Elevated Lp(a) Linked to MACE, Heart Failure After Acute MI

Elevated lipoprotein(a) [Lp(a)] measured at the time of an acute myocardial infarction (AMI) was independently associated with a higher risk of major adverse cardiovascular events (MACE) and heart failure (HF) hospitalization over a median follow-up of 3.6 years, according to a study published in Circulation Journal.¹

Lp(a) is a well-established risk factor for atherosclerotic cardiovascular disease, but its prognostic role after AMI has been little studied, the authors noted. It has drawn attention as a contributor to the residual cardiovascular risk that persists even with optimal lipid-lowering therapy.

Lp(a) of 24 mg/dL or Higher Tied to 41% Higher MACE Risk

The investigators analyzed 1235 patients enrolled in the NARA Myocardial Infarction (NARA-MI) registry at Nara Medical University Hospital in Japan between 2013 and 2022 who underwent emergency percutaneous coronary intervention (PCI) and had Lp(a) measured at admission. The mean age was 68.8 years, and 75.9% of patients were male.

Using receiver operating characteristic (ROC) curve analysis, the researchers identified 24 mg/dL as the optimal Lp(a) cutoff for predicting MACE, placing 269 patients in the high-Lp(a) group and 966 in the low-Lp(a) group. MACE was defined as all-cause death, nonfatal myocardial infarction (MI), HF hospitalization, or unplanned coronary revascularization.

MACE occurred in 48.0% of the high-Lp(a) group vs 38.3% of the low-Lp(a) group (P = .004). In multivariable Cox regression analysis, Lp(a) of 24 mg/dL or higher remained an independent predictor of MACE (HR, 1.41; 95% CI, 1.15-1.73; P = .001). The association held in a sensitivity analysis censored at 5 years (HR, 1.42; 95% CI, 1.13-1.77; P = .002). However, rates of all-cause death, nonfatal MI, and unplanned revascularization did not differ significantly between groups.

HF Hospitalization Risk Rose 87% With High Lp(a)

The strongest signal was for HF. HF hospitalization occurred in 9.3% of the high-Lp(a) group vs 5.0% of the low-Lp(a) group (P = .008), and high Lp(a) independently predicted HF hospitalization after adjustment (HR, 1.87; 95% CI, 1.15-3.04; P = .016). That association emerged even though B-type natriuretic peptide levels at admission and use of guideline-directed cardioprotective medications did not differ significantly between groups.

Of the 73 patients hospitalized for HF, 39.7% had HF with preserved ejection fraction (HFpEF), 35.6% had HF with mildly reduced ejection fraction, and 24.7% had HF with reduced ejection fraction. HFpEF hospitalizations were numerically more frequent in the high-Lp(a) group (3.7% vs 2.0%), although that difference was not statistically significant (P = .092).

The authors suggested Lp(a)-driven atherosclerosis could increase arterial stiffness and, in turn, afterload, a known contributor to HFpEF, but noted that this mechanism remains hypothetical because their cohort lacked systematic diastolic function and arterial stiffness data.

Weak Discrimination and Lp(a)HORIZON Miss Temper the Findings

The ROC-derived cutoff showed limited discriminatory power (area under the curve, 0.535). The cutoff is lower than the 30 mg/dL threshold commonly used in prior epidemiological studies and the 50 mg/dL level considered high risk in Western populations; the authors noted that Japanese cohorts have lower Lp(a) levels. The study was single-center, has not been validated in an independent cohort, and measured Lp(a) only during hospitalization.

Whether lowering Lp(a) improves outcomes remains unproven, the authors cautioned. The phase 3 Lp(a)HORIZON trial (NCT04023552), which tested that question, enrolled 8323 patients with elevated Lp(a) and established cardiovascular disease. In September 2026, Novartis announced that pelacarsen, an investigational antisense oligonucleotide, lowered Lp(a) levels but did not meet the trial's primary end point of reducing a composite of cardiovascular death, nonfatal MI, nonfatal stroke, and urgent coronary revascularization requiring hospitalization vs placebo.²

“High Lp(a) was an independent prognostic marker of MACE in patients with AMI,” concluded the authors of the study.¹ “High Lp(a) was also independently associated with subsequent HF hospitalization, including HFpEF after AMI. Our results suggest the potential role of Lp(a) in post-AMI risk stratification. Further prospective and interventional studies are warranted to confirm these findings and elucidate the therapeutic implications of lowering Lp(a).”

References

1. Wang Y, Ueda T, Okamura A, et al. High lipoprotein(a) is a predictor of adverse events and heart failure in patients with acute myocardial infarction. Circ J. Published online October 16, 2026. doi:10.1253/circj.CJ-26-0268
2. Novartis announces Lp(a)HORIZON phase III topline results for pelacarsen in patients with elevated Lp(a) and established cardiovascular disease (CVD). News release. Novartis. September 4, 2026. Accessed October 19, 2026. https://www.novartis.com/us-en/news/media-releases/novartis-announces-lpahorizon-phase-iii-topline-results-pelacarsen-patients-elevated-lpa-and-established-cardiovascular-disease-cvd