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Erectile dysfunction in patients with plaque psoriasis: the relation of depression and cardiovascular factors

Subjects

Abstract

Psoriasis is a chronic inflammatory skin disease and seems to be associated with erectile dysfunction (ED). ED is a predictor of future cardiovascular disease. It is important to identify ED early and investigate cardiovascular problems in psoriasis patients. The sample consisted of 191 psoriasis patients and 191 healthy men. One hundred and one of 191 (52.9%) patients with psoriasis were indicative of ED, compared with 40.3% in control group, reflecting an age-adjusted odds ratio of 1.965 in favor of the psoriasis group. A univariate analysis in the psoriasis group indicated that age, hypertension, hyperlipidemia, diabetes mellitus and depressive symptoms were the risk factors for ED. The multivariate logistic regression model indicated that increasing age, hypertension, hyperlipidemia and depressive symptoms were independent risk factors for ED in psoriasis. The more severe depressive symptoms increased the risk of ED and especially moderate–severe ED. The diagnosis of ED may help prevent emotional and physical discomfort in men and aid in identifying reversible cardiovascular risk factors. Screening of ED may become a part of routine care in the management of psoriasis patients.

Introduction

Psoriasis is a chronic, immune-mediated, genetic skin disease affecting up to 2% of the world’s population.1 Previous studies carried out in Asia, including China and Hong Kong, demonstrated that the prevalence of psoriasis varies between 0.2% and 1.5% regionally.2 Recent years have seen an increase in studies examining the relationship between psoriasis and erectile dysfunction (ED), an alteration that can cause significant changes in the quality of life.3, 4, 5, 6 The estimated prevalence of sexual dysfunction in patients with psoriasis ranged from 22.6 to 71.3%.7 However, no study of ED among male patients with psoriasis has been reported in China until now. ED is frequently overlooked in routine clinical evaluations among Chinese patients, who have different culture and health-seeking behaviors than other populations.

An association between ED, depressive symptoms and cardiovascular disease has long been recognized. Tasliyurt et al.8 found that depression is independently associated with ED in psoriasis patients. The presence of ED and depression are known to predict future cardiovascular disease.9, 10 A growing body of evidence documents that ED is an independent marker of cardiovascular disease risk and an all-cause mortality.11, 12, 13 Early diagnosis of ED may allow timely modification of remediable risk factors, and provide a unique opportunity for the prevention of cardiovascular disease.14 Management of men with ED who are at low risk for cardiovascular disease should focus on risk-factor control; men at high risk, including those with cardiovascular symptoms, should be referred to a cardiologist.11 Hence, it is of great importance to identify early-on the presence of ED and to investigate cardiovascular problems in psoriasis patients.

Therefore, the aim of this study is to investigate the prevalence of ED in patients with psoriasis compared with healthy people, and to explore the association of ED with risk factors for cardiovascular disease and depressive symptoms in patients with psoriasis.

Materials and methods

Participants

We conducted a pilot study with a prospective observational cross-sectional design. We recruited adult men who were diagnosed with plaque psoriasis in five hospital dermatology departments (Guangdong Provincial Dermatology Hospital, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangfo Hospital affiliated to Guangzhou Medical University and Guangzhou Nansha Central Hospital) between 1 August 2014 and 31 January 2015. We included patients with plaque psoriasis. Healthy subjects who were selected from the Center of Health Examination were regarded as the control group. Controls were matched on age in intervals of 10 years (21–30, 31–40, 41–50, 51–60 and >60). Male patients aged 18 years or over were eligible for inclusion. The patients with chronic diseases such as pulmonary, hepatic, renal, hematological, neurologic, malignancy, psychosis or similar psychiatric disorders and the patients using antidepressant, diuretics, beta-blockers, inhibitors of 5-alpha reductase or other drugs that are known to interfere with erectile dysfuncion were excluded. Ethical approval for the study was obtained in each of the participating centers and all the subjects gave informed consent.

