Shahnam Sharif1, Yolanda van der Graaf2, Hendrik M Nathoe3, Harold W de Valk4, Frank L J Visseren1, Jan Westerink5. 1. Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands. 2. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. 3. Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands. 4. Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands. 5. Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands j.westerink-3@umcutrecht.nl.
Abstract
OBJECTIVE: To 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 METHODS: We 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 HbA1c. RESULTS: A 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). CONCLUSIONS: In 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.
OBJECTIVE: To 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 METHODS: We 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 HbA1c. RESULTS: A 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). CONCLUSIONS: In 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.