Recent PublicationsThere are over 300
research
articles published in medical journals using the
Busselton data. Many of these can be accessed through PubMed
using
"Busselton" as a key word. A comprehensive list of research
publications are also listed here. Below are brief descriptions and summaries of recent scientific papers that have been published in medical journals and highlight the important discoveries being made using the Busselton data. Eur J Endocrinol. 2011 Feb 11. [Epub ahead of print] A meta-analysis of the associations between common variation in the PDE8B gene and thyroid hormone parameters; including assessment of longitudinal stability of associations over time and effect of thyroid hormone replacement. Taylor P, Panicker V, Sayers A, Shields B, Iqbal A, Bremner A, Beilby J, Leedman P, Hattersley A, Vaidya B, Frayling T, Evans J, Tobias JH, Timpson NJ, Walsh JP, Dayan CM. P Taylor, Henry Wellcome Labarotories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, United Kingdom. Objective Common variants in PDE8B are associated with TSH, but apparently without any effect on thyroid hormone levels which is difficult to explain. Furthermore the stability of the association has not been examined in longitudinal studies or in patients on levothyroxine. Design Four cohorts were used (N=2,557) the Busselton Health Study (thyroid function measured on 2 occasions), DEPTH, EFSOCH (selective cohorts) and WATTS (individuals on levothyroxine). Methods Meta-analysis to clarify associations between the rs4704397 SNP in PDE8B on TSH, T3 and T4 levels. Results Meta-analysis confirmed that genetic variation in PDE8B was associated with TSH (p=1.64x10-10 0.20 SD/allele, 95%CI 0.142, 0.267) and identified a possible new association with free T4 (p=0.023, -0.07 SD/allele, 95% CI -0.137, -0.01) no association was seen with free T3 (p=0.218). The association between PDE8B and TSH was similar in 1981 (0.14 SD/allele, 95%CI 0.04, 0.238) and 1994 (0.20 SD/allele, 95%CI 0.102, 0.300) and even more consistent between PDE8B and free T4 in 1981 (-0.068 SD/allele, 95% CI: -0.167, 0.031) and 1994 (-0.07 SD/allele, 95%CI: -0.170, 0.030). No associations were seen between PDE8B and thyroid hormone parameters in individuals on levothyroxine. Conclusion Common genetic variation in PDE8B is associated with reciprocal changes in TSH and free T4 levels that are consistent over time and lost in individuals on levothyroxine. These findings identify a possible genetic marker reflecting variation in thyroid hormone output that will be of value in epidemiological studies and provides additional evidence that PDE8B is involved in TSH signaling in the thyroid. Respirology. 2011 Feb;16(2):359-66 Functional haplotypes in the PTGDR gene fail to associate with asthma in two Australian populations. Jamrozik EF, Warrington N, McClenaghan J, Hui J, Musk AW, James A, Beilby JP, Hansen J, DE Klerk NH, Palmer LJ. Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, West Perth, Western Australia, Australia. BACKGROUND AND OBJECTIVE: Haplotypes in the promoter region of the prostanoid DP receptor (PTGDR) gene have been shown to functionally influence gene transcription and to be associated with asthma in two previous case-control studies in Caucasians. This study tested the association of PTGDR haplotypes with asthma phenotypes in two large Caucasian-Australian populations. These results were incorporated in a meta-analysis with previously published data to determine the overall role for these haplotypes in the risk of asthma. METHODS: Three PTGDR promoter-region single nucleotide polymorphisms (SNP) were genotyped in 368 individuals from the Western Australian Twin Child Health study and 2988 individuals from the Busselton Health Study. Logistic regression and transition disequilibrium tests were used to assess whether SNP genotypes and three SNP haplotypes were associated with doctor-diagnosed asthma or intermediate quantitative traits. Longitudinal data from the Busselton Health Study were used to examine whether PTGDR influences changes in lung function over time. Meta-analysis incorporated the findings of this study with those of two previous studies in Caucasian populations. RESULTS: Cross-sectional associations between PTGDR haplotypes and asthma phenotypes were non-significant (P > 0.05) in both populations. Longitudinal analyses of PTGDR and lung function were also non-significant. Meta-analysis, however, suggested that haplotype TCT was significantly associated with decreased risk of asthma (OR = 0.76; P = 0.02) while haplotype CCC was not significantly associated with asthma (OR = 1.30; P = 0.07). CONCLUSIONS: These results suggest that despite the non-significant findings in the present study populations, PTGDR promoter haplotypes may account for a small but significant proportion of the risk of asthma in Caucasian populations. Genet. 2010 Oct 8;11:140. The longitudinal association of common susceptibility variants for type 2 diabetes and obesity with fasting glucose level and BMI. Webster RJ, Warrington NM, Beilby JP, Frayling TM, Palmer LJ. Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, Crawley, WA, Australia. BACKGROUND: Variation in the effects of genetic variants on physiological traits over time or with age may alter the trajectories of these traits. However, few studies have investigated this possibility for variants associated with type 2 diabetes or obesity, and these show little consensus. We aimed to characterise the possible longitudinal associations of common diabetes-susceptibility variants in the KCNJ11, PPARG, TCF7L2, IGF2BP2, CDKAL1, SLC30A8 and HHEX gene loci, with fasting glucose level; and of an obesity-associated variant in the FTO gene, with body mass index (BMI). METHODS: The study analysed data from the Busselton Health Study (n = 4,554). Cross-sectional association analyses included family data and used the total association test. Longitudinal association analyses of unrelated participant data (n = 2,864) used linear mixed-effects models. RESULTS: In cross-sectional analyses, we observed associations of the T allele at the IGF2BP2 single nucleotide polymorphism (SNP) rs4402960 with raised fasting glucose (p = 0.045), and the A allele at the FTO SNP rs9939609 with raised BMI (p = 0.003). Longitudinal analyses showed no significant associations between SNPs and changes in fasting glucose or BMI in the same individuals, either over mean follow-up times of 18.7 and 21.8 years respectively, or with age during adulthood. CONCLUSIONS: There was no indication that the effects of common type 2 diabetes variants on fasting glucose varied with age during adulthood or over time. Am J Hum Genet. 2010 Sep 10;87(3):430-5. A locus on chromosome 1p36 is associated with thyrotropin and thyroid function as identified by genome-wide association study.
Cancer Epidemiol Biomarkers Prev. 2010 Sep;19(9):2238-46 SERUM MESOTHELIN FOR
EARLY DETECTION OF THE ASBESTOS-INDUCED CANCER MALIGANT MESOTHELIOMA. Creaney
J, Olsen NJ, Brims F, Dick IM, Musk AW, de Klerk NH, Skates SJ, Robinson BW. BACKGROUND:
Malignant mesothelioma is an aggressive, almost uniformly fatal tumour,
primarily caused by exposure to asbestos. Since the recent discovery that serum
mesothelin is a sensitive and highly specific biomarker for mesothelioma one of
the key issues raised is whether mesothelin levels represent a useful screening
test for asbestos-exposed at-risk individuals. In this study soluble mesothelin
was determined in sequential serum samples collected from asbestos-exposed
individuals prior to the development of mesothelioma. METHODS:
Archival serum samples from 106 individuals who developed mesothelioma and 99
asbestos exposed individuals from the Wittenoom Cancer Surveillance Program and
from 109 non-asbestos exposed individuals from the Busselton Health Survey were identified and serum mesothelin
concentrations were determined using the MESOMARK assay. RESULTS:
Longitudinal mesothelin levels determined in healthy asbestos exposed
individuals over a period of 4 years were stable (Pearson's r=0.96;
p<0.0001). There was no correlation between mesothelin concentration and
cumulative asbestos exposure. Mesothelin concentrations were greater than a
threshold of 2.5nM in the penultimate serum sample before the diagnosis of
mesothelioma in 17 of 106 people. Using an increase above the 95% confidence
interval of the mean of a given individual's longitudinal mesothelin results,
33 out of 82 individuals had increasing mesothelin levels before diagnosis. CONCLUSION:
In a population with a high pre-test probability of developing mesothelioma the
serum biomarker mesothelin is elevated in absolute terms in 15% and in relative
terms in 40% of the group.Impact: Future studies examining a combination of
biomarkers could improve sensitivity of screening. J Sleep Res. 2011 Mar;20(1pt2):241-249 Gastro-oesophageal reflux
symptoms are related to the presence and severity of obstructive sleep apnoea. Shepherd
KL, James Department
of Pulmonary Physiology, West Australian Sleep Disorders Research Institute, Summary:
Repetitive airway occlusion during sleep in patients with obstructive sleep
apnoea (OSA) results in the generation of negative intrathoracic pressures and
ends in arousal, both of which may predispose to reflux during sleep (nocturnal
reflux). We aimed to determine and compare the prevalence of nocturnal reflux
symptoms and their sleep-associated risk factors in untreated OSA patients, OSA
patients using continuous positive airway pressure (CPAP) therapy, and the
general population. Gastro-oesophageal reflux and sleep questionnaires were
completed by 1116 patients with polysomnography diagnosed OSA and by 1999
participants of the 2007 Busselton
population health survey. Of the OSA patients, 137 completed the reflux
questionnaire before and after treatment. Risk of OSA in the general population
was assessed using the Respir
Physiol Neurobiol. 2010 Jul 31;172(3):162-8.. Reference equations for
respiratory system resistance and reactance in adults. Brown
NJ, Xuan W, Salome CM, Berend N, Hunter ML, Musk AW, James AL, King GG. The
Woolcock Institute of Medical Research, Glebe, NSW, AIM:
To determine reference equations for respiratory system resistance and
reactance in a large randomly selected sample from a general, predominantly
Caucasian population. METHODS:
A prospective respiratory health survey of the general population in RESULTS:
904 Eligible subjects (341 male) aged 18-92 years had technically satisfactory
measurements. Reference equations were established for males and females
separately. Both resistance and reactance were predicted by height and weight.
