Chronic hyperglycemia in type 2 diabetes increases the risk of microvascular events. However, there is continuing uncertainty about its effect on macrovascular outcomes and death. We conducted a meta-analysis of prospective studies to estimate the association of glycosylated hemoglobin level with the risk of all-cause mortality and cardiovascular outcomes among patients with type 2 diabetes. We systematically searched the MEDLINE database through April 2011 by using Medical Subject Heading search terms and a standardized protocol. We included prospective cohort studies that reported data of glycosylated hemoglobin level on the risk of incident cardiovascular events and all-cause mortality. Relative risk estimates (continuous and categorical variables) were derived or abstracted from each cohort study. Twenty six studies were included in this analysis with a mean follow-up rang of 2.2–16 years. The pooled relative risk associated with a 1% increase in glycosylated hemoglobin level among patients with type 2 diabetes was 1.15 (95% CI, 1.11 to 1.20) for all-cause mortality, 1.17 (95% CI, 1.12 to 1.23) for cardiovascular disease, 1.15 (95% CI, 1.10 to 1.20) for coronary heart disease, 1.11 (95% CI, 1.05 to 1.18) for heart failure, 1.11 (95% CI, 1.06 to 1.17) for stroke, and 1.29 (95% CI, 1.18 to 1.40) for peripheral arterial disease, respectively. In addition, a positive dose-response trend existed between glycosylated hemoglobin level and cardiovascular outcomes. Chronic hyperglycemia is associated with an increased risk for cardiovascular outcomes and all-cause mortality among patients with type 2 diabetes, likely independently from other conventional risk factors.

Background and Purpose—: The association of total and high-density lipoprotein (HDL) cholesterol with stroke risk is unclear, especially regarding hemorrhagic stroke. Methods—: We prospectively investigated the associations of serum total and HDL cholesterol and total/HDL cholesterol ratio with total and type-specific stroke incidence among 58 235 Finnish people aged 25 to 74 years and free of coronary heart disease and stroke at baseline. Results—: During a mean follow-up period of 20.1 years, 3914 participants developed stroke events (3085 ischemic, 497 intracerebral hemorrhage, and 332 subarachnoid hemorrhage). The multivariable-adjusted hazard ratios at different levels of total cholesterol (<5 [reference], 5–5.9, 6–6.0, ≥7.0 mmol/L) were 1.00, 1.05, 1.16, and 1.22 for total stroke ( P _trend =0.036) and 1.00, 1.06, 1.19, and 1.27 for ischemic stroke ( P _trend =0.02) in men and 1.00, 0.58, 0.61, and 0.50 for intracerebral hemorrhagic stroke ( P _trend =0.02) in women, respectively. Low levels of HDL cholesterol and high total/HDL cholesterol ratio were associated with increased risks of total and ischemic stroke in both men and women. These associations disappeared in men but remained significant in women after further adjustment for body mass index, blood pressure, and history of diabetes. Conclusions—: The study showed a positive association between total cholesterol and total and ischemic stroke risks in men and an inverse association between total cholesterol and intrahemorrhagic stroke risk in women. The inverse association of HDL cholesterol and a positive association of total/HDL cholesterol ratio with total and ischemic stroke risks were found in men and women. These associations attenuated after adjustment for body mass index, blood pressure, and history of diabetes.