Annette Dobson

Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations

BACKGROUND From the mid-1980s to mid-1990s, the WHO MONICA Project monitored coronary events and classic risk factors for coronary heart disease (CHD) in 38 populations from 21 countries. We assessed the extent to which changes in these risk factors explain the variation in the trends in coronary-event rates across the populations. METHODS In men and women aged 35-64 years, non-fatal myocardial infarction and coronary deaths were registered continuously to assess trends in rates of coronary events. We carried out population surveys to estimate trends in risk factors. Trends in event rates were regressed on trends in risk score and in individual risk factors. FINDINGS Smoking rates decreased in most male populations but trends were mixed in women; mean blood pressures and cholesterol concentrations decreased, bodymass index increased, and overall risk scores and coronary-event rates decreased. The model of trends in 10-year coronary-event rates against risk scores and single risk factors showed a poor fit, but this was improved with a 4-year time lag for coronary events. The explanatory power of the analyses was limited by imprecision of the estimates and homogeneity of trends in the study populations. INTERPRETATION Changes in the classic risk factors seem to partly explain the variation in population trends in CHD. Residual variance is attributable to difficulties in measurement and analysis, including time lag, and to factors that were not included, such as medical interventions. The results support prevention policies based on the classic risk factors but suggest potential for prevention beyond these.

How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review

Abstract Objective To assess how well B-type natriuretic peptide (BNP) predicts prognosis in patients with heart failure. Design Systematic review of studies assessing BNP for prognosis in patients with heart failure or asymptomatic patients. Data sources Electronic searches of Medline and Embase from January 1994 to March 2004 and reference lists of included studies. Study selection and data extraction We included all studies that estimated the relation between BNP measurement and the risk of death, cardiac death, sudden death, or cardiovascular event in patients with heart failure or asymptomatic patients, including initial values and changes in values in response to treatment. Multivariable models that included both BNP and left ventricular ejection fraction as predictors were used to compare the prognostic value of each variable. Two reviewers independently selected studies and extracted data. Data synthesis 19 studies used BNP to estimate the relative risk of death or cardiovascular events in heart failure patients and five studies in asymptomatic patients. In heart failure patients, each 100 pg/ml increase was associated with a 35% increase in the relative risk of death. BNP was used in 35 multivariable models of prognosis. In nine of the models, it was the only variable to reach significance—that is, other variables contained no prognostic information beyond that of BNP. Even allowing for the scale of the variables, it seems to be a strong indicator of risk. Conclusion Although systematic reviews of prognostic studies have inherent difficulties, including the possibility of publication bias, the results of the studies in this review show that BNP is a strong prognostic indicator for both asymptomatic patients and for patients with heart failure at all stages of disease.

Population Versus Clinical View of Case Fatality From Acute Coronary Heart Disease Results From the WHO MONICA Project 1985–1990

BACKGROUND The clinical view of case fatality (CF) from acute myocardial infarction (AMI) in those reaching the hospital alive is different from the population view. Registration of both hospitalized AMI cases and out-of-hospital coronary heart disease (CHD) deaths in the WHO MONICA Project allows both views to be reconciled. The WHO MONICA Project provides the largest data set worldwide to explore the relationship between CHD CF and age, sex, coronary event rate, and first versus recurrent event. METHODS AND RESULTS All 79,669 events of definite AMI or possible coronary death, occurring from 1985 to 90 among 5,725,762 people, 35 to 64 years of age, in 29 MONICA populations are the basis for CF calculations. Age-adjusted CF (percentage of CHD events that were fatal) was calculated across populations, stratified for different time periods, and related to age, sex, and CHD event rate. Median 28-day population CF was 49% (range, 35% to 60%) in men and 51% (range, 34% to 70%) in women and was particularly higher in women than men in populations in which CHD event rates were low. Median 28-day CF for hospitalized events was much lower: in men 22% (range, 15% to 36%) and in women 27% (range, 19% to 46%). Among hospitalized events CF was twice as high for recurrent as for first events. CONCLUSIONS Overall 28-day CF is halved for hospitalized events compared with all events and again nearly halved for hospitalized 24-hour survivors. Because approximately two thirds of 28-day CHD deaths in men and women occurred before reaching the hospital, opportunities for reducing CF through improved care in the acute event are limited. Major emphasis should be on primary and secondary prevention.

