Body mass index is a stronger predictor of alanine aminotransaminase levels than alcohol consumption

Background and Aims:  The relative effects of obesity compared to alcohol on liver injury are uncertain. We examined their effects on alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) levels in a population-based cohort. Methods:  Adult residents (2610: 1326 males, 1284 females) from Busselton, Australia, participated in a cross-sectional survey determining alcohol intake as determined by a validated questionnaire, anthropometric measurements and serum analysis. Alcohol consumption was classified as never, light (420 g/week). Results:  The majority of subjects were either overweight (41%) or obese (17%). A minority of subjects were moderate (25%) or heavy drinkers (4%). Body mass index (BMI) and waist circumference were strongly associated with ALT and GGT (P 0.2 for all tests). Conclusions:  Excess weight is more common than excessive alcohol consumption in the community and confers a greater risk of elevated aminotransaminase levels

Serum ferritin and cardiovascular disease: A 17-Year Follow-up study in Busselton, Western Australia

The association between serum ferritin level and coronary heart disease (CHD) and stroke events was evaluated in a long-term Western Australia prospective study in 1981–1998. The cohort consisted of the 1,612 men and women aged 40–89 years who participated in the 1981 Busselton Health Survey and who were free of cardiovascular disease at that time. Serum ferritin levels were obtained from serum samples stored frozen since 1981. The outcomes of interest were time to first CHD event (hospital admission or death) and time to first stroke event. Case-cohort sampling was used to reduce costs and preserve serum but still allow efficient analysis. Ferritin assays were performed for 217 CHD cases, 118 stroke cases, and a random sample of 450 of the total cohort. Proportional hazards regression models were used to obtain age-adjusted and multivariate-adjusted hazard ratios for ferritin level in relation to CHD and stroke. The hazard ratio for the highest tertile group compared with the lowest group was 0.96 (95% confidence interval: 0.60, 1.53) for CHD and 1.43 (95% confidence interval: 0.78, 2.64) for stroke. Little or no evidence was found that ferritin level was a risk factor for cardiovascular disease

Population-based study of the relationship between mutations in the hemochromatosis (HFE) gene and arthritis

Background and Aim:  Mutations in the hemochromatosis (HFE) gene are carried by one in three individuals of British Isles descent and may result in increased iron stores. These increased iron stores could potentially induce or exacerbate diseases, such as arthritis, in which iron has a role in pathogenesis. Although arthritis is a well-known association of clinically overt hereditary hemochromatosis, controversy surrounds the role of mutations in the HFE gene as risk factors for arthritis. The aim of the present study was to determine whether mutations in the HFE gene are associated with an increased prevalence of arthritis. Methods:  A population-based study was conducted in Busselton, Western Australia, of the prevalence of arthritis in 1372 individuals of British Isles descent. Participants completed a questionnaire and general physical examination. Analysis for C282Y and H63D HFE mutations was undertaken. Unadjusted and adjusted odds ratios (OR) were calculated for the relationship between HFE mutations and the prevalence of self-reported, doctor-diagnosed arthritis. Results:  There was no association between the presence of HFE mutations and the prevalence of self-reported, doctor-diagnosed arthritis (C282Y/wild type (WT) adjusted OR = 1.041 (95% confidence interval (CI) 0.68–1.61), H63D/WT OR = 0.76 (95% CI 0.53–1.08), C282Y/C282Y OR = 0.39 (95% CI 0.04–3.63), C282Y/H 63D OR = 0.808 (95% CI 0.27–2.42), H63D/H63D OR = 0.419 (95% CI 0.13–1.36)). Overall adjusted OR for arthritis in participants with one or more HFE mutations was 0.81 (95% CI 0.61–1.09). Conclusions:  Mutations of the HFE gene are not risk factors for arthritis in populations of British Isles descent

A Cross-Sectional community study of serum iron measures and cognitive status in older adults

The relationship of iron status with cognition and dementia risk in older people is contentious. We have examined the longitudinal relationship between serum ferritin and cognition in 800 community-dwelling Australians 60 years or older. Iron studies (serum iron, transferrin saturation, serum ferritin) were performed in 1994/5 and 2003/4 and clinical and cognitive assessments were conducted in 2003/4 for 800 participants of the Busselton Health Study. All participants completed the Cambridge Cognitive test (CAMCOG). Those with CAMCOG scores 0.05). In participants without dementia (n=749), neither serum ferritin in 1994/5 or 2003/4 nor change in serum ferritin between these times was related to total CAMCOG or executive function scores, with or without adjustment for gender, age, National Adult reading test, or stroke history (all p> 0.05). No relationships were observed between ferritin and cognition for participants with possible or probable dementia (n=51). All participants identified as HFE C282Y homozygous or with serum ferritin >1,000 ng/ml had normal CAMCOG scores. We conclude abnormal body iron stores (low or high) are unlikely to have clinically significant effects on cognition or dementia risk in community-dwelling older people

Effects of HFE gene mutations and alcohol on iron status, liver biochemistry and morbidity

Background and Aims:  The aims of the present study were to determine: (i) whether alcohol consumption is greater in individuals with HFE mutations; and (ii) whether common HFE mutations modify the effects of alcohol on serum iron and liver biochemistry or morbidity. Methods:  The residents of the town of Busselton in Western Australia were subject to cross-sectional health surveys between 1966 and 1983. In 1994/1995 all surviving participants of the earlier surveys were invited to take part in a follow-up survey. Logistic, linear and Poisson log-linear regression analyses were performed in 1490 men and 1452 women from the 1994/1995 survey to assess the relationships between HFE mutations, alcohol, iron levels, liver biochemistry and morbidity. Results:  Heavy or moderate alcohol consumption was present in 7% or 36% of men and 0.5% or 12% of women, respectively. Alcohol consumption strongly influenced levels of serum ferritin and gamma glutamyl transpeptidase (GGT) and mean cell volume (MCV) in men and women but only alanine aminotransferase (ALT) levels in women. These effects were independent of HFE gene mutations. Hospital admission rates for respiratory disorders were higher in men with the C282Y mutation. Conclusions:  Alcohol consumption strongly influences serum ferritin and GGT levels and MCV in men and women but only ALT levels in women, and these effects are independent of HFE mutations. HFE gene mutations do not predispose to moderate or heavy alcohol consumption. The C282Y mutation is associated with increased respiratory admission rates in men

A prospective study of infection and cardiovascular diseases: the Busselton Health Study

Background: Infectious agents might play a role in the aetiology of cardiovascular diseases. The aim was to determine the association of antibodies to implicated infectious agents with coronary heart disease (CHD) and stroke in a population-based prospective study. Design: This study was based on a cohort of 1612 cardiovascular disease-free adults in the 1981 Busselton Health Survey. Primary risk factors were measured from stored serum and case-cohort sampling was used to reduce costs and preserve serum. The outcomes of interest were time to first CHD or stroke event Serum antibody tests were carried out for all 218 CHD cases, all 119 stroke cases and a random subset of 451 subjects. Methods: Sera were tested for antibodies to Chlamydia pneumoniae (IgG and IgA), and for IgG antibodies to Helicobacter pylori and cytomegalovirus (CMV). The association between serum antibody and risk of cardiovascular diseases was analysed using Cox proportional hazards regression. Results: The estimated population prevalence was 24% for C. pneumoniae IgG, 7% for C. pneumoniae IgA, 58% for H. pylori and 85% had CMV antibody levels greater than 15 AU/mL. The estimated relative risk of CHD was around 1.2 for all antibodies examined, except for C. pneumoniae IgA for which it was less than one, and the estimated relative risk of stroke was around 0.85, however in all cases the 95% confidence interval included one. Conclusions: This study of an Australian population does not support an association between serum antibody levels to C. pneumoniae, H. pylori and CMV with development of cardiovascular diseases

Noncitrus fruits as novel dietary environmental modifiers of iron stores in people with or without HFE gene mutations

OBJECTIVE To investigate whether citrus fruit, noncitrus fruit, and other dietary factors act as environmental modifiers of iron status in the absence or presence of hemochromatotic HFE gene mutations. PARTICIPANTS AND METHODS Iron studies, HFE genotypic analyses, and dietary data from a survey conducted from March 21, 1994, through December 15, 1995, were analyzed for a group of 2232 residents (1105 men, 1127 women) aged 20 to 79 years recruited from the community electoral roll of Busselton in Western Australia. Data were analyzed by linear regression analysis and analysis of covariance. RESULTS Higher levels of fresh fruit intake (excluding citrus fruits and citrus juices) had a significant protective effect (P=.002) against high body iron status as gauged by ferritin levels in men, irrespective of HFE genotype. Consumption of 2 or more pieces of fruit per day on average reduced mean serum ferritin levels by 20% compared with average consumption of less than 1 piece of fruit per day. This effect was not observed in women. Consumption of citrus fruits and citrus juices had no significant effects in either sex. No protective effects were observed for tea consumption or any other dietary factors studied. Red meat and alcohol consumption correlated with high body iron stores (P.05). CONCLUSION Noncitrus fruits are environmental modifiers of iron status independent of HFE genotype. This could have important implications for the provision of evidence-based dietary advice to patients with other iron-storage disorders

