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Matthew W Knuiman

Publications and source records attributed to Matthew W Knuiman.

18 recordsLinked to original sources

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.

Adult↗

Neighborhood environmental factors correlated with walking near home: Using SPACES.

PURPOSE: The physical environment plays an important role in influencing participation in physical activity, although the specific factors that are correlated with different patterns of walking remain to be determined. We examined correlations between physical environmental factors and self-reported walking for recreation and transport near home. METHODS: The local neighborhood environments (defined as a 400-m radius from the respondent's home) of 1678 adults were assessed for their suitability for walking. The environmental data were collected during 2000 using the Systematic Pedestrian and Cycling Environmental Scan (SPACES) instrument together with information from other sources. We used logistic regression modeling to examine the relationship between the attributes of the physical environment and the self-reported walking behavior undertaken near home. RESULTS: Functional features were correlated with both walking for recreation (odds ratio (OR) 1.62; 95% confidence interval (CI): 1.20-2.19) and for transport (OR 1.30; 95% CI: 0.97-1.73). A well-maintained walking surface was the main functional factor associated with walking for recreation (OR 2.04; 95% CI: 1.43-2.91) and for transport (OR 2.13; 95% CI: 1.53-2.96). Destination factors, such as shops and public transport, were significantly correlated with walking for transport (OR 1.80; 95% CI: 1.33-2.44), but not recreation. CONCLUSION: The findings suggest that neighborhoods with pedestrian facilities that are attractive and comfortable and where there are local destinations (such as shops and public transport) are associated with walking near home.

Adult↗

Folate levels and cancer morbidity and mortality: prospective cohort study from Busselton, Western Australia.

PURPOSE: To test a community population for the hypothesis that carcinogenesis is related to blood folate levels. METHODS: Prospective analysis of cancer mortality data for a cohort of 964 men (person-time follow up: 20,254 years) and 1024 women (person-time follow up: 24,970 years) and morbidity data for a subcohort, all of whom participated in the 1969 Busselton (Western Australia) Health survey. Outcome measures were adjusted hazard ratios according to baseline folate levels for total cancer mortality and morbidity and site specific mortality and morbidity for colorectal, lung, breast, and prostate cancers. RESULTS: In total, there were 278 cancer deaths--45 from colorectal cancer, 44 from lung cancer, 15 from breast cancer, and 31 from prostate cancer. Decreased serum folate levels showed an independent association with increased prostate cancer mortality risk, the adjusted hazard ratio per decrease of 2 microg/L was 1.56 (CI: 1.05, 2.38), men whose levels were in the lowest quartile had an adjusted hazard ratio of 4.79 (CI: 1.56, 14.43) for subsequent death from prostate cancer. The morbidity subcohort data showed that decreased red blood-cell folate was significantly associated with increased events due to breast cancer, the adjusted hazard ratio per decrease of 100 mug/L was 1.96 (CI: 1.22, 3.12), women in the lowest quartile of red cell folate levels had an adjusted hazard ratio of 6.46 (CI: 1.19, 35.07) for a subsequent breast cancer event. Mortality and morbidity from colorectal or lung cancers were not associated with folate levels. CONCLUSIONS: Independent associations, assessed over periods greater than 20 years, were demonstrated between decreased folate levels and increased risks of prostate cancer mortality and breast cancer morbidity.

Adult↗

What can Busselton population health surveys tell us about asthma in older people?

WHAT WE NEED TO KNOW: Do the characteristics of asthma differ in people older than 55 years compared with younger people with respect to risk factors (atopy, airway hyper-responsiveness and genetic variation), smoking, lung function and other illness? How do inflammation and remodelling of airways vary with age and with duration and severity of asthma? WHAT WE NEED TO DO: Continue collecting prevalence data for asthma and its risk factors. Assess (i) period and cohort effects on asthma and its risk factors and (ii) interactions between age, smoking, severity and duration of asthma, lung function and airway responsiveness, and other concurrent disease. Measure airway responsiveness and exhaled nitric oxide to detect airway abnormalities in older people and relate this to the diagnoses of asthma and other diseases.

