ArticlesLipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study
Introduction
Coronary heart disease is now the major cause of death worldwide. The human and economic costs of premature vascular disease are not confined to developed countries. Developing countries already account for most of the cases of coronary heart disease and indeed in regions such as south Asia, clinical events seem to be arising at a younger age and involve women more frequently than in the rest of the world. The INTERHEART study1, 2 showed that the same nine modifiable risk factors (smoking, exercise, fruit and vegetables, alcohol, hypertension, diabetes, abdominal obesity, psychosocial, high apolipoprotein B100 (ApoB)/apolipoprotein A1 (ApoA1) ratio) accounted for almost all the population-attributable risk (PAR) of myocardial infarction and that these same factors applied to all the major population groups in the world. Of these risk factors, the ApoB/ApoA1 ratio—an index of the proatherogenic and antiatherogenic lipoproteins in plasma—accounted for half the PAR.
Perhaps no issue in lipidology has been as contentious as whether ApoB and ApoA1 are better markers than are their cholesterol counterparts of risk of vascular disease. All the major guideline groups previously recommended a cholesterol-based approach, effectively excluding apolipoproteins from routine clinical use. However, the American Diabetes Association and the American College of Cardiology3 have stated that ApoB is the test of choice to assess the adequacy of statin treatment and should therefore be introduced into routine clinical practice. Several studies4, 5, 6, 7, 8 have shown that ApoB is a better marker of risk than is LDL cholesterol.4 Non-HDL cholesterol is better than LDL cholesterol9, 10 and, in some studies,11 but not in others,10, 12 is equal to ApoB. HDL must also be measured to estimate the full lipoprotein-related risk of vascular disease. However, the comparison of ApoA1 and HDL cholesterol concentrations has produced much more inconsistent results than has the comparison of ApoB and LDL cholesterol concentrations.
Ratios are particularly complex to compare because the final result might differ, dependent on the numerator and the denominator. For example in the Framingham Offspring Study13 the ratio of ApoB/ApoA1 and the traditional lipid ratios were equivalent but ApoB was a better risk factor than was total cholesterol, and HDL cholesterol was a much better risk factor than was ApoA1. Most epidemiological studies comparing the ApoB/ApoA1 and total cholesterol/HDL cholesterol ratios were made on the basis of few events. In AMORIS (Apolipoprotein-related MOrtality RISk),8 a large prospective epidemiological study, the ApoB/ApoA1 ratio was clearly better than any of the cholesterol ratios. However, the AMORIS study8 has been criticised because concentrations of LDL cholesterol and HDL cholesterol were not assessed by conventional methods.
We compared ApoB/ApoA1 with other cholesterol ratios as markers for the risk of acute myocardial infarction in all the major ethnic groups of the world.
Section snippets
Participants
The study enrolled 12 461 individuals with a first acute myocardial infarction and 14 637 age-matched (up to 5 years older or younger than the cases) and sex-matched controls from 262 centres in 52 countries in Asia, central, eastern, and western Europe, Middle East, Africa, North America, and South America, and Australia and New Zealand. All patients (irrespective of age) admitted to the coronary-care unit or equivalent cardiology ward within 24 h of initial symptoms were screened. Patients
Statistical analysis
Continuous variables were summarised with means or medians and were compared with ANOVA model-based tests. For comparison of means across subgroups, values were adjusted for age and sex with ANCOVA models. Sex-specific quintile values from controls were used to classify continuous variables. Univariate associations were explored with frequency tables and Pearson's χ2 tests for independent proportions. Unconditional logistic regression with adjustment for matching factors was used to control for
Results
Blood samples for analysis were available from patients (2209 women and 7136 men) and controls (2937 women and 9183 men) in different ethnic groups (table 1). Median ages of patients with myocardial infarction at presentation were 51 years in South Asians, 52 years in Arabs and Persians, 59 years in Latin Americans, 63 years in Chinese, and 62 years in Europeans. Patients had higher total cholesterol, non-HDL cholesterol, and ApoB concentrations, and lower HDL cholesterol and ApoA1
Discussion
In all ethnic groups and both sexes, the ApoB/ApoA1 ratio was a better risk marker of myocardial infarction than was the ratio of total cholesterol/HDL cholesterol. Importantly, the C statistic derived from the ROC analysis confirmed this finding. Moreover, although the risk associated with the ApoB/ApoA1 ratio decreased with age, mainly because the risk associated with ApoB became less pronounced, the ApoB/ApoA1 ratio was more associated with risk at all ages than were any of the cholesterol
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INTERHEART study investigators listed at end of paper