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Endothelial Dysfunction, Erectile Deficit, and Cardiovascular Disease: An Overview of the Pathogenetic Links (2022)
Federico De Leonardis, Gaia Colalillo, Enrico Finazzi Agrò, Roberto Miano, Andrea Fuschi and Anastasios D. Asimakopoulos
Abstract
Erectile dysfunction (ED) is a condition with multifactorial pathogenesis, quite common among men, especially those above 60 years old. A vascular etiology is the most common cause. The interaction between chronic inflammation, androgens, and cardiovascular risk factors determines macroscopically invisible alterations such as endothelial dysfunction and subsequent atherosclerosis and flow-limiting stenosis that affects both penile and coronary arteries. Thus, ED and cardiovascular disease (CVD) should be considered two different manifestations of the same systemic disorder, with a shared aetiological factor being endothelial dysfunction. Moreover, the penile arteries have a smaller size compared with coronary arteries; thus, for the same level of arteriopathy, a more significant blood flow reduction will occur in erectile tissue compared with coronary circulation. As a result, ED often precedes CVD by 2–5 years, and its diagnosis offers a time window for cardiovascular risk mitigation. Growing evidence suggests, in fact, that patients presenting with ED should be investigated for CVD even if they have no symptoms. Early detection could facilitate prompt intervention and a reduction in long-term complications. In this review, we provide an overview of the pathogenetic mechanisms behind arteriogenic ED and CVD, focusing on the role of endothelial dysfunction as the common denominator of the two disorders. Developed algorithms that may help identify those patients complaining of ED who should undergo detailed cardiologic assessment and receive intensive treatment for risk factors are also analyzed.
1. Introduction
Erectile dysfunction (ED) in men is defined as the inability to obtain or sustain an erection satisfactory for sexual intercourse. ED prevalence is directly correlated to patients’ age. Moreover, its incidence increases if specific subgroups of the population are taken into account (smokers, diabetics, obese, and people affected by cardiovascular diseases) [1].
There are multiple mechanisms that can lead to ED and include (i) psychological distress, (ii) neurological processes impairing the correct transmission of signals and stimuli that trigger the erection (i.e., multiple sclerosis, spinal cord injuries, neuropathies, and pelvic surgeries), (iii) hormonal imbalances, and (iv) all the vascular conditions that may alter normal blood flow and oxygen supply to tissues, such as smoking, diabetes, atherosclerosis, and more generally any condition that may disrupt endothelial homeostasis
Endothelial dysfunction, in particular, seems to share pathological mechanisms with and be the starting point of many of the aforementioned conditions, implying an interconnection between all these affections. This raises the question of whether there may be merit in ED early identification for the screening and prevention of cardiovascular disease (CVD) [2].
ED is still a topic that men feel shame talking about and seeking medical attention for, making such an important issue for men’s wellbeing probably underdiagnosed and underestimated.
There is no concrete data about ED prevalence in the global population, as different rates are encountered among various ethnicities and geographical areas, apparently being more common in North America and Southeast Asia [3,4]. Two studies analyzed ED incidence in the general male population in-depth, respectively, in Europe and the United States [5,6]. In the first study, the European Male Aging Study (EMAS), ED had a prevalence of 30% in the entire screened population, and it was directly correlated to age, surging at 64% incidence in men older than 70 yrs. As for the American study, the Massachusetts Male Aging Study (MMAS), ED of any degree was found to occur in 52% of the male population ranging from 40 to 70 years old, and once again with severity and occurrence directly related to the patient's age. In a more recent American study [1], in addition to the well-known correlation between ED and age, the incidence of ED was shown to be even higher when specific subgroups of the population were taken into accounts, such as in cases of concomitant smoking (13%), diabetes (51.3%), obesity (21.8%), and cardiovascular disease (50%).
Less data are available on how ED impacts the younger population. An increase in ED incidence was demonstrated in men younger than 40 years that was again potentially underestimated due to the scarce self-reporting of younger patients to clinicians. The rates of diagnosis of organic causes for ED in younger patients is increasing, bringing down the misconception that ED in such a population would be most uniquely due to psychological causes. This emphasizes the complexity and the interconnecting links of all the possible causes of ED, showing that some of them may remain unnoticed or be difficult to identify [7,8].
