Effects of Increasing High-Density Lipoprotein Cholesterol and Decreasing Low-Density Lipoprotein Cholesterol on the Incidence of First Acute Coronary Events (from the Air Force/Texas Coronary Atherosclerosis Prevention Study)

doi:10.1016/j.amjcard.2009.05.020

The American Journal of Cardiology

Volume 104, Issue 6, 15 September 2009, Pages 829-834

https://doi.org/10.1016/j.amjcard.2009.05.020 Get rights and content

Reducing low-density lipoprotein (LDL) cholesterol with statins reduces cardiovascular risk, but the associations between increases in high-density lipoprotein (HDL) cholesterol and cardiovascular risk at different LDL levels have been less well characterized. To evaluate the associations between the 1-year changes in HDL cholesterol and LDL cholesterol with lovastatin and subsequent acute major coronary events (AMCEs), we studied 2,928 patients in the lovastatin arm who were followed for 5.2 years in a post-hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). The percentage of HDL cholesterol increase and apolipoproteins at year 1 and the incidence of AMCEs thereafter were assessed stratified by the LDL cholesterol levels. With lovastatin, LDL cholesterol was reduced by 25% on average to 115 mg/dl at year 1, and HDL cholesterol increased 6.0%. Patients with both an increase in HDL cholesterol of ≥7.5% and LDL cholesterol of <115 mg/dl at year 1 had the lowest event rate (3.53/1,000 person-years; p = 0.028). Similar results were found for an increase in HDL cholesterol of ≥7.5% and a decrease in LDL cholesterol of >25%, as well as for apolipoproteins A-I and B. The 1-year percent increase in HDL cholesterol appeared to be associated with a reduction in AMCEs in subsequent follow-up (p = 0.07 with the percentage of HDL cholesterol increase analyzed continuously). Patients with an HDL cholesterol increase of ≥7.5% had an AMCE rate of 5.18 compared with 7.66/1,000 person-years in patients with a lower HDL cholesterol increase (p = 0.08). In conclusion, lovastatin therapy was associated with a greater risk reduction of AMCEs when LDL cholesterol was substantially reduced and the HDL cholesterol increased by ≥7.5%.

Section snippets

Methods

The study design for the AFCAPS/TexCAPS has been previously reported in detail.1, 2, 3 In brief, the AFCAPS/TexCAPS was a randomized, double-blind, placebo-controlled, primary prevention trial. The institutional review boards reviewed and approved the study protocol and informed consent document. Eligible subjects included postmenopausal women aged 55 to 73 years and men aged 45 to 73 years who had no previous history or present signs or symptoms of definite myocardial infarction, angina,

Results

After exclusion of patients who had had an AMCE in the first year (n = 23), those without an AMCE in the first year, but with ≤1 year of follow-up (n = 11), and those who did not have HDL cholesterol measured at year 1 (n = 342), 2,928 patients were eligible for analysis (Table 1). The baseline characteristics of these patients were comparable to those of the entire population randomized to lovastatin.

An additional 60 patients (including 1 patient with an AMCE) were excluded from the incidence

Discussion

The present analysis found that increases in serum HDL cholesterol of ≥7.5%, in tandem with decreases in LDL cholesterol of >25% or to an absolute LDL cholesterol concentration <115 mg/dl at statin treatment year 1, were associated with a significantly reduced incidence of a subsequent first major coronary event during the next 4 years in men and women without initial cardiovascular disease but with low HDL cholesterol levels. As demonstrated in a previous study using data also from the

Acknowledgment

Assistance in manuscript preparation was provided by Stephen W. Gutkin, BA, Rete Biomedical Communications Corporation (Wyckoff, New Jersey). Within the past 5 years, Mr. Gutkin has served as a paid consultant to the sponsor and its affiliates (including Merck/Schering-Plough, North Wales, Pennsylvania), as well as Abbott (Abbott Park, Illinois), Auxilium (Malvern, Pennsylvania), Bristol-Myers Squibb (Princeton, New Jersey), Cumberland (Nashville, Tennessee), Eli Lilly (Indianapolis, Indiana)

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: This study and its report were supported by Merck & Co., Inc., North Wales, Pennsylvania.

: Drs. Cui, Watson, Girman, and Shapiro are employees and shareholders of Merck & Co., Inc., North Wales, Pennsylvania. Dr. Gotto is a consultant for Genentech (South San Francisco, California), Kowa (Nagoya, Japan), Merck (Whitehouse Station, New Jersey) and Merck/Schering-Plough (Kenilworth, New Jersey), is on the board of directors of Aegerion (Bridgewater, New Jersey) and Arisaph Pharmaceuticals (Boston, Massachusetts), and is a member of the advisory boards for DuPont (Wilmington, Delaware) and Novartis (Cambridge, Massachusetts). Dr. Clearfield is a consultant and speaker for AstraZeneca (Wilmington, Delaware) and Merck & Co., Inc. (North Wales, Pennsylvania).

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Preventive cardiologyEffects of Increasing High-Density Lipoprotein Cholesterol and Decreasing Low-Density Lipoprotein Cholesterol on the Incidence of First Acute Coronary Events (from the Air Force/Texas Coronary Atherosclerosis Prevention Study)

Section snippets

Methods

Results

Discussion

Acknowledgment

Air Force/Texas Coronary Atherosclerosis Prevention studyPrimary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS

J Am Med Assoc

Relation between baseline and on-treatment lipid parameters and first acute major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)

Circulation

Design and rationale of the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)

Am J Cardiol

Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol

Clin Chem

Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge

Clin Chem

The Centers for Disease Control-National-Heart-Lung-And-Blood-institute Lipid Standardization Program—an approach to accurate and precise lipid measurements

Clin Lab Med

Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis

JAMA

Cholesterol and lipids in the risk of coronary artery disease—the Framingham Heart Study

Can J Cardiol

High-density lipoprotein cholesterol as a predictor of coronary heart disease risk: the PROCAM experience and pathophysiological implications for reverse cholesterol transport

Atherosclerosis

High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies

Circulation

High-density lipoprotein—the clinical implications of recent studies

N Engl J Med

Preventive cardiology
Effects of Increasing High-Density Lipoprotein Cholesterol and Decreasing Low-Density Lipoprotein Cholesterol on the Incidence of First Acute Coronary Events (from the Air Force/Texas Coronary Atherosclerosis Prevention Study)