Association between Proenkephalin A and cardiovascular outcomes in ambulatory Veterans

Proenkephalin (PENK) is a novel biomarker of kidney function associated with cardiovascular risk in patients with cardiovascular disease. Its association with cardiovascular outcomes in ambulatory individuals is less described. In an observational study of 199 ambulatory Veterans enrolled from April to September 2010, we assessed PENK's association with major adverse cardiac events (MACE - cardiovascular death, heart failure [HF] hospitalization, myocardial infarction [MI], or stroke) and individual outcomes of all-cause mortality, incident HF, and cardiovascular death using Cox regression. We also assessed the association of PENK with left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and left ventricular mass index (LVMi) with linear regression. The mean age was 66 ± 12 years, 99 % were men, and 76 % were White, with median follow-up of 12.7 years. Each two-fold higher PENK was associated with a 73 % higher risk of MACE in unadjusted analysis (HR 1.73; 95 % CI 1.00, 2.99; p = 0.043), though this association lost significance after adjusting for confounders (HR 1.69; 95 % CI 0.90-3.15; p = 0.098). PENK was not associated with all-cause mortality, incident HF or cardiovascular death, although risk estimates were elevated with wide confidence intervals for incident HF and cardiovascular death. PENK was not associated with LVMi or LVEDd but had a non-linear relationship with LVEF with low and high PENK associated with lower LVEF. In conclusion, PENK may be associated with a higher risk of MACE in ambulatory Veterans with diverse health statuses; however, further studies are needed. Abbreviations: PENK: Proenkephalin A; MACE: Major Adverse Cardiac Events.