Lipoprotein(a), MACE, and Baseline Atherosclerotic CVD Status

Quick Takes

  • Among patients in this cohort who had a history of ASCVD, those above the 71st Lp(a) percentile had a 21% increased risk for MACE, with a plateau in risk at the ~70th percentile.
  • Among patients without established ASCVD, there was a continuously higher risk for MACE with increasing Lp(a), such that those in the 91st–100th Lp(a) percentile group had the highest relative risk of MACE.
  • Thus, the Lp(a) threshold for risk assessment may differ based on baseline ASCVD status.

Study Questions:

What is the association between lipoprotein(a) [Lp(a)] and major adverse cardiovascular events (MACE) among patients with and without baseline atherosclerotic cardiovascular disease (ASCVD)?


This retrospective study included data from the Mass General Brigham Lp(a) Registry and the Research Patient Data Registry. All patients who had Lp(a) testing as part of routine care from January 1, 2000 to July 1, 2019 were included. Participants were excluded if they were younger than 18 years old, had severe renal disease, a malignant neoplasm, or died during the covariate assessment window. Lp(a) percentile groups were generated with the reference group set at the 1st–50th Lp(a) percentiles. The primary outcome of interest was incident MACE, which included nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization, or cardiovascular mortality. Cause of death was determined using the National Death Index and the Massachusetts Office of Vital Statistics.


A total of 21,410 patients underwent Lp(a) testing with a mass-based or particle-based assay during the study period, of which 16,419 met inclusion criteria. Of the 16,419 included patients, the median age was 60 years (interquartile range [IQR] 49-72), 41% were female, and 10,181 (62%) had a history of ASCVD. Those with a history of ASCVD were more likely to be older and have a greater burden of traditional modifiable cardiovascular risk factors. Patients with a history of ASCVD had higher median Lp(a) levels than those without ASCVD (37.8 nmol/L vs. 31.1 nmol/L, p < 0.001).

Over a median follow-up of 11.9 years (IQR 6.2-14.4), nonfatal MI occurred in 1,1067 (6.5%), nonfatal ischemic stroke occurred in 1,373 (8.4%), and cardiovascular mortality occurred in 2,416 (14.7%) of the entire cohort. Among the 10,181 (62%) patients with baseline ASCVD, individuals in the 71st–90th percentile group had a 21% increased hazard of MACE (adjusted hazard ratio [HR], 1.21; p < 0.001), which was similar to that of individuals in the 91st–100th group (adjusted HR, 1.26; p < 0.001). Among the 6,238 individuals without established ASCVD, there was a continuously higher hazard of MACE with increasing Lp(a), and individuals in the 91st-100th Lp(a) percentile group had the highest relative risk with an adjusted HR of 1.93 (p < 0.001).


The authors conclude that in a large, contemporary US cohort, elevated Lp(a) is independently associated with long-term MACE among individuals with and without baseline ASCVD. These results suggest that the threshold for risk assessment may be different in primary versus secondary prevention cohorts.


These data suggest that the measurement of Lp(a) may assist providers to identify patients at higher risk for future ASCVD including cardiovascular mortality. However, this risk may differ for those with established ASCVD versus those without.

Clinical Topics: Dyslipidemia, Advanced Lipid Testing, Lipid Metabolism, Prevention

Keywords: Atherosclerosis, Lipoprotein(a)

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