The aim of this study is to evaluate whether penile peak systolic velocity (PSV) varies in patients with erectile dysfunction (ED) due to artery insufficiency associated with abnormalities in other arterial districts or not. To accomplish this, cavernous artery PSV was determined 10, 20 and 30 min after intracavernously administering alprostadil by means of echo-color Doppler to a total of 65 consecutive patients (age range 52–78 years). In all, 18 patients had ED alone (group A) and served as controls, 15 had ED plus atheroma plaques and/or marked intima-media thickness of the common carotid artery (group B); 17 had ED plus lower limb artery abnormalities; 17 had ED plus carotid and lower limb artery abnormalities (group D). Group B and C patients had a similar PSV, which turned out to be significantly lower than that in group A. Group D patients had the lowest PSV, which proved to be significantly lower than that in groups A, B and C. This study shows that a more generalized peripheral atherosclerotic process is associated with a severer penile artery insufficiency. Therefore, ED patients with a severe arterial insufficiency should undergo an extensive echo-duplex examination.
In middle-aged men, alterations of arterial or venous blood flow into and out of the penis, respectively, are the most common cause of organic erectile dysfunction (ED). They figure either as the main cause of the disease or a collateral abnormality inherent in concomitant illnesses.1, 2 ED is frequently caused by pelvic arterial insufficiency due to atherosclerosis; its sentinel relationship to generalized atherosclerosis has been sufficiently appraised.3 In particular, hemodynamic impairment (low penile brachial pressure index) has been found to be associated with other signs of atherosclerotic disease such as ischemic heart disease and arterial leg disease, as well as with major vascular events such as myocardial infarction, cerebrovascular accidents and intermittent claudication.4, 5
On the other hand, patients with ED but no clinically evident cardiovascular diseases manifest a peripheral vascular defect in endothelium-dependent and independent vasodilation. This is likely to be due to oxidative stress (elevated production of reactive oxygen species and proinflammatory cytokines), which prevents the capacity of the endothelium from generating vasodilating factors, particularly nitric oxide, before the development of other overt functional or structural systemic vascular diseases.6 In almost 70% of cases, ED may therefore become evident before angina symptoms appear.7
Thus, although arterial ED may be among the first signs of a still unrecognized generalized atherosclerosis,7, 8, 9 various risk factors, such as age, hypertension, diabetes, hyperlipidemia and cigarette smoking have proved to be associated with atherosclerosis (mainly manifesting itself in the form of increased intima-media thickness (IMT) of the common carotid artery)10 and arterial ED.3 Only limited information is available on the assessment of penile arterial flow velocity when atherosclerosis is in progress. The present study was therefore carried out to evaluate whether the cavernous peak systolic velocity (PSV) was different in arterial ED patients with or without abnormalities of other vascular beds. To accomplish this, we selected patients with ED due to arterial insufficiency and carotid and/or lower limb artery abnormalities.
Patients and methods
We enrolled 65 consecutive patients (mean age 60.7 years, range 52–78 years) with ED (median duration 3.6 years, range 1.6–7.0 years) due to arterial insufficiency (defined as blood-flow velocity <30 cm/s and nontemporal systolic peak progression)11 diagnosed by means of dynamic echo-color Doppler following intracavernous administration of alprostadil. Each patient underwent duplex ultrasonography (combined real-time and Doppler ultrasonography) of the carotid and lower limb arteries so that the presence of coincidental peripheral atherosclerosis could be evaluated. The protocol was approved by the Institutional Review Board and an informed written consent was obtained from each patient.
Clinical history and physical examination
All the patients were asked for information regarding their habits, medical history and to fulfill the five-item version of the International Index of Erectile Function (IIEF) questionnaire.12 Clinical history included the identification of the main vascular risk factors, such as cigarette smoking, hypertension, hyperlipidemia and diabetes mellitus. In particular, patients were considered smokers if they smoked more than 20 cigarettes a day for at least 1 year. Hypertension was defined as systolic blood pressure ⩾140 mmHg and/or diastolic blood pressure as ⩾90 mmHg. About 90% of the population with hypertension had hypertensive disease according to WHO stages I and II.13 The majority of them were treated with a combination of two or more antihypertensive agents. Hyperlipidemia was defined as a total serum cholesterol concentration exceeding 200 mg/dl and/or total cholesterol/high-density lipoprotein (HDL) ratio greater than five and/or serum triglyceride concentration exceeding 140 mg/dl. Diabetes mellitus was defined by clinical history and/or the results of the 75 g oral glucose tolerance test (fasting glycemia ⩾126 mg/dl and/or glycemia 120 min after oral glucose loading ⩾200 mg/dl).14
A clinical examination was conducted to evaluate the presence of penile malformations, reduced testicular volume (<12 ml according to Prader's orchidometer), penile sensitivity, cremasteric reflex and femoral artery pulsation. The physical examination also included auscultation of any carotid arterial murmurs and palpation of the arteries in the penis and lower extremities.
