Current smoking and the risk of non-fatal myocardial infarction in the WHO MONICA Project populations

Background: Cohort studies have shown that smoking has a substantial influence on coronary heart disease mortality in young people. Population based data on non-fatal events have been sparse, however. Objective: To study the impact of smoking on the risk of non-fatal acute myocardial infarction (MI) in young middle age people. Methods: From 1985 to 1994 all non-fatal MI events in the age group 35 - 64 were registered in men and women in the WHO MONICA ( multinational monitoring of trends and determinants in cardiovascular disease) project populations ( 18 762 events in men and 4047 in women from 32 populations from 21 countries). In the same populations and age groups 65 741 men and 66 717 women participated in the surveys of risk factors ( overall response rate 72%). The relative risk of non-fatal MI for current smokers was compared with non-smokers, by sex and five year age group. Results: The prevalence of smoking in people aged 35 - 39 years who experienced non-fatal MI events was 81% in men and 77% in women. It declined with increasing age to 45% in men aged 60 - 64 years and 36% in women, respectively. In the 35 - 39 years age group the relative risk of non-fatal MI for smokers was 4.9 (95% confidence interval (CI) 3.9 to 6.1) in men and 5.3 ( 95% CI 3.2 to 8.7) in women, and the population attributable fractions were 65% and 55%, respectively. Conclusions: During the study period more than half of the non-fatal MIs occurring in young middle age people can be attributed to smoking.

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

The epsilon4 allele of apolipoprotem E (APOE), and the plasma levels of APOE, amyloid beta-protein precursor, arnyloid 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) mumol/L. The MTHFR genotype had no obvious impact on Hey 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 Hey 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 Hey and Alzheimer's disease.

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

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 B-12 0.5 mg, and vitamin B-6 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-mumol/L (95% CI, 2.7 to 4.7) reduction in total homocysteine (tHcy). Conclusions - Lowering tHcy by 3.7 mumol/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.

Prevalence of peripheral arterial disease: persistence of excess risk in former smokers

Objective: To determine the age-standardised prevalence of peripheral arterial disease (PAD) and associated risk factors, particularly smoking. Method: Design: Cross-sectional survey of a randomly selected population. Setting: Metropolitan area of Perth, Western Australia. Participants: Men aged between 65-83 years. Results: The adjusted response fraction was 77.2%. Of 4,470 men assessed, 744 were identified as having PAD by the Edinburgh Claudication Questionnaire and/or the ankle-brachial index of systolic blood pressure, yielding an age-standardised prevalence of PAD of 15.6% (95% confidence intervals (CI): 14.5%, 16.6%). The main risk factors identified in univariate analyses were increasing age, smoking current (OR=3.9, 95% CI 2.9-5.1) or former (OR=2.0, 95% CI 1.6-2.4), physical inactivity (OR=1.4, 95% CI 1.2-1.7), a history of angina (OR=2.2, 95% CI 1.8-2.7) and diabetes mellitus (OR=2.1, 95% CI 1.7-2.6). The multivariate analysis showed that the highest relative risk associated with PAD was current smoking of 25 or more cigarettes daily (OR=7.3, 95% CI 4.2-12.8). In this population, 32% of PAD was attributable to current smoking and a further 40% was attributable to past smoking by men who did not smoke currently. Conclusions: This large observational study shows that PAD is relatively common in older, urban Australian men. In contrast with its relationship to coronary disease and stroke, previous smoking appears to have a long legacy of increased risk of PAD. Implications: This research emphasises the importance of smoking as a preventable cause of PAD.

Trends in five-year survival and risk of recurrent stroke after first-ever stroke in the Perth community stroke study

Background: Few studies provide information on trends in the long-term outcome of stroke. We aimed to determine trends in survival and recurrent stroke, over 5 years after first-ever stroke, for 2 cohorts of patients enrolled in the Perth Community Stroke Study in 1989 90 and 1995-96. Methods: For 12-month periods beginning February 1989 and February 1995, all individuals with an acute stroke who were resident in a geographically-defined and representative region of Perth, Western Australia, were registered and followed-up prospectively 5 years after the index event. Results: The 5-year cumulative risk of death was 59% (95% confidence interval (CI) 53%, 65%) and 58% (95% CI 52%, 65%) for the 1989-90 and 1995-96 cohorts, respectively (p = 0.94). The 5-year cumulative risk of first recurrent stroke was 32% (95% CI 25%, 40%) and 23% (95% CI 16%, 30%) for the 1989-90 and 1995-96 cohorts, respectively (p = 0.07). Conclusions: Although no statistically significant improvement occurred in 5-year survival after first-ever stroke in Perth between 1989-90 and 1995-96, there was a statistically nonsignificant trend towards a smaller cumulative risk of recurrent stroke over 5 years after a first-ever stroke. Serial community-based studies of the incidence and outcome of stroke are an important means of monitoring the translation of proven preventive interventions to improvements in population health. Copyright (C) 2005 S. Karger AG, Basel.