For all the participants, we gathered information on age, disease duration, systemic treatment (including acitretin, methotrexate, cyclosporine, fumaric acid esters, hydroxycarbamide or biologic therapies), alcohol abuse, smoking history and the presence of any established atherosclerotic disease (current or previous angina, myocardial infarction, stroke, transient ischemic attack or peripheral vascular disease). Detailed physical examinations were also performed on all the subjects. Physical activity level was determined using the standard question ‘How frequently do you engage in intense physical activity (at least 30 min of intense walking)?’ and scored 0 (never), 1 (occasionally), 2 (one to three times per week), 3 (three to five times per week), 4 (more than five times per week). Body mass index was calculated as weight in kg per square of height in meters. Blood pressure was taken in a sitting posture twice and the average of the two measurements was used. Serum samples were taken from subjects to determine the chemical parameters, such as triglyceride, total cholesterol, HDL cholesterol, LDL cholesterol and fasting blood glucose levels.

All the participants were asked whether they were, or would like to be, sexually active. Those who answered yes to this question completed the International Index of Erectile Function-5 (IIEF-5),15 a validated index of erectile function, and the Center for Epidemiologic Studies Depression Scale (CES-D),16 a self-reported depression scale for research in the general population. The CES-D, which was used to evaluate depressive symptoms, is made-up of 20 items, four of which are reverse scored (#4, 8, 12 and 16). The score ranges from 0 to 60, with the higher scores indicating the presence of more depressive symptoms. Although a score of 16 is typically considered to be the threshold for clinical depression in Western countries, a score of 25 is frequently defined as the threshold for depression in Eastern Asia.17 So we choose cutoff scores of 16 and 25 and divided depressive symptoms into three categories: ‘none, CES-D score I tertile’, ‘mild, CES-D score II tertile’ and ‘significant, CES-D score III tertile’.

Completed questionnaires were placed in sealed envelopes and left in an enclosed box at reception, which was emptied at the end of each day. Other than age, no additional patient-identifiable information was recorded. Each patient was assigned a unique identifying number, and data were transferred to a Microsoft Excel spreadsheet. We encouraged patients who reported problems of sexual dysfunction or depression to receive a consultation with a medical doctor.

Statistical analyses

Data are shown as mean values±s.d., and categorical variables are given as percentages of the two groups, psoriasis vs control. For group comparisons involving binary data, we used the chi-square test. Comparisons involving continuous data were made using the independent samples t-test. In addition, a univariate analyses of each variable was carried out in the psoriasis group, with the binary outcome of interest ED (IIEF-5 score 21) or no ED (IIEF-5 score >21), and those with a likelihood P-value <0.05 were initially included in the multivariate logistic regression to identify independent risk factors for ED in psoriasis patients. Odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated. The results were considered significant if P<0.05. All the statistical calculations were performed using SPSS 21.0 software (SPSS, Chicago, IL, USA).

Results

During the cross-sectional phase of the study, 516 men were invited to participate in the study, including 230 plaque psoriasis patients and 286 healthy men. And 24 (10.4%) psoriasis patients and 64 (22.4%) healthy men declined. Six in 206 psoriasis patients and 8 in 222 healthy men stated that they were not sexually active, and were excluded from further analysis. A further 32 patients were excluded because they did not complete the IIEF-5, the primary outcome of interest. Analysis was therefore carried out on 382 (74.0%) men: 191 (50%) had a clinical diagnosis of plaque psoriasis and 191 (50%) healthy men as the control group. The flow of participants is shown in Figure 1.

Figure 1
figure1

Flow of participants in the study. ED, erectile dysfunction.

Table 1 summarizes the characteristics of the two groups between plaque psoriasis patients and healthy people. The mean age was 45.5±9.8 years in the patient group and 45.6±9.6 years in the healthy group (P=0.920). In the patient group, the average of disease duration was 10.2±7.9 years, systemic treatment was 87.4, and 38.2% of patients with plaque psoriasis reported genital skin involvement. There were no significant differences between the study groups for smoking, alcoholic beverages and physical activity. The body mass index of patient and control groups were 24.1±2.6 and 23.8±2.4, respectively, and the difference was not statistically significant (P=0.242). Associated conditions, including hypertension (P=0.004), hyperlipidemia (P=0.05) and diabetes mellitus (P=0.041), seemed more prevalent in the plaque psoriasis group. Differences in atherosclerotic disease were not statistically significant. And there was significant difference of CES-D score between psoriasis patients (15.0±8.4) and healthy men (11.3±5.1; P<0.001).

