Prediction of recurrent event in patients with coronary heart disease: the EUROASPIRE Risk Model.

AIMS: Most patients with established atherosclerotic cardiovascular disease (CVD) are at very high risk for developing recurrent events. Since this risk varies a lot between patients there is a need to identify those in whom an even more intensive secondary prevention strategy should be envisaged. Using data from the EUROASPIRE IV and V cohorts of coronary heart disease (CHD) patients from 27 European countries, we aimed at developing and internally and externally validating a risk model predicting recurrent CVD events in patients aged < 75 years. METHODS AND RESULTS: Prospective data were available for 12 484 patients after a median follow-up time of 1.7 years. The primary endpoint, a composite of fatal CVD or new hospitalizations for non-fatal myocardial infarction (MI), stroke, heart failure, coronary artery bypass graft, or percutaneous coronary intervention (PCI), occurred in 1424 patients. The model was developed based on data from 8000 randomly selected patients in whom the association between potential risk factors and the incidence of the primary endpoint was investigated. This model was then validated in the remaining 4484 patients. The final multivariate model revealed a higher risk for the primary endpoint with increasing age, a previous hospitalization for stroke, heart failure or PCI, a previous diagnosis of peripheral artery disease, self-reported diabetes and its glycaemic control, higher non-high-density lipoprotein cholesterol, reduced renal function, symptoms of depression and anxiety and living in a higher risk country. The model demonstrated excellent internal validity and proved very adequate in the validation cohort. Regarding external validity, the model demonstrated good discriminative ability in 20 148 MI patients participating in the SWEDEHEART register. Finally, we developed a risk calculator to estimate risks at 1 and 2 years for patients with stable CHD. CONCLUSION: In patients with CHD, fatal and non-fatal rates of recurrent CVD events are high. However, there are still opportunities to optimize their management in order to prevent further disease or death. The EUROASPIRE Risk Calculator may be of help to reach this goal.

Potential for optimizing management of obesity in the secondary prevention of coronary heart disease.

AIMS: Prevention guidelines have identified the management of obese patients as an important priority to reduce the burden of incident and recurrent cardiovascular disease. Still, studies have demonstrated that over 80% of patients with coronary heart disease (CHD) fail to achieve their weight target. Here, we describe advice received and actions reported by overweight CHD patients since being discharged from hospital and how weight changes relate to their risk profile. METHODS AND RESULTS: Based on data from 10 507 CHD patients participating in the EUROASPIRE IV and V studies, we analysed weight changes from hospital admission to the time of a study visit ≥6 and <24 months later. At hospitalization, 34.9% were obese and another 46.0% were overweight. Obesity was more frequent in women and associated with more comorbidities. By the time of the study visit, 19.5% of obese patients had lost ≥5% of weight. However, in 16.4% weight had increased ≥5%. Weight gain in those overweight was associated with physical inactivity, non-adherence to dietary recommendations, smoking cessation, raised blood pressure, dyslipidaemia, dysglycaemia, and lower levels of quality of life. Less than half of obese patients was considering weight loss in the coming month. CONCLUSIONS: The management of obesity remains a challenge in the secondary prevention of CHD despite a beneficial effect of weight loss on risk factor prevalences and quality of life. Cardiac rehabilitation programmes should include weight loss interventions as a specific component and the incremental value of telehealth intervention as well as recently described pharmacological interventions need full consideration.

Risk factors for major adverse cardiovascular events after the first acute coronary syndrome.