Adult↗

Spouse selection and environmental effects on spouse correlation in lung function measures.

PURPOSE: Concordance between spouses may be due to partner selection factors and/or the effects of marriage/environment. The extent to which partner selection factors contribute to spouse concordance has important implications for heritability studies. The aim of this study was to examine the magnitude of spouse correlation in lung function measures and its relationship to duration of marriage. METHODS: Cross-sectional and longitudinal data collected over the period 1969 to 1995 for 2615 couples from the Busselton Health Study have been analyzed using the program FISHER. RESULTS: Unadjusted correlations were around 0.45 for forced expiratory volume in 1 second (FEV1) and 0.25 for FEV1/FVC (forced vital capacity) and were reduced to 0.05 and 0.10, respectively, after adjustment for age, height, and smoking. No trend with marriage duration was apparent in both cross-sectional and longitudinal analyses but there was a significant downward trend in the correlations with age at marriage. CONCLUSIONS: The findings indicate that observed correlations in lung function measures are mostly due to partner selection factors and that partner selection factors have greater influence for couples that marry at younger ages. Family studies that aim to identify and separate genetic from other influences on lung function measures should not regard the mother-father correlation as due to common environment effects.

Adult↗

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.

Alanine Transaminase↗

Correlates of habitual snoring and witnessed apnoeas in Busselton, Western Australia.

OBJECTIVE: The aim of this study was to identify potential body size, behavioural and respiratory risk factors for habitual snoring and witnessed apnoeas in a general population. METHODS: Correlates of these conditions were studied in a sample of 3,577 adults aged 25-74 years who participated in a comprehensive health survey in Busselton, Western Australia, during 1994/95. Logistic regression was used to assess associations after age and gender adjustment and also in multivariate models. RESULTS: The prevalence of both conditions was higher in men and rose with age. After controlling for age, gender and body mass index no additional body size variable remained significantly associated with witnessed apnoeas, whereas both waist-hip ratio and neck-height ratio remained significantly associated with habitual snoring. Among behavioural variables, smoking showed the strongest association, and among respiratory symptoms, asthma for habitual snoring and bronchitis for witnessed apnoeas had significant independent associations. CONCLUSIONS AND IMPLICATIONS: This study has confirmed obesity and smoking as key determinants of habitual snoring and witnessed apnoeas. It has also shown that a number of measures of obesity are independently related to habitual snoring and that asthma and bronchitis may also play a role, independently of obesity.

Adult↗

Determinants of diabetes-attributable non-blood glucose-lowering medication costs in type 2 diabetes: the Fremantle Diabetes Study.

OBJECTIVE: To prospectively examine the magnitude and predictors of diabetes-attributable non-blood glucose-lowering (non-BGL) medication costs in type 2 diabetes. RESEARCH DESIGN AND METHODS: Detailed data from 593 community-dwelling patients were available over 4.3 +/- 0.4 years. Diabetes-attributable costs (in year 2000 Australian dollars [A$]) were calculated by applying a range of attributable proportions for each complication for which medication was prescribed. RESULTS: Non-BGL medications accounted for 75% of all prescription medication costs over the study period, and one-third were attributable to diabetes. The median annual cost (in A$) of non-BGL medications per patient increased from A$220 to A$429 over 4 years (P < 0.001), whereas the diabetes-attributable contribution increased from A$31 (range 15-40) to A$159 (range 95-219) per patient (P < 0.001). Diabetes-attributable hospital costs remained stable during the study. Diabetes-attributable non-BGL costs were skewed and, therefore, square root transformed before regression analysis. Independent baseline determinants of square root cost/year were coronary heart disease, systolic blood pressure, total serum cholesterol, ln(serum triglycerides), ln(albumin-to-creatinine ratio), serum creatinine, education, and, negatively, male sex and fasting plasma glucose (P </= 0.043; R(2) = 29%). Projected to the Australian population, diabetes-attributable non-BGL medication costs for patients with type 2 diabetes totaled A$79 million/year. CONCLUSIONS: The median annual cost of diabetes-attributable non-BGL medications increased fivefold over 4 years. This increase was predicted by vascular risk factors and complications at baseline. Better-educated patients had higher costs, probably reflecting improved health care access. Men and patients with higher fasting plasma glucose levels had lower costs, suggesting barriers to health care and/or poor self-care. The contemporaneous containment of hospital costs may be due to the beneficial effect of increased medication use.

