Oral postmenopausal hormone therapy, C-reactive protein, and cardiovascular outcomes

Abstract

Objectives: This study examines C-reactive protein (CRP) levels predicting cardiovascular events (CVEs) among hormone therapy (HT) users and nonusers.

Methods: CRP levels are higher in women who use oral HT than those in nonusers; however, whether the same CRP cut-points determine increased cardiovascular risk remains unanswered. CRP was measured at baseline in 10,953 HT users and 15,838 nonusers in the Women's Health Study. In HT nonusers and users, Cox proportional hazard models adjusted for age, cardiovascular risk factors, body mass index, and menopause status were constructed using American Heart Association/Centers for Disease Control and Prevention recommended CRP cut-points for low, average, and high cardiovascular risk as well as HT nonuser- and user-derived quantiles of CRP to predict incident CVEs.

Results: CVE risk increased with logarithm CRP for both HT users and nonusers. After adjusting for cardiovascular risk factors including lipids, the multivariable relative risk (RR) per log unit of CRP was 1.27 (95% CI, 1.13-1.44) for HT nonusers and 1.22 (95% CI, 1.07-1.40) for HT users. To compare the risk associated with American Heart Association/Centers for Disease Control and Prevention CRP categories across HT use groups, we fit a model in which nonusers with a CRP level lower than 1 mg/L were the reference group. After adjusting for other risk factors including lipids, HT users with a CRP level of 3 mg/L or higher had an RR of 1.93 (1.38-2.69), whereas nonusers had an RR of 1.92 (1.35-2.72).

Conclusions: CRP predicts CVE in a linear relationship among both HT users and nonusers. CRP levels of 3 mg/L or higher were associated with increased cardiovascular risk in both nonusers and HT users.

Trial registration: ClinicalTrials.gov NCT00000479.

Figure 1

Relative risks* for cardiovascular events for AHA/CDC CRP categories in 10,953 HT users and 15,838 non-users, compared to a common referent group (non-users with CRP <1 mg/dl). ^* Adjusted for age, postmenopausal status, body mass index, family history of myocardial infarction, hypertension, diabetes, smoking, hyperlipidemia treatment, total/HDL cholesterol ratio, and randomized treatment assignment. Follow-up censored at change in HT use status.