AIMS: To evaluate risk factors for major adverse cardiac event (MACE) after the first acute coronary syndrome (ACS) and to examine the prevalence of risk factors in post-ACS patients. METHODS: We used Finnish population-based myocardial infarction register, FINAMI, data from years 1993-2011 to identify survivors of first ACS (n = 12686), who were then followed up for recurrent events and all-cause mortality for three years. Finnish FINRISK risk factor surveys were used to determine the prevalence of risk factors (smoking, hyperlipidaemia, diabetes and blood pressure) in post-ACS patients (n = 199). RESULTS: Of the first ACS survivors, 48.4% had MACE within three years of their primary event, 17.0% were fatal. Diabetes (p = 4.4 × 10-7), heart failure (HF) during the first ACS attack hospitalization (p = 6.8 × 10-15), higher Charlson index (p = 1.56 × 10-19) and older age (p = .026) were associated with elevated risk for MACE in the three-year follow-up, and revascularization (p = .0036) was associated with reduced risk. Risk factor analyses showed that 23% of ACS survivors continued smoking and cholesterol levels were still high (>5mmol/l) in 24% although 86% of the patients were taking lipid lowering medication. CONCLUSION: Diabetes, higher Charlson index and HF are the most important risk factors of MACE after the first ACS. Cardiovascular risk factor levels were still high among survivors of first ACS.

Lifestyle and impact on cardiovascular risk factor control in coronary patients across 27 countries: Results from the European Society of Cardiology ESC-EORP EUROASPIRE V registry.

AIMS: The aim of this study was to determine whether the Joint European Societies guidelines on secondary cardiovascular prevention are followed in everyday practice. DESIGN: A cross-sectional ESC-EORP survey (EUROASPIRE V) at 131 centres in 81 regions in 27 countries. METHODS: Patients (<80 years old) with verified coronary artery events or interventions were interviewed and examined ≥6 months later. RESULTS: A total of 8261 patients (females 26%) were interviewed. Nineteen per cent smoked and 55% of them were persistent smokers, 38% were obese (body mass index ≥30 kg/m2), 59% were centrally obese (waist circumference: men ≥102 cm; women ≥88 cm) while 66% were physically active <30 min 5 times/week. Forty-two per cent had a blood pressure ≥140/90 mmHg (≥140/85 if diabetic), 71% had low-density lipoprotein cholesterol ≥1.8 mmol/L (≥70 mg/dL) and 29% reported having diabetes. Cardioprotective medication was: anti-platelets 93%, beta-blockers 81%, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers 75% and statins 80%. CONCLUSION: A large majority of coronary patients have unhealthy lifestyles in terms of smoking, diet and sedentary behaviour, which adversely impacts major cardiovascular risk factors. A majority did not achieve their blood pressure, low-density lipoprotein cholesterol and glucose targets. Cardiovascular prevention requires modern preventive cardiology programmes delivered by interdisciplinary teams of healthcare professionals addressing all aspects of lifestyle and risk factor management, in order to reduce the risk of recurrent cardiovascular events.

Incidence of cardiovascular events in patients with stabilized coronary heart disease: the EUROASPIRE IV follow-up study.

The EUROASPIRE surveys (EUROpean Action on Secondary Prevention through Intervention to Reduce Events) demonstrated that most European coronary patients fail to achieve lifestyle, risk factor and therapeutic targets. Here we report on the 2-year incidence of hard cardiovascular (CV) endpoints in the EUROASPIRE IV cohort. EUROASPIRE IV (2012-2013) was a large cross-sectional study undertaken at 78 centres from selected geographical areas in 24 European countries. Patients were interviewed and examined at least 6 months following hospitalization for a coronary event or procedure. Fatal and non-fatal CV events occurring at least 1 year after this baseline screening were registered. The primary outcome in our analyses was the incidence of CV death or non-fatal myocardial infarction, stroke or heart failure. Cox regression models, stratified for country, were fitted to relate baseline characteristics to outcome. Our analyses included 7471 predominantly male patients. Overall, 222 deaths were registered of whom 58% were cardiovascular. The incidence of the primary outcome was 42 per 1000 person-years. Comorbidities were strongly and significantly associated with the primary outcome (multivariately adjusted hazard ratio HR, 95% confidence interval): severe chronic kidney disease (HR 2.36, 1.44-3.85), uncontrolled diabetes (HR 1.89, 1.50-2.38), resting heart rate ≥ 75 bpm (HR 1.74, 1.30-2.32), history of stroke (HR 1.70, 1.27-2.29), peripheral artery disease (HR 1.48, 1.09-2.01), history of heart failure (HR 1.47, 1.08-2.01) and history of acute myocardial infarction (HR 1.27, 1.05-1.53). Low education and feelings of depression were significantly associated with increased risk. Lifestyle factors such as persistent smoking, insufficient physical activity and central obesity were not significantly related to adverse outcome. Blood pressure and LDL-C levels appeared to be unrelated to cardiovascular events irrespective of treatment. In patients with stabilized CHD, comorbid conditions that may reflect the ubiquitous nature of atherosclerosis, dominate lifestyle-related and other modifiable risk factors in terms of prognosis, at least over a 2-year follow-up period.

