Justo Sierra-Johnson, M.D., M.S., Virend K. Somers, M.D., Ph.D., and Francisco Lopez- Jimenez, M.D., M.S., Mayo Clinic, Division of Cardiovascular Diseases, 200 First Street SW, Rochester MN 55905, E-mail: sierrajohnson.justo@mayo.edu, somers.virend@mayo.edu, lopez@mayo.edu

ApoB/ApoAI Ratio

Apolipoproteins are important structural and functional proteins in lipoprotein particles, which transport lipids. Recent reports suggest that measurements of apolipoprotein B/apolipoprotein AI (apoB/apoAI) ratio may improve the prediction of risk for cardiovascular disease [1-4]. ApoB/apoAI ratio may represent the balance between pro-atherogenic and anti-atherogenic lipoproteins [5]. In several clinical studies, serum ApoB concentrations and the apoB/ApoA-I ratio have been reported to predict cardiovascular risk better than any of the cholesterol indices [6].

Metabolic Syndrome

The metabolic syndrome represents the clustering of coronary heart disease (CHD) risk factors that are often associated with insulin resistance [7-9]. Individuals with the metabolic syndrome have an increased risk of cardiovascular morbidity and mortality in most studies. While this risk may be due to the sum of the effects of the component risk factors, the disease mechanisms through which the metabolic syndrome increases CHD risk have not been elucidated.

Our Study

Our recent study [10] aimed to assess whether the metabolic syndrome was associated with a high apoB/AI ratio in a representative sample of the U.S. population, such as NHANES III. For this we analyzed data from 2,964 subjects, mean age 48 years; 1,516 men and 1,448 women.

We compared the mean values of the apoB/apoAI ratio in subjects with and without the metabolic syndrome. We reported that overall, median distribution of the apoB/apoAI ratio was significantly higher (p < 0.0001) in subjects with the ATP-III metabolic syndrome (0.90) than without (0.69). ApoB/apoAI ratio was associated significantly with each of the metabolic syndrome components in descending order of magnitude: low HDL-cholesterol (OR 5.7), high triglycerides (OR 4.7), high waist circumference (OR 2.6), high fasting glucose (OR 1.9), and high blood pressure (OR 1.5). The apoB/apoAI ratio was also different between subjects with and without the metabolic syndrome. Mean values of apoB/apoAI increased significantly as the numbers of metabolic syndrome components increased in both men (p < 0.0001) and women (p < 0.0001). After excluding HDL-cholesterol and triglycerides as criteria for metabolic syndrome, the association between means persisted (ANOVA p < 0.0001) in both men and women. ApoB/apoAI was significantly associated with the presence of the metabolic syndrome (OR 5.1, p < 0.0001). We concluded that apoB/apoAI ratio was strongly associated with the presence of individual metabolic syndrome components and with the metabolic syndrome itself.

Practical Implications

An elevated apoB/apoAI ratio may constitute an important feature of the metabolic syndrome, and is an additional mechanism to explain the increased cardiovascular risk in subjects with this syndrome.

References

1. Meisinger C, Loewel H, Mraz W, Koenig W. Prognostic value of apolipoprotein B and A-I in the prediction of myocardial infarction in middle-aged men and women: results from the MONICA/KORA Augsburg cohort study. Eur Heart J 2005;26:271-78.

2. Vaessen SF, Schaap FG, Kuivenhoven JA, et al. Apolipoprotein A-V, triglycerides and risk of coronary artery disease: the prospective Epic-Norfolk Population Study. J Lipid Res 2006;47(9):2064-70.

3. Dunder K, Lind L, Zethelius B, Berglund L, Lithell H. Evaluation of a scoring scheme, including proinsulin and the apolipoprotein B/apolipo-protein AI ratio, for the risk of acute coronary events in middle-aged men: Uppsala Longitudinal Study of Adult Men (ULSAM). Am Heart J 2004;148:596-601.

4. Jiang R, Schulze MB, Li T, et al. Non-HDL cholesterol and apolipoprotein B predict cardiovascular disease events among men with type 2 diabetes. Diabetes Care 2004;27:1991-97.

5. Walldius G, Jungner I. The apoB/apoA-I ratio: a strong, new risk factor for cardiovascular disease and a target for lipid-lowering therapy--a review of the evidence. J Intern Med. 2006;259(5):493-519.

6. Walldius G, Jungner I, Aastveit AH, Holme I, Furberg CD, Sniderman AD. The apoB/apoA-I ratio is better than the cholesterol ratios to estimate the balance between plasma proatherogenic and antiatherogenic lipoproteins and to predict coronary risk. Clin Chem Lab Med 2004;42:1355-63.

7. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.

8. Federation ID. The IDF consensus worldwide definition of the metabolic syndrome. Available at: http://www.idf.org/webdata/docs/IDF_Metasyndrome_definition.pdf. Accessed January 18, 2007.

9. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005;112:2735-52.

10. Sierra-Johnson J, Somers VK, Kuniyoshi FSH, et al. Comparison of apolipoprotein B/apolipoprotein AI in subjects with - vs - without the metabolic syndrome. Am J Cardiol 2006;15;98(10):1369-73.