Low testosterone in men predicts impaired arterial elasticity and microvascular function

Metabolic syndrome in men with sexual dysfunction

Effect of sodium and potassium supplementation on vascular and endothelial function: a randomized controlled trial

BackgroundDevelopment of instruments capable of detecting early stage vascular disease has increased interest in employing arterial stiffness (e.g. pulse wave velocity (PWV), augmentation index (AIx)) and endothelial dysfunction (e.g. reactive hyperemia index (RHI)) to diagnose atherosclerotic disease before occurrence of a cardiovascular event. However, amongst the equipment designed for this purpose, there is insufficient information regarding each of these parameters to establish appropriate cutoffs to distinguish between healthy and unhealthy blood vessels. To address these limitations, the study was designed to establish the upper arterial stiffness and endothelial function thresholds in a healthy population, by comparing the outputs from different instruments capable of measuring PWV, AIx and RHI.MethodsA systematic comparison of PWV, AIx and RHI was conducted to determine the inter-relationships between these parameters of vascular functionality. Outputs were obtained non-invasively using three instruments, the VP-1000 (VP), SphygmoCor (SC), and EndoPAT (EP), in 40 apparently healthy males and females.ResultsCorrelations were found between the brachial-ankle PWV and radial-ankle PWV (by VP and SC), and PWV (VP) with AIx (SC). The interchangeability of these outputs was demonstrated by the Bland Altman test, making it feasible to extrapolate cut-offs for radial-ankle PWV and AIx equivalent to brachial-ankle PWV that signify healthy vessels. In contrast, RHI showed no association with AIx, suggesting these endothelial and arterial parameters are functionally distinct.ConclusionsIt was concluded that it is possible to compare the vascular function outputs of different instruments and identify healthy from unhealthy vessels, even though the approaches for quantifying the underlying physiological processes may differ. In this way, non-invasive determination of arterial function could be a new paradigm for detecting existing early stage asymptomatic atherosclerotic disease in individuals using techniques that are amenable to the clinical setting.

Erectile dysfunction is associated with low total serum testosterone levels and impaired flow-mediated vasodilation in intermediate risk men according to the framingham risk score

Sodium and potassium intake present a J-shaped relationship with arterial stiffness and carotid intima-media thickness

To investigate the relationship between low testosterone levels and prostate cancer detection risk in a biopsy population. In all, 681 men who underwent initial 12-core transrectal prostate biopsy at our institution were included in this retrospective study. Patients were divided into groups with low (<300ng/dL) and normal testosterone levels (≥300ng/dL). Clinical and pathological data were analysed. Among 681 men, 86 men (12.6%) had low testosterone levels, 143 (32.7%) had a positive biopsy, and 99 (14.5%) had high-grade prostate cancer. The mean age, prostate-specific antigen (PSA) level, PSA density, body mass index (BMI), number of abnormal digital rectal examination (DRE) findings, and diabetes mellitus (DM) history were significantly different between the low and normal level testosterone groups. A low testosterone level was significantly associated with a higher risk of detection of overall prostate cancer than a normal testosterone level in univariate analysis (odds ratio [OR] 2.545, P = 0.001), but not in multivariate analysis adjusting for parameters such as age, PSA, prostate volume, BMI, abnormal DRE findings and DM (OR 1.583, P = 0.277). Meanwhile, a low testosterone level was significantly related to a higher rate of high-grade prostate cancer compared with a normal testosterone level in univariate (OR 3.324, P<0.001) and multivariate analysis adjusting for other parameters (OR 2.138, P = 0.035). Low testosterone level is an independent risk factor for high-grade prostate cancer detection at biopsy. Therefore, checking testosterone levels could help to determine whether prostate biopsy should be carried out.

Testosterone levels in men begin declining in the early years of adulthood, with a 1-2% reduction/year. Low testosterone levels in men are associated with obesity, metabolic syndrome, diabetes mellitus, dyslipidaemia, hypertension and increased cardiovascular mortality. However, observational studies of testosterone levels in males and their relationship with peripheral arterial disease (PAD) have yielded mixed results; only some cohorts show a clear association with low free testosterone levels. This discrepancy may, in part, be due to methodological issues with estimating free testosterone but also to different effects of testosterone on the vessel wall and metabolism. While testosterone improves glycaemic control, has anti-obesity effects and induces vasodilation, it also stimulates platelet aggregation and increases the haematocrit. Androgen deprivation treatment for advanced prostate cancer may be associated with elevated cardiovascular risk, as is testosterone abuse for performance enhancement. On the other hand, judicious treatment of male hypogonadism or testosterone treatment of trans-men appears to be safe.

