Search

Statin-associated muscle symptoms are frequently reported and often lead to discontinuation of statin therapy with an increased risk of cardiovascular events. In vitro studies suggest that statin-mediated inhibition of the mevalonate pathway leads to muscle cell toxicity. We aimed to determine the relationship between mevalonate, LDL-cholesterol, and atorvastatin metabolites in patients with coronary heart disease and self-perceived muscle side effects. Furthermore, we assessed the correlation between mevalonate in blood and muscle and the relationship to statin intolerance due to muscle symptoms. We used blood plasma from a randomized crossover trial (n = 70) and muscle biopsies and plasma from a subgroup in a subsequent open intervention study (n = 26). Both studies tested atorvastatin 40 mg/day. Seven patients did not tolerate ≥3 statins throughout the follow-up and were classified as statin-intolerant. Mevalonate in blood plasma decreased during atorvastatin treatment (median difference -38%, range -77% to 43%, p < 0.001), whereas mevalonate in muscle tissue was not lowered (0.05%, range -47% to 145%). Mevalonate correlated poorly with LDL-cholesterol and atorvastatin metabolites (Spearman's rho -0.28 to 0.10). The statin-intolerant patients had a smaller reduction in circulating mevalonate compared with the tolerant patients; median difference -8.1 (-22 to 3.5) nmol/L versus -25 (-93 to 12) nmol/L, p = 0.028. A similar observation was made for LDL-cholesterol. Cutoffs based on these biomarkers classified >50% correctly as tolerant. Inhibition of the mevalonate pathway does not appear to be the mechanism underlying statin intolerance in the present study. Further studies of mevalonate as a biomarker for statin tolerance are needed to clarify the potential., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Aims: Objective methods to determine statin adherence are requested to improve lipid management. We have recently established a method to detect reduced adherence to atorvastatin therapy with cut-off values based on the sum of atorvastatin and its major metabolites in the blood. We aimed to validate this method in patients with and without cardiovascular disease, and optimize previous cut-off values., Methods and Results: The pharmacokinetic study included 60 participants treated with atorvastatin 20 mg (N = 20), 40 mg (N = 20), and 80 mg (N = 20). Atorvastatin was then stopped and blood samples collected from day zero to day four. Quantification of the parent drug and its metabolites in blood plasma was performed with a liquid chromatography-tandem mass spectrometry assay. The cut-off values for reduced adherence were validated and optimized by calculating diagnostic sensitivity and specificity. Our candidate cut-off value of dose-normalized six-component sum of atorvastatin plus metabolites <0.10 nM/mg provided a sensitivity of 97% and a specificity of 93% for detecting ≥2 omitted doses. An optimized cut-off <0.062 nM/mg provided a sensitivity of 90% and a specificity of 100%. An alternative simplified two-component metabolite sum with a cut-off value <0.05 nM/mg provided a sensitivity of 98% and a specificity of 76%. An optimized cut-off <0.02 nM/mg provided a sensitivity of 97% and a specificity of 98%., Conclusion: This validation study confirms that our direct method discriminates reduced adherence from adherence to atorvastatin therapy with high diagnostic accuracy. The method may improve lipid management in clinical practice and serve as a useful tool in future studies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Proper prescription and high adherence to intensive lipid lowering drugs (LLD) in patients with coronary heart disease (CHD) are crucial and strongly recommended. The aim of this study is to investigate long-term treatment patterns and adherence to LLD following hospitalization for a CHD event., Methods: Patients admitted to two Norwegian hospitals with a CHD event from 2011 to 2014 (N = 1094) attended clinical examination and completed a questionnaire, median 16 months later. Clinical data were linked to pharmacy dispensing data from 2010 to 2020. The proportions using high-intensity statin therapy (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) and non-statin LLD after the CHD event were assessed. Adherence was evaluated by proportion of days covered (PDC) and gaps in treatment., Results: Median age at hospitalization was 63 (IQR 12) years, 21 % were female. Altogether, 1054 patients (96 %) were discharged with a statin prescription, while treatment was dispensed in 85 % within the following 90 days. During median 8 (SD 2.5) years follow-up, the proportion using high-intensity statin therapy