Apolipoprotein Assessment

Overview:

Studies have shown that the ratio of apolipoprotein A-1:apolipoprotein B may correlate better with increased risk of coronary artery disease (CAD) than total cholesterol, and LDL:HDL ratio.

In 1971, Alaupovic suggested that apolipoproteins should be measured when assessing the relation of lipids and lipoproteins to CHD.2 Many patients with CHD were found to have normal serum and cholesterol levels. It was postulated that the chemical composition of the lipoproteins was more important for understanding the process of CHD than their blood levels. Subsequent studies have demonstrated that apolipoproteins are better discriminators than lipids and lipoproteins in patients with CHD and their relatives.

A number of studies have shown that apo A-1 and apo B correlate better with evidence of CHD than do lipoprotein measurements alone. In an investigation of first-degree relatives of patients with CHD, serum apo A-1 levels were significantly lower and apo B levels were significantly higher than those of healthy controls. Apo B was a better discriminator between male relatives, and apo A-1 was a better discriminator between female relatives and CHD patients. Furthermore, the percentage of correctly classified subjects increased by 12% when apo A-1 and apo B measurements were added as variables.

Avogaro et al found that serum apo A-1 and apo B levels, as well as various ratios using apolipoprotein measurements, were the variables that best discriminated male myocardial infarction survivors from age- and sex-matched controls.3

In 1983, Maciejko et al compared apo A-1 and HDL cholesterol measurements for their ability to identify male patients with angiographically assessed CHD.4 Analysis of their results indicated that apo A-1 alone misclassified 12.9% of the individuals compared to a misclassification error of 21.3% for HDL cholesterol alone. When apo A-1 and HDL cholesterol were used in combination, a misclassification error of 10.6% resulted. More recent studies have drawn similar conclusions.

When apo A-1, apo B, lipids, and lipoprotein cholesterol were measured in school-aged children (mean age of 10 years), apo A-1 and apo B levels were associated with a history of myocardial infarction in their parents. In striking contrast, the levels of serum lipids and lipoprotein-cholesterol values in these children were not related to myocardial infarction in either parent. Although no definite relationship between childhood apolipoprotein levels and adult CHD can be drawn, the results indicate that apolipoprotein measurements are more related to clinical disease than are conventional lipid measurements.5

Although the relationship of triglyceride measurements and CHD remains controversial, apolipoprotein measurements may be of benefit in identifying patients with hypertriglyceridemia who are at risk for CHD. Maciejko has suggested that apo B levels are helpful in differentiating primary causes of hypertriglyceridemia, provided that secondary causes (diabetes, alcohol ingestion, uremia, acromegaly, emotional stress or stress from acute illness, and certain drugs such as estrogen or beta blockers) have been ruled out. In familial endogenous hypertriglyceridemia, the apo B concentrations will be low while the patient with hypertriglyceridemia from familial combined hyperlipidemia will have a high apo B level.

Apolipoprotein measurements are also useful in the differentiation of familial hyper- or hypolipidemias. As mentioned, apo B may be used to differentiate familial combined hyperlipidemia from familial hypertriglyceridemia. Apo B measurements will also provide laboratory evidence of hyperapobetalipoproteinemia with excess apo B, whereas apo B deficiency states are found in abetalipoproteinemia, hypobetalipoproteinemia, familial hypobetalipoproteinemia with chylomicronemia, and abetalipoproteinemia with normotriglyceridemia. Apo A-1 deficiency states include Tangier disease, hypoalphalipoproteinemia, and HDL deficiency.

These studies indicated that apolipoprotein measurements can provide clarification in a variety of clinical states involving dyslipidemias. The Maciejko, Kottke, and Naito studies have concluded that apolipoprotein concentrations have greater discrimination in classifying patients who have or are predisposed to CHD and are more stable parameters than are lipids and lipoproteins.6 Lipids and lipoproteins are dynamic molecules whose concentration and composition are continually changing due to normal biologic variation, whereas apo A-1 and apo B levels are less affected, with change reflecting disease rather than biologic variability. In summary, apo A-1 and apo B measurements may be useful in the presence of the following conditions:

• Borderline elevations of cholesterol

• High cholesterol:HDL ratio with normal cholesterol

• Borderline elevations of LDL

• Normolipidemic children with a positive family history

• Normolipidemic adults with a positive family history

• Primary dyslipoproteinemias

1. Contois JH, McConnell JP, Sethi AA, et al. Apolipoprotein B and cardiovascular disease risk: Position statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices. Clin Chem. 2009; 55(3):407-419. PubMed 19168552

2. Alaupovic P. Apolipoproteins and lipoproteins. Atherosclerosis. 1971; 13(2):141-146. PubMed 5560875

3. Avogaro P, Bon GB, Cazzolato G, et al. Relationship between apolipoproteins and chemical components of lipoproteins in survivors of myocardial infarction. Atherosclerosis. 1980; 37(1):69-76. PubMed 7426089

4. Maciejko JJ, Holmes DR, Kottke BA, et al. Apolipoprotein A-1 as a marker of angiographically assessed coronary-artery disease. N Engl J Med. 1983; 309(7):385-389. PubMed 6410239

5. Kottke BA, Zinsmeister AR, Holmes DR Jr, et al. Apolipoproteins and coronary artery disease. Mayo Clin Proc. 1986; 61(5):313-320. PubMed 3702492

6. Naito HK. The association of serum lipids, lipoproteins, and apolipoproteins with coronary artery disease assessed by coronary arteriography. Ann N Y Acad Sci. 1985; 454:230-238. PubMed 3865610