A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction.

Stampfer, Meir J.; Sacks, Frank M.; Salvini, Simonetta; Willett, Walter C.; Hennekens, Charles H.

doi:10.1056/nejm199108083250601

Cited by 1,163Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismParaoxonase enzyme and polymorphisms

A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction.

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Stampfer, Meir J., Sacks, Frank M., Salvini, Simonetta, Willett, Walter C., Hennekens, Charles H.·1991·New England Journal of Medicine

DOI 10.1056/nejm199108083250601

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Abstract

BACKGROUND: The independent contributions of subfractions of high-density lipoprotein (HDL) cholesterol (HDL2 and HDL3) and apolipoproteins in predicting the risk of myocardial infarction are unclear. Prospective data are sparse, but HDL2 is widely believed to be a more important predictor than HDL3. METHODS: Blood samples were collected at base line from 14,916 men (ages, 40 to 84 years) who were participants in the Physicians' Health Study. After five years of follow-up, plasma samples from 246 men with new myocardial infarction (case subjects) were analyzed together with specimens from 246 men matched to them for age and smoking status who had not had a myocardial infarction. RESULTS: The levels of total cholesterol and apolipoprotein B-100 were significantly associated with an increased risk of myocardial infarction (data on levels of low-density lipoprotein cholesterol were unavailable). Both HDL cholesterol and HDL2 levels were associated with a substantially decreased risk of myocardial infarction, but the HDL3 level was the strongest predictor; the relative risk was 0.3 (95 percent confidence interval, 0.2 to 0.6) for those in the fifth of the group with the highest HDL3 levels, as compared with the fifth with the lowest levels. The benefit of a higher HDL cholesterol level was most pronounced among those with lower total cholesterol levels. Levels of apolipoprotein A-I and apolipoprotein A-II were also associated with decreased risk. However, the levels of HDL subfractions and apolipoproteins did not add significantly to the value of a multivariate model that included the ratio of total to HDL cholesterol in predicting myocardial infarction, whereas that ratio remained a significant independent predictor of risk. After adjustment for other risk factors, a change of one unit in the ratio of total to HDL cholesterol was associated with a 53 percent change in risk (95 percent confidence interval, 26 percent to 85 percent). CONCLUSIONS: This study underscores the importance of HDL cholesterol in predicting the risk of myocardial infarction and demonstrates protective effects of both the HDL3 and HDL2 subfractions of HDL cholesterol. We found little or no predictive value for the levels of apolipoproteins A-I, A-II, and B or HDL subfractions after conventional risk factors and the ratio of total to HDL cholesterol were considered.

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Epidemiological studies have not provided conclusive evidence that measurement of HDL size contributes to risk prediction.
“Epidemiological studies have not provided conclusive evidence that measurement of HDL size contributes to risk prediction (36, 50 -55).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [50]
The Discussion (pp. 6–7) reports that HDL2 and HDL3 subfractions did not add significantly to myocardial-infarction risk prediction after established factors were considered, and says further studies are needed before using their concentrations clinically. The Laboratory Analyses (p. 2) describe measurements of subfraction cholesterol, not direct measurements of HDL particle size, so the paper supports the claim's caution about added predictive value but not its specific wording about measuring size. (LLM, conf=0.83)
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Decreased HDL2 and HDL3 cholesterol, Apo A-I and Apo A-II, and increased risk of myocardial infarction.
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Self-citation
HDL, HDL2, and HDL3 subfractions, and the risk of acute myocardial infarction. A prospective population study in eastern Finnish men.
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High density lipoprotein subfractions and the risk of coronary heart disease: 9-years follow-up in the Caerphilly Study
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Total Cholesterol, HDL Cholesterol, Its Subfractions, Apoprotein A-I and A-II in Patients with Old Myocardial Infarction: Comparison with Normal Controls
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Value of HDL Cholesterol, Apolipoprotein A-I, Lipoprotein A-I, and Lipoprotein A-I/A-II in Prediction of Coronary Heart Disease
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Authors: Stampfer, M. J., Sacks, F. M., Salvini, S., Willett, W. C., & Hennekens, C. H.
Affiliations: Brigham and Women's Hospital (US)
ORCID: Stampfer, Meir J.
Sacks, Frank M.
Willett, Walter C.
Hennekens, Charles H.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 1991-08-08
Volume: 325
Issue: 6
Pages: 373-381
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejm199108083250601
OpenAlex: W2337032743
Cited by: 1,163
References: 56
Citations by year: 2026: 6 · 2025: 5 · 2024: 10 · 2023: 10 · 2022: 7 · 2021: 12 · 2020: 14 · 2019: 12 · 2018: 18 · 2017: 17 · 2016: 24 · 2015: 31 · 2014: 34 · 2013: 33 · 2012: 31
FWCI: 80.75
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (HL-34595, HL 26490, R01HL034595)
National Cancer Institute (R01CA042182, CA 42182)
Topics: Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
Keywords: myocardial infarction, HDL cholesterol, HDL2, HDL3, apolipoprotein B-100, apolipoprotein A-I, apolipoprotein A-II, TC/HDL-C ratio, cardiovascular risk prediction, total cholesterol, men, Physicians' Health Study, lipoprotein subfractions, risk factors, coronary heart disease prevention, statin therapy
MeSH terms: Adult, Aged, Aged, 80 and over, Apolipoproteins, Apolipoproteins A, Apolipoproteins B, Cholesterol, Humans, Cholesterol, HDL, Male, Middle Aged, Myocardial Infarction, Prospective Studies, Risk Factors

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A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction.

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