Low-attenuation plaque-mediated NSTEMI in a patient with sarcoidosis and high Lp(a)

Current coronary artery disease (CAD) risk assessment with risk calculators, including the Predicting Risk of cardiovascular disease EVENTs (PREVENT) equation, lipoprotein(a) [Lp(a)] screening, and coronary artery calcium (CAC) scoring, can miss individuals with vulnerable plaque. Low-attenuation plaque (LAP) is a high-risk imaging feature associated with higher myocardial infarction (MI) risk.

To describe a patient with a CAC score of 0 and low estimated CAD risk by conventional tools who nonetheless harbored extensive high-risk, low-attenuation plaque, and to define an imaging and biomarker phenotype in whom coronary CT angiography may add value despite reassuring standard risk metrics.

A 54-year-old man with recently diagnosed hyperlipidemia (low-density lipoprotein-cholesterol [LDL-C] of 136 mg/dL) and controlled sarcoidosis presented with syncope and exertional dyspnea. He was evaluated with coronary computed tomography angiography (CCTA), CT-based fractional flow reserve (FFR), artificial intelligence-enabled quantitative plaque analysis, and comprehensive risk assessment including the PREVENT equation, Lp(a), apolipoprotein B, polygenic risk scoring, and coronary inflammation by fat attenuation indexing.

Despite a CAC score of 0, CCTA revealed extensive noncalcified plaque and severe left anterior descending stenosis (>75%). CT-based FFR confirmed physiologically significant stenosis, with FFR of 0.72 (normal >0.8). Artificial intelligence-enabled quantitative plaque analysis revealed 100% noncalcified plaque and 30% LAP, the highest LAP reported to our knowledge. CAD risk was 3.0% by the PREVENT equation, Lp(a) was 191 nmol/L (normal <75 nmol/L), apolipoprotein B was 72 mg/dL (normal <90 mg/dL), polygenic risk was 6%, and coronary inflammation by fat attenuation indexing was low risk. The patient experienced a non-ST-segment elevation MI while awaiting outpatient catheterization and underwent revascularization.

This case suggests that markedly elevated Lp(a), in the setting of above-optimal LDL-C, can promote vulnerable, lipid-rich plaque even at relatively low cumulative LDL-C exposure. It also defines a patient phenotype that may warrant further risk stratification with CCTA despite a CAC score of 0: those with elevated Lp(a) and at least 1 additional risk enhancer, such as a chronic inflammatory disease like sarcoidosis.