Long-Term Associations between Human Cytomegalovirus Antibody Levels with All-Cause Mortality and Cardiovascular Outcomes in an Australian Community-Based Cohort.

Human cytomegalovirus (HCMV) infection has been shown to increase the risk of cardiovascular events and all-cause death among individuals with clinically apparent cardiovascular disease (CVD). Whether this association exists in individuals with no history of CVD remains unclear. Serum levels of HCMV IgG antibody were measured using an ELISA in 2050 participants aged 40-80 years from the 1994/1995 Busselton Health Survey who did not have CVD at baseline. Outcomes were all-cause death, cardiovascular death, acute coronary syndrome (ACS) and major adverse coronary and cerebrovascular events (MACCE, composite of all-cause death, ACS, stroke and coronary artery revascularisation procedures). Cox proportional hazards regression analysis was used to investigate HCMV antibody levels as a predictor of death and cardiovascular outcomes during follow-up periods of 5, 10 and 20 years. At baseline, participants had a mean age of 56 years and 57% were female. During the 20-year follow-up, there were 448 (21.9%) deaths (including 152 from CVD), 139 (6.8%) participants had ACS and 575 (28.0%) had MACCE. In the fully adjusted model, levels of HCMV antibody at 20 years was associated with all-cause death (HR 1.04; 95% CI 1.00, 1.07, p = 0.037) but not with CVD death, ACS or MACCE. Levels of HCMV antibody are associated with all-cause death but not with cardiovascular outcomes in adults without pre-existing CVD.

Meeting the Australian 24-Hour Movement Guidelines for the Early Years is associated with better social-emotional development in preschool boys.

24-hour Movement Guidelines for the Early Years promote that achieving all three-movement behaviour (sleep, sedentary behaviour and physical activity) recommendations is important for child health and development. We examined the association between meeting all, none and combinations of the Australian 24-Hour Movement Guidelines for the Early Years and social-emotional development in 1363 preschool (2-5 years) boys (52%) and girls. The PLAYCE study (Perth, Western Australia) parent survey collected data on children's social-emotional development (Strengths & Difficulties Questionnaire), screen time, sleep and socio-demographic factors. Physical activity was measured using seven-day accelerometry. Only 8% of preschoolers met all three guidelines (5% met none). A higher proportion of boys than girls met physical activity-related guideline combinations (physical activity only, physical activity plus screen, physical activity plus sleep, all), while more girls than boys met sleep only guidelines (all p < 0.05). In boys, meeting all guidelines, compared with none, was associated with a lower total difficulties score (adjusted difference in means -1.90; 95%CI: -3.88, -0.10). Meeting the screen only guideline or the screen plus sleep guidelines, compared with none, were associated with lower total difficulties, conduct problems and hyperactivity scores in boys (all p < 0.05). Meeting the physical activity plus sleep guidelines, compared with none, were associated with lower total difficulties and conduct problems scores in boys (all p < 0.05). No significant associations were found for girls. These findings highlight the positive impact for boys social-emotional development in meeting all guidelines. Future guideline development should consider dose-response evidence to identify guideline thresholds for specific health and developmental outcomes for boys and girls.

Alcohol Consumption and Cardiovascular Outcomes in Patients With Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study.

Low-level alcohol consumption is associated with reduced cardiovascular disease (CVD) in the general population. It is unclear whether this association is seen in patients with nonalcoholic fatty liver disease (NAFLD) who have an increased risk of CVD. We examined the association between alcohol consumption and CVD-related outcomes in subjects with NAFLD from a general population cohort. Subjects participating in the 1994-1995 Busselton Health survey underwent clinical and biochemical assessment. NAFLD was identified using the Fatty Liver Index of >60, and alcohol consumption quantified using a validated questionnaire. CVD hospitalizations and death during the ensuing 20 years were ascertained using the Western Australian data linkage system. A total of 659 of 4,843 patients were diagnosed with NAFLD. The average standard drinks per week was 8.0 for men and 4.0 for women. Men consuming 8-21 drinks per week had a 38% (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.43-0.90) lower risk of CVD hospitalization as compared with men consuming 1-7 drinks per week. With both men and women combined, consumption of 8-21 drinks per week was associated with a 32% (HR 0.68, 95% CI 0.49-0.93) reduction in CVD hospitalization in minimally adjusted and 29% (HR 0.71, 95% CI 0.51-0.99) in fully adjusted models. No protective association was observed with binge drinking. There was no association between alcohol consumption and CVD death. Conclusion: Low to moderate alcohol consumption is associated with fewer CVD hospitalizations but not CVD death in subjects with NAFLD.