Aged↗

Is sialic acid an independent risk factor for cardiovascular disease? A 17-year follow-up study in Busselton, Western Australia.

PURPOSE: To investigate the relationship between serum sialic acid level and risk of coronary heart disease (CHD) and stroke in men and women without diagnosed cardiovascular disease. METHODS: A prospective case-cohort study over the period 1981 to 1998 involving 151 CHD cases, 87 stroke cases, and a random sub-cohort of 340 was used. Sialic acid levels were determined by enzymatic method from frozen serum. Cox proportional hazards regression was used to estimate the relative risks of CHD and stroke for sialic acid tertiles and for continuous sialic acid level after adjustment for age, blood pressure, body mass index, cholesterol, triglycerides, diabetes, and smoking. RESULTS: The multivariate-adjusted relative risk of CHD associated with a 25 mg/dl increase in sialic acid was 1.22 (95% CI: 1.02-1.45) overall, 1.40 (95% CI: 1.11-1.76) in women, and 1.06 (95% CI: 0.82-1.37) in men. The overall relative risk for stroke was 1.13 (95% CI: 0.87-1.46) and for CHD and stroke combined it was 1.17 (95% CI: 0.99-1.37) CONCLUSIONS: Serum sialic acid may be a long-term predictor of CHD events in adults (especially women) who are currently clinically free of cardiovascular disease. Further studies are needed to determine whether this association can be explained by sialic acid being a marker of accelerated atherosclerosis or inflammation.

Adult↗

Homocysteine and cardiovascular disease: a 17-year follow-up study in Busselton.

STUDY OBJECTIVE: Prospective assessment of serum homocysteine level in relation to risk of coronary heart disease (CHD) and stroke. DESIGN: Case-cohort study with 17 years follow up. METHODS: Homocysteine was measured from stored serum. Proportional hazards regression models were used to obtain adjusted hazard ratios. RESULTS: There was no significant overall relationship between homocysteine and cardiovascular disease after controlling for known confounders. For women, removal of creatinine from the multivariate model resulted in a significant relationship. CONCLUSIONS: These results provide little support for a significant independent relationship between level of homocysteine and risk of CHD or stroke in men and women with no evidence of pre-existing cardiovascular disease.

Adult↗

Evaluating the impact of repeated community-wide health surveys on cardiovascular morbidity and mortality in the busselton population.

OBJECTIVE: To evaluate the impact of repeated community-wide mass health examinations on cardiovascular mortality and hospital morbidity trends in Busselton. METHOD: Population census, hospital admission and death data were used to calculate and compare cardiovascular mortality rates from 1965 to 1998 and hospital morbidity rates from 1971 to 1998 in Busselton residents aged 40 to 84 years with the remainder of the south-west region of Western Australia. RESULTS: Among men aged 40-69 years, the calendar year trends in standardised cardiovascular mortality and morbidity ratios were relatively flat and non-significant. Among women aged 40-69 years, the mortality ratio declined significantly up to 1989 (p = 0.03) but not over the whole period (p = 0.12), and the downward trend in the morbidity ratio did not reach statistical significance (p = 0.21). Among men aged 70-84 years, both the mortality and morbidity ratios rose significantly over time, whereas among women aged 70-84 years the mortality ratios showed a flat trend and the morbidity ratios a rising trend. These increasing trends were opposite to what was expected if the surveys had a beneficial impact. CONCLUSION: This analysis of trends, while failing to demonstrate a clear benefit of repeated mass health screenings on cardiovascular event rates, also highlights the difficulties in evaluating the longer-term impact on event rates of such programs and suggests that negative conclusions should be made with caution.

