Clinical and psychological factors in coronary heart disease patients with statin associated muscle side-effects.

BACKGROUND: To compare clinical and psychological factors among patients with self-perceived statin-associated muscle symptoms (SAMS), confirmed SAMS, and refuted SAMS in coronary heart disease patients (CHD). METHODS: Data were obtained from a cross-sectional study of 1100 CHD outpatients and a study of 71 CHD outpatients attending a randomized, double-blinded, placebo-controlled, crossover study to test effects of atorvastatin 40 mg/day on muscle symptom intensity. Clinical and psychosocial factors were compared between patients with and without SAMS in the cross-sectional study, and between patients with confirmed SAMS and refuted SAMS in the randomized study. RESULTS: Bilateral, symmetric muscle symptoms in the lower extremities during statin treatment were more prevalent in patients with confirmed SAMS compared to patients with refuted SAMS (75% vs. 41%, p = 0.01) in the randomized study. No significant differences in psychological factors (anxiety, depression, worry, insomnia, type D personality characteristics) were detected between patients with and without self-perceived SAMS in the cross-sectional study, or between patients with confirmed SAMS and refuted SAMS, in the randomized study. CONCLUSIONS: Patients with confirmed SAMS more often present with bilateral lower muscle symptoms compared to those with refuted SAMS. Psychological factors were not associated with self-perceived SAMS or confirmed SAMS. A careful pain history and a search for alternative causes of muscle symptoms are likely to promote communication in patients with SAMS, and may reduce the risk for statin discontinuation.

Statin-associated muscle symptoms in coronary patients: design of a randomized study.

Objectives. Estimate the effect of atorvastatin on muscular symptom intensity in coronary patients with subjective statin-associated muscle symptoms (SAMS) and to determine the association with blood levels of atorvastatin and its metabolites, to obtain an objective marker for true SAMS. Design. A randomized, double-blinded, cross-over study will include 80 coronary patients with subjectively reported SAMS during ongoing atorvastatin therapy or previous muscle symptoms that led to discontinuation of atorvastatin. Patients will be randomized to 7-weeks treatment with atorvastatin 40 mg/day in the first period and matched placebo in the second 7-weeks period, or placebo in the first period and atorvastatin in the second period. Each period is preceded by 1-week wash-out. A control group (n = 40) without muscle symptoms will have 7 weeks open treatment with atorvastatin 40 mg/day. Blood samples will be collected at baseline and at the end of each treatment period, and muscular symptoms will be rated by the patients weekly using a Visual Analogue Scale (VAS). The primary outcome is the difference in aggregated mean VAS scores between the last three weeks of atorvastatin treatment and of placebo treatment. The main purpose is to develop an objective marker for true SAMS, by comparing SAMS associated with blinded atorvastatin treatment with blood concentrations of atorvastatin and its metabolites. Diagnostic and discrimination performance will be determined. Conclusions. The study provides new knowledge on SAMS in coronary patients and may contribute to more personalized statin treatment and monitoring, fewer side-effects and consequently improved adherence and lipid management in future practice.

Managing patients with prediabetes and type 2 diabetes after coronary events: individual tailoring needed - a cross-sectional study.

