Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a)

JAMA. 1995 Dec 13;274(22):1771-4.


Objective: To determine if lowering elevated low-density lipoprotein cholesterol (LDL-C) levels offsets the adverse effect of raised lipoprotein(a) (Lp[a]) levels on coronary artery disease (CAC) in men.

Design: Randomized, double-blind, placebo-controlled trial of lipid lowering for CAD.

Setting: Post hoc analysis of the Familial Atherosclerosis Treatment Study.

Participants: A total of 146 men aged 62 years or younger with CAD and apolipoprotein B levels of at least 125 mg/dL.

Intervention: Patients received a Step II Diet and lovastatin (40 mg daily) plus colestipol (30 g daily), niacin (4 g daily) plus colestipol, or placebo (plus colestipol if LDL-C > 90th percentile) for 2.5 years. They were grouped by their LDL-C responses: "minimal" if LDL-C decreased by 10% or less from baseline (mean [SD] change, +6% [13%]) and "substantial" if LDL-C decreased more than 10% (mean [SD] change, -40% [16%]).

Main outcome measure: Impact of lowering elevated LDL-C on the cardiac event rate (death, myocardial infarction, and revascularization for refractory ischemia) and CAD change associated with elevated Lp(a).

Results: In multivariate analyses, the best correlate of baseline CAD severity was Lp(a) (r = 0.30; P < .001). For 36 patients with minimal LDL-C reduction, CAD progression correlated only with in-treatment Lp(a) levels (r = 0.45; P < .01), but for 84 patients with substantial LDL-C reduction, disease regressed and its change correlated with in-treatment LDL-C (r = 0.24; P < .05) but not with Lp(a) (r = -0.05). Lipoprotein(a) levels were not significantly altered in either group. For 40 patients with Lp(a) at the 90th percentile or higher, events were frequent (39%) if reduction of LDL-C was minimal, but were few (9%) if reduction was substantial (relative risk, 0.23; 95% confidence interval, 0.06 to 0.99).

Conclusions: In men with CAD and elevated LDL-C, Lp(a) levels were dominant correlates of baseline disease severity, its progression, and event rate over 2.5 years. However, with substantial LDL-C reductions, persistent elevations of Lp(a) were no longer atherogenic or clinically threatening. This provides a possible direction for treatment in such patients with elevated Lp(a) and LDL-C.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Cholesterol, LDL / blood*
  • Coronary Disease / complications
  • Coronary Disease / mortality
  • Coronary Disease / physiopathology*
  • Disease Progression
  • Double-Blind Method
  • Humans
  • Lipoprotein(a) / blood*
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology
  • Reoperation
  • Risk Factors
  • Severity of Illness Index


  • Cholesterol, LDL
  • Lipoprotein(a)