Cardiovascular disease (CVD) is the number one cause of death globally. High quality dietary patterns such as the DASH diet and the Mediterranean diet are shown to be effective at improving endothelial function and other vascular risk factors in older adults and those with comorbid conditions. To our knowledge, no study has examined the relation between overall diet quality and vascular function in healthy young adults, which could have implications for preventing CVD onset. We aimed to test the hypothesis that lower diet quality, assessed by diet index scores, would be associated with greater arterial stiffness and poorer endothelial function in healthy, non-hypertensive young adults. Seventeen men and 28 women ages 27.0±0.9 y with normal blood pressure (systolic BP: 112±2 mmHg; diastolic BP: 70±1 mmHg), non-obese body mass index (BMI) (23.4±0.4 kg/m2) and no diagnosed chronic disease completed this cross-sectional study. Two DASH diet scores, the alternative Mediterranean diet score (aMED), and the Healthy Eating Index-2015 (HEI-2015) were calculated from 3-day diet records analyzed with NDSR software. Augmentation index (AIx) and carotid-femoral pulse wave velocity (PWV) were measured using the SphygmoCor XCEL system. Brachial artery flow mediated dilation (FMD) was assessed using ultrasound. Separate multiple linear regression analyses with appropriate physiological variables included in the models (for AIx: height, heart rate, age, and sex; for PWV: mean arterial pressure, BMI, age, and sex; for FMD: age and sex) were used to assess the relation between the dietary indexes and vascular outcomes. Average Mellen DASH score was 2.6±0.2 (out of 9), Fung DASH score was 24.1±0.8 (out of 40), aMED score was 3.9±0.3 (out of 9), and HEI-2015 was 60.8±1.9 (out of 100). Average AIx was 6.4±1.7%, average PWV was 5.5±0.1 m/s, and average FMD was 7.9±2.7%. The Mellen DASH score, the aMED score, and the HEI-2015 were inversely associated with AIx, though the associations did not reach statistical significance (B=-1.416, 95% CI: -3.415, 0.583, p=0.16; B=-1.223, 95% CI: -2.833, 0.388, p=0.133; and B=-0.159, 95% CI: -0.386, 0.069, p=0.167, respectively). No other associations between diet index scores and AIx, PWV, or FMD approached statistical significance. Our results suggest that overall diet quality, as assessed using dietary indexes, is not associated with arterial stiffness or endothelial function in healthy young adults. Notably, however, there was room for improvement in our participants’ diet index scores. Intervention studies are warranted to determine how improving diet quality may affect these vascular outcomes in this population.

The goal of this study was to examine the relationship between serum testosterone levels and insulin sensitivity and mitochondrial function in men. A total of 60 men (mean age 60.5 +/- 1.2 years) had a detailed hormonal and metabolic evaluation. Insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp. Mitochondrial function was assessed by measuring maximal aerobic capacity (V(O2max)) and expression of oxidative phosphorylation genes in skeletal muscle. A total of 45% of subjects had normal glucose tolerance, 20% had impaired glucose tolerance, and 35% had type 2 diabetes. Testosterone levels were positively correlated with insulin sensitivity (r = 0.4, P < 0.005). Subjects with hypogonadal testosterone levels (n = 10) had a BMI >25 kg/m(2) and a threefold higher prevalence of the metabolic syndrome than their eugonadal counterparts (n = 50); this relationship held true after adjusting for age and sex hormone-binding globulin but not BMI. Testosterone levels also correlated with V(O2max) (r = 0.43, P < 0.05) and oxidative phosphorylation gene expression (r = 0.57, P < 0.0001). These data indicate that low serum testosterone levels are associated with an adverse metabolic profile and suggest a novel unifying mechanism for the previously independent observations that low testosterone levels and impaired mitochondrial function promote insulin resistance in men.

