The influence of baseline risk on the relation between HbA1c and risk for new cardiovascular events and mortality in patients with type 2 diabetes and symptomatic cardiovascular disease.

BACKGROUND: Strict glycaemic control in patients with type 2 diabetes has proven to have microvascular benefits while the effects on CVD and mortality are less clear, especially in high risk patients. Whether strict glycaemic control would reduce the risk of future CVD or mortality in patients with type 2 diabetes and pre-existing CVD, is unknown. This study aims to evaluate whether the relation between baseline HbA1c and new cardiovascular events or mortality in patients with type 2 diabetes and pre-existing cardiovascular disease (CVD) is modified by baseline vascular risk. METHODS: A cohort of 1096 patients with type 2 diabetes and CVD from the Second Manifestations of ARTerial Disease (SMART) study was followed. The relation between HbA1c at baseline and future vascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality was evaluated with Cox proportional hazard analyses in a population that was stratified for baseline risk for vascular events as calculated with the SMART risk score. The mean follow-up duration was 6.9 years for all-cause mortality and 6.4 years for vascular events, in which period 243 and 223 cases were reported, respectively. RESULTS: A 1 % increase in HbA1c was associated with a higher risk for all-cause mortality (HR 1.18, 95 % CI 1.06-1.31). This association was also found in the highest SMART risk quartile (HR 1.33, 95 % CI 1.11-1.60). There was no relation between HbA1c and the occurrence of cardiovascular events during follow-up (HR 1.03, 95 % CI 0.91-1.16). The interaction term between HbA1c and SMART risk score was not significantly related to any of the outcomes. CONCLUSION: In patients with type 2 diabetes and CVD, HbA1c is related to the risk of all-cause mortality, but not to the risk of cardiovascular events. The relation between HbA1c and all-cause mortality in patients with type 2 diabetes and vascular disease is not dependent on baseline vascular risk.

The relation between HbA1c and cardiovascular events in patients with type 2 diabetes with and without vascular disease.

OBJECTIVE: Poor glycemic control is related to vascular events in patients with type 2 diabetes, but the presence of vascular disease might influence this relation. We evaluated the relation between glycemic control (HbA1c level) and new cardiovascular events and mortality in patients with type 2 diabetes, with and without vascular disease. RESEARCH DESIGN AND METHODS: In a cohort of 1,687 patients with type 2 diabetes enrolled in the Second Manifestations of Arterial Disease (SMART) study, the continuous relation between HbA1c and cardiovascular events (composite of myocardial infarction, stroke, and vascular mortality) and all-cause mortality was evaluated with Cox proportional hazard analyses stratified for the presence of vascular disease. RESULTS: During a median follow-up time of 6.1 years (interquartile range 3.1-9.5 years), a new cardiovascular event developed in 293 patients and 340 patients died. In all patients, the hazard ratio (HR) of the relation between HbA1c level and cardiovascular events was 1.06 (95% CI 0.97-1.17). A 1 percentage point higher HbA1c level was related to a 27% higher risk of a cardiovascular event in patients with type 2 diabetes without vascular disease (HR 1.27 [95% CI 1.06-1.51]), but not in patients with vascular disease (HR 1.03 [95% CI 0.93-1.15], P for interaction = 0.195). A 1 percentage point higher HbA1c level was related to a 16% higher risk of death (HR 1.16 [95% CI 1.06-1.28]) in patients with vascular disease and a nonsignificant 13% higher risk of all-cause mortality (HR 1.13 [95% CI 0.97-1.31]) in patients without vascular disease. CONCLUSIONS: In patients with type 2 diabetes, there is a modest, but not statistically significant, relation between HbA1c level and cardiovascular events, and, as there was no statistically significant interaction, this relation was not different for patients with or without clinical manifestation of vascular disease.