BACKGROUND: Understanding the determinants associated with prediabetes and type 2 diabetes in coronary patients may help to individualize treatment and modelling interventions. We sought to identify sociodemographic, medical and psychosocial factors associated with normal blood glucose (HbA1c < 5.7%), prediabetes (HbA1c 5.7-6.4%), and type 2 diabetes. METHODS: A cross-sectional explorative study applied regression analyses to investigate the factors associated with glycaemic status and control (HbA1c level) in 1083 patients with myocardial infarction and/or a coronary revascularization procedure. Data were collected from hospital records at the index event and from a self-report questionnaire and clinical examination with blood samples at 2-36 months follow-up. RESULTS: In all, 23% had type 2 diabetes, 44% had prediabetes, and 33% had normal blood glucose at follow-up. In adjusted analyses, type 2 diabetes was associated with larger waist circumference (Odds Ratio 1.03 per 1.0 cm, p = 0.001), hypertension (Odds Ratio 2.7, p < 0.001), lower high-density lipoprotein cholesterol (Odds Ratio 0.3 per1.0 mmol/L, p = 0.002) and insomnia (Odds Ratio 2.0, p = 0.002). In adjusted analyses, prediabetes was associated with smoking (Odds Ratio 3.3, p = 0.001), hypertension (Odds Ratio 1.5, p = 0.03), and non-participation in cardiac rehabilitation (Odds Ratio 1.7, p = 0.003). In patients with type 2 diabetes, a higher HbA1c level was associated with ethnic minority background (standardized beta [ß] 0.19, p = 0.005) and low drug adherence (ß 0.17, p = 0.01). In patients with prediabetes or normal blood glucose, a higher HbA1c was associated with larger waist circumference (ß 0.13, p < 0.001), smoking (ß 0.18, p < 0.001), hypertension (ß 0.08, p = 0.04), older age (ß 0.16, p < 0.001), and non-participation in cardiac rehabilitation (ß 0.11, p = 0.005). CONCLUSIONS: Along with obesity and hypertension, insomnia and low drug adherence were the major modifiable factors associated with type 2 diabetes, whereas smoking and non-participation in cardiac rehabilitation were the factors associated with prediabetes. Further research on the effect of individual tailoring, addressing the reported significant predictors of failure, is needed to improve glycaemic control. TRIAL REGISTRATION: Retrospectively registered at ClinicalTrials.gov: NCT02309255 , December 5th 2014.

Prevalence and treatment of atherogenic dyslipidemia in the primary prevention of cardiovascular disease in Europe: EURIKA, a cross-sectional observational study.

BACKGROUND: Atherogenic dyslipidemia is associated with poor cardiovascular outcomes, yet markers of this condition are often ignored in clinical practice. Here, we address a clear evidence gap by assessing the prevalence and treatment of two markers of atherogenic dyslipidemia: elevated triglyceride levels and low levels of high-density lipoprotein cholesterol. METHODS: This cross-sectional observational study assessed the prevalence of two atherogenic dyslipidemia markers, high triglyceride levels and low high-density lipoprotein cholesterol levels, in the study population from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA; N = 7641; of whom 51.6% were female and 95.6% were White/Caucasian). The EURIKA population included European patients, aged at least 50 years with at least one cardiovascular risk factor but no history of cardiovascular disease. RESULTS: Over 20% of patients from the EURIKA population have either triglyceride or high-density lipoprotein cholesterol levels characteristic of atherogenic dyslipidemia. Furthermore, the proportions of patients with one of these markers were higher in subpopulations with type 2 diabetes mellitus or those already calculated to be at high risk of cardiovascular disease. Approximately 55% of the EURIKA population who have markers of atherogenic dyslipidemia are not receiving lipid-lowering therapy. CONCLUSIONS: A considerable proportion of patients with at least one major cardiovascular risk factor in the primary cardiovascular disease prevention setting have markers of atherogenic dyslipidemia. The majority of these patients are not receiving optimal treatment, as specified in international guidelines, and thus their risk of developing cardiovascular disease is possibly underestimated. TRIAL REGISTRATION: The present study is registered with ClinicalTrials.gov (ID: NCT00882336).

The role of medical and psychosocial factors for unfavourable coronary risk factor control.

