Higher serum free testosterone is associated with better cognitive function in older men, while total testosterone is not. The Health In Men Study

Objective To determine the relationship of total and free serum testosterone to cognitive performance in older men. Design Cross‐sectional study of a population‐based sample. Participants A total of 2932 men aged 70–89 years. Measurements Cognitive function was assessed using the Standardized Mini‐Mental State Examination (SMMSE). Early morning sera were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using the Vermeulen method. Results There were weak positive correlations between SMMSE score and serum free testosterone (Spearman's rho = 0·06, P = 0·001) and total testosterone (r = 0·04, P = 0·027), and a weak negative correlation with LH (r = ?0·07, P < 0·001). Men with SMMSE scores in the top quintile had higher serum free testosterone compared with those in the lowest quintile [median (interquartile range, IQR): 278 (228–335) vs. 262 (212–320) pmol/l, P = 0·003], but similar total testosterone [15·2 (11·9–18·8) vs. 14·8 (11·6–18·3) nmol/l, P = 0·118]. Increasing age, non‐English‐speaking background, lower educational attainment, presence of clinically significant depressive symptoms, and cardiovascular morbidity were associated with the lowest cognitive performance quintile. After their effects were taken into account in a multivariate analysis, serum free testosterone ≥ 210 pmol/l was associated with reduced likelihood of poor cognitive performance on the SMMSE [odds ratio (OR) 0·71, 95% confidence interval (CI) 0·52–0·97]. Conclusions In community‐dwelling older men, serum free testosterone ≥ 210 pmol/l is associated with better cognitive performance. In this context, calculated free testosterone seems to be a more informative measure of androgen status than total testosterone. Studies examining the contribution of androgens to age‐related cognitive decline should incorporate an assessment of free testosterone concentration.     

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.     

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.     

70岁以上心房颤动患者导管射频消融治疗临床分析

目的 分析70岁以上心房如动(房颤)患者导管射频消融治疗成功率及术后复发危险因素.方技,选择导管射频消融的70岁以上房颤患者107例,收集患者临床和电生理资料,采用Cox比例风险回归模型分析房颤消融术后复发危险因素.结果 107例患者中,阵发性房颤89例.持续性房颤18例.平均随访(25.2±11.5)个月,单次消融成...     

Complete arterial revascularisation in patients older than 70 years.

BACKGROUND: Coronary artery bypass grafting (CABG) using left internal thoracic artery and vein grafts is standard in patients of advanced age. A number of these patients, however, present without suitable vein grafting material and thus require the use of arterial conduits. In order to investigate the safety and efficacy of complete arterial revascularisation, we have compared the perioperative results of patients older than 70 years with conventional CABG and complete arterial revascularisation. PATIENTS AND METHODS: Group I (n = 172) with conventional CABG in 1999 was compared with 152 patients (group II) with complete arterial CABG between 1996 and July 2000. There were no significant differences regarding age, gender, left ventricular ejection fraction or incidence of three-vessel disease or left main stenosis. The proportion of reoperations was significantly higher in group II (16 %) vs. group I (4 %). RESULTS: A mean of 3.7 +/- 0.7 anastomoses (I) versus 4.0 +/- 0.9 (II) were performed per patient (p = n. s.). Mean operating time (I: 210 +/- 46 min; II: 194 +/- 46 min) and bypass time (I: 87 +/- 25 min; II: 78 +/- 29 min) were significantly lower in group II. Ischemic time (I: 46 +/- 22 min; II: 49 +/- 21 min) was not significantly different. The incidence of sternal dehiscence was 2.9 % (I: n = 5) vs. 1.3 % (II: n = 2). Hospital mortality was 4.6 % in group I vs. 3.9 % (II). CONCLUSION: Complete arterial revascularisation is a safe option in patients aged over 70. It remains to be shown whether it may also have advantage in the long term.     

