The effect of audit and feedback and implementation support on guideline adherence and patient outcomes in cardiac rehabilitation: a study protocol for an open-label cluster-randomized effectiveness-implementation hybrid trial.

BACKGROUND: Providing secondary prevention through structured and comprehensive cardiac rehabilitation programmes to patients after a myocardial infarction (MI) reduces mortality and morbidity and improves health-related quality of life. Cardiac rehabilitation has the highest recommendation in current guidelines. While treatment target attainment rates at Swedish cardiac rehabilitation centres is among the highest in Europe, there are considerable differences in service delivery and variations in patient-level outcomes between centres. In this trial, we aim to study whether centre-level guideline adherence and patient-level outcomes across Swedish cardiac rehabilitation centres can be improved through a) regular audit and feedback of cardiac rehabilitation structure and processes through a national quality registry and b) supporting cardiac rehabilitation centres in implementing guidelines on secondary prevention. Furthermore, we aim to evaluate the implementation process and costs. METHODS: The study is an open-label cluster-randomized effectiveness-implementation hybrid trial including all 78 cardiac rehabilitation centres (attending to approximately 10 000 MI patients/year) that report to the SWEDEHEART registry. The centres will be randomized 1:1:1 to three clusters: 1) reporting cardiac rehabilitation structure and process variables to SWEDEHEART every six months (audit intervention) and being offered implementation support to implement guidelines on secondary prevention (implementation support intervention); 2) audit intervention only; or 3) no intervention offered. Baseline cardiac rehabilitation structure and process variables will be collected. The primary outcome is an adherence score measuring centre-level adherence to secondary prevention guidelines. Secondary outcomes include patient-level secondary prevention risk factor goal attainment at one-year after MI and major adverse coronary outcomes for up to five-years post-MI. Implementation outcomes include barriers and facilitators to guideline adherence evaluated using semi-structured focus-group interviews and relevant questionnaires, as well as costs and cost-effectiveness assessed by a comparative health economic evaluation. DISCUSSION: Optimizing cardiac rehabilitation centres' delivery of services to meet standards set in guidelines may lead to improvement in cardiovascular risk factors, including lifestyle factors, and ultimately a decrease in morbidity and mortality after MI. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT05889416 . Registered 2023-03-23.

Management and outcome in foreign-born vs native-born patients with myocardial infarction in Sweden.

BACKGROUND: Previous studies on disparities in healthcare and outcome have shown conflicting results. The aim of this study was to assess differences in baseline characteristics, management, and outcome in myocardial infarction (MI) patients, by country of birth. METHODS: In total, 194 259 MI patients (64% male, 15% foreign-born) from the nationwide SWEDEHEART registry were included and compared by geographic region of birth. The primary outcome was one-year major adverse cardiovascular events (MACE) including all-cause death, MI, and stroke. Secondary outcomes were long-term MACE (up to 12 years), the individual components of MACE, 30-day mortality, management, and risk factors. Logistic regression, Cox proportional hazard models and propensity score matching (PSM), accounting for baseline differences, were used. RESULTS: Foreign-born patients were younger, often male, and had a higher cardiovascular (CV) risk factor burden, including smoking, diabetes, and hypertension. In PSM analyses, Asia-born patients had higher likelihood of revascularisation (OR 1.16, 95% CI 1.04-1.30), statins and betablocker prescription at discharge and a 34% lower risk of 30-day mortality. Furthermore, no statistically significant differences were found in the primary outcomes except for Asia-born patients having lower risk of one-year MACE (HR 0.85, 95% CI 0.73-0.98), driven by lower mortality (HR 0.72, 95% CI 0.57-0.91). The results persisted over long-term follow-up. CONCLUSIONS: This study shows that in a system with universal healthcare coverage in which acute and secondary preventive treatments do not differ by country of birth, foreign-born patients, despite higher CV risk factor burden, will do at least as well as native-born patients.

Provision of professional interpreters and Heart School attendance for foreign-born compared with native-born myocardial infarction patients in Sweden.

