title: Determinants of residual risk in secondary prevention patients treated with high- versus low-dose statin therapy: the Treating to New Targets (TNT) study.
abstract: BACKGROUND
  Cardiovascular events occur among statin-treated patients, albeit at lower rates. Risk factors for this "residual risk" have not been studied comprehensively. We aimed to identify determinants of this risk above and beyond lipid-related risk factors.
  
  
  RESULTS
  A total of 9251 coronary patients with low-density lipoprotein cholesterol <130 mg/dL randomized to double-blind atorvastatin 10 or 80 mg/d in the Treating to New Targets (TNT) study had complete on-treatment 1-year lipid data. Median follow-up was 4.9 years. The primary end point was major cardiovascular events (n=729): coronary death, nonfatal myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. Multivariable determinants of increased risk were older age (adjusted hazard ratio [aHR], 1.13 per 1 SD [8.8 years]; 95% confidence interval [CI], 1.04-1.23), increased body mass index (aHR, 1.09; 95% CI, 1.02-1.17 per 4.5 kg/m(2)), male sex (aHR, 1.33; 95% CI, 1.07-1.65), hypertension (aHR, 1.38; 95% CI, 1.17-1.63), diabetes mellitus (aHR, 1.33; 95% CI, 1.11-1.60), baseline apolipoprotein B (aHR, 1.19; 95% CI, 1.11-1.28 per 19 mg/dL), and blood urea nitrogen (aHR, 1.10; 95% CI, 1.03-1.17 per 4.9 mg/dL), in addition to current smoking, prior cardiovascular disease, and calcium channel blocker use. Determinants of decreased risk were high-dose statin (aHR, 0.82; 95% CI, 0.70-0.94), aspirin use (aHR, 0.67; 95% CI, 0.56-0.81), and baseline apolipoprotein A-I (aHR, 0.91; 95% CI, 0.84-0.99 per 25 mg/dL). On-treatment 1-year lipids or apolipoproteins were not additionally associated with risk in multivariable models. Known baseline variables performed moderately well in discriminating future cases from noncases (Harrell c index=0.679).
  
  
  CONCLUSIONS
  Determinants of residual risk in statin-treated secondary prevention patients included lipid-related and nonlipid factors such as baseline apolipoproteins, increased body mass index, smoking, hypertension, and diabetes mellitus. A multifaceted prevention approach should be underscored to address this risk.
  
  
  BACKGROUND
  URL: http://clinicaltrials.gov. Unique identifier: NCT00327691.
authors.affiliation: Brigham and Women's Hospital, Boston, MA 02215, USA. smora@partners.org
authors.forename: Samia
authors.initials: S
authors.lastname: Mora
authors.forename: Nanette K
authors.initials: NK
authors.lastname: Wenger
authors.forename: David A
authors.initials: DA
authors.lastname: Demicco
authors.forename: Andrei
authors.initials: A
authors.lastname: Breazna
authors.forename: S Matthijs
authors.initials: SM
authors.lastname: Boekholdt
authors.forename: Benoit J
authors.initials: BJ
authors.lastname: Arsenault
authors.forename: Prakash
authors.initials: P
authors.lastname: Deedwania
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: David D
authors.initials: DD
authors.lastname: Waters
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D015992:Body Mass Index; D016887:Cardiopulmonary Resuscitation; D008078:Cholesterol, LDL / Q000097:blood; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D005260:Female; D006323:Heart Arrest / Q000517:prevention & control / Q000628:therapy; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D011758:Pyrroles / Q000627:therapeutic use*; D012306:Risk; D012737:Sex Factors; D020521:Stroke / Q000517:prevention & control
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin