Lipoprotein(a) and CAD & MI: JACC: Adv., February 2026
High levels of lipoprotein(a) (Lp(a)) are associated with the premature onset of obstructive coronary artery disease (CAD) and more extensive vessel involvement, including a 2.4-fold higher risk of ST-segment elevation myocardial infarction (STEMI), and carry a 15.9-fold higher risk for recurrent myocardial infarction (MI), as a recent study has shown.
The study has been published in the Journal of the American College of Cardiology (JACC): Advances in February 2026.
Breaking the Lp(a) Risk Profile
While it is established that Lp(a) serves as an independent genetic risk factor for MI, a significant knowledge gap persists regarding its specific influence on angiographic disease complexity and distinct MI phenotypes. Addressing this gap, the study aimed to investigate how very high Lp(a) levels independently affect the timing of diagnosis, clinical presentation, the anatomical extent of atherosclerotic CAD, and the occurrence of MI.
Study Overview
The investigation employed a retrospective nested subcohort design, matching 446 patients with very high Lp(a) levels (>230 nmol/L) to 223 low-level controls (≤7 nmol/L) in a 2:1 ratio within a tertiary hospital setting. Blinded investigators utilized multivariable logistic regression and Kaplan-Meier curves to evaluate primary endpoints, including time-to-first CAD diagnosis and multivessel disease prevalence, while excluding minors and individuals with insufficient data. Researchers used Invasive Coronary Angiography (ICA) to evaluate the anatomical complexity of lesions—quantified by the Synergy Between PCI with Taxus and Cardiac Surgery-1 (SYNTAX-1) score—and tracked outcomes until December 2024.
Key Clinical Findings of the Study Include:
- Earlier Clinical Detection: The study demonstrated that individuals with extreme Lp(a) levels were diagnosed with obstructive CAD significantly sooner than controls, with a mean detection age of 54 years compared to 57 years.
- Increased Anatomical Complexity: Research found that very high Lp(a) was associated with an increased prevalence of multivessel disease, yielding an adjusted odds ratio of 1.43 per 100 nmol/L increase.
- Predominance of STEMI: Investigation revealed that the high-risk group faced a 2.42-fold higher likelihood of presenting with STEMI, suggesting a link to more vulnerable plaque phenotypes.
- Extreme Recurrence Risk: Findings highlighted a dramatic 15.9-fold higher risk for recurrent MI in patients with levels above 230 nmol/L, emphasizing the particle's role in persistent cardiovascular vulnerability.
- Higher Revascularization Rates: Analysis indicated that revascularization procedures, encompassing both Percutaneous Coronary Intervention (PCI) and Coronary Artery Bypass Grafting (CABG), were nearly twice as common in the high-Lp(a) cohort at 20.6%.
Clinical Implications for Secondary Prevention
For practicing physicians, routine measurement of Lp(a) in the cardiac catheterization laboratory is essential for identifying younger patients with aggressive atherosclerosis and guiding more intensive, individualized secondary prevention strategies to mitigate the high risk of recurrent events. While acute measurements are typically stable, a follow-up assessment in the outpatient setting can establish a definitive baseline for long-term care as new therapeutic options emerge.
Reference
Coerkamp CF, Verpalen VA, Bouhbouh K, et al. Lipoprotein(a) and the Early Diagnosis, Complexity, and Extent of Coronary Artery Disease and Myocardial Infarction. JACC Adv. 2026;5(2):102542.
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