Development of stress reactivity in white-crowned sparrow nestlings: total corticosterone response increases with age, while free corticosterone response remains low

Activation of the adrenocortical response to stress during development can have fundamental consequences over the lifetime of the organism; as such, many organisms are less responsive to stress during critical developmental periods. In this study, we evaluated stress reactivity in nestling white-crowned sparrows, examining corticosterone and binding globulin levels in response to both restraint stress and ACTH challenge. Restraint stress induced a significant corticosterone response in both 4 to 6- and 7 to 9-day-old nestlings, but not in the youngest group (1-3 days); this non-significant increase in corticosterone in the youngest birds resembles the mammalian hyporesponsive period, wherein young animals are resistant to most stressors. Binding globulin levels appear to extend this period of low reactivity: when free corticosterone levels were calculated, only the oldest age group (7-9 day) showed a significant response to restraint. ACTH challenge data revealed that all ages of white-crowned sparrow nestlings responded to exogenous ACTH treatment with significant elevation of corticosterone, although early-stage nestlings did not reach adult levels of response.     

Trimetazidine in pectoris patients older than 65 years with stable angina

AIM: To study efficacy of trimetazidine including action on quality of life in patients over 65 years of age with stable angina pectoris. MATERIAL: Seventy two patients (75% men, age 65-80 years) with stable class II-III angina not completely controlled by baseline conventional combined antianginal therapy (nitrates, beta-blockers, and calcium antagonists). METHODS: Trimetazidine (60 mg/day) was added to baseline therapy for 12 weeks. Clinical evaluation before and after trimetazidine included registration of symptoms, analysis of parameters of treadmill exercise tests (Bruce protocol) including characteristics of post test recovery and assessment of quality of life (Seattle Angina Questionnaire). RESULTS: Sixty nine patients concluded the protocol. The use of trimetazidine was associated with significant (p<0.0001) improvement of quality of life, significant prolongation of exercise time before 1 mm ST depression (p<0.0005), exercise time before appearance of angina (p<0.0001), time before angina cessation after end of exercise (p<0.01), significant reduction of number of anginal attacks (p<0.01), and diminishment of consumption of short acting nitrates (p<0.01). CONCLUSION: Addition of trimetazidine to conventional antianginal therapy in elderly patients was associated with improved quality of life, increased exercise tolerance and decreased clinical signs of stable angina.     

Determinants of serum total and free testosterone levels in women over the age of 65 years

CONTEXT: Little is known about testosterone (T) levels and their determinants in women of late postmenopausal age. OBJECTIVE: We describe levels of total and free T and selected factors that influence these levels in a random sample of older women. DESIGN: Levels of serum total T and free T by microdialysis were measured using ultrasensitive assays in 347 community-dwelling women aged 65-98 yr enrolled in the Cardiovascular Health Study. Cross-sectional analyses were performed to define factors associated with total and free T levels. RESULTS: In adjusted models: 1) total T levels declined with age until 80, whereas free T levels did not vary by age; 2) women with bilateral oophorectomy had 23% lower total T and 16% lower free T levels than those with at least one intact ovary; 3) oral estrogen users had total and free T levels that were 47% lower than never users; 4) obese women had 47% higher total T and 20% higher free T levels, and overweight women had 24% higher total T and 14% higher free T levels, than normal weight women; and 5) free T levels were 51% higher in black women. Corticosteroid users had 75% lower total T and 43% lower free T levels than nonusers. CONCLUSIONS: Bilateral oophorectomy, estrogen use, corticosteroid use, and low body mass index are independent risk factors for lower T levels in women aged 65 yr and over. Although highly prevalent in women of this age, the physiological significance of low T levels in late postmenopausal women requires further investigation.     

Migration is associated with lower total, but not free testosterone levels in South Asian men