OBJECTIVES: This project aims to identify socio-demographic, medical and psychosocial factors (study factors) associated with coronary risk control and prognosis, and to test their impact in a representative sample of coronary heart disease (CHD) patients. DESIGN: The first phase includes a cross-sectional study designed to explore the association between the study factors and coronary risk factor control in CHD patients. Data from hospital records, a questionnaire, clinical examination and blood samples were collected. The independent effects of study factors on subsequent coronary events will be explored prospectively by controlling for baseline coronary risk factors. In the second phase, we will test the effect of tailored interventions to modify the study factors associated with unfavourable risk profile in phase I. RESULTS: In all 1366 patients (21% women), aged 18-80 years with a coronary event on average 17 (2-38) months prior to study participation were identified (83% participation rate). Of the 239 patients who refused participation, 229 patients consented to analysis of hospital record data (non- participants). CONCLUSIONS: If the study variables contribute to CHD risk factors and prognosis, the present project may be important for the development of prevention programs by tailoring these to the patients perceived needs and behaviour profiles.

A systematic review of studies in the contributions of the work environment to ischaemic heart disease development.

BACKGROUND: There is need for an updated systematic review of associations between occupational exposures and ischaemic heart disease (IHD), using the GRADE system. INCLUSION CRITERIA: (i) publication in English in peer-reviewed journal between 1985 and 2014, (ii) quantified relationship between occupational exposure (psychosocial, organizational, physical and other ergonomic job factors) and IHD outcome, (iii) cohort studies with at least 1000 participants or comparable case-control studies with at least 50 + 50 participants, (iv) assessments of exposure and outcome at baseline as well as at follow-up and (v) gender and age analysis. Relevance and quality were assessed using predefined criteria. Level of evidence was then assessed using the GRADE system. Consistency of findings was examined for a number of confounders. Possible publication bias was discussed. RESULTS: Ninety-six articles of high or medium high scientific quality were finally included. There was moderately strong evidence (grade 3 out of 4) for a relationship between job strain and small decision latitude on one hand and IHD incidence on the other hand. Limited evidence (grade 2) was found for iso-strain, pressing work, effort-reward imbalance, low support, lack of justice, lack of skill discretion, insecure employment, night work, long working week and noise in relation to IHD. No difference between men and women with regard to the effect of adverse job conditions on IHD incidence. CONCLUSIONS: There is scientific evidence that employees, both men and women, who report specific occupational exposures, such as low decision latitude, job strain or noise, have an increased incidence of IHD.

C-reactive protein levels in patients at cardiovascular risk: EURIKA study.

BACKGROUND: Elevated C-reactive protein (CRP) levels are associated with high cardiovascular risk, and might identify patients who could benefit from more carefully adapted risk factor management. We have assessed the prevalence of elevated CRP levels in patients with one or more traditional cardiovascular risk factors. METHODS: Data were analysed from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, ClinicalTrials.gov Identifier: NCT00882336), which included patients (aged ≥50 years) from 12 European countries with at least one traditional cardiovascular risk factor but no history of cardiovascular disease. Analysis was also carried out on the subset of patients without diabetes mellitus who were not receiving statin therapy. RESULTS: In the overall population, CRP levels were positively correlated with body mass index and glycated haemoglobin levels, and were negatively correlated with high-density lipoprotein cholesterol levels. CRP levels were also higher in women, those at higher traditionally estimated cardiovascular risk and those with greater numbers of metabolic syndrome markers. Among patients without diabetes mellitus who were not receiving statin therapy, approximately 30% had CRP levels ≥3 mg/L, and approximately 50% had CRP levels ≥2 mg/L, including those at intermediate levels of traditionally estimated cardiovascular risk. CONCLUSIONS: CRP levels are elevated in a large proportion of patients with at least one cardiovascular risk factor, without diabetes mellitus who are not receiving statin therapy, suggesting a higher level of cardiovascular risk than predicted according to conventional risk estimation systems. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00882336.

Retrospective record review in proactive patient safety work - identification of no-harm incidents.

BACKGROUND: In contrast to other safety critical industries, well-developed systems to monitor safety within the healthcare system remain limited. Retrospective record review is one way of identifying adverse events in healthcare. In proactive patient safety work, retrospective record review could be used to identify, analyze and gain information and knowledge about no-harm incidents and deficiencies in healthcare processes. The aim of the study was to evaluate retrospective record review for the detection and characterization of no-harm incidents, and compare findings with conventional incident-reporting systems. METHODS: A two-stage structured retrospective record review of no-harm incidents was performed on a random sample of 350 admissions at a Swedish orthopedic department. Results were compared with those found in one local, and four national incident-reporting systems. RESULTS: We identified 118 no-harm incidents in 91 (26.0%) of the 350 records by retrospective record review. Ninety-four (79.7%) no-harm incidents were classified as preventable. The five incident-reporting systems identified 16 no-harm incidents, of which ten were also found by retrospective record review. The most common no-harm incidents were related to drug therapy (n = 66), of which 87.9% were regarded as preventable. CONCLUSIONS: No-harm incidents are common and often preventable. Retrospective record review seems to be a valuable tool for identifying and characterizing no-harm incidents. Both harm and no-harm incidents can be identified in parallel during the same record review. By adding a retrospective record review of randomly selected records to conventional incident-reporting, health care providers can gain a clearer and broader picture of commonly occurring, no-harm incidents in order to improve patient safety.

Achievement of treatment goals for primary prevention of cardiovascular disease in clinical practice across Europe: the EURIKA study.

AIMS: Most studies on the primary prevention of cardiovascular disease (CVD) have been limited to patients at high CVD risk. We assessed the achievement of treatment goals for CVD risk factors among patients with a substantial variation in CVD risk. METHODS AND RESULTS: This study was conducted with 7641 outpatients aged ≥50 years, free of clinical CVD and with at least one major CVD risk factor, selected from 12 European countries in 2009. Risk factor definition and treatment goals were based on the 2007 European guidelines on CVD prevention. Cholesterol fractions and glycated haemoglobin (HbA1c) were measured in a central laboratory. Cardiovascular disease risk was estimated with the SCORE equation. Patients' mean age was 63 years (48% men), and 40.1% had a high CVD risk. Among treated hypertensives (94.2%), only 38.8% achieved the blood pressure target of <140/90 mmHg [between-country range (BCR): 32.1-47.5%]. Among treated dyslipidaemic patients (74.4%), 41.2% attained both the total- and LDL-cholesterol target of <5 and <3 mmol/L, respectively (BCR: 24.3-68.4%). Among treated type 2 diabetic patients (87.2%), 36.7% achieved the <6.5% HbA1c target (BCR: 23.4-48.4%). Among obese patients on non-pharmacological treatment (92.2%), 24.7% reached the body mass index target of <30 kg/m(2) (BCR: 12.7-37.1%). About one-third of controlled patients on treatment were still at high remaining CVD risk. Although most patients were advised to reduce excess weight and to follow a low-calorie diet, less than half received written recommendations. CONCLUSIONS: In Europe, a large proportion of patients in primary prevention have CVD risk factors that remain uncontrolled, and lifestyle counselling is not well implemented; moreover, there is substantial between-country variation, which indicates additional room for improvement. Raised residual CVD risk is relatively frequent among patients despite control of their primary risk factors and should be addressed.

Excess risk attributable to traditional cardiovascular risk factors in clinical practice settings across Europe - The EURIKA Study.

