– Lipoprotein (a) [Lp(a)] levels are higher in individuals of African ancestry (AA) than in individuals of European ancestry (EA). We examined associations of genetically predicted Lp(a) levels with 1) atherosclerotic cardiovascular disease (ASCVD) subtypes: coronary heart disease (CHD), cerebrovascular disease (CVD), peripheral artery disease (PAD), and abdominal aortic aneurysm (AAA); and 2) non-ASCVD phenotypes, stratified by ancestry. – We performed 1) Mendelian randomization (MR) analyses for previously reported cardiovascular associations, and 2) phenome-wide MR (MR-PheWAS) analyses for novel associations. Analyses were stratified by ancestry in electronic MEdical Records and GEnomics, United Kingdom Biobank, and Million Veteran Program cohorts separately and in a combined cohort of 804,507 EA and 103,580 AA participants. – In MR analyses using the combined cohort, a 1-standard deviation (SD) genetic increase in Lp(a) level was associated with ASCVD subtypes in EA – odds ratio and 95% confidence interval for CHD 1.28(1.16-1.41); CVD 1.14(1.07-1.21); PAD 1.22(1.11-1.34); AAA 1.28(1.17-1.40); in AA the effect estimate was lower than in EA and nonsignificant for CHD 1.11(0.99-1.24) and CVD 1.06(0.99-1.14) but similar for PAD 1.16(1.01-1.33) and AAA 1.34(1.11-1.62). In EA, a 1-SD genetic increase in Lp(a) level was associated with aortic valve disorders 1.34(1.10-1.62), mitral valve disorders 1.18(1.09-1.27), congestive heart failure 1.12(1.05-1.19), and chronic kidney disease 1.07(1.01-1.14). In AA no significant associations were noted for aortic valve disorders 1.08(0.94-1.25), mitral valve disorders 1.02(0.89-1.16), congestive heart failure 1.02(0.95-1.10), or chronic kidney disease 1.05(0.99-1.12). MR-PheWAS identified novel associations in EA with arterial thromboembolic disease, non-aortic aneurysmal disease, atrial fibrillation, cardiac conduction disorders, and hypertension. – Many cardiovascular associations of genetically increased Lp(a) that were significant in EA were not significant in AA. Lp(a) was associated with ASCVD in four major arterial beds in EA but only with PAD and AAA in AA. Additional, novel cardiovascular associations were detected in EA.
For latest news and updates