Residual risk of cardiovascular mortality in patients with coronary heart disease: the EUROASPIRE risk categories.

BACKGROUND: The EUROASPIRE I, II and III surveys revealed high prevalences of modifiable risk factors in the high priority group of coronary patients all over Europe. The potential to further reduce coronary heart disease (CHD) morbidity and mortality rates is still considerable. We report here on the relative risk of cardiovascular disease (CVD) death associated with common modifiable risk factor levels based on the mortality follow-up of patients participating in the first two EUROASPIRE surveys. We also present a novel simple risk classification system (ERC) that can be used in the management of patients with existing CHD. METHODS: The study cohort consisted of a consecutive sample of CHD patients aged ≤ 70 years from 12 European countries. Baseline data gathered in 1995-2000 through standardized methods, were linked to cardiovascular mortality in 5216 patients according to an accelerated failure time model. RESULTS: During 28,143 person-years of follow-up, 332 patients died from cardiovascular disease denoting a CVD mortality risk of 12.3 per 1000 person-years in men and 10.2 per 1000 person-years in women. In multivariate analysis, fasting glucose, total cholesterol and smoking emerged as the strongest independent modifiable predictors of cardiovascular mortality. CONCLUSIONS: The results of the mortality follow-up of the EUROASPIRE I and II CHD patients emphasize the continuing risk from elevated glucose and total cholesterol levels and underline the importance of smoking cessation in secondary prevention. The ERC risk tool that we developed may prove helpful to obtain these goals in the setting of secondary prevention.

Development of coronary heart disease and ischemic stroke in relation to fasting and 2-hour plasma glucose levels in the normal range.

BACKGROUND: Individuals who had normoglycemia but whose 2-hour plasma glucose (2hPG) concentrations did not return to the fasting plasma glucose (FPG) levels during an oral glucose tolerance test (OGTT) have been shown to have increased cardiovascular mortality. This is further investigated regarding to the first events of coronary heart disease (CHD) and ischemic stroke (IS). METHOD: Data from 9 Finnish and Swedish cohorts comprising 3743 men and 3916 women aged 25 to 90 years who had FPG < 6.1 mmol/l and 2hPG < 7.8 mmol/l and free of CVD at enrollment were analyzed. Hazard ratios (HRs) for first CHD and IS events were estimated for the individuals with 2hPG > FPG (Group II) compared with those having 2hPG ≤ FPG (Group I). RESULTS: A total of 466 (115) CHD and 235 (106) IS events occurred in men (women) during a median follow-up of 16.4 years. Individuals in Group II were older and had greater body mass index, blood pressure, 2hPG and fasting insulin than those in Group I in both sexes. Multivariate adjusted HRs (95% confidence intervals) for incidence of CHD, IS, and composite CVD events (CHD + IS) in men were 1.13 (0.93-1.37), 1.40 (1.06-1.85) and 1.20 (1.01-1.42) in the Group II as compared with those in the Group I. The corresponding HRs in women were 1.33 (0.83-2.13), 0.94 (0.59-1.51) and 1.11 (0.79-1.54), respectively. CONCLUSION: Within normoglycemic range individuals whose 2hPG did not return to their FPG levels during an OGTT had increased risk of CHD and IS.

EUROASPIRE III. Management of cardiovascular risk factors in asymptomatic high-risk patients in general practice: cross-sectional survey in 12 European countries.

