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.

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.

Medical and Psychosocial Factors Associated With Low Physical Activity and Increasing Exercise Level After a Coronary Event.

PURPOSE: The reasons why many coronary patients are inactive or have a low level of physical activity (PA) are not completely understood. We identified medical and psychosocial factors associated with PA status and increasing exercise level after a coronary event. METHODS: A cross-sectional study investigated the factors associated with PA in 1101 patients hospitalized with myocardial infarction (MI) and/or a revascularization procedure. Data were collected from hospital records, a self-report questionnaire, and a clinical examination. PA was categorized as inactivity, low activity, and adequate activity (≥ moderate intensity of 30 min ≥2-3 times/wk), an overall summary PA-index was measured as a continuous variable, and self-reported PA increase since the index event was measured on a 0- to 10-point Likert Scale. RESULTS: In all, 18% reported inactivity, 42% low, and 40% adequate activity at follow-up after median 16 mo. In multiadjusted linear regression analyses, low PA-index was significantly associated with smoking, obesity, unhealthy diet, depression, female, low education, MI as index diagnosis, and ≥1 previous coronary event. Motivation, risk and illness perceptions, and low reported need of help to increase PA were significantly associated with self-reported increasing PA level in adjusted continuous analyses. CONCLUSIONS: Daily smoking, obesity, unhealthy diet, and depression were the major potentially modifiable factors associated with insufficient PA, whereas high motivation and risk and illness perceptions were associated with increasing PA level. Further research on the effect of interventions tailored to the reported significant factors of failure is needed to improve PA level in CHD patients.

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.

Serum uric acid levels are associated with cardiovascular risk score: A post hoc analysis of the EURIKA study.

BACKGROUND: Reports are conflicting on whether serum uric acid (sUA) levels are independently associated with increased cardiovascular (CV) death risk. METHODS: This post hoc analysis assessed the relationship between sUA levels and CV death risk score in 7531 patients from the cross-sectional, multinational EURIKA study (NCT00882336). Patients had at least one CV risk factor but no clinical CV disease. Ten-year risk of CV death was estimated using SCORE-HDL and SCORE algorithms, categorized as low (<1%), intermediate (1% to <5%), high (≥5% to <10%) or very high (≥10%). RESULTS: Mean serum sUA levels increased significantly with increasing CV death risk category in the overall population and in subgroups stratified by diuretics use or renal function (all P<0.0001). Multivariate ordinal logistic regression analyses, adjusted for factors significantly associated with CV death risk in univariate analyses (study country, body mass index, number of CV risk factors and comorbidities, use of lipid lowering therapies, antihypertensives and antidiabetics), showed a significant association between sUA levels and SCORE-HDL category in the overall population (OR: 1.39 [95% CI: 1.34-1.44]) and all subgroups (using diuretics: 1.32 [1.24-1.40]; not using diuretics: 1.46 [1.39-1.53]; estimated glomerular filtration rate [eGFR]<60ml/min/1.73m2: 1.30 [1.22-1.38]; eGFR≥60ml/min/1.73m2: 1.44 [1.38-1.51]; all P<0.0001). Similar results were obtained when using SCORE. CONCLUSIONS: Higher sUA levels are associated with progressively higher 10-year CV death risk score in patients with at least one CV risk factor but no CV disease.

Optimal blood pressure control after coronary events: the challenge remains.

We identified sociodemographic, medical, and psychosocial factors associated with unfavorable blood pressure (BP) control in 1012 patients, hospitalized with myocardial infarction and/or a coronary revascularization procedure. This cross-sectional study collected data from hospital records, a comprehensive self-report questionnaire, clinical examination, and blood samples after 2-36 (mean 17) months follow-up. Forty-six percent had unfavorable BP control (≥140/90 [80 in diabetics] mm Hg) at follow-up. Low socioeconomic status and psychosocial factors did not predict unfavorable BP control. Patients with unfavorable BP used on average 1.9 (standard deviation 1.1) BP-lowering drugs at hospital discharge, and the proportion of patients treated with angiotensin inhibitors and beta-blockers decreased significantly (P < .001) from discharge to follow-up. Diabetes (odds ratio [OR] 2.4), higher body mass index (OR 1.05 per 1.0 kg/m2), and older age (OR 1.04 per year) were significantly associated with unfavorable BP control in adjusted analyses. Only age (standardized beta [ß] 0.24) and body mass index (ß 0.07) were associated with systolic BP in linear analyses. We conclude that BP control was insufficient after coronary events and associated with obesity and diabetes. Prescription of BP-lowering drugs in hypertensive patients seems suboptimal. Overweight and intensified drug treatment thus emerge as the major factors to target to improve BP control.

The role of cardiac rehabilitation in secondary prevention after coronary events.

Background Coronary risk factor control in Europe is suboptimal and there are large variations in the nature of cardiac rehabilitation (CR) programmes offered to coronary heart disease patients. We aim to explore characteristics and risk factor control in patients recruited from two neighbouring hospitals offering CR with different content. Methods In a cross-sectional study, 1127 Norwegian patients hospitalized with acute myocardial infarction and/or a revascularization procedure attended a clinical visit and completed a questionnaire at 2-36 months' follow-up. The hospital of Vestfold provides comprehensive CR, while the hospital of Drammen provides mainly exercise-based CR. Results At follow-up, patients in Vestfold performed more physical activity ( p = 0.02), were less obese ( p = 0.02) and reported better medication adherence ( p = 0.02) than patients in Drammen. The perceived need for information and follow-up was higher in Drammen than Vestfold ( p < 0.001). The CR participation rate in Vestfold was 75% compared with 18% in Drammen. CR participation in Vestfold was associated with higher prevalence of smoking cessation ( p = 0.001), lower low-density lipoprotein cholesterol ( p = 0.01) and better medication adherence ( p = 0.02) compared with non-CR, in adjusted analyses. No differences in diet, body weight, or blood pressure control were found between CR and non-CR. Conclusions Vestfold, with comprehensive CR, had a higher participation rate and more risk factors on target than Drammen. Participation in CR in Vestfold was associated with higher levels of smoking cessation and medication adherence, and lower low-density lipoprotein cholesterol, but overall risk factor control is still deficient, underlining the need for improved understanding of barriers to optimal risk factor control.