Clinical study
The relation of C-reactive protein levels to total and cardiovascular mortality in older U.S. women☆

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Abstract

Purpose

To determine whether serum C-reactive protein levels, a sensitive indicator of inflammation, are associated with the risk of cardiovascular mortality among older women.

Methods

We conducted a case-cohort study within the Study of Osteoporotic Fractures, a population-based study involving 9704 women aged ≥65 years from four U.S. centers. We randomly selected 400 women from the entire cohort plus an additional random sample of 92 women from the 1125 women in the cohort who had died during the first 6 years of follow-up. Baseline serum C-reactive protein levels were measured using a high-sensitivity immunoassay. Cause-specific mortality was ascertained by review of death certificates and hospitalization records. Multivariable Cox proportional hazards regression was used to determine the association between C-reactive protein levels and cardiovascular mortality.

Results

During 6 years of follow-up, 150 of the 492 women died, including 52 who died of cardiovascular disease. After adjusting for potential confounders, women with C-reactive protein levels in the highest quartile (>3.0 mg/L) had a 8.0-fold (95% confidence interval [CI]: 2.2 to 29) greater risk of cardiovascular mortality than those in the lowest quartile (≤1.0 mg/L). The association remained strong in women who did not smoke or take estrogen, and when early deaths were excluded. Women who smoked and whose C-reactive protein levels were above the first quartile had a very high risk of cardiovascular mortality (relative risk [RR] = 13; 95% CI: 3.4 to 47). C-reactive protein levels were not associated with noncardiovascular mortality (RR = 0.92; 95% CI: 0.4 to 2.1).

Conclusion

C-reactive protein level was an independent predictor of cardiovascular mortality in older women.

Section snippets

Study sample

We enrolled 9704 women living in four geographic regions (Baltimore, Maryland; Pittsburgh, Pennsylvania; Minneapolis, Minnesota; and Portland, Oregon) between September 1986 and October 1988. The women were 65 years or older, ambulatory, and living independently at enrollment. African American women were excluded because of their low risk of hip fracture. The institutional review boards at the four clinical sites and the coordinating center approved the study protocol. All participants gave

Results

Among the 52 women in the final sample who died of cardiovascular disease, 22 of the deaths were due to coronary heart disease and 16 were due to stroke. Women who died of cardiovascular disease were older, had less formal education, and reported being in worse health compared with women who were alive after 6 years of follow-up (Table 1). Women who died of cardiovascular disease were also more likely to smoke, have hypertension, and have diabetes, and were less likely to be taking estrogen.

Discussion

We found that minimally elevated serum C-reactive protein levels were associated with increased mortality from cardiovascular disease for at least 6 years among older women. This association was consistent in women who did and did not smoke. Adjustment for conventional risk factors strengthened the association modestly.

These results are similar to those of previous studies involving men and women 11, 12, 13, 14, 15, even though our study comprised the oldest cohort of women and focused on

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    ☆

    This work was supported in part by Public Health Service grants AG05407, AR35582, AG05394, AR35584, AR35583, NS36016, and HL46696.

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