Table 1 Descriptive characteristics of the study population

Sexual dysfunction

The proportion of ED in plaque psoriasis patients was significantly higher than in the control group (52.9 vs 40.3% respectively; P=0.018). ED was classified as mild in 19.9%, mild to moderate in 17.3%, moderate in 9.9% and severe in 5.8% of plaque psoriasis patients; and as mild in 21.5%, mild to moderate in 13.1%, moderate in 4.2% and severe in 1.6% of control group participants. Differences in moderate (P=0.04) and severe ED (P=0.053) were statistically significant between plaque psoriasis patients and the control group (Table 1).

A simple age (per 5 years)-adjusted logistic model was used to compare the plaque psoriasis group and control group, with regard to ED prevalence. This resulted in an age-adjusted OR of 1.965 in favor of the psoriasis group (95% CI=1.243–3.107; P=0.004). However, in a rigorous multivariable logistic regression model, psoriasis was not found to be an independent risk factor for ED after adjusting for age (per 5 years), hypertension, hyperlipidemia, diabetes mellitus and depressive symptoms risk factors.

Cardiovascular factors and sexual dysfunction in plaque psoriasis patients

As ED occurred more commonly in patients with plaque psoriasis, we wanted to screen for the cardiovascular risk factors in those with documented ED. Table 2 displays the unadjusted ORs from the initial univariate analyses and the adjusted ORs from the final fitted multivariate logistic model. In each case, 95% CI and P-values are given. In the univariate logistic analyses, age (per 5 years), hypertension, hyperlipidemia and diabetes mellitus, were risk factors for ED. And ED was not related to disease duration, systemic treatment, genital skin involvement, smoker, alcoholic beverages, physical activity and body mass index in psoriasis patients. In the final multivariate logistic model, increasing age, hypertension and hyperlipidemia were found to be independent risk factors for ED, with estimated ORs (95% CI) of 1.641 (1.274–2.115), 2.790 (1.087–7.164) and 2.471 (1.024–5.963), respectively. The model fit the data well, with the Hosmer–Lemeshow test yielding a P-value of 0.243.

Table 2 Univariable and multivariable logistic regression analyses in psoriasis

Depressive symptoms and sexual dysfunction in plaque psoriasis patients

It was shown that in the univariate analyses, a higher CES-D score was a risk factor for ED. In the multivariate analysis, the CES-D score was also determined to be an independent risk factor for ED, with an estimated OR (95% CI) of 1.084 (1.032–1.138).

To better understand the impact of the severity of mood disturbances as measured by the CES-D scores on ED or moderate–severe ED, we performed logistic regression models considering ED or moderate–severe ED as the dependent variable and less severe (CES-D score second vs first tertile) or more severe (CES-D score third vs first tertile) depressive symptoms as the concomitant presence (Table 3). An age-adjusted OR showed that more severe depressive symptoms increased the risk of not only ED in general, but also especially moderate–severe ED (Table 3).

Table 3 Age adjusted odds ratio for (moderate–severe) ED according to the severity of depressive symptoms (n=191)

Discussion

To our knowledge, this study evaluated the prevalence of ED and depressive symptoms and cardiovascular risk factors in male patients with plaque psoriasis. We found significantly higher ED prevalence in plaque psoriasis patients compared with healthy controls after adjusting for age. ED was found to be related to increasing age, the presence of hypertension, hyperlipidemia and depression in patients with psoriasis. More severe depressive symptoms were associated with ED, particularly moderate–severe ED.

ED is an important health problem that has negative impacts on the social lives and mental health of patients, as well as their partners. However, Chinese patients often feel embarrassed to discuss this topic. In our research, although some doctors may have been concerned about potentially awkward or embarrassing exchanges in the clinic, we found that discussing erectile problems with patients is an acceptable topic of conversation when approached in a straightforward and sensitive manner, not only among male doctors, but also female doctors. The prevalence of ED was 52.9% in plaque psoriasis patients and 40.3% in controls, based on the IIEF-5. However, some participants declined the IIEF-5 questionnaire, and it is possible that the true prevalence of ED may be higher than what we have indicated.

