Healthier lifestyle predicts higher circulating testosterone in older men: the Health In Men Study

Objective Circulating testosterone declines during male ageing, and low testosterone may predispose to ill health. We sought to determine whether greater participation in healthy behaviours predicted reduced risk of subsequent lower circulating testosterone in older men. Design Cross‐sectional analysis of a population‐based follow‐up study. Participants A total of 3453 men aged 65–83 years. Measurements Lifestyle score, a tally of eight prudent health‐related behaviours, was determined during 1996–99. Early morning sera collected in 2001–04 were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using mass action equations. Results Mean (± SD) time between collection of lifestyle data and blood sampling was 5·7 ± 0·9 years. Lifestyle score correlated with subsequent total testosterone (r = 0·06, P < 0·001) and SHBG (r = 0·07, P < 0·001), but not free testosterone (r = 0·03, P = 0·08) or LH (r = –0·03, P = 0·12). In multivariate analyses, higher lifestyle scores (4 and above) predicted reduced risk of total testosterone and SHBG in the lowest quartile of values. For the highest category (≥ 7), odds ratio (95% CI) for total testosterone and SHBG in the lowest quartile were 0·37 (0·18–0·77) and 0·26 (0·13–0·54), respectively. Lower lifestyle scores including and excluding body mass index predicted higher risk of total testosterone and SHBG in the lowest quartiles. Conclusions In men > 65 years old, higher lifestyle score reflecting greater engagement in healthy behaviours predicts higher subsequent total testosterone and SHBG levels. This relationship appears cumulative and may reflect interaction between lifestyle and insulin sensitivity. Successfully promoting healthy behaviours in older men could ameliorate the age‐related decline in circulating testosterone.     

Hyperkyphotic posture predicts mortality in older community-dwelling men and women: a prospective study

OBJECTIVES: To determine the association between hyperkyphotic posture and rate of mortality and cause-specific mortality in older persons. DESIGN: Prospective cohort study. SETTING: Rancho Bernardo, California. PARTICIPANTS: Subjects were 1,353 participants from the Rancho Bernardo Study who had measurements of kyphotic posture made at an osteoporosis visit between 1988 and 1991. MEASURES: Kyphotic posture was measured as the number of 1.7-cm blocks that needed to be placed under the participant's head to achieve a neutral head position when lying supine on a radiology table. Demographic and clinical characteristics and health behaviors were assessed at a clinic visit using standard questionnaires. Participants were followed for an average of 4.2 years, with mortality and cause of death confirmed using review of death certificates. RESULTS: Hyperkyphotic posture, defined as requiring one or more blocks under the occiput to achieve a neutral head position while lying supine, was more common in men than women (44% in men, 22% of women, P<.0001). In age- and sex-adjusted analyses, persons with hyperkyphotic posture had a 1.44 greater rate of mortality (95% confidence interval (CI)=1.12-1.86, P=.005). In multiply adjusted models, the increased rate of death associated with hyperkyphotic posture remained significant (relative hazard=1.40, 95% CI=1.08-1.81, P=.012). In cause-specific mortality analyses, hyperkyphotic posture was specifically associated with an increased rate of death due to atherosclerosis. CONCLUSION: Older men and women with hyperkyphotic posture have higher mortality rates.     

Higher free thyroxine levels are associated with frailty in older men: the Health In Men Study

Objective Frailty is common in the elderly and predisposes to ill‐health. Some symptoms of frailty overlap those of thyroid dysfunction, but it is unclear whether differences in thyroid status influence risk of frailty. We evaluated associations between thyroid status and frailty in older men. Design Cross‐sectional epidemiological study. Participants Community‐dwelling men aged 70–89 years. Measurements Circulating thyrotropin (TSH) and free thyroxine (FT₄) were assayed. Frailty was assessed as ≥3 of the Fatigue, Resistance, Ambulation, Illnesses and Loss (FRAIL) scale’s 5 domains: fatigue; resistance (difficulty climbing flight of stairs); ambulation (difficulty walking 100 m); illness (>5); or weight loss (>5%), blinded to hormone results. Results Of 3943 men, 27 had subclinical hyperthyroidism, 431 subclinical hypothyroidism and 608 were classified as being frail (15·4%). There was an inverse log‐linear association of TSH with FT₄. There was no association between TSH and frailty. After adjusting for covariates, men with FT₄ in the highest two quartiles had increased odds of being frail (Q3:Q1, odds ratio [OR] = 1·32, 95% confidence interval [CI] = 1·01–1·73 and Q4:Q1, OR = 1·36, 95% CI = 1·04–1·79, P = 0·010 for trend). Higher FT₄ was associated with fatigue (P = 0·038) and weight loss (P < 0·001). The association between FT₄ and frailty remained significant when the analysis was restricted to euthyroid men. Conclusions High‐normal FT₄ level is an independent predictor of frailty among ageing men. This suggests that even within the euthyroid range, circulating thyroxine may contribute to reduced physical capability. Further studies are needed to clarify the utility of thyroid function testing and the feasibility of preventing or reversing frailty in older men.     

