Adult height and cancer mortality in Asia: the Asia Pacific Cohort Studies Collaboration.

BACKGROUND: The observation that taller people experience an increased risk of selected cancers is largely restricted to Caucasian cohorts. These associations may plausibly differ in Asian populations. For the first time, we make direct comparison in the same analyses of the associations between height and a series of malignancies in Australasian (Caucasian) and Asian populations. METHODS: Analyses were based on the Asia Pacific Cohort Studies Collaboration of 506 648 study participants (408 381 Asia, 98 267 Australasia) drawn from 38 population-based cohort studies. Cox proportional hazards regression was used to estimate the relationship between height and cancer rates. RESULTS: A total of 3 272 600 person-years of follow-up gave rise to 7497 cancer deaths (4415 in Asia; 3082 in Australasia). After multiple adjustments and left censoring, taller individuals experienced increased rates of carcinoma of the intestine (men and women); all cancers, liver, lung, breast, 'other' malignancies (all women); and cancers of the prostate and bladder (men). No consistent regional (Asia versus Australasia) or sex differences were observed. CONCLUSIONS: In the present study, taller men and women had an elevated risk of selected malignancies. These associations did not differ appreciably between Asian and Caucasian populations.

Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables.

Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes.

Function after spinal treatment, exercise and rehabilitation (FASTER): improving the functional outcome of spinal surgery.

BACKGROUND: The life-time incidence of low back pain is high and diagnoses of spinal stenosis and disc prolapse are increasing. Consequently, there is a steady rise in surgical interventions for these conditions. Current evidence suggests that while the success of surgery is incomplete, it is superior to conservative interventions. A recent survey indicates that there are large differences in the type and intensity of rehabilitation, if any, provided after spinal surgery as well as in the restrictions and advice given to patients in the post-operative period. This trial will test the hypothesis that functional outcome following two common spinal operations can be improved by a programme of post-operative rehabilitation that combines professional support and advice with graded active exercise and/or an educational booklet based on evidence-based messages and advice. METHODS/DESIGN: The study design is a multi-centre, factorial, randomised controlled trial with patients stratified by surgeon and operative procedure. The trial will compare the effectiveness and cost-effectiveness of a rehabilitation programme and an education booklet for the postoperative management of patients undergoing discectomy or lateral nerve root decompression, each compared with "usual care"using a 2 x 2 factorial design. The trial will create 4 sub-groups; rehabilitation-only, booklet-only, rehabilitation-plus-booklet, and usual care only. The trial aims to recruit 344 patients, which equates to 86 patients in each of the four sub-groups. All patients will be assessed for functional ability (through the Oswestry Disability Index - a disease specific functional questionnaire), pain (using visual analogue scales), and satisfaction pre-operatively and then at 6 weeks, 3, 6 and 9 months and 1 year post-operatively. This will be complemented by a formal analysis of cost-effectiveness. DISCUSSION: This trial will determine whether the outcome of spinal surgery can be enhanced by either a post-operative rehabilitation programme or an evidence-based advice booklet or a combination of the two and as such will contribute to our knowledge on how to manage spinal surgery patients in the post-operative period.

Association of smoking and smoking cessation with major causes of mortality in the Asia Pacific Region: the Asia Pacific Cohort Studies Collaboration.