OBJECTIVE: Serum testosterone measurement is an integral part of the endocrine assessment of men. Little is known about its variation in relation to migration. We examined within a South Asian group the effect of migration to the UK on androgen levels. DESIGN: Circulating testosterone and SHBG concentrations were measured in 97 Gujarati men resident in India and in 79 men from the same villages of origin living in Birmingham, UK. Free testosterone was calculated by Vermeulen's method. Insulin sensitivity (HOMA-S) was determined from paired fasting plasma intact insulin and glucose values. RESULTS: Circulating testosterone was significantly lower in UK Gujarati men (17.2 nmol/l [15.7-18.7]) vs. Indian Gujarati men (21.7 [20.0-23.5]) (P = 0.0002) (age-adjusted median [95% CI]). There was no difference by migration status in circulating free testosterone. Sex hormone binding globulin (SHBG) levels were lower in UK migrants (16.8 nmol/l [15.5-18.1]) than in nonmigrants (21.9 nmol/l [20.5-23.3]) (P < 0.0001). Testosterone level correlated positively with insulin sensitivity (HOMA-S) (rho 0.16, P = 0.04). In multivariate analysis, total testosterone was independently and positively associated with logSHBG (normalized beta (beta) = 0.29, P = 0.002) and independently and negatively with waist circumference (beta = -0.19, P = 0.04), in a model also including height, age, migration status, leptin and fasting insulin. CONCLUSION: Lower circulating testosterone in UK Gujarati men and its association with markers of insulin sensitivity suggest a profound influence of body composition change with migration on testosterone levels. The lower SHBG in this group restores parity in free testosterone. Account should be taken of SHBG in interpreting testosterone levels in men, as well as in women.     

Relation of total and free testosterone and sex hormone-binding globulin with cardiovascular risk factors in men aged 24-45 years. The Cardiovascular Risk in Young Finns Study

BackgroundTotal and free testosterone decrease gradually in men with advancing age but it is not completely known how lower levels of testosterone are related with various cardiovascular risk factors. We studied the levels of total testosterone, calculated free testosterone and sex hormone-binding globulin (SHBG), and their relations with cardiovascular risk factors in young Finnish men.MethodsThe study cohort consisted of 24–45-year-old men participating the Cardiovascular Risk in Young Finns Study in the follow-up surveys performed in 2001 (N = 1024) and 2007 (N = 991). Levels of total testosterone, SHBG, lipids, glucose, insulin, blood pressure and anthropometric factors were measured and free testosterone was calculated.ResultsIn multivariable analyses adjusted for age, body mass index and life-style factors (alcohol consumption, smoking and physical activity), total and calculated free testosterone were inversely correlated with triglycerides (both P < 0.0001), insulin (P = 0.0004 and P = 0.01), systolic blood pressure (P = 0.007 and P = 0.01), and directly with high-density lipoprotein (HDL) cholesterol (P < 0.0001 and P = 0.003). SHBG was inversely correlated with triglycerides and insulin, and directly with HDL-cholesterol (all P < 0.001). In longitudinal analyses, lower levels of testosterone and SHBG were associated with higher levels of triglycerides and insulin six years later (all P < 0.01). Baseline level of SHBG was directly associated with HDL-cholesterol (P < 0.0001).ConclusionIn young and middle-aged men, higher levels of testosterone and SHBG are associated with favourable cardiovascular risk profile characterized by lower levels of triglycerides, insulin and systolic blood pressure, and higher levels of HDL-cholesterol.     

Effects of exercise training on cardiorespiratory function in men and women older than 60 years of age

This study reports the physiologic effects of up to 14 months of aerobic exercise in 101 older (greater than 60 years) men and women. After an extensive baseline physiologic assessment (Time 1), in which aerobic capacity and blood lipids were measured, subjects were randomized to an aerobic exercise condition (cycle ergometry, 3 times per week for 1 hour), nonaerobic yoga (2 times per week for 1 hour), or a waiting list nonexercise control group for 4 months, and then underwent a second (Time 2) assessment. At the completion of the second assessment, all remaining subjects completed 4 months of aerobic exercise and were reevaluated (Time 3). Subjects were given the option of participating in 6 additional months of supervised aerobic exercise, and all available subjects completed a fourth assessment (Time 4) 14 months after their initial baseline evaluation. Results indicated that subjects generally exhibited a 10 to 15% improvement in peak oxygen consumption after 4 months of aerobic exercise training, and a 1 to 6% improvement in aerobic power with additional aerobic exercise training. On the other hand, subjects, especially men, continued to have improvements in submaximal exercise performance (i.e., anaerobic threshold). In addition, aerobic exercise was associated with an improved lipid profile; subjects participating in aerobic exercise for up to 14 months exhibited increased levels of high-density lipoprotein cholesterol. Maintenance of regular aerobic exercise for an extended time interval is associated with greater cardiovascular benefits among older adults than has been reported previously.     

