Insulin resistance in non-diabetic subjects is associated with increased incidence of myocardial infarction and death.

AIMS: To compare the incidence of myocardial infarction and death in non-diabetic subjects with and without insulin resistance. METHODS: Population-based prospective cohort study, in Malmö, Sweden, of 4748 non-diabetic subjects (60% women), aged 46-68 years, with no history of myocardial infarction or stroke. The prevalence of insulin resistance was established by the homeostasis model assessment (HOMA) and defined as values above the sex-specific 75th percentile (1.80 for women and 2.12 for men). Incidence of myocardial infarction and death is based on record linkage with local and national registers. Cox's proportional hazards model was used to assess the influence of insulin resistance after adjustment for age, sex, hyperglycaemia, raised arterial blood pressure, dyslipidaemia, central obesity, smoking and leisure-time physical activity. RESULTS: Sixty-two subjects suffered a coronary event, and 93 subjects died during the 6-year follow-up period. Insulin resistance was after adjustment for other factors included in the insulin resistance syndrome and other potential confounders, associated with an increased incidence of coronary events (relative risk (RR) 2.18; 95% confidence interval (CI) 1.22-3.87; P = 0.008) and deaths (RR 1.62; 1.03-2.55; P = 0.038). CONCLUSIONS: Insulin resistance, as assessed by the HOMA method, was in this cohort of middle-aged non-diabetic subjects associated with an increased incidence of myocardial infarction and death. This risk remained when smoking, low physical activity and factors included in the insulin resistance syndrome were taken into account in a stepwise regression model. Diabet. Med. 19, 470-475 (2002

Using big data from health records from four countries to evaluate chronic disease outcomes: a study in 114 364 survivors of myocardial infarction

Aims: to assess the international validity of using hospital record data to compare long-term outcomes in heart attack survivors. Methods and results: we used samples of national, ongoing, unselected record sources to assess three outcomes: cause death; a composite of myocardial infarction (MI), stroke, and all-cause death; and hospitalized bleeding. Patients aged 65 years and older entered the study 1 year following the most recent discharge for acute MI in 2002–11 [n = 54 841 (Sweden), 53 909 (USA), 4653 (England), and 961 (France)]. Across each of the four countries, we found consistent associations with 12 baseline prognostic factors and each of the three outcomes. In each country, we observed high 3-year crude cumulative risks of all-cause death (from 19.6% [England] to 30.2% [USA]); the composite of MI, stroke, or death [from 26.0% (France) to 36.2% (USA)]; and hospitalized bleeding [from 3.1% (France) to 5.3% (USA)]. After adjustments for baseline risk factors, risks were similar across all countries [relative risks (RRs) compared with Sweden not statistically significant], but higher in the USA for all-cause death [RR USA vs. Sweden, 1.14 (95% confidence interval 1.04–1.26)] and hospitalized bleeding [RR USA vs. Sweden, 1.54 (1.21–1.96)]. Conclusion: the validity of using hospital record data is supported by the consistency of estimates across four countries of a high adjusted risk of death, further MI, and stroke in the chronic phase after MI. The possibility that adjusted risks of mortality and bleeding are higher in the USA warrants further study

Health economic analysis of ticagrelor in patients with acute coronary syndromes intended for non-invasive therapy

