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CLINICAL RESEARCH: ATHEROSCLEROSIS

Plasma triglycerides and type III hyperlipidemia are independently associated with premature familial coronary artery disease

Paul N. Hopkins, MD, MSPH^_*,_*, Lily L. Wu, PhD^_*,, Steven C. Hunt, PhD^_* and Eliot A. Brinton, MD^_*

^_* Cardiovascular Genetics, Department of Internal Medicine, Cardiology Division, University of Utah School of Medicine, Associated Regional and University Pathologists, Salt Lake City, Utah
Department of Pathology, University of Utah School of Medicine, Associated Regional and University Pathologists, Salt Lake City, Utah

Manuscript received September 1, 2004; revised manuscript received November 22, 2004, accepted November 29, 2004.

^_* Reprint requests and correspondence: Dr. Paul N. Hopkins, University of Utah, Cardiovascular Genetics Research, 410 Chipeta Way, Room 167, Salt Lake City, Utah 84108 (Email: paul{at}ucvg.med.utah.edu).

OBJECTIVES: This study was designed to explore contributions of plasma total triglycerides (TGs) and type III hyperlipidemia to the risk of premature familial coronary artery disease (CAD).

BACKGROUND: Although plasma TGs are recognized as a risk factor for CAD, the independence of this association from related risk factors remains controversial. Also, the degree of CAD risk conferred by excess remnants of TG-rich lipoproteins in type III hyperlipidemia remains unclear.

METHODS: We analyzed lipids by ultracentrifugation in a series of 653 cases with premature familial CAD (myocardial infarction or revascularization by age 55 years in men or age 65 years in women, with similar onset in at least one other first-degree relative) and in 1,029 control subjects. The relationship of CAD risk to various strata of plasma TGs, high-density lipoprotein (HDL) cholesterol, and type III hyperlipidemia, and interactions among these variables were examined by multiple logistic regression, adjusting for other CAD risk factors.

RESULTS: The odds ratio for CAD with elevated plasma TG rose progressively to 11.4 in those with TGs 500 to 799 mg/dl (95% confidence interval 3.4 to 38.0, p < 0.0001) compared with <100 mg/dl, even after correction for HDL cholesterol, other elements of the metabolic syndrome, and other CAD risk factors. Risk of CAD associated with type III hyperlipidemia (found in 3.4% of cases) was also markedly increased independent of other risk factors (odds ratios of 5 to 10 depending on the model, all with p < 0.002).

CONCLUSIONS: The association between the plasma TG level and premature familial CAD is strong, graded, and independent. Risk of CAD is also strikingly elevated with type III hyperlipidemia.

Abbreviations and Acronyms   BMI = body mass index   CABG = coronary artery bypass grafting   CAD = coronary artery disease   CI = confidence interval   HDL = high-density lipoprotein   LDL = low-density lipoprotein   TG = triglyceride

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