BACKGROUND: Although the dangers of smoking, and the benefits of quitting, are well established and understood in the West, smoking remains popular among Asian men. We investigated the associations between smoking (including ex-smoking) and major causes of mortality in Asian men and women, and compared with Australians and New Zealanders (ANZ). METHODS: An overview of 34 cohort studies in the Asia Pacific region involving 512 676 individuals (81% from Asia), followed up for a median of 6.7 years (20 804 deaths). RESULTS: Mortality rates for cause-specific and all causes of mortality were systematically higher for current compared with never smokers. Hazard ratios (HR) for overall and cause-specific mortality comparing current-smokers with never smokers, ex- smokers with current-smokers and comparing numbers of cigarettes smoked per day, were higher for ANZ than Asia (p<0.001). For overall mortality, the HR (95% CI) comparing current-smoking with not was 1.37 (1.23 to 1.53) and 1.33 (1.26 to 1.40) in Asian men and women respectively. The corresponding figures in ANZ were 1.95 (1.81 to 2.09) and 1.85 (1.69 to 2.02). The HR for quitting in ANZ was 0.67 (0.63 to 0.71) and 0.66 (0.58 to 0.74) in men and women respectively. Quitting smoking had a significant benefit among Asian men, the HR was 0.88 (0.81 to 0.97) after ignoring the first 3 years of follow-up. There was no evidence of benefit for Asian women, for whom ex-smoking is rare. CONCLUSIONS: Allowing for the recent uptake of smoking in Asia, its effects are comparable to those observed in ANZ. Stringent tobacco control measures and smoking cessation strategies are urgently required in Asia.

How free of tobacco smoke are 'smoke-free' homes?

UNLABELLED: The risks of exposure to environmental tobacco smoke (ETS) are well established and 'harm reduction' strategies such as smoking outside to protect infants and children from exposure to ETS have been advocated for some time. The aim of this study was to assess the validity of self-reported smoking levels in residential settings. The participants were families (n = 92) randomly selected from lower socioeconomic areas of Perth, Western Australia. Each household was monitored for vapor phase nicotine and particulates with an aerodynamic diameter of < or = 10 microm (PM(10)). Of the 42% (39) households who reported that someone smoked cigarettes at home, only four (4%) said that smoking occurred inside the house. There was a 'moderate' agreement between parental-reported tobacco smoking and levels of nicotine (kappa = 0.55, P < 0.01). There were significant differences in the median levels of air nicotine (P < 0.01) and PM(10) (P < 0.05) between households in which smoking was reported as only occurring outside, and the smoke-free households. PRACTICAL IMPLICATIONS: The study outcome suggests that a strategy based on the separation of children and smoking activity is inadequate to protect the former from ETS at home, and that health professionals should give parents unambiguous advice to give up smoking in order to make their homes a completely smoke-free environment.

Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.

CONTEXT: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Systolic blood pressure, diabetes and the risk of cardiovascular diseases in the Asia-Pacific region.

OBJECTIVE: To assess the association between systolic blood pressure (SBP) and cardiovascular diseases (CVD) among participants with and without diabetes from cohorts in the Asia-Pacific region. RESEARCH DESIGN AND METHODS: Hazards ratios and 95% confidence intervals (CI) for CVD were calculated from Cox models, stratified by sex and region and adjusted for age using individual participant data from 36 cohort studies. Repeat measurements of SBP were used to adjust for regression dilution bias. RESULTS: During follow-up, 7387 fatal or non-fatal cardiovascular endpoints were recorded among 368 307 participants (6.4% with diabetes). SBP was associated with coronary heart disease (CHD), ischaemic stroke and haemorrhagic stroke in a continuous log-linear fashion among individuals with diabetes, as well as those without diabetes. Overall, each 10 mmHg higher usual SBP was associated with 18% (95% CI: 9-27%) and 23% (19-26%) greater risk for CHD among those with and without diabetes, respectively. The corresponding values for ischaemic stroke were 29% (14-45%) and 43% (37-50%), and for haemorrhagic stroke, 56% (32-83%) and 74% (66-82%). The test for heterogeneity by diabetes status in each of these associations was not significant (P >or= 0.10). CONCLUSIONS: Systolic blood pressure is an important marker of risk of CVD in people with and without diabetes. A given reduction in systolic blood pressure is likely to have a similar relative effect on reducing the risk of a cardiovascular event, regardless of diabetes status.

Five-year survival from breast cancer in Western Australia over a decade.