OBJECTIVE: To determine whether the 2003 Joint European Societies' guidelines on cardiovascular disease prevention in people at high cardiovascular risk have been followed in general practice. DESIGN: Cross-sectional survey. METHODS: The EUROASPIRE survey was carried out in 2006-2007 in 66 general practices in 12 European countries. Patients without a history of coronary or other atherosclerotic disease either started on antihypertensive and/or lipid-lowering and/or antidiabetes treatments were identified retrospectively, interviewed and examined at least 6 months after the start of medication. RESULTS: Four thousand, three hundred and sixty-six high-risk individuals (57.7% females) were interviewed (participation rate 76.7%). Overall, 16.9% smoked cigarettes, 43.5% had body mass index ≥30 kg/m, 70.8% had blood pressure ≥140/90 mmHg (≥130/80 in people with diabetes mellitus), 66.4% had total cholesterol ≥5.0 mmol/l (≥4.5 mmol/l in people with diabetes) and 30.2% reported a history of diabetes. The risk factor control was very poor, with only 26.3% of patients using antihypertensive medication achieving the blood pressure goal, 30.6% of patients on lipid-lowering medication achieving the total cholesterol goal and 39.9% of patients with self-reported diabetes having haemoglobin A1c ≤6.1%. The use of blood pressure-lowering medication in people with hypertension was: ß-blockers 34.1%, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers 60.8%, calcium channel blockers 26.3%, diuretics 36.9%. Statins were prescribed in 47.0% of people with hypercholesterolemia. About 22.0% of all patients were on aspirin or other antiplatelet medication. CONCLUSION: The EUROASPIRE III survey in general practice shows that the lifestyle of people being treated as high cardiovascular risk is a major cause of concern with persistent smoking and high prevalence of both obesity and central obesity. Blood pressure, lipid and glucose control are completely inadequate with most patients not achieving the targets defined in the prevention guidelines. Primary prevention needs a systematic, comprehensive, multidisciplinary approach, which addresses lifestyle and risk factor management by general practitioners, nurses and other allied health professionals, and a health care system which invests in prevention.

Cardiovascular disease mortality in Europeans in relation to fasting and 2-h plasma glucose levels within a normoglycemic range.

OBJECTIVE: To study mortality in relation to fasting plasma glucose (FPG) and 2-h plasma glucose levels within the normoglycemic range. RESEARCH DESIGN AND METHODS: Data from 19 European cohorts comprising 12,566 men and 10,874 women who had FPG <6.1 mmol/l and 2-h plasma glucose <7.8 mmol/l at baseline examination were analyzed. Multivariate-adjusted hazard ratios (HRs) and 95% CIs for deaths from cardiovascular disease (CVD), non-CVD, and all causes were estimated for individuals whose 2-h plasma glucose > FPG (group II) compared with those whose 2-h plasma glucose ≤ FPG (group I). RESULTS: A total of 827 (246) CVD and 611 (351) non-CVD and 1,438 (597) all-cause deaths occurred in men (women). Group II was older and had higher BMI, blood pressure, and fasting insulin than group I. The multivariate-adjusted HRs (95% CIs) for CVD, non-CVD, and all-cause mortality were 1.22 (1.05-1.41), 1.09 (0.92-1.29), and 1.16 (1.04-1.30) in men and 1.40 (1.03-1.89), 0.99 (0.79-1.25), and 1.13 (0.94-1.35) in women, respectively, for group II as compared with group I. HRs were 1.25 (1.05-1.50), 1.09 (0.89-1.34), and 1.18 (1.03-1.35) in men and 1.60 (1.03-2.48), 1.05 (0.78-1.42), and 1.18 (0.93-1.51) in women, respectively, after additional adjustment for fasting insulin in a subgroup of individuals. CONCLUSIONS: In individuals with both FPG and 2-h plasma glucose within the normoglycemic range, high 2-h plasma glucose was associated with insulin resistance and increased CVD mortality.

Cardiovascular prevention guidelines in daily practice: a comparison of EUROASPIRE I, II, and III surveys in eight European countries.

BACKGROUND: The first and second EUROASPIRE surveys showed high rates of modifiable cardiovascular risk factors in patients with coronary heart disease. The third EUROASPIRE survey was done in 2006-07 in 22 countries to see whether preventive cardiology had improved and if the Joint European Societies' recommendations on cardiovascular disease prevention are being followed in clinical practice. METHODS: EUROASPIRE I, II, and III were designed as cross-sectional studies and included the same selected geographical areas and hospitals in the Czech Republic, Finland, France, Germany, Hungary, Italy, the Netherlands, and Slovenia. Consecutive patients (men and women /=30 kg/m(2)) increased from 25.0% in EUROASPIRE I, to 32.6% in II, and 38.0% in III (p=0.0006). The proportion of patients with raised blood pressure (>/=140/90 mm Hg in patients without diabetes or >/=130/80 mm Hg in patients with diabetes) was similar (58.1% in EUROASPIRE I, 58.3% in II, and 60.9% in III; p=0.49), whereas the proportion with raised total cholesterol (>/=4.5 mmol/L) decreased, from 94.5% in EUROASPIRE I to 76.7% in II, and 46.2% in III (p<0.0001). The frequency of self-reported diabetes mellitus increased, from 17.4%, to 20.1%, and 28.0% (p=0.004). INTERPRETATION: These time trends show a compelling need for more effective lifestyle management of patients with coronary heart disease. Despite a substantial increase in antihypertensive and lipid-lowering drugs, blood pressure management remained unchanged, and almost half of all patients remain above the recommended lipid targets. To salvage the acutely ischaemic myocardium without addressing the underlying causes of the disease is futile; we need to invest in prevention.