Childhood asthma and cardiovascular morbidity and mortality in adulthood: The Busselton Health Study.

BACKGROUND: Long-term childhood asthma studies that investigate adult outcomes other than respiratory morbidity are lacking. This study examines the associations of childhood asthma and the occurrence of cardiovascular disease (CVD) events and mortality in adulthood. METHODS: A cohort of 4430 school children (aged 17 years) who attended the Busselton Health Study between 1967 and 1983 were analyzed. Self-reported history of doctor-diagnosed asthma was determined based on the questionnaire. Subsequent CVD events (hospital admissions or death) up to 2014 were identified using the Western Australia Data Linkage System. Cox regression models were used to investigate the impact of childhood asthma on CVD events and mortality in adulthood. A subgroup of 2153 participants who re-attended a survey in young adulthood was also analyzed. RESULTS: A total of 462 (10%) of the cohort had childhood asthma. During follow-up, 867 participants experienced a CVD event and 22 participants died from CVD. Childhood asthma was not associated with the risk of CVD events in adulthood (HR, 1.12; 95% CI: 0.91-1.39; p = .2833) and this persisted after adjustment for confounders. Childhood asthma was not associated with coronary heart disease events (HR, 0.72; 95% CI: 0.40-1.30; p = .2761), heart failure events (HR, 0.55; 95% CI: 0.07-4.13; p = .5604) or CVD mortality (HR, 0.91; 95% CI: 0.21-3.89; p = .8987) in adulthood. CONCLUSION: Childhood asthma is not associated with the risk of CVD events and mortality in adulthood.

U-Shaped Relationship of Leukocyte Telomere Length With All-Cause and Cancer-Related Mortality in Older Men.

BACKGROUND: Telomeres are essential DNA-protein complexes whose attrition results in cellular dysfunction and senescence. Leukocyte telomere length (LTL) correlates with tissue telomere length, representing a biomarker for biological age. However, its predictive value for mortality risk, and for cardiovascular versus cancer deaths, in older adults remains uncertain. METHOD: We studied 3608 community-dwelling men aged 77.0 ± 3.6 years. Leukocyte telomere length was measured using multiplex quantitative PCR, expressed as amount of telomeric DNA relative to single-copy control gene (T/S ratio). Deaths from any cause, cardiovascular disease (CVD), and cancer were ascertained using data linkage. Curve fitting used restricted cubic splines and Cox regression analyses adjusted for age, cardiometabolic risk factors, and prevalent disease. RESULTS: There was a U-shaped association of LTL with all-cause mortality. Men with T/S ratio in the middle quartiles had lower mortality (quartiles, Q2 vs Q1, hazard ratio [HR] = 0.86, 95% confidence interval [CI] 0.77-0.97, p = .012; Q3 vs Q1 HR = 0.88, CI 0.79-0.99, p = .032). There was no association of LTL with CVD mortality. There was a U-shaped association of LTL with cancer mortality. Men with LTL in the middle quartiles had lower risk of cancer death (Q2 vs Q1, HR = 0.73, CI 0.59-0.90, p = .004; Q3 vs Q1, HR = 0.75, CI 0.61-0.92, p = .007). CONCLUSIONS: In older men, both shorter and longer LTL are associated with all-cause mortality. A similar U-shaped association was seen with cancer deaths, with no association found for cardiovascular deaths. Further research is warranted to explore the prognostic utility of LTL in ageing.

Childhood asthma increases respiratory morbidity, but not all-cause mortality in adulthood: The Busselton Health Study.

