Genetic Association Estimate for Lipoprotein(a)-Lowering Therapies

A mendelian randomization analysis revealed that Lipoprotein(a) [ Lp(a)]concentration must be lowered by approximately 100 mg/dL to achieve the same reduction in coronary heart disease (CHD) risk as can be achieved by lowering low-density lipoprotein cholesterol (LDL-C) level by 38.67 mg/dL. The analysis involved more than 80 000 patients and more than 150 000 controls, 53% were men, all white, and the mean age was 57.5 years. The association of genetically predicted Lp(a) with CHD risk was linearly proportional to the absolute change in Lp (a) concentration. A 10-mg/dL lower genetically predicted Lp(a) concentration was associated with a 5.8% lower CHD risk (odds ratio [OR], 0.942), whereas a 10-mg/dL lower genetically predicted LDL-C level estimated using an LDL-C genetic score was associated with a 14.5% lower CHD risk (OR, 0.855). Thus, a 101.5-mg/dL change in Lp(a) concentration had the same association with CHD risk as a 38.67-mg/dL (ie, 1 mmol/L) change in LDL-C level. The association of genetically predicted Lp(a) concentration with CHD risk appeared to be independent of changes in LDL-C level owing to genetic variants that mimic the relationship of statins, PCSK9 inhibitors, and ezetimibe with CHD risk. Previous studies have indicated that plasma Lp(a) is causally associated with the risk of CHD. Source: https://jamanetwork.com/