Perception of worsening health predicts mortality in older men: The Health in Men Study (HIMS)

The main purpose of this study was to determine the most robust predictor of mortality among global self-rated health (SRH), time-comparative SRH or a combination of both measures. We also sought to determine factors associated with global SRH and time-comparative SRH measures. A prospective cohort study of 5583 community-dwelling older men aged 70 years or over living in Perth, Western Australia, was used. Older age, depressive symptoms, low social support, sensory impairment, presence of pain, and high Charlson score index were associated with both SRH measures. Global and time-comparative SRH were independent predictors of all-cause mortality (adjusted hazard ratio, HR=1.24 vs. 1.41 respectively); and the risk of death was almost doubled in those with both negative global SRH and perception of worsening health over the preceding 12 months (adjusted HR 1.98, 95%CI 1.58-2.47). In this group, the rate of death was especially high during the initial four years of follow up. We concluded that the two measures of SRH are likely to reflect the same domains of health, and the simultaneous use of both measures is the best predictor of short to medium term mortality.     

Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age

PURPOSE: Because the effects of androgen replacement on lipoprotein levels are uncertain, we sought to determine the effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in elderly men. SUBJECTS AND METHODS: One hundred and eight healthy men more than 65 years of age who had serum testosterone concentrations >1 SD below the mean for young men were randomly assigned to receive either testosterone (54 men; 6 mg/day) or placebo (54 men) transdermally in a double-blind fashion for 36 months. Serum concentrations of lipids and apolipoproteins were measured, and cardiovascular events recorded. RESULTS: Serum total cholesterol concentrations decreased in both the testosterone-treated men and placebo-treated men, but the 3-year mean (+/- SD) decreases in the two groups (testosterone treated, -17 +/- 29 mg/dL; placebo treated, -12 +/- 38 mg/dL) were not significantly different from each other (P = 0.4). Similarly, serum low-density lipoprotein (LDL) cholesterol levels decreased in both treatment groups, but the decreases in the two groups (testosterone treated, -16 +/- 24 mg/dL; placebo treated, -16 +/- 33 mg/dL) were similar (P = 1.0). Levels of high-density lipoprotein (HDL) cholesterol, triglycerides, and apolipoproteins A-I and B did not change. Lipoprotein(a) levels increased in both groups by similar amounts (testosterone treated, 3 +/- 9 mg/dL; placebo treated, 4 +/- 6 mg/dL; P = 1.0). The number of cardiovascular events was small and did not differ significantly between the testosterone-treated men (9 events) and the placebo-treated men (5 events) during the 3-year study (relative risk = 1.8; 95% confidence interval: 0.7 to 5.0). CONCLUSIONS: As compared with placebo, transdermal testosterone treatment of healthy elderly men for 3 years did not affect any of the lipid or apolipoprotein parameters that we measured. The effect of testosterone treatment on cardiovascular events was unclear, because the number of events was small.     

Early right atrial pacing after myocardial infarction. II. Results in 77 patients with predischarge angina pectoris, congestive heart failure, or age older than 70 years

Seventy-seven consecutive postinfarction patients who had either predischarge angina pectoris or congestive heart failure, or who were older than 70 years of age, underwent right atrial (RA) pacing before hospital discharge. In 60% of these patients, ischemic changes developed during RA pacing; this high yield of positive response indicates advanced coronary arterial disease. During a mean follow-up of 15 months, these patients had a high mortality rate (18%) and a reinfarction rate of 9%. RA pacing separated this a priori high-risk group into lower- and higher-risk subsets. Of the 46 patients with a positive RA pacing response, 6 had reinfarction, while none of the 31 patients with a negative RA pacing response had reinfarction (p = 0.04); 10 of the 14 cardiac deaths were among the patients who had positive RA pacing responses at discharge (p = not significant). Thus, of the 20 major cardiac events, 16 occurred among those with positive RA pacing responses (p less than 0.05). Predischarge clinical symptoms, however, were not good predictors of subsequent major cardiac events. We conclude that RA pacing can be safely performed even in high-risk and elderly patients and a positive response can identify those who have a poorer prognosis. Therefore, for postinfarction patients who, according to the prevailing criteria, are excluded from treadmill testing, we advocate the use of RA pacing.