ranged 62-68 %, whereas the use of ezetimibe increased from 4 to 26 %. PDC <0.8 was found in 22 % of statin users and 26 % of ezetimibe users. The proportions with a treatment gap exceeding 180 days were 22 % for statins and 28 % for ezetimibe. Smoking at hospitalization and negative affectivity were significantly associated with reduced statin adherence, regardless of adherence measure., Conclusions: In this long-term follow-up of patients with CHD, less than 70 % used high-intensity statin therapy with only small changes over time, and only 25 % used additional treatment with ezetimibe. We identified factors associated with reduced statin adherence that may be target for interventions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:IE and CB are affiliated with Oslo Economics and have completed consultancy assignments outside the submitted work for several public and private institutions in recent years. HS is affiliated with Steno Diabetes Center Aarhus and has received consultancy fees from Novartis, Arla Foods AMBA, Bristol-Myers Squibb, Pfizer and Neumirna outside the submitted work. EH, ES and TD reports no conflicts of interest. SH has received lecture fees from Sanofi, Novartis, and Pfizer outside the submitted work. JM received lecture fees from Sanofi, Novartis, Boehringer Ingelheim, and Bayer outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: The evidence for beta-blocker therapy after myocardial infarction (MI) is randomized trials conducted more than 30 years ago, and the continued efficacy has been questioned., Design and Methods: The ongoing Danish (DANBLOCK) and Norwegian (BETAMI) randomized beta-blocker trials are joined to evaluate the effectiveness and risks of long-term beta-blocker therapy after MI. Patients with normal or mildly reduced left ventricular ejection fraction (LVEF ≥ 40%) will be randomized to open-label treatment with beta-blockers or no such therapy. The event-driven trial will randomize ∼5700 patients and continue until 950 primary endpoints have occurred. As of July 2023, 5228 patients have been randomized. Of the first 4000 patients randomized, median age was 62 years, 79% were men, 48% had a ST-segment elevation myocardial infarction (STEMI), and 84% had a normal LVEF. The primary endpoint is a composite of adjudicated recurrent MI, incident heart failure (HF), coronary revascularization, ischaemic stroke, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest. The primary safety endpoint includes a composite of recurrent MI, HF, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest 30 days after randomization. Secondary endpoints include each of the components of the primary endpoint, patient-reported outcomes, and other clinical outcomes linked to beta-blocker therapy. The primary analysis will be conducted according to the intention-to-treat principle using a Cox proportional hazards regression model. End of follow-up is expected in December 2024., Conclusion: The combined BETAMI-DANBLOCK trial will have the potential to affect current clinical practice for beta-blocker therapy in patients with normal or mildly reduced LVEF after MI., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To evaluate the effects of a multi-component intervention for smokers hospitalized for atherosclerotic cardiovascular disease (ASCVD) on the participation rate in community-based cessation programmes and the use of cessation drugs. Additionally, to explore the impact on the cessation rates at 6 months., Methods and Results: A randomized parallel-group study was conducted at a Norwegian secondary care hospital in 2021. The intervention group was: (i) counselled using motivational interviewing techniques during hospitalization; (ii) given an information leaflet, detailing the cessation programme; and (iii) referred to the community-based smoking cessation treatment including a post-discharge pro-active telephone invitation. The control group received usual care and the same information leaflet containing clear contact details for initiating participation. Data were collected at baseline, 1, 3, and 6 months. Among 99 smokers hospitalized with ASCVD, 40 were excluded. Of 59 randomized patients, 4 were lost to follow-up and 55 completed the study. The mean age was 65.1 (standard deviation 9.3) years, 35% were female, and 88% had smoked >20 years. Co-morbidity was prevalent (mean Charlson score 4.8). The intervention group was more likely to participate in the smoking cessation treatment {48 vs. 7%, difference: 41% [95% confidence interval (CI): 14%, 63%]} and used cessation drugs more frequently [59 vs. 21%, difference: 38% (95% CI: 17%, 59%)]. At the 6 months point prevalence, we observed notable between-group differences in self-reported cessation rate (48 vs. 25%)., Conclusion: The intervention significantly increased the participation rate at community-based smoking cessation programmes and the use of cessation drugs among multi-morbid smokers hospitalized for ASCVD., Competing Interests: Conflict of interest: J.M. reports having received modest lecture fees from Novartis, Sanofi, and Boehringer Ingelheim, outside the submitted work. S.T. reports having received modest lecture fees from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and MSD, outside the submitted work. K.P. reports having received modest lecture fees from Novo Nordisk, outside the submitted work. No other conflict of interests was reported., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Statin-associated muscle symptoms (SAMS) is a prevalent cause of statin discontinuation. It is challenging and time-consuming for clinicians to assess whether symptoms are caused by the statin or not, and diagnostic biomarkers are requested. Atorvastatin metabolites have been associated with SAMS. We aimed to compare atorvastatin pharmacokinetics between coronary heart disease (CHD) patients with and without clinically statin intolerance and statin-dependent histopathological alterations in muscle tissue. Secondarily we aimed to assess genetic variants relevant for the observed pharmacokinetic variables., Methods: Twenty-eight patients with CHD and subjective SAMS were included in the exploratory MUSE biomarker study in 2020. Participants received atorvastatin 40 mg/day for seven weeks followed by no statins for eight weeks. Muscle biopsies and blood were collected at the end of each period. Four patients were categorized as clinically intolerant to ≥3 statins prior to study start whereas four patients had signs of muscle cell damage during treatment., Results: We found significantly lower levels of atorvastatin acids, and higher lactone/acid ratios in the statin intolerant, both in muscle and plasma. With optimal cut-off, the combination of 2-OH-atorvastatin acid and the 2-OH-atorvastatin lactone/acid ratio provided sensitivity, specificity, and predictive values of 100 %. Patients with variants in UGT1A1 and UGT1A3 had higher lactone metabolite levels than those with wild type, both in muscle and plasma., Conclusion: Atorvastatin metabolites appear promising as biomarkers for the identification of clinical statin intolerance in patients with self-perceived SAMS, but the findings have to be confirmed in larger studies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JM reports having received modest lecture fees from Novartis and Bayer, outside the submitted work. The other authors have nothing to declare., (© 2024 The Authors.)

Background: There is limited knowledge from Norway on clinical characteristics, self-care and health literacy in patients admitted to hospital with acute heart failure. Our aim was to identify these factors in this group., Material and Method: We included patients admitted with acute heart failure over a period of six months (2022/2023) at Drammen Hospital and Vestfold Hospital Trust. Cardiac nurses collected information from the patients, including self-assessed knowledge on an ordinal scale from 0 (little knowledge) to 10 (good knowledge). Clinical frailty scores were calculated and data from the hospital records were recorded., Results: Of 136 patients with acute heart failure, 81 were included. Median age was 79 (range 35-95) years, 35 (43 %) were women. A total of 35 (43 %) had been admitted with heart failure exacerbation in the past year. The patients had a median of 5 (1-10) diagnoses, and the median score on the clinical frailty scale was 4 (1-7), corresponding to 'vulnerable'. A total of 63 (78 %) had been diagnosed with heart failure before admission to hospital. Of these, 13 (21 %) were unaware of the diagnosis, and their self-assessed knowledge was median 3 (25th and 75th percentile, 0-5) for management of heart failure, 2 (25th and 75th percentile, 0-5) for lifestyle interventions and 0 (25th and 75th percentile, 0-2) for heart medications. Altogether 42 out of 63 (67 %) weighed themselves weekly, 13 (21 %) measured their blood pressure, while 3 (5 %) had a self-care plan. Of 50 patients with left ventricle ejection fraction ≤ 40 %, 32 (64 %) were discharged with betablockers and angiotensin II receptor blockers or a combination drug with a neprilysin inhibitor, whereas 11 (22 %) were also prescribed SGLT2 inhibitors and mineralocorticoid receptor antagonists., Interpretation: The included patients were multimorbid and had a low level of self-care and health literacy. There is potential to optimise well-documented medicinal treatment.

