LDL-C or apoB as the Best Target for Reducing Coronary Heart Disease

Should Apob be Implemented into Clinical Practice?

Helena Vaverkova

Disclosures

Clin Lipidology. 2011;6(1):35-48. 

In This Article

Review of Prospective Studies Comparing apoB & LDL-C as Predictors of Coronary Artery Disease & Cardiovascular Risk

Numerous prospective studies have shown that apoB predicts CHD in both genders, and is better than LDL-C in this respect.[21–29] The largest from these studies was the AMORIS, which observed 98,722 men and 76,831 women over the age of 60 years for approximately 5 years.[24] In this study, by use of different multivariate analyses, apoB proved to be more significant than LDL-C and added predictive power to that of LDL-C for prediction of the risk of fatal MI. After adjusting for age and traditional risk factors, including LDL-C, apoB remained a significant predictor of MI, with a relative risk of 1.33 (95% CI: 1.17–1.51) and 1.53 (95% CI: 1.25–1.88) for a 1 standard deviation increase in men and women, respectively. On the other hand, LDL-C was an insignificant risk factor in women and only modestly associated with MI in men.

Another major finding of the AMORIS was that in individuals with concentrations of LDL-C below the median, apoB was a better predictor of risk than LDL-C (according to receiver operating characteristic analysis). This is a very important finding as almost 50% of coronary patients may have plasma cholesterol concentrations of less than 200 mg/dl (5.2 mmol/l) and a large proportion of coronary patients with normal cholesterol levels have elevated apoB concentrations.

This finding can be explained by the presence of sdLDL and is in agreement with the results from the Québec Cardiovascular study,[25] which showed that the risk of MI is higher in individuals who have high LDL-C and a high concentration of apoB than in those with high concentrations of LDL-C and low apoB.

A further important finding of the AMORIS is that apoB and apoA-I added power to predict fatal MI not only in men and women under 70 years of age but also for those aged 70 years or more. Total cholesterol loses its predictive power in people aged 70 years or older, while apoB, apoA-I and the apoB:apoA-I ratio remain important risk predictors of MI in this age category.

Numerically, the steepest increase in risk of MI was obtained in the AMORIS for the apoB:apoA-I ratio, which increased approximately 3.8-fold in men and just below threefold in women when the risk for those in the highest quartile was compared with those in the lowest quartile.

Thompson and Danesh performed a meta-analysis of these prospective studies of apoB.[30] In this meta-analysis, apoB was a significant predictor of CHD, with a relative risk of approximately 2.0 for the upper compared with the lower tertile.

Recently, Contois et al., in the position statement from the American Association for Clinical Chemistry (AACC) Lipoproteins and Vascular Diseases Division Working Group on Best Practices, presented a comprehensive overview of the published prospective studies of apoB.[31] All but one of these studies found a statistically significant association of apoB with CHD, even after adjustment for nonlipid risk factors. These studies were conducted among several different populations – Swedish,[24] Canadian,[21,25] American,[22,23,28] British,[32] Chinese[27] and Danish[26] – which very strongly supports the view that apoB is an important independent risk factor of CHD. Among the studies reporting both apoB and LDL-C, apoB was consistently the stronger risk factor.

Nuclear magnetic resonance represents another tool for how to quantify the number of LDL particles.[11] Several cross-sectional and prospective studies proved that LDL particle concentration is more predictive of CVD than LDL-C,[10,33–36] especially at low LDL-C levels.[10]

Thus, prospective studies support the concept that the number of atherogenic particles is a more important indicator of risk than the amount of cholesterol transported in these particles.

Recently, the Emerging Risk Factors Collaboration (ERFC) evaluated the association of major lipids and apolipoproteins with the risk of vascular disease in a meta-analysis of 68 long-term prospective studies, involving a total of 302,430 participants without any known history of CHD or stroke.[37] Hazard ratios for CHD were adjusted for HDL-C, TGs, age, sex, smoking status, history of diabetes mellitus, systolic blood pressure and BMI. The AMORIS (175,553 participants) provided data for the ERFC. Nevertheless, it could not be included in this meta-analysis because it did not measure baseline levels of all aforementioned parameters. Thus, only 22 studies in this meta-analysis, with a total of 91,307 participants, had information on apoB and apoA-I and all other parameters for adjustment (which is only a little more than half of the participants included in AMORIS). These studies were usually small and apolipoproteins were measured with various techniques – some of which were not up-to-date.

Hazard ratios of non-HDL-C and HDL-C in the aforementioned ERFC meta-analysis were nearly identical to those seen with apoB and apoA-I. The ERFC concluded that current discussions about whether to measure cholesterol levels or apolipoproteins in vascular risk assessment should hinge more on practical considerations (e.g., cost, availability and standardizations of assays) than on major differences in the strength of epidemiological associations.[37]

In this ERFC meta-analysis, TGs were not independently related to CHD risk after controlling for HDL-C, non-HDL-C and other risk factors, which is in contrast with findings of previous meta-analyses.[38] From these results, it is evident that the results depend mostly on the statistical adjustments used rather than on biological plausibility.

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