Absolute cardiovascular risk: the missing denominator in Lp(a)-guided aspirin therapy in primary prevention

We read with interest the meta-analysis by Lopes et al. evaluating aspirin for primary prevention among individuals with elevated lipoprotein(a) (Lp[a]) or high-risk LPA genotypes.1 While the authors conclude that routine aspirin use is not supported in this population, we believe an important clinical issue warrants greater emphasis: any aspirin-related benefit in elevated Lp(a) is likely dependent on baseline absolute atherosclerotic cardiovascular disease (ASCVD) risk rather than Lp(a) status alone. Current primary prevention guidelines consistently emphasize that aspirin benefit is determined by the balance between ischaemic and bleeding risk.2 Accordingly, one would expect the greatest potential benefit among patients with elevated Lp(a) who also have high background ASCVD risk due to the presence of diabetes, hypertension, chronic kidney disease (CKD), smoking, elevated low-density lipoprotein cholesterol (LDL-C), or advanced subclinical atherosclerosis. The studies included in this meta-analysis differed substantially in baseline risk. Women′s Health Study enrolled relatively healthy middle-aged women, Aspirin in Reducing Events in the Elderly included elderly adults, Multi-Ethnic Study of Atherosclerosis involved community-dwelling participants, Third National Health and Nutrition Examination Survey (NHANES III) reflected a historical pre-modern prevention cohort, and Chronic Renal Insufficiency Cohor specifically included patients with CKD.1 Given this marked clinical heterogeneity, further analyses, including meta-regression analyses according to baseline ASCVD risk or the prevalence of major risk factors such as diabetes, would be of particular interest to determine whether aspirin effect varies according to baseline ASCVD risk.