Introduction: Clinically significant symptoms of depression and anxiety in coronary heart disease (CHD) patients are common and associated with adverse outcomes. Psychological treatments have shown limited effectiveness and more effective treatments have been requested. Attention training technique (ATT), a component of metacognitive therapy, can potentially be effective as a stand-alone treatment for anxiety and depression. In an open study, ATT delivered face-to-face in a group format was feasible and potentially effective for improving depression and anxiety symptoms in CHD patients. The next progressive step is to test the effectiveness of ATT in a randomized controlled trial. This paper describes the methodology of this trial., Methods: ATT-CHD is a randomized wait-list (WL) controlled study. Eligible CHD patients from two hospitals with Hospital Anxiety and Depression Scale (HADS)-Anxiety and/or HADS-Depression subscales scores ≥8 will be randomized into ATT ( n  = 32) or WL control ( n  = 32). After 6-8 weeks, WL patients will be allocated to ATT. Participants will be evaluated pre-, mid- and post-treatment, and at 6-months follow-up using changes in HADS as primary outcome. Secondary outcomes will be changes in psychiatric disorders, rumination, worry, type D-personality, metacognitions, insomnia, quality of life, and C-Reactive protein (CRP)., Discussion: To our knowledge, this will be the first WL-controlled randomized study testing the effectiveness of group-based ATT as treatment of symptoms of anxiety and depression in CHD patients. It will also explore correlations between changes in psychological distress and CRP. A qualitative analysis will reveal patients' experience with ATT including processes that may facilitate or serve as barriers to effectiveness. Recruitment into the study commenced in December 2022., Ethics and Dissemination: The Regional Committees for Medical and Health Research Ethics (REK), Norway has granted approval for the study (ID 52002). The trial results will be published in peer-reviewed journals. According to Norwegian legislation, the Norwegian Data Protection Authority, and the Committee of Ethics, we are not allowed to share original study data publicly., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05621408 pre-inclusion. There were no significant changes of methods or outcomes after study start., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dammen, Tunheim, Munkhaugen, Klungsøyr and Papageorgiou.)

Background: Little is known regarding the prevalence of psychiatric disorders in patients with both coronary heart disease (CHD) and type D personality, and whether these patients may benefit from psychotherapy that modifies metacognitive beliefs implicated in disorder maintenance. This study explored prevalence rates among these patients and associations between type D characteristics, rumination and metacognitions., Methods: Forty-seven consecutive patients with CHD who scored positive for type D personality were included in this pre-planned study. Participants underwent structured clinical interviews for mental and personality disorders and completed questionnaires assessing rumination and metacognitions., Results: Mean age was 53.8 (SD 8.1) years and 21.3% were female. At least one mood disorder or anxiety disorder was found in 70.2% and 61.7% of the patients. The most common disorders were major depressive disorder (59.6%), social phobia (40.4%), and generalized anxiety disorder (29.8%). At least one personality disorder was detected in 42.6%. Only 21% reported ongoing treatment with psychotropic medication whereas none had psychotherapy. Metacognitions and rumination were significantly associated with negative affectivity (0.53-0.72, p  < .001) but not social inhibition., Conclusion: Mood and anxiety disorders were highly prevalent and relatively untreated among these patients. Future studies should test the metacognitive model for type D personality.

