Current issues of ACP Journal Club are published in Annals of Internal Medicine


C-reactive protein levels were associated with cardiovascular events in apparently healthy women

ACP J Club. 1999 Jan-Feb;130:22. doi:10.7326/ACPJC-1999-130-1-022

Source Citation

Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation. 1998 Aug 25;98:731-3.



In apparently healthy women, are increased levels of high-specificity C-reactive protein associated with an increased risk for cardiovascular events?


A nested case-control study (Women's Health Study).


United States.


At baseline, all women had no history of cardiovascular events (myocardial infarction, stroke, coronary artery bypass grafting, or percutaneous transluminal coronary angioplasty). 122 women who reported a first cardiovascular event confirmed by chart audit, autopsy report, or death certificate during follow-up were matched on age and smoking status with 244 women who had not reported a cardiovascular event. Mean age was 59.3 years.

Assessment of risk factors

Baseline C-reactive protein levels were reported in quartiles (< 1.5, 1.5 to 3.7, 3.8 to 7.3, and > 7.3 mg/L), with the lowest level given the relative risk (RR) of 1.0. Baseline cardiovascular risk factors were ascertained (exercise, body mass index, hypercholesterolemia, hypertension, diabetes mellitus, and family history of cardiovascular events).

Main outcome measures

Confirmed self- or family-reported cardiovascular events.

Main results

Compared with women in the control group, those with a cardiovascular event had a higher level of C-reactive protein (3.75 vs 6.45 mg/L, P < 0.001). After adjustment for risk factors, women in the highest C-reactive protein quartile had a 4.1-fold increase in risk over women in the lowest quartile for any cardiovascular event (RR 4.1, 95% CI 1.7 to 9.9, P = 0.002) and a 5.5-fold increase for combined myocardial infarction or stroke (RR 5.5, CI 1.8 to 16.6, P = 0.002). A dose-response relation was shown between increasing levels of C-reactive protein and development of cardiovascular events and combined myocardial infarction or stroke (P = 0.002 for both). When other cardiovascular factors were included in the analysis, an increased risk for development of cardiovascular events was shown for women with high levels of C-reactive protein who had no family history of premature atherosclerosis (RR 6.6, P = 0.001), had no evidence of diabetes mellitus (RR 4.9, P = 0.001), did not smoke (RR 4.5, P = 0.001), had no history of hyperlipidemia (RR 3.9, P = 0.002), and had no history of hypertension (RR 2.8, P = 0.03).


Apparently healthy women who developed cardiovascular events had baseline levels of high-specificity C-reactive protein that were higher than those of women who did not develop cardiovascular events.

Source of funding: National Institutes of Health.

For correspondence: Dr. P.M. Ridker, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. FAX 617-734-1437.


Do elevated C-reactive protein levels identify persons who are at risk for cardiovascular events? In a previous publication (1), Ridker and colleagues did a case-control analysis of C-reactive protein levels in men at risk for myocardial infarction and ischemic stroke and found that persons with cardiovascular events had high baseline levels of C-reactive protein. They also showed a dose-response relation between high C-reactive protein levels and peripheral artery disease in men (2). Continuing to explore this relation and extend its generalizability, they now have compared baseline C-reactive protein levels in women who developed cardiovascular events to C-reactive protein levels in women who did not develop such events.

Both the case-patients and the control-patients were apparently healthy when the blood samples were drawn. A dose-response relation among quartiles of C-reactive protein levels and estimated risk for cardiovascular events was found. Because C-reactive protein levels were obtained from only a few healthy women (244 of 28 141), predictive values cannot be calculated. A cohort study would clarify the potential performance characteristics of C-reactive protein levels as a predictor of cardiovascular events. This important study adds to the growing body of literature suggesting that cardiovascular disease is linked to inflammation.

Margretta Diemer, MD, MPH
Walter Reed Army Medical CenterWashington, DC, USA


1. Ridker PM, Cushman M, Stampfer MJ, Tracy R, Hennekens CH. Inflammation, aspirin and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973-9.

2. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. Circulation. 1998;97:425-8.