2. Physiology of Erection and Physiopathology of Vasculogenic ED
The necessary event for the male sexual act to start is the acquisition and maintenance of penile erection, which involves an interplay between hormonal, psychological, neurological, and vascular pathways.
*Given the complexity of the interplay between various pathways that cause an erection, it should be erroneous to think of ED pathophysiology in a dichotomous way (organic vs. psychological pathways). ED is a multifactorial disorder deriving from the synergy of social context, psychological well-being, and organic processes. Consequently, there are plenty of ways in which these linked processes can become disrupted, ultimately causing ED.
3. The Endothelium: Summary of Its Functions
4. Endothelial Dysfunction and ED
5. ED and CVD
6. ED Therapeutic Approach
7. Cardiologic Assessment Recommendations for Patients Affected by ED
8. Conclusions
ED is a multifactorial disorder with a really intricate pathogenesis. Vasculogenic ED and CVD should be considered as two different representations of the same disorder since they share common risk factors and pathophysiological mechanisms, with the main being endothelial dysfunction.
Screening and diagnosing ED is essential for the primary and secondary prevention of CVDs, as the assessment of ED represents an easy and low-cost prognostic tool if compared to various cardiovascular biomarkers or more invasive exams. For men believed to have predominantly vasculogenic erectile dysfunction, initial cardiovascular risk stratification should be performed, for example, by applying the Framingham Risk Score. The management of men with erectile dysfunction who are at low risk for cardiovascular disease should focus on risk-factor control, whereas men at high risk, mostly including those with active cardiovascular symptoms, should be referred to a cardiologist before starting any kind of therapy for ED. Intermediate-risk men should undergo noninvasive evaluation for subclinical atherosclerosis and usually be re-stratified in any of the two previous groups. In conclusion, the penile vascular bed could be a sensitive indicator of systemic vascular disease, making ED the herald of major cardiovascular events. With the latter being the leading cause of morbidity and mortality in Western countries, cardiovascular risk stratification and risk-factor management should be promptly suggested in all men with vasculogenic erectile dysfunction. Further efforts to raise awareness about the potential role of ED in the early diagnosis and prevention of CVDs are required.
Federico De Leonardis, Gaia Colalillo, Enrico Finazzi Agrò, Roberto Miano, Andrea Fuschi and Anastasios D. Asimakopoulos
Abstract
Erectile dysfunction (ED) is a condition with multifactorial pathogenesis, quite common among men, especially those above 60 years old. A vascular etiology is the most common cause. The interaction between chronic inflammation, androgens, and cardiovascular risk factors determines macroscopically invisible alterations such as endothelial dysfunction and subsequent atherosclerosis and flow-limiting stenosis that affects both penile and coronary arteries. Thus, ED and cardiovascular disease (CVD) should be considered two different manifestations of the same systemic disorder, with a shared aetiological factor being endothelial dysfunction. Moreover, the penile arteries have a smaller size compared with coronary arteries; thus, for the same level of arteriopathy, a more significant blood flow reduction will occur in erectile tissue compared with coronary circulation. As a result, ED often precedes CVD by 2–5 years, and its diagnosis offers a time window for cardiovascular risk mitigation. Growing evidence suggests, in fact, that patients presenting with ED should be investigated for CVD even if they have no symptoms. Early detection could facilitate prompt intervention and a reduction in long-term complications. In this review, we provide an overview of the pathogenetic mechanisms behind arteriogenic ED and CVD, focusing on the role of endothelial dysfunction as the common denominator of the two disorders. Developed algorithms that may help identify those patients complaining of ED who should undergo detailed cardiologic assessment and receive intensive treatment for risk factors are also analyzed.
1. Introduction
Erectile dysfunction (ED) in men is defined as the inability to obtain or sustain an erection satisfactory for sexual intercourse. ED prevalence is directly correlated to patients’ age. Moreover, its incidence increases if specific subgroups of the population are taken into account (smokers, diabetics, obese, and people affected by cardiovascular diseases) [1].