Introduction: Health-related quality of life (HRQoL) is an important treatment target in patients with coronary heart disease (CHD) and is associated with poor outcomes. Therefore, it is of clinical importance to identify the key determinants of HRQoL among these patients. There is, however, limited knowledge of how a comprehensive set of psychosocial factors influence HRQoL. We aimed to determine the relative associations of clinical and psychosocial factors with mental and physical components of HRQoL in a sample of CHD outpatients., Methods: This cross-sectional study included 1,042 patients 2-36 (mean 16) months after a CHD event recruited from two general Norwegian hospitals with a combined catchment area making up 7% of the Norwegian population, representative with regards to demographic and clinical factors. We collected data on HRQoL, demographics, comorbidities, coronary risk factors, and psychosocial factors. HRQoL was assessed using the Short Form 12 (SF12), which comprises a Mental Component Scale (MCS), and the Physical Component Scale (PCS). Crude and multi-adjusted linear regression analyses were used to investigate the association between covariates and MCS and PCS., Results: Mean age was 61 [standard deviation (SD) 10] years, 20% were females, 18% had type D personality, 20% significant depression symptoms, 14% significant symptoms of anxiety whereas 45% reported insomnia. The presence of type D personality (β: -0.19), significant symptoms of depression (β: -0.15), and the presence of insomnia (β: -0.13) were negatively associated with MCS, but not PCS in multi-adjusted analyses. The presence of chronic kidney disease (β: -0.11) was associated with reduced MCS, whereas the presence of chronic obstructive pulmonary disease (β: -0.08) and low physical activity (β: -0.14) were negatively associated with PCS. Younger age was associated with lower MCS, whereas older age was associated with lower PCS., Discussion: We conclude that Type D personality, depressive symptoms, insomnia, and chronic kidney disease were the strongest determinants of the mental component of HRQoL. Assessing and managing these psychological factors among CHD outpatients may improve their mental HRQoL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Frøjd, Munkhaugen, Papageorgiou, Sverre, Moum and Dammen.)

Self-perceived statin-associated muscle symptoms (SAMS) are prevalent, but only a minority is drug-dependent. Diagnostic biomarkers are not yet identified. The local statin exposure in skeletal muscle tissue may correlate to the adverse effects. We aimed to determine whether atorvastatin metabolites in blood reflect the corresponding metabolite levels in skeletal muscle, and whether genetic variants of statin transporters modulate this relationship. We also addressed atorvastatin metabolites as potential objective biomarkers of SAMS. Muscle symptoms were examined in patients with coronary disease and self-perceived SAMS during 7 weeks of double-blinded treatment with atorvastatin 40 mg/day and placebo in randomized order. A subset of 12 patients individually identified with more muscle symptoms on atorvastatin than placebo (confirmed SAMS) and 15 patients with no difference in muscle symptom intensity (non-SAMS) attended the present follow-up study. All received 7 weeks of treatment with atorvastatin 40 mg/day followed by 8 weeks without statins. Biopsies from the quadriceps muscle and blood plasma were collected after each treatment period. Strong correlations (rho > 0.7) between muscle and blood plasma concentrations were found for most atorvastatin metabolites. The impact of the SLCO1B1 c.521T>C (rs4149056) gene variant on atorvastatin's systemic pharmacokinetics was translated into muscle tissue. The SLCO2B1 c.395G>A (rs12422149) variant did not modulate the accumulation of atorvastatin metabolites in muscle tissue. Atorvastatin pharmacokinetics in patients with confirmed SAMS were not different from patients with non-SAMS. In conclusion, atorvastatin metabolite levels in skeletal muscle and plasma are strongly correlated, implying that plasma measurements are suitable proxies of atorvastatin exposure in muscle tissue. The relationship between atorvastatin metabolites in plasma and SAMS deserves further investigation., (© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Introduction: Data on the association between Type D personality, its traits negative affectivity (NA) and social inhibition (SI), and risk of major adverse cardiac events (MACE) in coronary outpatients is sparse. Furthermore, the associations between Type D subgroups and cardiovascular risk factors are largely unknown., Methods: We investigated i) Type D personality, NA and SI and risk of recurrent MACE, and ii) the relationship between Type D subgroups and risk factors in a coronary population. This prospective cohort study included 1083 patients` median 16 months after a myocardial infarction and/or a revascularization procedure who were followed-up for 4.2 (SD 0.4) years. Type D personality was assessed by DS14. Anxiety and depression, statin adherence, and risk factors were assessed by patients' self-report and a clinical examination with blood samples. MACE, defined as cardiovascular death, myocardial infarction, revascularization, stroke or heart failure, were obtained from hospital records from index event to end of study lasting 5.7 years. Data were analyzed by Cox proportional hazard regression., Results: In all, 352 MACE occurred in 230 patients after average 4.2 years follow-up. Higher NA score was associated with MACE after adjustment for age, risk factors and comorbidity (HR 1.02 per unit increase, 95% CI 1.00-1.05), whereas we found a weaker, not statistically significant estimated effect of higher SI score. After additional adjustment for symptoms of anxiety and depression, we found a weaker, not statistically significant association between NA and MACE (HR 1.01 per unit increase, 95% CI 0.98-1.05). Low statin adherence and smoking were more prevalent in the Type D and high NA group., Discussion: Our results indicate that the NA trait is related to worse prognosis in outpatients with coronary artery disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Torgersen, Sverre, Weedon-Fekjær, Andreassen, Munkhaugen and Dammen.)

