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Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a)
V M Maher1, B G Brown, S M Marcovina
1Department of Medicine, University of Washington School of Medicine, Seattle, USA.
Insights
Lowering low-density lipoprotein cholesterol (LDL-C) significantly reduces coronary artery disease (CAD) progression and events in men with high lipoprotein(a) (Lp[a]). Substantial LDL-C reduction mitigates the atherogenic risk of elevated Lp(a) levels.
Area of Science:
- Cardiovascular Medicine
- Lipid Metabolism
- Atherosclerosis Research
Background:
- Elevated lipoprotein(a) (Lp[a]) is a significant risk factor for coronary artery disease (CAD).
- The interaction between Lp(a) and low-density lipoprotein cholesterol (LDL-C) in CAD progression remains an area of investigation.
Purpose of the Study:
- To investigate whether reducing elevated LDL-C levels can counteract the adverse effects of high Lp(a) on CAD in men.
- To assess the impact of LDL-C reduction on CAD severity, progression, and cardiac events in the presence of elevated Lp(a).
Main Methods:
- A post hoc analysis of a randomized, double-blind, placebo-controlled trial involving 146 men with established CAD.
- Participants received lipid-lowering therapy (lovastatin plus colestipol or niacin plus colestipol) or placebo for 2.5 years.
- Patients were categorized based on LDL-C reduction: 'minimal' (≤10% decrease) or 'substantial' (>10% decrease).
Main Results:
- Elevated Lp(a) levels strongly correlated with baseline CAD severity.
- In patients with substantial LDL-C reduction, CAD regressed, and this regression correlated with LDL-C changes, not Lp(a) levels.
- For patients with high Lp(a), cardiac events were significantly lower (9%) with substantial LDL-C reduction compared to minimal reduction (39%).
Conclusions:
- In men with CAD and elevated LDL-C, Lp(a) is a key determinant of disease severity and progression.
- Substantial LDL-C reduction effectively neutralizes the atherogenic and clinical threat posed by elevated Lp(a) levels.
- Aggressive LDL-C lowering represents a viable therapeutic strategy for patients with co-existing high Lp(a) and LDL-C.
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.