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

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.