Treatment patterns and adherence to lipid-lowering drugs during eight-year follow-up after a coronary heart disease event.

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.

A multi-component intervention increased access to smoking cessation treatment after hospitalization for atherosclerotic cardiovascular disease: a randomized trial.

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.

Atorvastatin Metabolite Pattern in Skeletal Muscle and Blood from Patients with Coronary Heart Disease and Statin-Associated Muscle Symptoms.

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.

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.

The prevalence and predictors of elevated C-reactive protein after a coronary heart disease event.

Objective An interleukin-beta antagonist reduces the risk of subsequent cardiovascular events in coronary patients with high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L. It remains to be defined how large the coronary population at inflammatory risk is, and what the predictors of elevated risk are. Methods A cross-sectional study investigated the proportion of patients with elevated hs-CRP (i.e. ≥2 mg/L) and the respective demographic and clinical predictors in 971 patients without concomitant inflammatory diseases who had been hospitalized with myocardial infarction (80%) and/or a revascularization procedure. Data were collected from hospital records, a self-report questionnaire and a clinical examination with blood samples. Results After 2-36 month follow-up, 39% ( n = 378) had hs-CRP ≥ 2 mg/L, among whom 64% ( n = 243) had low-density lipoprotein cholesterol (LDL-C) ≥1.8 mmol/L and 47% ( n = 176) used a low-intensity statin regime. Only 24% had both LDL and hs-CRP at target range, 27% had elevation of both, whereas 12% had hs-CRP ≥ 2 mg/L and LDL-C < 1.8 mmol/L. Somatic comorbidity (odds ratio (OR) 1.3/1.0 point on the Charlson score), ≥1 previous coronary event (OR 2.4), smoking (OR 2.2), higher body mass index (OR 1.2/1.0 kg/m2), high LDL-C (OR 1.4/1.0 mmol/L) and higher anxiety scores (OR 1.1/1.0 point increase on the Hospital Anxiety and Depression Scale-Anxiety subscale score) were significantly associated with hs-CRP ≥2 mg/L in adjusted analyses. Conclusions Elevated hs-CRP was frequently observed after a coronary event and associated with unfavourable LDL-C and unhealthy lifestyles and psychosocial distress. Intensified statin therapy and strategies to target these modifiable factors are the encouraged first steps to reduce inflammation and improve LDL-C in these patients.

Medical and sociodemographic factors predict persistent smoking after coronary events.

BACKGROUND: Understanding the determinants of persistent smoking after a coronary event constitutes the basis of modelling interventions of smoking cessation in secondary prevention programs. We aim to identify the potentially modifiable medical, sociodemographic and psychosocial factors, comprising the study factors, associated with unfavourable risk factor control after CHD events. METHODS: A cross-sectional explorative study used logistic regression analysis to investigate the association between study factors and smoking status in 1083 patients hospitalized with myocardial infarction and/or coronary revascularization. Hospital record data, a self-report questionnaire, clinical examination and blood samples were applied. RESULTS: At the index hospitalization, 390 patients were smoking and at follow-up after 2-36 months 167 (43%) of these had quit, while 230 reported persistent smoking. In adjusted analyses, unemployed or disability benefits (Odds ratio (OR) 4.1), low education (OR 3.5), longer smoking duration (OR 2.3) and not having ST-elevation myocardial infarction (STEMI) as index event (OR 2.3) were significantly associated with persistent smoking. Psychosocial factors at follow-up were not associated with persistent smoking. Smokers reported high motivation for cessation, with 68% wanting help to quit. Only 42% had been offered nicotine replacement therapy or other cessation aids. Smokers rated use of tobacco as the most important cause of their coronary disease (6.8 on a 1-10 Likert scale). CONCLUSIONS: Low socioeconomic status, prior duration of smoking, and not having STEMI as index event were associated with persisting smoking. Persistent smokers in this study seem to have an acceptable risk perception and were motivated to cease smoking, but needed assistance through cessation programs including prescription of pharmacological aids. TRIAL REGISTRATION: Registered at ClinicalTrials.gov: NCT02309255 , registered retrospectively.

Medical and psychosocial factors and unfavourable low-density lipoprotein cholesterol control in coronary patients.

