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CLINICAL RESEARCH: LIPIDS AND ATHEROSCLEROSIS

Clinical Significance of High-Density Lipoprotein Cholesterol in Patients With Low Low-Density Lipoprotein Cholesterol

Emil M. deGoma, MD^_*,_*, Nicholas J. Leeper, MD^_* and Paul A. Heidenreich, MD, MS^_*,

^_* Department of Cardiology, Stanford University Hospital, Stanford, California
Department of Cardiology, Veterans Administration Palo Alto Health Care System, Palo Alto, California.

Manuscript received May 2, 2007; revised manuscript received July 23, 2007, accepted July 24, 2007.

^_* Reprint requests and correspondence: Dr. Emil M. deGoma, 300 Pasteur Drive, Falk Cardiovascular Research Center, Department of Cardiology, Stanford University Hospital, Stanford, California 94305. (Email: edegoma{at}stanford.edu).

Objectives: We sought to evaluate the significance of high-density lipoprotein cholesterol (HDL-C) in the context of low low-density lipoprotein cholesterol (LDL-C).

Background: Earlier studies support an inverse correlation between circulating HDL-C and coronary risk in patients with normal or elevated LDL-C.

Methods: This study involved 4,188 patients attending the Palo Alto Veterans Administration Medical Center or affiliated clinics with LDL-C levels below 60 mg/dl. Outcomes were examined 1 year after the index LDL-C date. The combined primary end point was myocardial injury or hospitalization from ischemic heart disease. The secondary end point was all-cause mortality.

Results: Mean HDL-C levels (mg/dl) by quartile (Q) were: Q1 28 mg/dl, Q2 36 mg/dl, Q3 43 mg/dl, and Q4 63 mg/dl. The rate of myocardial injury or hospitalization for ischemic heart disease showed an inverse relationship to HDL-C (adjusted odds ratios: Q1 1.59 [95% confidence interval (CI) 1.16 to 2.19], Q2 1.39 [95% CI 1.01 to 1.92], Q3 1.33 [95% CI 0.96 to 1.84], and Q4 reference) that persisted regardless of statin use or recent myocardial injury. Analyzing HDL-C as a continuous variable revealed a 10% [95% CI 3% to 17%] increase in the combined end point of myocardial injury or hospitalization for ischemic heart disease for every 10-mg/dl decrease in HDL-C. The unadjusted and adjusted incidence of all-cause mortality demonstrated a U-shaped relationship to HDL-C (adjusted odds ratios: Q1 1.13 [95% CI 0.79 to 1.62], Q2 0.97 [95% CI 0.67 to 1.40], Q3 0.74 [95% CI 0.50 to 1.09], and Q4 reference).

Conclusions: The inverse relationship between HDL-C and coronary risk persists even among patients with LDL-C below 60 mg/dl, although a U-shaped relationship is observed between HDL-C and all-cause mortality.

Abbreviations and Acronyms   HDL-C = high-density lipoprotein cholesterol   ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification   IHD = ischemic heart disease   LDL-C = low-density lipoprotein cholesterol   MI = myocardial infarction   OR = odds ratio   Q = quartile   TnI = troponin I

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