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Erectile dysfunction, physical activity and metabolic syndrome: differences in markers of atherosclerosis.

ABSTRACT: Erectile dysfunction (ED), impaired arterial elasticity, elevated resting heart rate as well as increased levels of oxidized LDL and fibrinogen associate with future cardiovascular events. Physical activity is crucial in the prevention of cardiovascular diseases (CVD), while metabolic syndrome (MetS) comprises an increased risk for CVD events. The aim of this study was to assess whether markers of subclinical atherosclerosis are associated with the presence of ED and MetS, and whether physical activity is protective of ED.57 MetS (51.3 ± 8.0 years) and 48 physically active (PhA) (51.1 ± 8.1 years) subjects participated in the study. ED was assessed by the International Index of Erectile Function (IIEF) questionnaire, arterial elasticity by a radial artery tonometer (HDI/PulseWave™ CR-2000) and circulating oxLDL by a capture ELISA immunoassay. Fibrinogen and lipids were assessed by validated methods. The calculation of mean daily energy expenditure of physical exercise was based on a structured questionnaire.ED was more often present among MetS compared to PhA subjects, 63.2% and 27.1%, respectively (p < 0.001). Regular physical exercise at the level of > 400 kcal/day was protective of ED (OR 0.12, 95% CI 0.017-0.778, p = 0.027), whereas increased fibrinogen (OR 4.67, 95% CI 1.171-18.627, p = 0.029) and elevated resting heart rate (OR 1.07, 95% CI 1.003-1.138, p = 0.04) were independently associated with the presence of ED. In addition, large arterial elasticity (ml/mmHgx10) was lower among MetS compared to PhA subjects (16.6 ± 4.0 vs. 19.6 ± 4.2, p < 0.001), as well as among ED compared to non-ED subjects (16.7 ± 4.6 vs. 19.0 ± 3.9, p = 0.008). Fibrinogen and resting heart rate were highest and large arterial elasticity lowest among subjects with both MetS and ED.Markers of subclinical atherosclerosis associated with the presence of ED and were most evident among subjects with both MetS and ED. Thus, especially MetS patients presenting with ED should be considered at high risk for CVD events. Physical activity, on its part, seems to be protective of ED.ClinicalTrials.gov NCT01119404.

SUBMITTER: Pohjantahti-Maaroos H

PROVIDER: S-EPMC3157429 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Erectile dysfunction, physical activity and metabolic syndrome: differences in markers of atherosclerosis.

Pohjantähti-Maaroos Hanna H Palomäki Ari A Hartikainen Juha J

BMC cardiovascular disorders 20110627

<h4>Background</h4>Erectile dysfunction (ED), impaired arterial elasticity, elevated resting heart rate as well as increased levels of oxidized LDL and fibrinogen associate with future cardiovascular events. Physical activity is crucial in the prevention of cardiovascular diseases (CVD), while metabolic syndrome (MetS) comprises an increased risk for CVD events. The aim of this study was to assess whether markers of subclinical atherosclerosis are associated with the presence of ED and MetS, and ...[more]

