Erectile dysfunction (ED) affects 18 million men in the United States alone¹1. Spessoto LC, Facio FN Jr, Arruda JG, Arruda PF, Gatti M, Antoniassi TS, et al. Association of hypertension with erectile function in chronic peripheral arterial insufficiency patients. J Clin Med Res. 2016;8(8):582-4.. Its prevalence is 52% among men aged from 40 to 70 years and 70% among those older than 70²2. Vlachopoulos CV, Terentes-Printzios DG, Ioakeimidis NK, Aznaouridis KA, Stefanadis CI. Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: a systematic review and meta-analysis of cohort studies. Circ Cardiovasc Qual Outcomes. 2013;6(1):99-109.. This condition may be related to changes in penile blood flow since the etiology is vascular in 60% of patients¹1. Spessoto LC, Facio FN Jr, Arruda JG, Arruda PF, Gatti M, Antoniassi TS, et al. Association of hypertension with erectile function in chronic peripheral arterial insufficiency patients. J Clin Med Res. 2016;8(8):582-4..

Cardiovascular disease (CVD) and ED share the same risk factors, such as age, smoking, hypertension, obesity, diabetes mellitus, sedentary lifestyle, depression, and metabolic syndrome¹1. Spessoto LC, Facio FN Jr, Arruda JG, Arruda PF, Gatti M, Antoniassi TS, et al. Association of hypertension with erectile function in chronic peripheral arterial insufficiency patients. J Clin Med Res. 2016;8(8):582-4.^,33. Vestergaard N, Søgaard P, Torp-Pedersen C, Aasbjerg K. Relationship between treatment of erectile dysfunction and future risk of cardiovascular disease: a nationwide cohort study. Eur J Prev Cardiol. 2017;24(14):1498-505.. Such factors lead to endothelial dysfunction, the formation of atherosclerotic plaque, and the inflammation of small blood vessels and are, therefore, related to both cardiovascular events and ED. The evaluation of the temporal relation between ED and subclinical CVD may encourage a change in risk behaviors and prevent the occurrence of CVD⁴4. Querichelli AFA, Faria MHS, Raimundo SRO, Fácio Jr FN, Spessoto LCF. Does erectile dysfunction improve the assessment of cardiovascular risk? J Xiangya Med. 2019;4(36):1-2.. Studies have demonstrated that patients with ED have an increased risk for cardiovascular events and mortality and that ED may be a symptom or even an independent predictor of coronary artery disease (CAD)¹1. Spessoto LC, Facio FN Jr, Arruda JG, Arruda PF, Gatti M, Antoniassi TS, et al. Association of hypertension with erectile function in chronic peripheral arterial insufficiency patients. J Clin Med Res. 2016;8(8):582-4.^,22. Vlachopoulos CV, Terentes-Printzios DG, Ioakeimidis NK, Aznaouridis KA, Stefanadis CI. Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: a systematic review and meta-analysis of cohort studies. Circ Cardiovasc Qual Outcomes. 2013;6(1):99-109..

Arterial hypertension is related to the development of atherosclerosis and is one of the risk factors for the development of CAD and ED but is also a protective factor against ED in patients with CAD, as it improves penile function¹1. Spessoto LC, Facio FN Jr, Arruda JG, Arruda PF, Gatti M, Antoniassi TS, et al. Association of hypertension with erectile function in chronic peripheral arterial insufficiency patients. J Clin Med Res. 2016;8(8):582-4.. In ED, the increase in vascular pressure initially improves penile flow and perfusion but is harmful in the long term since it implies an increase in atherosclerosis and arterial occlusion¹1. Spessoto LC, Facio FN Jr, Arruda JG, Arruda PF, Gatti M, Antoniassi TS, et al. Association of hypertension with erectile function in chronic peripheral arterial insufficiency patients. J Clin Med Res. 2016;8(8):582-4.. In urology, the pharmacological treatment of ED is based on the use of vasodilators, especially the class of phosphodiesterase-5 (PDE-5) inhibitors, which improve blood flow and sexual performance (sildenafil, vardenafil, tadalafil, and avanafil)⁵5. Korkmaz-Icöz S, Radovits T, Szabó G. Targeting phosphodiesterase 5 as a therapeutic option against myocardial ischaemia/ reperfusion injury and for treating heart failure. Br J Pharmacol. 2018;175(2):223-31..

