Copeptin and risk of incident stroke, coronary heart disease and cardiovascular mortality in older men with and without diabetes: The British Regional Heart Study

Objective: To examine the association between copeptin (a surrogate marker of arginine vasopressin) and incident stroke, coronary heart disease (CHD) and cardiovascular mortality in older men with and without diabetes. Research design and methods: A prospective study of 3536 men aged 60-79 years followed up for an average 13 years during which there were 437 major CHD events [fatal and non-fatal myocardial infarction (MI)], 323 stroke events (fatal and non-fatal) and 497 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). Results: No association was seen between copeptin and incident stroke or CVD mortality in those without diabetes after adjustment for conventional CV risk factors, renal dysfunction, insulin and NT-proBNP. By contrast elevated copeptin was associated with increased risk of stroke and CVD mortality in men with diabetes after these adjustment Compared to those in the lowest tertile of copeptin the adjusted relative hazards ratio for stroke and CVD deaths were 2.36 (1.01,5.54) and 1.99 (1.01,3.92) respectively for men in the top tertile. Risk of stroke and CVD mortality remained increased after exclusion of men with prevalent stroke or MI. Copeptin showed significantly increased risk of CHD in both groups of men but these associations were attenuated after exclusion of those with previous MI/stroke. Conclusion- Copeptin was independently associated with increased risk of incident stroke and CVD mortality in men with diabetes but not in men without diabetes. Targeting the arginine vasopressin system may have beneficial effects on CVD mortality and stroke risk in older men with diabetes