BACKGROUND: Physicians involved in primary prevention are key players in CVD risk control strategies, but the expected reduction in CVD risk that would be obtained if all patients attending primary care had their risk factors controlled according to current guidelines is unknown. The objective of this study was to estimate the excess risk attributable, firstly, to the presence of CVD risk factors and, secondly, to the lack of control of these risk factors in primary prevention care across Europe. METHODS: Cross-sectional study using data from the European Study on Cardiovascular Risk Prevention and Management in Daily Practice (EURIKA), which involved primary care and outpatient clinics involved in primary prevention from 12 European countries between May 2009 and January 2010. We enrolled 7,434 patients over 50 years old with at least one cardiovascular risk factor but without CVD and calculated their 10-year risk of CVD death according to the SCORE equation, modified to take diabetes risk into account. RESULTS: The average 10-year risk of CVD death in study participants (N = 7,434) was 8.2%. Hypertension, hyperlipidemia, smoking, and diabetes were responsible for 32.7 (95% confidence interval 32.0-33.4), 15.1 (14.8-15.4), 10.4 (9.9-11.0), and 16.4% (15.6-17.2) of CVD risk, respectively. The four risk factors accounted for 57.7% (57.0-58.4) of CVD risk, representing a 10-year excess risk of CVD death of 5.66% (5.47-5.85). Lack of control of hypertension, hyperlipidemia, smoking, and diabetes were responsible for 8.8 (8.3-9.3), 10.6 (10.3-10.9), 10.4 (9.9-11.0), and 3.1% (2.8-3.4) of CVD risk, respectively. Lack of control of the four risk factors accounted for 29.2% (28.5-29.8) of CVD risk, representing a 10-year excess risk of CVD death of 3.12% (2.97-3.27). CONCLUSIONS: Lack of control of CVD risk factors was responsible for almost 30% of the risk of CVD death among patients participating in the EURIKA Study.

The relationship between directly measured statin adherence, self-reported adherence measures and cholesterol levels in patients with coronary heart disease.

BACKGROUND AND AIMS: We aimed to determine the relationship between statin adherence measured directly, and by self-report measures and serum cholesterol levels. METHODS: Patients prescribed atorvastatin (N = 373) participated in a cross-sectional study 2-36 months after a coronary event. Self-reported adherence included statin adherence the past week, the 8-item Morisky medication adherence scale (MMAS-8), and the Gehi et al. adherence question. Atorvastatin was measured directly in spot blood plasma by a novel liquid chromatography tandem mass-spectrometry method discriminating adherence (0-1 doses omitted) and reduced adherence (≥2 doses omitted). Participants were unaware of the atorvastatin analyses at study participation. RESULTS: Mean age was 63 (SD 9) years and 8% had reduced atorvastatin adherence according to the direct method. In patients classified with reduced adherence by the direct method, 40% reported reduced statin adherence, 32% reported reduced adherence with the MMAS-8 and 22% with the Gehi question. In those adherent by the direct method, 96% also reported high statin adherence, 95% reported high adherence on the MMAS-8 whereas 94% reported high adherence on the Gehi question. Cohen's kappa agreement score with the direct method was 0.4 for self-reported statin adherence, 0.3 for the Gehi question and 0.2 for the MMAS-8. Adherence determined by the direct method, self-reported statin adherence last week, and the Gehi question was inversely related to LDL-cholesterol levels with a p-value of <0.001, 0.001 and 0.004, respectively. CONCLUSIONS: Plasma-statin measurements reveal reduced adherence with higher sensitivity than self-report measures, relate to cholesterol levels, and may prove to be a useful tool to improve lipid management.

Optimising implementation of European guidelines on cardiovascular disease prevention in clinical practice: what is needed?

Cardiovascular disease is a model example of a preventable condition for which practice guidelines are particularly important. In 2016, the joint task force created by the European Society of Cardiology (ESC) together with 10 other societies released the new version of the European guidelines on cardiovascular disease prevention. To facilitate the implementation of the ESC guidelines, a dedicated prevention implementation committee has been established within the European Association of Preventive Cardiology. The paper will first explore potential barriers to the guidelines' implementation. It then develops a discussion that seeks to inform the future development of the committee's work, including a new definition of the guidelines' stakeholders (health policy-makers, healthcare professionals and health educators, patient organisations, entrepreneurs and the general public), future activities within four specific areas: strengthening awareness of the guidelines among stakeholders; supporting organisational changes to facilitate the guidelines' implementation; motivating stakeholders to utilise the guidelines; and present ideas on new implementation strategies. Providing multifaceted cooperation between healthcare professionals, healthcare management executives and health policy-makers, the novel approach proposed in this paper should contribute to a wider use of the 2016 ESC guidelines and produce desired effects of less cardiovascular disease morbidity and mortality. Furthermore, the solutions presented within the paper may constitute a benchmark for the implementation of practice guidelines in other medical disciplines.