Adult↗

Significant nonsurgical risk factors for endophthalmitis after cataract surgery: EPSWA fourth report.

PURPOSE: Endophthalmitis remains a devastating complication of cataract surgery, despite improved methods of prophylaxis and surgical technique. The current study was conducted to identify sociodemographic, environmental, and clinical risk factors for the development of postoperative endophthalmitis, using population-based administrative data from Western Australia. METHODS: The Western Australian Data Linkage System identified all patients who underwent cataract surgery, along with those in whom postoperative endophthalmitis subsequently developed, from 1980 to 2000 inclusive. Cases of endophthalmitis were cross-referenced with other sources and validated by medical record review. After selection and preliminary analysis of potential risk factors, multivariate logistic regression modeling was used to estimate odds ratios for the selected variables. RESULTS: Over the 21 years, 210 cases of endophthalmitis occurred after 117,083 cataract procedures, yielding a cumulative incidence rate of 1.79 per 1000 procedures. The incidence of endophthalmitis decreased for extracapsular extraction over the whole period, but not for phacoemulsification over the recent 12 years. There was no risk-adjusted difference in the incidence rate of endophthalmitis for the various cataract surgery procedure types. However, a significantly higher risk was found in patients aged over 80 years, in having surgery in private hospitals, and to a lesser degree in having same-day surgery and surgery in winter. Cataract surgery with lacrimal or eyelid procedures dramatically increased the risk of endophthalmitis. CONCLUSIONS: It may be possible to reduce the incidence rate of postoperative endophthalmitis by almost 80% with a systematic approach to the management of elderly patients, hospital stay, and clinical protocols.

Age Factors↗

Allergy, atopy, and cancer: a prospective study of the 1981 Busselton cohort.

The associations among certain allergic disorders, atopy upon skin-prick testing, and specific cancers were evaluated in a prospective study. Information regarding history of asthma and hay fever was collected by questionnaire from 3,308 cancer-free participants in the 1981 Busselton Health Survey. A subset of 1,005 participants also underwent skin-prick testing. The cohort was followed for a new diagnosis of cancer or death until the end of 1999. Cox proportional hazards regression analysis was used to estimate adjusted hazard ratios (relative risks) for breast, prostate, colorectal, lung, and hematologic cancers and melanoma. Having a skin reaction to house dust mites nearly tripled the risk of prostate cancer (relative risk = 2.90, 95% confidence interval: 1.26, 6.68). History of asthma and hay fever were associated with a trend toward a reduced risk of colorectal cancer and increased risk of leukemia, but these results were not statistically significant. Hay fever was associated with melanoma risk in men but not in women. No association was found between breast and lung cancers and allergic disorders or atopy.

Allergens↗

Folate and vitamin B-12 and risk of fatal cardiovascular disease: cohort study from Busselton, Western Australia.

OBJECTIVE: To test the hypothesis that the incidence of fatal coronary heart disease and cardiovascular disease in a general population is related to serum and red cell folate and vitamin B-12 concentrations. DESIGN: Cohort study with follow up of 29 years. SETTING: Busselton, Western Australia. PARTICIPANTS: 1419 men and 1531 women aged 20 to 90 years, who were alive more than three years after their participation in the 1969 Busselton health survey. 2314 (78.4%) had no cardiovascular disease at the initial survey. MAIN OUTCOME MEASURES: Hazard ratios for fatal coronary heart disease and cardiovascular disease in men and women according to baseline concentrations of serum and red cell folate and serum vitamin B-12. RESULTS: 213 men and 159 women died from coronary heart disease, and 342 men and 302 women died from cardiovascular disease. Serum and red cell folate concentrations showed a moderate positive correlation (r=0.26, P<0.001) but otherwise serum and red cell folate and serum B-12 concentrations were not strongly correlated with each other or with other standard risk factors. After age and standard risk factors were adjusted for, there was no independent association between folate and B-12 concentrations and death from coronary heart disease or cardiovascular disease in the full cohort or the subcohort with no cardiovascular disease at baseline. The multivariate adjusted hazard ratio for death from cardiovascular disease in the lowest versus the highest category of red cell folate concentration was 1.05 (95% confidence interval 0.77 to 1.43) in men and 1.10 (0.81 to 1.51) in women. CONCLUSIONS: These findings do not support the hypothesis that lower folate and B-12 concentrations increase the risk of fatal cardiovascular disease in a general population. The routine use of these vitamins for preventing cardiovascular disease should await evidence from clinical trials.

