adults Linked to Risk of Incident Coronary Heart Disease (CHD), ischemic stroke, and heart failure (HF).

Additionally, investigators used cox proportional hazards regression models to examine associations between LDL-C exposure and incident CVD events.


Out of the 4 cohort studies, a total of 18,288 participants were included. They had a mean age of 56.4 years at index visit, including 10,309 women (56.4%) and 7979 men (43.6%).

Through a median follow-up of 16 years, investigators observed a total of 1165 incident CHD, 599 ischemic stroke, and 1145 HF events.

Further, the team used the multivariable Cox proportional hazards regression model that adjusted for most recent LDL-C levels measured during middle age and other CVD risk factors.

As a result, the hazard ratios for CHD included 1.57 (95% CI, 1.10 - 2.23, P = .01), for cumulative LDL-C level, 1.69 (95% CI, 1.23 - 2.31, P <.001) for TWA LDL-C level, and 0.88 (95% CI, 0.69 - 1.12, P = .28) for LDL-C slope.

Investigators noted a lack of association between any LDL-C variables and ischemic stroke or heart failure.

They found that associations were similar in women (HR 1.82; 95% CI, 1.07 - 3.10) and in men (HR 1.67; 95% CI, 1.06 - 2.64).

In participants who never used lipid-lowering medication (n = 15,626), data show TWA LDL-C level remained significantly associated with incident CHD (HR 1.54; 95% CI, 1.08 - 2.18).


As a result, greater exposure to LDL-C and TWA-C at young adulthood and middle age were associated with an increased risk of CHD, which remained after adjustment for the most recent LDL-C level during middle age.

“These findings suggest that previous levels of LDL-C may inform strategies for primary prevention of CHD and that maintaining optimal LDL-C levels throughout young adulthood and middle age may reduce the lifetime risk of developing atherosclerotic CVD,” investigators wrote.

The study, “Association Between Cumulative Low-Density Lipoprotein Cholesterol Exposure During Young Adulthood and Middle Age and Risk of Cardiovascular Events,” was published online in JAMA Cardiology.