title: Effects of combination lipid therapy on coronary stenosis progression and clinical cardiovascular events in coronary disease patients with metabolic syndrome: a combined analysis of the Familial Atherosclerosis Treatment Study (FATS), the HDL-Atherosclerosis Treatment Study (HATS), and the Armed Forces Regression Study (AFREGS).
abstract: We examined the impact of metabolic syndrome (MS) on coronary stenosis progression and major cardiovascular (CV) events and investigated the mitigating effects of low-density lipoprotein (LDL) cholesterol lowering and LDL cholesterol lowering plus high-density lipoprotein (HDL) cholesterol increasing. This analysis combined individual patient data from 445 subjects who participated in 3 double-blinded, randomized, placebo-controlled trials (FATS, HATS, and AFREGS) comparing intensive lipid therapy to placebos on coronary stenosis progression by quantitative coronary angiography and on major CV events. The primary end points were change in mean proximal coronary diameter stenosis (Delta%S(prox)) over 3 years and the frequency of the predefined composite of coronary artery disease death, nonfatal myocardial infarction, stroke, and revascularization due to worsening ischemia. Patients with MS had 50% more rapid coronary stenosis progression and 64% increased CV event frequency compared to those without. More rapid coronary stenosis progression was significantly and independently associated with a 3.5-fold increased event risk (p <0.001). Combination lipid therapy significantly decreased stenosis progression by 83% (Delta%S(prox) 0.5 vs 2.9, p <0.001) in patients with MS and induced a small net regression in those without (Delta%S(prox) -0.3 vs 2.0, p <0.001). Combination therapy decreased the event rate by 54% (13% vs 28%, p = 0.03) in those with MS and by 82% (3% vs 17%, p = 0.002) without. On average, each 10% decrease in LDL cholesterol or 10% increase in HDL cholesterol was significantly associated with a 0.3 Delta%S(prox) decrease. Each 10% decrease in LDL cholesterol or 10% increase in HDL cholesterol was associated with 11% (p = 0.02) or 22% (p <0.001) event risk decrease. In conclusion, patients with MS have significantly more rapid coronary stenosis progression and a higher frequency of CV events. Greater stenosis progression rate is associated with a higher event rate. LDL cholesterol-lowering and HDL cholesterol-increasing therapies independently and significantly decrease coronary stenosis progression and decrease CV events.
authors.affiliation: Department of Medicine, Division of Cardiology, University of Washington School of Medicine, Seattle, Washington, USA. xueqiao@u.washington.edu
authors.forename: Xue-Qiao
authors.initials: XQ
authors.lastname: Zhao
authors.forename: Richard A
authors.initials: RA
authors.lastname: Krasuski
authors.forename: Jefferson
authors.initials: J
authors.lastname: Baer
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Whitney
authors.forename: Blazej
authors.initials: B
authors.lastname: Neradilek
authors.forename: Alan
authors.initials: A
authors.lastname: Chait
authors.forename: Santica
authors.initials: S
authors.lastname: Marcovina
authors.forename: John J
authors.initials: JJ
authors.lastname: Albers
authors.forename: B Greg
authors.initials: BG
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D017023:Coronary Angiography; D023921:Coronary Stenosis / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D008875:Middle Aged; D008889:Military Personnel; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012307:Risk Factors; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors