Testosterone level and mortality in elderly men with systolic chronic heart failure.
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ABSTRACT:
SUBMITTER: Wu HY
PROVIDER: S-EPMC3739581 | biostudies-other | 2011 Sep
REPOSITORIES: biostudies-other
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Project description:Data from a cardiopulmonary exercise (CPX) test are used to determine prognosis in patients with chronic heart failure (HF). However, few published studies have simultaneously compared the relative prognostic strength of multiple CPX variables.The study sought to describe the strength of the association among variables measured during a CPX test and all-cause mortality in patients with HF with reduced ejection fraction (HFrEF), including the influence of sex and patient effort, as measured by respiratory exchange ratio (RER).Among patients (n = 2,100, 29% women) enrolled in the HF-ACTION (HF-A Controlled Trial Investigating Outcomes of exercise traiNing) trial, 10 CPX test variables measured at baseline (e.g., peak oxygen uptake [Vo2], exercise duration, percent predicted peak Vo2 [%ppVo2], ventilatory efficiency) were examined.Over a median follow-up of 32 months, there were 357 deaths. All CPX variables, except RER, were related to all-cause mortality (all p < 0.0001). Both %ppVo2 and exercise duration were equally able to predict (Wald chi-square: ?141) and discriminate (c-index: 0.69) mortality. Peak Vo2 (ml·kg(-1)·min(-1)) was the strongest predictor of mortality among men (Wald chi-square: 129) and exercise duration among women (Wald chi-square: 41). Multivariable analyses showed that %ppVo2, exercise duration, and peak Vo2 (ml·kg(-1)·min(-1)) were similarly able to predict and discriminate mortality. In men, a 10% 1-year mortality rate corresponded to a peak Vo2 of 10.9 ml·kg(-1)·min(-1) versus 5.3 ml·kg(-1)·min(-1) in women.Peak Vo2, exercise duration, and % ppVo2 carried the strongest ability to predict and discriminate the likelihood of death in patients with HFrEF. The prognosis associated with a given peak Vo2 differed by sex. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437).
| S-EPMC4761107 | biostudies-literature
Project description:ObjectivesThis study examines the associations between total testosterone levels and dialysis mortality.MethodsElderly men who initiate hemodialysis in Taoyuan General Hospital from January 2012 to June 2017 were enrolled. We reviewed clinical characteristics and biochemical data from start of dialysis and followed over a 5-year period after dialysis. Body composition parameters were assessed 3-6 months after dialysis. Skeletal muscle mass index (SMMI) was defined by skeletal muscle mass divided by squared height. We defined those with lowest tertile of testosterone values as low testosterone group. Adjusted hazard ratios (aHRs) and 95% confidence interval (95% CI) for mortality and cumulative survival curves were evaluated by Cox hazards model and Kaplan-Meier method. The discriminative power of SMMI and testosterone levels was calculated according to the area under the curve and the receiver operating characteristic curve (AUROC).ResultsFrom a total of 137 elderly hemodialysis patients, the range of lowest, middle, and highest tertile of testosterone values was <6.25 nmol/L, 6.25-10.5 nmol/L, and >10.5 nmol/L. After multivariate adjustment other than SMMI, total testosterone levels at baseline were a significant predictor for mortality aHR(95% CI): 0.79 (0.70-0.91). The unadjusted and adjusted c-statistics of SMMI vs testosterone values to predict overall were 770 (0.688-0.852) vs 0.779 (0.691-0.866) and 855 (0.812-0.886) vs 0.812 (0.744-0.856) (Ps < .05), whereas the capacity of c-statistics was similar (?2 = 0.143 and 2.709, Ps > .05).ConclusionsTotal testosterone value was a predictor for mortality. It was noninferior to SMMI in predicting dialysis mortality.