Age was a predictor of reactance only. CONCLUSIONS:
These data provide reference equations for forced oscillatory parameters, in
well-characterized Caucasian subjects, with no respiratory symptoms, from a
large general population. Mult
Scler. 2010 May;16(5):526-32. Influence of HLA-DRB1
allele heterogeneity on disease risk and clinical course in a West Australian
MS cohort: a high-resolution genotyping study. Wu
JS, James I, Wei Qiu, Castley A, Christiansen FT, Carroll WM, Mastaglia FL,
Kermode AG. Centre
of Neuromuscular and Neurological Disorders, University of Western Australia,
and Department of Neurology, Sir Charles Gairdner Hospital, Queen Elizabeth
Medical Centre, Perth, Western Australia, Australia. BACKGROUND:
Previous studies on the influence of HLA-DRB1 alleles on multiple sclerosis
(MS) susceptibility and clinical course have mostly employed the 2-point
genotyping method. OBJECTIVE:
To assess the influence of HLA-DRB1 alleles and allele interactions on disease
risk and clinical course in a large West Australian MS patient cohort using
high-resolution genotyping. METHODS:
Four digit HLA-DRB1 genotyping was performed on a group of 466 clinically
definite or probable MS patients from the Perth Demyelinating Diseases Database
and 189 healthy Caucasian controls from the
Busselton Community Health Study. RESULTS:
In addition to the known risk allele HLA-DRB1*1501, evidence of increased
susceptibility to MS was found for three additional alleles, DRB1*0405,
DRB1*1104 and DRB1*1303, though the power was insufficient to sustain
significance for these when crudely Bonferroni corrected over all alleles
considered. DRB1*0701 was found to be protective even after correction for
multiple comparisons. In addition we found evidence that the DRB1*04 sub-allele
HLA-DRB1*0407 and HLA-DRB1*0901 may be protective. Among the diplotypes, the
highest estimated risk was in HLA-DRB1*1501/*0801 heterozygotes and DRB1*1501
homozygotes and the lowest in HLA-DRB1*0701/*0101 heterozygotes. There was no
significant gender association with HLA-DRB1*1501 overall, but the
HLA-DRB1*1501/*1104 risk genotype was significantly associated with female
gender. HLA-DRB1*1501 was the strongest risk allele in both primary progressive
MS and relapsing-remitting MS. CONCLUSION:
Our results demonstrate the advantages of high-resolution HLA genotyping in
recognizing risk-modifying alleles and allele combinations in this patient
cohort and in recognizing the differential effects of HLA-DRB1*04 and DRB1*11
sub-alleles. Clin
Chem. 2010 May;56(5):799-804. Comparison of cystatin C
and creatinine as predictors of cardiovascular events in a community-based
elderly population. Beilby
J, Divitini ML, Knuiman MW, Rossi E, Hung J. Biochemistry
Section, PathWest, Queen Elizabeth II Medical Centre, BACKGROUND:
Reduced renal function is an established risk factor for cardiovascular events.
We compared 3 measures of renal function--serum cystatin C, serum creatinine,
and calculated creatinine clearance--as predictors of subsequent cardiovascular
events in a community-based population of elderly individuals. METHODS:
Comprehensive cardiovascular risk factor data were available for 1410 surviving
participants of previous Busselton
health surveys who were >or=60 years old. Hazard ratios for risk of
incident coronary heart disease and cardiovascular disease over 10 years of
follow-up were derived for each baseline measure of renal function by use of
Cox regression. RESULTS:
All measures of renal function were significantly related to risks of morbidity
and mortality from coronary heart disease and cardiovascular disease. There
were 453 incident cardiovascular disease events; and the age- and sex-adjusted
hazard ratios (95% CIs) were 1.34 (1.23-1.46), 1.32 (1.20-1.45), and 1.22
(1.06-1.41) per 1-SD deterioration in cystatin C, creatinine, and creatinine
clearance, respectively. All 3 measures gave approximately the same
age-adjusted relative risk estimates. After further adjustment for established
cardiovascular risk factors, the relative risk estimates were all reduced but
remained statistically significant (P < 0.05). Cystatin C was not a
significant predictor for cardiovascular disease after adjustment for
creatinine clearance. CONCLUSIONS:
In relation to predicting risk for coronary heart disease or cardiovascular
disease over a 10-year follow-up in a community-based population of elderly
subjects, there was no evidence that cystatin C was a better risk predictor
than creatinine or creatinine clearance. J
Alzheimers Dis. 2010;20(2):617-23. A cross-sectional
community study of serum iron measures and cognitive status in older adults. Milward
EA, Bruce DG, Knuiman MW, Divitini ML, Cole M, Inderjeeth CA, Clarnette RM,
Maier G, Jablensky A, Olynyk JK. The
School of Biomedical Sciences, 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 <84 underwent expert
clinical review for cognitive disorders, including the Clinical Dementia Rating
scale. Mean serum iron (18.3 micromol/l) and transferrin saturation (28.5%) in
2003/4 did not differ significantly from 1994/5 whereas mean serum ferritin
decreased from 162 microg/l in 1994/5 to 123 microg/l in 2003/4, possibly
reflecting aging or dietary changes. No relationships were observed between
serum iron or transferrin saturation and presence or absence of dementia (p>
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. J
Clin Endocrinol Metab. 2010 Mar;95(3):1095-104. Epub 2010 Jan 22. Thyrotropin and thyroid
antibodies as predictors of hypothyroidism: a 13-year, longitudinal study of a
community-based cohort using current immunoassay techniques. Walsh
JP, Bremner AP, Feddema P, Leedman PJ, Brown SJ, O'Leary P. Department
of Endocrinology and Diabetes, Context:
Longitudinal studies of risk factors for hypothyroidism are required to inform
debate regarding the TSH reference range. There are limited longitudinal data
on the predictive value of thyroid antibodies measured by automated immunoassay
(as opposed to semiquantitative methods). Methods: We measured TSH, free T(4),
thyroid peroxidase antibodies (TPOAbs), and thyroglobulin antibodies (TgAbs)
using the Immulite platform on sera from 1184 participants in the 1981 and 1994
Busselton Health Surveys. Outcome
measures at follow-up were hypothyroidism, defined as TSH greater than 4.0
mU/liter or on thyroxine treatment; and overt hypothyroidism, defined as TSH
above 10.0 mU/liter or on thyroxine treatment. Receiver-operator characteristic
analysis was used to determine optimal cutoffs for baseline TSH, TPOAbs, and
TgAbs as predictors of hypothyroidism. Results: At 13 yr follow-up, 110
subjects (84 women) had hypothyroidism, of whom 42 (38 women) had overt
hypothyroidism. Optimal cutoffs for predicting hypothyroidism were baseline TSH
above 2.5 mU/liter, TPOAbs above 29 kIU/liter, and TgAbs above 22 kIU/liter,
compared with reference range upper limits of 4.0 mU/liter, 35 kIU/liter, and
55 kIU/liter, respectively. In women with positive thyroid antibodies (TPOAbs
or TgAbs), the prevalence of hypothyroidism at follow-up (with 95% confidence
intervals) was 12.0% (3.0-21.0%) when baseline TSH was 2.5 mU/liter or less,
55.2% (37.1-73.3%) for TSH between 2.5 and 4.0 mU/liter, and 85.7% (74.1-97.3%)
for TSH above 4.0 mU/liter. Conclusions: The use of TSH cutoffs of 2.5 and 4.0
mU/liter, combined with thyroid antibodies, provides a clinically useful
estimate of the long-term risk of hypothyroidism. Respirology.
2009 Aug;14(6):814-21. Risk factors for
adult-onset asthma: a 14-year longitudinal study. Jamrozik
E, Knuiman MW, James A, Divitini M, Musk AW. Busselton Health Study, BACKGROUND
AND OBJECTIVES: Few longitudinal studies have examined the risk factors and
natural history of adult-onset asthma. This study assessed the subject
characteristics and lifestyle factors that predicted the new diagnosis of
asthma in adulthood and how these factors changed over time in those who
developed asthma compared with those who do not. METHODS:
The study enrolled 1554 adults from the Busselton
Health Study seen in 1981 and again in 1994-1995 who initially reported
never having had doctor-diagnosed asthma. Questionnaire measures were used to
assess doctor-diagnosed asthma, respiratory history and tobacco smoking.