Objective Understanding the determinants of low-density lipoprotein cholesterol (LDL-C) control constitutes the basis of modelling interventions for optimal lipid control and prognosis. We aim to identify medical and psychosocial (study) factors associated with unfavourable LDL-C control in coronary patients. Methods A cross-sectional explorative study used logistic and linear regression analysis to investigate the association between study factors and LDL-C in 1095 patients, hospitalized with myocardial infarction and/or a coronary revascularization procedure. Data were collected from hospital records, a comprehensive self-report questionnaire, clinical examination and blood samples after 2-36 months follow-up. Results Fifty-seven per cent did not reach the LDL-C target of 1.8 mmol/l at follow-up. Low socioeconomic status and psychosocial factors were not associated with failure to reach the LDL-C target. Statin specific side-effects (odds ratio 3.23), low statin adherence (odds ratio 3.07), coronary artery by-pass graft operation as index treatment (odds ratio 1.95), ≥ 1 coronary event prior to the index event (odds ratio 1.81), female gender (odds ratio 1.80), moderate- or low-intensity statin therapy (odds ratio 1.62) and eating fish < 3 times/week (odds ratio 1.56) were statistically significantly associated with failure to reach the LDL-C target, in adjusted analyses. Only side-effects (standardized ß 0.180), low statin adherence ( ß 0.209) and moderate- or low-intensity statin therapy ( ß 0.228) were associated with LDL-C in continuous analyses. Conclusions Statin specific side-effects, low statin adherence and moderate- or low-intensity statin therapy were the major factors associated with unfavourable LDL-C control. Interventions to improve LDL-C should ensure adherence and prescription of sufficiently potent statins, and address side-effects appropriately.

Unfavourable risk factor control after coronary events in routine clinical practice.

BACKGROUND: Risk factor control after a coronary event in a recent European multi-centre study was inadequate. Patient selection from academic centres and low participation rate, however, may underscore failing risk factor control in routine clinical practice. Improved understanding of the patient factors that influence risk factor control is needed to improve secondary preventive strategies. The objective of the present paper was to determine control of the major risk factors in a coronary population from routine clinical practice, and how risk factor control was influenced by the study factors age, gender, number of coronary events, and time since the index event. METHODS: A cross-sectional study determined risk factor control and its association with study factors in 1127 patients (83% participated) aged 18-80 years with acute myocardial infarction and/or revascularization identified from medical records. Study data were collected from a self-report questionnaire, clinical examination, and blood samples after 2-36 months (median 16) follow-up. RESULTS: Twenty-one percent were current smokers at follow-up. Of those smoking at the index event 56% continued smoking. Obesity was found in 34%, and 60% were physically inactive. Although 93% were taking blood-pressure lowering agents and statins, 46% were still hypertensive and 57% had LDL cholesterol >1.8 mmol/L at follow-up. Suboptimal control of diabetes was found in 59%. The patients failed on average to control three of the six major risk factors, and patients with >1 coronary events (p < 0.001) showed the poorest overall control. A linear increase in smoking (p < 0.01) and obesity (p < 0.05) with increasing time since the event was observed. CONCLUSIONS: The majority of coronary patients in a representative Norwegian population did not achieve risk factor control, and the poorest overall control was found in patients with several coronary events. New strategies for secondary prevention are clearly needed to improve risk factor control. Even modest advances will provide major health benefits. TRIAL REGISTRATION: Registered at ClinicalTrials.gov (ID NCT02309255 ).

Risk Factors for Long-Term Mortality after Hospitalization for Community-Acquired Pneumonia: A 5-Year Prospective Follow-Up Study.

BACKGROUND: Contributors to long-term mortality in patients with community-acquired pneumonia (CAP) remain unclear, with little attention paid to pneumonia etiology. We examined long-term survival, causes of death, and risk factors for long-term mortality in adult patients who had been hospitalized for CAP, with emphasis on demographic, clinical, laboratory, and microbiological characteristics. METHODS: Two hundred and sixty-seven consecutive patients admitted in 2008-2011 to a general hospital with CAP were prospectively recruited and followed up. Patients who died during hospital stay were excluded. Demographic, clinical, and laboratory data were collected within 48 hours of admission. Extensive microbiological work-up was performed to establish the etiology of CAP in 63% of patients. Mortality data were obtained from the Norwegian Cause of Death Registry. Cox regression models were used to identify independent risk factors for all-cause mortality. RESULTS: Of 259 hospital survivors of CAP (median age 66 years), 79 (30.5%) died over a median of 1,804 days (range 1-2,520 days). Cumulative 5-year survival rate was 72.9% (95% CI 67.4-78.4%). Standardized mortality ratio was 2.90 for men and 2.05 for women. The main causes of death were chronic obstructive pulmonary disease (COPD), vascular diseases, and malignancy. Independent risk factors for death were the following (hazard ratio, 95% CI): age (1.83 per decade, 1.47-2.28), cardiovascular disease (2.63, 1.61-4.32), COPD (2.09, 1.27-3.45), immunocompromization (1.98, 1.17-3.37), and low serum albumin level at admission (0.75 per 5 g/L higher, 0.58-0.96), whereas active smoking was protective (0.32, 0.14-0.74); active smokers were younger than non-smokers (P < 0.001). Microbial etiology did not predict mortality. CONCLUSIONS: Results largely confirm substantial comorbidity-related 5-year mortality after hospitalization for CAP and the impact of several well-known risk factors for death, and extend previous findings on the prognostic value of serum albumin level at hospital admission. Pneumonia etiology had no prognostic value, but this remains to be substantiated by further studies using extensive diagnostic microbiological methods in the identification of causative agents of CAP.