The aim of the present study was to investigate whether 5-year survival of patients with breast cancer in Western Australia has improved over time. We used a population-based study conducted in the State of Western Australia, to identify all cases of invasive breast cancer cases diagnosed in 1989, 1994 and 1999. Information on presentation, investigation and management was extracted from medical records of each case and status at 5 years after date of diagnosis was determined. Comparison of 5-year overall survival for women diagnosed in the three calendar years, and hazard ratios for survival calculated for prognostic variables were measured. We found that survival from breast cancer has improved in Western Australia since 1989. Earlier diagnosis, living in the Perth metropolitan area and use of breast-conserving surgery are associated with better survival, irrespective of year of diagnosis. Further research needs to be carried out to determine the reason for this improvement.

The impact of modifiable risk factors on mortality from prostate cancer in populations of the Asia-Pacific region.

Mortality from cancer of the prostate is increasing in the Asia-Pacific, when much of this region is undergoing a transition to a Western lifestyle. The role that lifestyle factors play in prostate cancer appears limited, but existing data mainly are from the West. We conducted an individual participant data analysis of 24 cohort studies involving 320,852 men (83% in Asia). Cox proportional hazard models were used to quantify associations between risk factors and mortality from prostate cancer. There were 308 deaths from prostate cancer (14% in Asia) during 2.1 million person-years of follow-up. The age-adjusted hazard ratio (95% confidence interval; CI) for men with body mass index (BMI) 28 kg/m2 or more, compared with below 25, was 1.55 (1.12 - 2.16); no such significant relationship was found for height or waist circumference. The BMI result was unchanged after adjustment for other variables, was consistent between Asia and Australia/New Zealand (ANZ) and did not differ with age. There was no significant relationship with diabetes, glucose or total cholesterol (p > or = 0.18). Smoking, alone, showed different effects in the two regions, possibly due to the relative immaturity of the smoking epidemic in Asia. In ANZ, the multiple-adjusted hazard ratio for an extra 5 cigarettes per day was 1.12 (95%CI: 1.03 - 1.22), whereas in Asia it was 0.77 (0.56 - 1.05). Body size is an apparently important determinant of prostate cancer in the Asia-Pacific. Evidence of an adverse effect of smoking is conclusive only in the predominantly Caucasian parts of the region.

Rural-urban differences in the presentation, management and survival of breast cancer in Western Australia.

From all women diagnosed with invasive breast cancer in 1999 in Western Australia, rural and urban women were compared with regard to mode of detection, tumour characteristics at presentation, diagnostic investigations, treatment and survival. Women from rural areas with breast cancer (n=206, 23%) were less likely to have open biopsy with frozen section (P<0.001), breast-conserving surgery (P<0.001), adjuvant radiotherapy (P=0.004) and hormonal therapy (P=0.03), and were less likely to be treated by a high caseload breast cancer surgeon (P<0.001). Adjusting for age and tumour characteristics, rural women had an increased likelihood of death within 5 years of breast cancer diagnosis (HR 1.62, 95% CI 1.10-2.38). This difference was not significant after adjustment for treatment factors (HR 1.36, 95% CI 0.90-2.04).

The fraction of ischaemic heart disease and stroke attributable to smoking in the WHO Western Pacific and South-East Asian regions.

BACKGROUND: Tobacco will soon be the biggest cause of death worldwide, with the greatest burden being borne by low and middle-income countries where 8/10 smokers now live. OBJECTIVE: This study aimed to quantify the direct burden of smoking for cardiovascular diseases (CVD) by calculating the population attributable fractions (PAF) for fatal ischaemic heart disease (IHD) and stroke (haemorrhagic and ischaemic) for all 38 countries in the World Health Organization Western Pacific and South East Asian regions. DESIGN AND SUBJECTS: Sex-specific prevalence of smoking was obtained from existing data. Estimates of the hazard ratio (HR) for IHD and stroke with smoking as an independent risk factor were obtained from the approximately 600,000 adult subjects in the Asia Pacific Cohort Studies Collaboration (APCSC). HR estimates and prevalence were then used to calculate sex-specific PAF for IHD and stroke by country. RESULTS: The prevalence of smoking in the 33 countries, for which relevant data could be obtained, ranged from 28-82% in males and from 1-65% in females. The fraction of IHD attributable to smoking ranged from 13-33% in males and from <1-28% in females. The percentage of haemorrhagic stroke attributable to smoking ranged from 4-12% in males and from <1-9% in females. Corresponding figures for ischaemic stroke were 11-27% in males and <1-22% in females. CONCLUSIONS: Up to 30% of some cardiovascular fatalities can be attributed to smoking. This is likely an underestimate of the current burden of smoking on CVD, given that the smoking epidemic has developed further since many of the studies were conducted.