| S-EPMC6817078 | biostudies-literature
Project description:We have previously reported that asymptomatic systolic heart failure (HF) is characterized by an impaired renal response to volume expansion due to lack of activation of urinary cGMP which is corrected by subcutaneous (SQ) BNP. In the current study, we sought to define the cardiorenal response to intravascular volume expansion after 12 weeks of SQ BNP therapy.We utilized a double-blinded, placebo-controlled study to compare 12 weeks of twice-daily SQ BNP 10?µg/kg (n = 22) or placebo (n = 12) in asymptomatic systolic HF. Subjects underwent two study visits: baseline and after 12 weeks of therapy. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular volume expansion. The primary endpoint was change in urinary sodium excretion in response to volume expansion at 12 weeks, and we observed a greater increase in urinary sodium excretion [166 (77, 290) vs. 15 (-39, 72) mEq/min; P = 0.02] with SQ BNP treatment vs. placebo. Secondary endpoints included change in urine flow and glomerular filtration rate (GFR) in response to volume expansion at 12 weeks. We observed a significant increase in urine flow (P < 0.01) and trend for differential response in GFR (P = 0.08) with SQ BNP treatment vs. placebo.Among patients with asymptomatic systolic HF, twice-daily SQ BNP therapy improved the cardiorenal response to volume expansion at 12-week follow-up. Further studies are warranted to determine if these beneficial physiological observations with chronic natriuretic peptide administration translate into a delay in the progression to symptomatic HF.
| S-EPMC4874857 | biostudies-literature
Project description:Compared with no alcohol consumption, heavy alcohol intake is associated with a higher rate of heart failure (HF) whereas light-to-moderate intake may be associated with a lower rate. However, several prior studies did not exclude former drinkers, who may have changed alcohol consumption in response to diagnosis. This study aimed to investigate the association between alcohol intake and incident HF.We conducted a prospective cohort study of 33 760 men aged 45 to 79 years with no HF, diabetes mellitus, or myocardial infarction at baseline participating in the Cohort of Swedish Men Study. We excluded former drinkers. At baseline, participants completed a food frequency questionnaire and reported other characteristics. HF was defined as hospitalization for or death from HF, ascertained by Swedish inpatient and cause-of-death records from January 1, 1998, through December 31, 2011. We constructed Cox proportional hazards models to estimate multivariable-adjusted incidence rate ratios. During follow-up, 2916 men were hospitalized for (n=2139) or died (n=777) of incident HF. There was a U-shaped relationship between total alcohol intake and incident HF (P=0.0004). There was a nadir at light-to-moderate alcohol intake: consuming 7 to <14 standard drinks per week was associated with a 19% lower multivariable-adjusted rate of HF compared with never drinking (incidence rate ratio, 0.81; 95% confidence interval, 0.69-0.96).In this cohort of Swedish men, there was a U-shaped relationship between alcohol consumption and HF incidence, with a nadir at light-to-moderate intake. Heavy intake did not seem protective.
| S-EPMC4511919 | biostudies-literature
Project description:Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and to determine definitively whether testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this set of trials. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, common approaches to treatment and monitoring, and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data and safety monitoring board, the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in participant selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone deficient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary outcomes for each trial were identifying those of the highest clinical importance and identifying the minimum clinically important differences between treatment arms for sample size estimation. Potential limitations Setting the serum testosterone concentration sufficiently low to ensure that most men would be unequivocally testosterone deficient, as well as many other entry criteria, resulted in screening approximately 30 men in person to randomize one participant. Conclusion Designing The Testosterone Trials as a coordinated set of seven trials afforded many important scientific and logistical advantages but required an intensive recruitment and screening effort.
