Abstract
BackgroundCardiovascular disease and kidney damage are tightly associated in people with type 2 diabetes. Experimental evidence supports a causal role for vasopressin (or antidiuretic hormone) in the development of diabetic kidney disease (DKD). Plasma copeptin, the COOH-terminal portion of pre-provasopressin and a surrogate marker of vasopressin, was shown to be positively associated with the development and progression of DKD. Here we assessed the association of plasma copeptin with the risk of cardiovascular events during follow-up in two prospective cohorts of type 2 diabetic patients, and we examined if this association could be mediated by deleterious effects of vasopressin on the kidney.MethodsWe studied 3098 and 1407 type 2 diabetic patients from the French cohorts DIABHYCAR and SURDIAGENE, respectively. We considered the incidence during follow-up (median: 5 years) of a combined end point composed of myocardial infarction, coronary revascularization, hospitalization for congestive heart failure, or cardiovascular death. Copeptin concentration was measured in baseline plasma samples by an immunoluminometric assay.ResultsThe cumulative incidence of cardiovascular events during follow-up by sex-specific tertiles of baseline plasma copeptin was 15.6% (T1), 18.7% (T2) and 21.7% (T3) in DIABHYCAR (p = 0.002), and 27.7% (T1), 34.1% (T2) and 47.6% (T3) in SURDIAGENE (p < 0.0001). Cox proportional hazards survival regression analyses confirmed the association of copeptin with cardiovascular events in both cohorts: hazard ratio with 95% confidence interval for T3 vs. T1 was 1.29 (1.04–1.59), p = 0.02 (DIABHYCAR), and 1.58 (1.23–2.04), p = 0.0004 (SURDIAGENE), adjusted for sex, age, BMI, duration of diabetes, systolic blood pressure, arterial hypertension, HbA1c, total cholesterol, HDL-cholesterol, triglycerides, estimated glomerular filtration rate (eGFR), urinary albumin concentration (UAC), active tobacco smoking, and previous history of myocardial infarction at baseline. No interaction was observed between plasma copeptin and eGFR (p = 0.40) or UAC (p = 0.61) categories on the risk of cardiovascular events in analyses of pooled cohorts.ConclusionsPlasma copeptin was positively associated with major cardiovascular events in people with type 2 diabetes. This association cannot be solely accounted for by the association of copeptin with kidney-related traits.
Highlights
Cardiovascular disease and kidney damage are tightly associated in people with type 2 diabetes
We looked for interactions between plasma copeptin and markers of kidney function at baseline in the association of copeptin with Cardiovascular disease (CVD) risk to evaluate if this association could be accounted for by deleterious effects of vasopressin on the kidney
We considered the incidence of cardiovascular events during follow-up, a combined end point composed of coronary heart disease, congestive heart failure (CHF) or cardiovascular death
Summary
Cardiovascular disease and kidney damage are tightly associated in people with type 2 diabetes. Experimental evidence supports a causal role for vasopressin (or antidiuretic hormone) in the development of diabetic kidney disease (DKD). The COOH-terminal portion of pre-provasopressin and a surrogate marker of vasopressin, was shown to be positively associated with the development and progression of DKD. The COOH-terminal portion of preprovasopressin and a surrogate marker of vasopressin, was shown to be positively associated with the decline in kidney function in the general population [11, 12, 17], and with the development and progression of DKD in type 1 and type 2 diabetes [10, 13, 16]. We looked for interactions between plasma copeptin and markers of kidney function at baseline in the association of copeptin with CVD risk to evaluate if this association could be accounted for by deleterious effects of vasopressin on the kidney
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