High lipoprotein(a) and high BMI jointly confer the highest risk of ASCVD in both primary and secondary prevention

Background Novel pharmaceuticals lower body mass index (BMI) and reduce risk of atherosclerotic cardiovascular disease (ASCVD), yet indications for BMI 27-30 require additional risk factors. High lipoprotein(a), present in 1 in 5 individuals, is a genetically determined risk factor for ASCVD not included in current overweight treatment guidelines. We hypothesised that high lipoprotein(a) and high BMI jointly confer the highest risk of ASCVD. Methods Prospective observational cohort study of 512,687 individuals without and 14,161 with ASCVD from two cohorts of the general European population. During follow-up, 39,255 developed ASCVD in primary prevention and 3,501 in secondary prevention. Findings: In both primary and secondary prevention, high lipoprotein(a) and BMI were independently associated with increased risk of ASCVD. In primary prevention, 10-year absolute risk in women and men aged 60-69 with lipoprotein(a) ≥95th percentile (≥95 mg/dL,≥202 nmol/L) and BMI≥30, were 15% and 26% in cohort #1, and 9% and 19% in cohort #2, respectively (Figure 1). Corresponding risks for lipoprotein(a) ≥95th percentile and BMI 27-30 were 14% and 24%, and 7% and 16%, and for lipoprotein(a) ≤50th percentile (≤9 mg/dL,17 nmol/L) and BMI ≥30, 9% and 16%, and 5% and 11%, respectively. At all ages and in both sexes, risks were higher for high lipoprotein(a) and BMI 27-30 versus BMI≥30 and low lipoprotein(a). In secondary prevention, risks of ASCVD were highest for lipoprotein(a) ≥95th percentile and BMI≥27. Interpretation: High lipoprotein(a) and high BMI jointly confer the highest risk of ASCVD in both primary and secondary prevention.