PMID: 21707993

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Project description:IntroductionErectile dysfunction (ED) is more common in men with type 2 diabetes mellitus (T2DM), obesity, and/or the metabolic syndrome (MetS).AimThe aim of this study is to investigate the associations among proxy measures of diabetic severity and the presence of MetS with ED in a nationally representative U.S. data sample.MethodsWe performed a cross-sectional analysis of adult participants in the 2001-2004 National Health and Nutrition Examination Survey.Main outcome measuresED was ascertained by self-report. T2DM severity was defined by calculated measures of glycemic control and insulin resistance (IR). IR was estimated using fasting plasma insulin (FPI) levels and the homeostasis model assessment of IR (HOMA-IR) definition. We classified glycemic control using hemoglobin-A1c (HbA1c) and fasting plasma glucose (FPG) levels. MetS was defined by the American Heart Association and National Heart, Lung, and Blood Institute criteria. Logistic regression models, adjusted for sociodemographics, risk factors, and comorbidities, were fitted for each measure of T2DM severity, MetS, and the presence of ED.ResultsProxy measures of glycemic control and IR were associated with ED. Participants with FPG between 100-126 mg/dL (5.6-7 mmol/L) and ? 126 mg/dL (>7 mmol/L) had higher odds of ED, odds ratio (OR) 1.22 (confidence interval or CI, 0.83-1.80), and OR 2.68 (CI, 1.48-4.86), respectively. Participants with HbA1c 5.7-6.4% (38.8-46.4 mmol/mol) and ? 6.5% (47.5 mmol/mol) had higher odds of ED (OR 1.73 [CI, 1.08-2.76] and 3.70 [CI, 2.19-6.27], respectively). When FPI and HOMA-IR were evaluated by tertiles, there was a graded relation among participants in the top tertile. In multivariable models, a strong association remained between HbA1c and ED (OR 3.19 [CI,1.13-9.01]). MetS was associated with >2.5-fold increased odds of self reported ED (OR 2.55 [CI, 1.85-3.52]).ConclusionsPoor glycemic control, impaired insulin sensitivity, and the MetS are associated with a heightened risk of ED.

Project description:BackgroundThe association between subclinical cardiovascular disease and subsequent development of erectile dysfunction (ED) remains poorly described.HypothesisAmong multiple subclinical atherosclerosis and vascular dysfunction measurements, coronary artery calcium (CAC) score best predicts ED.MethodsAfter excluding participants taking ED medications at baseline, we studied 1862 men age 45 to 84 years free of known cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA) with comprehensive baseline subclinical vascular disease phenotyping and ED status assessed at MESA visit 5 (9.4 ± 0.5 years after baseline) using a standardized question on ED symptoms. Multivariable logistic regression was used to assess the associations between baseline measures of vascular disease (atherosclerosis domain: CAC, carotid intima-media thickness, carotid plaque, ankle-brachial index; vascular stiffness/function domain: aortic stiffness, carotid stiffness, brachial flow-mediated dilation) and ED symptoms at follow-up.ResultsMean baseline age was 59.5 ± 9 years, and 839 participants (45%) reported ED symptoms at follow-up. Compared with symptom-free individuals, participants with ED had higher baseline prevalence of CAC score >100 (36.4% vs 17.2%), carotid intima-media thickness Z score >75th percentile (35.3% vs 16.6%), carotid plaque score ≥2 (39% vs 21.1%), carotid distensibility <25th percentile (34.6% vs 17.1%), aortic distensibility <25th percentile (34.2% vs 18.7%), and brachial flow-mediated dilation <25th percentile (28.4% vs 21.3%); all P < 0.01. Only CAC >100 (odds ratio: 1.43, 95% confidence interval: 1.09-1.88) and carotid plaque score ≥2 (odds ratio: 1.33, 95% confidence interval: 1.02-1.73) were significantly associated with ED.ConclusionsSubclinical vascular disease is common in men who later self-report ED. Early detection of subclinical atherosclerosis, particularly advanced CAC and carotid plaque, may provide opportunities for predicting the onset of subsequent vascular ED.

