Effects of Aerobic Fitness and Adiposity on Coagulation Biomarkers in Men vs. Women with Elevated Blood Pressure

A hypercoagulable state is a potential mechanism linking elevated blood pressure (BP), adiposity and a sedentary lifestyle to development of coronary heart disease (CHD). We examined relationships among aerobic fitness and adiposity in 76 sedentary subjects with elevated BP. Blood levels of plasminogen activator inhibitor-1 (PAI-1), D-dimer, von Willebrand factor (vWF) and thrombomodulin were assessed as biomarkers of coagulation. In individuals with elevated BP, percent body fat and fitness were associated with biomarkers indicative of a hypercoagulable state, even after demographic and metabolic factors were considered. D-dimer was positively associated with percent body fat (beta=0.37, p=0.003). PAI-1 was higher in men than in women (beta=-0.31, p=0.015) and associated with lower VO2peak (beta=-0.35, p=0.024). Thrombomodulin was positively associated with VO2peak (beta=0.56, p< 0.01). vWF was not significantly associated with fitness or adiposity. Our results emphasise that both percent body fat and physical fitness are important in the maintenance of haemostatic balance.

The prevalence of erectile dysfunction and its association with antiretroviral therapy in HIV-infected men: the Swiss HIV Cohort Study

Here, we aimed to determine the prevalence of erectile dysfunction (ED) among HIV-infected men and its association with components of antiretroviral therapy.

[Approach to prostate cancer in men older than 75 years: active or passive?]

Based on the exponential aging of the population and the increasing life expectancy in industrialized western countries, prostate cancer (PCa) in elderly men is becoming a disease of increasing significance. Consensus exists that men over the age of 75 years should not be screened for PCa; however, higher age as a single parameter should not exclude men from being diagnosed with prostate cancer and treated accordingly. It is well-known that overdiagnosis and overtreatment are frequent in this age group. Competing mortality risks of men older than 75 years may supersede the risk of dying from PCa several fold. Both the treating physician and the patient himself should therefore balance the possible risks and benefits of diagnosing and treating prostate cancer concerning the impact on quality of life. This is of special importance when taking into account that the complication rates of curative treatment modalities are higher in older patients than in younger men and that hormonal treatment might have negative effects especially in older men.Age, existing comorbidities, cognitive and physical status in combination with specific tumor parameters are useful tools for an individualized treatment.Therapy should be considered for healthy, active men aged 75 years or older who present with high-risk PCa and/or with a PSA doubling time <12 months. Elderly men who are unfit or have low to intermediate risk PCa will most likely not benefit from treatment.

Of marsupials and men: "Backdoor" dihydrotestosterone synthesis in male sexual differentiation

Following development of the fetal bipotential gonad into a testis, male genital differentiation requires testicular androgens. Fetal Leydig cells produce testosterone that is converted to dihydrotestosterone in genital skin, resulting in labio-scrotal fusion. An alternative 'backdoor' pathway of dihydrotestosterone synthesis that bypasses testosterone has been described in marsupials, but its relevance to human biology has been uncertain. The classic and backdoor pathways share many enzymes, but a 3α-reductase, AKR1C2, is unique to the backdoor pathway. Human AKR1C2 mutations cause disordered sexual differentiation, lending weight to the idea that both pathways are required for normal human male genital development. These observations indicate that fetal dihydrotestosterone acts both as a hormone and as a paracrine factor, substantially revising the classic paradigm for fetal male sexual development.

Effects of sleep fragmentation on the arousability to resistive loading in NREM and REM sleep in normal men

STUDY OBJECTIVE: In healthy subjects, arousability to inspiratory resistive loading is greater during rapid eye movement (REM) sleep compared with non-REM (NREM) sleep but is poorest in REM sleep in patients with sleep apnea. We therefore examined the hypothesis that sleep fragmentation impairs arousability, especially from REM sleep. DESIGN: Two blocks of 3 polysomnographies (separated by at least 1 week) were performed randomly. An inspiratory-loaded night followed either 2 undisturbed control nights (LN(C)) or 2 acoustically fragmented nights (LN(F)) SETTING: Sleep laboratory. PARTICIPANTS: Sixteen healthy men aged 20 to 29 years. INTERVENTIONS: In both loaded nights, an inspiratory resistive load was added via a valved facemask every 2 minutes during sleep and turned off either when arousal occurred or after 2 minutes. MEASUREMENTS AND RESULTS: During LN(F), arousability remained significantly greater in REM sleep (71% aroused within 2 minutes) compared with stage 2 (29%) or stage 3/4 (16%) sleep. After sleep fragmentation, arousability was decreased in stage 2 sleep (LN(F): 29%; LN(C): 38%; p < .05) and low in early REM sleep, increasing across the night (p < .01). In stage 3/4 sleep, neither an attenuation nor a change across the night was seen after sleep fragmentation. CONCLUSIONS: Mild sleep fragmentation is already sufficient to attenuate arousability in stage 2 sleep and to decrease arousability in early, compared with late, REM sleep. This means that sleep fragmentation affects the arousal response to increasing resistance and that the effects are different in stage 2 and REM sleep. The biologic reason for this increase in the arousal response in REM sleep across the night is not clear.

