The Clinical Study On Monocyte-to-high-density Lipoprotein Ratio And Arterial Erectile Dysfunction In Young Men

Erectile dysfunction(ED)is a common clinical disease that comprises the inability to achieve or maintain sufficient erectile function for satisfaction during sexual activity,which affects men’s health and family stability.A previous large study predicted that nearly 322 million people will be affected by ED in 2025.Many biological factors contribute to ED,involving vascular,neurogenic,hormonal,psychogenic and other etiologies.According to the etiological differences,There three categories of ED:psychogenic,organic,or mixed psychogenic and organic.Among these,organic ED is the most common type.Most patients with organic ED exhibit vascular ED.There three categories of Vascular ED:arterial ED,venous ED,and mixed vascular obstacles ED;The most serious sub-type is arterial ED.Endothelial dysfunction and atherosclerosis are known to play crucial roles in the etiology of arterial ED.Inflammation and lipid accumulation are two hallmarks of atherosclerosis.Lipid accumulation causes multiple structural vascular abnormalities,which result in penile artery flow-limiting stenosis.These changes reduce blood flow to the penis during erections and lead to the decline of erectile function.Long-term stimulation of inflammation causes vascular endothelial dysfunction,seriously reducing erectile function.Monocytes play key roles in the release of proinflammatory cytokines and contribute to all stages of inflammation.High-density lipoprotein(HDL)is an important anti-inflammatory effector that acts by inhibiting the oxidation of low-density lipoprotein(LDL)and protecting the endothelium from the destructive effects of LDL.HDL has also been shown to alleviate the pro-inflammatory and pro-oxidant effects of monocyte activity.The monocyte-to-HDL ratio(MHR)has been proposed for the evaluation of risk assessment and prediction of cardiovascular events.Because arterial ED shares an underlying pathogenesis similar to that of cardiovascular disease,we hypothesized that the MHR may be associated with arterial ED.Furthermore,ED has generally been regarded as an age-related disease,because most men develop signs and symptoms of ED after 65 years of age.However,recent studies showed that the incidence of ED is on the rise in men under the age of 40.The MHR is reportedly associated with ED.However,the relationships of arterial and venous ED with MHR remain unknown,especially in younger men.We performed this study to explore whether the MHR can be used in the diagnosis and prevention of arterial ED.Materials and methods1.Patient characteristicsThis observational study protocol was approved by the Ethics Committee at the Second Hospital of Shandong University.All participants provided written informed consent.We prospectively screened patients who visited the Urology Department at the Second Hospital of Shandong University(Jinan,China)for ED from March 2016 to March 2020.All patients completed the International Index of Erectile Function-5 questionnaire;only those with an International Index of Erectile Function-5 score≤21 were considered for inclusion in the study.The other inclusion criterion was an age of 20 to 40 years.Exclusion criteria were diabetes,metabolic syndrome,malignant tumor,pelvic surgery or trauma,spinal cord injury,cardiovascular and/or hematologic diseases,psychogenic disorders,hormonal disorders(e.g.,hyperprolactinemia or hypogonadism),cerebrovascular events,neurological disorders.Overall,340 male patients with ED and 60 healthy male volunteers from the Health and Physical Examination Center at the Second Hospital of Shandong University were enrolled in this study.The healthy volunteers were married with no prior medical history;all had normal and harmonious sexual function(International Index of Erectile Function-5 score>21)during the study period.2.Study designAll patients completed the following clinical assessments:nocturnal penile tumescence assessment(NPT),neurophysiological tests(NT),and penile color Doppler ultrasonography(pDUS).The patients also underwent collection of other basic data including medical history and physical examination findings(Figure 1)Healthy controls did not undergo NPT,NT or pDUS assessments but completed the other assessments.Venous blood samples were collected from each participant for the assessment of hormone profile values,fasting blood glucose,and lipids.All samples were stored in tubes coated with ethylenediaminetetraacetic acid.NPT assessments were performed with the Rigiscan(?)device(Timm Medical