Hyperglycemia and incidence of ischemic and hemorrhagic stroke-comparison between fasting and 2-hour glucose criteria.

BACKGROUND AND PURPOSE: We examined the impact of hyperglycemia on ischemic and hemorrhagic stroke incidence comparing criteria based on fasting plasma glucose (FPG) and 2-hour plasma glucose (2-hour PG). METHODS: Data from 9 European cohorts comprising 18 360 individuals between 25 to 90 years of age were collaboratively analyzed. The maximum length of follow-up varied between 4.9 to 36.8 years. Hazards ratios (95% confidence intervals) for stroke incidence were estimated using Cox-proportional hazards model adjusting for known risk factors. RESULTS: In individuals without a prior history of diabetes, the multivariate-adjusted hazards ratio for ischemic stroke corresponding to 1 SD increase in FPG was 1.12 (1.02 to 1.22) and in 2-hour PG 1.14 (1.05 to 1.24). Adding 2-hour PG to the model with FPG significantly improved the prediction of the model for the incidence of ischemic stroke (chi(2)=4.72, P=0.03), whereas FPG did not improve the 2-hour PG model prediction (chi(2)=0.25, P=0.62). A significantly increased hazard ratio was also observed for previously diagnosed diabetes (2.26 [1.51 to 3.38]) and for screen-detected diabetes defined by FPG (1.48 [1.08 to 2.02]) and 2-hour PG (1.60 [1.18 to 2.16]). None of the criteria predicted hemorrhagic stroke. CONCLUSIONS: Diabetes defined by either of the criteria predicted the future risk of ischemic stroke but not the hemorrhagic stroke. The prediction is stronger for elevated 2-hour PG than for FPG levels.

EUROASPIRE III: a survey on the lifestyle, risk factors and use of cardioprotective drug therapies in coronary patients from 22 European countries.

AIM: The aim of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events III (EUROASPIRE III) survey was to determine whether the Joint European Societies' guidelines on cardiovascular prevention are being followed in everyday clinical practice and to describe the lifestyle, risk factor and therapeutic management in patients with coronary heart disease (CHD) in Europe. METHODS: The EUROASPIRE III survey was carried out in 2006-2007 in 76 centres from selected geographical areas in 22 countries in Europe. Consecutive patients, with a clinical diagnosis of CHD, were identified retrospectively and then followed up, interviewed and examined at least 6 months after their coronary event. RESULTS: Thirteen thousand nine hundred and thirty-five medical records (27% women) were reviewed and 8966 patients were interviewed. At interview, 17% of patients smoked cigarettes, 35% were obese and 53% centrally obese, 56% had a blood pressure >or=140/90 mmHg (>or=130/80 in people with diabetes mellitus), 51% had a serum total cholesterol >or=4.5 mmol/l and 25% reported a history of diabetes of whom 10% had a fasting plasma glucose less than 6.1 mmol/l and 35% a glycated haemoglobin A1c less than 6.5%. The use of cardioprotective medication was: antiplatelets 91%; beta-blockers 80%; angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers 71%; calcium channel blockers 25% and statins 78%. CONCLUSION: The EUROASPIRE III survey shows that large proportions of coronary patients do not achieve the lifestyle, risk factor and therapeutic targets for cardiovascular disease prevention. Wide variations in risk factor prevalences and the use of cardioprotective drug therapies exist between countries. There is still considerable potential throughout Europe to raise standards of preventive care in order to reduce the risk of recurrent disease and death in patients with CHD.

Hyperglycemia and stroke mortality: comparison between fasting and 2-h glucose criteria.

