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CLINICAL RESEARCH: LIPIDS AND CORONARY DISEASE

Beyond Low-Density Lipoprotein Cholesterol

Respective Contributions of Non–High-Density Lipoprotein Cholesterol Levels, Triglycerides, and the Total Cholesterol/High-Density Lipoprotein Cholesterol Ratio to Coronary Heart Disease Risk in Apparently Healthy Men and Women

Benoit J. Arsenault, PhD^_*,, Jamal S. Rana, MD, PhD, Erik S.G. Stroes, MD, PhD^||, Jean-Pierre Després, PhD^_*,, Prediman K. Shah, MD, John J.P. Kastelein, MD, PhD^||, Nicholas J. Wareham, MBBS, PhD^#, S. Matthijs Boekholdt, MD, PhD^¶,_* and Kay-Tee Khaw, MBBChir^_**

^_* Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, Québec, Canada
Departments of Anatomy and Physiology, Faculty of Medicine, Université Laval, Québec, Québec, Canada
Division of Kinesiology, Department of Social and Preventive Medicine, Université Laval, Québec, Québec, Canada
Cedars-Sinai Heart Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California
^|| Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
^¶ Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands
^# Medical Research Council Epidemiology Unit, Institute of Public Health, University of Cambridge, Cambridge, United Kingdom
^_** Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, United Kingdom

Manuscript received April 17, 2009; revised manuscript received June 16, 2009, accepted July 12, 2009.

^_* Reprint requests and correspondence: Dr. S. Matthijs Boekholdt, Academic Medical Center, Department of Cardiology, P.O. Box 22660, 1100 DD, Amsterdam, the Netherlands (Email: S.M.Boekholdt{at}amc.uva.nl).

Objectives: This study was designed to test the hypothesis that at any low-density lipoprotein cholesterol (LDL-C) level, other lipid parameters such as non–high-density lipoprotein cholesterol (HDL-C) levels, triglyceride (TG) levels, and the total cholesterol (TC)/HDL-C are still associated with an increased coronary heart disease (CHD) risk.

Background: Although LDL-C is considered to be the primary target of lipid-lowering therapy, other parameters of the lipoprotein-lipid profile may more closely associated with CHD risk.

Methods: In the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Norfolk prospective population study, 21,448 participants without diabetes or CHD between age 45 and 79 years were followed for 11.0 years. A total of 2,086 participants developed CHD during follow-up.

Results: Among individuals with low LDL-C levels (<100 mg/dl), after adjustment for age, sex, smoking, systolic blood pressure, waist circumference, physical activity, and hormone replacement therapy (in women), those with non–HDL-C >130 mg/dl had a hazard ratio (HR) for future CHD of 1.84 (95% confidence interval [CI]: 1.12 to 3.04) when compared with those with non–HDL-C levels <130 mg/dl. In a similar model, individuals with TG levels >150 mg/dl had an HR of 1.63 (95% CI: 1.02 to 2.59) when compared with those with TG levels <150 mg/dl, and individuals with a TC/HDL-C ratio >5 had an HR of 2.19 (95% CI: 1.22 to 3.93) when compared with those with a TC/HDL-C ratio <5.

Conclusions: In this prospective study, independently of their plasma LDL-C levels, participants with high non–HDL-C levels, high TG levels, or with an elevated TC/HDL-C ratio were at increased CHD risk. CHD risk assessment algorithms as well as lipid targets of lipid-lowering trials may also need to consider other easily available parameters such as non–HDL-C.

Key Words: low-density lipoprotein cholesterol • non–high-density lipoprotein cholesterol • triglycerides • total to high-density lipoprotein cholesterol ratio • coronary heart disease

Abbreviations and Acronyms   CHD = coronary heart disease   CI = confidence interval   HDL = high-density lipoprotein   HDL-C = high-density lipoprotein cholesterol   HR = hazard ratio   LDL = low-density lipoprotein   LDL-C = low-density lipoprotein cholesterol   TC = total cholesterol   TG = triglyceride

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