The effect of increased lipid intake on hormonal responses during aerobic exercise in endurance-trained men

In view of the growing health problem associated with obesity, clarification of the regulation of energy homeostasis is important. Peripheral signals, such as ghrelin and leptin, have been shown to influence energy homeostasis. Nutrients and physical exercise, in turn, influence hormone levels. Data on the hormonal response to physical exercise (standardized negative energy balance) after high-fat (HF) or low-fat (LF) diet with identical carbohydrate intake are currently not available. The aim of the study was to investigate whether a short-term dietary intervention with HF and LF affects ghrelin and leptin levels and their modulators, GH, insulin and cortisol, before and during aerobic exercise. Eleven healthy, endurance-trained male athletes (W(max) 365 +/- 29 W) were investigated twice in a randomized crossover design following two types of diet: 1. LF - 0.5 g fat/kg body weight (BW) per day for 2.5 days; 2. HF - 0.5 g fat/kg BW per day for 1 day followed by 3.5 g fat/kg BW per day for 1.5 days. After a standardized carbohydrate snack in the morning, metabolites and hormones (GH, ghrelin, leptin, insulin and cortisol) were measured before and at regular intervals throughout a 3-h aerobic exercise test on a cycloergometer at 50% of W(max). Diet did not significantly affect GH and cortisol concentrations during exercise but resulted in a significant increase in ghrelin and decrease in leptin concentrations after LF compared with HF diet (area under the curve (AUC) ghrelin LF vs HF: P < 0.03; AUC leptin LF vs HF: P < 0.02, Wilcoxon rank test). These data suggest that acute negative energy balance induced by exercise elicits a hormonal response with opposite changes of ghrelin and leptin. In addition, the hormonal response is modulated by the preceding intake of fat.

Ultrasound assessment of detrusor thickness in men-can it predict bladder outlet obstruction and replace pressure flow study?

PURPOSE: We estimated the diagnostic accuracy of ultrasound detrusor thickness measurement for BOO and investigated whether this method can replace PFS for the diagnosis of BOO in some patients with lower urinary tract symptoms. MATERIALS AND METHODS: Detrusor thickness was measured by linear ultrasound (7.5 MHz) at a filling volume of greater than 50% of cystometric capacity in 102 men undergoing PFS for LUTS. All patients with prior treatment for bladder outlet obstruction and those with underlying neurological disorders were excluded from analysis. Detrusor thickness was correlated with PFS data. Obstruction was defined according to the Abrams-Griffiths nomogram. RESULTS: Detrusor thickness was significantly higher (p <0.0001) in obstructed (61 cases, median detrusor thickness 2.7 mm, IQR 2.4 to 3.3) compared to unobstructed (18 cases, median detrusor thickness 1.7 mm, IQR 1.5 to 2) as well as equivocal (23 cases, median detrusor thickness 1.8 mm, IQR 1.5 to 2.2) cases. A weak to medium Spearman correlation was found between detrusor thickness and PFS parameters. For a diagnosis of BOO, detrusor thickness of 2.9 mm or greater had a positive predictive value of 100%, a negative predictive value of 54%, specificity of 100% and sensitivity of 43%. ROC analysis revealed that detrusor thickness had a high predictive value for BOO with an AUC of 0.88 (95% CI 0.81-0.94). CONCLUSIONS: In men with LUTS without prior treatment and/or neurological disorders, ultrasonographically assessed detrusor thickness 2.9 mm or greater has a high predictive value for BOO and can replace PFS for the diagnosis of BOO. However, this cutoff value needs to be validated in a larger study population.

Responsiveness and habituation of soluble icam-1 to acute psychosocial stress in men: determinants and efect of stress-hemoconcentration

We studied the psychophysiology of soluble intercellular adhesion molecule-1 (sICAM-1) in 25 apparently healthy middle-aged men who underwent an acute psychosocial stressor three times with one week apart. Measures of the biological stress response were obtained at week one and three. The magnitude of the sICAM-1 stress response showed no habituation between visits. At week one, cognitive stress appraisal independently predicted integrated sICAM-1 area under the curve (AUC) between rest, immediately post-stress, and 45 min and 105 min post-stress (beta=.67, p=.012, deltaR(2)=.41). Diastolic blood pressure AUC (beta=-.45, p=.048, deltaR(2)=.21) and heart rate (AUC) (beta=.44, p=.055, deltaR(2)=.21) were independent predictors of sICAM-1 (AUC) at week three. Adjustment for hemoconcentration yielded a decrease in sICAM-1 levels from rest to post-stress (p<.001). Stress responsiveness of plasma sICAM-1 was predicted by stress perception and hemodynamic reactivity and affected by stress-hemoconcentration but unrelated to cortisol reactivity and not readily adapting to stress repeats.

