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The apo B/A-I Ratio — A Stronger Predictor of Cardiovascular Events Than LDL, HDL, or Total Cholesterol, Triglycerides, or Lipid Ratios

For a number of years, evidence has been accumulating from clinical trials that assessing the levels of apolipoprotein (apo) B, a constituent of atherogenic lipoproteins; apo A-I, a component of antiatherogenic high-density lipoprotein (HDL) cholesterol; and the apo B/A-I ratio will provide better prediction of future cardiovascular events than measuring serum low-density lipoprotein (LDL)-cholesterol levels. In 2004, the global INTERHEART study of risk factors for acute myocardial infarction (MI) in 52 countries concluded that “the apo B/A-I ratio was the most important risk factor in all geographic regions.1

Now new data from the long-term follow-up of a prospective trial and analyses of major clinical trials of lipid-lowering therapy show that the predictive power of the apo B/A-I ratio is superior to, and cannot be improved by adding, any other lipid parameter or ratio.

Göran Walldius, MD, PhD (King Gustaf V Research Institute, Karolinska Institute, Stockholm, and AstraZeneca, Mölndal, Sweden), believes that the apo B/A-I ratio should be included in new guidelines for risk evaluation.2 Individuals with seemingly normal LDL cholesterol (< 3.3 mmol/L, 127.1 mg/dL) may in fact have high apo B values, revealing the presence of many small, dense LDL particles, thus indicating substantial risk, On the other hand, these individuals can be identified by their high apo B/A-I ratio. Patients with metabolic syndrome and type 2 diabetes can also easily be identified.

The apo B/A-1 ratio is easy to use (and easy to explain to patients) because the risk is integrated into 1 number, and it indicates the cholesterol balance between potentially atherogenic and antiatherogenic particles, Prof. Walldius pointed out. “Cardiologists, diabetologists, and endocrinologists are jumping onboard this new way of thinking, because the hallmark of this is that it is easier and simpler,” he said. It should be under discussion by guideline committees, he suggested. However, during ensuing discussions, US delegates blamed a lack of standardization as the reason why US organizations have not moved forward to adopt measurement of the apo B/A-I ratio with greater enthusiasm, despite many calls for guidelines to do so.

AMORIS study: Apolipoprotein-Related Mortality Risk

Prof. Walldius and colleagues at the Karolinska Institute originally reported in 2001 that the apo B/A-I ratio is of potentially greater value than LDL cholesterol for predicting risk for fatal MI in men and women on the basis of a study in 175,553 individuals recruited from screening programs.1 In the prospective Apolipoprotein-related MOrtality RISk (AMORIS) trial,3 plasma levels of apo B, apo A-I, total cholesterol, and triglycerides were measured and the apo B/A-I ratio calculated. Mean follow-up was 66.8 months for 98,722 men and 64.4 months for 76,831 women, during which 864 men and 359 women had a fatal MI.

In an updated analysis after a mean follow-up of 10.3 years, during which 1111 subjects had died from stroke and 3409 from ischemic coronary heart disease (CHD), including 2213 from MI, the apo B/A-I ratio was again shown to be a strong predictor of stroke. After adjustment for age, sex, total cholesterol, and triglycerides, this ratio was superior to LDL-cholesterol levels alone and any other cholesterol ratio in predicting risk (all at least P < .025). Thus, the odds ratio (OR) of the apo B/A-I ratio for all strokes was 2.07 (P < .0001). The strongest association was for ischemic stroke. Low apo A-I was a common abnormality in all stroke subtypes, including subarachnoidal and hemorrhagic strokes. The OR (adjusted for stroke) was 4.25 for MI and 3.38 for all ischemic CHD (both P < .0001). In all conditions, risk was log-linearly related to the apo B/A-I ratio.

IDEAL study: Incremental Decrease in Events Through Aggressive Lipid Lowering

An analysis of the Incremental Decrease in Events through Aggressive Lipid Lowering (IDEAL) study, presented by Anders G. Olsson, MD, PhD (Linköping University Linköping, Sweden), showed that apo B/A-I was superior to LDL/HDL cholesterol in predicting the reduction in risk for major cardiac events achieved by statin therapy in the IDEAL trial.4

References

  1. Yusuf S, Hawken S, Ounpuu S, et al; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937-952.
  2. Walldius G, Jungner I. The apo B/apo A-I ratio — a new predictor of fatal stroke, myocardial infarction and other ischaemic diseases — stronger than LDL and lipid ratios. Atherosclerosis. 2006;7(suppl):468. Abstract Th-W50.6.
  3. Walldius G, Jungner I, Holme I, et al. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet. 2001;358:2026-2033
  4. Durrington PN, Livingstone S, Charlton-Menys V, et al. Apolipoproteins as predictors of cardiovascular risk in the Collaborative Atorvastatin Diabetes Study (CARDS). Atherosclerosis. 2006;7(suppl):37. Abstract Mo-W14:4.