Published Online
on June 9, 2003

A more recent version of this article appeared on July 1, 2003

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Submitted on November 25, 2002
Revised on April 1, 2003
Accepted on April 4, 2003

Increased Levels of C-Reactive Protein After Oral Hormone Replacement Therapy May Not Be Related to an Increased Inflammatory Response

Antonello Silvestri MD, Otavio Gebara MD, Cristiana Vitale MD, Mauricio Wajngarten MD, Filippo Leonardo MD, Josè A.F. Ramires MD, Massimo Fini MD, Giuseppe Mercuro MD, and Giuseppe M.C. Rosano MD, PhD^*

From the Cardiovascular Research Unit (A.S., C.V., F.L., M.F., G.M.C.R.), San Raffaele-Roma, Tosinvest Sanità, Italy, and INCOR (O.G., M.W., J.A.F.R., G.M.), University of Sao Paulo, Brazil.

^* To whom correspondence should be addressed. E-mail: giuseppe.rosano{at}sanraffaele.it.

Background--It has been suggested that hormone replacement therapy (HRT) in postmenopausal women is associated with an increased inflammatory response that may trigger acute cardiovascular events. This suggestion is mainly based on the finding of elevated C-reactive protein (CRP) levels after HRT. The aim of the present study was to evaluate a broad spectrum of vascular inflammation markers in 389 postmenopausal women with increased cardiovascular risk at baseline and after either 6 months of HRT (126 women) or no HRT (263 women).

Methods and Results--Compared with baseline, CRP levels significantly increased after HRT (0.9±0.2 versus 1.6±0.4 mg/L, P<0.01); on the contrary, soluble intracellular adhesion molecule-1 decreased from 208±57 to 168±37 ng/mL (P<0.01) after HRT. Similarly, vascular cell adhesion molecule-1 decreased from 298±73 to 258±47 ng/mL (P<0.01), plasma E-selectin levels were reduced from 17.8±5.6 to 14.8±3.9 ng/mL (P<0.01), interleukin-6 levels decreased from 1.51±0.22 to 1.29±0.28 pg/mL, and s-thrombomodulin plasma levels decreased from 4.8±0.7 to 4.3±0.9 ng/mL (P<0.01). No significant changes in either CRP or vascular inflammatory marker were detected in women not taking HRT.

Conclusions--The discrepancy between increased plasma levels of CRP and reduced plasma levels of all other markers of inflammation suggests that the increased CRP levels after oral HRT may be related to metabolic hepatic activation and not to an acute-phase response. HRT seems to be associated with an overall decrease in vascular inflammation.

Key words: cardiovascular diseases • inflammation • interleukins

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