| S-EPMC4182174 | biostudies-literature
Project description:Elevated resting heart rate (HR) and low systolic blood pressure (SBP) are related to poor outcomes in heart failure (HF). The association between visit-to-visit variation in SBP and HR and risk in HF is unknown.In Systolic Heart Failure Treatment with the If inhibitor ivabradine Trial (SHIFT) patients, we evaluated relationships between mean HR, mean SBP, and visit-to-visit variations (coefficient of variation [CV]=SD/mean×100%) in SBP and HR (SBP-CV and HR-CV, respectively) and primary composite endpoint (cardiovascular mortality or HF hospitalization), its components, all-cause mortality, and all-cause hospitalization. High HR and low SBP were closely associated with risk for primary endpoint, all-cause mortality, and HF hospitalization. The highest number of primary endpoint events occurred in the highest HR tertile (38.8% vs 16.4% lowest tertile; P<0.001). For HR-CV, patients at highest risk were those in the lowest tertile. Patients in the lowest thirds of mean SBP and SBP-CV had the highest risk. The combination of high HR and low HR-CV had an additive deleterious effect on risk, as did that of low SBP and low SBP-CV. Ivabradine reduced mean HR and increased HR-CV, and increased SBP and SBP-CV slightly.Beyond high HR and low SBP, low HR-CV and low SBP-CV are predictors of cardiovascular outcomes with additive effects on risk in HF, but with an unknown effect size. Beyond HR reduction, ivabradine increases HR-CV. Low visit-to-visit variation of HR and SBP might signal risk of cardiovascular outcomes in systolic HF.URL: http://www.isrctn.com/. Unique identifier: ISRCTN70429960.
| S-EPMC4802472 | biostudies-other
Project description:ObjectivesThe purpose of the present study was to translate our laboratory investigations to establish safety and efficacy of 8 weeks of chronic SC B-type natriuretic peptide (BNP) administration in human Stage C heart failure (HF).BackgroundB-Type natriuretic peptide is a cardiac hormone with vasodilating, natriuretic, renin-angiotensin inhibiting, and lusitropic properties. We have previously demonstrated that chronic cardiac hormone replacement with subcutaneous (SC) administration of BNP in experimental HF resulted in improved cardiovascular function.MethodsWe performed a randomized double-blind placebo-controlled proof of concept study comparing 8 weeks of SC BNP (10 μg/kg bid) (n = 20) with placebo (n = 20) in patients with ejection fraction <35% and New York Heart Association functional class II to III HF. Primary outcomes were left ventricular (LV) volumes and LV mass determined by cardiac magnetic resonance imaging. Secondary outcomes include LV filling pressure by Doppler echo, humoral function, and renal function.ResultsEight weeks of chronic SC BNP resulted in a greater reduction of LV systolic and diastolic volume index and LV mass index as compared with placebo. There was a significantly greater improvement of Minnesota Living with Heart Failure score, LV filling pressure as demonstrated by the reductions of E/e' ratio, and decrease in left atrial volume index as compared with placebo. Glomerular filtration rate was preserved with SC BNP, as was the ability to activate plasma 3',5'-cyclic guanosine monophosphate (p < 0.05 vs. placebo).ConclusionsIn this pilot proof of concept study, chronic protein therapy with SC BNP improved LV remodeling, LV filling pressure, and Minnesota Living with Heart Failure score in patients with stable systolic HF on optimal therapy. Renin-angiotensin was suppressed, and glomerular filtration rate was preserved. Subcutaneous BNP represents a novel, safe, and efficacious protein therapeutic strategy in human HF. Further studies are warranted to determine whether these physiologic observations can be translated into improved clinical outcomes and ultimately delay the progression of HF. (Cardiac Hormone Replacement With BNP in Heart Failure: A Novel Therapeutic Strategy; NCT00252187).
| S-EPMC3555560 | biostudies-literature
Project description:We sought to identify prognostic factors of long-term mortality, specific for the underlying etiology of chronic systolic heart failure (CHF).Between 1995 and 2009 baseline characteristics, treatment and follow-up data from 2318 CHF-patients due to ischemic (ICM; 1100 patients) or dilated cardiomyopathy (DCM; 1218 patients) were prospectively compared. To calculate hazard ratios with 95%-confidence intervals cox regression was used. We respectively established etiology-specific multivariable models of independent prognostic factors. During the follow-up period of up to 14.8 years (mean = 53.1 ± 43.5 months; 10,264 patient-years) 991 deaths (42.8%) occurred. In the ICM-cohort, 5-year-survival was 53.4% (95% CI: 49.9-56.7%), whereas in DCM-patients it was higher (68.1% (95% CI: 65.1-71.0%)). Age, ejection fraction, or hyponatremia were independent predictors for mortality in both cohorts, whereas diabetes, COPD, atrial fibrillation and a heart rate of ≥ 80/min carried independent predictive power only in ICM-patients.This study demonstrates the disparity of prognostic value of clinically derived risk factors between the two main causes of CHF. The effects of covariables in DCM-patients were lower, suggesting a less modifiable disease through risk factors considering mortality risk. An etiology-specific prognostic model may improve accuracy of survival estimations in CHF.