Project description:IntroductionMetabolic syndrome (MetS) amplifies the risks of atherosclerosis. Despite well-known sexual dimorphism in atherosclerosis, underlying mechanisms are poorly understood. Our previous findings highlight a proatherogenic protein, thrombospondin-1 (TSP-1), in hyperglycemia- or hyperleptinemia (mimicking obesity)-induced atherosclerosis. However, the role of TSP-1 in the development of atherosclerosis prompted by co-existing hyperglycemia and obesity, characteristic of MetS, is unknown. The goal of this study was to examine sex-specific differences in lesion progression in a model of combined MetS and atherosclerosis (KKAyApoE) and interrogate how these differences relate to TSP-1 expression.MethodsMale and female KKAy+/-ApoE-/- (with ectopic agouti gene expression) and age-matched non-agouti KKAy-/-ApoE-/- littermates were placed on a standard laboratory diet from 4 to 24 weeks age followed by blood and tissue harvests for biochemical, molecular, and aortic root morphometric studies.ResultsMetabolic profiling confirmed MetS phenotype of KKAy+/-ApoE-/-; however, only male genotypes were glucose intolerant with elevated VLDL-cholesterol and VLDL-triglyceride levels. Aortic root morphometry demonstrated profound lipid-filled lesions, increased plaque area, and augmented inflammatory and SMC abundance in MetS vs non-MetS males. This increase in lesion burden was accompanied with elevated TSP-1 and attenuated LMOD-1 (SM contractile marker) and SRF (transcriptional activator of SM differentiation) expression in male MetS aortic vessels. In contrast, while lipid burden, plaque area, and TSP-1 expression increased in MetS and non-MetS female mice, there was no significant difference between these genotypes. Increased collagen content was noted in MetS and non-MetS genotypes, specific to female mice. Measurement of plasma testosterone revealed a link between the atherogenic phenotype and abnormally high or low testosterone levels. To interrogate whether TSP-1 plays a direct role in SMC de-differentiation in MetS, we generated KKAy+/- mice with and without global TSP-1 deletion. Immunoblotting showed increased SM contractile markers in male KKAy+/-TSP-1-/- aortic vessels vs male KKAy+/-TSP-1+/ +. In contrast, TSP-1 deletion had no effect on SM contractile marker expression in female genotypes.ConclusionTogether, the current study implicates a role of plasma testosterone in sex-specific differences in atherosclerosis and TSP-1 expression in MetS vs non-MetS mice. Our data suggest a sex-dependent differential role of TSP-1 on SMC de-differentiation in MetS. Collectively, these findings underscore a fundamental link between TSP-1 and VSMC phenotypic transformation in MetS.

Project description:Penile echo-color Doppler ultrasound (PCDU) is the gold standard for the diagnosis of arterial erectile dysfunction (ED). Its reliability in patients with anxiety was questioned, due to false-positive results. To assess the penile hemodynamic response to intracavernous injection (ICI) of alprostadil in patients with anxiety-related ED. Patients with non-organic ED and a 5-item International Index of Erectile Function (IIEF-5) score ranging between 5 and 7 were enrolled. They were asked to compile the 7-item Generalized Anxiety Disorder (GAD-7) questionnaire to assess the degree of anxiety and were divided according to the GAD-7 score in Group 1 with minimal level of anxiety (n = 20), Group 2 with mild anxiety (n = 20), Group 3 with moderate anxiety (n = 20), and Group 4 with severe anxiety (n = 20). Peak systolic velocity (PSV) and the end-diastolic velocity (EDV) were sampled in all patients, through PCDU in the flaccid state, and 5, 10, 15, and 20 min after ICI of alprostadil at the standard dose of 10 μg. In penile flaccidity, the patients showed a mean PSV of 8.0 ± 4.0 cm/s. The degree of anxiety was found to significantly influence both PSV and EDV at all assessed time-points. Particularly, it was negatively associated with the PSV at time 5 (r = -0.9, p < 0.01), 10 (r = -0.9, p < 0.01), 15 (r = -0.9, p < 0.01), and 20 (r = -0.7, p < 0.01) minutes, and positively with the EDV at time 5 (r = 0.7, p < 0.01), 10 (r = 0.6, p < 0.01), 15 (r = 0.5, p < 0.01), and 20 (r = 0.3, p < 0.01) minutes. Although all patients showed a mean dynamic PSV > 25 cm/s (which excluded an arterial ED according to the current guidelines), a peculiar hemodynamic pattern was found in patients with severe anxiety. In these patients, normal PSV values were reached only after 20 min from ICI, suggesting a "late-responder" profile. If further studies confirm the existence of a distinct hemodynamic profile in patients with severe anxiety, sampling the PSV and the EDV values could be proposed, for detecting patients with severe anxiety-related ED. Dynamic PCDU could be considered an accurate diagnostic test in patients with non-organic ED, since zero false-positive results were found in the present study. PSV in the flaccid state is not able to discriminate between arterial- or non-organic ED.

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Erectile dysfunction, physical activity and metabolic syndrome: differences in markers of atherosclerosis.

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Erectile dysfunction, physical activity and metabolic syndrome: differences in markers of atherosclerosis.

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