HDL Cholesterol as a Residual Risk Factor for Vascular Events and All-Cause Mortality in Patients With Type 2 Diabetes

Abstract

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

The risk of mortality among people with type 2 diabetes in Latin America: A systematic review and meta‐analysis of population‐based cohort studies

“…Our results showed an increased risk of death for patients with T2DM similarly than previous studies conducted in high‐income countries . However, the strength of the association seems to be stronger in LA compared with other regions.…”

“…As the diabetes is less controlled in LA, it can be assumed that mortality because of T2DM may be higher . Metabolic control in general is also important because uncontrolled lipid profiles may increase mortality among people with T2DM . Ethnicity, genetics as well as cultural and health backgrounds may account for differences in T2DM mortality .…”

Predictors of intra-hospital mortality in patients with diabetic foot ulcers in Nigeria: data from the MEDFUN Study.

“…Diabetes mellitus is a cause of low HDL and low HDL is a risk factor for cardiovascular disease in the diabetic patient. 39 Furthermore, cardiovascular disease is reported to be the most prevalent cause of death in diabetic patients. 40,41 Co-morbid conditions that predicted mortality in this study were anemia, hypotension, cardiac failure, and renal impairment.…”

Response to Comment on Sharif et al. HDL Cholesterol as a Residual Risk Factor for Vascular Events and All-Cause Mortality in Patients With Type 2 Diabetes. Diabetes Care 2016;39:1424–1430

“…(1) on our recent article on HDL cholesterol (HDL-c) as a residual risk factor for vascular events and all-cause mortality in patients with type 2 diabetes (T2D) (2). The findings of our study in the Second Manifestations of ARTerial disease (SMART) cohort showed that higher HDL-c is related to an unexpected higher risk of cardiovascular events (hazard ratio [HR] 1.10, 95% CI 1.07-1.21) and all-cause mortality (HR 1.14, 95% CI 1.07-1.21) in patients with very low levels of LDL cholesterol (LDL-c) (,2.0 mmol/L).…”

“…The SMART cohort (7) is a unique cohort consisting of 1,829 high-risk T2D patients of whom 61% receive lipid-lowering treatment (29% usual dose; 32% intensive lipid-lowering therapy) (2). These patients have a median duration of diabetes of 4 years (interquartile range [IQR] 1-9) and the majority (66%) has clinical manifest vascular disease (2). The cohort studied by Aryan et al (1) seems to consist of a healthier study population compared with the SMART cohort (e.g., age 55 6 10 years vs. 60 6 10 years; males 44% vs. 70%).…”