High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study

doi:10.1016/S0140-6736(01)07098-2

The Lancet

Volume 358, Issue 9298, 15 December 2001, Pages 2026-2033

https://doi.org/10.1016/S0140-6736(01)07098-2 Get rights and content

Summary

Background

Apolipoprotein B (apoB) and apolipoprotein A-I (apoA-I) are thought to be better predictors of acute myocardial infarction than total cholesterol and LDL-cholesterol. We investigated whether apoB and apoA-I are predictors of risk of fatal myocardial infarction. We also aimed to establish whether apoB and apoA-I add further information about risk of fatal myocardial infarction to that obtained with total cholesterol, triglycerides, and LDL-cholesterol.

Methods

We recruited 175553 individuals mainly from screening programmes. We measured concentrations of apoB, apoA-I, total cholesterol, and triglycerides, and calculated apoB/apoA-I ratio and concentrations of LDL-cholesterol and HDL-cholesterol. The relation between death from acute myocardial infarction and initial values for apoB, apoA-I, and the other lipids was examined.

Findings

Mean follow-up was 66·8 months (SD 41·3) for 98722 men and 64·4 months (41·4) for 76831 women. 864 men and 359 women had fatal myocardial infarction. In univariate analyses adjusted for age and in multivariate analyses adjusted for age, total cholesterol, and triglycerides, the values for apoB and apoB/apoA-I ratio were strongly and positively related to increased risk of fatal myocardial infarction in men and in women. ApoA-I was noted to be protective. In multivariate analysis, apoB was a stronger predictor of risk than LDL-cholesterol in both sexes.

Interpretation

Although LDL-cholesterol and HDL-cholesterol are known risk factors, we suggest that apoB, apoB/apoA-I, and apoA-I should also be regarded as highly predictive in evaluation of cardiac risk. Although increased throughout the range of values of LDL-cholesterol, apoB and apoA-I might be of greatest value in diagnosis and treatment in men and women who have common lipid abnormalities, but have normal or low concentrations of LDL-cholesterol.

Introduction

Hypercholesterolaemia, high concentrations of LDL-cholesterol in particular, is generally accepted as one of the strongest risk factors for atherosclerotic cardiovascular disease and mortality, at least in individuals under 70 years of age.¹ Hypertriglyceridaemia, although generally associated with low HDL-cholesterol, is recognised as an independent risk factor for atherosclerosis.² Results of several studies have suggested that apolipoprotein B (apoB) in atherogenic particles—mainly LDL,3, 4, 5 but also VLDL, intermediate density lipoprotein, and lipoprotein (a)1, 2—and apolipoprotein A-I (apoA-I) in anti-atherogenic particles, such as HDL types,6, 7, 8 could improve the prediction of risk of coronary artery disease.

Early prospective studies with apolipoproteins yielded mixed results, because methods, procedures, and population-based reference values were not standardised.⁹ WHO-International Federation of Clinical Chemistry (IFCC) has standardised reference materials for measurement of concentrations of apoB and apoA-I,10, 11 and population results have subsequently been reported.12, 13, 14, 15, 16, 17 The prospective Quebec Cardiovascular Study¹⁸ showed the importance of apoB in estimation of coronary risk; similar results have also been published.19, 20 Large prospective studies of men and women with standardised techniques are awaited.3, 14, 18

One of us (IJ) has developed automated methods for measurement of apoB and apoA-I, and we have used these methods to screen large populations to improve information about dyslipoproteinaemias. In 1985, we started the AMORIS (Apolipoprotein-related MOrtality RISk) study.²¹ The aim of AMORIS is to assess the predictive power of apoB, apoA-I, and the apoB/apoA-I ratio in a large population in which no individual is excluded because of any clinical signs or symptoms of atherosclerotic or any other disease or because of current treatment.

Our objective was therefore to investigate which marker—apoB, apoA-I, or the apoB/apoA-I ratio—had the strongest relation with death from acute myocardial infarction and from sudden death in a certain individual. Furthermore, we looked at whether apoB and apoA-I add predictive information to conventional risk factor analyses of total cholesterol and triglycerides, and whether apoB is equal to or better than LDL-cholesterol for prediction of cardiac risk.

Section snippets

Study population

The AMORIS database includes data obtained from 175553 Swedish men and women with a mean age of 47·1 years (SD 13·1) and 49·7 years (15·0), respectively. No personal data were included. The original AMORIS population investigated in 1985–89 has been described elsewhere.21, 22 In the present study, we also included data from individuals recruited in 1990–96.

Individuals came mainly from the greater Stockholm area, but some were from other areas of Sweden. They were either healthy and were

Results

Follow-up of men and women was for a mean of 66·8 months (SD 41·3) and 64·4 months (41·4), respectively. Table 1 shows concentrations of lipids and apolipoproteins in the whole study population by age decade and sex. The mean concentration of total cholesterol in men and women was closely similar at just under 6·0 mmol/L. The mean concentration of triglycerides differed slightly between men and women. The highest value for both lipids was seen in men aged between 50 and 69 years and in women

Discussion

Our results accord with and extend the well known effect of total cholesterol, triglycerides, and LDL-cholesterol on risk of acute myocardial infarction. We also showed the well known anti-atherogenic effects of HDL-cholesterol.

Our main finding was that apoB, apoA-I, and the ratio of apoB/apoA-I are important risk factors for fatal myocardial infarction. This result considerably extends previous work suggesting that apolipoproteins play a significant part as risk factors.3, 4, 5, 6, 7, 8, 18, 19

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ArticlesHigh apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Study population

Results

Discussion

J Lipid Res

Atherosclerosis

Am J Cardiol

Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention

Eur Heart J

Plasma apolipoproteins A-I and B in survivors of myocardial infarction and in a control group

Clin Chem

Apolipoprotein B and coronary artery disease in women: a cross-sectional study in women undergoing their first coronary angiography

Arterioscler Thromb Vasc Biol

The role of lipoprotein A-I and lipoprotein A-I/A-II in predicting coronary artery disease

Arterioscler Thromb Vasc Biol

Relationship between HDL-cholesterol and apolipoprotein A-I and the severity of coronary artery disease

Eur Heart J

Quantitation of plasma apolipoproteins in the primary and secondary prevention of coronary artery disease

Ann Intern Med

International Federation of Clinical Chemistry standardization project for measurements of apolipoproteins A-I and B. III. Comparability of apolipoprotein A-I values by use of international reference material

Clin Chem

International Federation of Clinical Chemistry standardization project for measurements of apolipoproteins A-I and B. IV. Comparability of apolipoprotein B values by use of international reference material

Clin Chem

Serum concentrations of apolipoprotein A-I, apolipoprotein B, and lipoprotein (a) in a population sample

Clin Chem

Reference intervals for plasma apolipoprotein A-I determined with a standardized commercial immunoturbidimetric assay: results from the Framingham Offspring Study

Clin Chem

Reference intervals for plasma apolipoprotein B determined with a standardized commercial immunoturbidimetric assay: results from the Framingham Offspring Study

Clin Chem

Apolipoprotein B and A-I distributions in the United States, 1988–1991: results of the National Health and Nutrition Examination Survey III (NHANES III)

Clin Chem

Reference values of plasma apolipoproteins A-I and B, and association with nonlipid risk factors in the populations of two Canadian provinces: Quèbec and Saskatchewan

Can J Cardiol

Articles
High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study