title: Association Between Paradoxical HDL Cholesterol Decrease and Risk of Major Adverse Cardiovascular Events in Patients Initiated on Statin Treatment in a Primary Care Setting.
abstract: OBJECTIVE
  Statin-induced changes in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are unrelated. Many patients initiated on statins experience a paradoxical decrease in HDL-C. The aim of this study was to evaluate the association between a decrease in HDL-C and risk of major adverse cardiovascular events (MACE).
  
  
  METHODS
  Data from 15,357 primary care patients initiated on statins during 2004-2009 were linked with data from mandatory national hospital, drug-dispensing, and cause-of-death registers, and were grouped according to HDL-C change: decreased ≥0.1 mmol/L, unchanged ±0.1 or ≥0.1 mmol/L increased. To evaluate the association between decrease in HDL-C and risk of MACE, a sample of propensity score-matched patients from the decreased and unchanged groups was created, using the latter group as reference. MACE was defined as myocardial infarction, unstable angina pectoris, ischaemic stroke, or cardiovascular mortality. Cox proportional hazards models were used to estimate relative risks.
  
  
  RESULTS
  HDL-C decreased in 20%, was unchanged in 58%, and increased in 22% of patients initiated on statin treatment (96% treated with simvastatin). The propensity score-matched sample comprised 5950 patients with mean baseline HDL-C and LDL-C of 1.69 and 4.53 mmol/L, respectively. HDL-C decrease was associated with 56% higher MACE risk (hazard ratio 1.56; 95% confidence interval 1.12-2.16; p < 0.01) compared with the unchanged HDL-C group.
  
  
  CONCLUSIONS
  Paradoxical statin-induced reduction in HDL-C was relatively common and was associated with increased risk of MACE.
authors.affiliation: AstraZeneca, 151 85, Södertälje, Sweden. paal.hasvold@astrazeneca.com.|Medical Faculty, University of Oslo, 0424, Oslo, Norway. paal.hasvold@astrazeneca.com.
authors.forename: Pål
authors.initials: P
authors.lastname: Hasvold
authors.affiliation: Statisticon AB, 753 22, Uppsala, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Thuresson
authors.affiliation: Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala University, 751 05, Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Sundström
authors.affiliation: Institute of Environmental Medicine, Karolinska Institute, 171 77, Stockholm, Sweden.|Medical Evidence and Observational Research, AZ R&D, Mölndal, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Hammar
authors.affiliation: Medical Faculty, University of Oslo, 0424, Oslo, Norway.|Department of Cardiology, Oslo University Hospital, Oslo, Norway.
authors.forename: Sverre E
authors.initials: SE
authors.lastname: Kjeldsen
authors.affiliation: Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, 751 05, Uppsala, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Johansson
authors.affiliation: Department of Sports Medicine, Norwegian School of Sport Sciences, PO Box 4014, Ulleval Stadion, 0806, Oslo, Norway.
authors.forename: Ingar
authors.initials: I
authors.lastname: Holme
authors.affiliation: AstraZeneca, 151 85, Södertälje, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Bodegård
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D011320:Primary Health Care; D016016:Proportional Hazards Models; D012306:Risk; D020521:Stroke / Q000453:epidemiology; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors