Zlatko Fras

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/m2) 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.

Statin intolerance - an attempt at a unified definition. Position paper from an International Lipid Expert Panel.

Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin associated muscle symptoms (SAMS), and avoided the use of the term ‘statin intolerance’. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10–15% of patients. In clinical practice, statin intolerance limits effective treatment of patients at risk of, or with, cardiovascular disease. Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore, the aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented.

Lipid lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel

Arrigo F.G. Cicero, University of Bologna Alessandro Colletti, University of Bologna Gani Bajraktari, University Clinical Centre of Kosovo Olivier Descamps, Centres Hospitaliers Jolimont Dragan M. Djuric, University of Belgrade Marat Ezhov, Russian Cardiology Research and Production Centre Zlatko Fras, University Medical Centre Ljubljana Niki Katsiki, Aristotle University of Thessaloniki Michel Langlois, AZ Sint-Jan Hospital Gustavs Latkovskis, University of Latvia

Passive smoking and smoking cessation among patients with coronary heart disease across Europe: results from the EUROASPIRE III survey

AIMS Passive smoking is the inhalation of environmental tobacco smoke (ETS) and is a risk factor for coronary heart disease (CHD). We aimed to describe the frequency of passive smoking among patients with CHD and to investigate the association between ETS exposure and smoking cessation. METHODS AND RESULTS The EUROASPIRE III survey was conducted in 2006-07 among CHD patients up to 80 years of age from 22 European regions. Patients were interviewed and examined on average 15 months after hospital admission for CHD. Information was obtained on smoking prior to hospital admission, smoking at interview, and ETS exposure at home, at work, and at other locations. Breath carbon monoxide was measured to validate self-reported non-smoking. Among 8729 patients, 6060 (69.4%) were non-smokers prior to hospital admission, of whom 10.3% reported ETS exposure at home, 7.2% at work, and 13.8% at other locations. Overall, 24.2% of non-smokers were exposed to ETS at any place. Among the 2669 patients who were smoking prior to hospital admission, the likelihood of cessation at interview was lower in those with ETS exposure at home than in those without [25.3 vs. 58.1%; adjusted odds ratio (OR) 0.26, 95% confidence interval (CI) 0.20-0.33]. This finding applied also to ETS exposure at work (32.2 vs. 52.7%; adjusted OR 0.56, 95% CI 0.42-0.76) and at other locations (38.0 vs. 52.8%; adjusted OR 0.63, 95% CI 0.48-0.84). CONCLUSION A noteworthy proportion of non-smokers with CHD are exposed to ETS. Passive smoking may jeopardize smoking cessation among CHD patients.

Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration

BACKGROUND The potential for global collaborations to better inform public health policy regarding major non-communicable diseases has been successfully demonstrated by several large-scale international consortia. However, the true public health impact of familial hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide. METHODS The EAS FHSC will maximise the potential exploitation of currently available and future FH data (retrospective and prospective) by bringing together regional/national/international data sources with access to individuals with a clinical and/or genetic diagnosis of heterozygous or homozygous FH. A novel bespoke electronic platform and FH Data Warehouse will be developed to allow secure data sharing, validation, cleaning, pooling, harmonisation and analysis irrespective of the source or format. Standard statistical procedures will allow us to investigate cross-sectional associations, patterns of real-world practice, trends over time, and analyse risk and outcomes (e.g. cardiovascular outcomes, all-cause death), accounting for potential confounders and subgroup effects. CONCLUSIONS The EAS FHSC represents an excellent opportunity to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH patients.

Statin plus ezetimibe treatment in clinical practice: the SI-SPECT (Slovenia (SI) Statin Plus Ezetimibe in Cholesterol Treatment) monitoring of clinical practice study

ABSTRACT Background: Poor results from lipid-lowering therapy are mainly due to inadequate dosing and increased adverse effects with high-dose statin monotherapy or drug combinations. Objectives: The SI-SPECT (Slovenia (SI) Statin Plus Ezetimibe in Cholesterol Treatment) study evaluated the effectiveness of either ezetimibe (EZE) 10 mg as monotherapy or co-administered with on-going statin treatment (S + EZE) in clinical practice. Design and methods: A total of 1053 dyslipidaemic patients (52% men, age 60.3 years, 42.9% with CHD, 32.0% with diabetes mellitus and 69.6% with hypertension) were enrolled. The majority (n = 986; 93.6%) were treated with EZE as ‘add-on’ to their already prescribed statin, the rest only received EZE (n = 67). Main outcome measures: Baseline lipid levels were compared with those obtained 16 weeks after initiating treatment. Results: Total (TC) and low density lipoprotein cholesterol (LDL-C), as well as triglycerides (TG) decreased significantly with S + EZE (by 25.3%, 31.4% and 28.9%, respectively; p < 0.0001 for all comparisons), while monotherapy with EZE resulted in a decrease of 20.8% for TC ( p < 0.0001), 28.0% for LDL-C ( p < 0.0001) and 28.8% for TG ( p = 0.016). At the end of the study 43.9% of patients achieved target TC (< 5.0 mmol/L for primary prevention and < 4.5 mmol/L for secondary prevention), 50.5% target LDL-C (< 3.0 mmol/L for primary prevention and < 2.5 mmol/L for secondary prevention) and 61.6% target TG (< 2.0 mmol/L). The overall incidence of adverse effects during the treatment period, and probably related to EZE use, was low (n = 6, 0.6% of patients). Conclusions: (1) S + EZE combination therapy was effective and safe irrespective of the statin used, (2) the S + EZE combination resulted in significantly more patients reaching their recommended target lipid levels and (3) the lipid-lowering efficacy of EZE in monotherapy as well as of the S + EZE combination was related to initial lipid values. The much greater decrease of TG than expected could be, at least in part, due to better control/compliance regarding diet and drug treatment during the study and adherence to the need for an overnight fast before sampling.