Serum triglycerides as a risk factor for cardiovascular diseases in the Asia-Pacific region.

BACKGROUND: The importance of serum triglyceride levels as a risk factor for cardiovascular diseases is uncertain. METHODS AND RESULTS: We performed an individual participant data meta-analysis of prospective studies conducted in the Asia-Pacific region. Cox models were applied to the combined data from 26 studies to estimate the overall and region-, sex-, and age-specific hazard ratios for major cardiovascular diseases by fifths of triglyceride values. During 796,671 person-years of follow-up among 96,224 individuals, 670 and 667 deaths as a result of coronary heart disease (CHD) and stroke, respectively, were recorded. After adjustment for major cardiovascular risk factors, participants grouped in the highest fifth of triglyceride levels had a 70% (95% CI, 47 to 96) greater risk of CHD death, an 80% (95% CI, 49 to 119) higher risk of fatal or nonfatal CHD, and a 50% (95% CI, 29% to 76%) increased risk of fatal or nonfatal stroke compared with those belonging to the lowest fifth. The association between triglycerides and CHD death was similar across subgroups defined by ethnicity, age, and sex. CONCLUSIONS: Serum triglycerides are an important and independent predictor of CHD and stroke risk in the Asia-Pacific region. These results may have clinical implications for cardiovascular risk prediction and the use of lipid-lowering therapy.

Homocysteine-lowering treatment with folic acid, cobalamin, and pyridoxine does not reduce blood markers of inflammation, endothelial dysfunction, or hypercoagulability in patients with previous transient ischemic attack or stroke: a randomized substudy of the VITATOPS trial.

BACKGROUND AND PURPOSE: Epidemiological and laboratory studies suggest that increasing concentrations of plasma homocysteine (total homocysteine [tHcy]) accelerate cardiovascular disease by promoting vascular inflammation, endothelial dysfunction, and hypercoagulability. METHODS: We conducted a randomized controlled trial in 285 patients with recent transient ischemic attack or stroke to examine the effect of lowering tHcy with folic acid 2 mg, vitamin B12 0.5 mg, and vitamin B6 25 mg compared with placebo on laboratory markers of vascular inflammation, endothelial dysfunction, and hypercoagulability. RESULTS: At 6 months after randomization, there was no significant difference in blood concentrations of markers of vascular inflammation (high-sensitivity C-reactive protein [P=0.32]; soluble CD40L [P=0.33]; IL-6 [P=0.77]), endothelial dysfunction (vascular cell adhesion molecule-1 [P=0.27]; intercellular adhesion molecule-1 [P=0.08]; von Willebrand factor [P=0.92]), and hypercoagulability (P-selectin [P=0.33]; prothrombin fragment 1 and 2 [P=0.81]; D-dimer [P=0.88]) among patients assigned vitamin therapy compared with placebo despite a 3.7-micromol/L (95% CI, 2.7 to 4.7) reduction in total homocysteine (tHcy). CONCLUSIONS: Lowering tHcy by 3.7 micromol/L with folic acid-based multivitamin therapy does not significantly reduce blood concentrations of the biomarkers of inflammation, endothelial dysfunction, or hypercoagulability measured in our study. The possible explanations for our findings are: (1) these biomarkers are not sensitive to the effects of lowering tHcy (eg, multiple risk factor interventions may be required); (2) elevated tHcy causes cardiovascular disease by mechanisms other than the biomarkers measured; or (3) elevated tHcy is a noncausal marker of increased vascular risk.