BACKGROUND: Long-term childhood asthma studies that investigate adult outcomes other than lung function are lacking. This study examines the associations of childhood asthma and the occurrence of respiratory events and all-cause mortality in adulthood. METHODS: A cohort of 4430 school children (aged to 17 years) who attended the Busselton Health Study between 1967 and 1983 were analysed. Self-reported history of asthma was determined using questionnaires. Participants were followed until 2014 for respiratory disease-related events (hospital admissions or death) and all-cause mortality using the Western Australia Data Linkage System. Cox regression models were used to investigate the impact of childhood asthma on respiratory events and all-cause mortality in adulthood. A subgroup of 2153 participants who re-attended a survey in young adulthood was also analysed. RESULTS: A total of 462 (10%) of the cohort had childhood asthma. During follow-up 791 participants experienced a respiratory event and 140 participants died. Childhood asthma was associated with an increased risk of respiratory events in adulthood (unadjusted HR 1.84, 95% CI 1.52 to 2.23; P < 0.0001). The result remained significant after adjusting for adult-onset asthma, FEV1, body mass index, smoking, dusty job, hay fever, and respiratory symptoms (adjusted HR 1.68, 95% CI 1.07 to 2.64; P = 0.0247). Childhood asthma was not associated with all-cause mortality in adulthood (unadjusted HR 1.08, 95% CI 0.63 to 1.84; P = 0.7821). CONCLUSION: Childhood asthma is associated with increased risk of respiratory disease-related hospital admissions and death but not all-cause mortality in adulthood.

Over the limit? Testing non-linear associations between alcohol outlets and young adults' alcohol consumption.

INTRODUCTION AND AIMS: By specifying a threshold at which the number of liquor licences has the most impact on local populations, authorities can work to restrict licence approvals and help prevent alcohol-related harm. DESIGN AND METHODS: Raine Study Generation 2 participants reported their alcohol intake at 22 years (n = 843) and liquor licences within 1600 m of participants' homes were mapped. Analyses examined associations between licences (all licences, on-premise licences, liquor stores) and alcohol intake (g ethanol per day). Two models were fitted: (i) forced a straight-line relationship; and (ii) allowed a curved relationship via restricted cubic splines. RESULTS: The straight-line and curved models showed significant relationships with all licences (P = 0.002 and P = 0.002 respectively) and on-premise licences (P = 0.006 and P = 0.01 respectively), but not liquor stores (P = 0.065 and P = 0.13 respectively). The straight-line model indicated that alcohol consumption increased, on average, by 0.15 g per day for each additional licence and 0.17 g per day for each additional on-premise licence. The curved model indicated that consumption increased by around 0.4 g per day for each additional licence from 0 to 10, but increases were negligible for additional licences beyond 10. The curved model provided a better overall fit to the data than the straight-line model (R2 9.52% vs. 9.18%), but the improvement in fit did not quite reach statistical significance (P = 0.08). The curvature was similar, but less pronounced for on-premise licences (R2 9.11% vs. 8.95%; P = 0.23). DISCUSSION AND CONCLUSIONS: Results suggest a possible saturation point at which additional licences have a smaller effect on the alcohol intake of 22-year-olds living in metropolitan Perth.

Childhood BMI and the occurrence of respiratory disease-related hospital admissions or death in adulthood: the Busselton Health Study.

PURPOSE: Few studies have investigated the association of childhood obesity with respiratory disease-related outcomes in adulthood and findings are inconsistent. The aim of this study was to examine the associations of body mass index (BMI) in childhood with the occurrence of respiratory events in adulthood. METHODS: We analyzed a cohort of 4537 school-aged children who attended the Busselton Health Study. Height and weight were measured and generated BMI z-scores were categorized into four groups. Participants were followed for respiratory disease-related hospital admissions or death using the Western Australia Data Linkage System. The associations between childhood BMI and respiratory events in adulthood were investigated using Cox regression models. A subgroup of 2196 that reattended a survey in young adulthood was also analyzed. RESULTS: During the 122,781 person-years of follow-up, 810 participants experienced a respiratory event. Childhood BMI group was not associated with risk of respiratory event in adulthood (hazard ratio for BMI z ≥ 1 vs. < -1 = 0.90; 95% CI, 0.70-1.17; P = .295) and this persisted after adjustment for selected confounders in the subgroup (hazard ratio 0.80; 95% CI, 0.43-1.48; P = .476). CONCLUSIONS: Childhood BMI is not associated with risk of respiratory events in adulthood.

Associations of plasma IGF1, IGFBP3 and estradiol with leucocyte telomere length, a marker of biological age, in men.

