Copeptin as a predictive marker of incident heart failure.

Aims: Heart failure (HF) is a common disease with increasing prevalence and poor prognosis. The vasopressin (VP) marker copeptin predicts development of diabetes mellitus, diabetic heart disease, coronary artery disease, and premature mortality. Copeptin is elevated in HF patients and predicts a worse outcome. This study aims to investigate whether copeptin can predict HF development.

Methods: Copeptin was analysed in 5297 individuals (69.6% men) without prevalent HF from the Malmö Preventive Project, a population-based prospective cohort. Cox proportional hazards models were used to analyse risk of incident HF by copeptin levels after adjusting for conventional cardiovascular risk factors.

Results: During a median follow-up time of 11.1 years, 350 subjects (6.6%) were diagnosed with HF. Of these events, 99 were classified as myocardial infarction (MI) related HF and 251 as non-MI-related HF. Individuals in the top quartile of copeptin had, after multivariate adjustment for conventional risk factors (age, sex, systolic blood pressure, diabetes mellitus, body mass index, antihypertensive therapy, smoking, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), a significantly increased risk of developing HF by 1.63 [confidence interval (CI) 1.20-2.21] for HF compared with the reference quartile 1. After adjustment for conventional risk factors, the hazard ratio (HR) per standard deviation increase of log-transformed copeptin for any HF was 1.30 (95% CI 1.17-1.46), whereas it was 1.39 (CI 1.13-1.71) for MI-related HF and 1.26 (CI 1.11-1.44) for non-MI-related HF. The associations remained after additional adjustment for estimated glomerular filtration rate [HR 1.24 (95% CI: 1.10-1.40)] and for pro atrial natriuretic peptide on top of conventional risk factors [HR 1.14 (95% CI: 1.02-1.28)].

Conclusions: Elevated copeptin predicts development of HF in older adults. Copeptin is a risk marker of VP-driven HF susceptibility and a candidate to guide prevention efforts of HF targeting the VP system.