PDE-5 inhibitors diminish the catabolism of cyclic guanosine monophosphate (cGMP) through the inhibition of the enzyme PDE-5, which results in the relaxation of smooth muscles and consequent vasodilation, besides offering a cardioprotective effect related to the action of nitric oxide⁵5. Korkmaz-Icöz S, Radovits T, Szabó G. Targeting phosphodiesterase 5 as a therapeutic option against myocardial ischaemia/ reperfusion injury and for treating heart failure. Br J Pharmacol. 2018;175(2):223-31.. The discovery that PDE-5 is also expressed in the myocardium led to a change in views regarding the direct effect of these inhibitors on this tissue⁶6. Hutchings DC, Anderson SG, Caldwell JL, Trafford AW. Phosphodiesterase-5 inhibitors and the heart: compound cardioprotection? Heart. 2018;104(15):1244-50.. The expression of PDE-5 suggests that inhibitors of this enzyme exert beneficial effects on the heart through changes in regional and systemic hemodynamics related to anti-apoptotic and anti-inflammatory properties as well as reductions in hypertrophy, ventricular arrhythmia, myocardial fibrosis, and oxidative stress⁵5. Korkmaz-Icöz S, Radovits T, Szabó G. Targeting phosphodiesterase 5 as a therapeutic option against myocardial ischaemia/ reperfusion injury and for treating heart failure. Br J Pharmacol. 2018;175(2):223-31..

There is evidence of the effectiveness of PDE-5 inhibitors in heart failure with reduced ejection fraction. Such evidence is sustained by the effects on pulmonary vasodilation, cardiac remodeling, improved diastolic function, reductions in fibrosis and interstitial inflammation, and an improvement in coronary microcirculation⁶6. Hutchings DC, Anderson SG, Caldwell JL, Trafford AW. Phosphodiesterase-5 inhibitors and the heart: compound cardioprotection? Heart. 2018;104(15):1244-50.. Regarding myocardial infarction, the use of PDE-5 inhibitors seems to increase the tolerance threshold for ischemia/angina and is related to a lower mortality rate after the event⁶6. Hutchings DC, Anderson SG, Caldwell JL, Trafford AW. Phosphodiesterase-5 inhibitors and the heart: compound cardioprotection? Heart. 2018;104(15):1244-50.. For pulmonary hypertension, treatment with PDE-5 inhibitors is effective due to vasodilation, a reduction in cell proliferation, and the stimulation of apoptosis, which have the potential to reduce pulmonary pressure⁷7. Nguyen H, Amanullah AM. Therapeutic potentials of phosphodiesterase-5 inhibitors in cardiovascular disease. Rev Cardiovasc Med. 2014;15(2):158-67..

In a retrospective study conducted in Denmark, patients in treatment with PDE-5 inhibitors for ED with no history of cardiovascular disease had a lower risk of acute myocardial infarction in comparison to the general male population³3. Vestergaard N, Søgaard P, Torp-Pedersen C, Aasbjerg K. Relationship between treatment of erectile dysfunction and future risk of cardiovascular disease: a nationwide cohort study. Eur J Prev Cardiol. 2017;24(14):1498-505.. Moreover, the risk of heart failure and all cardiovascular diseases diminished in the first three years after the start of treatment for ED³3. Vestergaard N, Søgaard P, Torp-Pedersen C, Aasbjerg K. Relationship between treatment of erectile dysfunction and future risk of cardiovascular disease: a nationwide cohort study. Eur J Prev Cardiol. 2017;24(14):1498-505.. This effect may be explained by the pharmacological action of PDE-5 inhibitors through the reduction of systolic blood pressure after the beginning of treatment, the long-term cardioprotective effect, or factors associated with behavioral changes in patients³3. Vestergaard N, Søgaard P, Torp-Pedersen C, Aasbjerg K. Relationship between treatment of erectile dysfunction and future risk of cardiovascular disease: a nationwide cohort study. Eur J Prev Cardiol. 2017;24(14):1498-505..

Since the recognition of this vasodilating effect, the interest in employing PDE-5 inhibitors for the treatment of CVD has increased and these drugs are currently used in patients with ischemic heart disease, congestive heart failure, pulmonary hypertension, Raynaud's phenomenon, peripheral vascular disease, and cerebral hypoperfusion⁷7. Nguyen H, Amanullah AM. Therapeutic potentials of phosphodiesterase-5 inhibitors in cardiovascular disease. Rev Cardiovasc Med. 2014;15(2):158-67.. Further prospective, randomized, clinical investigations are needed to explore the therapeutic potential of PDE-5 inhibitors as well as determine the effectiveness and safety of these drugs with regards to the cardioprotective effect.

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