Time Trends in Lifestyle, Risk Factor Control, and Use of Evidence-Based Medications in Patients With Coronary Heart Disease in Europe: Results From 3 EUROASPIRE Surveys, 1999-2013.

BACKGROUND: The EUROASPIRE (European Action on Secondary and Primary Prevention by Intervention to Reduce Events) cross-sectional surveys describe time trends in lifestyle and risk factor control among coronary patients between 1999 and 2013 in Belgium, Czech Republic, Finland, France, Ireland, the Netherlands, Poland, Slovenia, and the United Kingdom as part of the EuroObservational Research Programme under the auspices of European Society of Cardiology. OBJECTIVES: This study sought to describe time trends in lifestyle, risk factor control, and the use of evidence-based medication in coronary patients across Europe. METHODS: The EUROASPIRE II (1999 to 2000), III (2006 to 2007), and IV (2012 to 13) surveys were conducted in the same geographical areas and selected hospitals in each country. Consecutive patients (≤70 years) after coronary artery bypass graft, percutaneous coronary intervention, or an acute coronary syndrome identified from hospital records were interviewed and examined ≥6 months later with standardized methods. RESULTS: Of 12,775 identified coronary patients, 8,456 (66.2%) were interviewed. Proportion of current smokers was similar across the 3 surveys. Prevalence of obesity increased by 7%. The prevalence of raised blood pressure (≥140/90 mm Hg or ≥140/80 mm Hg with diabetes) dropped by 8% from EUROASPIRE III to IV, and therapeutic control of blood pressure improved with 55% of patients below target in IV. The prevalence of low-density lipoprotein cholesterol ≥2.5 mmol/l decreased by 44%. In EUROASPIRE IV, 75% were above the target low-density lipoprotein cholesterol <1.8 mmol/l. The prevalence of self-reported diabetes increased by 9%. The use of evidence-based medications increased between the EUROASPIRE II and III surveys, but did not change between the III and IV surveys. CONCLUSIONS: Lifestyle habits have deteriorated over time with increases in obesity, central obesity, and diabetes and stagnating rates of persistent smoking. Although blood pressure and lipid management improved, they are still not optimally controlled and the use of evidence-based medications appears to have stalled apart from the increased use of high-intensity statins. These results underline the importance of offering coronary patients access to modern preventive cardiology programs.

EUROASPIRE IV: A European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries.

