LDL Particle Numbers, Size, Not Predictive for CAD

January 29, 2007

January 29, 2007 (Amsterdam, the Netherlands) – Measuring LDL particle numbers (LDL-P) to predict coronary artery disease risk in healthy individuals should not become part of routine practice, the authors of a new case-control study conclude [ 1]. Dr Karim El Harchaoui (Academic Medical Center, Amsterdam, the Netherlands) and colleagues report their findings online January 22, 2007 in the Journal of the American College of Cardiology.

Coauthor Dr Matthijs Boekholdt (Academic Medical Center) told heartwire that, in patients with only moderately elevated LDL-C, clinicians would do better to pay attention to HDL levels and triglycerides as markers for future CAD risk rather than worrying about testing LDL-P.

"Although it's good to be aware of LDL-P, it's expensive to test. We show that HDL-C and triglycerides provide similar predictive information. Most doctors do not look at HDL-C or triglycerides because, unlike LDL-C, treatment for these parameters is not mainstream clinical practice. It would be more useful to be aware of these results, particularly in those with the metabolic syndrome, abdominal obesity, or diabetes," he said.

LDL-P not predictive of CAD after adjustment for HDL, triglycerides

El Harchaoui et al explain that some studies have suggested that assessment of the number of LDL particles and their size may have stronger associations with coronary artery disease than levels LDL-C.

Hence they assessed the relationship of LDL-P and particle size as measured by a relatively new technique--nuclear magnetic resonance spectroscopy--with the risk of future CAD in more than 25 000 subjects with moderately elevated LDL-C in the European Prospective Investigation into Cancer and Nutrition (EPIC) -Norfolk.

They matched 1003 cases of individuals who developed CAD during a six-year follow-up with 1885 control subjects and calculated the odds ratios (ORs) for future CAD. They also evaluated whether LDL-P could improve upon the Framingham risk score to predict CAD.

LDL-P (OR 2.00 for top vs bottom quartiles) was more closely associated with the occurrence of future CAD than LDL-C (OR 1.73) and was related to CAD on top of the Framingham risk score even after adjustment for LDL-C.


But after adjustment for HDL-C and triglycerides, LDL-P was no longer more predictive than LDL-C. Nor was LDL particle size associated with CAD risk, following adjustment for LDL-P.

ORs by quartile for future CAD after taking into account the Framingham risk score

Measure

1

2

3

4

p

LDL-C

1.00

1.17

1.09

1.24

0.15

LDL-P

1.00

1.10

1.22

1.34

0.02

Non-HDL-C

1.00

0.98

1.03

1.38

0.04



"These findings do not support routine use of LDL-P in CAD risk-assessment strategies in primary prevention," say the researchers.

LDL-P could be useful to characterize patients

Boekholdt told heartwire that if clinicians paid more attention to the standard lipid tests, they could better target those at risk.

"Most doctors tend to ignore abnormal HDL and triglyceride levels because there is not much you cando about them." The demise of torcetrapib, which raised HDL levels and was touted as the next big thing in CAD prevention, means there is little left in the physician's armamentarium to target HDL, he says. And although niacin raises HDL levels, "there are no cardiovascular end-point studies," he notes.

Physicians are also aware of the elevated risk with increased triglycerides, but unlike statins, fibrates are not mainstream clinical practice, he explains.

In these cases, LDL-P could be useful to characterize patients, he says, although he acknowledges that the test is expensive and not widely available.

"At any given LDL-C level, if you have two people and one has increased LDL-P while the other has normal LDL-P, the one with the increased LDL-P is at greater risk of CAD, and this tends to coincide with people who have metabolic dyslipidemia [which usually includes low HDL-C levels and high triglycerides]," he said.

"Recognition that patients with low HDL-C and/or high triglycerides often have elevated numbers of LDL-P without having elevated LDL-C may enable their LDL-related CAD risk to be managed more effectively," the authors write.

"There is some evidence that people treated with statins who achieve a good LDL level but still have high LDL-P remain at high risk," Boekholdt added. "It may be that their risk could be reduced by giving them an even higher dose of a statin."

  1. El Harchaoui K, van der Steeg WA, Stroes ESG, et al. Value of low-density lipoprotein particle number and size as predictors of coronary artery disease in apparently healthy men and women. The EPIC-Norfolk Prospective Population Study. J Am Coll Cardiol 2007; 49:547-553.

The complete contents of Heartwire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

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