Adult↗

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.

Adult↗

Changing methods of imaging the common bile duct in the laparoscopic cholecystectomy era in Western Australia: implications for surgical practice.

OBJECTIVE: To assess changes in the use of endoscopic retrograde cholangiopancreatography (ERCP), intraoperative cholangiography (IOC), and surgical exploration of the common bile duct (CBD) associated with the introduction of laparoscopic cholecystectomy (LC). SUMMARY BACKGROUND DATA: The optimal strategy for dealing with potential stones of the CBD during LC remains controversial. METHODS: The authors conducted a population-based study of all cases of cholecystectomy (20,084) in Western Australia in the periods before, during, and after the introduction of LC (1988-1994). Index admissions were linked to previous or subsequent admissions for ERCP. Factors associated with ERCP were analyzed by multivariate regression models. RESULTS: Between 1988 and 1994, admissions for ERCP almost doubled, whereas the use of IOC decreased from 71% to 51%. Different trends were found for open and laparoscopic procedures. Exploration of the CBD declined because of the infrequent use of this procedure in LC. Preoperative ERCP was significantly more common in older patients and men; the reverse was found for IOC. There was an adjusted 3.5-fold increase in preoperative ERCP both during and after the introduction of LC. The adjusted odds ratios for IOC were 0.48 and 0.52 for these periods. CONCLUSIONS: The introduction of LC was associated with increasing reliance on ERCP to image the CBD and a decrease in the use of IOC. These changes were observed in both LC and open cholecystectomy. They suggest that the use of ERCP before cholecystectomy has partly replaced IOC for visualization of the CBD for suspected stones. Although more than 40% of patients undergoing LC had IOC, surgeons appear to be reluctant to perform surgical exploration of the CBD when stones are present. Savings in terms of both complications and cost can be expected if preoperative ERCPs performed for suspicion of uncomplicated CBD stones are replaced by IOC.

Acute Disease↗

The impact of smoking on use of hospital services: the Busselton study.

OBJECTIVE: To use the Busselton study to estimate the impact of smoking on hospital use in Australia. METHODS: People on the electoral roll in Busselton in 1978 were invited to attend a survey where smoking habits were measured. 3,230 people aged 25 to 79 at the survey were followed until 1994 by record linkage to death records and to the Western Australian Hospital Morbidity Data System. Hyper Poisson regression was used to estimate ratios of hospital separation rates and mean bed day usage according to the 1978 smoking status. RESULTS: Compared with never smokers, current smokers had hospital separation rates that were 1.32 (95% confidence interval 1.16-1.49) times higher and used 1.40 (1.20-1.65) times as many hospital bed days. Former smokers had rates midway between never and current smokers. Separations due to neoplasms, circulatory disorders and respiratory disorders were all more frequent in current than in never smokers. Estimates of hospital use in Australia due to smoking were about two times higher than those previously published using different methods. CONCLUSIONS: Smoking is a major contributor to hospital use in Australia. People who stop smoking reduce their risk of hospitalisation. IMPLICATIONS: Smoking has a major impact on hospital use, which can be reduced by successful smoking cessation programs.

Adult↗

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 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.

Adult↗