OBJECTIVE: We investigated stroke mortality in individuals in different categories of glycemia and compared hazard ratios (HRs) corresponding to a 1-SD increase in 2-h plasma glucose and fasting plasma glucose (FPG) criteria. RESEARCH DESIGN AND METHODS: We examined data from 2-h 75-g oral glucose tolerance tests taken from 13 European cohorts comprising 11,844 (55%) men and 9,862 (45%) women who were followed up for a median of 10.5 years. A multivariate adjusted Cox proportional hazards model was used to estimate HRs for stroke mortality. RESULTS: In men and women without a prior history of diabetes, multivariate adjusted HRs for stroke mortality corresponding to a 1-SD increase in FPG were 1.02 (95% CI 0.83-1.25) and 1.52 (1.22-1.88) and those in 2-h plasma glucose 1.21 (1.06-1.38) and 1.31 (1.06-1.61), respectively. Addition of 2-h plasma glucose to the model with FPG significantly improved prediction of stroke mortality in men (chi2 = 10.12; P = 0.001) but not in women (chi2 = 0.01; P = 0.94), whereas addition of FPG to 2-h plasma glucose improved stroke mortality in women (chi2 = 4.08; P = 0.04) but not in men (chi2 = 3.29; P = 0.07). CONCLUSIONS: Diabetes defined by either FPG or 2-h plasma glucose increases the risk of stroke mortality. In individuals without a history of diabetes, elevated 2-h postchallenge glucose is a better predictor than elevated fasting glucose in men, whereas the latter is better than the former in women.

Coronary events in persons aged 75 years or older in Finland from 1995 to 2002: the FINAMI study.

The authors used population-based myocardial infarction (MI) register data to examine trends in incidence, case fatality, treatment strategies of MI, and coronary heart disease (CHD) mortality in persons aged 75 to 99 years in 4 areas of Finland during 1995 through 2002. This age group contributed 53% (n=13,977) of all CHD events, and 65% occurred in women. CHD mortality declined among men annually by 3.5% and 1.0% in the 75- to 84-year-old and 85- to 99-year-old age groups, respectively. Among women, it declined by 2.2% per year in the 75- to 84-year-old age group but increased by 1.3% per year in the 85- to 99-year-old age group. MI attack rate did not change in men but increased significantly in women aged 85 to 99 years. Clinical management of MI in elderly patients was more conservative than in middle-aged patients. In conclusion, one-half of all CHD events occur among persons aged 75 years or older, and elderly patients with CHD represent an increasing burden to the health care system.

Prevalence of angina in women versus men: a systematic review and meta-analysis of international variations across 31 countries.

BACKGROUND: In the absence of previous international comparisons, we sought to systematically evaluate, across time and participant age, the sex ratio in angina prevalence in countries that differ widely in the rate of mortality due to myocardial infarction. METHODS AND RESULTS: We searched MEDLINE and EMBASE until February 2006 for healthy population studies published in any language that reported the prevalence of angina (Rose questionnaire) in women and men. We obtained myocardial infarction mortality rates from the World Health Organization. A total of 74 reports of 13,331 angina cases in women and 11,511 cases in men from 31 countries were included. Angina prevalence varied widely across populations, from 0.73% to 14.4% (population weighted mean 6.7%) in women and from 0.76% to 15.1% (population weighted mean 5.7%) in men, and was strongly correlated within populations between the sexes (r=0.80, P<0.0001). Angina prevalence showed a small female excess with a pooled random-effects sex ratio of 1.20 (95% CI 1.14 to 1.28, P<0.0001). This female excess was found across countries with widely differing myocardial infarction mortality rates in women (interquartile range 12.7 to 126.5 per 100,000), was particularly high in the American studies (1.40, 95% CI 1.28 to 1.52), and was higher among nonwhite ethnic groups than among whites. This sex ratio did not differ significantly by participant's age, the year the survey began, or the sex ratio for mortality due to myocardial infarction. CONCLUSIONS: Over time and at different ages, independent of diagnostic and treatment practices, women have a similar or slightly higher prevalence of angina than men across countries with widely differing myocardial infarction mortality rates.

Similarity of the impact of type 1 and type 2 diabetes on cardiovascular mortality in middle-aged subjects.