Objective: To analyze the relationship between ratio night/day of systolic blood pressure and arterial stiffness assessed with carotid intima-media thickness, pulse wave velocity and Augmentation Index. Methods: Design: Cross-sectional study. Setting and Participants: 262 hypertensive patients < 75 years included by consecutive sampling. Average age 54.96 ± 11.58 years, 61.5% males. Measurements: Monitoring ambulatory blood pressure (BP) of 24 hours and estimate systolic and diastolic ratio night/day. Pulse wave velocity (PWV), central blood pressure and Augmentation index (AIx) measured with the SphygmoCor System. Carotid intima-media thickness (IMT) measured with ultrasound. Results: The mean awake BP were 129.45/79.85 mmHg and asleep BP 114.26/66.30 mmHg. IMT mean was 0.74 ± 0.12 mm, and the maximum mean 0.91 ± 0.14 mm. PWV was 9.09 ± 2.21 m/sec. Increase aortic pressure was 14.16 ± 8.82 mmHg, Central pulse pressure (PP) 43.83 ± 13.66 mmHg, Central AIx 30.57 ± 13.30, Central AIx adjusted FC 75 l/m 28.95 ± 11.18 and Peripheral AIx 92.49 ± 21.13. We found positive correlation of systolic ratio night/day with IMT mean (r = 0.268, p = 0.000), IMT maximum mean (r = 0.279, p = 0.000), PWV (r = 0.226, p = 0.000), aortic PP (r = 0.281, p = 0.000), increased central blood pressure (r = 0.234, P = 0.000) and central AIx (0.153, p = 0.013). In multiple linear regression (Stepwise) after adjusting for age, sex and antihypertensive drugs, and considering as dependent variable the ratio night / day, persists in equation, central PP and IMT maximum mean. Conclusions: Ratio night/day of systolic blood pressure was positively associated with markers of arterial stiffness and could be a predictor of atherosclerotic vascular injury.

Effect of regulated vitamin D increase on vascular markers in patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials

To investigate the carotid-radial pulse wave velocity, augmentation index, and flow-mediated dilation of the brachial artery and factors possibly influencing them in women with rheumatoid arthritis and systemic lupus erythematosus. A total of 63 women with rheumatoid arthritis, 31 with systemic lupus erythematosus, and 72 controls, aged 18-55 years, were examined. Parameters of arterial stiffness, augmentation index and carotid-radial pulse wave velocity, were obtained by applanation tonometry (Sphygmocor (v.7.01) AtCor Medical). Flow-mediated dilatation of the brachial artery, reflecting endothelial function was determined by ultrasound system (Logiq 7, General Electric). The groups of women with rheumatoid arthritis and systemic lupus erythematosus lupus differed from controls regarding augmentation index (P<0.001; P=0.008) and did not differ between each other. Women with systemic lupus erythematosus differed from controls regarding pulse wave velocity (P=0.018), while women with rheumatoid arthritis - did not. Flow-mediated dilatation in both the groups of diseases was not different from controls. In rheumatoid arthritis patients, mean blood pressure was the main explanatory factor for augmentation index and pulse wave velocity; vessel diameter and high-density lipoprotein cholesterol - for flow-mediated dilatation. In women with systemic lupus erythematosus, pulse wave velocity was not related to any of the pending parameters; augmentation index was dependent on organ damage index, age, and mean blood pressure, and flow-mediated dilatation on vessel diameter, body mass index, and disease duration. The mean blood pressure was the major and the only one risk factor of arterial stiffening in rheumatoid arthritis, while the disease damage index played the most important role in the systemic lupus erythematosus group. The mean blood pressure in the systemic lupus erythematosus group was not as important as in the rheumatoid arthritis group, though may have a partial influence.

Aetiologic and predisposing factors are still controversial about Peyronie's disease (PD). However, it is thought to be the result of connective tissue disorder or healing defect. Androgens are known to affect collagen metabolism and wound healing in the body. The aim of this study was to investigate the relationship between PD and low testosterone levels. One hundred and forty-seven Peyronie patients and 137 healthy volunteers were included in the study. In both groups, demographic data, medical history, physical examination and erectile capacity were recorded. Blood samples were collected from all subjects in the early morning hours after an overnight fast. The mean level of serum total testosterone was lower in men with PD compared with the controls (3.9±1.1 vs. 4.2±1.7ng/ml respectively) (p=.062). However, statistically significant relationship was not found between PD and low serum testosterone levels. There was no significant correlation between penile plaque dimension or penile curvature degree and testosterone levels. Large randomised-controlled prospective studies are needed to reveal this possible association.

