Inflammatory markers and the risk of coronary heart disease in men and women.

Abstract

BACKGROUND:

Few studies have simultaneously investigated the role of soluble tumor necrosis factor alpha (TNF-alpha) receptors types 1 and 2 (sTNF-R1 and sTNF-R2), C-reactive protein, and interleukin-6 as predictors of cardiovascular events. The value of these inflammatory markers as independent predictors remains controversial.

METHODS:

We examined plasma levels of sTNF-R1, sTNF-R2, interleukin-6, and C-reactive protein as markers of risk for coronary heart disease among women participating in the Nurses' Health Study and men participating in the Health Professionals Follow-up Study in nested case-control analyses. Among participants who provided a blood sample and who were free of cardiovascular disease at baseline, 239 women and 265 men had a nonfatal myocardial infarction or fatal coronary heart disease during eight years and six years of follow-up, respectively. Using risk-set sampling, we selected controls in a 2:1 ratio with matching for age, smoking status, and date of blood sampling.

RESULTS:

After adjustment for matching factors, high levels of interleukin-6 and C-reactive protein were significantly related to an increased risk of coronary heart disease in both sexes, whereas high levels of soluble TNF-alpha receptors were significant only among women. Further adjustment for lipid and nonlipid factors attenuated all associations; only C-reactive protein levels remained significant. The relative risk among all participants was 1.79 for those with C-reactive protein levels of at least 3.0 mg per liter, as compared with those with levels of less than 1.0 mg per liter (95 percent confidence interval, 1.27 to 2.51; P for trend <0.001). Additional adjustment for the presence or absence of diabetes and hypertension moderately attenuated the relative risk to 1.68 (95 percent confidence interval, 1.18 to 2.38; P for trend = 0.008).

CONCLUSIONS:

Elevated levels of inflammatory markers, particularly C-reactive protein, indicate an increased risk of coronary heart disease. Although plasma lipid levels were more strongly associated with an increased risk than were inflammatory markers, the level of C-reactive protein remained a significant contributor to the prediction of coronary heart disease.

• Authors: Jennifer K Pai, Tobias Pischon, Jing Ma, JoAnn E Manson, Susan E Hankinson, Kaumudi Joshipura, Gary C Curhan, Nader Rifai, Carolyn C Cannuscio, Meir J Stampfer, Eric B Rimm
• Journal: The New England journal of medicine (N Engl J Med) Vol. 351 Issue 25 Pg. 2599-610 (Dec 16 2004) ISSN: 1533-4406 [Electronic] United States
• PMID: 15602020 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2004 Massachusetts Medical Society.

Chemical References

• Interleukin-6
• Receptors, Tumor Necrosis Factor, Type I
• Receptors, Tumor Necrosis Factor, Type II
• C-Reactive Protein

Topics

• Adult
• Aged
• C-Reactive Protein (analysis)
• Cardiovascular Diseases (blood, epidemiology, immunology)
• Case-Control Studies
• Female
• Follow-Up Studies
• Humans
• Interleukin-6 (blood)
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Receptors, Tumor Necrosis Factor, Type I (blood)
• Receptors, Tumor Necrosis Factor, Type II (blood)
• Risk
• Sex Factors