| S-EPMC5497234 | biostudies-other
Project description:Testosterone deficiency in patients with heart failure (HF) is associated with decreased exercise capacity and mortality; however, its impact on hospital readmission rate is uncertain. Furthermore, the relationship between testosterone deficiency and sympathetic activation is unknown.We investigated the role of testosterone level on hospital readmission and mortality rates as well as sympathetic nerve activity in patients with HF.Total testosterone (TT) and free testosterone (FT) were measured in 110 hospitalized male patients with a left ventricular ejection fraction < 45% and New York Heart Association classification IV. The patients were placed into low testosterone (LT; n = 66) and normal testosterone (NT; n = 44) groups. Hypogonadism was defined as TT < 300 ng/dL and FT < 131 pmol/L. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography in a subpopulation of 27 patients.Length of hospital stay was longer in the LT group compared to in the NT group (37 ± 4 vs. 25 ± 4 days; p = 0.008). Similarly, the cumulative hazard of readmission within 1 year was greater in the LT group compared to in the NT group (44% vs. 22%, p = 0.001). In the single-predictor analysis, TT (hazard ratio [HR], 2.77; 95% confidence interval [CI], 1.58-4.85; p = 0.02) predicted hospital readmission within 90 days. In addition, TT (HR, 4.65; 95% CI, 2.67-8.10; p = 0.009) and readmission within 90 days (HR, 3.27; 95% CI, 1.23-8.69; p = 0.02) predicted increased mortality. Neurohumoral activation, as estimated by MSNA, was significantly higher in the LT group compared to in the NT group (65 ± 3 vs. 51 ± 4 bursts/100 heart beats; p < 0.001).These results support the concept that LT is an independent risk factor for hospital readmission within 90 days and increased mortality in patients with HF. Furthermore, increased MSNA was observed in patients with LT.
| S-EPMC4592174 | biostudies-literature
Project description:Patients with chronic heart failure (CHF) experience progressive deterioration of functional capacity and quality of life (QoL). This prospective, randomized, controlled trial assesses the effect of exercise training (ET) protocol on functional capacity, rehospitalization, and QoL in CHF patients older than 70 years compared with a control group. A total of 343 elderly patients with stable CHF (age, 76.90±5.67, men, 195, 56.9%) were randomized to ET (TCG, n=170) or usual care (UCG, n=173). The ET protocol involved supervised training sessions for 3 months in the hospital followed by home-telemonitored sessions for 3 months. Assessments, performed at baseline and at 3 and 6 months, included: ECG, resting echocardiography, NT-proBNP, 6-minute walk test (6MWT), Minnesota Living with Heart Failure Questionnaire, and comprehensive geriatric assessment with the InterRAI-HC instrument. As compared to UCG, ET patients at 6 months showed: i) significantly increased 6MWT distance (450±83 vs. 290±97 m, p=0.001); ii) increased ADL scores (5.00±2.49 vs. 6.94±5.66, p=0.037); iii) 40% reduced risk of rehospitalisation (hazard ratio=0.558, 95%CI, 0.326-0.954, p=0.033); and iv) significantly improved perceived QoL (28.6±12.3 vs. 44.5±12.3, p=0.001). In hospital and home-based telemonitored exercise confer significant benefits on the oldest CHF patients, improving functional capacity and subjective QoL and reducing risk of rehospitalisation.
| S-EPMC4931840 | biostudies-other