Daytime sleepiness predicts mortality and cardiovascular disease in older adults. The Cardiovascular Health Study Research Group

INTRODUCTION: As part of the baseline examination in the Cardiovascular Health Study, sleep disturbance symptoms including snoring and daytime sleepiness, were assessed as potential risk factors or precipitants of cardiovascular disease (CVD). Because of the association of sleep disturbance with poorer health and the possible associations of sleep apnea with CVD, we hypothesized that those with poorer sleep or daytime sleepiness may be at increased risk of mortality or incident CVD. SETTING: Participants (n = 5888) were recruited in 1989, with an additional minority cohort recruited in 1993, in four US communities for a cohort study designed to evaluate risk factors for cardiovascular disease. METHODS: An interview-administered questionnaire regarding health and sleep habits with ongoing ascertainment of total mortality and cardiovascular disease morbidity and mortality, including total CVD morbidity and mortality, incident myocardial infarction, and congestive heart failure. RESULTS: Daytime sleepiness was the only sleep symptom that was significantly associated with mortality in both men and women. The unadjusted hazard ratio was 2.12 (1.66, 2.72) in women and 1.40 (1.12, 1.73) in men. Men who reported difficulty falling asleep also had an increased mortality rate (HR = 1.43 (1.14, 1.80)) which was not seen in women. The risks were attenuated with adjustment for age but remained significant for daytime sleepiness in women (HR = 1.82 (1.42, 2.34)) and for difficulty falling asleep in men. (HR = 1.29 (1.03, 1.63)). Frequent awakenings, early morning awakening, and snoring were not associated with a significantly increased risk of mortality in these older men and women. Crude event rates were evaluated for total incident cardiovascular morbidity and mortality, incident myocardial infarction, and incident congestive heart failure (CHF). Incident CVD rates were higher in both men and women with daytime sleepiness. The aged adjusted HR was 1.35 (95% CI = 1.03, 1.76) in men and was 1.66 (95% CI = 1.28, 2.16) in women. Incident CVD was not higher in those with any other sleep disturbance including snoring. The risk of CVD events associated with daytime sleepiness was attenuated but remained significant in women after adjustment for age. Incident myocardial infarction (MI) rates were also higher in women with daytime sleepiness but were not significantly higher in men. Incident CHF rates were increased in both men and women with daytime sleepiness. In men, the age adjusted HR was 1.49 (95% CI, 1.12- 1.98) and in women, was 2.21 (95% CI, 1.64-2.98). Women reporting both daytime sleepiness and frequent awakening had a hazard ratio of 2.34 (95% CI, 1.66-3.29) for incident CHF compared with those with daytime sleepiness but without frequent awakening. This interaction was not found in men. CONCLUSIONS: In this study, daytime sleepiness was the only sleep disturbance symptom that was associated with mortality, incident CVD morbidity and mortality, MI, and CHF. These findings were stronger in women than men, i.e., the associations persisted for mortality, CVD, and CHF in women after adjustment for age and other factors. Thus, a report of daytime sleepiness identifies older adults at increased risk for total and cardiovascular mortality, and is an independent risk factor in women.     

Increasing kyphosis predicts worsening mobility in older community-dwelling women: a prospective cohort study

OBJECTIVES: To determine whether increasing kyphosis angle was independently associated with poorer mobility as measured according to the Timed Up and Go Test (TUG), after controlling for other established risk factors. DESIGN: Prospective cohort study. SETTING: Eleven clinical centers in the United States. PARTICIPANTS: Two thousand seven hundred seventy‐seven women aged 55 to 80 randomized to the placebo arms of the Fracture Intervention Trial, a randomized controlled trial of the effect of alendronate on risk for osteoporotic fractures. MEASUREMENTS: The primary predictor was change in kyphosis angle, measured using the Debrunner Kyphometer; the outcome was change in mobility, measured as performance time on the TUG. Covariates were baseline age, kyphosis angle, body mass index (BMI), self‐reported health status, grip strength, change in total hip bond mineral density (BMD), and number of vertebral fractures over a mean of 4.4 years. RESULTS: Greater kyphosis angle predicted longer mobility performance times (P<.001), independent of other significant predictors of worsening mobility including age, baseline kyphosis, health status, grip strength, BMI, change in hip BMD, and new vertebral fractures. TUG performance times increased by 0.02 seconds (95% confidence interval (CI)=0.01–0.03) for every 5° increase in kyphosis angle, more than the increase in mobility time of 0.01 seconds (95% CI=0.005–0.03) over 1 year observed in this cohort. CONCLUSION: Increasing kyphosis angle is independently associated with worsening mobility. Interventions are needed to prevent or reduce increasing kyphosis and mobility decline.     

