Robert J. MacInnis

Body-mass index and mortality among 1.46 million white adults.

BACKGROUND A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. METHODS We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). RESULTS The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. CONCLUSIONS In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9.

Effect of physical activity and body size on survival after diagnosis with colorectal cancer

Background: Physical inactivity and obesity increase the risk of colorectal cancer but little is known about whether they influence prognosis after diagnosis. Methods: Incident cases of colorectal cancer were identified among participants of the Melbourne Collaborative Cohort Study, a prospective cohort study of 41 528 Australians recruited from 1990 to 1994. Participants diagnosed with their first colorectal cancer between recruitment and 1 August 2002 were eligible. At the time of study entry, body measurements were taken and participants were interviewed about their physical activity. Information on tumour site and stage, treatments given, recurrences, and deaths were obtained from systematic review of the medical records. Results: A total of 526 cases of colorectal cancer were identified. Median follow up among survivors was 5.5 years, and 208 deaths had occurred, including 181 from colorectal cancer. After adjusting for age, sex, and tumour stage, exercisers had an improved disease specific survival (hazard ratio 0.73 (95% confidence interval (CI) 0.54–1.00)). The benefit of exercise was largely confined to stage II–III tumours (hazard ratio 0.49 (95% CI 0.30–0.79)). Increasing per cent body fat resulted in an increase in disease specific deaths (hazard ratio 1.33 per 10 kg (95% CI 1.04–1.71)). Similarly, increasing waist circumference reduced disease specific survival (hazard ratio 1.20 per 10 cm (95% CI 1.05–1.37)). Conclusions: Increased central adiposity and a lack of regular physical activity prior to the diagnosis of colorectal cancer is associated with poorer overall and disease specific survival.

Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial.

Objectives: To determine whether vitamin D supplementation can reduce the incidence of falls and fractures in older people in residential care who are not classically vitamin D deficient.

Serum vitamin D and falls in older women in residential care in Australia

Objectives: To determine the prevalence of vitamin D deficiency in older people in residential care and the influence that the level of vitamin D may have on their incidence of falls.

BMI and all-cause mortality in older adults: a meta-analysis

BACKGROUND Whether the association between body mass index (BMI) and all-cause mortality for older adults is the same as for younger adults is unclear. OBJECTIVE The objective was to determine the association between BMI and all-cause mortality risk in adults ≥65 y of age. DESIGN A 2-stage random-effects meta-analysis was performed of studies published from 1990 to 2013 that reported the RRs of all-cause mortality for community-based adults aged ≥65 y. RESULTS Thirty-two studies met the inclusion criteria; these studies included 197,940 individuals with an average follow-up of 12 y. With the use of a BMI (in kg/m2) of 23.0-23.9 as the reference, there was a 12% greater risk of mortality for a BMI range of 21.0-21.9 and a 19% greater risk for a range of 20.0-20.9 [BMI of 21.0-21.9; HR (95% CI): 1.12 (1.10, 1.13); BMI of 20.0-20.9; HR (95% CI): 1.19 (1.17, 1.22)]. Mortality risk began to increase for BMI >33.0 [BMI of 33.0-33.9; HR (95% CI): 1.08 (1.00, 1.15)]. Self-reported anthropometric measurements, adjustment for intermediary factors, and exclusion of early deaths or preexisting disease did not markedly alter the associations, although there was a slight attenuation of the association in never-smokers. CONCLUSIONS For older populations, being overweight was not found to be associated with an increased risk of mortality; however, there was an increased risk for those at the lower end of the recommended BMI range for adults. Because the risk of mortality increased in older people with a BMI <23.0, it would seem appropriate to monitor weight status in this group to address any modifiable causes of weight loss promptly with due consideration of individual comorbidities.

Circulating steroid hormones and the risk of prostate cancer.

Epidemiologic studies have failed to support the hypothesis that circulating androgens are positively associated with prostate cancer risk and some recent studies have even suggested that high testosterone levels might be protective particularly against aggressive cancer. We tested this hypothesis by measuring total testosterone, androstanediol glucuronide, androstenedione, DHEA sulfate, estradiol, and sex hormone–binding globulin in plasma collected at baseline in a prospective cohort study of 17,049 men. We used a case-cohort design, including 524 cases diagnosed during a mean 8.7 years follow-up and a randomly sampled subcohort of 1,859 men. The association between each hormone level and prostate cancer risk was tested using Cox models adjusted for country of birth. The risk of prostate cancer was ∼30% lower for a doubling of the concentration of estradiol but the evidence was weak (Ptrend = 0.07). None of the other hormones was associated with overall prostate cancer (Ptrend ≥ 0.3). None of the hormones was associated with nonaggressive prostate cancer (all Ptrend ≥ 0.2). The hazard ratio [HR; 95% confidence interval (95% CI)] for aggressive cancer almost halved for a doubling of the concentration of testosterone (HR, 0.55; 95% CI, 0.32-0.95) and androstenedione (HR, 0.51; 95% CI, 0.31-0.83), and was 37% lower for a doubling of the concentration of DHEA sulfate (HR, 0.63; 95% CI, 0.46-0.87). Similar negative but nonsignificant linear trends in risk for aggressive cancer were obtained for free testosterone, estradiol, and sex hormone–binding globulin (Ptrend = 0.06, 0.2, and 0.1, respectively). High levels of testosterone and adrenal androgens are thus associated with reduced risk of aggressive prostate cancer but not with nonaggressive disease. (Cancer Epidemiol Biomarkers Prev 2006;15(1):86–91)