Height, weight and spirometric measures of lung function were measured. Atopy
was assessed by skin prick tests. Logistic regression analysis was used to
identify risk factors for adult-onset asthma and changes over time. RESULTS:
Reported wheeze, rhinitis, chronic cough, smoking and lower levels of lung
function in 1981 each predicted asthma diagnosis by 1994-1995. Neither initial
skin-prick reactivity nor newly positive skin-prick tests at follow up were
associated with adult-onset asthma. Those diagnosed with asthma were more
likely to have new wheeze, new rhinitis, new habitual snoring, weight gain and
excess decline in lung function. CONCLUSIONS:
Adult-onset asthma has risk factors that are distinct from those observed in
childhood asthma. The presence of upper airway symptoms including rhinitis, as
well as lifestyle factors, such as smoking, predicts those at greatest risk.
However, neither pre-existing atopy nor new atopy as measured by skin prick
tests was associated with adult-onset asthma. Eur
Respir J. 2010 Feb;35(2):273-8. Epub 2009 Jul 30. Changes in the prevalence
of asthma in adults since 1966: the Busselton health study. James
AL, Knuiman MW, Divitini ML, Hui J, Hunter M, Palmer LJ, Maier G, Musk AW. Dept
of Pulmonary Physiology/West Australian Sleep Disorders Research Institute,
Level 5, G Block,
Am
J Gastroenterol. 2009 Jul;104(7):1715-22. Epub 2009 Jun 2. Serum alanine
aminotransferase, metabolic syndrome, and cardiovascular disease in an
Australian population. Olynyk
JK, Knuiman MW, Divitini ML, Davis TM, Beilby J, Hung J. School
of Medicine and Pharmacology, OBJECTIVES:
Elevations of serum alanine aminotransferase (ALT) are common and have been
associated with metabolic syndrome (Met S) and cardiovascular risk. The aim of
this study was to determine whether elevated ALT concentrations are predictive
of Met S or cardiovascular events. METHODS:
In 1994/95, surviving participants of the previously conducted Busselton health population surveys
completed a series of clinical and biochemical assessments. Using the Western
Australian Health Department data linkage system, admissions for cardiovascular
disease (CVD) were determined for 15 years before the survey (from 1980 to
1994). Incident CVD events during the 10-year follow-up period to the end of
2004 were also ascertained. Met S was defined using NCEP ATP III (2005)
criteria. RESULTS:
3,719 Subjects (1,544 men and 2,175 women), aged 25-84 years who did not have
serologically diagnosable chronic liver diseases or excessive consumption of
alcohol, had their levels of ALT measured. The prevalence of Met S was 17% in
men and 15% in women. In age-adjusted analyses, ALT was significantly
associated with Met S and each of its five components and the association with
Met S remained significant after adjustment for insulin resistance. There was
no positive association between ALT and incident CVD events over the 10-year
follow-up period in age-adjusted or multivariate-adjusted analyses. CONCLUSIONS:
The findings from this Australian population-based cohort study support a
strong association between ALT concentration and Met S independent of insulin
resistance. Serum ALT level does not appear to contribute significantly to
cardiovascular risk assessment. Med
J Aust. 2009 Apr 20;190(8):429-32. Screening for coeliac
disease using anti-tissue transglutaminase antibody assays, and prevalence of
the disease in an Australian community. Chin
MW, Mallon DF, Cullen DJ, Olynyk JK, Mollison LC, Pearce CB. Department
of Hepatology, OBJECTIVES:
To determine (i) the prevalence of positive results of anti-tissue
transglutaminase (anti-tTG) antibody assays and coeliac disease (CD) in a rural
Australian community; and (ii) whether confirmatory testing of a positive assay
result with an alternative anti-tTG assay improved the positive predictive
value of the test in population screening for CD. DESIGN:
Retrospective analysis in December 2004 of stored serum samples taken in
1994-1995 from 3011 subjects in the Busselton
Health Study follow-up. Assays for IgA and IgG anti-tTG antibodies were
performed, and positive or equivocal samples were retested with a different
commercial anti-tTG assay. Available subjects with one or more positive assay
results were interviewed, had serum collected for repeat anti-tTG assays and
for HLA-DQ2 and HLA-DQ8 haplotyping and, if appropriate, gastroscopy and
duodenal biopsy were performed. In unavailable subjects, HLA-DQ2 and -DQ8
haplotyping was performed on stored sera. Total serum IgA levels were assessed
in subjects with initially negative assay results. MAIN
OUTCOME MEASURE: Prevalence of anti-tTG positivity and biopsy-proven CD. RESULTS:
In 47 of 3011 serum samples (1.56%), at least one anti-tTG assay gave positive
results: 31 of the subjects who provided these sera were available for clinical
review, and 21 were able to have a gastroscopy. Seventeen subjects (0.56%) were
diagnosed with definite CD (14 were confirmed at gastroscopy, and three
unavailable subjects had three positive results of anti-tTG assays and an HLA
haplotype consistent with CD); in a further 12 unavailable subjects, CD status
was considered equivocal, with one or more positive anti-tTG assay results and
an HLA haplotype consistent with CD. If these subjects were regarded as having
CD, the prevalence of CD would be 0.96%. The positive predictive value when all
three anti-tTG assays gave positive results was 94%, but fell to 45.2% with
only one positive result. CONCLUSIONS:
The prevalence of anti-tTG antibodies in this population is 1.56%; the
prevalence of CD is at least 0.56%. The utility of a single, positive result of
an anti-tTG assay in screening for CD in the community is poor, and repeat
and/or collateral assessment with different assays may decrease the need for
gastroscopy and distal duodenal biopsy. Intern
Med J. 2010 Apr;40(4):286-92. Epub 2009 Mar 23. An Australian
cardiovascular risk equation for type 2 diabetes: the Fremantle Diabetes Study. BACKGROUND:
There is no valid cardiovascular disease (CVD) risk prediction equation for
Australians with diabetes. The aim of this study is to develop and validate a
multivariate risk function for 5-year cardiovascular risk prediction in
Australian type 2 diabetes patients. METHODS:
The Fremantle Diabetes Study is a community-based longitudinal observational
study. A total of 1240 type 2 diabetic patients (95.8% of the baseline cohort)
with all required risk factor data were followed from baseline (1993-1996) for
5 years or until they experienced a cardiovascular event or died, whichever
came first. CVD during follow up was defined as hospitalization for/with
myocardial infarction or stroke, and death from cardiac or cerebrovascular
causes or sudden death. Validation of the algorithm was performed on an
independent diabetic cohort from the Busselton
Health Study. RESULTS:
During 5570 patient-years of follow up, 185 (14.9%) had at least one CVD event
and 175 (14.1%) died (57.7% from CVD). Variables in the final model comprised
age, sex, prior CVD, ln(urinary albumin : creatinine ratio), lnHbA(1c), ln(high
density lipoprotein-cholesterol), Southern European ethnic background and
Aboriginality. The mean 5-year predicted risk of a CVD event was 15.5%. Applied
to the Busselton cohort,
discrimination of the model was good (AUC = 0.84, P < 0.001) as was the
goodness-of-fit (Hosmer-Lemeshow C-test, P= 0.85) and accuracy (mean squared
error (95% confidence interval) = 0.09 (0-0.76)). The positive and negative
predictive values for a 10% 5-year CVD risk cut-off were 23.4% and 97.7%
respectively. CONCLUSION:
This simple diabetes-specific 5-year CVD risk equation is the first validated,
population-based Australian model. It should have a role in diabetes management
in primary and specialist care. J
Clin Sleep Med. 2009 Feb 15;5(1):15-20. Is sleep apnea an
independent risk factor for prevalent and incident diabetes in the Busselton
Health Study? Woolcock
Institute of Medical Research, BACKGROUND:
Cross-sectional analyses of North American population-based cohorts and one
nonsignificant longitudinal analysis have suggested that obstructive sleep
apnea (OSA) is a risk factor for diabetes mellitus. However, this observation
has yet to be replicated outside the METHODS:
Residents of the Western Australian town of RESULTS:
Of 399 participants at baseline, 295 had complete data and did not have
diabetes at baseline; 9 incident cases were observed within 4 years. At
baseline moderate-severe OSA was associated with a univariate, but not
multivariate, increased risk of diabetes (odds ratio = 4.37, 95% CL = 1.12,
17.12). Longitudinally, moderate-severe OSA was a significant univariate and
independent risk factor for incident diabetes (fully adjusted OR = 13.45, 95%
CL = 1.59, 114.11). CONCLUSIONS:
Moderate-severe sleep apnea was a significant risk factor for incident diabetes
in this Australian population-based cohort. However, the confidence intervals
were wide and meta-analyses or studies with greater power will be required to
verify the relationship between sleep apnea and the incidence of diabetes in
community-based populations. Am
J Gastroenterol. 2009 Apr;104(4):861-7. Epub 2009 Mar 17. NAFLD as a risk factor
for the development of diabetes and the metabolic syndrome: an eleven-year
follow-up study. Adams
LA, Waters OR, Knuiman MW, Elliott RR, Olynyk JK. School
of Medicine and Pharmacology, OBJECTIVES:
Non-alcoholic fatty liver disease (NAFLD) uncommonly results in cirrhosis and
liver-related death; however, its impact on the development of metabolic
complications remains unclear. We sought to determine whether NAFLD with
elevated aminotransaminase (ALT) levels was a risk factor for incident diabetes
or the metabolic syndrome (MS) over an 11-year period. METHODS:
Adult residents of RESULTS:
A total of 358 subjects, 68% male (109 NAFLD, 249 non-NAFLD), mean age (s.d.)