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.

Readiness for smoking cessation in coronary heart disease patients across Europe: results from the EuroAspire III survey

Background Readiness for smoking cessation is an important predictor of quit attempts and cessation success. We aimed to investigate the prevalence and correlates of readiness for smoking cessation in coronary heart disease (CHD) patients. Design The EUROpean Action on Secondary and Primary Prevention by Intervention to Reduce Events III (EUROASPIRE III) survey is a cross-sectional study conducted in 2006–2007 among CHD patients <80 years of age from 22 European regions. Methods Patients were interviewed on average 15 months after hospital admission for an acute coronary event or procedure. Readiness for smoking cessation was assessed using the smoking stages of change (SSC) short form questionnaire. Breath carbon monoxide was measured to validate self-reported non-smoking. Results Among 2585 patients who were smoking prior to hospital admission, 25.6%, 16.8%, 8.1%, 5.6% and 44.0% were in the precontemplation (no intention to quit), contemplation (thinking of quitting), preparation (planning to quit), action (having quit within six months) and maintenance (having quit more than six months ago) stages, respectively. Significant multivariable correlates of advancement in SSC showed positive associations of older age and attended cardiac rehabilitation and negative associations of severe depressive symptoms, longer smoking duration and environmental tobacco smoke (ETS) exposure. Conclusions One-quarter of CHD patients across Europe who were smoking prior to hospitalisation have no intention to quit, and an additional quarter is thinking of quitting or planning to quit. Patients who are younger, do not attend cardiac rehabilitation, have severe depressive symptoms, have been smoking for longer periods of time and are exposed to ETS may need to be specifically targeted in cessation interventions.

Regular exercise behaviour and intention and symptoms of anxiety and depression in coronary heart disease patients across Europe: Results from the EUROASPIRE III survey

Background Regular exercise lowers the risk of cardiovascular death in coronary heart disease (CHD) patients. We aimed to investigate regular exercise behaviour and intention in relation to symptoms of anxiety and depression in CHD patients across Europe. Design This study was based on a multicentre cross-sectional survey. Methods In the EUROpean Action on Secondary and Primary Prevention through Intervention to Reduce Events (EUROASPIRE) III survey, 8966 CHD patients <80 years of age from 22 European countries were interviewed on average 15 months after hospitalisation. Whether patients exercised or intended to exercise regularly was assessed using the Stages of Change questionnaire in 8330 patients. Symptoms of anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale. Total physical activity was measured by the International Physical Activity Questionnaire in patients from a subset of 14 countries. Results Overall, 50.3% of patients were not intending to exercise regularly, 15.9% were intending to exercise regularly, and 33.8% were exercising regularly. Patients with severe symptoms of depression less frequently exercised regularly than patients with symptoms in the normal range (20.2%, 95% confidence interval (CI) 14.8–26.8 vs 36.7%, 95% CI 29.8–44.2). Among patients not exercising regularly, patients with severe symptoms of depression were less likely to have an intention to exercise regularly (odds ratio 0.62, 95% CI 0.46–0.85). Symptoms of anxiety did not affect regular exercise intention. In sensitivity analysis, results were consistent when adjusting for total physical activity. Conclusions Lower frequency of regular exercise and decreased likelihood of exercise intention were observed in CHD patients with severe depressive symptoms. Severe symptoms of depression may preclude CHD patients from performing regular exercise.

Moderate-dose atorvastatin improves arterial endothelial function in patients with angina pectoris and normal coronary angiogram: a pilot study

Introduction Endothelial dysfunction could contribute to the pathophysiology of angina pectoris (AP) in patients with normal coronary angiograms. Besides lipid-lowering effects, statins exert pleiotropic effects including improving endothelial function. Material and methods Our double-blind study included 58 patients with AP, noninvasively confirmed myocardial ischemia and a normal coronary angiogram. The effect of once-daily 20 mg atorvastatin (A) was compared with placebo (P) for 6 months. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery, and microcirculation by peripheral arterial tonometry (EndoPAT) measuring the reactive hyperemia index (RHI), indicating microcirculatory endothelial function, and the augmentation index (AI), an indicator of arterial stiffness. The impact of AP on the quality of life was monitored using the Seattle Angina Questionnaire (SAQ). Results Brachial artery endothelial dysfunction was found in 91.4% of patients at study entry, and subnormal RHI in 41%. Group A showed an improvement of FMD compared with group P, both at 3 and 6 months (+120.8% vs. –21.2%, and +70.8% vs. –1.9%, respectively, p < 0.001). No difference was detected in the RHI. Rate-normalized AI showed an improvement (−114.49% group A vs. –30.77% group P, p = 0.077), although the differences between the groups were not significant. According to the SAQ, an improvement was found in almost all observed variables with the exception of the issue of quality of life (QoL), where patients in both groups assessed their QoL at the control study visits as poorer compared with baseline. Conclusions Moderate-dose atorvastatin therapy improves endothelial function of large conduit arteries in patients with AP and a normal coronary angiogram, which probably reflects positive effects on coronary artery endothelial function. No effect was found with vascular effects at the level of the peripheral microcirculation.