Fig. 24.1
Management of hypertensive patients with CVD (a) or without known CVD (b). *Low-risk patients include those with complete revascularization (e.g., via coronary artery bypass grafting, stenting, or angioplasty), patients with asymptomatic controlled hypertension, those with mild valvular disease, and patients with left ventricular dysfunction/heart failure (NYHA classes I and II) who achieved five metabolic equivalents of the task (METS) without ischemia on recent exercise testing. **Indeterminate risk patients include diabetics, those with mild or moderate stable angina pectoris, past myocardial infarction (2–8 weeks) without intervention awaiting exercise electrocardiography, congestive heart failure (NYHA class III), and noncardiac sequelae of atherosclerotic disease (e.g., peripheral artery disease and a history of stroke or transient ischemic attack); this patient with ED may require assessment for additional vascular disease using carotid intima-media thickness or ankle-brachial index and subsequent reclassification to low or high risk. ***High-risk patients include those with unstable or refractory angina pectoris, uncontrolled hypertension, congestive heart failure (NYHA class IV), recent myocardial infarction without intervention (2 weeks), high-risk arrhythmia (exercise-induced ventricular tachycardia, implanted internal cardioverter defibrillator with frequent shocks, and poorly controlled atrial fibrillation), obstructive hypertrophic cardiomyopathy with severe symptoms, and moderate to severe valve disease, particularly aortic stenosis. ‡Where appropriate CVD cardiovascular disease, FRS Framingham risk score, PDE5i phosphodiesterase type 5 inhibitors, RF risk factor, Tth testosterone therapy; NYHA New York Heart Association. From Vlachopoulos et al. [19]
24.5.2 Step 2: The Use of Biomarkers in the Therapy of ED
The key question that must be answered is whether the use of a new biomarker (vascular or circulating) can determine a therapeutic approach (e.g., choice of drug, dose of drug) or the likelihood of response to an agent [18, 19, 25, 26]. In a man with arterial hypertension who is starting therapy with PDE-5 inhibitors for the first time, baseline testosterone levels in conjunction with penile Doppler evaluation can potentially aid in the prediction of response to treatment. As mentioned above, regarding baseline testosterone, it has been shown that a low testosterone level may inhibit the effectiveness of PDE-5 inhibitors [22]. Aging and cardiovascular risk factors (i.e., hypertension, diabetes) are associated with several changes in arterial structure and function, part of them related to decline of circulating levels of testosterone [19, 22, 25, 26]. These changes may be responsible, to an extent, for the lack of efficacy of ED treatments in men with low androgen level as an important component of vasculogenic ED. Furthermore, the dynamic penile color duplex Doppler ultrasonography (using 20 μg intracavernous prostaglandin E1 and audiovisual stimulation) is required for secure diagnosis of vasculogenic ED. Importantly, sporadic studies have shown that non-responders to PDE-5 inhibitors have ultrasonographically documented severe penile vascular disease [27].
24.5.3 Step 3: Treatment Strategies
Figure 24.2 shows the flow chart for the proposed treatment algorithm. Treatment of ED in hypertensive patients requires certain steps. First, in hypertensive men with ED resulting from antihypertensive drugs, the physician may substitute current treatment with drugs with a better profile regarding sexual side effects (nebivolol or renin-angiotensin system blocker) [28]. If ED persists, the combination of PDE-5 inhibitors and antihypertensive drugs with favorable effect on sexual function [16, 20] is the next choice [29]. Testosterone replacement therapy should be reserved for ED patients who have biochemical evidence of testosterone deficiency [18, 22]. Often such a hormonal disorder is revealed in patients who are non-responders to PDE-5 inhibitors. Intracavernous self-injection, penile prostheses, low-intensity extracorporeal shock wave therapy, and stent implantation in focal atherosclerotic lesions of the internal pudendal arteries with endovascular stents constitute also common path for men with ED refractory to PDE-5 inhibitors [30–32].
Fig. 24.2
Proposed algorithm for the management of erectile dysfunction in hypertensive patients who take antihypertensive drugs. ED erectile dysfunction, PDE-5i phosphodiesterase-5 inhibitors, *unless contraindicated or current antihypertensive drug therapy is absolutely indicated
It should be emphasized that (a) data regarding combination antihypertensive drug therapy are remarkably lacking. As the majority of hypertensive patients take two or more drugs, it seems to be of great importance to know the effect of different combination regimens [29, 33]. (b) Although most data obtained during a formal evaluation, comprising of medical history, questionnaires, physical examination, and first-line tests (testosterone levels, penile Doppler), are very important in assessing the patient’s characteristics and ED etiology, they do not help in selecting the best PDE-5 inhibitor for a given patient. (c) Finally, ED patients should be informed about the correct way of sexual medication usage. Although it sounds obvious, it is important to emphasize that improper drug usage is a common reason for lack of efficacy.
24.6 Conclusion
A comprehensive approach is needed both for identifying sexual dysfunction earlier and individualizing treatment. It is important to recognize that ED contributes to a reduction of therapeutic compliance and aggravates further the quality of life among men who already suffer from essential hypertension and other comorbidities. Available data point towards significant benefits in erectile function when prior antihypertensive drug therapy is switched to either nebivolol or renin-angiotensin system blockers. PDE-5 inhibitors, a class of agents that has offered new perspectives in the management of ED, are effective and safe in hypertensive patients, but their use should follow appropriate consultation. Testosterone deficiency should be searched for and therapy should be offered in hypertensive males with clinical evidence of this disorder. Further evidence is warranted to elucidate the effects of antihypertensive drug therapy on erectile function, especially regarding the combination of antihypertensive drugs and the combination of antihypertensive drugs with PDE-5 inhibitors.
References
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Düsing R (2005) Sexual dysfunction in male patients with hypertension: influence of antihypertensive drugs. Drugs 65:773–786PubMedCrossRef
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