59.9 (11.6) years, attended follow-up 11.1 years after the initial assessment.
After excluding subjects with diabetes at baseline, those with NAFLD were more
likely to have developed diabetes on follow-up (20/106, 18.9% vs. 15/246, 6.1%;
P<0.001). After excluding subjects with MS at baseline, those with NAFLD were
more likely to have developed MS at follow-up (27/81, 33.3% vs. 51/226, 22.6%;
P=0.056). However, in multivariate logistic regression models, NAFLD was no
longer a significant independent predictor of the development of diabetes or MS
after adjusting for baseline waist circumference, hypertension, and insulin
resistance. None of the subjects developed liver complications. CONCLUSIONS:
Subjects with NAFLD and elevated ALT levels are at an increased risk of
developing diabetes and the MS. This may be because of the presence of
associated metabolic risk factors. Eur
J Cardiovasc Prev Rehabil. 2009 Apr;16(2):235-41. Utility of the metabolic
syndrome and its components in the prediction of incident cardiovascular
disease: a prospective cohort study. Knuiman
MW, Hung J, Divitini ML, Davis TM, Beilby JP. BACKGROUND:
To investigate the prognostic importance of the metabolic syndrome (MetS) on
incident cardiovascular disease (CVD). DESIGN:
Prospective cohort study. METHODS:
The study was based on 10-year follow-up of 3041 men and women aged 25-84 years
without CVD or diabetes who participated in the 1994/1995 Busselton Health Survey. Hazards ratio (HRs) from Cox regression
models were used to describe the effect of the MetS as a dichotomous
classification and as the number of risk components on incident coronary heart
disease (CHD), stroke and all CVD events. RESULTS:
All cardiovascular and metabolic risk factors studied showed a strong
association with the number of MetS risk components. The age-adjusted and
sex-adjusted HR for the MetS was 1.70 (95% confidence interval: 1.15-2.51) for
incident CHD but this was reduced to almost unity after adjustment for
cardiovascular risk factors or the homoeostasis model assessment measure of
insulin resistance. However, the number of MetS risk components remained
significant (P<0.01) with those having 3+ risk components with a three-fold
increase in risk compared with those with no risk components (adjusted HR:
3.59, 95% confidence interval: 1.43-8.99). CONCLUSION:
Consideration of the number of MetS risk components seems to be more
informative than the (dichotomous) MetS classification when determining risk in
clinical practice. Identification of people without any MetS risk components is
clinically valuable, as these people seem to have a substantially reduced risk
of developing CHD. Intern
Med J. 2009 Aug;39(8):532-8. Epub 2008 Aug 16. Serum testosterone levels
correlate with haemoglobin in middle-aged and older men. Yeap
BB, Beilin J, Shi Z, Knuiman MW, Olynyk JK, Bruce DG, Milward EA. BACKGROUND:
Lower testosterone levels are associated with anaemia in older men and women.
The relation between testosterone and haemoglobin (Hb) in younger and
middle-aged men is less well defined. The aim of the study was to examine the
association between testosterone and Hb levels in men spanning middle to older
ages. METHODS: A cross-sectional analysis of 492 men aged
30.7-94.5 years from the Busselton
Health Survey, RESULTS:
Haemoglobin correlated to total and free testosterone concentrations (r= 0.13,
P= 0.003 and r= 0.20, P < 0.001, respectively). Hb and SHBG were inversely correlated
(r=-0.14, P= 0.001). Hb increased across lowest to highest quartiles of total
testosterone (P= 0.02) and free testosterone (P < 0.001), but not SHBG.
After adjusting for age, waist circumference, smoking status, alcohol
consumption, renal function and ferritin, total testosterone was associated
with Hb (beta= 0.037, P= 0.003) as was free testosterone (beta= 2.32, P <
0.001), whereas SHBG was not associated. CONCLUSION:
Testosterone concentration modulates Hb levels in community-dwelling men across
a wide age range. Further studies are needed to clarify implications of this
association between testosterone and Hb in men. Diabetologia.
2009 Jan;52(1):106-14. Epub 2008 Nov 19. The association of common
genetic variants in the APOA5, LPL and GCK genes with longitudinal changes in
metabolic and cardiovascular traits. Webster
RJ, Warrington NM, Weedon MN, Hattersley AT, McCaskie PA, Beilby JP, Palmer LJ,
Frayling TM. Centre
for Genetic Epidemiology and Biostatistics, University of Western Australia, B
Block, Queen Elizabeth II Medical Centre, Nedlands, WA 6009, Australia.
bwebster@meddent.uwa.edu.au AIMS/HYPOTHESIS:
Common genetic variants influence plasma triacylglycerol, HDL-cholesterol
(HDL-C) and glucose levels in cross-sectional studies. However, the
longitudinal effects of these established variants have not been studied. Our
aim was to examine the longitudinal associations of four such variants in the
apolipoprotein A-V (APOA5), lipoprotein lipase (LPL), and glucokinase (GCK)
genes with fasting glucose or lipid levels. METHODS:
The individuals analysed were participants in the Busselton Health Survey (n = 4,554). Cross-sectional analyses of
family data used the total association test. Longitudinal association analyses
of unrelated participant data (n = 2,864) used linear mixed-effects models. RESULTS:
The findings of cross-sectional association analyses replicated those of
previous studies. We observed associations of the G and C alleles at the APOA5
single nucleotide polymorphisms (SNPs) rs662799 and rs3135506 with raised
triacylglycerol levels (p = 0.0003 and p < 0.0001, respectively), the 447X
allele at the LPL SNP rs328 with reduced triacylglycerol levels (p = 0.0004)
and raised HDL-C levels (p = 0.0004), and the A allele of the GCK SNP rs1799884
with raised fasting glucose level (p = 0.015). Longitudinal association
analyses showed that most of these associations did not change in the same
individuals over an average follow-up time of 17.4 years, though there was some
evidence that the association of the 447X allele of rs328 with raised HDL-C
level significantly increased with age (p = 0.01), and that the association of
the C allele of rs3135506 with raised triacylglycerol level significantly
increased over time (p = 0.0007). CONCLUSIONS/INTERPRETATION:
The current study suggests that the effects of established gene variants on
lipid and glucose traits do not tend to alter with age during adulthood or over
time. Sleep.
2008 Aug 1;31(8):1079-85. Sleep apnea as an
independent risk factor for all-cause mortality: the Busselton Health Study. Woolcock
Institute of Medical Research, BACKGROUND:
Previously published cohort studies in clinical populations have suggested that
obstructive sleep apnea (OSA) is a risk factor for mortality associated with
cardiovascular disease. However, it is unknown whether sleep apnea is an
independent risk factor for all-cause mortality in a community-based sample
free from clinical referral bias. METHODS:
Residents of the Western Australian town of RESULTS:
Among the 380 participants, 18 had moderate-severe OSA (RDI > or = 15/hr, 6
deaths) and 77 had mild OSA(RDI 5 to < 15/hr, 5 deaths). Moderate-to-severe
OSA was independently associated with greater risk of all-cause mortality
(fully adjusted hazard ratio [HR] = 6.24, 95% CL 2.01, 19.39) than non-OSA (n =
285, 22 deaths). Mild OSA (RDI 5 to < 15/hr) was not an independent risk
factor for higher mortality (HR = 0.47, 95% CL 0.17, 1.29). CONCLUSIONS:
Moderate-to-severe sleep apnea is independently associated with a large
increased risk of all-cause mortality in this community-based sample. J
Gastroenterol Hepatol. 2008 Jul;23(7 Pt 1):1089-93. Epub 2008 Jun 28. Body mass index is a
stronger predictor of alanine aminotransaminase levels than alcohol
consumption. School
of Medicine and Pharmacology, 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 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 < 0.0001 for all tests). Alcohol consumption was modestly associated with
ALT in females (P = 0.01) but not in males (P = 0.9). In contrast, GGT was significantly
associated with alcohol in both genders (P < 0.0005). The risk of an
elevated ALT was seven-fold higher with obesity but only two-fold higher with
moderate or heavy alcohol use. Obesity accounted for half of all elevated ALT
levels in the cohort, whereas alcohol excess was responsible for less than 10%.
