Mass General Brigham registry finds high Lp(a) carries the same heart attack risk as having two traditional risk factors combined (J Am Heart Assoc 2024)

Original title: Association of Lipoprotein (a) and Standard Modifiable Cardiovascular Risk Factors With Incident Myocardial Infarction: The Mass General Brigham Lp(a) Registry

J Am Heart Assoc · 18 May 2024 · 8

Shiyovich A, Berman AN, Besser SA, Biery DW, Kaur G, Divakaran S, Singh A, Huck DM, Weber B, Plutzky J, Di Carli MF, Nasir K et al.

This retrospective study of the Mass General Brigham Lp(a) Registry included 6,238 patients (median age 54, 45% women) without severe kidney dysfunction, malignancy, or prior atherosclerotic cardiovascular disease who had Lp(a) measured between 2000 and 2019. Standard modifiable risk factors (SMuRFs), diabetes, dyslipidaemia, hypertension, and smoking, were assessed alongside high Lp(a) (above the 90th percentile) or low Lp(a) (below the 50th percentile). Over a median 8.8-year follow-up, acute myocardial infarction incidence rose with SMuRF count in both high and low Lp(a) groups, but was significantly higher for high versus low Lp(a) across every SMuRF subgroup, with high Lp(a) conferring risk comparable to having two SMuRFs. After adjusting for confounders and SMuRF count, high Lp(a) remained independently associated with myocardial infarction (hazard ratio 2.9, 95% CI 2.0-4.3, P < 0.001). In patients without prior cardiovascular disease, high Lp(a) carries a substantial, independent first-heart-attack risk regardless of how many traditional risk factors are present.

Original abstract

Background: Lipoprotein (a) [Lp(a)] is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. We aimed to evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI).

Methods And Results: This retrospective study used the Mass General Brigham Lp(a) Registry, which included patients aged ≥18 years with an Lp(a) measurement between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease. Diabetes, dyslipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as >90th percentile, and low Lp(a) was defined as <50th percentile. The primary outcome was fatal or nonfatal AMI. A combination of natural language processing algorithms, International Classification of Diseases (ICD) codes, and laboratory data was used to identify the outcome and covariates. A total of 6238 patients met the eligibility criteria. The median age was 54 (interquartile range, 43-65) years, and 45% were women. Overall, 23.7% had no SMuRFs, and 17.8% had ≥3 SMuRFs. Over a median follow-up of 8.8 (interquartile range, 4.2-12.8) years, the incidence of AMI increased gradually, with higher number of SMuRFs among patients with high (log-rank P=0.031) and low Lp(a) (log-rank P<0.001). Across all SMuRF subgroups, the incidence of AMI was significantly higher for patients with high Lp(a) versus low Lp(a). The risk of high Lp(a) was similar to having 2 SMuRFs. Following adjustment for confounders and number of SMuRFs, high Lp(a) remained significantly associated with the primary outcome (hazard ratio, 2.9 [95% CI, 2.0-4.3]; P<0.001).

Conclusions: Among patients with no prior atherosclerotic cardiovascular disease, high Lp(a) is associated with significantly higher risk for first AMI regardless of the number of SMuRFs.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.