Inflammatory markers and the risk of coronary heart disease in men and women.
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.
Pai
Jennifer K
JK
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Pischon
Tobias
T
Ma
Jing
J
Manson
JoAnn E
JE
Hankinson
Susan E
SE
Joshipura
Kaumudi
K
Curhan
Gary C
GC
Rifai
Nader
N
Cannuscio
Carolyn C
CC
Stampfer
Meir J
MJ
Rimm
Eric B
EB
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D012306:Risk; D012737:Sex Factors
D015850:Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D002097:C-Reactive Protein