No synergistic effect was observed between BMI or waist circumference and
alcohol on ALT or 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. Mayo
Clin Proc. 2008 May;83(5):543-9. Noncitrus fruits as novel dietary
environmental modifiers of iron stores in people with or without HFE gene
mutations. Milward
EA, Baines SK, Knuiman MW, Bartholomew HC, Divitini ML, Ravine DG, Bruce DG,
Olynyk JK. School
of Biomedical Sciences and Hunter Medical Research Institute, 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),
consistent with previous studies, but did not interact with fruit with regard
to effects on serum ferritin (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. Clin
Endocrinol (Oxf). 2008 Oct;69(4):648-52. Epub 2008 Mar 12. Significant inverse
relationship between serum free T4 concentration and body mass index in
euthyroid subjects: differences between smokers and nonsmokers. Makepeace
AE, Bremner AP, O'Leary P, Leedman PJ, Feddema P, Michelangeli V, Walsh JP. Department
of Endocrinology and Diabetes, OBJECTIVE:
There are conflicting data regarding the relationship between thyroid function
and body mass index (BMI) in euthyroid subjects, and it is uncertain whether
tobacco smoking modifies this relationship. The objective of this study was to
examine the relationships between thyroid function, BMI and smoking in
euthyroid subjects. DESIGN:
Linear regression models were used to examine the relationships between serum
free T4, serum TSH, BMI and smoking in a cross-sectional, community-based
sample of 1853 euthyroid subjects in RESULTS:
There was a significant negative relationship between free T4 and BMI: after
adjustment for age and sex, each 1 pmol/l increase in free T4 was associated
with a decrease in BMI of 0.12 kg/m(2) (95% CI 0.06, 0.18; P < 0.001). The
mean BMI +/- SD of subjects in the highest quintile of free T4 concentration
was 24.4 +/- 3.5 kg/m(2), compared with 26.1 +/- 3.8 kg/m(2) for the lowest
quintile. The relationship between free T4 and BMI was statistically
significant (adjusted for age and sex) in subjects who had never smoked (P =
0.001) and former smokers (P = 0.011), but not in current smokers (P = 0.77).
There was no significant relationship between TSH and BMI: after adjustment for
age and sex, each 1 mU/l increase in TSH was associated with an increase in BMI
of 0.08 kg/m(2) (95% CI -0.16, 0.32; P = 0.53). CONCLUSIONS:
In euthyroid subjects, small differences in free T4 are associated with
differences in BMI. This relationship is not present in current smokers. We
speculate that this may be relevant to weight changes associated with smoking
cessation. Prev
Med. 2008 Jul;47(1):71-6. Epub 2008 Feb 15. Are the associations
between diet and C-reactive protein independent of obesity? Hickling
S, Hung J, Knuiman M, Divitini M, Beilby J. OBJECTIVES:
To determine the relative magnitude of the effect of dietary factors on
circulating C-reactive protein (CRP) levels, controlling for BMI. METHODS:
1808 men and 2269 women attended the 1994/95 follow-up survey from the Busselton Health Study, RESULTS:
After controlling for BMI, CRP levels were associated with red meat intake
(males only, p=0.001), fruit intake (males p<0.0001, females p=0.029),
potato intake (males p=0.008, females p=0.029), using wholemeal bread (males
p=0.014, females p=0.018), using polyunsaturated fats as a spread and in
cooking (females only, p=0.005), and rarely or never adding salt to food (males
p=0.012, females p=0.004). The overall diet score was significantly
(negatively) related to CRP in males (p<0.0001) and females (p<0.0001). The
relative decrease in CRP from a moderately healthy diet, compared to an
unhealthy diet was 37% in men and 24% in women. This was comparable to a
difference in BMI of at least 3 kg/m(2) (or a difference in weight of
approximately 9 kg for a person of average height). CONCLUSION:
A healthy diet and lower weight have independent beneficial effects of similar
magnitude on CRP levels. Hum
Genet. 2008 Apr;123(3):297-306. Epub 2008 Feb 6. A genome-wide association
scan for asthma in a general Australian population. Hui
J, Oka A, James A, Palmer LJ, Musk AW, Beilby J, Inoko H. Western
Australian Institute for Medical Research and UWA Centre for Medical Research,
B Block, QEII Medical Centre, The University of Western Australia, Nedlands,
WA, 6009, Australia. jhui@cyllene.uwa.edu.au To
date, almost every chromosome has been implicated in genetic susceptibility to
asthma to some degree. When compared with single nucleotide polymorphism,
microsatellite markers exhibit high levels of heterozygosity and therefore
provide higher statistical power in association. The objective of this study
was to perform a genome-wide association study using 23,465 in-house
microsatellite markers to detect asthma susceptibility regions in the Busselton population. In this study,
three separate pooled DNA screenings yielded 18 markers with significantly
different estimated frequencies in the three separate "case and
control" pools: each pool consisting of 60 males and 60 females. These
markers were evaluated by individual typing in 360 cases and 360 controls. Two
markers showed significant differences between cases and controls (P = 0.001
and P = 0.003). Regions surrounding the two markers were subjected to
high-density association mapping with a total of 14 additional markers. We were
able to confirm and fine map the association in these two regions by typing 14
additional microsatellite markers (1805A09 (D18S0325i), P = 0.002; 1806D05
(D18S0181i), P = 0.001). Each region contains a predicted gene that showed
strong associations with asthma. Further studies are underway to characterize
the novel candidate asthma susceptibility genes identified in this genome-wide
study. Am
J Cardiol. 2008 Jan 15;101(2):193-8. Prevalence and risk
factor correlates of elevated C-reactive protein in an adult Australian
population. Hung
J, Knuiman MW, Divitini ML, Davis T, Beilby JP. School
of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, University of
Western Australia, Perth, Western Australia. jhung@cyllene.uwa.edu.au Measurement
of the inflammatory biomarker C-reactive protein (CRP) is advocated for
coronary heart disease risk assessment. The distribution and correlates of CRP
in the general population should be known before it is used in clinical
practice. CRP was measured in 1,761 men and 2,248 women aged 25 to 84 years who
attended the 1994/1995 Busselton Health Survey. Prevalences of increased
CRP >3 mg/L for age groups 25 to 39, 40 to 59, and 60 to 84 years were
15.7%, 20.6%, and 38.7%, respectively, in men and 21.2%, 22.1%, and 33.7%,
respectively, in women not on hormone therapy. Logistic regression analysis
identified independent predictors of increased CRP in men as obesity (odds
ratio [OR] 3.5, 95% confidence interval [CI] 2.4 to 5.0), smoking (OR 3.1, 95%
CI 2.1 to 4.5), hypertension (OR 1.6, 95% CI 1.1 to 2.3), and low high-density
lipoprotein cholesterol (OR 1.4, 95% CI 1.0 to 1.8). In women, predictors were
obesity (OR 7.8, 95% CI 5.8 to 10.6), hypertension (OR 1.4, 95% CI 1.0 to 1.9),
high triglycerides (OR 1.6, 95% CI 1.1 to 2.4), vigorous exercise (OR 0.7, 95%
CI 0.5 to 0.9), oral contraceptive use (OR 4.6, 95% CI 3.3 to 6.5), and hormone
replacement therapy (OR 2.8, 95% CI 1.9 to 4.0). Overall, risks of increased
CRP attributable to the presence of an abnormal or borderline coronary heart
disease risk factor were 59% for men and 64% for women. In conclusion, despite
gender-related differences in cardiovascular risk, increased CRP occurred
commonly in men and women. Because increased CRP was largely attributable to
conventional coronary heart disease risk factors, measurement of CRP may have
limited utility for risk screening and primary prevention.
Heart
Lung Circ. 2008 Apr;17(2):90-5. Epub 2007 Sep 11. C-reactive protein and
interleukin-18 levels in relation to coronary heart disease: prospective cohort
study from Busselton Western Hung
J, Knuiman MW, Divitini ML, School
of Medicine & Pharmacology, Sir Charles Gairdner Hospital Unit, University
of Western Australia, Nedlands, Western Australia, Australia.
jhung@cyllene.uwa.edu.au BACKGROUND:
Elevated levels of inflammatory markers are associated with incident coronary
heart disease (CHD), but it remains controversial whether these markers provide
incremental predictive value to conventional risk factors. We investigated the
relationship between C-reactive protein (CRP) and interleukin-18 (IL-18) levels
and risk of CHD in men and women without initial cardiovascular disease. METHODS:
A prospective case-cohort design over the period 1981-2001 involving 253
incident CHD cases and a random sub-cohort of 441 subjects was used. Cox
proportional hazards regression was used to estimate the relative risks (RRs)
of CHD for continuous and tertiles of CRP and IL-18 after controlling for
conventional risk factors. RESULTS:
The multivariate-adjusted RR of CHD associated with one unit increase in log
CRP in the overall population was 1.29 (1.07, 1.55; trend P=0.008). Men and
women in the top compared to bottom third of CRP distribution had an adjusted
RR for CHD of 1.65 (1.03-2.65; P=0.036). The multivariate RR for continuous log
IL-18 was 1.34 in men, 1.63 in women and 1.36 overall, and none reached
statistical significance. CONCLUSIONS:
Baseline CRP but not IL-18 levels are independently predictive of future CHD.