Mental health and socio-economic variations in Australian suicide

This paper investigates the relationship between suicide rates and prevalence of mental disorder and suicide attempts, across socio-economic status (SES) groups based on area of residence. Australian suicide data (1996-1998) were analysed in conjunction with area-based prevalences of mental disorder derived from the National Survey of Mental Health and Well-Being (1997). Poisson regression models of suicide risk included age, quintile of area-based SES, urban-rural residence, and country of birth (COB), with males and females analysed separately. Analysis focussed on the association between suicide and prevalences of (ICD-10) affective disorders, anxiety disorders, substance use disorders and suicide attempts by SES group. Prevalences of other psychiatric symptomatology, substance use problems, health service utilisation, stressful life-events and personality were also investigated. Significant increasing gradients were evident from high to low SES groups for prevalences of affective disorders, anxiety disorders (females only), and substance use disorders (males only); sub-threshold drug and alcohol problems and depression; and suicide attempts and suicide (males only). Prevalences of mental disorder, other sub-threshold mental health items and suicide attempts were significantly associated with suicide, but in most cases associations were reduced in magnitude and became statistically non-significant after adjustment for COB, urban-rural residence, and SES. For male suicide the relative risk (RR) in the lowest SES group compared to the highest was 1.40 (95% CI 1.29-1.52, p < 0.001) for all ages, and 1.46 (95% CI 1.27-1.67, p < 0.001) for male youth (20-34 years). This relationship was not substantially modified in males when regression models included prevalences of affective disorders, and other selected mental health variables and demographic factors. From a population perspective, SES remained significantly associated with suicide after controlling for the prevalence of mental disorders and other psychiatric symptomatology. Mental conditions and previous suicidal behaviour may play an intermediary role between SES and suicide, but this study suggests that an independent relationship between suicide and SES also exists. (c) 2005 Elsevier Ltd. All rights reserved.

Gestational diabetes mellitus: From consensus to action on screening and treatment

The 1998 consensus guidelines on the management of gestational diabetes mellitus from the Australasian Diabetes in Pregnancy Society emphasised that, “due to a lack of good quality randomised controlled clinical trials in the area of [gestational diabetes mellitus], these guidelines are based on what is a reasonable consensus of informed opinion in Australasia”.1 The clear benefits of treating women with gestational diabetes according to these guidelines have now been demonstrated by the Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS).2 This study randomised 1000 women with gestational diabetes to either routine antenatal care or to an intervention that comprised home glucose monitoring, review by a diabetes educator, dietitian and physician, and insulin therapy if glycaemic targets were not met. Serious adverse perinatal outcomes occurred in 1% of the intervention group versus 4% of the routine-care group (adjusted relative risk, 0.33 [95% CI, 0.14–0.75]). The percentage of infants who were large for gestational age was lower in the intervention group (13% v 22%), with no increase in those who were small for gestational age. Although induction of labour was more common in the intervention group (39% v 29%), rates of caesarean delivery were similar (around 31%). Measures of maternal quality of life were more favourable in the intervention group. To prevent one serious perinatal outcome, 34 women needed to be treated. The 1998 guidelines were equivocal in regard to screening for gestational diabetes, allowing either for universal screening or for selective screening based on clinical risk factors in relatively lowrisk populations. In the light of the findings of ACHOIS, we believe that universal screening should now be accepted and implemented.