AIMS: To determine whether the Joint European Societies guidelines on cardiovascular prevention are being followed in everyday clinical practice of secondary prevention and to describe the lifestyle, risk factor and therapeutic management of coronary patients across Europe. METHODS AND RESULTS: EUROASPIRE IV was a cross-sectional study undertaken at 78 centres from 24 European countries. Patients <80 years with coronary disease who had coronary artery bypass graft, percutaneous coronary intervention or an acute coronary syndrome were identified from hospital records and interviewed and examined ≥ 6 months later. A total of 16,426 medical records were reviewed and 7998 patients (24.4% females) interviewed. At interview, 16.0% of patients smoked cigarettes, and 48.6% of those smoking at the time of the event were persistent smokers. Little or no physical activity was reported by 59.9%; 37.6% were obese (BMI ≥ 30 kg/m(2)) and 58.2% centrally obese (waist circumference ≥ 102 cm in men or ≥88 cm in women); 42.7% had blood pressure ≥ 140/90 mmHg (≥140/80 in people with diabetes); 80.5% had low-density lipoprotein cholesterol ≥ 1.8 mmol/l and 26.8% reported having diabetes. Cardioprotective medication was: anti-platelets 93.8%; beta-blockers 82.6%; angiotensin-converting enzyme inhibitors/angiotensin receptor blockers 75.1%; and statins 85.7%. Of the patients 50.7% were advised to participate in a cardiac rehabilitation programme and 81.3% of those advised attended at least one-half of the sessions. CONCLUSION: A large majority of coronary patients do not achieve the guideline standards for secondary prevention with high prevalences of persistent smoking, unhealthy diets, physical inactivity and consequently most patients are overweight or obese with a high prevalence of diabetes. Risk factor control is inadequate despite high reported use of medications and there are large variations in secondary prevention practice between centres. Less than one-half of the coronary patients access cardiac prevention and rehabilitation programmes. All coronary and vascular patients require a modern preventive cardiology programme, appropriately adapted to medical and cultural settings in each country, to achieve healthier lifestyles, better risk factor control and adherence with cardioprotective medications.

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.

Thoracoabdominal calcifications predict cardiovascular disease mortality in type 2 diabetic and nondiabetic subjects: 18-year follow-up study.

OBJECTIVE To evaluate cardiovascular disease (CVD) and total mortality associated with thoracoabdominal calcifications. RESEARCH DESIGN AND METHODS Thoracoabdominal calcifications of native radiograms were evaluated in 833 subjects with type 2 diabetes and 1,292 subjects without diabetes, aged 45-64 years, without prior evidence of CVD. The type 2 diabetic and nondiabetic study cohorts were followed up for 18 years. RESULTS After adjustment for conventional risk factors, marked thoracoabdominal calcifications predicted CVD/total mortality with hazard ratio (HR) (95% CI) of 1.5 (0.8-3.0)/1.8 (1.1-2.9) in type 2 diabetic men, 3.0 (1.6-5.7)/3.1 (1.9-5.0) in type 2 diabetic women, 5.0 (2.2-12)/4.0 (2.2-7.4) in nondiabetic men, and 7.8 (1.8-34)/3.0 (1.3-7.0) in nondiabetic women and in the presence of C-reactive protein below/over 3 mg/l with HR of 2.4 (1.3-4.4)/3.0 (1.4-6.1) in type 2 diabetic subjects and 4.0 (1.5-10.8)/6.6 (2.7-16.0) in nondiabetic subjects. CONCLUSIONS Thoracoabdominal calcifications in native radiograms are significant predictors of CVD and total mortality, especially in type 2 diabetic and nondiabetic women with elevated high-sensitivity C-reactive protein level.

The effect of fatty or lean fish intake on inflammatory gene expression in peripheral blood mononuclear cells of patients with coronary heart disease.