However CRP provides only modest additional predictive value over conventional
risk factors and the benefit of a prevention strategy based on CRP still needs
to be established. Br
J Cancer. 2007 Sep 3;97(5):686-7. Epub 2007 Aug 7. Left-handedness and risk
of breast cancer. Fritschi
L, Divitini M, Talbot-Smith A, Knuiman M. Western
Australian Institute for Medical Research, Nedlands, Left-handedness
may be an indicator of intrauterine exposure to oestrogens, which may increase
the risk of breast cancer. Women (n=1786) from a 1981 health survey in Busselton were followed up using death
and cancer registries. Left-handers had higher risk of breast cancer than
right-handers and the effect was greater for post-menopausal breast cancer
(hazard ratio=2.59, 95% confidence interval 1.11-6.03). J
Clin Endocrinol Metab. 2007 Sep;92(9):3599-603. Epub 2007 Jun 26. Age-related changes in
serum testosterone and sex hormone binding globulin in Australian men:
longitudinal analyses of two geographically separate regional cohorts. Liu
PY, Beilin J, Meier C, Nguyen TV, Center JR, Leedman PJ, Seibel MJ, Eisman JA,
Handelsman DJ. Department
of Andrology, Concord Hospital and ANZAC Research Institute, University of
Sydney, Sydney, New South Wales 2139, Australia. BACKGROUND:
Cross-sectional studies from different populations show a variable decline in
blood testosterone concentrations as men age. Few population representative
cohorts have been followed up over time. OBJECTIVE:
The objective of the study was to quantify longitudinally the change in serum
testosterone and SHBG concentrations with age in two well-defined,
representative but geographically widely separated regional Australian cohorts. SUBJECTS
AND SETTING: The Busselton cohort
comprises individuals aged 18-90 yr residing in RESULTS:
Longitudinal analyses show the following: 1) total testosterone declines
comparably (P > 0.9) by 1.3% (Busselton)
and 0.9% (Dubbo) per annum with the same rates of decline when analyses were
restricted to men older than 60 yr of age; 2) annual changes in SHBG were also
very similar in age-restricted analyses (2.3% vs. 2.5%, P = 0.48); and 3) the
annual increase in SHBG was steeper in middle-aged and older men (P < 10(-3)
vs. young men). These longitudinal changes were all up to 4-fold greater in
magnitude, compared with cross-sectional analyses of baseline data. CONCLUSION:
In two separate regional Australian populations, blood testosterone fell and
SHBG increased comparably with age. Age-related changes in blood testosterone
and SHBG previously described in urban-dwelling men are the same in men who
reside in smaller regional cities of another continent. Longitudinal study of
risk factors for habitual snoring in a general adult population: the Busselton
Health Study. Knuiman
M, James A, Divitini M, Bartholomew H. BACKGROUND:
The aim of this longitudinal study was to identify body size, behavioral, and
respiratory risk factors for the development of habitual snoring in a general
adult population. METHODS:
The sample for this study comprised 967 adults aged 25 to 74 years who reported
not snoring in the 1981 Busselton Health Survey and who also attended the
1994-1995 follow-up survey. Logistic regression was used to identify and
quantify the effect of baseline and change risk factors for the development of
habitual snoring. RESULTS:
A total of 13% had become habitual snorers by 1994-1995. Male gender (odds
ratio [OR], 3.5) and baseline body mass index (OR, 1.4 per 3.4 kg/m(2)) were
significant predictors of habitual snoring; after accounting for these
variables, no other baseline body size, behavioral, or respiratory/allergy variables
were significantly related to the development of habitual snoring. However,
change in body mass index over the 14-year follow-up period (OR, 1.55 per 2.3
kg/m(2)), development of asthma (OR, 2.8), and commencement of smoking (OR,
2.2) were additional significant independent risk factors for development of
habitual snoring. CONCLUSIONS:
This study has confirmed male gender, obesity, and weight gain as key
determinants of habitual snoring, and has indicated that development of asthma
and taking up smoking also play a role. Maintaining a healthy weight and not
smoking are recommended lifestyle preventive strategies to reduce the risk of
sleep-disordered breathing and its sequelae. Subclinical thyroid dysfunction
and blood pressure: a community-based study. Walsh
JP, Bremner AP, Bulsara MK, O'Leary P, Leedman PJ, Feddema P, Michelangeli V. Department
of Endocrinology and Diabetes, OBJECTIVE:
Overt hypothyroidism and hyperthyroidism are associated with hypertension, but
it is uncertain whether the same is true of subclinical hypothyroidism and
hyperthyroidism. DESIGN, SUBJECTS
AND MEASUREMENTS: Cross-sectional study of 2033 participants (aged 17-89 years)
in the Busselton Thyroid Study who
did not have a history of thyroid disease. Systolic blood pressure (SBP),
diastolic blood pressure (DBP) and the prevalence of hypertension (defined as
SBP >or=140 mmHg, DBP >or=90 mmHg or on treatment for hypertension) in
subjects with thyroid dysfunction and euthyroid subjects were compared using
linear regression models. Subjects with treated hypertension (N = 299) were
excluded from analyses of SBP and DBP but included in analyses of hypertension
prevalence. RESULTS:
Mean SBP, DBP and the prevalence of hypertension did not differ significantly
between subjects with subclinical hypothyroidism (N = 105) and euthyroid
subjects (N = 1859), nor did they differ between subjects with serum TSH
concentrations in the upper reference range (2.0-4.0 mU/l; N = 418) and those
with TSH concentrations in the lower reference range (0.4-2.0 mU/l; N = 1441).
The prevalence of hypertension was higher in subjects with subclinical
hyperthyroidism than euthyroid subjects (prevalence odds ratio 2.8, 95%
confidence interval 1.3-6.0 adjusted for age, age(2) and sex), but this was
based on a small number of subjects with subclinical hyperthyroidism (N = 35). CONCLUSIONS:
Subclinical hypothyroidism is not associated with hypertension. The observed
association between subclinical hyperthyroidism and hypertension requires
confirmation in a larger sample. Tissue
Antigens. 2006 Aug;68(2):127-34. The association between
non-melanoma skin cancer and a young dimorphic Alu element within the major
histocompatibility complex class I genomic region. Dunn
DS, Inoko H, Kulski JK. Centre
for Bioinformatics and Biological Computing, School for Information Technology,
A
non-melanoma skin cancer (NMSC) susceptibility locus within the major
histocompatibility complex (MHC) class I region was previously identified
telomeric of the HLA-C gene using high-density microsatellite markers. Here, we
have extended the previous microsatellite study by using the same DNA samples
obtained from 154 NMSC patients and 213 normal controls from the town of Busselton in Western Australia and
examined the relationship between five polymorphic Alu insertions (POALINs)
within the MHC class I region and their association with NMSC. The genotype
distribution of the AluyTF insertion that is located within the NMSC
susceptibility region telomeric of the HLA-C gene was significantly increased
according to the Fisher's exact test in the NMSC patients, and it was not in
Hardy-Weinberg equilibrium in the control group. There was no difference
between the cancer patients and controls for the genotypes of the AluyMICB
locus within intron 1 of the MICB gene and the other three POALINs (AluyHJ,
AluyHG and AluyHF) that are located within the genomic region of the HLA-A, -G
and -F gene cluster. The test for significant linkage disequilibrium for 10
pairs of POALIN loci and estimations of two locus POALIN haplotype frequencies
also revealed AluyTF differences between the cases and controls. In conclusion,
the MHC class I POALIN, AluyTF, that is located within the NMSC susceptibility
locus and near the HLA-C gene was strongly associated with NMSC. This finding,
using five different polymorphic Alu insertion markers, supports the previous
microsatellite association study that one or more genes located in close
proximity to the AluyTF insertion has a potential role in NMSC. Clin
Exp Allergy. 2006 Jun;36(6):728-34. AluyMICB dimorphism
within the class I region of the major histocompatibility complex is associated
with asthma and airflow obstruction in the Busselton population. Hui
J, Palmer LJ, James UWA
Centre for Medical Research, Western Australian Institute for Medical Research,
The University of Western Australia, and Western Australian Sleep Disorders
Research Institute, Sir Charles Gairdner Hospital, Western Australia.