OBJECTIVE: Effects of insulin-like growth factor 1 (IGF1) and its binding proteins (IGFBPs) on ageing, and their interaction with sex hormones, remain uncertain. We examined associations of plasma IGF1, IGFBP1, IGFBP3, estradiol and testosterone, with leucocyte telomere length (LTL), a marker of biological age, in 2999 community-dwelling men aged 70-84 years. METHODS: Plasma IGF1, IGFBP1 and IGFBP3 measured using immunoassay, sex hormones using mass spectrometry. LTL measured by PCR, expressed as ratio of telomeric to single-copy control gene DNA (T/S ratio). Linear regression models adjusted for age and cardio-metabolic risk factors, median splits defined low/high groups. RESULTS: Mean age was 76.7 ± 3.2 years. IGF1 and IGFBP3 showed age-adjusted correlations with LTL (coefficient 0.59, P = 0.001 and 0.45, P = 0.013 respectively), IGFBP1 did not. In multivariable-adjusted models IGF1 and IGFBP3 (but not IGFBP1) were associated with LTL (T/S ratio 0.015 higher per 1 s.d. increase in IGF1, P = 0.007, and 0.011 per 1 s.d. IGFBP3, P = 0.049). IGF1 and estradiol were independently associated with longer telomeres (T/S ratio 0.012 higher per 1 s.d. increase in estradiol, P = 0.027, when included in model with IGF1). Testosterone was not associated with LTL. Men with both high IGF1 (>133 µg/L) and high estradiol (>70 pmol/L) had longer LTL compared to men with lower values (multivariable-adjusted T/S ratio 1.20 vs 1.16, P = 0.018). CONCLUSIONS: Higher IGF1 and IGFBP3 are independently associated with longer telomeres in older men. Additive associations of higher IGF1 and higher estradiol with telomere length are present. Further studies are needed to determine whether these hormonal exposures cooperate to slow biological aging.

Lower serum 25-hydroxyvitamin D is associated with colorectal and breast cancer, but not overall cancer risk: a 20-year cohort study.

Studies of the relationship between circulating 25-hydroxyvitamin D (25(OH)D) and cancer risk have been inconsistent. We hypothesized that serum 25(OH)D was associated with total non-skin cancer incidence and mortality, and/or specifically with colorectal, lung, breast or prostate cancer in an Australian cohort. Serum 25(OH)D was measured in 3818 participants (2166 females) in the 1994/1995 Busselton Health Survey aged 25 to 84 years at baseline. Cancer mortality and events over 20 years follow-up were determined by data linkage. The mean serum 25(OH)D concentration was 60.6 ±â€¯18.0 nmol/L, with 28%, 54% and 18% of participants in the lower (<50 nmol/L), middle (50-75 nmol/L) and higher (≥75 nmol/L) vitamin D status groups, respectively. During follow-up (excluding the first 2 years), 212 participants died from non-skin cancer and 634, 110 and 44 participants had non-skin, colorectal and lung cancer events, respectively; 113 women had breast cancer and 122 men had prostate cancer events. For colorectal cancer, lower circulating 25(OH)D was associated with significantly higher risk compared with the middle group (covariate-adjusted HR 1.62, 95% CI 1.04, 2.53). For breast cancer, women with a higher 25(OH)D level had lower risk than women in the middle group (HR 0.38, 95% CI 0.16, 0.89) and the lower group (HR 0.37, 95% CI 0.15, 0.89). Serum 25(OH)D was not associated with overall cancer death or event, or with lung or prostate cancer. In this community-based cohort, lower 25(OH)D levels were associated with increased risk of colorectal and breast cancer, but not overall cancer risk.

Healthcare-seeking behaviour and utilization of treatment in a community-based screening study for obstructive sleep apnoea in Busselton, Western Australia.