Self-rated health and mortality in older men and women: a time-dependent covariate analysis

Although the relation between self-rated health (SRH) and mortality is widely known, most of the studies have relied in baseline measurements unheeding the dynamics of the phenomenon. Our aim was to analyze how SRH both as a constant and as a time-dependent covariate predicts mortality in older men and women and to compare these different approaches. Subjects consisted of 110 male and 208 female (n=318) residents in the city of Jyv?skyl?, central Finland, aged 75 years at the baseline in 1989. The follow-up data was gathered in 1994 and mortality was followed for 10 years. Results showed that poor SRH was strongly associated with higher mortality risk in women in all models. In men, the association was found only in time-dependent and 5 year follow-up models and these associations were explained by baseline health status. To conclude, our analyses showed that there are gender differences in association between SRH and mortality and that the use of time-dependent covariate in a Cox regression model enables advantage to be taken of all the information in a longitudinal study design.     

Serum androgens and risk of atrial fibrillation in older men: The Cardiovascular Health Study

Background

Decline in serum androgens is common among older men and has been associated with cardiovascular disease, although its role in risk of atrial fibrillation (AF) has not been well defined.

Hypothesis

Low serum androgens are associated with an increased risk of AF.

Methods

We examined the prospective associations between testosterone, its more active metabolite dihydrotestosterone (DHT), and sex hormone–binding globulin (SHBG) with risk of AF among 1019 otherwise healthy men with average age 76.3 ±4.9 years in the Cardiovascular Health Study.

Results

After median follow‐up of 9.5 years, 304 (30%) men developed AF. We detected a nonlinear association with risk of incident AF in both free and total DHT, in which subjects with the lowest levels had a higher risk of incident AF. After adjustment for demographics, clinical risk factors, left atrial diameter, and serum NT‐proBNP levels, men with free DHT <0.16 ng/dL were at increased risk compared with men with higher levels (hazard ratio: 1.48, 95% confidence interval: 1.01–2.17, P <0.05). Sensitivity analyses confirmed that the increased risk was not cutpoint‐specific, with a significant association noted up to cutpoints <~0.2 ng/dL. We also detected a complex nonlinear association between SHBG and incident AF, in which subjects in the middle quintile (52.9–65.3 nmol/L) had increased risk.

Conclusions

Among older men, low free DHT is associated with an increased risk of incident AF. Further studies are needed to explore mechanisms for this association.     

Systemic inflammation (Interleukin 6) predicts all-cause mortality in men: results from a 9-year follow-up of the MEMO Study

This study aimed to investigate the association of biomarkers among circulating pro-inflammatory cytokines with all-cause mortality in elderly community dwellings of the MEMO study, Germany. All-cause mortality (cancer, cardiovascular diseases (CVD), and other causes of death) was assessed in a general population sample (N = 385) of the elderly (age 65–83 years) 9 years after baseline assessment in 1998. As markers of inflammation, a variety of cytokines (IL-1beta, IL-4sR, IL-6, IL-8, IL-10, IL-12, TNF-alpha) were assessed in serum. Cox proportional Hazard model was used to estimate the association of cytokines with all-cause mortality over 9 years. In total, 110 deaths had occurred during follow-up (cancer N = 36; CVD N = 56; other = 18). Deaths were more frequent in male (N = 76, 37.4%) as compared to females (N = 40, 21.9%; p = 0.001). Among individual cytokines, IL-1 beta, IL-6, IL-8, IL-10, and TNF-alpha were associated with all-cause mortality, of which IL-6, IL-8, and IL-10 remained significant after adjusting for confounders. When the upper tertiles of these cytokines were compared to the lower tertiles, only IL-6 was consistently related to all-cause mortality independently of the level of adjustment and showing a dose–response relationship between IL-6 tertiles and risk of death. This effect originated in the male population. The study shows that IL-6 is a powerful predictor of all-cause mortality in male elderly community dwellings. Higher levels of IL-6 may reflect a chronic low-level systemic inflammation prospectively increasing the risk of death in the elderly.     