jhui@cyllene.uwa.edu.au AIM:
To examine the association between the Alu dimorphism within the first intron
of the MICB gene and asthma and airflow obstruction. Background The highly
polymorphic non-classical MHC class I polypeptide-related (MIC) genes, MICA and
MICB, encode stress inducible glycoproteins, which are expressed on a variety
of epithelial cells, including those of the lungs. METHODS:
AluyMICB genotyping was performed on 1109 subjects from the Busselton Health Study. From a standard
questionnaire, 359 individuals indicated that they had been diagnosed by a
doctor with asthma. Lung function was assessed by the forced expired volume in
1 second (FEV1) and expressed as a percent of the predicted value. Airflow
obstruction was defined as FEV1<80% predicted. RESULTS:
In men, a dominant relationship was found between the AluyMICB DD genotype and
asthma (P=0.006; chi2(2)=7.65). Furthermore, multivariate analysis adjusted for
age, height, weight and body mass index (BMI) showed a relationship between DD
genotype and asthma in men in a dominant model (odds ratio (OR)=1.97; 95%
confidence interval (CI)=1.11-3.51; P=0.021). In women, an association was
found between the AluyMICB II genotype and FEV1 percent predicted as a
continuous variable (P=0.001). When adjusted for age and BMI, it showed a
significant relationship between AluyMICB and airflow obstruction in a dominant
model (OR=14.11%, 95% CI 3.29-60.57, P<0.001). However, no association was
found between the AluyMICB II genotypes and airflow obstruction in men. CONCLUSION:
These findings suggest the possible involvement of a MHC class I gene in
abnormal airway structure in women and airway function in men. J
Clin Rheumatol. 2006 Jun;12(3):109-13. Primary osteoarthritis in
the ankle joint is associated with finger metacarpophalangeal osteoarthritis
and the H63D mutation in the HFE gene: evidence for a hemochromatosis-like
polyarticular osteoarthritis phenotype. Carroll
GJ. ArthroCare
Pty Ltd., BACKGROUND
AND AIM: Osteoarthritis (OA) can occur in the ankle joint. It also occurs in an
appreciable proportion of subjects with hereditary hemochromatosis (HH). Might
these conditions have common genetic characteristics? The aim of this study was
to test the hypothesis that HFE gene mutations are associated with primary
osteoarthritis in the ankle joint. METHODS:
Consecutive referred patients who had primary or secondary (posttraumatic) OA
of the ankle joint were assessed by a single rheumatologist and had a full
physical and joint examination. Plain x-rays of the ankle joint, other
clinically involved osteoarthritic joints, iron studies, HFE genotyping, and Hb
electrophoresis were performed. The significance of differences was evaluated
by 2-tailed Fisher exact test. RESULTS:
Fourteen patients met the inclusion criteria for primary ankle OA and 6 met the
criteria for secondary ankle OA. One of the 14 had had a previous subtalar
joint fusion and was excluded. Among the remaining 13, 7 had OA in the index
and/or middle finger metacarpophalangeal joints (MCP2,3 OA) with radiologic
features similar to those found in hemochromatotic arthropathy (HA).
Furthermore, 11 of the 13 had at least one HFE mutation, one subject in this
group was homozygous for H63D, one was compound heterozygous for C282Y and
S65C, and one was compound heterozygous for H63D and S65C. Eight were heterozygous
for H63D. The 13 subjects were compared with the 6 secondary ankle OA subjects
and with a previously studied population cohort (n = 3011) from the town of CONCLUSIONS:
A strong and statistically significant association was observed between HFE
gene mutations and primary OA in the ankle joint. The frequent presence of
MCP2,3 OA in these patients suggests the existence of a type 2 polyarticular OA
phenotype that closely resembles the arthropathy of HH and which appears to be
clinically differentiable from type 1 OA or nodal generalized OA (NGOA). HFE
gene mutations may be a marker for the type 2 polyarticular OA phenotype and a
clue to OA pathogenesis. J
Gastroenterol Hepatol. 2006 Mar;21(3):595-8. Population-based study of
the relationship between mutations in the hemochromatosis (HFE) gene and
arthritis. Sherrington
CA, Knuiman MW, Divitini ML, Bartholomew HC, Cullen DJ, Olynyk JK. Department
of Gastroenterology, BACKGROUND
AND AIM: Mutations in the hemochromatosis (HFE) gene are carried by one in
three individuals of METHODS:
A population-based study was conducted in 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 J
Rheumatol. 2006 Apr;33(4):741-3. HFE gene mutations are
associated with osteoarthritis in the index or middle finger
metacarpophalangeal joints. Carroll
GJ. University
Department of Medicine, OBJECTIVE:
. To test the hypothesis that possession of either C282Y or H63D mutations in
the HFE gene is associated with primary osteoarthritis (OA) in joints commonly
affected in hemochromatotic arthropathy. METHODS:
HFE genotyping was performed in 87 patients with radiologically proven OA in 3
joint regions: index or middle finger metacarpophalangeal joints (MCP2,3; n =
52), elbow joints (n = 8), ankle, intertarsal or tarsometatarsal joints
(ankle/IT/TMT; n = 27); and in 56 patients with radiologically proven OA in
finger interphalangeal (IP) joints, but not MCP2,3 joints (IP OA control
group). HFE mutation frequencies in these groups were also compared to those in
a similar population (Busselton
population control group). RESULTS:
A statistically significant association between HFE mutations and OA was
observed for the MCP2,3 joints (p = 0.0001) and the ankle/IT/TMT joint group (p
= 0.002) as well as for the 3 joint regions collectively (p = 0.0001), but not
for the elbow joints (p = 0.062). Comparison with the Busselton population controls showed similar statistically
significant associations, except for the elbow and ankle/IT/TMT groups, where
similar trends were observed. CONCLUSION:
HFE gene mutations are associated with OA in the MCP2,3 joints. These mutations
may be markers for a polyarticular OA phenotype. Clin
Endocrinol (Oxf). 2006 Jan;64(1):97-104. Investigations of thyroid
hormones and antibodies based on a community health survey: the Busselton
thyroid study. O'Leary
PC, Feddema PH, Michelangeli VP, Leedman PJ, Chew GT, Knuiman M, Kaye J, Walsh
JP. Clinical
Biochemistry, Women's and Children's Health Service, OBJECTIVE:
Overt or subclinical thyroid dysfunction is common within the community, yet
the significance of subtle anomalies in thyroid function tests remains
contentious. The aims of this study were to: (a) establish reference intervals
for serum-free thyroxine (FT4), thyroid-stimulating hormone (TSH) and thyroid
antibodies (antithyroperoxidase, TPOAb and antithyroglobulin, TgAb) in the Busselton community of south-western SUBJECTS
AND DESIGN: In 1981, 2115 adults residing in Busselton participated in a cross-sectional health survey that
involved blood collection and a questionnaire on lifestyle and general health
history. MEASUREMENTS:
Serum samples were analysed for FT4, TSH, TPOAb and TgAb by immunochemiluminescent
assays. RESULTS:
Based on standard statistical approaches and using guidelines recommended by
the National Academy of Clinical Biochemistry (NACB), reference intervals were
derived for each analyte: 9-23 pmol/l for FT4, 0.4-4.0 mIU/l (TSH), < 35 KIU/l
(TPOAb) and < 55 KIU/l (TgAb). The prevalence of elevated thyroid antibodies
was 12.4% among subjects without a history of thyroid disease and is more
common in women than in men. Elevated thyroid antibody levels were observed at
both extremes of TSH abnormality, but were more commonly increased when TSH
levels were above 4.0 mIU/l (63% subjects) than for those with TSH levels
0.4-4.0 mIU/l (7.8% subjects). CONCLUSIONS:
This study establishes the prevalence of antibodies to thyroperoxidase and
thyroglobulin in a community-based sample and reference intervals for free T4
and TSH. When the NACB decision limits are applied to older men or women, there
is a markedly increased number with 'elevated' autoantibody levels compared to
sex- and age-specific reference intervals. Ann
Epidemiol. 2006 Mar;16(3):206-12. Epub 2005 Dec 15. Folate levels and cancer
morbidity and mortality: prospective cohort study from Rossi
E, Hung J, Beilby JP, Knuiman MW, Divitini ML, Bartholomew H. Pathcentre,
QEII Medical Centre, 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 ( 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. Clin
Endocrinol (Oxf). 2005 Dec;63(6):670-5. Thyroid dysfunction and
serum lipids: a community-based study. Walsh
JP, Bremner AP, Bulsara MK, O'leary P, Leedman PJ, Feddema P, Michelangeli V. Department
of Endocrinology and Diabetes, OBJECTIVE:
It is uncertain whether subclinical hypothyroidism (SCH) is associated with
hypercholesterolaemia, particularly in subjects with SCH and serum TSH < or
= 10 mU/l. Design, PATIENTS
AND MEASUREMENTS: Cross-sectional study of 2108 participants in a 1981
community health survey in RESULTS:
In the group as a whole, serum total cholesterol was higher in subjects with
SCH (N = 119) than in euthyroid subjects (N = 1906) (mean +/- SD 6.3 +/- 1.3
mmol/l vs. 5.8 +/- 1.2 mmol/l, P < 0.001 unadjusted, P = 0.061 adjusted for
age, age(2) and sex). Serum total cholesterol was similarly elevated in
subjects with SCH and TSH < or = 10 mU/l (N = 89) (6.3 +/- 1.3 mmol/l, P
< 0.001 unadjusted, P = 0.055 adjusted for age, age(2) and sex). In the
subgroup analysis, LDL-C was higher in subjects with SCH (N = 30) than in
euthyroid subjects (N = 580) (4.1 +/- 1.2 mmol/l vs. 3.5 +/- 1.0 mmol/l, P <
0.01 unadjusted, P = 0.024 adjusted for age, age(2) and sex). LDL-C was
significantly increased in subjects with SCH and TSH < or = 10 mU/l (N = 23)
(4.3 +/- 1.3 mmol/l, P < 0.001 unadjusted, P = 0.002 adjusted for age,
age(2) and sex). CONCLUSION:
SCH is associated with increased serum LDL-C concentrations, which is
significant after adjustment for age, age(2) and sex. Arch
Intern Med. 2005 Nov 28;165(21):2467-72. Subclinical thyroid
dysfunction as a risk factor for cardiovascular disease. Walsh
JP, Bremner AP, Bulsara MK, O'Leary P, Leedman PJ, Feddema P, Michelangeli V. Department
of Endocrinology and Diabetes, BACKGROUND:
There have been few large epidemiological studies examining the association
between thyroid dysfunction and cardiovascular disease. In particular, it is
uncertain if subclinical hypothyroidism is a risk factor for cardiovascular
disease. METHODS:
Serum thyrotropin and free thyroxine concentrations were measured in 2108
archived serum samples from a 1981 community health survey in RESULTS:
In the cross-sectional analysis, subjects with subclinical hypothyroidism (n =
119) had a significantly higher prevalence of coronary heart disease than
euthyroid subjects (n = 1906) (age- and sex-adjusted prevalence odds ratio, 1.8;
95% confidence interval, 1.0-3.1; P = .04). In the longitudinal analysis of
subjects with subclinical hypothyroidism (n = 101), there were 21
cardiovascular deaths observed compared with 9.5 expected (age- and
sex-adjusted hazard ratio, 1.5; 95% confidence interval, 1.0-2.4; P = .08) and
33 coronary heart disease events observed compared with 14.7 expected (age- and
sex-adjusted hazard ratio, 1.7; 95% confidence interval, 1.2-2.4; P < .01).