Patients were excluded from the study if they had severe (WHO stage III) hypertension and/or were on a complicated multidrug antihypertensive regimen, and if they had severe hyperlipidemia (total serum cholesterol concentration exceeding 280 mg/dl and/or serum triglyceride concentration exceeding 350 mg/dl) and/or glycemia >200 mg/dl.14
Echo-color Doppler evaluation
All the patients underwent dynamic echo-color Doppler of the penile arteries with pulsed Doppler analysis, following intracavernous injection of 15–20 μg of alprostadil to determine changes in the cavernous artery diameters and in PSV. Following injection, PSV was evaluated after 10, 20 and 30 min. A PSV<30 cm/s and nontemporal peak systolic progression suggested arterial disease.11
Carotid and lower limb arterial assessments were performed according to specific general ultrasound principles,15 involving both a grading of any stenosis and an attempt to characterize the plaque or IMT.
A carotid or lower limb stenosis of >50% diameter reduction was judged to be significant from the hemodynamic point of view.16, 17 Plaques were classified as homogeneous if they were relatively uniform in texture, that is usually consisting of dense fibrous tissue and/or containing areas of variable echo pattern. They were defined as heterogeneous if there was at least one well-defined focal sonolucent area and its surface was irregular.15 The IMT of the carotid arteries was measured by means of B-mode ultrasonography using a 7.5 MHz high-resolution transducer (Esaote) with the subject in a supine position. IMT, that is the distance from the leading edge of the first echogenic line to the leading edge of the second echogenic line, was measured at three different points on each side of the carotid artery; the maximal value was used as a selection criterion.
In all, 18 patients proved to be affected by ED alone (group A) and made up the control group; 15 had ED plus atheroma plaques and/or marked IMT of the common carotid artery (group B); 17 had ED plus lower limb artery abnormalities; 17 had ED plus carotid and lower limb artery abnormalities (group D).
Results are shown as mean±s.e.m. throughout the study, unless otherwise indicated. The data were analyzed by means of one-way analysis of variance (ANOVA) followed by Duncan's multiple range test or χ2 analysis, accordingly. The SPSS 9.0 software for Windows was used for statistical evaluation. A statistically significant difference was accepted when P<0.05.
The mean age of the control group was not significantly different from that of patients of groups B, C and D (Table 1). The patients of group D had a significantly longer ED duration, whereas the ED severity, evaluated by means of the IIEF-5 questionnaire, and IIEF-5 score frequency distribution were similar in the four groups with arterial ED (Table 1).
Patients with arterial abnormalities at the carotid (group B) or lower limb (group C) levels had similar PSV but a significantly lower one compared to that of the control group. Interestingly, patients with signs of peripheral atherosclerosis in both districts had PSV not only lower than that of the controls (group A), but also significantly lower than that of patients of groups B and C, suggesting that a severer peripheral atherosclerosis may be associated with a more profound impairment of penile artery blood flow (Figure 1). PSV medians and 95% confidence intervals are shown in Table 2.
Arterial risk factors
The frequency of arterial risk factors in the four groups of ED patients studied is reported in Figure 2. Cigarette smoking did not differ significantly in the various groups of patients. On average, 35–40% of the patients smoked cigarettes, which seemed to act as an amplifier of the other arterial risk factor effects. Indeed, smoking alone was not detected in any patients; it was always associated with at least another arterial risk factor, mainly hypertension or diabetes in all groups. Hypertension was present in a relevant proportion of patients (range 67–93%) and it was significantly more frequent in patients of group D. Hyperlipidemia and diabetes were present in a significantly higher number of ED patients with diffuse peripheral atherosclerosis. No particular association was detected between any specific risk factor or combination of factors and atherosclerotic localization or diffusion. From a total of 133 risk factors present alone or in different combinations, smoking accounted for 18.8%, hypertension for 38.4%, hyperlipidemia for 16.5% and diabetes for 26.3%.
A single risk factor (other than smoking) was found in about one-fourth of group A patients, but its frequency decreased to zero in patients of group D (Table 3). A significantly higher number of patients with two risk factors was detected in group C, whereas three risk factors were present in about half of the patients with a more generalized peripheral atherosclerosis (P<0.05 vs other groups). No patient had all four risk factors.