Objectives: Smoking is common in patients with cardiovascular disease. Despite strong recommendations for cessation and the existence of efficacious pharmacological and behavioral interventions, cessation rates remain low. Therefore, in this study, we explore perceived facilitators and barriers to smoking cessation in patients with atherosclerotic cardiovascular disease who have participated in a cessation intervention study., Methods: Participants ( N = 10) from the intervention arm of a randomized controlled study with access to free cessation support and pharmacological aids completed a semi-structured, in-depth telephone interview after a 6-monthfollow-up between October 2021 and July 2022. The interviews were audio recorded, transcribed, and analyzed according to principles of thematic analysis., Results: The mean age was 65.7 (range: 55-79) years, and three of the 10 participants were women. Among the participants, five had quit smoking, three had relapsed, and two were persistent smokers. The themes identified encompassed barriers and facilitators to cessation, both including individual and contextual factors. Barriers included the upsides of smoking, difficult life situations, addiction to smoking, smoking in social circles, perceived lack of support and understanding from health professionals. Facilitators included intrinsic motivation, concerns about the health condition, financial implications, specific behavioral strategies, positive influence from the social environment, and helpful components of the cessation intervention., Conclusion: Smokers with cardiovascular disease who have attended a cessation intervention study report several facilitators weighted against barriers, interacting with the intention to cease smoking. The most important potentially modifiable factors of significance for cessation identified may be addressed through motivational interviews and focus groups with other smokers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Getz, Munkhaugen, Lie and Dammen.)

Aims: In clinical practice, many patients do not reach the recommended treatment targets for LDL-cholesterol levels. We aimed to examine treatment patterns and adherence for patients on lipid lowering drugs in Norway to inform future strategies to improve therapies., Methods and Results: We obtained information on all dispensed statins, ezetimibe, and proprotein convertase subtilisin/-kexin 9 (PCSK9) inhibitors 2010-2019 from the Norwegian Prescription Database. Treatment gaps were assessed assuming patients take one tablet per day and were defined to occur if a patient did not refill a prescription when the previous one should have been depleted. Treatment was defined as discontinued when the preceding prescription would have been used and no new subsequent prescription was filled. The mean proportion of days covered (PDC) was calculated by aggregating the total number of tablets dispensed during each calendar year and dividing by 365. Patients 80 years were excluded. A considerable proportion of statin users in Norway had long treatment gaps or discontinuation in treatment. The 19.6% of the patients had treatment gaps of 180 days or more, and 10.8% had gaps or greater than 365 days. Similar results were found for patients on antidiabetics and hypertensives. PDC ranged from 84.9% for simvastatin to 72.2% for ezetimibe (2019). The most common lipid lowering drugs in 2019 were atorvastatin, simvastatin, and ezetimibe., Conclusion: There is a great potential for improving drug adherence and optimizing lipid lowering therapy by switching to more effective statins in greater doses, and more often add ezetimibe and PCSK9 inhibitors to treatment., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Hospital admissions of patients with chest pain considered as low risk for acute coronary syndrome contribute to increased costs and crowding in