Copeptin and the risk of incident stroke, CHD and cardiovascular mortality in older men with and without diabetes: The British Regional Heart Study.

S Goya Wannamethee,Paul Welsh,Lucy Lennon,Olia Papacosta,Peter H Whincup,Naveed Sattar

doi:10.1007/s00125-016-4011-7

Abstract

Aims/hypothesisThis study aimed to examine the association between copeptin (a surrogate marker of arginine vasopressin) and incident stroke, CHD and cardiovascular mortality in older men with and without diabetes.MethodsWe conducted a prospective study of 3536 men aged 60–79 years who were followed for an average of 13 years. During this period, there were 437 major CHD events (fatal and non-fatal myocardial infarction [MI]), 323 stroke events (fatal and non-fatal) and 497 cardiovascular disease (CVD) deaths. Prevalent diabetes was defined on the basis of a history of doctor-diagnosed diabetes or fasting blood glucose ≥7.0 mmol or HbA1c ≥6.5% (48 mmol/mol) (n = 428).ResultsNo association was seen between copeptin and incident stroke or CVD mortality in men without diabetes after adjustment for conventional cardiovascular risk factors, renal dysfunction, and insulin and N-terminal pro B-type natriuretic peptide levels. In contrast, elevated copeptin levels were associated with an increased risk of stroke and CVD mortality in men with diabetes after these adjustments. Compared with those in the lowest tertile of copeptin, men in the top tertile had adjusted relative HRs for stroke and CVD death of 2.34 (95% CI 1.04, 5.27) and 2.21 (1.12, 4.36), respectively. The risk of stroke and CVD mortality remained increased after the exclusion of men with prevalent stroke or MI. Higher levels of copeptin were associated with increased risk of CHD in the diabetic and non-diabetic groups, but these associations were attenuated after exclusion of individuals with a previous stroke or MI.Conclusions/interpretationCopeptin was independently associated with an increased risk of incident stroke and CVD mortality in men with diabetes, but not in men without diabetes. Targeting the arginine vasopressin system might have beneficial effects on CVD mortality and stroke risk in older men with diabetes.

Highlights

Cardiovascular disease (CVD) is the leading cause of death in patients with type 2 diabetes mellitus [1, 2]
We examined the association between copeptin and incident stroke, as well as CHD events and CVD mortality, in men with and without diabetes
Copeptin was positively associated with incident CHD in men both with and without diabetes, but these associations were to a large extent associated with pre-existing CVD as the exclusion of individuals with myocardial infarction (MI)/stroke attenuated the association in both groups

Summary

Introduction

Cardiovascular disease (CVD) is the leading cause of death in patients with type 2 diabetes mellitus [1, 2]. Vasopressin receptors are widely distributed throughout the brain [6] They are present in neurons, astrocytes and their perivascular processes, blood vessel endothelial and smooth muscle cells, and the choroid plexus. These locations suggest that vasopressin may participate in regulating vascular resistance in the cerebral circulation and water homeostasis in the brain [6]. Human and animal studies have indicated that the AVP system may play a role in glucose homeostasis, insulin resistance, and lipid and fat metabolism [7,8,9], and vasopressin has been reported to be elevated in patients with type 2 diabetes [10]. Copeptin has been established as a reliable marker of the circulating AVP concentration in routine clinical practice [11]

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