BACKGROUND: Little is known about the effect of fish consumption on gene expression of inflammation-related genes in immune cells in coronary heart disease (CHD). AIM OF THE STUDY: We sought to evaluate the effect of a fatty fish (FF) or a lean fish (LF) diet on the modulation of inflammatory and endothelial function-related genes in peripheral blood mononuclear cells (PBMCs) of subjects with CHD, and its association with serum fatty acid (FA) profile and lipid metabolic compounds. METHODS: Data from 27 patients randomized into an 8-week FF (n = 10; mean +/- SD: 4.3 +/- 0.4 portions of fish per week), LF (n = 11; 4.7 +/- 1.1 portions of fish per week), or control diet (n = 6; 0.6 +/- 0.4 portions of fish per week) were analyzed. The mRNA expression was measured using real-time PCR. RESULTS: The effect of the intervention on the mRNA expression of the genes studied did not differ among groups. In the FF group, however, the decrease in arachidonic acid to eicosapentaenoic acid (AA:EPA) ratio in cholesterol ester and phospholipid fractions strongly correlated with the change in IL1B mRNA levels (r (s) = 0.60, P = 0.06 and r (s) = 0.86, P = 0.002, respectively). In the LF group, the decrease in palmitic acid and total saturated FAs in cholesterol esters correlated with the change in intercellular cell adhesion molecule-1 (ICAM1) expression (r (s) = 0.64, P = 0.04 for both). Circulating levels of soluble ICAM-1 decreased only in the LF group (P < 0.05). CONCLUSIONS: The intake of FF or LF diet did not alter the expression of inflammatory and endothelial function-related genes in PBMCs of patients with CHD. However, the decrease in AA:EPA ratio in serum lipids in the FF group may induce an anti-inflammatory response at mRNA levels in PBMCs. A LF diet might benefit endothelial function, possibly mediated by the changes in serum FA composition.

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.

Antibodies against oxidized LDL and cardiolipin and mortality in patients with coronary heart disease.

The association between antibodies against oxidized LDL (oxLDL) and cardiolipin and the risks of death and cardiovascular disease events were evaluated in patients with established coronary heart disease (CHD). The patients (mean age: 61 years, range: 33-74 years) were participants in the EUROASPIRE study; 108 of them had undergone coronary artery bypass surgery, 106 had balloon angioplasty, 101 had a diagnosis of acute myocardial infarction (AMI), and 98 acute myocardial ischemia. Antibodies against oxLDL and cardiolipin were measured and incidence of CHD events and deaths were followed up for 5 years in 284 men and 129 women. During the follow-up 36 patients died and 21 had AMI. After adjustment for cardiovascular disease risk factors the relative risks (RR [95% confidence interval]) of death were 1 (reference), 2.50 (0.97-6.49) and 2.21 (0.85-5.80) in increasing tertile categories of anti-oxLDL antibody titers, respectively (P for trend 0.16). The risks of CHD-death or AMI combined were 1 (reference), 2.61 (1.02-6.65) and 1.06 (0.37-3.03) in increasing tertile categories of anticardiolipin antibody titers, respectively (P for trend 0.03). In conclusion, the results suggest that antibodies against oxLDL and cardiolipin are not major predictors of risks of death and CHD events in patients with established CHD.

Association between Chlamydia pneumoniae antibodies and intimal calcification in femoral arteries of nondiabetic patients.

BACKGROUND: Chlamydia pneumoniae, a gram-negative bacterium, has been suggested to be a risk factor for atherosclerosis. Calcium is a well-known component of atherosclerotic plaques, but it is uncertain whether infectious agents play a role in the calcification process of the arteries. PATIENTS: To address this issue we investigated the association of Chlamydia antibodies with intimal arterial calcification as assessed by soft tissue radiograms from the thigh region of 1373 nondiabetic Finnish individuals aged 45 to 64 years. RESULTS: At baseline, radiologically detectable intimal calcification in femoral arteries was found in 172 (27%) of 638 men and 43 (6%) of 735 women (P<.001). The presence of intimal artery calcifications was strongly related to conventional atherosclerotic risk factors and to Chlamydia antibodies. In Cox regression analysis, association of Chlamydia antibodies with intimal artery calcification persisted after extensive adjustment for other cardiovascular risk factors (P =.04). A dose-response relationship was observed between Chlamydia antibodies and intimal femoral artery calcification (P =.006). The presence of intimal artery calcification was strongly associated with an increased risk of future coronary heart disease mortality (P<.001). CONCLUSION: Chlamydia antibodies are strongly associated with intimal calcification of the femoral arteries.