Delayed response and lack of habituation in plasma interleukin-6 to acute mental stress in men

Acute mental stress induces a significant increase in plasma interleukin (IL)-6 levels as a possible mechanism for how psychological stress might contribute to atherosclerosis. We investigated whether the IL-6 response would habituate in response to a repetitively applied mental stressor and whether cortisol reactivity would show a relationship with IL-6 reactivity. Study participants were 21 reasonably healthy men (mean age 46+/-7 years) who underwent the Trier Social Stress Test (combination of a 3-min preparation, 5-min speech, and 5-min mental arithmetic) three times with an interval of 1 week. Plasma IL-6 and free salivary cortisol were measured immediately before and after stress, and at 45 and 105 min of recovery from stress. Cortisol samples were also obtained 15 and 30 min after stress. Compared to non-stressed controls, IL-6 significantly increased between rest and 45 min post-stress (p=.022) and between rest and 105 min post-stress (p=.001). Peak cortisol (p=.034) and systolic blood pressure (p=.009) responses to stress both habituated between weeks one and three. No adaptation occurred in diastolic blood pressure, heart rate, and IL-6 responses to stress. The areas under the curve integrating the stress-induced changes in cortisol and IL-6 reactivity were negatively correlated at visit three (r=-.54, p=.011), but not at visit one. The IL-6 response to acute mental stress occurs delayed and shows no adaptation to repeated moderate mental stress. The hypothalamus-pituitary-adrenal axis may attenuate stress reactivity of IL-6. The lack of habituation in IL-6 responses to daily stress could subject at-risk individuals to higher atherosclerotic morbidity and mortality.

Anticipatory cognitive stress appraisal and the acute procoagulant stress response in men

OBJECTIVE: Acute mental stress elicits blood hypercoagulability. Following a transactional stress model, we investigated whether individuals who anticipate stress as more threatening, challenging, and as exceeding their coping skills show greater stress reactivity of the coagulation activation marker D-dimer, indicating fibrin generation in plasma. METHODS: Forty-seven men (mean age 44 +/- 14 years; mean blood pressure [MBP] 101 +/- 12 mm Hg; mean body mass index [BMI] 26 +/- 3 kg/m(2)) completed the Primary Appraisal Secondary Appraisal (PASA) scale before undergoing the Trier Social Stress Test (combination of mock job interview and mental arithmetic task). Heart rate, blood pressure, plasma catecholamines, and D-dimer levels were measured before and after stress, and during recovery up to 60 minutes poststress. RESULTS: Hemodynamic measures, catecholamines, and D-dimer changed across all time points (p values <.001). The PASA "Stress Index" (integrated measure of transactional stress perception) correlated with total D-dimer area under the curve (AUC) between rest and 60 minutes poststress (r = 0.30, p = .050) and with D-dimer change from rest to immediately poststress (r = 0.29, p = .046). Primary appraisal (combined "threat" and "challenge") correlated with total D-dimer AUC (r = 0.37, p = .017), D-dimer stress change (r = 0.41, p = .004), and D-dimer recovery (r = 0.32, p = .042). "Challenge" correlated more strongly with D-dimer stress change than "threat" (p = .020). Primary appraisal (DeltaR(2) = 0.098, beta = 0.37, p = .019), and particularly its subscale "challenge" (DeltaR(2) = 0.138, beta = 0.40, p = .005), predicted D-dimer stress change independently of age, BP, BMI, and catecholamine change. CONCLUSIONS: Anticipatory cognitive appraisal determined the extent of coagulation activation to and recovery from stress in men. Particularly individuals who anticipated the stressor as more challenging and also more threatening had a greater fibrin stress response.

A coronary heart disease risk model for predicting the effect of potent antiretroviral therapy in HIV-1 infected men

BACKGROUND: Many HIV-infected patients on highly active antiretroviral therapy (HAART) experience metabolic complications including dyslipidaemia and insulin resistance, which may increase their coronary heart disease (CHD) risk. We developed a prognostic model for CHD tailored to the changes in risk factors observed in patients starting HAART. METHODS: Data from five cohort studies (British Regional Heart Study, Caerphilly and Speedwell Studies, Framingham Offspring Study, Whitehall II) on 13,100 men aged 40-70 and 114,443 years of follow up were used. CHD was defined as myocardial infarction or death from CHD. Model fit was assessed using the Akaike Information Criterion; generalizability across cohorts was examined using internal-external cross-validation. RESULTS: A parametric model based on the Gompertz distribution generalized best. Variables included in the model were systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, triglyceride, glucose, diabetes mellitus, body mass index and smoking status. Compared with patients not on HAART, the estimated CHD hazard ratio (HR) for patients on HAART was 1.46 (95% CI 1.15-1.86) for moderate and 2.48 (95% CI 1.76-3.51) for severe metabolic complications. CONCLUSIONS: The change in the risk of CHD in HIV-infected men starting HAART can be estimated based on typical changes in risk factors, assuming that HRs estimated using data from non-infected men are applicable to HIV-infected men. Based on this model the risk of CHD is likely to increase, but increases may often be modest, and could be offset by lifestyle changes.