Effects of body iron stores and haemochromatosis genotypes on coronary heart disease outcomes in the Busselton health study

Background: Increased iron stores and haemochromatosis gene mutations may be risk factors for coronary heart disease. The aims of this study were to determine in a stable community population whether increased iron stores or haemochromatosis gene mutations were risk factors for coronary heart disease. Design Cross-sectional and prospective cohort studies. Methods: We evaluated 1185 men and 1141 women aged 20–79 years of predominantly Anglo-Celtic descent from the 1994–95 assessment of the Busselton population in Western Australia. Subjects underwent haemochromatosis genotyping, serum iron studies, clinical, biochemical and ECG evaluation for coronary heart disease and associated risk factors. Hospital admissions or death from cardiovascular disease were determined by linkage with the Western Australian morbidity and mortality database. The study design was cross-sectional for the 1994–95 cohort comparing coronary heart disease cases with unaffected subjects and unaffected subjects were followed prospectively until December 1998. Results: Cross-sectional and prospective cohort analyses demonstrated that elevated serum iron parameters or possession of either the C282Y or H63D mutations in the HFE gene were not predictive of increased risk for coronary heart disease in men or women. Conclusions: Increased iron stores or haemochromatosis gene mutations are not significant risk factors for coronary heart disease

Metabolic mediators of the effects of body-mass index, overweight, and obesity on coronary heart disease and stroke: A pooled analysis of 97 prospective cohorts with 1·8 million participants

Background Body-mass index (BMI) and diabetes have increased worldwide, whereas global average blood pressure and cholesterol have decreased or remained unchanged in the past three decades. We quantified how much of the effects of BMI on coronary heart disease and stroke are mediated through blood pressure, cholesterol, and glucose, and how much is independent of these factors. Methods We pooled data from 97 prospective cohort studies that collectively enrolled 1·8 million participants between 1948 and 2005, and that included 57 161 coronary heart disease and 31 093 stroke events. For each cohort we excluded participants who were younger than 18 years, had a BMI of lower than 20 kg/m2, or who had a history of coronary heart disease or stroke. We estimated the hazard ratio (HR) of BMI on coronary heart disease and stroke with and without adjustment for all possible combinations of blood pressure, cholesterol, and glucose. We pooled HRs with a random-effects model and calculated the attenuation of excess risk after adjustment for mediators. Findings The HR for each 5 kg/m2 higher BMI was 1·27 (95% CI 1·23-1·31) for coronary heart disease and 1·18 (1·14-1·22) for stroke after adjustment for confounders. Additional adjustment for the three metabolic risk factors reduced the HRs to 1·15 (1·12-1·18) for coronary heart disease and 1·04 (1·01-1·08) for stroke, suggesting that 46% (95% CI 42-50) of the excess risk of BMI for coronary heart disease and 76% (65-91) for stroke is mediated by these factors. Blood pressure was the most important mediator, accounting for 31% (28-35) of the excess risk for coronary heart disease and 65% (56-75) for stroke. The percentage excess risks mediated by these three mediators did not differ significantly between Asian and western cohorts (North America, western Europe, Australia, and New Zealand). Both overweight (BMI ≥25 to <30 kg/m2) and obesity (BMI ≥30 kg/m2) were associated with a significantly increased risk of coronary heart disease and stroke, compared with normal weight (BMI ≥20 to <25 kg/m2), with 50% (44-58) of the excess risk of overweight and 44% (41-48) of the excess risk of obesity for coronary heart disease mediated by the selected three mediators. The percentages for stroke were 98% (69-155) for overweight and 69% (64-77) for obesity. Interpretation Interventions that reduce high blood pressure, cholesterol, and glucose might address about half of excess risk of coronary heart disease and three-quarters of excess risk of stroke associated with high BMI. Maintenance of optimum bodyweight is needed for the full benefits