Concordance/discordance between plasma apolipoprotein B levels and the cholesterol indexes of atherosclerotic risk

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Abstract

The objective of the present study was to examine concordance/discordance among 4 atherogenic indexes of cardiovascular risk: plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol, and apolipoprotein B-100 (apoB). Analyses were conducted in a cohort of 2,103 men without coronary artery disease (CAD) at the onset of the Quebec Cardiovascular Study. Although there were strong and highly significant correlations among the 4 risk indexes (0.78 < r < 0.97), only 50% of all subjects had concordant apoB and LDL cholesterol levels (i.e., values that fell into the same quintile of the population distribution). Moreover, concordance/discordance was not the same throughout the range of both variables; it was greater at the extremes of their respective distributions (65%), but significantly less in the midpoints (<40%). ApoB appeared to be more concordant with non-HDL cholesterol than with LDL cholesterol, although >1/3 of all subjects had discordant levels. Kappa analysis confirmed that there was only fair agreement between apoB and total or LDL cholesterol (0.38 and 0.36, respectively) and only moderate agreement between non-HDL cholesterol and apoB (0.47). Finally, a significant proportion of subjects (528 of 2,103) who had disproportionately higher apoB levels than would have been predicted based on their LDL cholesterol concentrations was more obese and manifested several features of the metabolic syndrome. They also had a significantly increased cardiovascular risk. In summary, plasma apoB and the various cholesterol indexes are complementary rather than competitive indexes of atherosclerotic risk and provide further evidence as to why measurement of apoB should be part of a standard lipoprotein assessment of CAD risk.

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Apolipoprotein A-I and B levels and the risk of ischemic heart disease during a five-year follow-up of men in the Québec cardiovascular study.

Laura Bernard, S Moorjani, B Cantin … (1996)

Results obtained largely from case-control studies have suggested that an elevated plasma concentration of apolipoprotein (apo) B may be considered an important risk factor for ischemic heart disease (IHD). Prospective data on the relevance of measuring apo A-I and apo B levels in the assessment of IHD risk, however, remain sparse as well as controversial. Plasma lipid, apo B, and apo A-I levels as well as other risk factors were evaluated at baseline in 1985 in a sample of 2155 men (45 to 76 years old) who were followed for a period of 5 years for clinical signs of IHD. Proportional-hazards analyses indicated that plasma apo B concentrations measured at entry were strongly associated with onset of IHD (relative rate, 1.4; 95% confidence interval [CI], 1.2 to 1.7), independent of covariables such as age, smoking, diabetes mellitus, and systolic blood pressure. Controlling for triglycerides, HDL cholesterol, and total/HDL cholesterol ratio did not eliminate the relationship between plasma apo B levels and IHD. The association between apo A-I and IHD was of lower magnitude (relative rate, 0.85; 95% CI, 0.7 to 1.0), and adjustment for selected plasma lipid and lipoprotein levels eliminated this association. Stepwise logistic regression analysis revealed that, among metabolic variables, apo B was the strongest correlate of IHD. These prospective results emphasize the importance of apo B as a risk factor for IHD. Apo B may be regarded as a relevant tool in the assessment of IHD risk in men, because it may provide information that would not be obtained from the conventional lipid-lipoprotein profile.

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Apolipoproteins versus lipids as indices of coronary risk and as targets for statin treatment.

J. Frohlich, J J Spek, G Walldius … (2003)

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Correlation of non-high-density lipoprotein cholesterol with apolipoprotein B: effect of 5 hydroxymethylglutaryl coenzyme A reductase inhibitors on non-high-density lipoprotein cholesterol levels.

Christie Ballantyne, Thomas C. Andrews, Judith Hsia … (2001)

Apolipoprotein B has been shown to be a better predictor of coronary heart disease than low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol may also be a better parameter for coronary heart disease risk assessment and as a target for therapy. Data from the Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS) were used to assess the correlation between lipid and apolipoprotein B levels before and after lipid-lowering therapy and to examine the effects of 5 hydroxymethylglutaryl coenzyme A reductase inhibitors on lipids and apolipoprotein B. The 54-week study randomized 3,916 hypercholesterolemic patients to atorvastatin, fluvastatin, lovastatin, pravastatin, or simvastatin, initiated at recommended starting doses with titrations as needed at weeks 6, 12, and 18 to achieve National Cholesterol Education Program LDL targets. Compared with LDL cholesterol, non-HDL cholesterol correlated better with apolipoprotein B levels at baseline (r = 0.914, p <0.0001) and at week 54 (r = 0.938, p <0.0001), and the correlation was strong across all baseline triglyceride strata. At starting doses, atorvastatin (10 mg) lowered non-HDL cholesterol by 33.3% compared with 26.6% with simvastatin (10 mg), 24.1% with lovastatin (20 mg), 17.2% with fluvastatin (20 mg), and 17.0% with pravastatin (10 mg). Atorvastatin also provided greater reductions in non-HDL cholesterol after dose titration, and a greater percentage of patients taking atorvastatin achieved non-HDL cholesterol targets. Baseline triglyceride did not affect non-HDL cholesterol reductions with any of the 5 hydroxymethylglutaryl coenzyme A reductase inhibitors. Fewer patients achieved non-HDL cholesterol targets than LDL cholesterol targets, particularly among high-risk patients, implying that if non-HDL cholesterol was used as a target for treatment, more patients would need to be treated more aggressively than National Cholesterol Education Program guidelines require.