It is well recognized that multiple comorbidities have been associated with psoriasis, such as cardiovascular disease,18, 19, 20 obesity,21, 22, 23 type 2 diabetes24 and metabolic syndrome.25 Unlike the other Chinese population study23 (the sample number was 4452 in the psoriasis group and 1166 in the control group), we did not find the difference in body mass index between psoriasis patient and control groups to be statistically significant. That’s maybe our sample size was smaller than it. ED shares these risk factors with psoriasis. Currently, a few studies document the influence of psoriasis on patients’ sexual functioning. It is reported that about 58% of male patients with psoriasis recorded a score indicative of ED compared with 49% of patients with other skin diseases.3 Moreover, sexual activity has been shown to be especially impaired in patients with severe psoriasis and patients with psoriatic arthritis.26 A large-scale nationwide study suggests that male patients with psoriasis are at increased risk of developing ED compared with a control population, after adjusting for age, monthly income, number of health-care visits, systemic treatment and underlying comorbidities.27 We were able to demonstrate a 1.965-fold increase in the odds of ED occurring in patients with plaque psoriasis compared with controls in a simple age-adjusted analysis. However, in a rigorous multivariate logistic regression model, psoriasis was found to not be an independent risk factor for ED after adjusting for many other risk factors. This is not surprising given our small sample size and the high prevalence of ED in the control group.

ED is itself a cardiovascular risk factor. It is recognized that a major cause of ED is atherosclerosis affecting the pelvic vasculature.28 Consistent with previous studies, the present work also found that ED was significantly related to cardiovascular factors such as hypertension, hyperlipidemia, diabetes mellitus and atherosclerotic disease in psoriasis patients. In the multivariate logistic model, hypertension and hyperlipidemia were the independent risk factors for ED. This means that we must pay attention to psoriasis patients with cardiovascular risk factors, especially hypertension and hyperlipidemia. It was reported that patients with moderate to severe psoriasis had increased risks of coronary heart disease compared with the general population,29, 30 but patients may often begin as asymptomatic. The time interval between the onset of ED and the occurrence of cardiac symptoms and cardiovascular events has been estimated at 2–3 years and 3–5 years, respectively, offering a window of opportunity for intervention.30 Hence, screening this population for ED might be a useful tool for stratifying cardiovascular risk. Current guidelines for the management of patients with ED is that the presence of ED in any individual mandates a screen for cardiovascular risk factors, and in high-risk patients, an active investigation is required to exclude occult cardiovascular disease until proven otherwise.31, 32, 33

As in other studies,8 the present study confirms a strong association between ED and depressive symptoms, leading to a significant decline in the quality of life for men who have psoriasis and ED. But the sample size was very small. It only enrolled 37 psoriasis patients. A recent meta-analysis confirmed the presence of a bidirectional association between depression and sexual dysfunction.34 The etiological mechanisms for the apparent bidirectional association are unclear and likely complex. However, despite the specific pathogenetic mechanisms linking depressive symptoms and ED in particular, depressive symptoms represent another independent risk factor in men with ED35 and in those with plaque psoriasis in our research. This study indicates that depressive symptoms, and more severe manifestations of mood change in particular, constitute risk factors for developing ED. Moreover, more severe depressive symptoms further increase the risk of ED and moderate–severe ED in male plaque psoriasis patients.

There are several limitations to this study. We recognize that our sampling technique was not truly random, raising the possibility of selection bias. There is also the chance that observer bias or inter-observer variability influenced results.

In conclusion, the present data explore the prevalence of, and depression and cardiovascular risk factors for, ED in patients with plaque psoriasis. Given the strong evidence for early diagnosis of ED as a possible risk factor for cardiovascular diseases, screening of sexual dysfunction may become a part of the routine care provided for psoriasis patients. Physicians should also pay attention to the depressive symptoms and cardiovascular risk factors in those with documented ED. Investigating male erectile function may aid in evaluating the cardiovascular status and identifying the increased risk of cardiovascular events in patients with plaque psoriasis.

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Ji, S., Zang, Z., Ma, H. et al. Erectile dysfunction in patients with plaque psoriasis: the relation of depression and cardiovascular factors. Int J Impot Res 28, 96–100 (2016). https://doi.org/10.1038/ijir.2016.6

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