Objective: To investigate the cost effectiveness of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) in the Platelet Inhibition and Patient Outcomes (PLATO) study who were scheduled for non-invasive management. Methods: A previously developed cost effectiveness model was used to estimate long-term costs and outcomes for patients scheduled for non-invasive management. Healthcare costs, event rates and health-related quality of life under treatment with either ticagrelor or clopidogrel over 12 months were estimated from the PLATO study. Long-term costs and health outcomes were estimated based on data from PLATO and published literature sources. To investigate the importance of different healthcare cost structures and life expectancy for the results, the analysis was carried out from the perspectives of the Swedish, UK, German and Brazilian public healthcare systems. Results: Ticagrelor was associated with lifetime quality-adjusted life-year (QALY) gains of 0.17 in Sweden, 0.16 in the UK, 0.17 in Germany and 0.13 in Brazil compared with generic clopidogrel, with increased healthcare costs of €467, €551, €739 and €574, respectively. The cost per QALY gained with ticagrelor was €2747, €3395, €4419 and €4471 from a Swedish, UK, German and Brazilian public healthcare system perspective, respectively. Probabilistic sensitivity analyses indicated that the cost per QALY gained with ticagrelor was below conventional threshold values of cost effectiveness with a high probability. Conclusions: Treatment of patients with ACS scheduled for 12 months’ non-invasive management with ticagrelor is associated with a cost per QALY gained below conventional threshold values of cost effectiveness compared with generic clopidogrel. Trial registration number NCT000391872

Mortality in GOLD stages of COPD and its dependence on symptoms of chronic bronchitis

BACKGROUND: The GOLD classification of COPD severity introduces a stage 0 (at risk) comprising individuals with productive cough and normal lung function. The aims of this study were to investigate total mortality risks in GOLD stages 0–4 with special focus on stage 0, and furthermore to assess the influence of symptoms of chronic bronchitis on mortality risks in GOLD stages 1–4. METHOD: Between 1974 and 1992, a total of 22 044 middle-aged individuals participated in a health screening, which included a spirometry as well as recording of respiratory symptoms and smoking habits. Individuals with comorbidity at baseline (diabetes, stroke, cancer, angina pectoris, or heart infarction) were excluded from the analyses. Hazard ratios (HR 95% CI) of total mortality were analyzed in GOLD stages 0–4 with individuals with normal lung function and without symptoms of chronic bronchitis as a reference group. HR:s in smoking individuals with symptoms of chronic bronchitis within the stages 1–4 were calculated with individuals with the same GOLD stage but without symptoms of chronic bronchitis as reference. RESULTS: The number of deaths was 3674 for men and 832 for women based on 352 324 and 150 050 person-years respectively. The proportion of smokers among men was 50% and among women 40%. Self reported comorbidity was present in 4.6% of the men and 6.6% of the women. Among smoking men, Stage 0 was associated with an increased mortality risk, HR; 1.65 (1.32–2.08), of similar magnitude as in stage 2, HR; 1.41 (1.31–1.70). The hazard ratio in stage 0 was significantly higher than in stage 1 HR; 1.13 (0.98–1.29). Among male smokers with stage 1; HR: 2.04 (1.34–3.11), and among female smokers with stage 2 disease; HR: 3.16 (1.38–7.23), increased HR:s were found in individuals with symptoms of chronic bronchitis as compared to those without symptoms of chronic bronchitis. CONCLUSION: Symptoms fulfilling the definition of chronic bronchitis were associated with an increased mortality risk among male smokers with normal pulmonary function (stage 0) and also with an increased risk of death among smoking individuals with mild to moderate COPD (stage 1 and 2)

Are non-responders in a quitline evaluation more likely to be smokers?

BACKGROUND: In evaluation of smoking cessation programs including surveys and clinical trials the tradition has been to treat non-responders as smokers. The aim of this paper is to assess smoking behaviour of non-responders in an evaluation of the Swedish national tobacco cessation quitline a nation-wide, free of charge service. METHODS: A telephone interview survey with a sample of people not participating in the original follow-up. The study population comprised callers to the Swedish quitline who had consented to participate in a 12 month follow-up but had failed to respond. A sample of 84 (18% of all non-responders) was included. The main outcome measures were self-reported smoking behaviour at the time of the interview and at the time of the routine follow-up. Also, reasons for not responding to the original follow-up questionnaire were assessed. For statistical comparison between groups we used Fischer's exact test, odds ratios (OR) and 95% confidence intervals (CI) on proportions and OR. RESULTS: Thirty-nine percent reported to have been smoke-free at the time they received the original questionnaire compared with 31% of responders in the original study population. The two most common reasons stated for not having returned the original questionnaire was claiming that they had returned it (35%) and that they had not received the questionnaire (20%). Non-responders were somewhat younger and were to a higher degree smoke-free when they first called the quitline. CONCLUSION: Treating non-responders as smokers in smoking cessation research may underestimate the true effect of cessation treatment

