1. ¹Department of Cardiology, Cardiothoracic Centre, St. Thomas' Hospital, London, United Kingdom.
2. ²Department of Chemical Pathology, St. Thomas' Hospital, London, United Kingdom.

Correspondence: Dr. Anthony S. Wierzbicki, Department of Chemical Pathology, St. Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, United Kingdom, E-mail: Anthony.Wierzbicki@kcl.ac.uk

^*Pfizer Inc. supported this investigation. Drs. Wierzbicki and Jackson have both received lecture honoraria, travel and grant support from Pfizer Inc.

Received 17 June 2005; Revised 28 January 0000; Accepted 2 February 2006.

Abstract

Background: Erectile dysfunction is related to endothelial function. Cardiovascular risk factors determine endothelial function. Sildenafil is effective in treatment of erectile dysfunction but shows variable results. This study investigated the relationship of cardiovascular risk factors to acute and chronic responses to sildenafil.

Methods: Cardiovascular risk factors and acute and chronic pulse wave responses to a single 50-mg dose of sildenafil were assessed in 45 patients with erectile dysfunction confirmed by low international index of erectile function (IIEF) score before and after chronic therapy with sildenafil.

Results: On recruitment all patients showed evidence of erectile dysfunction with an IIEF score of 5 points (1 to 20 points). Chronic sildenafil therapy resulted in an increase of IIEF score of 13 points (range -1 to +24 points) and 24 patients (53%) achieved an IIEF score 21 points. Improvement in erectile function in response to sildenafil (rⁿ = 0.79; P < .001) was dependent on initial erectile function (P = .002) and baseline apolipoprotein B (P = .01). Vascular responses to acute treatment with sildenafil were assessed using pulse wave analysis. Acute changes in stiffness index induced by sildenafil (rⁿ = 0.65; P < .001) were related to apolipoprotein A-1 (P = .006), B (P = .02), and lipoprotein(a) (P = .008) concentrations, whereas reflection index (rⁿ = 0.69; P < .001) was related to pulse pressure (P < .001), albumin-to-creatinine ratio (P = .007), and lipoprotein(a) (P = .02).

Conclusions: The extent of acute and chronic effects of sildenafil on erectile function and pulse wave profiles is determined by metabolic cardiovascular risk factors. Improved cardiovascular risk factor control is likely to increase the efficacy of phosphodiesterase-5 inhibitor therapy in the treatment of erectile dysfunction.