"Test, score and scope": a selection strategy for safe reduction of upper gastrointestinal endoscopies in young dyspeptic patients referred from primary care.

OBJECTIVE: To test the ability of pre-endoscopic clinical evaluation to predict clinically relevant findings of upper gastrointestinal endoscopy. MATERIAL AND METHODS: Patients (341) who had been referred to upper gastrointestinal endoscopy for further evaluation of dyspeptic symptoms were included in this prospective, single-blinded study. Prior to endoscopy, the patients underwent a standardized clinical evaluation consisting of 1) a symptom questionnaire, 2) serological testing for Helicobacter pylori antibody and 3) determination of blood hemoglobin. Based upon this evaluation, patients were assigned to one of three defined risk groups. Group A comprised patients with known risk factors for diseases that would require further therapeutic or diagnostic management. Patients in groups B and C had no such risk factors. Patients in group C had heartburn or regurgitation as a predominant symptom, whereas patients in group B did not. The prevalence of clinically relevant findings upon upper endoscopy was then compared for these three groups. RESULTS: The prevalence of clinically relevant endoscopic findings in risk groups A, B and C were 20.1, 2.4 and 1.6%, respectively (p<0.01 for both A versus B and A versus C). Furthermore, 89% of those with clinically relevant endoscopic findings belonged to group A, which comprised a total of 45% of the patients studied. In groups B and C, the prevalence of disease was similar to the area-specific prevalence in the general population without dyspeptic symptoms. CONCLUSIONS: By using a simple standardized questionnaire, H. pylori serology and a hemoglobin reading in the evaluation of dyspeptic patients under 45 years of age, the need for endoscopy can be reduced by 55%.

The pathogenesis of gastrointestinal bacterial overgrowth.

The normal indigenous intestinal microflora consists of about 10(15) bacteria that under physiological conditions reside mainly in the lower gastrointestinal tract. Bacterial overgrowth implies abnormal bacterial colonization of the upper gut, resulting from failure of specific defense mechanisms restricting colonization under physiological conditions. At present two types of bacterial overgrowth with defined pathogenesis can be distinguished: (1) gastric overgrowth with upper respiratory tract microflora resulting from selective failure of the gastric acid barrier, and (2) gastrointestinal overgrowth with Gram-negative bacilli (enteric bacteria) resulting from failure of intestinal clearance. Helicobacter pylori-induced gastritis of the oxyntic mucosa is the main cause of acquired failure of the gastric acid barrier, which is common among the healthy elderly. Intestinal clearance may fail as the result of impaired intestinal peristalsis or anatomical abnormalities that alter luminal flow. Impaired peristalsis is associated with conditions interfering with intestinal neuromuscular function including myopathic, neuropathic, autoimmune, infectious, inflammatory, metabolic, endocrine, and neoplastic diseases. Anatomical abnormalities are mainly the result of gastrointestinal surgery, intestinal diverticula or fistula. Combined failure of intestinal clearance and the gastric acid barrier results in more severe colonization with Gram-negative bacilli. Gram-negative bacilli are uncommon in the upper gut of otherwise healthy individuals with gastric hypochlorhydria, being acquired (H. pylori) or drug-induced. Significant bacterial overgrowth with Gram-negative bacilli is a rational in the search for an explanation to optimize clinical management. The clinical significance of colonization with upper respiratory tract microflora remains unclear. Translocation of live bacteria, their metabolic products, or antigens from a small bowel colonized by Gram-negative bacilli play a role in the pathogenesis of spontaneous bacterial peritonitis in hepatic disease and in certain types of sepsis, indicating that further studies can point to new patient populations with potential benefit from medical treatment.