As already stated, ED carries by itself an independent risk for both prevalent CAD and future CV events. Several tests that measure the general atherosclerotic burden (not necessarily obstructive) either in the coronary circulation (i.e., coronary calcium score by electron-beam computed tomography) or in extra-coronary vessels (i.e., ankle-brachial index, carotid intima-media thickness) along with functional arterial indices (flow-mediated dilatation) or mixed (functional and structural) arterial indices (aortic stiffness and wave reflection indices) are also considered surrogate markers of CVD [4, 13, 30]. ED has been associated with all the above mentioned markers of overall atherosclerotic burden (Table 9.1). It would be extremely clinically useful to identify potential biomarkers that would predict future CV event in the ED population. These biomarkers of generalized vascular disease discussed above are potential such candidates. However, to the best of our knowledge, carotid-femoral pulse wave velocity (cfPWV) is the only biomarker of generalized vascular disease that independently predicts future major adverse cardiac events (MACE) in ED and has the ability to reclassify patients in the proper CV risk group over and beyond traditional CV risk factors [8]. cfPWV is a validated noninvasive assessment of aortic stiffness, which has been shown to have an independent predictive value for cardiovascular events and all-cause mortality [31–33]. In addition, pulse pressure, a crude index of arterial stiffness, has also been shown to predict outcome in ED patients [34]. It should be noted that the rest abovementioned indices have not shown a predictive ability specifically in ED patients since relevant studies are lacking. However, based on their ability in various populations, they are expected to show such performance in ED patients.

Hormonal testing (testosterone or prolactin) has been shown to be an independent predictor of CV events in ED patients. In specific, while total testosterone levels <8 nmol/L are associated with increased chance of MACE, for each 10 ng/mL increment of prolactin levels (in ED patients without pathological hyperprolactinemia, prolactin <735 mU/L or 35 ng/ mL), the risk for MACE is decreased by 5 % [8, 35]. We also demonstrated in a group of hypertensive patients consisting primarily of patients with ED that the predictive ability of total testosterone is incremental to Framingham risk score and has the potential to reclassify these patients to their appropriate CV risk group [36]. Furthermore, albuminuria (micro- or macro-), as assessed by albumin/creatinine ratio >3.5 mg/mmol and albumin excretion ratio >30 mg/day, predicts outcome in diabetic patients with and without ED [10, 21]. Interestingly, assessment of both flaccid and dynamic peak systolic velocity (PSV) (flaccid PSV < 13 cm/s and dynamic PSV < 25 cm/s) in penile Doppler is a prognostic marker for incident major CV events [37].

Finally, office-based assessment of cardiovascular risk using conventional risk factor algorithms, such as Framingham risk score and Systematic COronary Risk Evaluation (SCORE), is important for initial risk stratification [4]. In 2012 the Third Princeton Consensus Conference addressed the role of screening and lifestyle modifications in ED patients according to CVD risk [38]. On the foundations of Princeton III recommendations, a practical clinical algorithm has been recently proposed [4] (Fig. 9.2). Therefore, inclusion of such biomarkers and CV risk scores in the assessment of ED patients may aid in identifying which asymptomatic ED patient should be further investigated and how aggressively should be treated [4].

Improvement of ED by lifestyle interventions, common to those recommended for reduction of CVD risk, might per se be beneficial in terms of erectile function and prognosis. After the initial ED evaluation and prior to administration of specific ED treatment, exercise ability should be considered to estimate CV risk associated with sexual activity [39]. A recent meta-analysis of 14 studies established a significant association between acute cardiac events and episodic physical or/and sexual activity that was attenuated among individuals with high levels of habitual physical activity.

Of special interest is the effect of pharmacological treatment of ED, as it appears that this may also have a beneficial impact on risk [40]. Indeed, Frantzen et al. [41] showed that 2 years after the introduction of sildenafil, the RR of the incidence of CVD among men with ED compared with healthy men significantly decreased from 1.7 to 1.1. Furthermore, Gazzaruso et al. [10] showed that type 5 phosphodiesterase inhibitors offer a marginal protection against the development of major adverse cardiac events in CAD diabetic patients with ED.

Testosterone treatment for hypogonadal ED patients as well as its effect on cardiovascular outcomes is a highly debated subject. Systematic reviews and meta-analyses of testosterone therapy show a neutral or small unfavorable effect on cardiovascular outcomes [42, 43]. However, the Testosterone in Older Men With Mobility Limitations (TOM) trial [44], which randomized community-dwelling men 65 years and older with limitations in mobility and total serum testosterone levels lower than 350 ng/dL to placebo or testosterone gel for 6 months showed more cardiovascular events in the testosterone arm. However, the clinical applicability of these findings is limited by the usage of an off-label, high, and rapid escalation dosing regimen and by the inclusion of frail elderly men with impaired mobility. Furthermore, in a recent retrospective study [45] testosterone users were found to have an increased risk of cardiovascular outcomes; however, the study is hampered by methodological shortcomings in analysis and credibility of data report. Based on these results testosterone treatment must be reserved for patients who (1) are symptomatic (ED or reduced libido) of testosterone deficiency and (2) they have biochemical evidence of low testosterone (total testosterone <8 nmol/L or 230 ng/dL) with respect to its contraindications and limitations as well as close follow-up [4, 38].

Drugs used in cardiovascular disease prevention and treatment, such as drugs of the renin-angiotensin-aldosterone system and statins, apart from reducing cardiovascular risk appear to have a beneficial effect on ED itself. It is rational to believe that these drugs will have a beneficial effect in cardiovascular outcomes of ED patients as well [46]. Limited data have demonstrated a significant role of statins in improving the prognosis of diabetics with CAD that included a significant proportion of ED patients [10]. Undoubtedly, more data are needed and future follow-up studies should ideally collect information on ED treatment and investigate their effect on prognosis [47].

In summary, CVD and ED share common risk factors, while evidence-based studies have identified pathophysiological links, such as endothelial dysfunction and inflammation. ED also confers an independent risk for future CV events. The usual 3-year time frame between the onset of ED symptoms and a CV event offers an opportunity for risk mitigation and potentially improvement of outcomes. Current literature and guidelines [48] support implementation of ED into clinical practice and stress the need to establish standardized methods to diagnose ED and to investigate the potential effect of use of biomarkers and ED treatment on CV events and all-cause mortality.