the emergency departments. This study aims to estimate the cost-effectiveness of assessing these patients in a primary care emergency setting, using the European Society of Cardiology (ESC) 0/1-h algorithm for high-sensitivity cardiac troponin T, compared to routine hospital management., Methods: A cost-effectiveness analysis was conducted. For the primary care estimates, costs and health care expenditure from the observational OUT-ACS (One-hoUr Troponin in a low-prevalence population of Acute Coronary Syndrome) study were compared with anonymous extracted administrative data on low-risk patients at a large general hospital in Norway. Patients discharged home after the hs-cTnT assessment were defined as low risk in the primary care cohort. In the hospital setting, the low-risk group comprised patients discharged with a non-specific chest pain diagnosis (ICD-10 codes R07.4 and Z03.5). Loss of health related to a potential increase in acute myocardial infarctions the following 30-days was estimated. The primary outcome measure was the costs per quality-adjusted life year (QALY) of applying the ESC 0/1-h algorithm in primary care. The secondary outcomes were health care costs and length of stay in the two settings., Results: Differences in costs comprise personnel and laboratory costs of applying the algorithm at primary care level (€192) and expenses related to ambulance transports and complete hospital costs for low-risk patients admitted to hospital (€1986). Additional diagnostic procedures were performed in 31.9% (181/567) of the low-risk hospital cohort. The estimated reduction in health care cost when using the 0/1-h algorithm outside of hospital was €1794 per low-risk patient, with a mean decrease in length of stay of 18.9 h. These numbers result in an average per-person QALY gain of 0.0005. Increased QALY and decreased costs indicate that the primary care approach is clearly cost-effective., Conclusion: Using the ESC 0/1-h algorithm in low-risk patients in emergency primary care appears to be cost-effective compared to standard hospital management, with an extensive reduction in costs and length of stay per patient., (© 2022. The Author(s).)

Psychological distress, including depression and anxiety, and Type-D personality are prevalent in patients with coronary heart disease (CHD) and associated with poor cardiovascular outcomes. Worry and rumination may be among the core features responsible for driving psychological distress in these patients. However, the nature of associations between these constructs remains to be delineated, yet they may have implications for the assessment and treatment of CHD patients. This study aimed to (1) explore the factorial structure and potential overlap between measures of depression, anxiety and the Type-D personality factors known as negative affectivity and social inhibition, and (2) examine how these constructs relate to worry and rumination in a sample of 1,042 CHD outpatients who participated in the in the cross-sectional NORwegian CORonary Prevention study. We conducted confirmatory factor analyses ( n = 1,042) and regression analyses ( n = 904) within a structural equation modeling framework. Results showed all constructs to have acceptable factor structure and indicated an overlap between the constructs of depression and negative affectivity. Worry was most strongly associated with anxiety, whereas rumination was most strongly associated with depression and negative affectivity. The results suggest conceptual similarities across the measures of depression and negative affectivity. They further suggest that intervention efforts could benefit from targeting worry and/or rumination in the treatment of CHD outpatients presenting with symptoms of psychological distress., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tunheim, Dammen, Baardstu, Moum, Munkhaugen and Papageorgiou.)