How much alcohol and how often? Population based case-control study of alcohol consumption and risk of a major coronary event

Abstract Objective:To quantify the effects of quantity and frequency of alcohol consumption on risk of acute myocardial infarction and coronary death. Design:Case-control study. Setting:Lower Hunter region of New South Wales, Australia, 1983-94. Subjects:Men and women aged 35-69 years. Main outcome measure:Acute myocardial infarction or coronary death. Results:Alcohol consumption patterns were compared between 11 511 cases of acute myocardial infarction or coronary death and 6077 controls randomly selected from the same study population. After adjusting for the effects of age, smoking, and medical history, men and women who consumed one or two drinks of alcohol on five or six days a week had a reduction in risk of a major coronary event compared with men and women who were non-drinkers (odds ratios: men 0.31 (95% confidence interval 0.22 to 0.45); women 0.33 (0.18 to 0.59)). A similar reduction in risk was found after excluding non-drinkers who were formerly moderate to heavy drinkers. An acute protective effect of alcohol consumption was also found for regular drinkers who consumed one or two drinks in the 24 hours preceding the onset of symptoms (odds ratios: men 0.74 (0.51 to 1.09); women 0.43 (0.20 to 0.95)). Conclusions:Frequency and quantity of alcohol consumption are important in assessing the risk of a major coronary event. Risk is lowest among men who report one to four drinks daily on five or six days a week and among women who report one or two drinks daily on five or six days a week.

Variability in the risk of major gastrointestinal complications from nonaspirin nonsteroidal anti-inflammatory drugs

BACKGROUND We have assessed the extent to which the risk of serious gastrointestinal complications from nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) varies with the age and sex of recipients, use of aspirin or alcohol, administration by the oral or rectal route, and dose and choice of drug. METHODS A case-control study was performed with prospective recruitment of cases of gastrointestinal bleeding or ulcer perforation and age- and sex-matched controls. Information on preadmission drug use obtained by structured interview. RESULTS Six hundred forty-four patients and 1268 controls were recruited. The odds ratio for upper gastrointestinal complications in users compared with nonusers of NANSAIDs increased with age: < or = 59 years, odds ratio 2.0; 60-79 years, odds ratio 3.0; > or = 80 years, odds ratio 4.2; and was higher in women (5.4) than in men (1.9). There was a linear dose-response curve that was steeper in women than in men. Combined exposure suggested additive risks: NANSAIDs and aspirin, odds ratio 6.7; NANSAIDs and alcohol, odds ratio 6.0 NANSAIDs by the oral route were associated with an odds ratio of 2.3, compared with 11.4 with rectal administration. Piroxicam was associated with the highest risk, odds ratio 4.8; and ibuprofen the lowest risk, odds ratio 0.7. CONCLUSIONS A number of factors can alter the risk of major gastrointestinal complications with NANSAIDs and need to be considered when individual prescribing decisions are made.

Smoking and relative body weight: an international perspective from the WHO MONICA Project.

STUDY OBJECTIVE: To investigate the magnitude and consistency of the associations between smoking and body mass index (BMI) in different populations. DESIGN: A cross sectional study. SETTING AND PARTICIPANTS: About 69,000 men and women aged 35-64 years from 42 populations participating in the first WHO MONICA survey in the early and mid 1980s. MAIN RESULTS: Compared to never smokers, regular smokers had significantly (p < 0.05) lower median BMI in 20 (men) and 30 (women) out of 42 populations (range -2.9 to 0.5 kg/m2). There was no population in which smokers had a significantly higher BMI than never smokers. Among men, the association between leanness and smoking was less apparent in populations with relatively low proportions of regular smokers and high proportions of ex-smokers. Ex-smokers had significantly higher BMI than never smokers in 10 of the male populations but in women no consistent pattern was observed. Adjustment for socioeconomic status did not affect these results. CONCLUSIONS: Although in most populations the association between smoking and BMI is similar, the magnitude of this association may be affected by the proportions of smokers and ex-smokers in these populations.

Cold periods and coronary events: an analysis of populations worldwide.

Study objective: To investigate the association between cold periods and coronary events, and the extent to which climate, sex, age, and previous cardiac history increase risk during cold weather. Design: A hierarchical analyses of populations from the World Health Organisation’s MONICA project. Setting: Twenty four populations from the WHO’s MONICA project, a 21 country register made between 1980 and 1995. Patients: People aged 35–64 years who had a coronary event. Main results: Daily rates of coronary events were correlated with the average temperature over the current and previous three days. In cold periods, coronary event rates increased more in populations living in warm climates than in populations living in cold climates, where the increases were slight. The increase was greater in women than in men, especially in warm climates. On average, the odds for women having an event in the cold periods were 1.07 higher than the odds for men (95% posterior interval: 1.03 to 1.11). The effects of cold periods were similar in those with and without a history of a previous myocardial infarction. Conclusions: Rates of coronary events increased during comparatively cold periods, especially in warm climates. The smaller increases in colder climates suggest that some events in warmer climates are preventable. It is suggested that people living in warm climates, particularly women, should keep warm on cold days.