OBJECTIVES: To investigate whether in-home screening for obstructive sleep apnoea (OSA) promotes healthcare-seeking or lifestyle modification behaviour. We also examined the uptake and adherence rates to different treatment options, the factors affecting adherence, and the impact of treatment on health-related quality of life. DESIGN: Follow-up survey of adults at high risk of OSA. SETTING: Community-based sample. PARTICIPANTS: Adults who completed an in-home sleep study in the 2005-07 or 2010-15 Busselton surveys of adults with apnoea-hypopnoea index (AHI) > 15 (n = 192). MEASUREMENTS: The follow-up questionnaire was administered in 2016 and assessed healthcare-seeking and lifestyle modification behaviour, treatment utilization and adherence, and health-related quality of life. RESULTS: Of the 159 that recalled receiving a result from their in-home sleep study, 65% (n = 103) sought help and/or made lifestyle changes, 49% (n = 78) discussed the results with their GP, 21% (n = 33) underwent a confirmatory study and 33% (n = 53) started treatment. The most common treatment used was continuous positive airway pressure (CPAP) (72%) and adherence rates were high (84%). Self-reported snoring, breathing pauses, daytime tiredness and AHI were identified as predictors of whether people displayed healthcare-seeking behaviour. CONCLUSIONS: This study provides promising evidence that in-home screening for OSA could contribute towards relieving the associated morbidity, especially if health promotion strategies including education are implemented.

Higher circulating androgens and higher physical activity levels are associated with less central adiposity and lower risk of cardiovascular death in older men.

OBJECTIVE: Low endogenous sex hormones and low physical activity (PA) levels have been associated with CVD risk. Whether these interact to influence CVD outcomes remains unclear. We assessed whether sex hormone concentrations and PA were additively associated with lower central adiposity and CVD risk. PATIENTS: 3351 community-dwelling men, mean age 77 years. MEASUREMENTS: Baseline testosterone (T), dihydrotestosterone (DHT) and oestradiol (E2) were assayed. Levels of PA were ascertained by questionnaire. Men were stratified using median splits into high hormone + high PA (H/H), high hormone + low PA (H/L); low hormone + high PA (L/H) and low hormone + low PA (L/L) groups. RESULTS: A total of 865 CVD events and 499 CVD deaths occurred during 10-year mean follow-up. Men with higher T, DHT or SHBG and higher PA had the lowest BMI, waist circumference and risk of metabolic syndrome. Men with higher T had the lowest risk of incident CVD events, irrespective of PA level. Men with higher T or DHT and higher PA had the lowest risk of dying from CVD (eg, hazard ratios for T/PA H/H 0.76 P = 0.031; H/L 0.85 P = 0.222; L/H 0.80 P = 0.075; L/L 1.00). CONCLUSION: Higher circulating androgens and higher PA were associated with less central adiposity at baseline and fewer CVD deaths during follow-up. These findings are consistent with a potential additive effect of androgens and PA on cardiometabolic outcomes in older men.

A 5α-reductase (SRD5A2) polymorphism is associated with serum testosterone and sex hormone-binding globulin in men, while aromatase (CYP19A1) polymorphisms are associated with oestradiol and luteinizing hormone reciprocally.

CONTEXT: Pituitary luteinizing hormone (LH) stimulates testicular production of testosterone (T) which is metabolized to dihydrotestosterone (DHT) by 5α-reductase and to oestradiol (E2) by aromatase. How the activity of population variants in these enzymes impacts on gonadal function is unclear. We examined whether polymorphisms in 5α-reductase (SRD5A2) and aromatase (CYP19A1) genes predict circulating sex hormone concentrations. DESIGN: Cross-sectional analysis of 1865 community-dwelling men aged 50.4 ± 16.8 years. MEASUREMENTS: Early morning sera assayed for T, DHT and E2 (mass spectrometry), and SHBG and LH (immunoassay). Two SRD5A2 and eleven CYP19A1 polymorphisms were analysed by PCR. Regression models were adjusted for age and cardiometabolic risk factors. RESULTS: SRD5A2 polymorphism rs9282858 GA vs. GG was associated with higher serum T (+1.5 nmol/L, P < 0.001) and higher SHBG (+3.3 nmol/L, P = 0.001). CYP19A1 polymorphisms were associated with higher serum E2 and lower LH in reciprocal fashion, from which the two-copy haplotype rs10046 = T/rs2899470 = G/rs11575899 = I/rs700518 = G/rs17703883 = T was associated with higher E2 (63.4 vs. 56.5 pmol/L, P = 0.001) and lower LH (3.9 vs. 4.5 IU/L, P = 0.001) compared to null copies. Conversely, rs10046 = C/rs2899470 = T/rs11575899 = D/rs700518 = A/rs17703883 = C was associated with lower E2 (51.8 vs. 62.0 pmol/L, P = 0.001) and higher LH (5.7 vs. 3.9 IU/L, P < 0.001). These haplotypes were associated primarily with differences in E2 in men <65 years and LH in men ≥65 years. CONCLUSIONS: A 5α-reductase polymorphism predicts circulating T and SHBG, while aromatase polymorphisms predict E2 and LH in reciprocal fashion. Age and aromatase polymorphisms interact to affect E2 and LH. How these functional polymorphisms impact on male reproductive and general health outcomes requires further study.

