Assessment of Vascular Risk in Men With Erectile Dysfunction
Assessment of Vascular Risk in Men With Erectile Dysfunction
The endothelium is a single layer of cells that lines the lumen of the blood vessels. It serves as an interface between blood components and vascular tissues and regulates vascular tone, coagulation, and inflammation. The endothelium, which responds to shear stress, produces and responds to multiple signalling molecules, most notably nitric oxide (NO). Endothelial NO possesses antiatherogenic, antithrombotic, and anti-inflammatory properties and promotes vasodilation of the vascular smooth muscle. Cardiovascular risk factors including dyslipidemia, hypertension, and diabetes are associated with endothelial dysfunction, which is characterised by impaired vasodilation, reduced production of NO, and increased permeability to plasma constituents including low-density lipoproteins. These events cause vasoconstriction, platelet aggregation, and leucocyte adhesion. Impaired endothelial function is an independent predictor of cardiovascular events.
Erectile dysfunction may be classified as predominantly psychogenic, organic, or mixed. Most organic ED is vascular in nature, and endothelial dysfunction is believed to be the aetiologic link between CVD and vasculogenic ED. Because decreased penile vascular flow may reflect underlying endothelial dysfunction, penile blood flow has been suggested as an additional diagnostic test to identify ED patients at risk for CVD. Decreased penile blood flow appears to be sensitive enough to correlate with silent coronary ischaemia before overt manifestations of CAD. Furthermore, reductions in penile blood flow in both the flaccid state or during stimulation with vasodilators have been associated with an increased risk of a major cardiovascular event. Although the literature strongly supports an association between ED and endothelial dysfunction, mechanistic studies have not been performed. Hence, the possibility that these conditions result from a common disease, rather than a cause-and-effect relationship, cannot be ruled out.
A number of studies have demonstrated that endothelial dysfunction leading to ED is rarely limited to the penile vessels. Kaiser et al. reported that patients with ED but without overt systemic vascular disease had impairments in peripheral endothelium-dependent and -independent vasodilation in the absence of traditional cardiovascular risk factors. There was also a significant relationship between the number of circulating endothelial microparticles and the severity of ED in diabetic men. In men with type 2 diabetes and ED, reductions in blood pressure and platelet aggregation in response to intravenous L-arginine were attenuated compared with those without ED. Endothelial cell activation is an important early manifestation of the atherosclerotic process. Bocchio et al. studied endothelin-1, intercellular adhesion molecules, soluble cell adhesion molecules and P-selectin in men with and without ED. They found that these products were increased in the blood of men with ED, even before penile blood flow was reduced. Vlachopoulos et al. reported that presence and severity of ED was associated with markers and mediators of subclinical inflammation [e.g. high-sensitivity C-reactive protein (hsCRP), cytokines] and endothelial-prothrombotic activation (e.g. von Willebrand Factor plasminogen activator inhibitor-1, fibrinogen) in men with and without CAD. Additional emerging independent markers of vasculogenic ED presence and severity include endothelial cell-derived factors that participate in the regulation of corporal muscle tone (e.g. endothelin-1, angiotensin II, C natriuretic peptide, asymmetric dimethyl-arginine) or indicate increased endothelial cell damage or repair (e.g. endothelin-1, monocyte oxidative activity, endothelial microparticles, endothelial progenitor cells). Despite ample published support for endothelial dysfunction as a pathophysiologic link between CVD and vasculogenic ED, the lack of a simple, cost-effective, sensitive, and specific method of assessment limits the utility of endothelial function as a predictor of cardiovascular events.
Endothelial/Vascular Dysfunction: The ED/CVD Common Denominator
The endothelium is a single layer of cells that lines the lumen of the blood vessels. It serves as an interface between blood components and vascular tissues and regulates vascular tone, coagulation, and inflammation. The endothelium, which responds to shear stress, produces and responds to multiple signalling molecules, most notably nitric oxide (NO). Endothelial NO possesses antiatherogenic, antithrombotic, and anti-inflammatory properties and promotes vasodilation of the vascular smooth muscle. Cardiovascular risk factors including dyslipidemia, hypertension, and diabetes are associated with endothelial dysfunction, which is characterised by impaired vasodilation, reduced production of NO, and increased permeability to plasma constituents including low-density lipoproteins. These events cause vasoconstriction, platelet aggregation, and leucocyte adhesion. Impaired endothelial function is an independent predictor of cardiovascular events.
Erectile dysfunction may be classified as predominantly psychogenic, organic, or mixed. Most organic ED is vascular in nature, and endothelial dysfunction is believed to be the aetiologic link between CVD and vasculogenic ED. Because decreased penile vascular flow may reflect underlying endothelial dysfunction, penile blood flow has been suggested as an additional diagnostic test to identify ED patients at risk for CVD. Decreased penile blood flow appears to be sensitive enough to correlate with silent coronary ischaemia before overt manifestations of CAD. Furthermore, reductions in penile blood flow in both the flaccid state or during stimulation with vasodilators have been associated with an increased risk of a major cardiovascular event. Although the literature strongly supports an association between ED and endothelial dysfunction, mechanistic studies have not been performed. Hence, the possibility that these conditions result from a common disease, rather than a cause-and-effect relationship, cannot be ruled out.
A number of studies have demonstrated that endothelial dysfunction leading to ED is rarely limited to the penile vessels. Kaiser et al. reported that patients with ED but without overt systemic vascular disease had impairments in peripheral endothelium-dependent and -independent vasodilation in the absence of traditional cardiovascular risk factors. There was also a significant relationship between the number of circulating endothelial microparticles and the severity of ED in diabetic men. In men with type 2 diabetes and ED, reductions in blood pressure and platelet aggregation in response to intravenous L-arginine were attenuated compared with those without ED. Endothelial cell activation is an important early manifestation of the atherosclerotic process. Bocchio et al. studied endothelin-1, intercellular adhesion molecules, soluble cell adhesion molecules and P-selectin in men with and without ED. They found that these products were increased in the blood of men with ED, even before penile blood flow was reduced. Vlachopoulos et al. reported that presence and severity of ED was associated with markers and mediators of subclinical inflammation [e.g. high-sensitivity C-reactive protein (hsCRP), cytokines] and endothelial-prothrombotic activation (e.g. von Willebrand Factor plasminogen activator inhibitor-1, fibrinogen) in men with and without CAD. Additional emerging independent markers of vasculogenic ED presence and severity include endothelial cell-derived factors that participate in the regulation of corporal muscle tone (e.g. endothelin-1, angiotensin II, C natriuretic peptide, asymmetric dimethyl-arginine) or indicate increased endothelial cell damage or repair (e.g. endothelin-1, monocyte oxidative activity, endothelial microparticles, endothelial progenitor cells). Despite ample published support for endothelial dysfunction as a pathophysiologic link between CVD and vasculogenic ED, the lack of a simple, cost-effective, sensitive, and specific method of assessment limits the utility of endothelial function as a predictor of cardiovascular events.
Source...