Impaired glucose tolerance predicts all-cause mortality among older men at high risk for cardiovascular disease in China

AimsTo investigate the potential association between impaired glucose tolerance (IGT) and all-cause mortality among older men at high risk for cardiovascular disease (CVD) in China.MethodsIn this prospective observational study, 460 older men aged ≥60 years were determined to have either IGT or normal glucose tolerance (NGT) based on an oral glucose tolerance test conducted between May 2005 and May 2007. IGT and NGT were diagnosed according to the 1999 WHO diagnostic criteria. All subjects were followed until March 2017. The primary outcome studied was all-cause mortality. Multivariate Cox models were used to estimate relative risk for all-cause mortality.ResultsDuring a mean follow-up of 11.2 years, forty-three (21.4%) subjects in the IGT group and twenty-nine (11.2%) subjects in the NGT group died (HR 2.05, 95% CI 1.28–3.28, P = 0.003). Multivariate Cox proportional-hazards analysis demonstated that IGT was significantly associated with increased risk for all-cause mortality, composite cardiovascular outcome, nonfatal stroke and heart failure after adjusting for potential confounding factors. Logistic regression analysis showed that IGT at baseline (P < 0.05) rather than incident type 2 diabetes was a risk factor of all-cause mortality.ConclusionsIGT was significantly associated with all-cause mortality in older Chinese men at high risk for CVD.     

In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health in Men Study

OBJECTIVE: An age-related decline in serum total and free testosterone concentration may contribute to ill health in men, but limited data are available for men > 70 years of age. We sought to determine the distribution and associations of reduced testosterone concentrations in older men. DESIGN: The Health in Men Study is a community-representative prospective cohort investigation of 4263 men aged > or = 70 years. Cross-sectional hormone data from 3645 men were analysed. METHODS: Early morning sera were assayed for total testosterone, sex hormone binding globulin (SHBG) and LH. Free testosterone was calculated using the Vermeulen method. RESULTS: Mean (+/- s.d.) serum total testosterone was 15.4 +/- 5.6 nmol/l (444 +/- 162 ng/dl), SHBG 42.4 +/- 16.7 nmol/l and free testosterone 278 +/- 96 pmol/l (8.01 +/- 2.78 ng/dl). Total testosterone correlated with SHBG (Spearman's r = 0.6, P < 0.0001). LH and SHBG increased with age (r = 0.2, P < 0.0001 for both). Instead of declining, total testosterone increased marginally (r = 0.04, P = 0.007) whilst free testosterone declined with age (r = -0.1, P < 0.0001). Free testosterone was inversely correlated with LH (r = -0.1, P < 0.0001). In multivariate analyses, increasing age, body mass index (BMI) and LH were associated with lower free testosterone. CONCLUSIONS: In men aged 70-89 years, modulation of androgen action may occur via an age-related increase in SHBG and reduction in free testosterone without a decline in total testosterone concentration. Increasing age, BMI and LH are independently associated with lower free testosterone. Further investigation would be required to assess the clinical consequences of low serum free testosterone, particularly in older men in whom total testosterone may be preserved.     

Association between depression and mortality in older adults: the Cardiovascular Health Study

BACKGROUND: Studies of the association between depressive symptoms and mortality in elderly populations have yielded contradictory findings. To address these discrepancies, we test this association using the most extensive array of sociodemographic and physical health control variables ever studied, to our knowledge, in a large population-based sample of elderly individuals. OBJECTIVE: To examine the relation between baseline depressive symptoms and 6-year all-cause mortality in older persons, systematically controlling for sociodemographic factors, clinical disease, subclinical disease, and health risk factors. METHODS: A total of 5201 men and women aged 65 years and older from 4 US communities participated in the study. Depressive symptoms and 4 categories of covariates were assessed at baseline. The primary outcome measure was 6-year mortality. RESULTS: Of the 5201 participants, 984 (18.9%) died within 6 years. High baseline depressive symptoms were associated with a higher mortality rate (23.9%) than low baseline depression scores (17.7%) (unadjusted relative risk [RR], 1.41; 95% confidence interval [CI], 1.22-1.63). Depression was also an independent predictor of mortality when controlling for sociodemographic factors (RR, 1.43; 95% CI, 1.23-1.66), prevalent clinical disease (RR, 1.25; 95% CI, 1.07-1.45), subclinical disease indicators (RR, 1.35; 95% CI, 1.15-1.58), or biological or behavioral risk factors (RR, 1.42; 95% CI, 1.22-1.65). When the best predictors from all 4 classes of variables were included as covariates, high depressive symptoms remained an independent predictor of mortality (RR, 1.24; 95% CI, 1.06-1.46). CONCLUSIONS: High levels of depressive symptoms are an independent risk factor for mortality in community-residing older adults. Motivational depletion may be a key underlying mechanism for the depression-mortality effect.