Cross-sectional associations of sex hormones with leucocyte telomere length, a marker of biological age, in a community-based cohort of older men.

CONTEXT: Telomeres protect chromosomes from damage, and shorter leucocyte telomere length (LTL) is a marker of advancing biological age. The association between testosterone (T) and its bioactive metabolites, dihydrotestosterone (DHT) and oestradiol (E2) with telomere length, particularly in older men, is uncertain. The study aimed to clarify associations of sex hormones with LTL in older men. PARTICIPANTS AND METHODS: We used cross-sectional data from 2913 men aged 76.7 ± 3.2 years with morning blood samples assayed for T, DHT, E2 (mass spectrometry), and sex hormone-binding globulin (SHBG, immunoassay), to correlate sex hormones with LTL measured using PCR and expressed as T/S ratio in multivariable linear regression models adjusted for age, cardiometabolic risk factors and cardiovascular disease history. RESULTS: Average difference per decade of age was T -0.46 nmol/L, DHT -0.11 nmol/L, E2 -7.5 pmol/L, SHBG +10.2 nmol/L and LTL (T/S ratio) -0.065. E2 correlated with T/S ratio (r = 0.038, P = 0.039) and SHBG was inversely correlated (r = -0.053, P = 0.004). After multivariable adjustment, E2 was associated with T/S ratio (per 1 SD increase E2: coefficient 0.011, P = 0.043), T and DHT were not associated. When E2 and SHBG were simultaneously included, E2 remained positively (coefficient 0.014, P = 0.014) and SHBG inversely (coefficient -0.013, P = 0.037) associated with T/S ratio. CONCLUSIONS: In older men, neither T nor DHT is associated with LTL while E2 is independently associated with LTL and SHBG is inversely associated, thus relating sex hormone exposure to lower biological age. Further research is needed to determine causality and clarify the role of sex hormones in male ageing.

A prospective cohort examination of haematological parameters in relation to cancer death and incidence: the Busselton Health Study.

BACKGROUND: Cancer risk is associated with serum iron levels. The aim of this study was to evaluate whether haematological parameters reflect serum iron levels and may also be associated with cancer risk. METHODS: We studied 1564 men and 1769 women who were enrolled in the Busselton Health Study, Western Australia. Haematological parameters evaluated included haemoglobin (Hb), mean cell volume (MCV), mean cell haemoglobin (MCH) and mean cell haemoglobin concentration (MCHC) and red cell distribution width (RCDW). Statistical analyses included t-tests for quantitative variables, chi-square tests for categorical variables and Cox proportional hazards regression modelling for cancer incidence and death. RESULTS: There was marginal evidence of an association between MCV (as a continuous variable) and non-skin cancer incidence in women (HR 1.15, 95% CI 1.013, 1.302; p = 0.030) but the hazard ratio was attenuated to non-significance after adjustment for serum ferritin (SF), iron and transferrin saturation (TS) (HR 1.11, 95% CI 0.972, 1.264; p = 0.126). There was strong evidence of an association between MCHC and prostate cancer incidence in men; the estimated hazard ratio for an increase of one SD (0.5) in MCHC was 1.27 (95% CI 1.064, 1.507; p = 0.008). These results remained significant after further adjustment for SF and iron; the estimated hazard ratio for an increase of one SD (0.5) in MCHC was 1.25 (p = 0.014, 95% CI 1.05 to 1.48). CONCLUSIONS: The MCHC and MCV were associated with cancer incidence in a Western Australian population, although only MCHC remained associated with prostate cancer after adjusting with serum iron and TS (circulating iron) and SF (storage iron). Haematological parameters are thus of limited utility in population profiling for future cancer risk.