Efficacy and Safety of Glycoprotein IIb/IIIa Inhibitors on Top of Ticagrelor in STEMI: A Subanalysis of the ATLANTIC Trial

BACKGROUND: Glycoprotein IIb/IIIa inhibitors (GPIs) in combination with clopidogrel improve clinical outcome in ST-elevation myocardial infarction (STEMI); however, finding a balance that minimizes both thrombotic and bleeding risk remains fundamental. The efficacy and safety of GPI in addition to ticagrelor, a more potent P2Y12-inhibitor, have not been fully investigated. METHODS: 1,630 STEMI patients who underwent primary percutaneous coronary intervention (PCI) were analyzed in this subanalysis of the ATLANTIC trial. Patients were divided in three groups: no GPI, GPI administration routinely before primary PCI, and GPI administration in bailout situations. The primary efficacy outcome was a composite of death, myocardial infarction, urgent target revascularization, and definite stent thrombosis at 30 days. The safety outcome was non-coronary artery bypass graft (CABG)-related PLATO major bleeding at 30 days. RESULTS: Compared with no GPI (n\u2009=\u2009930), routine GPI (n\u2009=\u2009525) or bailout GPI (n\u2009=\u2009175) was not associated with an improved primary efficacy outcome (4.2% no GPI vs. 4.0% routine GPI vs. 6.9% bailout GPI; p\u2009=\u20090.58). After multivariate analysis, the use of GPI in bailout situations was associated with a higher incidence of non-CABG-related bleeding compared with no GPI (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.32-6.64; p\u2009=\u20090.03). However, routine GPI use compared with no GPI was not associated with a significant increase in bleeding (OR 1.78, 95% CI 0.88-3.61; p\u2009=\u20090.92). CONCLUSION: Use of GPIs in addition to ticagrelor in STEMI patients was not associated with an improvement in 30-day ischemic outcome. A significant increase in 30-day non-CABG-related PLATO major bleeding was seen in patients who received GPIs in a bailout situation

Maternal educational level and risk of gestational hypertension: the Generation R Study.

We examined whether maternal educational level as an indicator of socioeconomic status is associated with gestational hypertension. We also examined the extent to which the effect of education is mediated by maternal substance use (that is smoking, alcohol consumption and illegal drug use), pre-existing diabetes, anthropometrics (that is height and body mass index (BMI)) and blood pressure at enrolment. This was studied in 3262 Dutch pregnant women participating in the Generation R Study, a population-based cohort study. Level of maternal education was established by questionnaire at enrolment, and categorized into high, mid-high, mid-low and low. Diagnosis of gestational hypertension was retrieved from medical records using standard criteria. Odds ratios (OR) of gestational hypertension for educational levels were calculated, adjusted for potential confounders and additionally adjusted for potential mediators. Adjusted for age and gravidity, women with mid-low (OR: 1.52; 95% CI: 1.02, 2.27) and low education (OR: 1.30; 95% CI: 0.80, 2.12) had a higher risk of gestational hypertension than women with high education. Additional adjustment for substance use, pre-existing diabetes, anthropometrics and blood pressure at enrolment attenuated these ORs to 1.09 (95% CI: 0.70, 1.69) and 0.89 (95% CI: 0.50, 1.58), respectively. These attenuations were largely due to the effects of BMI and blood pressure at enrolment. Women with relatively low educational levels have a higher risk of gestational hypertension, which is largely due to higher BMI and blood pressure levels from early pregnancy. The higher risk of gestational hypertension in these women is probably caused by pre-existing hypertensive tendencies that manifested themselves during pregnancy

