A pooled US cohorts study suggests that maintaining an optimal level of low-density lipoprotein cholesterol (LDL-C) throughout young adulthood and middle age can minimize the lifetime risk for atherosclerotic cardiovascular disease (CVD). The study included data of 18 288 participants (mean age 56.4, 56.4% women) collected from 1971 to 2017 from 4 prospective cohort studies in the US. During a median follow-up of 16 years, 1165 coronary heart disease (CHD), 599 ischemic stroke, and 1145 heart failure (HF) 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 1.57, 1.69, and 0.88, for cumulative LDL-C level, time-weighted average LDL-C level, and LDL-C slope, respectively. There was a dose-response association between cumulative exposure to LDL-C and CHD risk without evidence for a clear threshold. No association was found between any of the LDL-C variables and ischemic stroke or HF. The findings are in line with Mendelian randomization and longitudinal epidemiological studies, and support that not only the current level, but also a lifelong exposure to elevated LDL-C is associated with atherosclerotic CVD. The study suggests that achieving optimal lipid levels early in life and maintaining throughout adulthood may prevent incident CHD events better than the current paradigm of deferring lowering LDL-C levels to later in life when atherosclerosis is likely already advanced. Healthy diet and other lifestyle modifications may be the safest way of maintaining optimal LDL-C levels throughout life, with pharmacological therapy if lifestyle modifications are not enough. Source: https://jamanetwork.com/