Lower Circulating Androgens Are Associated with Overall Cancer Risk and Prostate Cancer Risk in Men Aged 25-84 Years from the Busselton Health Study.

Androgens, notably testosterone (T), have been implicated in development of several common cancers and prostate cancer; however, precise mechanisms remain unclear. This study assessed prospective associations of serum T, dihydrotestosterone (DHT) and estradiol (E2) with overall cancer (excluding skin cancer), prostate, colorectal and lung cancer risk in 1574 community-dwelling men aged 25-84 years. Sex hormones were assayed using mass spectrometry and men were followed for 20 years with outcomes ascertained using data linkage. Over 20 years, there were 289, 116, 48 and 22 men who developed any cancer, prostate cancer, colorectal cancer and lung cancer, respectively. Androgens in the lowest quartile were associated with an increased overall cancer risk (HR = 1.36, 95% CI 1.05-1.76, p = 0.020 for T; and HR = 1.30, 95% CI 1.00-1.69, p = 0.049 for DHT comparing the lowest vs other quartiles). T in the lowest quartile was associated with an increased risk of prostate cancer (HR = 1.53, 95% CI 1.02-2.29, p = 0.038 comparing the lowest vs other quartiles). The association between androgens and overall cancer risk remained similar after excluding prostate cancer outcomes; however, results were not significant. There were no associations of T, DHT or E2 with colorectal or lung cancer risk; however, LH in the highest quartile was associated with an increased risk of lung cancer (HR = 4.55, 95% CI 1.70-12.19, p = 0.003 for the highest vs other quartiles). Whether T is a biomarker of poor health in men with any cancer or prostate cancer requires further confirmation as does the nature and mechanism of the association of a high LH with future lung cancer.

High-sensitivity cardiac troponin I and risk of incident atrial fibrillation hospitalisation in an Australian community-based cohort: The Busselton health study.

OBJECTIVE: The identification of individuals at risk of atrial fibrillation (AF) remains a challenge. We investigated whether high-sensitive cardiac troponin I (hs-cTnI) is an independent predictor of incident atrial fibrillation (AF) hospitalisation in an Australian community-based cohort. METHODS: Serum hs-cTnI was measured in 1641 men and 2189 women in the Busselton Health Study 1994/1995 Cohort aged 25-84 years at baseline. Data on incident AF hospitalisation over 20 years follow-up were obtained by data linkage. RESULTS: Hs-cTnI was detectable (>1.2 ng/L) in 65.5% of participants (males 81.4%, females 53.6%) at baseline. There were 179 (10.9%) AF events in men and 208 (9.5%) in women. In the multivariable-adjusted model, hs-cTnI was a significant predictor of AF event with hazard ratio 1.21 (95% CI 1.11-1.32, P < 0.001) in the whole cohort, 1.17 (95% CI 1.01-1.35, P = 0.037) in men and 1.22 (95% CI 1.08-1.37, P = 0.001) in women for a doubling of baseline hs-cTnI. In women, a graded and significant increase in risk of AF was observed across hs-cTnI categories from ≥1.3 ng/L, whereas in men only the highest category (≥6.0 ng/L) had significantly increased risk compared with individuals with hs-cTnI ≤1.2 ng/L. Addition of categorical hs-cTnI to standard risk factors for AF improved risk estimation in females (C-statistic increment 0.006, P = 0.04) but not males (increment 0.005, P = 0.12) and net reclassification improvement was not significant in either sex. CONCLUSIONS: High-sensitive cTnI level is an independent predictor of incident AF hospitalisation in a community-based cohort but does not improve risk stratification.

Obstructive airway disease in 46-65-year-old people in Busselton, Western Australia, 1966-2015.

