Background Type 2 diabetes is a condition associated with a state of low-grade inflammation caused by adipose tissue dysfunction and insulin resistance. High sensitive-CRP (hs-CRP) is a marker for systemic low-grade inflammation and higher plasma levels have been associated with cardiovascular events in various populations. The aim of the current study is to evaluate the relation between hs-CRP and incident cardiovascular events and all-cause mortality in high-risk type 2 diabetes patients. Methods Prospective cohort study of 1679 type 2 diabetes patients included in the Second Manifestations of ARTerial disease (SMART). Cox proportional hazard models were used to evaluate the risk of hs-CRP on cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality. Hs-CRP was log-transformed for continuous analyses. Findings were adjusted for age, sex, BMI, current smoking and alcohol use, non-HDL-cholesterol and micro-albuminuria. Results 307 new cardiovascular events and 343 deaths occurred during a median follow-up of 7.8 years (IQR 4.2–11.1). A one unit increase in log(hs-CRP) was related to an increased vascular- and all-cause mortality risk (HR 1.21, 95% CI 1.01–1.46 and HR 1.26, 95% CI 1.10–1.45 respectively). No relation was found between log(hs-CRP) and myocardial infarction or stroke. The relations were similar in patients with and without previous vascular disease. Conclusion Low grade inflammation, as measured by hs-CRP, is an independent risk factor for vascular- and all-cause mortality but not for cardiovascular events in high-risk type 2 diabetes patients. Chronic low-grade inflammation may be a treatment target to lower residual cardiovascular risk in type 2 diabetes patients.

OBJECTIVETo evaluate whether low HDL cholesterol (HDL-c) levels are a risk factor for cardiovascular disease and mortality in patients with type 2 diabetes and whether it remains a residual risk factor when attaining low LDL cholesterol (LDL-c) treatment goals or when LDL-c is treated with intensive lipid-lowering therapy. RESEARCH DESIGN AND METHODSWe performed a prospective cohort study of 1,829 patients with type 2 diabetes included in the Second Manifestations of ARTerial disease (SMART) cohort. Cox proportional hazard models were used to evaluate the risk of HDL-c on cardiovascular events and all-cause mortality. Analyses were performed in strata of LDL-c levels (<2.0, 2.0-2.5, and >2.5 mmol/L) and lipid-lowering therapy intensity and were adjusted for age, sex, BMI, smoking, alcohol, LDL-c, triglycerides, systolic blood pressure, estimated glomerular filtration rate, glucose, and HbA 1c . RESULTSA total of 335 new cardiovascular events and 385 deaths occurred during a median follow-up of 7.0 years (interquartile range 3.9-10.4). No relation was found between plasma HDL-c and cardiovascular events (hazard ratio [HR] 0.97, 95% CI 0.93-1.01) or all-cause mortality (HR 0.99, 95% CI 0.96-1.03). Subgroup analysis supported effect modification by plasma LDL-c levels. In patients with LDL-c levels <2.0 mmol/L, higher HDL-c was related to higher risk for all-cause mortality (HR 1.14, 95% CI 1.07-1.21). Higher HDL-c was also related to higher risk for cardiovascular events in patients with LDL-c levels <2.0 mmol/L (HR 1.10, 95% CI 1.07-1.21) in contrast to patients with LDL-c levels between 2.0 and 2.5 mmol/L (HR 0.85, 95% CI 0.75-0.95) and >2.5 mmol/L (HR 0.96, 95% CI 0.91-1.00). CONCLUSIONSIn high-risk patients with type 2 diabetes with LDL-c levels <2.0 mmol/L, higher HDL-c at baseline is unexpectedly related to a higher risk for cardiovascular events and all-cause mortality in contrast to high-risk patients with type 2 diabetes with LDL-c levels between 2.0 and 2.5 mmol/L.As a result of aging, urbanization, and associated lifestyle changes, the prevalence of type 2 diabetes is globally increasing (1). In an attempt to lower the high risk for cardiovascular disease in patients with type 2 diabetes, emphasis has been placed on improving glycemic control, lowering blood pressure, and improving the dyslipidemia

Aim To quantify the risk of different non‐invasive arterial stiffness measurements with macrovascular disease and all‐cause mortality in high‐risk people with Type 2 diabetes. Methods We conducted a prospective cohort study of 1910 people with Type 2 diabetes included in the Second Manifestations of ARTerial disease (SMART) study. Arterial stiffness was assessed by brachial artery pulse pressure, normal range (≥0.9) ankle–brachial index and carotid artery distension. Cox regression was used to evaluate the effects of arterial stiffness on risk of cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all‐cause mortality. Results A total of 380 new cardiovascular events and 436 deaths occurred during a median (interquartile range) follow‐up of 7.5 (4.1–11.0) years. A 10‐mmHg higher brachial pulse pressure was related to higher hazard of cardiovascular events (hazard ratio 1.09, 95% CI 1.02 to 1.16) and all‐cause mortality (hazard ratio 1.10, 95% CI 1.03 to 1.16). A 0.1‐point lower ankle–brachial index within the normal range was related to a higher hazard of cardiovascular events (hazard ratio 1.13, 95% CI 1.01 to 1.27) and all‐cause mortality (hazard ratio 1.17, 95% CI 1.04 to 1.31). A one‐unit (10−3×kPa−1) lower carotid artery distensibility coefficient was related to a higher hazard of vascular mortality (hazard ratio 1.04, 95% CI 1.00 to 1.09) and all‐cause mortality (hazard ratio 1.04, 95% CI 1.00 to 1.07). Conclusion Increased arterial stiffness, as measured by either increased pulse pressure, normal‐range ankle–brachial index or carotid artery distensibility coefficient, is related to increased hazard of cardiovascular events and all‐cause mortality in people with Type 2 diabetes.

Aim To quantify the magnitude and specific contributions of known cardiovascular risk factors leading to higher cardiovascular risk and all‐cause mortality caused by type 2 diabetes (T2D). Methods Mediation analysis was performed to assess the relative contributions of known classical risk factors for vascular disease in T2D (insulin resistance, systolic blood pressure, renal function, LDL‐cholesterol, triglycerides and micro‐albuminuria), and what proportion of the effect of T2D on cardiovascular events and all‐cause mortality these factors mediate in the Second Manifestations of ARTerial disease (SMART) cohort consisting of 1910 T2D patients. Results Only 35% (95% CI 15‐71%) of the excess cardiovascular risk caused by T2D is mediated by the classical cardiovascular risk factors. The largest mediated effect was through insulin resistance [proportion of mediated effect (PME) 18%, 95% CI 3‐37%], followed by elevated triglycerides (PME 8%, 95% CI 4‐14%) and micro‐albuminuria (PME 7%, 95% CI 3‐17%). Only 42% (95% CI 18‐73%) of the excess mortality risk was mediated by the classical risk factors considered. The largest mediated effect was by micro‐albuminuria (PME 18%, 95% CI 10‐29%) followed by insulin resistance (PME 15%, 95% CI 1‐33%). Conclusion A substantial amount of the increased cardiovascular risk and all‐cause mortality caused by T2D cannot be explained by traditional vascular risk factors. Future research should focus on identifying non‐classical pathways that might further explain the increased cardiovascular and mortality risk caused by T2D.

Thiopental anesthesia causes arrhythmias sec, whereas anesthesia in general predisposes for drug-induced TdP in the CAVB dog. In combination with dofetilide, T + I has a more arrhythmic outcome than P + I or P + H.