HDL Cholesterol, HDL Particle Size and Apolipoprotein A-I: Significance for Cardiovascular Risk — The IDEAL & EPIC-Norfolk Studies

Wim A. van der Steeg, M.D.; Christopher P. Cannon, M.D., F.A.C.C.



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The European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study is part of the largest prospective evaluation of diet and health ever undertaken. The entire EPIC study involves more than half a million people in 10 countries. The EPIC-Norfolk portion of this effort is a prospective population study of 25,663 men and women aged 45-79 years residing in Norfolk, United Kingdom, who completed a baseline questionnaire survey and attended a clinic visit.

EPIC should produce much more specific information about the effect of diet and lifestyle on long-term health than previous studies. Moreover, the database includes the potential for many other studies given the detailed information collected on height, weight, waist and hip measurements, and blood samples stored in liquid nitrogen. To date, some 100 papers have been published using the EPIC-Norfolk cohort.

For example, the data have been used in a series of studies to determine the value of lipid subfractions in clinical risk assessment. In early 2007, Harchaoui and colleagues reported in JACC the results of a nested case-control study of EPIC-Norfolk participants.[1] Several lines of evidence had suggested that small, dense low-density lipoprotein (LDL) particles are more highly atherogenic than larger-sized particles, yet the traditional lipid profile cannot discern whether elevated levels of LDL reflect small or large particles. EPIC-Norfolk participants were used to find individuals who developed coronary artery disease (CAD) during 6-year follow-up (cases, n = 1,003) and for control subjects (n = 1,885), who were matched for age, gender, and enrollment time.

The investigators compared the ability of LDL particle number (LDL-P), LDL particle size (LDL-S), and several established cardiovascular risk factors to predict the first cardiac event in these subjects. LDL-S correlated inversely with risk for coronary artery disease, and LDL-P was more predictive than LDL alone (Figure 1); however, after adjusting for high-density lipoprotein cholesterol (HDL-C) and triglycerides, neither test was superior. The study confirmed that LDL-P and LDL-S add additional information to cardiovascular risk, but little additional information compared to non-HDL-C.

Figure 1.

Odds Ratios for Future CAD by Quartile of LDL-C and LDL-P*

They concluded that their findings do not support routine use of LDL-P in CAD risk assessment strategies for primary prevention. However, the added recognition that patients with low HDL-C and/or high triglycerides often have elevated numbers of LDL particles without having elevated LDL-C may enable their LDL-related CAD risk to be managed more effectively.


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