The Coronary Artery Revascularisation in Diabetes (CARDia) trial: background, aims, and design.

BACKGROUND: Patients with diabetes have an increased incidence and severity of ischemic heart disease, which leads to an increased requirement for coronary revascularization. Comparative information regarding mode of revascularization--coronary artery bypass graft surgery surgery (CABG) or percutaneous coronary intervention (PCI)--is limited, mainly confined to a subanalysis of the Bypass Angioplasty Revascularization (BARI) trial, suggesting a mortality benefit of CABG over PCI. No prospective trial has specifically compared these modes of revascularization in patients with diabetes. OBJECTIVE: The Coronary Artery Revascularisation in Diabetes (CARDia) trial is designed to address the hypothesis that optimal PCI is not inferior to modern CABG as a revascularization strategy for diabetics with multivessel or complex single-vessel coronary disease. The primary end point is a composite of death, nonfatal myocardial infarction, and cerebrovascular accident at 1 year. METHOD: A total of 600 patients with diabetes are to be randomized to either PCI or CABG, with few protocol restrictions on operative techniques or use of new technology. This gives a power of 80% to detect non-inferiority of PCI assuming that the PCI 1-year event rate is 9%. A cardiac surgeon and a cardiologist must agree that a patient is suitable for revascularization by either technique prior to recruitment into the study. Twenty-one centers in the United Kingdom and Ireland are recruiting patients. Data on cost effectiveness, quality of life, and neurocognitive function are being collected. Long-term (3-5 year) follow-up data will also be collected.

Surgical caseload and outcomes for women with invasive breast cancer treated in Western Australia.

We have assessed the outcomes for all women diagnosed with invasive breast cancer in Western Australia during 1989, 1994 and 1999, and compared the results for surgeons who treat 20 or more cases per year with those of surgeons who treat less. Women treated by high caseload surgeons were more likely to retain their breast (53.3% vs. 36.7%, p<0.001), have adjuvant radiotherapy (50.0% vs. 30.6%, p<0.001), and be alive after 4 years (1989, 86% vs. 82%; 1994, 89% vs. 84%; 1999, 90% vs. 79%, HR 0.71, p=0.03). Adjusting for age and year of diagnosis, women were not more likely to be treated with adjuvant chemotherapy (29.2% vs. 20.9%, p=0.28). In 1989 35% of women were treated by high caseload surgeons. By 1999 this had risen to 82%. The results confirm that women treated by high caseload surgeons have better outcomes.

Pathology reporting of breast cancer: trends in 1989-1999, following the introduction of mammographic screening in Western Australia.

BACKGROUND: A survey of pathology reporting of breast cancer in Western Australia in 1989 highlighted the need for improvement. The current study documents (1) changes in pathology reporting from 1989 to 1999 and (2) changes in patterns of histopathological prognostic indicators for breast cancer following introduction of mammographic screening in 1989. METHODS: Data concerning all breast cancer cases reported in Western Australia in 1989, 1994 and 1999 were retrieved using the State Cancer Registry, Hospital Morbidity data system, and pathology laboratory records. RESULTS: Pathology reports improved in quality during the decade surveyed. For invasive carcinoma, tumour size was not recorded in 1.2% of pathology reports in 1999 compared with 16.1% in 1989 (p<0.001). Corresponding figures for other prognostic factors were: tumour grade 3.3% and 51.6% (p<0.001), tumour type 0.2% and 4.1% (p<0.001), vascular invasion 3.7% and 70.9% (p<0.001), and lymph node status 1.9% and 4.5% (p = 0.023). In 1999, 5.9% of reports were not in a synoptic/checklist format, whereas all reports were descriptive in 1989 (p<0.001). For the population as a whole, the proportion of invasive carcinomas <1 cm was 20.9% in 1999 compared with 14.5% in 1989 (p<0.001); for tumours <2 cm the corresponding figures were 65.4% and 59.7% (p = 0.013). In 1999, 30.5% of tumours were histologically well-differentiated compared with 10.6% in 1989 (p<0.001), and 61.7% were lymph node negative in 1999 compared with 57.1% in 1989 (p = 0.006). Pure ductal carcinoma in situ (DCIS) constituted 10.9% and 7.9% of total cases of breast carcinoma in 1999 and 1989, respectively (p = 0.01). CONCLUSIONS: Quality of pathology reporting improved markedly over the period, in parallel with adoption of standardised synoptic pathology reports. By 1999, recording of important prognostic information was almost complete. Frequency of favourable prognostic factors generally increased over time, reflecting expected effects of mammographic screening.

