Prognostic Utility of Secretory Phospholipase A2 in Patients With Stable Coronary Artery Disease

Study Questions:

Does secretory phospholipase A2 (sPLA2) have independent prognostic information above established risk markers in patients with stable coronary artery disease (CAD)?

Methods:

Plasma sPLA2 activity was measured at baseline in 3,708 subjects in the PEACE randomized trial of trandolapril versus placebo in stable CAD. Median follow-up was 4.8 years. Cox regression was used to adjust for demographics, clinical risk factors, apolipoprotein B, apolipoprotein A1, and treatment.

Results:

After multivariable adjustment, sPLA2 was associated with an increased risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio, Q4:Q1 1.6; 95% confidence interval [CI], 1.1-2.1) and cardiovascular death or heart failure (1.9, 1.2-3.0). After multivariable assessment, increased activities of sPLA2 were associated with the risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio, 1.5; 95% CI, 1.06-2.0), independent of lipoprotein-associated PLA2 mass and C-reactive protein. SPLA2 modestly improved the area under the curve (AUC) over established clinical risk factors (AUC, 0.668-0.675; p = 0.01). SPLA2, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin T all were independently associated with cardiovascular death or heart failure, and each improved risk discrimination (p = 0.02, p < 0.001, p < 0.001, respectively).

Conclusions:

sPLA2 activity provides independent prognostic information beyond established risk markers in patients with stable CAD. SPLA2 may represent a therapeutic target for improving outcomes.

Perspective:

Secretory phospholipase A2 is a member of a family of enzymes that catalyze the phospholipids into fatty acids and lysophospholipids. Both of these are associated with the induction of arrhythmias. In addition, there are data to suggest that these entities participate in the development of atherosclerosis. Previous data from this same group have shown the predictive value of the analyte post-acute coronary syndrome. This analysis in the PEACE cohort, a cadre of patients with stable coronary disease, is particularly well done because it uses both high-sensitivity cardiac troponin T and NT-proBNP as covariates along with clinical covariates, and the prognostic significance of sPLA2 persists. Thus, this marker may be valuable as a marker of the progression of atherosclerotic disease.

Clinical Topics: Acute Coronary Syndromes, Dyslipidemia, Heart Failure and Cardiomyopathies, Atherosclerotic Disease (CAD/PAD), ACS and Cardiac Biomarkers, Lipid Metabolism, Statins, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Coronary Artery Disease, Myocardial Infarction, Acute Coronary Syndrome, Stroke, Follow-Up Studies, Atherosclerosis, Fatty Acids, Apolipoprotein A-I, Risk Factors, Lysophospholipids, Natriuretic Peptides, Prognosis, Phospholipases A2, Biological Markers, Cardiology, Indoles, Heart Failure, Phospholipids


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