There are multiple mechanisms that can lead to ED and include (i) psychological distress, (ii) neurological processes impairing the correct transmission of signals and stimuli that trigger the erection (i.e., multiple sclerosis, spinal cord injuries, neuropathies, and pelvic surgeries), (iii) hormonal imbalances, and (iv) all the vascular conditions that may alter normal blood flow and oxygen supply to tissues, such as smoking, diabetes, atherosclerosis, and more generally any condition that may disrupt endothelial homeostasis
Endothelial dysfunction, in particular, seems to share pathological mechanisms with and be the starting point of many of the aforementioned conditions, implying an interconnection between all these affections. This raises the question of whether there may be merit in ED early identification for the screening and prevention of cardiovascular disease (CVD) [2].
ED is still a topic that men feel shame talking about and seeking medical attention for, making such an important issue for men’s wellbeing probably underdiagnosed and underestimated.
There is no concrete data about ED prevalence in the global population, as different rates are encountered among various ethnicities and geographical areas, apparently being more common in North America and Southeast Asia [3,4]. Two studies analyzed ED incidence in the general male population in-depth, respectively, in Europe and the United States [5,6]. In the first study, the European Male Aging Study (EMAS), ED had a prevalence of 30% in the entire screened population, and it was directly correlated to age, surging at 64% incidence in men older than 70 yrs. As for the American study, the Massachusetts Male Aging Study (MMAS), ED of any degree was found to occur in 52% of the male population ranging from 40 to 70 years old, and once again with severity and occurrence directly related to the patient's age. In a more recent American study [1], in addition to the well-known correlation between ED and age, the incidence of ED was shown to be even higher when specific subgroups of the population were taken into accounts, such as in cases of concomitant smoking (13%), diabetes (51.3%), obesity (21.8%), and cardiovascular disease (50%).
Less data are available on how ED impacts the younger population. An increase in ED incidence was demonstrated in men younger than 40 years that was again potentially underestimated due to the scarce self-reporting of younger patients to clinicians. The rates of diagnosis of organic causes for ED in younger patients is increasing, bringing down the misconception that ED in such a population would be most uniquely due to psychological causes. This emphasizes the complexity and the interconnecting links of all the possible causes of ED, showing that some of them may remain unnoticed or be difficult to identify [7,8].
2. Physiology of Erection and Physiopathology of Vasculogenic ED
The necessary event for the male sexual act to start is the acquisition and maintenance of penile erection, which involves an interplay between hormonal, psychological, neurological, and vascular pathways.
*Given the complexity of the interplay between various pathways that cause an erection, it should be erroneous to think of ED pathophysiology in a dichotomous way (organic vs. psychological pathways). ED is a multifactorial disorder deriving from the synergy of social context, psychological well-being, and organic processes. Consequently, there are plenty of ways in which these linked processes can become disrupted, ultimately causing ED.
3. The Endothelium: Summary of Its Functions
4. Endothelial Dysfunction and ED
5. ED and CVD
6. ED Therapeutic Approach
7. Cardiologic Assessment Recommendations for Patients Affected by ED
8. Conclusions
ED is a multifactorial disorder with a really intricate pathogenesis. Vasculogenic ED and CVD should be considered as two different representations of the same disorder since they share common risk factors and pathophysiological mechanisms, with the main being endothelial dysfunction.
Screening and diagnosing ED is essential for the primary and secondary prevention of CVDs, as the assessment of ED represents an easy and low-cost prognostic tool if compared to various cardiovascular biomarkers or more invasive exams. For men believed to have predominantly vasculogenic erectile dysfunction, initial cardiovascular risk stratification should be performed, for example, by applying the Framingham Risk Score. The management of men with erectile dysfunction who are at low risk for cardiovascular disease should focus on risk-factor control, whereas men at high risk, mostly including those with active cardiovascular symptoms, should be referred to a cardiologist before starting any kind of therapy for ED. Intermediate-risk men should undergo noninvasive evaluation for subclinical atherosclerosis and usually be re-stratified in any of the two previous groups. In conclusion, the penile vascular bed could be a sensitive indicator of systemic vascular disease, making ED the herald of major cardiovascular events. With the latter being the leading cause of morbidity and mortality in Western countries, cardiovascular risk stratification and risk-factor management should be promptly suggested in all men with vasculogenic erectile dysfunction. Further efforts to raise awareness about the potential role of ED in the early diagnosis and prevention of CVDs are required.