Non-cancer mortality among people diagnosed with cancer (Australia)

Objective To investigate whether people diagnosed with cancer have an increased risk of death from non-cancer causes compared to the general population. Methods The non-cancer mortality of people diagnosed with cancer in Queensland (Australia) between 1982 and 2002 who had not died before 1 January 1993 was compared to the mortality of the total Queensland population, matching by age group and sex, and reporting by standardised mortality ratios. Results Compared to the non-cancer mortality in the general population, cancer patients (all cancers combined) were nearly 50% more likely to die of non-cancer causes (SMR = 149.9, 95% CI = [147-153]). This varied by cancer site. Overall melanoma patients had significantly lower non-cancer mortality, female breast cancer patients had similar non-cancer mortality to the general population, while increased non-cancer mortality risks were observed for people diagnosed with cervical cancer, colorectal cancer, prostate cancer, non-Hodgkin lymphoma and lung cancer. Conclusions Although cancer-specific death rates underestimate the mortality directly associated with a diagnosis of cancer, quantifying the degree of underestimation is difficult due to various competing explanations. There remains an important role for future research in understanding the causes of morbidity among cancer survivors, particularly those looking at both co-morbid illnesses and reductions in quality of life.

Cancer detection and mammogram volume of radiologists in a population-based screening programme

This study investigates the relationship between the number of screening mammograms read by radiologists and the screening breast cancer detection rate. Cancer detection rates for incident screens (all women aged >= 40 years) were compared by increasing categories of reader volume using Poisson regression. Data from New South Wales (NSW) for a 2 year period (2000-2001) were obtained from the BreastScreen NSW programme. Cancer detection rates increased with the number of mammograms read in the programme, reaching a plateau of approximately 40 per 10,000 after 1375 mammograms per year. No significant differences in cancer detection were evident above 875 mammograms (compared to below 875 mammograms) per year (RR = 0.79, 95% CI 0.63-0.99). (c) 2005 Elsevier Ltd. All rights reserved.

Breastfeeding, menopause, and epithelial ovarian cancer

No previous study has examined the modifying effect of menopausal status on the association between lactation and ovarian cancer risk. We recruited 824 epithelial ovarian cancer cases and 855 community controls in three Australian states, collecting reproductive and lactation histories by means of a contraceptive calendar and pregnancy and breastfeeding record. We report results in women with at least one liveborn infant for unsupplemented breastfeeding, in line with a biological model linking suppression of ovulation to reduction in ovarian cancer risk. We derived odds ratios from multiple logistic regression models including number of liveborn children, age, age at first or last birth, and other potential confounders, overall and by menopausal status. Estimates of relative risk of ovarian cancer per month of full lactation were 0.99 [95% confidence interval(CI) = 0.97-1.00] overall and 1.00 (95% CI = 0.99-1.01) and 0.98 (95% CI = 0.95-1.01) among post- and premenopausal women, respectively. We tailored a lactation variable to the incessant ovulation hypothesis by progressively discounting breastfeeding the longer after birth it occurred, finding odds ratios similar to those for the unmodified duration variable. We found no association of note among postmenopausal women. Breastfeeding seems to be somewhat protective against ovarian cancer, but only before menopause.

Risk factors for sudden unexpected cardiac death in Tasmanian men

Background: Sudden unexpected cardiac death (SUCD) accounts for approximately 25% of deaths from ischaemic heart disease (IHD) but is relatively poorly understood because of the difficulties involved in researching aetiology. Clinical differences between instances of SUCD and those cases of acute chest pain that survive long enough to be proven as myocardial infarction but are eventually fatal might reflect differences in aetiology. Aims: To determine the risk factors for sudden unexpected cardiac death in Tasmanian men. Methods: A population-based case-control method was used with the study population, an estimated 125,225 men aged 25-74 years living in the island State of Tasmania, Australia. The case group of 102 men who had a SUCD was validated using necropsy reports, hospital records and information provided by the usual general practitioner. Cases were matched with 204 community controls. Spouses or partners of eligible subjects answered a detailed questionnaire. Multi-variate odds ratios (ORs) for risk factors were calculated using stepwise analysis. Results: Risk factors measured included: smoking habit, treated hypertension, hypercholesterolaemia, diabetes mellitus, family history of LHD, alcohol intake and exercise habits. Independent risk factors for SUCD were: history of diabetes mellitus (OR=4.2, 95% CI: 1.39, 12.81), current smoking status (OR=3.5, 95% CI: 1.80, 6.82), and family history of IHD (OR=2.6, 95% CI: 1.34, 4.92). Conclusions: Some accepted risk factors for acute myocardial infarction (AMI) also predict sudden death in men with no history of coronary disease. Efforts to reduce smoking, the incidence of diabetes mellitus and mean blood pressure must be continued as SUCD is, by definition, untreatable but is potentially avoidable in many instances.

