title: HDL Cholesterol as a Residual Risk Factor for Vascular Events and All-Cause Mortality in Patients With Type 2 Diabetes.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Shahnam
authors.initials: S
authors.lastname: Sharif
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: van der Graaf
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Hendrik M
authors.initials: HM
authors.lastname: Nathoe
authors.affiliation: Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Harold W
authors.initials: HW
authors.lastname: de Valk
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Frank L J
authors.initials: FL
authors.lastname: Visseren
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands j.westerink-3@umcutrecht.nl.
authors.forename: Jan
authors.initials: J
authors.lastname: Westerink
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000097:blood* / Q000150:complications*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D014280:Triglycerides