Prognostic Utility of Erectile Dysfunction for Cardiovascular Disease
Prognostic Utility of Erectile Dysfunction for Cardiovascular Disease
Based on established relationships between endothelial dysfunction and CVD, as well as the potential bidirectional association between endothelial dysfunction and inflammation, pro-inflammatory markers have received considerable recent attention with respect to cardiovascular risk assessment. It has also come to light that most of these markers are up-regulated in men with ED, irrespective of the etiology of ED. For instance, among a wide range of proinflammatory and endothelial-prothrombotic markers, the combination of fibrinogen <225 mg/dL with interleukin-6 (IL-6) <1.24 pg/mL showed a very good negative predictive value for ED (91.7% [ie, very few false negative results]). Levels of high-sensitivity C-reactive protein (hsCRP) are significantly higher in men with ultrasonographically documented arteriogenic ED compared to subjects with normal penile arterial function. Furthermore, recent studies showed that improvement or normalization of sexual activity is associated with a favorable effect on markers of penile and peripheral endothelial function and pro-inflammatory biomarkers (hsCRP, IL-6). A routine measurement of these biomarkers, although useful, is not yet indicated.
Emerging independent markers of vasculogenic ED presence and severity include endothelial cell-derived factors that either participate in the regulation of corporal muscle tone (nitric oxide, endothelin-1, angiotensin II, C natriuretic peptide, asymmetric dimethyl-arginine) or indicate increased endothelial cell activation (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-Selectin) and damage or repair (endothelin-1, monocyte oxidative activity, endothelial microparticles, endothelial progenitor cells).
Tests that measure the atherosclerotic burden either in the coronary circulation (i.e., coronary calcium score by electron-beam computed tomography), coronary computed tomography angiography (CCTA), or in extracoronary vessels (ie, ankle brachial index, carotid intima-media thickness), along with functional arterial indices (flow-mediated dilatation) or mixed (functional and structural) arterial indices (aortic stiffness) are also considered surrogate markers of CVD. ED has been associated with several of the above-mentioned indices of atherosclerotic burden (Table III). Because ED represents an independent marker for cardiovascular events it would be clinically useful to identify potential biomarkers that would predict future CVD events in the ED population. The biomarkers of generalized vascular disease discussed above are such candidates and, based on their predictive ability in various populations, they are expected to be predictive of CVD events in ED patients. For example, 2-year data from the Coronary CT Angiography Evaluation For Clinical Outcomes International Multicenter registry (n = 15,223) suggested that, among patients without known CAD, CCTA measures of both non-obstructive and obstructive CAD aided stratification of risk for major adverse cardiac events. However, with the exception of arterial stiffness (indirect support through pulse pressure data), relevant studies supporting the predictive value of the above-mentioned indices for cardiovascular events in ED patients have not been performed. Thus, routine use of these tests is not indicated at present.
The Future: ED, CVD, and Prognostic Markers of Systemic Vascular Disease
Based on established relationships between endothelial dysfunction and CVD, as well as the potential bidirectional association between endothelial dysfunction and inflammation, pro-inflammatory markers have received considerable recent attention with respect to cardiovascular risk assessment. It has also come to light that most of these markers are up-regulated in men with ED, irrespective of the etiology of ED. For instance, among a wide range of proinflammatory and endothelial-prothrombotic markers, the combination of fibrinogen <225 mg/dL with interleukin-6 (IL-6) <1.24 pg/mL showed a very good negative predictive value for ED (91.7% [ie, very few false negative results]). Levels of high-sensitivity C-reactive protein (hsCRP) are significantly higher in men with ultrasonographically documented arteriogenic ED compared to subjects with normal penile arterial function. Furthermore, recent studies showed that improvement or normalization of sexual activity is associated with a favorable effect on markers of penile and peripheral endothelial function and pro-inflammatory biomarkers (hsCRP, IL-6). A routine measurement of these biomarkers, although useful, is not yet indicated.
Emerging independent markers of vasculogenic ED presence and severity include endothelial cell-derived factors that either participate in the regulation of corporal muscle tone (nitric oxide, endothelin-1, angiotensin II, C natriuretic peptide, asymmetric dimethyl-arginine) or indicate increased endothelial cell activation (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-Selectin) and damage or repair (endothelin-1, monocyte oxidative activity, endothelial microparticles, endothelial progenitor cells).
Tests that measure the atherosclerotic burden either in the coronary circulation (i.e., coronary calcium score by electron-beam computed tomography), coronary computed tomography angiography (CCTA), or in extracoronary vessels (ie, ankle brachial index, carotid intima-media thickness), along with functional arterial indices (flow-mediated dilatation) or mixed (functional and structural) arterial indices (aortic stiffness) are also considered surrogate markers of CVD. ED has been associated with several of the above-mentioned indices of atherosclerotic burden (Table III). Because ED represents an independent marker for cardiovascular events it would be clinically useful to identify potential biomarkers that would predict future CVD events in the ED population. The biomarkers of generalized vascular disease discussed above are such candidates and, based on their predictive ability in various populations, they are expected to be predictive of CVD events in ED patients. For example, 2-year data from the Coronary CT Angiography Evaluation For Clinical Outcomes International Multicenter registry (n = 15,223) suggested that, among patients without known CAD, CCTA measures of both non-obstructive and obstructive CAD aided stratification of risk for major adverse cardiac events. However, with the exception of arterial stiffness (indirect support through pulse pressure data), relevant studies supporting the predictive value of the above-mentioned indices for cardiovascular events in ED patients have not been performed. Thus, routine use of these tests is not indicated at present.
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