The impact of diabetes on survival among patients with first myocardial infarction

OBJECTIVE - The purpose of this paper is to estimate the impact of diabetes on survival among patients with first acute myocardial infarction, using data from the World Health Organization (WHO) Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) Project in Newcastle, New South Wales, Australia. RESEARCH DESIGN AND METHODS - The WHO MONICA Project is a community-based surveillance system that monitors coronary heart disease morbidity and mortality. All patients with suspected coronary events were observed for 28 days after the onset of symptoms. RESULTS - Of 5,322 patients with acute myocardial infarction and no previous history of ischemic heart disease (3,643 men and 1,679 women), 333 men (9%) and 224 women (13%) had a history of diabetes. The age-adjusted 28-day case fatality for women with diabetes (25%) was significantly higher than for women without diabetes (16%); relative risk 1.56 (95% CI: 1.19-2.04). The difference for men was also significant (25% with diabetes and 20% without diabetes); relative risk 1.25 (95% CI: 1.02-1.53). Age-specific case fatality increased significantly with age in both men and women without diabetes, but systematic age effects were not so apparent in patients with diabetes. Case fatality significantly decreased over the study period in patients without diabetes, but not among the diabetic patients. CONCLUSIONS - The increased risk of death in the diabetic patients remained after accounting for their poorer risk factor profiles; even if they reached the hospital alive, diabetic patients were also less likely to survive than nondiabetic patients. The relative impact of diabetes on survival is greater in women than in men.

The occurrence of cancer in a cohort of New South Wales coal miners

To describe the incidence of cancer in coal miners in New South Wales (NSW) between 1973 and 1992, an inception cohort of all male coal industry employees who entered the industry between 1 January 1973 and 31 December 1992 was constructed from the medical examination records of the Joint Coal Board. This cohort was matched with the NSW State Cancer Registry to determine the occurrence and type of cancer. In the cohort of 23 630 men, 297 developed 301 primary cancers in the 20-year period of observation. The standardised incidence ratio (SLR) for all cancers was 0.82. Stomach cancer has been reported to be common in coal miners but the SIR for stomach cancer was not higher than average in this cohort. A cluster of non-Hodgkin's lymphoma has been reported in a NSW coal mine but an increased risk of this cancer was not evident in the industry as a whole. Similarly a cluster of cases of brain tumour has been reported. In this cohort, the SIR for brain tumour was 1.05 (95 per cent confidence interval (CI) 0.57 to 1.76) and a risk for brain tumour remains unconfirmed. The SIR for malignant melanoma was 1.13 (CI 0.90 to 1.39) altogether and 2.02 (CI 1.31 to 2.98) for those workers who started in an open-cut mine. Overall, there does not appear to be a general risk of cancer in the NSW coal industry. Open-cut miners have an increased risk of malignant melanoma, which may be related to their exposure to the sun at work.

Validity of self-reported hysterectomy and tubal sterilisation

Both hysterectomy and tubal sterilisation offer significant protection from ovarian cancer, and the risk of cardiovascular disease in women is lowered after hysterectomy. Since little is known about the accuracy of women's self-reports of these procedures, we assessed their reliability and validity using data obtained in a case-control study of ovarian cancer. There was 100 per cent repeatability for both positive and negative histories of hysterectomy and tubal sterilisation among a small sample of women on reinterview. Verification of surgery was sought against surgeons' or medical records, or if these were unavailable, from randomly selected current general practitioners for 51 cases and 155 controls reporting a hysterectomy and 73 cases and 137 controls reporting a tubal sterilisation. Validation rate for self-reported hysterectomy against medical reports (32 cases, 96 controls) was 96 per cent (95 per cent confidence interval (CI) 91 to 99) and for tubal sterilisation (32 cases, 77 controls) it was 88 per cent (CI 81 to 93), which is likely to be an underestimate. Although findings are based on small numbers of women for whom medical reports could be ascertained, they are consistent with other findings that suggest women have good recall of past histories of hysterectomy and tubal sterilisation; this allows long-term effects of these procedures to be studied with reasonable accuracy from self-reports.