Opioid induced depression of sex hormones is a common finding in chronic pain patients receiving long-term opioids by oral, parenteral and even intrathecal routes of administration. The hypothalamic suppression by opioids leads to a hypogonadal state with low testosterone levels in males and subsequent low bone mineral density (BMD). We have studied the effects of intrathecally administered opioids on BMD in a group of male chronic pain patients. In addition, we have studied the effects of supplementary testosterone on bone metabolism to see if the adverse effects of intrathecal opioids can be reversed. Eleven of the 27 patients were on supplementary testosterone having previously been diagnosed as hypogonadal with low serum testosterone. Duration of testosterone supplementation was greater than 2years in all 11 patients. Both serum total and free testosterone levels were higher in patients on supplementary testosterone than in patients who did not receive this treatment. Of the 16 patients not on testosterone supplement, 14 (87%) had low serum testosterone levels (<10 nmol/L) and 11 (69%) had low or osteoporotic T scores. Within this group, low free testosterone was associated with low BMD scores, and this persisted after correcting for age. Eight of the patients on testosterone supplement had normal BMDT scores and three (27%) had low or osteoporotic T scores. T and age-corrected BMDZ scores were significantly greater in the 11 patients on testosterone supplements than BMD scores in the other 16 patients. Testosterone supplementation was found to largely correct the effects of intrathecal opioids on testosterone levels and BMD.

BACKGROUNDAge‐related vascular cognitive impairment and dementia (VCID), defined as cognitive decline caused by cerebromicrovascular pathologies, is a major public health issue that affects &gt;10 million individuals aged 65 and older in the US with annual healthcare costs totaling &gt;$100 billion. Aging is a major risk factor for the development of VCID and current strategies for VCID treatment are limited to targeting cardiovascular risk factors such as hypertension, diabetes mellitus, etc. Here, we hypothesized that aging, similarly to other risk factors, affects vasculature uniformly and that age‐related changes in the peripheral circulation can be used as an important tool to predict cognitive decline.METHODSFor our study, we have enrolled 55 healthy 22–92 yo individuals and divided them into two groups of young (&lt;45 yo) and aged (&gt;65 yo). Peripheral macrovascular and microvascular endothelial function was measured using a standard flow‐mediated dilation (FMD) and Laser Speckle Contrast Imaging tests (LSCI) in response to increased flow‐mediated shear stress after a 5‐min of blood flow restriction with arterial cuff. Pulse Wave Analysis was used to evaluate the augmentation index (AIx) as a measure of arterial stiffness. A principal component analysis (PCA) approach was used to create a vascular health index (VHI) that included all vascular measurements for each participant. Cognitive function including domain of learning, memory and executive function was measured via a selection of tests from the Cambridge Cognition CANTAB cognitive panel. A PCA approach was used to generate a cognitive impairment index for each participant.RESULTSSubjects from the aged group showed significantly impaired macrovascular endothelial function (FMD, 5.4±0.7% vs. 8.5±0.6% in young, p&lt;0.01) and increased arterial stiffness compared to young (AIx 28.9±1.7% vs 4.5±2.6% in young, p&lt;0.01). Microvascular endothelial function showed significantly lower skin perfusion in aged subjects (2.8±0.1% vs 3.4±0.1% in young, p=0.03) that correlated with FMD measurements (r=0.34, p=0.014), and significantly lower reperfusion rate in aged individuals (25.8±2.2PU/s vs 35.1±2.7 PU/s in young, p=0.01). PCA‐generated Vascular Health Index (VHI) showed a significant negative correlation with age (r=−0.55, p&lt;0.01). VHI correlated with the Cognitive Impairment Index (r=−0.44, p&lt;0.01).CONCLUSIONOur study demonstrates that deterioration of peripheral macro‐ and microvascular endothelial function is associated with and can predict VCID in healthy aged individuals.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.