Technologies,Inc.,Eden Prairie,MN,USA).All patients were asked to avoid insomnia-inducing activities,as well as caffeine and alcohol intake;they were also asked to empty the bladder before falling asleep.NPT assessments were performed for 3 consecutive nights.In the results of NPT assessments,only normal nocturnal erections were recorded;After NPT assessments,patients with abnormal results were subjected to pDUS via color Doppler flow imaging.A combination of phentolamine(0.1 ml)(0.5 mg/L)and papaverine(0.7 ml)(30 mg/L)was then injected into the penis near the base.A rubber band was placed around the base of the penis to prevent rapid drug diffusion in the bloodstream.Data concerning the peak systolic velocity(PSV)and end diastolic velocity(EDV)were recorded at the base of the bilateral cavernous arteries after intervals of 5 and 10 min.3.Statistical analysesStatistical analyses were performed using SPSS Statistics(version 22.0,SPSS Inc.,Chicago,IL,USA).Continuous quantitative data were expressed as the mean±standard deviation.Data normality was determined using the Kolmogorov-Smirnov test.One-way analysis of variance or the Kruskal-Wallis H test was used for multiple comparisons between groups.Spearman correlation was used to analyze the relationships of MHR with PSV or EDV.ROC analysis was performed to evaluate the sensitivity of MHR for detection of arterial ED.The relationship between 10-minutes PSV and MHR was analyzed by multivariate linear stepwise regression analysis in arterial ED.P<0.05 was considered statistically significant.3.Results This study initially enrolled 340 patients with ED and 60 healthy volunteers.Among the 340 patients,86 had normal NPT results,while 254 had abnormal NPT findings and were diagnosed with organic ED.Following pDUS,patients were finally diagnosed as follows:97 patients had mixed ED,95 patients had arterial ED,and 62 patients had venous ED.3.1.Comparison of demographic and venous blood characteristics between patients with ED and healthy controlsThe difference between the three groups was not statistically significant in any demographic or venous blood parameters,except LDL.The mean LDL levels were 2.45±0.97 mmol/L,2.06±0.63 mmol/L,and 2.14±0.42 mmol/L for the arterial ED,venous ED,and control groups,respectively(P<0.05).3.2.Monocyte count,HDL level,and MHR in patients with arterial ED differed from those measurements in patients with venous ED and controls There were significant differences in monocyte count,HDL level,and MHR among these three groups(P<0.001,P<0.001,and P<0.001 respectively).Multiple comparisons of monocyte count and HDL level were performed using Scheffe’s post hoc test.Multiple comparisons of MHR were performed using the Games-Howell test.Multiple comparison analyses showed that monocyte count and MHR were significantly greater in the arterial ED group than in the venous ED and control groups.In contrast,the HDL level was lower in the arterial ED group than in the other two groups.However,there were no significant differences in monocyte count,HDL level,or MHR between the venous ED and control groups.3.3 Penile vascular velocity was significantly correlated with MHR in patients with arterial EDMHR and monocyte count were significantly negatively correlated with 10-min PSV in patients with arterial ED(r=-0.392,P<0.01 vs.r=-0.297,P<0.01;),while HDL level was significantly positively correlated with 10-min PSV in those patients(r=0.303,P<0.01).There were no significant correlations of MHR,HDL level,or monocyte count with 10-min PSV in patients with venous ED(all P>0.05).In both arterial ED and venous ED groups,the MHR,HDL level,and monocyte count were not significantly correlated with 10-min EDV.3.4 MHR could reliably predict the risk of arterial EDReceiver operating characteristic curve regression analysis identified the following cut-off values for prediction of arterial ED:MHR>0.33(area under the curve:0.821,95%confidence interval:0.751-0.891)with a sensitivity of 75.8%and a specificity of 80.0%;monocyte count>0.45×109/L(area under the curve:0.735,95%confidence interval:0.651-0.819)with a sensitivity of 67.4%and specificity of 71.7%;and HDL level<1.27 mmol/L(area under the curve:0.747,95%confidence interval:0.667-0.826)with a sensitivity of 71.6%and specificity of 66.7%.3.5 Linear regression analyses confirmed that the MHR could predict the risk of arterial EDMultivariate linear stepwise regression analysis showed that the MHR had a significant predictive effect on 10-min PSV after controlling for confounders including age,smoking,alcohol consumption,body mass index(P<0.01).