Interleukin-6 and flow-mediated dilatation as markers of... : Menopause (original) (raw)

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Interleukin-6 and flow-mediated dilatation as markers of increased vascular inflammation in women receiving hormone therapy

Vitale, Cristiana MD; Cornoldi, Alessandra MD; Gebara, Otavio MD; Silvestri, Antonello MD; Wajngarten, Mauricio MD; Cerquetani, Elena MD; Fini, Massimo MD; Ramires, José Antonio F MD; Rosano, Giuseppe M C MD, PhD

From the 1Cardiovascular Research Unit Department of Medical Sciences, Fondazione San Raffaele IRCCS-Roma, Tosinvest Sanita', Roma, Italy; 2INCOR, Heart Institute from the Medical School University of São Paulo, São Paulo, Brazil; and 3Department of Cardiology, Policlinico Portuense, Roma, Italy.

Received August 30, 2004; revised and accepted February 14, 2005.

The present study was supported in part by an educational grant of the Associazione per le Ricerche Mediche ONLUS.

Address correspondence to: Giuseppe M. C. Rosano, MD, PhD, FACC, Cardiovascular Research Unit, Department of Medical Sciences, Fondazione San Raffaele IRCCS- Roma, Tosinvest Sanita', via della Pisana 235, 00163 Roma, Italy. E-mail: [email protected].

Objective:

The lack of a beneficial long-term cardiovascular effect of hormone therapy and the early incidence of cardiovascular adverse events observed in recent randomized studies have been related to a heightened inflammatory effect of hormone therapy.

Design:

We evaluated the effect of different postmenopause therapies on inflammatory markers and endothelial function in 205 postmenopausal women before and after therapy.

Results:

In all postmenopausal women, estrogens alone increased plasma levels of C-reactive protein (CRP) but decreased all other markers of inflammation including interleukin-6 (IL-6) (CRP: +75% ± 11%, intracellular adhesion molecule: −21% ± 4%, vascular cell adhesion molecule: −15% ± 6%, E-selectin: −18% ± 4%, s-thrombomodulin −10.5% ± 3.7%, IL-6 −14% ± 6%; percent changes, P < 0.01 compared with baseline). Raloxifene and tibolone did not significantly affect the overall inflammatory milieu. In a minority of patients, estrogen-progestogen associations and tibolone increased IL-6 levels and induced unfavorable changes on inflammation markers (CRP: +93% ± 8%, intracellular adhesion molecule: −3% ± 2%, vascular cell adhesion molecule: −5% ± 2%, E-selectin: +6% ± 2%, s-thrombomodulin: +5% ± 2%, IL-6: +12% ± 4%; percent changes compared with baseline). Patients with increased IL-6 levels were older and had a longer time since menopause. In all patients except those with increased IL-6 levels, hormone therapy improved endothelial function, whereas tibolone and raloxifene did not significantly change endothelial function compared with baseline. A worsening of endothelial function was detected in patients with increased IL-6 levels during therapy.

Conclusions:

Postmenopausal hormone therapy is associated with decreased vascular inflammation; however, in patients with a longer time since menopause, postmenopause hormone therapy may increase inflammation and worsen endothelial function. These unfavorable vascular effects may be detected by an elevation in IL-6 levels and by a lack of improvement in endothelial function.