Endothelial dysfunction without arterial stenosis, as well as atherosclerosis with definitive stenosis of blood vessels, contribute to ED. Indeed, atherosclerosis accounts for nearly half of all cases of ED in patients older than 50 years.2 Endothelial dysfunction and atherosclerosis of blood vessels that supply the penis are associated with the same cardiovascular risk factors (smoking, hypertension, hyperlipidemia and diabetes mellitus) that affect the coronary arteries.6, 7, 8 Recent evidence has clearly shown that penile artery abnormalities in these patients are an ominous sign of the presence of a generalized arterial/arteriolar insufficiency or of atherosclerotic disease in other parts of the body.3, 18 The assumption of ED as a sign of atherosclerosis is also supported by a correlation between retinal vascular disease and low cavernous PSV.19
Atherosclerotic lesions may progress over decades and their progression in various arterial districts seems to be associated with the presence of cardiovascular risk factors and/or host's response (chronic low-grade inflammation state) to the clinical management (dietetic and pharmacological strategies) of these factors.20, 21 In middle-aged men, although age, hypertension and hyperlipidemia were associated with baseline carotid IMT, total cholesterol level appeared to be the strongest determinant of the progression of carotid IMT.20
In the present study, performed on consecutive patients affected by ED, an isolated penile arterial dysfunction was found in a low percentage of cases, while the vast majority of the patients had a concomitant peripheral atherosclerosis, confirming our recent observations.18 Although group D patients with ED and multidistrict atherosclerosis had a mean age and ED grading similar to those of patients with ED alone or in combination with carotid or lower limb artery abnormalities, they had a significantly longer ED duration and a lower IIEF-5 score. Group D patients also comprised a higher percentage of patients with three variously combined arterial risk factors and a lower PSV.
The lack of a significantly different IIEF-5 score as well as of ED grading among patients with varied atherosclerotic extension cannot be definitively accounted for. However, since no significant difference between the IIEF5 scores of patients with a normal vascular response after intracavernous injection with PGE1, arterial insufficiency or venous leakage has been recently reported,22 it can be hypothesized that the IIEF5 questionnaire may not be sensitive enough to discriminate ED patients with the same underlying arterial pathogenesis although with different penile artery PSV. It is, however, noteworthy that patients of group D had a IIEF5 score that almost reached statistical significance compared to those of group A (P=0.06, unpaired Student's t-test). Therefore, IIEF score cannot be used as a tool to compare ED because of the various degrees of arterial insufficiency. In contrast, the very low cavernous PSV in patients with a more generalized atherosclerosis suggests that this parameter, in addition to identifying arterial insufficiency as the organic cause of ED, may suggest that atherosclerosis could extend to other than penis arterial districts. In middle-aged men with various cardiovascular risk factors, the finding of a low penile PSV stresses the need for a careful examination of other arterial districts in search of atherosclerotic ultrasound lesions even in the absence of clinical manifestations of peripheral atherosclerosis (intermittent claudication, vertigo).
The systemic effects of arterial risk factors such as cigarette smoking, hypertension, hyperlipidemia and diabetes are progressive, and their continuous presence accentuates the pathophysiological processes known to cause ED. In addition, these risk factors may work in an additive or synergistic fashion, thus further reducing penile blood flow, worsening atherosclerosis progression and negatively conditioning the response to ED treatment. Recent observation of an increased expression of transforming growth factor-β1 and its type II receptor associated with fibrosis,23 in the cavernous corpora of patients with vasculogenic ED, compared with those in controls or psychogenic ED patients, suggests the need for an early diagnosis of arterial ED, also when it occurs alone without other extragenital vascular abnormalities. Therefore, patients with arterial ED alone may be regarded as an important clinical model of atherosclerosis prevention, such as through an early management of their risk factors.
In conclusion, this study showed that patients with penile artery insufficiency and atherosclerosis in other arterial districts had a significantly lower PSV than the group with arterial ED alone. Therefore, ED patients with a severe arterial insufficiency should undergo extensive echo-Doppler ultrasonography.
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Cite this article
Vicari, E., Di Pino, L., La Vignera, S. et al. Peak systolic velocity in patients with arterial erectile dysfunction and peripheral arterial disease. Int J Impot Res 18, 175–179 (2006). https://doi.org/10.1038/sj.ijir.3901387
- erectile dysfunction
- carotid abnormalities
- risk factors
- lower limb artery abnormalities
- peak systolic velocity
International Journal of Impotence Research (2008)