Effect of atorvastatin on muscle symptoms in coronary heart disease patients with self-perceived statin muscle side effects: a randomized, double-blinded crossover trial.

AIMS: To estimate the effect of atorvastatin on muscle symptom intensity in coronary heart disease (CHD) patients with self-perceived statin-associated muscle symptoms (SAMS) and to determine the relationship to blood levels of atorvastatin and/or metabolites. METHODS AND RESULTS: A randomized multi-centre trial consecutively identified 982 patients with previous or ongoing atorvastatin treatment after a CHD event. Of these, 97 (9.9%) reported SAMS and 77 were randomized to 7-week double-blinded treatment with atorvastatin 40 mg/day and placebo in a crossover design. The primary outcome was the individual mean difference in muscle symptom intensity between the treatment periods, measured by visual-analogue scale (VAS) scores. Atorvastatin did not affect the intensity of muscle symptoms among 71 patients who completed the trial. Mean VAS difference (statin-placebo) was 0.31 (95% CI: -0.24 to 0.86). The proportion with more muscle symptoms during placebo than atorvastatin was 17% (n = 12), 55% (n = 39) had the same muscle symptom intensity during both treatment periods whereas 28% (n = 20) had more symptoms during atorvastatin than placebo (confirmed SAMS). There were no differences in clinical or pharmacogenetic characteristics between these groups. The levels of atorvastatin and/or metabolites did not correlate to muscle symptom intensity among patients with confirmed SAMS (Spearman's rho ≤0.40, for all variables). CONCLUSION: Re-challenge with high-intensity atorvastatin did not affect the intensity of muscle symptoms in CHD patients with self-perceived SAMS during previous atorvastatin therapy. There was no relationship between muscle symptoms and the systemic exposure to atorvastatin and/or its metabolites. The findings encourage an informed discussion to elucidate other causes of muscle complaints and continued statin use.

Rationale and methods of the European Study on Cardiovascular Risk Prevention and Management in Daily Practice (EURIKA).

BACKGROUND: The EURIKA study aims to assess the status of primary prevention of cardiovascular disease (CVD) across Europe. Specifically, it will determine the degree of control of cardiovascular risk factors in current clinical practice in relation to the European guidelines on cardiovascular prevention. It will also assess physicians' knowledge and attitudes about CVD prevention as well as the barriers impeding effective risk factor management in clinical practice. METHODS/DESIGN: Cross-sectional study conducted simultaneously in 12 countries across Europe. The study has two components: firstly at the physician level, assessing eight hundred and nine primary care and specialist physicians with a daily practice in CVD prevention. A physician specific questionnaire captures information regarding physician demographics, practice settings, cardiovascular prevention beliefs and management. Secondly at the patient level, including 7641 patients aged 50 years or older, free of clinical CVD and with at least one classical risk factor, enrolled by the participating physicians. A patient-specific questionnaire captures information from clinical records and patient interview regarding sociodemographic data, CVD risk factors, and current medications. Finally, each patient provides a fasting blood sample, which is sent to a central laboratory for measuring serum lipids, apolipoproteins, hemoglobin-A1c, and inflammatory biomarkers. DISCUSSION: Primary prevention of CVD is an extremely important clinical issue, with preventable circulatory diseases remaining the leading cause of major disease burden. The EURIKA study will provide key information to assess effectiveness of and attitudes toward primary prevention of CVD in Europe. A transnational study creates opportunities for benchmarking good clinical practice across countries and improving outcomes. (ClinicalTrials.gov number, NCT00882336).