The increased risk of coronary heart disease events remained significant after
further adjustment for standard cardiovascular risk factors. Subjects with
subclinical hyperthyroidism (n = 39) had no adverse outcomes. CONCLUSION:
Subclinical hypothyroidism may be an independent risk factor for coronary heart
disease. Aust
N Z J Public Health. 2005 Oct;29(5):412-5. Correlates of habitual
snoring and witnessed apnoeas in Knuiman
MW, James 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 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. J
Gastroenterol Hepatol. 2005 Sep;20(9):1435-41. Effects of HFE gene
mutations and alcohol on iron status, liver biochemistry and morbidity. Olynyk
JK, Knuiman MW, Divitini ML, Bartholomew HC, Cullen DJ, Powell LW. 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 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. Acta
Paediatr. 2005 Mar;94(3):275-80. Cholesterol tracking from
childhood to adult mid-life in children from the Busselton study. AIM:
To determine if subjects' cholesterol levels tracked relative to their peers
from early childhood to adult mid-life. METHODS:
Longitudinal study using subjects from the Busselton
Health Study. Data were available
from 1967 on a triennial basis until 1983, and a re-survey held in 1994. The
study included 1764 subjects aged 5-18 y at first measurement. Pearson's
correlation coefficient, adjusted for age and survey year, was used to examine
cholesterol tracking. The proportion of children who persisted with cholesterol
measurements in the extreme high quartile was assessed over time before and
after adjusting data for regression to the mean. The variability of the
children's cholesterol level was examined by track width using the method of
Porkka. RESULTS:
The correlation coefficients for tracking were from 0.35 to 0.55. Stronger
correlations coincided with shorter time periods between measurements. Before
adjustment for regression to the mean, 55-60% of children from the highest
quartile at first measurement remained in the same quartile 27 y later. After
adjustment for regression to the mean, the number of children with levels in
the extreme high quartile decreased, but 80% of these persisted in that quartile. CONCLUSION:
Intra-individual variations in cholesterol levels have an important influence
on population tracking levels and need to be considered when interpreting
tracking results from early childhood to adult mid-life. However, removing the
effect of regression to the mean by taking multiple measurements of cholesterol
will probably improve prediction for individuals. Med
J Aust. 2005 Jul 4;183(1 Suppl):S17-9. What can Busselton
population health surveys tell us about asthma in older people? James
West
Australian Sleep Disorders Research Institute/Department of Pulmonary
Physiology, Queen Elizabeth II Medical Centre, Level 5, G Block, Hospital
Avenue, Nedlands, WA 6009, Australia. 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. J
Clin Endocrinol Metab. 2005 Sep;90(9):5309-12. Epub 2005 Jun 14. Parity and the risk of
autoimmune thyroid disease: a community-based study. Walsh
JP, Bremner AP, Bulsara MK, O'Leary P, Leedman PJ, Feddema P, Michelangeli V. Department
of Endocrinology and Diabetes, CONTEXT:
Recent studies have suggested that fetal microchimerism (transplacental passage
of fetal cells followed by engraftment into maternal tissues) may play a role
in the pathogenesis of autoimmune thyroid disease. If that is true, then parity
should be a risk factor for autoimmune thyroid disease. OBJECTIVE:
The objective of this study was to examine parity as a risk factor for
autoimmune thyroid disease. Design, SETTING, AND PARTICIPANTS:
TSH, thyroid peroxidase antibody, and thyroglobulin antibody concentrations
were measured on archived sera from 1045 female participants in a 1981
community health survey in OUTCOME
MEASURES: Odds ratios (ORs) for positive thyroid antibodies (increased
concentration of either antibody) or thyroid dysfunction (abnormal serum TSH)
were used. RESULTS:
After adjustment for age, women who had previously been pregnant did not have a
significantly increased risk of positive thyroid antibodies [OR, 1.20; 95%
confidence interval (CI), 0.74-1.97; P = 0.46], raised TSH (OR, 0.93; 95% CI,
0.46-1.87; P = 0.84), or reduced TSH (OR, 0.87; 95% CI, 0.33-2.30; P = 0.79)
compared with women who had never been pregnant. For each additional pregnancy,
the OR was 1.02 (95% CI, 0.94-1.11; P = 0.57) for positive antibodies, 1.02
(95% CI, 0.91-1.14; P = 0.67) for raised TSH, and 1.03 (95% CI, 0.87-1.22; P =
0.73) for reduced TSH. Analysis using number of live births gave similar
results. The results were similar in younger and older women. CONCLUSIONS:
Parity is not a risk factor for thyroid autoimmunity or thyroid dysfunction.
These data do not support a key pathogenic role for fetal microchimerism in
chronic autoimmune thyroid disease. Aust
N Z J Public Health. 2004 Jun;28(3):267-72. Evaluating the impact of
repeated community-wide health surveys on cardiovascular morbidity and
mortality in the Busselton population. Knuiman
MW, Clarkson JP, Bulsara M, Bartholomew HC. 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 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. Ann
Epidemiol. 2005 Jan;15(1):39-43. Spouse selection and
environmental effects on spouse correlation in lung function measures. Knuiman
MW, Divitini ML, Bartholomew HC. 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. Am
J Respir Crit Care Med. 2005 Jan 15;171(2):109-14. . Decline in lung function
in the Busselton Health Study: the effects of asthma and cigarette smoking. James
AL, Palmer LJ, Kicic E, Maxwell PS, Lagan SE, Ryan GF, Musk AW. West
Australian Sleep Disorders Research Institute, Queen Elizabeth II Medical
Centre, Asthma
in adults may be associated with chronic airflow obstruction, possibly
resulting from airway disease in early life and/or a greater rate of decline in
lung function in adult life compared with those with asthma. Treatment and
cigarette smoking may also influence the rate of decline of lung function. The
aim of this analysis was to examine the level and rate of decline in lung
function in relationship to asthma and cigarette smoking in adults. Subjects (n
= 9,317) had participated as adults (> 18 years) in one or more of the
cross-sectional Busselton Health Surveys
between 1966 and 1981 or in the follow-up study of 1994/1995. The effects of
sex, doctor-diagnosed asthma, smoking status, and anthropometric data on the
level and rate of decline in FEV1 were examined in a linear mixed effects
model. At the age of 19 years, FEV1 was reduced in subjects with asthma but was
similar in smokers and nonsmokers. Males, taller subjects, smokers, and
subjects with asthma had greater declines in FEV1 with age. Smoking and asthma
had additive but not multiplicative effects on decline. Thus, asthma is
associated with reduced lung function at the beginning of adult life as well as
an increased rate of decline during adult life. Ann
Epidemiol. 2004 Oct;14(9):627-32. Is sialic acid an
independent risk factor for cardiovascular disease? A 17-year follow-up study
in Knuiman
MW,
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.  |
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