OBJECTIVE: To document the changing levels of tobacco smoking, respiratory symptoms, doctor-diagnosed asthma, and lung function in Busselton adults aged 46-65 years over the past 50 years. DESIGN, SETTING, PARTICIPANTS: Repeated cross-sectional population surveys (1966 to 2010-2015) of adults registered to vote in the Busselton shire, Western Australia, including a modified version of the British Medical Research Council questionnaire on respiratory symptoms. MAIN OUTCOME MEASURES: History of doctor-diagnosed asthma and chronic obstructive pulmonary disease (COPD), tobacco smoking history, respiratory medications used, spirometry parameters (forced expiratory volume in one second [FEV1], forced vital capacity [FVC]). RESULTS: The prevalence of tobacco smoking among men declined from 53% in 1966 to 12% in 2010-2015, and from 26% to 9% among women. The prevalence of ever-smoking (ie, smokers and ex-smokers) decreased from 80% to 57% for men but increased from 33% to 50% for women. The prevalence of doctor-diagnosed asthma increased, as did the use of long-acting bronchodilator aerosol medications by people with asthma and COPD. There have been no consistent changes in the prevalence of specific respiratory symptoms, but measures of lung function have significantly improved. CONCLUSIONS: Smoking rates declined as a result of changes in pricing, prohibitions on smoking and the feedback of survey results to Busselton participants. Significant improvements in lung function were measured, and it can be anticipated that the prevalence of other smoking-related diseases will also decline.

Vitamin D and respiratory health in the Busselton Healthy Ageing Study.

BACKGROUND AND OBJECTIVE: The relationship between vitamin D and respiratory disease was examined by cross-sectional analysis of a large community-based sample. METHODS: Serum 25-hydroxyvitamin D (25OHD) and history of respiratory disease, symptoms (recorded by questionnaire) and spirometry were measured in 5011 adults aged 45-69 years. Adjustments were made for age, sex, season and smoking (Model A), plus body mass index (BMI) and physical activity level (Model B), plus history of chronic diseases (Model C). RESULTS: Mean (SD) age was 58 (SD 6) years with 45% males, 10% current smokers and 12% taking vitamin D supplements. The prevalence of 25OHD level <50 nmol/L was 8.0%. In all the three models, 25OHD <50 nmol/L was significantly associated with asthma (Model C: odds ratio (OR): 1.32; 95% CI: 1.00, 1.73), bronchitis (1.54; 1.17, 2.01), wheeze (1.37; 1.10, 1.71) and chest tightness (1.42; 1.10, 1.83). Participants with vitamin D level > 100 nmol/L had higher forced vital capacity (FVC) in all the three models (1.17% higher, compared with the 50-100 nmol/L group in Model C). CONCLUSION: Low levels of serum 25OHD were independently associated with asthma, bronchitis, wheeze and chest tightness after three levels of adjustment for potential confounders. Higher vitamin D levels were associated with higher levels of lung function.

Serum 25-hydroxyvitamin D as a predictor of mortality and cardiovascular events: A 20-year study of a community-based cohort.

OBJECTIVE: Prospective studies, mostly from Europe and North America, suggest that serum 25-hydroxyvitamin D (25(OH)D) is inversely associated with mortality and cardiovascular disease (CVD) risk. Data from other regions are limited, and threshold levels for adverse cardiovascular outcomes are uncertain. We examined serum 25(OH)D as a predictor of total mortality and cardiovascular outcomes in an Australian cohort. DESIGN: A 20-year, community-based cohort study. PATIENTS: Participants in the 1994/1995 Busselton Health Survey (n = 3946, baseline age 25-84 years). MEASUREMENTS: Baseline serum 25(OH)D and mortality and cardiovascular outcomes to 2014 obtained by record linkage. RESULTS: The mean serum 25(OH)D concentration was 60.6 ± 18.0 nmol/L. During 20-year follow-up (excluding the first 2 years), 889 participants died (including 363 from CVD) and 944 experienced a CVD event (including 242 with heart failure). In the full cohort, controlling for Framingham risk score variables, higher baseline 25(OH)D was associated with significantly reduced all-cause mortality (adjusted HR 0.83 per SD increment of 25(OH)D, 95% CI 0.77-0.90), CVD death (HR 0.85, 95% CI 0.74-0.96) and heart failure (HR 0.81, 95% CI 0.69-0.94), but not CVD events (HR 0.99, 0.92-1.07). In restricted cubic spline regression models, serum 25(OH)D below 65 and 55 nmol/L was associated with higher total mortality and higher CVD mortality/heart failure, respectively. In participants without CVD at baseline (n = 3220), results were similar, but hazard ratios were attenuated and associations with CVD mortality no longer significant. CONCLUSIONS: In an Australian community-based cohort, baseline vitamin D levels below 55-65 nmol/L are predictive of all-cause mortality, CVD death and heart failure.