Proenkephalin for Cardiovascular and All-Cause Mortality: The REasons for Geographic and Racial Differences in Stroke Study (REGARDS) Study.
Academic Article
Overview
abstract
INTRODUCTION: Individuals with kidney dysfunction have greater risk of mortality, especially cardiovascular mortality, but current markers of kidney function, including estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), may not adequately capture this risk. Proenkephalin (PENK) is an emerging biomarker reflecting kidney glomerular function. We evaluated the association of PENK with all-cause and cardiovascular mortality in The REasons for Geographic and Racial Disparities in Stroke (REGARDS) cohort study and whether associations varied by sex and race. METHODS: PENK was measured in 1,021 Black and White participants randomly sampled from REGARDS. We evaluated the association of PENK with all-cause and cardiovascular mortality in nested multivariable Cox proportional hazard models adjusting for confounders including UACR and eGFR calculated using the 2021 CKD-EPI combined creatinine-cystatin C race-free equation. Effect modification by sex and race was tested. RESULTS: Mean age was 67 years, 50% were women, 50% were Black, mean eGFR was 82 mL/min/1.73 m2 and median UACR was 7.7 mg/g. There were 471 deaths and 142 cardiovascular deaths over a median follow-up of 11.6 years. When adjusting for comorbidities and UACR, each doubling of PENK was associated with higher risk of death (HR 1.22, 95% confidence interval [CI] 1.00-1.48, p = 0.05) but this association was not significant after adjusting for eGFR (HR 0.85, 95% CI: 0.65-1.10, p = 0.85). There was a significant interaction by sex (p-interaction = 0.004) with higher PENK levels associated with lower mortality in women. PENK was associated with cardiovascular mortality after adjusting for comorbidities and UACR (HR 1.70, 95% CI: 1.20-2.42, p = 0.004), but this was not significant when adjusting for eGFR (HR 1.36, 95% CI: 0.84-2.21, p = 0.20). There was no significant interaction by sex or race. CONCLUSION: PENK does not provide additional risk stratification for all-cause and cardiovascular mortality beyond current biomarker measures of eGFR.