Background: Poor statin adherence remains a public health concern associated with adverse outcomes. We evaluated the use of pharmacokinetic measurements to monitor adherence to simvastatin in patients with coronary heart disease (CHD)., Methods: Eighteen patients with CHD taking an evening dose of simvastatin 20 mg (n = 7), 40 mg (n = 5), or 80 mg (n = 6) were examined at steady-state pharmacokinetics. Ten patients were instructed to interrupt simvastatin dosing and return for blood sampling for the subsequent 3 days. Dose-normalized plasma concentrations of simvastatin lactone and simvastatin acid and the sum of the 2 were evaluated to discriminate between adherent dosing and dose omission. Bioanalytical quantification was performed using liquid chromatography-tandem mass spectrometry., Results: A simvastatin acid cutoff of 1.0 × 10 -2 nmol -1 ·L -1 ·mg -1 identified 100% of those omitting 2 doses and 60% of those omitting a single dose. Simvastatin acid showed superior ability to discriminate dose omission, as well as the best agreement between samples handled at ambient and cool temperatures (median deviation 3.5%; interquartile range -2.5% to 13%). The cutoff for a morning dose schedule, with a similar ability to discriminate, was estimated at 2.0 × 10 -3 nmol -1 ·L -1 ·mg -1 ., Conclusions: The present method discriminated between adherence and reduced adherence to simvastatin therapy in patients with CHD. Sample handling is feasible for routine practice, and the assessment of adherence can be performed by direct measurement of simvastatin acid in a blood sample, according to defined cutoff values. Further studies validating the cutoff value and utility for clinical application are encouraged., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Depression and anxiety symptoms are highly prevalent in coronary heart disease (CHD) patients and associated with poor outcome. Most psychological treatments have shown limited effectiveness on anxiety and depression in these patients. This study evaluates the feasibility of the attention training technique (ATT) in CHD patients with symptoms of anxiety and/or depression., Methods: Five consecutive CHD patients with significant depression and anxiety symptoms with Hospital Anxiety and Depression rating scale (HADS) -anxiety or -depression subscale score > 8 received 6 weekly group-sessions of ATT in an open trial. Outcomes included feasibility and symptoms measured by HADS, at baseline, post-treatment and at 6 months follow-up. We also assessed psychiatric diagnoses, type D personality, insomnia, worry, and rumination., Results: The sample comprised five men with a mean age of 59.9 (SD 4.4) years. Four of the patients attended all six sessions, and one patient attended all but one session. Mean HADS-A scores at baseline, post-treatment, and follow-up were 9.4 (SD 3.0), 4.2 (SD 3.0), and 4.0 (SD 2.5), and for HADS-D 8.6 (SD 3.3), 3.0 (SD 3.7), and 1.6 (SD 1.5), respectively. The results showed clinically significant changes in anxiety, depression, psychiatric disorders, insomnia, worry, and rumination. Statistically significant changes were found from pre- to post-treatment scores for HADS-A and worry, which were maintained at follow-up, and HADS-D scores significantly decreased from pre-treatment to 6-months follow-up., Conclusions: ATT in a group format appears to be a feasible stand-alone metacognitive treatment for CHD patients. An adequately powered randomized controlled trial is warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dammen, Tunheim, Munkhaugen and Papageorgiou.)

Epidemiological and clinical studies have found associations between depression and cardiovascular disease risk factors, and coronary artery disease patients with depression have worse prognosis. The genetic relationship between depression and these cardiovascular phenotypes is not known. We here investigated overlap at the genome-wide level and in individual loci between depression, coronary artery disease and cardiovascular risk factors. We used the bivariate causal mixture model (MiXeR) to quantify genome-wide polygenic overlap and the conditional/conjunctional false discovery rate (pleioFDR) method to identify shared loci, based on genome-wide association study summary statistics on depression (n = 450,619), coronary artery disease (n = 502,713) and nine cardiovascular risk factors (n = 204,402-776,078). Genetic loci were functionally annotated using FUnctional Mapping and Annotation (FUMA). Of 13.9K variants influencing depression, 9.5K (SD 1.0K) were shared with body-mass index. Of 4.4K variants influencing systolic blood pressure, 2K were shared with depression. ConjFDR identified 79 unique loci associated with depression and coronary artery disease or cardiovascular risk factors. Six genomic loci were associated jointly with depression and coronary artery disease, 69 with blood pressure, 49 with lipids, 9 with type 2 diabetes and 8 with c-reactive protein at conjFDR < 0.05. Loci associated with increased risk for depression were also associated with increased risk of coronary artery disease and higher total cholesterol, low-density lipoprotein and c-reactive protein levels, while there was a mixed pattern of effect direction for the other risk factors. Functional analyses of the shared loci implicated metabolism of alpha-linolenic acid pathway for type 2 diabetes. Our results showed polygenic overlap between depression, coronary artery disease and several cardiovascular risk factors and suggest molecular mechanisms underlying the association between depression and increased cardiovascular disease risk., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: OAA received speaker’s honorarium from Lundbeck and Sunovion, and is a consultant to HealthLytix.