Arrhythmias and mortality after myocardial infarction in diabetic patients. Relationship to diabetes treatment.

OBJECTIVE: To assess the relationship between clinical course after acute myocardial infarction (AMI) and diabetes treatment. RESEARCH DESIGN AND METHODS: Retrospective analysis of data from all patients aged 25-64 years admitted to hospitals in Perth, Australia, between 1985 and 1993 with AMI diagnosed according to the International Classification of Diseases (9th revision) criteria was conducted. Short- (28-day) and long-term survival and complications in diabetic and nondiabetic patients were compared. For diabetic patients, 28-day survival, dysrhythmias, heart block, and pulmonary edema were treated as outcomes, and factors related to each were assessed using multiple logistic regression. Diabetes treatment was added to the model to assess its significance. Long-term survival was compared by means of a Cox proportional hazards model. RESULTS: Of 5,715 patients, 745 (12.9%) were diabetic. Mortality at 28 days was 12.0 and 28.1% for nondiabetic and diabetic patients, respectively (P < 0.001); there were no significant drug effects in the diabetic group. Ventricular fibrillation in diabetic patients taking glibenclamide (11.8%) was similar to that of nondiabetic patients (11.0%) but was lower than that for those patients taking either gliclazide (18.0%; 0.1 > P > 0.05) or insulin (22.8%; P < 0.05). There were no other treatment-related differences in acute complications. Long-term survival in diabetic patients was reduced in those taking digitalis and/or diuretics but type of diabetes treatment at discharge had no significant association with outcome. CONCLUSIONS: These results do not suggest that ischemic heart disease should influence the choice of diabetes treatment regimen in general or of sulfonylurea drug in particular.

Hormonal factors and risk of aneurysmal subarachnoid hemorrhage: an international population-based, case-control study.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is more common in women than in men, but the role of hormonal factors in its etiology remains uncertain. The aim of this study was to examine the relationship between hormonal factors and risk of SAH in women. METHODS: This was a prospective, multicenter, population-based, case-control study performed in 4 major urban centers in Australia and New Zealand. Two hundred sixty-eight female cases of first-ever aneurysmal SAH occurred during 1995-1998. Controls were 286 frequency-matched women from the general population of each center. Outcome measures included risk of SAH associated with use of oral contraceptive pills (OCPs), hormone replacement therapy (HRT), and various endogenous hormonal factors including menstrual patterns, parity, age at birth of first child, and breast-feeding practices. RESULTS: Cases and controls did not differ with regard to menstrual and reproductive history except in age at birth of first child, where older age was associated with reduced risk of SAH (odds ratio [OR], 0.63; 95% CI, 0.43, 0.91). Relative to never use of HRT, the adjusted OR for ever use of HRT was 0.64 (95% CI, 0.41, 0.98), which did not alter significantly after further adjustment for possible confounding factors. Borderline evidence of an inverse association was detected for past use of HRT (adjusted OR, 0.59; 95% CI, 0.30, 1.13) and current use of HRT (adjusted OR, 0.67; 95% CI, 0.40, 1.13), but there was no evidence of an association for use of OCPs (adjusted OR, 0.97; 95% CI, 0.58, 1.60). CONCLUSIONS: The risks of SAH are lower in women whose first pregnancy is at an older age and women who have ever used HRT but not OCPs. The findings suggest an independent etiologic role for hormonal factors in the pathogenesis of aneurysmal SAH and provide support for a protective role for HRT on risk of SAH in postmenopausal women.