OBJECTIVE: To compare the risk of cardiovascular disease (CVD) death and the impact of hyperglycemia on the risk of CVD mortality associated with type 1 diabetes to that associated with type 2 diabetes. RESEARCH DESIGN AND METHODS: The study comprised 173 participants with type 1 diabetes, 834 participants with type 2 diabetes, and 1,294 nondiabetic participants, aged 45-64 years at baseline and free of CVD. The age of onset of diabetes was >30 years in both diabetic groups. RESULTS: During an 18-year follow-up, 86 participants with type 1 diabetes, 567 participants with type 2 diabetes, and 252 nondiabetic participants died. CVD mortality rates per 1,000 person-years were 23.1 (95% CI 16.9-31.9) in type 1 diabetic, 35.3 (30.8-40.4) in type 2 diabetic, and 4.6 (3.8-5.7) in nondiabetic participants. Adjusted hazard ratios for CVD mortality in participants with type 1 diabetes versus no diabetes was 3.6 (95% CI 2.2-5.7) in men and 13.3 (6.9-22.5) in women and in participants with type 2 diabetes versus no diabetes 3.3 (2.5-4.5) in men and 10.1 (6.7-17.4) in women. An increment of 1 unit (%) of GHb increased CVD mortality by 52.5% (95% CI 28.4-81.3) in type 1 diabetic subjects and by 7.5% (4.3-10.8) in type 2 diabetic participants. CONCLUSIONS: The impact of type 1 and type 2 diabetes on CVD mortality was similar. The effect of increasing hyperglycemia on the risk of CVD mortality was more profound in type 1 than in type 2 diabetic subjects.

Serum zinc level and coronary heart disease events in patients with type 2 diabetes.

OBJECTIVE: Low serum zinc level may predispose nondiabetic subjects to cardiovascular diseases. Our aim was to investigate whether serum zinc level predicts coronary heart disease (CHD) events in subjects with type 2 diabetes RESEARCH DESIGN AND METHODS: The original study population consisted of 1,059 patients with type 2 diabetes, aged 45-64 years. Mean duration of diabetes was 8 years. Serum zinc values were available from 1,050 subjects. CHD mortality and the incidence of nonfatal myocardial infarction (MI) were assessed in a 7-year follow-up. RESULTS: During the follow-up, 156 patients died from CHD and 254 patients had a fatal or nonfatal MI. Patients with serum zinc concentration < or = 14.1 micromol/l at baseline had a higher risk for death from CHD than patients with serum zinc level > 14.1 micromol/l (20.8 and 12.8%, respectively; P = 0.001) The risks for fatal or nonfatal MI were 30.5 and 22.0%, respectively (P = 0.005). In Cox regression analyses, low serum zinc concentration was significantly associated with CHD mortality (relative risk [RR] 1.7, P = 0.002) and all CHD events (RR 1.37, P = 0.030), even after adjustment for confounding variables. CONCLUSIONS: In this large cohort of type 2 diabetic patients, low serum zinc level was an independent risk factor for CHD events.

Retinopathy predicts cardiovascular mortality in type 2 diabetic men and women.

OBJECTIVE: To investigate the association of retinopathy with the risk of all-cause, cardiovascular disease (CVD), and coronary heart disease (CHD) mortality in type 2 diabetic subjects in a population-based 18-year follow-up study with particular emphasis on sex differences. RESEARCH DESIGN AND METHODS: Our study cohort comprised 425 Finnish type 2 diabetic men and 399 type 2 diabetic women who were free of CVD at baseline. The findings were classified based on standardized clinical ophthalmoscopy to categories of no retinopathy, background retinopathy, and proliferative retinopathy. The study end points were all-cause, CVD, and CHD mortality. RESULTS: Adjusted Cox model hazard ratios (95% CIs) of all-cause, CVD, and CHD mortality in men were 1.34 (0.98-1.83), 1.30 (0.86-1.96), and 1.18 (0.74-1.89), respectively, for background retinopathy and 3.05 (1.70-5.45), 3.32 (1.61-6.78), and 2.54 (1.07-6.04), respectively, for proliferative retinopathy and in women 1.61 (1.17-2.22), 1.71 (1.17-2.51), and 1.79 (1.13-2.85), respectively, for background retinopathy and 2.92 (1.41-6.06), 3.17 (1.38-7.30), and 4.98 (2.06-12.06), respectively, for proliferative retinopathy. CONCLUSIONS: Proliferative retinopathy in both sexes and background retinopathy in women predicted all-cause, CVD, and CHD death. These associations were independent of current smoking, hypertension, total cholesterol, HDL cholesterol, glycemic control of diabetes, duration of diabetes, and proteinuria. This suggests the presence of common background pathways for diabetic microvascular and macrovascular disease other than those included in the conventional risk assessment of CVD. The sex difference observed in the association of background retinopathy with macrovascular disease warrants closer examination.