Ressenyes

Index de les obres ressenyades: Alice BARTHEZ, Famille, travail et agricultur

Swedish snuff and incidence of cardiovascular disease. A population-based cohort study

<p>Abstract</p> <p>Background</p> <p>The relationship between smoking and an increased incidence of cardiovascular diseases is well known. Whether smokeless tobacco (snuff) is related to myocardial infarction (MI) or stroke is still controversial. Aim of this study was to explore whether snuff users have an increased incidence of MI or stroke.</p> <p>Methods</p> <p>A total of 16 754 women and 10 473 men (aged 45–73 years), without history of cardiovascular disease (CVD), belonging to the population-based "Malmö Diet and Cancer" study were examined. Incidence of MI and stroke were monitored over 10.3 years.</p> <p>Results</p> <p>Snuff was used by 737 (7.0%) men and 75 (0.4%) women, respectively. Among men, snuff was significantly associated with low occupation level, single civil status, high BMI and with current and former smoking. In women, snuff was associated with lower systolic blood pressure. A total of 964 individuals (3.5%), i.e.544 men (5.3%) and 420 (2.5%) women suffered a MI during the follow-up period. The corresponding numbers of incident stroke cases were 1048, i.e. 553 men (5.3%) and 495 (3.0%) women, respectively. Snuff was not associated with any statistically significant increased risk of MI or stroke in men or women. The relative risks (RR) in male snuff users compared to non-users were 1.05 (95% confidence interval (CI): 0.8–1.4, p = 0.740) for incident MI and 0.97 (0.7–1.4, p = 0.878) for stroke, after taking age and potential confounders into account. In women none of the 420 (2.5%) women who were snuff users had a MI and only one suffered a stroke during the follow-up.</p> <p>Conclusion</p> <p>Several life-style risk factors were more prevalent in snuff-users than in non-users. However, the present study does not support any relationship between snuff and incidence of cardiovascular disease in men.</p

Marital status and occupation in relation to short-term case fatality after a first coronary event - a population based cohort

<p>Abstract</p> <p>Background</p> <p>Although marital status and low occupation level has been associated with mortality, the relationship with case fatality rates (CFR) after a coronary event (CE) is unclear. This study explored whether incidence of CE and short-term CFR differ between groups defined in terms of marital status and occupation, and if this could be explained by biological and life-style risk factors.</p> <p>Methods</p> <p>Population-based cohort study of 33,224 subjects (67% men), aged 27 to 61 years, without history of myocardial infarction, who were enrolled between 1974 and 1992. Incidence of CE, and CFR (death during the first day or within 28 days after CE, including out-of-hospital deaths) was examined over a mean follow-up of 21 years.</p> <p>Results</p> <p>A total of 3,035 men (6.0 per 1000 person-years) and 507 women (2.4 per 1000) suffered a first CE during follow-up. CFR (during the 1^stday) was 29% in men and 23% in women. After risk factor adjustments, unmarried status in men, but not in women, was significantly associated with increased risk of suffering a CE [hazard ratios (HR) 1.10, 95% CI: 0.97-1.24; 1.42: 1.27-1.58 and 1.77: 1.31-2.40 for never married, divorced and widowed, respectively, compared to married]. Unmarried status, in both gender, was also related with an increased CFR (1^stday), taking potential confounders into account (odds ratio (OR) 2.14, 95% CI: 1.63-2.81; 1.91: 1.50-2.43 and 1.49: 0.77-2.89 for never married, divorced and widowed, respectively, compared to married men. Corresponding figures for women was 2.32: 0.93-5.81; 1.87: 1.04-3.36 and 2.74: 1.03-7.28. No differences in CFR (1^stday) were observed between occupational groups in neither gender.</p> <p>Conclusions</p> <p>In this population-based Swedish cohort, short-term CFR was significantly related to unmarried status in men and women. This relationship was not explained by biological-, life-style factors or occupational level.</p