Cumulative low-density lipoprotein cholesterol exposure during young adulthood and middle age is linked to CVD risk in later life

Low-density lipoprotein cholesterol (LDL-C) is a well-established major risk factor for cardiovascular disease (CVD), but most observational studies on the association between LDL-C and CVD have focused on LDL-C level at a single time point (usually in middle or older age), and few studies have characterized long-term exposures to LDL-C and their role in CVD risk.

At the end of September 2021, a new study exploring the associations of cumulative exposure to LDL-C or time-weighted average (TWA) LDL-Ce during young adulthood and middle age with incident CVD later in life was published online in JAMA Cardiology. This cohort study analyzed pooled data from 4 prospective cohort studies in the US (Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Framingham Heart Study Offspring Cohort, and Multi-Ethnic Study of Atherosclerosis). Participants were included if they had 2 or more LDL-C measures that were at least 2 years apart between ages 18 and 60 years, with at least 1 of the LDL-C measures occurring during middle age at 40 to 60 years. Data from 1971 to 2017 were collected and analyzed from September 25, 2020, to January 10, 2021.

A total of 18288 participants were included in the study. These participants had a mean (SD) age of 56.4 (3.7) years and consisted of 10 309 women (56.4%). During a median follow-up of 16 years, 1165 CHD, 599 ischemic stroke, and 1145 heart failure events occurred. In multivariable Cox proportional hazards regression models that adjusted for the most recent LDL-C level measured during middle age and for other CVD risk factors, the hazard ratios for CHD were as follows: 1.57 (95% CI, 1.10-2.23; P for trend = .01) for cumulative LDL-C level and 1.69 (95% CI, 1.23-2.31; P for trend <.001) for TWA LDL-C level. No association was found between any of the LDL-C variables and ischemic stroke or heart failure.

This cohort study showed that cumulative LDL-C and TWA LDL-C during young adulthood and middle age were associated with the risk of incident CHD, independent of midlife LDL-C level. These findings suggest that past levels of LDL-C may inform strategies for primary prevention of CHD and that maintaining optimal LDL-C levels at an earlier age may reduce the lifetime risk of developing atherosclerotic CVD.


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