Five-year survival after first-ever stroke and related prognostic factors in the Perth Community Stroke Study.

BACKGROUND AND PURPOSE: Few community-based studies have examined the long-term survival and prognostic factors for death within 5 years after an acute first-ever stroke. This study aimed to determine the absolute and relative survival and the independent baseline prognostic factors for death over the next 5 years among all individuals and among 30-day survivors after a first-ever stroke in a population of Perth, Western Australia. METHODS: Between February 1989 and August 1990, all individuals with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth, Western Australia, with a population of 138 708 people, were registered prospectively and assessed according to standardized diagnostic criteria. Patients were followed up prospectively at 4 months, 12 months, and 5 years after the index event. RESULTS: Three hundred seventy patients with first-ever stroke were registered, and 362 (98%) were followed up at 5 years, by which time 210 (58%) had died. In the first year after stroke the risk of death was 36.5% (95% CI, 31.5% to 41.4%), which was 10-fold (95% CI, 8.3% to 11.7%) higher than that expected among the general population of the same age and sex. The most common cause of death was the index stroke (64%). Between 1 and 5 years after stroke, the annual risk of death was approximately 10% per year, which was approximately 2-fold greater than expected, and the most common cause of death was cardiovascular disease (41%). The independent baseline factors among 30-day survivors that predicted death over 5 years were intermittent claudication (hazard ratio [HR], 1.9; 95% CI, 1.2 to 2.9), urinary incontinence (HR, 2.0; 95% CI, 1. 3 to 3.0), previous transient ischemic attack (HR, 2.4; 95% CI, 1.4 to 4.1), and prestroke Barthel Index <20/20 (HR, 2.0; 95% CI, 1.2 to 3.2). CONCLUSIONS: One-year survivors of first-ever stroke continue to die over the next 4 years at a rate of approximately 10% per year, which is twice the rate expected among the general population of the same age and sex. The most common cause of death is cardiovascular disease. Long-term survival after stroke may be improved by early, active, and sustained implementation of effective strategies for preventing subsequent cardiovascular events.

Homocysteine, Alzheimer genes and proteins, and measures of cognition and depression in older men.

The epsilon4 allele of apolipoprotein E (APOE), and the plasma levels of APOE, amyloid beta-protein precursor, amyloid beta1-40 (Abeta40) and homocysteine (Hcy) have all been correlated with the presence of dementia. Mutations in the methylnetetrahydrofolate reductase enzyme (MTHFR) have been associated with elevated levels of Hcy. This study explored the association of these factors with cognition and depression in community dwelling older men. Two hundred and ninety-nine men, mean age 78.9 years (SD 2.8), were studied in this cross-sectional survey. Mean plasma Hcy was 13.5 (SD 5.3) micromol/L. The MTHFR genotype had no obvious impact on Hcy levels. Ln Hcy and Ln Abeta40 were both inversely correlated with calculated glomerular filtration rate (cGFR), r = -0.41 (p < 0.001) and r = -0.28 (p < 0.001), respectively. There was a positive correlation between Ln Hcy and Ln Abeta40, r = 0.19 (p < 0.001), which remained significant after adjusting for cGFR, with a doubling of Hcy associated with a 24% increase of Abeta40. The e4 allele was associated with increased depressive symptoms as measured by the Geriatric Depression Scale-15, Odds ratio (OR) = 2.59 (95%CI 1.06-6.34) and poorer performance on the Clock Drawing Test, OR = 2.32 (95% CI: 1.25-4.29). There was a positive association between Abeta40 and Hcy, even after adjustment for cGFR in this sample of well, community dwelling older men. This association may help elucidate the link between elevated levels of Hcy and Alzheimer's disease.