Vasculogenic erectile dysfunction (ED) is considered an early manifestation of generalized arterial disease. ED is frequent in patients with established coronary artery disease (CAD) [5], it co-exists with occult CAD [6], and it is an independent predictor of CV outcomes [7]. In hypertensive patients, it is currently unknown whether ED is related to any additional risk on top of hypertension. Furthermore, data regarding the extent of hypertension-related TOD in hypertensive men with ED are scarce.

Ultrasound examination of the carotid arteries with measurement of intima-media thickness (IMT) or identification of the presence of plaques is a reliable surrogate of systemic atherosclerosis, including CAD [8]. The presence but not the severity of ED (as quantified by the International Index of Erectile Function-IIEFquestionnaire) has been associated with increased carotid IMT specifically in hypertensive patients [9]. Other studies have shown a trend towards a more severe impairment of vascular function and structure at penile arteries (by measurement of dynamic penile peak systolic velocity and IMT) in ED patients with higher carotid IMT [10, 11].

Measurement of carotid–femoral pulse wave velocity (PWV) provides a comprehensive non-invasive assessment of aortic stiffness [12, 13]. Aortic stiffness has been associated with the presence and severity of penile vascular disease as measured by penile Doppler in hypertensive (treated and never treated) individuals [9]. In men without hypertension or other traditional risk factors (as well as in individuals with early stage high blood pressure) aortic PWV level was similar between the ED patients and men with normal erectile function [14, 15].

Left ventricular hypertrophy (LVH) is highly prevalent among hypertensive patients. The association of LVH and increased CV morbidity and mortality has been convincingly documented [16]. Left ventricular diastolic function is impaired in ED patients with hypertension but without overt cardiovascular disease compared to men with normal erectile function [17], however, differences in LV structure are not evident between ED patients and non-ED subjects, at least in the early stages of hypertension [15].

A low ankle–brachial blood pressure index (ABI) signals peripheral artery disease (PAD) and, in general, advanced atherosclerosis, and relates to further development of CV morbidity and mortality [18]. In a study evaluating the relationship between ED and PAD, Polonsky et al. showed that ABI successfully identified PAD in men with ED and suggested that men with ED be targeted for ABI examination [19]. The association of ABI with ED in the context of hypertension has not been studied yet.

The finding of an impaired renal function in a hypertensive patient, expressed as increased urinary protein excretion and/or a reduced estimated glomerular filtration rate, constitutes a very potent predictor of future CV events and death [20]. The association of ED with glomerular filtration rate and albuminuria, particularly in men with hypertension has not been adequately addressed. Although albuminuria has been associated with ED in type 2 diabetes patients [21], data on the impact of ED in treated and untreated essential hypertensive patients are not yet available [22].

As there are no data on the predictive value of TOD specifically for hypertensive patients with ED, we rely on the evidence available from studies in patients either with hypertension or with ED. It should be noted, however, that patients in ED studies were to a large percentage hypertensives [7] (Table 6.2). Recent data show an independent predictive ability of aortic PWV for future cardiovascular events specifically in ED patients without established cardiovascular disease (Vlachopoulos et al. submitted). Subjects in the highest PWV tertile (>8.8 m/s) had a fourfold higher risk of MACE compared to those in the lowest PWV tertile (<7.6 m/s). When added to standard risk models, such as the Framingham Risk Score, aortic PWV reclassifies correctly a considerable percentage (27.6 %) of patients to a higher or lower risk category in the whole population. In addition, pulse pressure, a crude index of arterial stiffness, has also been shown to predict outcome in ED patients: the risk of cardiac events is increased by 60 % for each 10 mmHg increment in pulse pressure [23]. Microalbuminuria, as defined by albumin/creatinine ratio 3.4–34 mg/mmol and albumin excretion ratio 30–300 mg/day, is an easily measured non-circulating marker of microvascular injury. Microalbuminuria has been shown to predict CV events specifically in a population of diabetic ED patients with angiographically proven CAD; in this studied population, hypertension was highly prevalent [24].

Further to the identification of organs that can serve as risk predictors, it would be important to assess whether TOD regression predicts risk reduction. Such evidence, documented in hypertensive patients [3, 25], offers valuable information on whether specific treatment confers additional therapeutic benefit. Currently there are no data in the ED population to document the impact of antihypertensive drugs (with neutral or even a positive effect on erectile function) on TOD regression. Likewise, whether treatment-induced reduction in TOD affects incidence of adverse CV events is also an interesting, yet unexplored, field.

The frequent co-existence of hypertension and ED and the impact of antihypertensive drugs on sexual function raise the question whether ED is the result of hypertension per se, an adverse event of antihypertensive treatment, or a combination of both [26]. Several lines of evidence indicate that drugs used in the treatment of hypertension can indeed deteriorate sexual function, but such an effect appears mainly with older generation drugs (older beta blockers, diuretics), while newer agents (nebivolol, renin-angiotensin-aldosterone system blockers) might even improve sexual function [27]. On the other hand, hypertension appears to cause ED per se, through a multitude of mechanisms that include prolonged exposure to elevated levels of systemic blood pressure, endothelial dysfunction and circulation of vasoactive substances (with a pivotal role of angiotensin II) that lead to structural and functional alterations in the penile arteries [28]. Penile doppler studies have shown that the presence of hypertension is associated with a approximately twofold increase in the likelihood of having an abnormal penile blood flow [29]. Specifically, patients with hypertension exhibit a significantly low penile blood inflow and venous leakage as expressed by reduced penile peak systolic velocity (PSV) and increased end-diastolic velocity (EDV) respectively, compared to men without vascular risk factors.

Screening for vasculogenic ED as a TOD per se could be incorporated in diagnostic algorithms for the management and treatment of arterial hypertension [30] in men for three reasons: First, ED is easy to recognize and it gravely affects a man’s quality of life. Second, the presence of ED per se increases the risk for future CV events [7]. The predictive ability of ED is higher in young subjects and in subjects with intermediate baseline CV risk [7]. Third, testosterone deficiency, which is frequent in aged males who suffer from vasculogenic ED [31], is associated with subclinical organ damage (LVH, IMT, aortic stiffness, ABI) [31–33], and it is an important predictor of future CV events in men with hypertension [34].

ED as a TOD: The use of the Sexual Health Inventory for Men (SHIM) validated questionnaire for diagnosis and evaluation of ED as a TOD should be incorporated in the investigation of all hypertensive patients [35, 36]. Importantly, according to recent evidence validated questionnaires correlate with the vascular markers of TOD [9, 19, 37] (aortic PWV, carotid IMT, ABI) and improve the predictive value of ED for total CV events compared with a single question [7]. Evaluation of penile vasculature by dynamic color Doppler ultrasound (with intracavernous injection of alprostadil) still remains the cornerstone of the diagnostic workup of the patients with vasculogenic ED, by differentiating psychogenic and vasculogenic causes of ED [38, 39]. Penile doppler indices strongly correlate with atherosclerotic lesions in other vascular beds and major adverse CV events [40].