Ace inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension*

The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure (SBP) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy. Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits. Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each. The study was a balanced, randomized crossover design with five periods: placebo; angiotensin converting enzyme inhibitors; beta-blocking drugs; calcium-blocking drugs; and thiazide diuretics. Blood pressure (BP) was measured 24 to 26 h after the previous dose. A questionnaire for side effects was administered at each visit. Seventy-four patients entered the study. beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods. There were 9 of 66 patients on P, 9 of 46 on beta-blockers, 4 of 65 on calcium-blocking drugs, 4 of 65 on diuretic, and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects. Decreases in SBP compared to randomized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg. Blood pressure decrease correlated with placebo BP (P < .0005, r = 0.53 to 0.70). When corrected for placebo, target SBP (<140 mm Hg) was reached in between 6% to 15% of patients on monotherapy. Sequential monotherapy achieved target in 29%. Angiotensin converting enzyme inhibitors, calcium-blocking drugs, and diuretics had no more side effects than placebo. Patients on beta-blockers had more side effects and the well-being score was reduced. Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure. beta-Blockers were relatively ineffective, were frequently contraindicated, and had more side effects. Monotherapy achieved control in only a small number of patients. In elderly people with essential hypertension, therapy should be instituted with diuretics or calcium-blocking drugs, but combination therapy will usually be required to achieve goal.

Substantial Intentional Weight Loss and Mortality in the Severely Obese

Objective:To compare all-cause mortality in a surgical weight loss cohort with a similarly aged, obese population-based cohort. Summary Background Data:Significant weight loss following bariatric surgery improves the comorbidities associated with obesity. Improved survival as a result of surgical weight loss has yet to be clearly demonstrated using clinical data. Methods:The surgical weight loss cohort was a series of consecutive patients treated with a laparoscopic adjustable gastric band in Melbourne between June 1994 and April 2005. The Melbourne Collaborative Cohort Study (MCCS) provided a community control cohort, recruited between 1992 and 1994 and followed to June 2005 to determine vital status. Height and weight were recorded at baseline in both studies. Subjects between 37 and 70 years and with a body mass index (BMI) of ≥35 were included. Vital status was determined by follow-up and searching of death registries. Survival time was compared using Kaplan-Meier estimates, and hazard of death was determined using Cox regression, adjusting for sex, age at baseline, and BMI at baseline. Results:Of 966 weight loss patients (mean age 47 years, mean BMI 45 kg/m2), the median follow-up time was 4 years. Mean weight loss after 2 years was 22.8% ± 9% (58% of excess weight). The MCCS cohort included 2119 severely obese members (mean age, 55 years; mean BMI, 38 kg/m2; median follow-up time, 12 years). There were 4 deaths in the weight loss cohort and 225 deaths in the MCCS cohort. Weight loss patients had 72% lower hazard of death than the community control cohort (hazard ratio, 0.28; 95% confidence interval, 0.10–0.85). Conclusions:Substantial surgical weight loss in a morbidly obese population was associated with a significant survival advantage.

A Comparison of Adiposity Measures as Predictors of All‐cause Mortality: The Melbourne Collaborative Cohort Study

Objective: Our goal was to examine five different measures of adiposity as predictors of all‐cause mortality.

Changes in body composition as determinants of longitudinal changes in bone mineral measures in 8 to 26-year-old female twins.

Abstract: Between 1990 and 1998, we conducted a longitudinal study of 286 female twins aged 8 to 25 years at baseline (60 monozygotic (MZ) pairs, 44 dizygotic (DZ) pairs and 78 unpaired twins), measured on average 2.4 times (range 2–6) with an average of 1.8 years between measurements (range 0.7–6.7 years). Areal bone mineral density (ABMD) at the lumbar spine, total hip and femoral neck, total body bone mineral content (BMC), total body soft tissue composition (lean mass and fat mass) were measured by dual-energy X-ray absorptiometry, and height and menarchial status were also recorded. Median annual changes in height were negligible at 4 years post-menarche. During the “linear growth” period up to 4 years post-menarche, ABMD at the lumbar spine, total hip and femoral neck increased with annual change in lean mass by 1.7 (S.E. 0.1), 1.4 (0.1) and 1.0 (0.1) percent per kilogram per year, respectively (all p<0.001), independently of changes in fat mass or height. During the “post-linear growth” period, ABMD at the total hip and femoral neck increased with annual change in fat mass by 0.3 (0.1) and 0.5 (0.1) percent per kilogram per year (all p<0.01), independent of change in lean mass. Annual changes in total body BMC were associated with annual changes in lean mass (1.9 (0.2) percent per kilogram), in fat mass (1.3 (0.2) percent per kilogram) and in height (0.7) (0.2) percent per centimeter) during linear growth, and in fat mass (1.0 (0.1)) and lean mass (0.6 (0.1)) percent per kilogram post-linear growth (all p<0.001). We conclude that changes in bone mineral measures are strongly associated with changes in lean mass during linear growth, while post-linear growth, changes in fat mass are the predominant, although weaker, predictor. These findings suggest that the strong cross-sectional association between bone mineral measures and lean mass is established during growth and development, and that fat mass emerges as a more powerful determinant of bone change in healthy adult females.