TRENDS IN CIGARETTE SMOKING IN 36 POPULATIONS FROM THE EARLY 1980S TO THE MID-1990S: FINDINGS FROM THE WHO MONICA PROJECT

OBJECTIVES This report analyzes cigarette smoking over 10 years in populations in the World Health Organization (WHO) MONICA Project (to monitor trends and determinants of cardiovascular disease). METHODS Over 300,000 randomly selected subjects aged 25 to 64 years participated in surveys conducted in geographically defined populations. RESULTS For men, smoking prevalence decreased by more than 5% in 16 of the 36 study populations, remained static in most others, but increased in Beijing. Where prevalence decreased, this was largely due to higher proportions of never smokers in the younger age groups rather than to smokers quitting. Among women, smoking prevalence increased by more than 5% in 6 populations and decreased by more than 5% in 9 populations. For women, smoking tended to increase in populations with low prevalence and decrease in populations with higher prevalence; for men, the reverse pattern was observed. CONCLUSIONS These data illustrate the evolution of the smoking epidemic in populations and provide the basis for targeted public health interventions to support the WHO priority for tobacco control.

How soon after quitting smoking does risk of heart attack decline

A population-based case-control study (involving 1282 cases and 2068 controls) was conducted to examine the risk of myocardial infarction or coronary death after cigarette smokers quit smoking. The odds ratios for current smokers were significantly elevated compared to non-smokers (OR = 2.7 for men and OR = 4.7 for women). For ex-smokers odds ratios declined rapidly after quitting and after about 3 years they were not significantly different from unity. Fibrinogen concentrations measured in the controls only were higher in current smokers and ex-smokers up to 2 years after quitting than in non-smokers and after that time were similar to levels in non-smokers; however, most of the differences among categories of smokers were not statistically significant. These results support the hypothesis that risk of a coronary event in ex-smokers declines rapidly after quitting and within 2-3 years is similar to the risk for non-smokers.

Effectiveness of quadrivalent human papillomavirus vaccine for the prevention of cervical abnormalities: case-control study nested within a population based screening programme in Australia.

Objective To measure the effectiveness of the quadrivalent human papillomavirus (HPV) vaccine against cervical abnormalities four years after implementation of a nationally funded vaccination programme in Queensland, Australia. Design Case-control analysis of linked administrative health datasets. Setting Queensland, Australia. Participants Women eligible for free vaccination (aged 12-26 years in 2007) and attending for their first cervical smear test between April 2007 and March 2011. High grade cases were women with histologically confirmed high grade cervical abnormalities (n=1062) and “other cases” were women with any other abnormality at cytology or histology (n=10 887). Controls were women with normal cytology (n=96 404). Main outcome measures Exposure odds ratio (ratio of odds of antecedent vaccination (one, two, or three vaccine doses compared with no doses) among cases compared with controls), vaccine effectiveness ((1−adjusted odds ratio)×100), and number needed to vaccinate to prevent one cervical abnormality at first screening round. We stratified by four age groups adjusted for follow-up time, year of birth, and measures of socioeconomic status and remoteness. The primary analysis concerned women whose first ever smear test defined their status as a case or a control. Results The adjusted odds ratio for exposure to three doses of HPV vaccine compared with no vaccine was 0.54 (95% confidence interval 0.43 to 0.67) for high grade cases and 0.66 (0.62 to 0.70) for other cases compared with controls with normal cytology, equating to vaccine effectiveness of 46% and 34%, respectively. The adjusted numbers needed to vaccinate were 125 (95% confidence interval 97 to 174) and 22 (19 to 25), respectively. The adjusted exposure odds ratios for two vaccine doses were 0.79 (95% confidence interval 0.64 to 0.98) for high grade cases and 0.79 (0.74 to 0.85) for other cases, equating to vaccine effectiveness of 21%. Conclusion The quadrivalent HPV vaccine conferred statistically significant protection against cervical abnormalities in young women who had not started screening before the implementation of the vaccination programme in Queensland, Australia.