Objective: Interactive patient education, referred to as Heart School (HS), is an important part of cardiac rehabilitation (CR) after myocardial infarction (MI), which has been associated with improved outcomes. Little is known about HS attendance among foreign-born patients. The aims were to assess; 1) HS attendance in foreign-born versus native-born patients, 2) the association between the provision of professional interpreters and HS attendance, and 3) secondary prevention goal attainment after MI based on HS attendance. Methods: The provision of professional interpreters during post-MI follow-up was assessed by a questionnaire sent to all 78 Swedish CR sites. Patient-specific data was retrieved from the SWEDEHEART registry. The association between the provision of professional interpreters and HS attendance was estimated with logistic regression models. HS attendance and attainment of secondary prevention goals by country of birth were investigated. Results: In total, 8377 patients < 75 years (78 % male) were included. Foreign-born (19.8 %) had a higher prevalence of cardiovascular risk factors and were less likely to attend HS (33.7 vs 51.3 %, p < 0.001), adjusted odds ratio (OR) 0.59 (95 % confidence interval (CI) 0.52-0.68), compared with native-born patients. CR centers providing professional interpreters had higher HS attendance among foreign-born (adjusted OR 1.55, 95 % CI 1.20-2.01) but not among native-born patients. Attending HS was similarly associated with improved secondary prevention goal attainment in both groups. Conclusions: Despite similar positive association between HS attendance and attainment of secondary prevention goals, foreign-born patients attended HS less often. With the provision of professional interpreters, HS attendance increased in foreign-born patients.

A retrospective nationwide analysis of evolocumab use in Sweden and its effect on low-density lipoprotein cholesterol levels.

Background: Treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduces low-density lipoprotein cholesterol (LDL-C) levels and decreases the incidence of major ischaemic events in clinical trials. However, less is known about the efficacy of PCSK9 inhibition in clinical practice. This study aimed to describe the change in LDL-C levels over time and LDL-C goal achievement in patients with/without atherosclerotic cardiovascular disease (ASCVD), who were prescribed evolocumab in clinical practice, and to describe adherence to and persistence with treatment. Methods: Patients in Sweden with at least one evolocumab prescription filled between July 2015 and May 2020 were included. Medical history and lipid-lowering therapy (LLT) were sourced from national registries. LDL-C levels before and after treatment initiation were assessed using medical records. Persistence with and adherence to evolocumab and oral LLT were assessed up to 12 months after treatment initiation using the refill-gap method and proportion of days covered, respectively. Results: Of the 2,360 patients with at least one prescription for evolocumab, 2,341 were included; 1,858 had ASCVD. Persistence with (76%) and adherence to (86%) evolocumab were high throughout the 12 months following initiation. Mean LDL-C levels decreased by 53% (95% confidence interval [CI]: 51-55%) in patients adherent to evolocumab (n = 567) and 59% (95% CI: 55-63%) in patients adherent to evolocumab and oral LLT (n = 186). Similar reductions in LDL-C were observed in patients with/without ASCVD. Reduced LDL-C levels remained stable during follow-up. Amongst patients adherent to evolocumab and those adherent to evolocumab and oral LLT, 23 and 55% achieved the LDL-C goal of <1.4 mmol/L, respectively. Conclusions: The evolocumab LDL-C-lowering effect observed in clinical trials was confirmed in clinical practice in Sweden, particularly in patients also treated with oral LLT. During follow-up, adherence to and persistence with evolocumab were high, with stable reduced levels of LDL-C during observation.

Physical fitness in male adolescents and atherosclerosis in middle age: a population-based cohort study.

OBJECTIVES: To examine the associations between physical fitness in male adolescents and coronary and carotid atherosclerosis in middle age. METHODS: This population-based cohort study linked physical fitness data from the Swedish Military Conscription Register during adolescence to atherosclerosis data from the Swedish CArdioPulmonary bioImage Study in middle age. Cardiorespiratory fitness was assessed using a maximal cycle-ergometer test, and knee extension muscular strength was evaluated through an isometric dynamometer. Coronary atherosclerosis was evaluated via Coronary Computed Tomography Angiography (CCTA) stenosis and Coronary Artery Calcium (CAC) scores, while carotid plaques were evaluated by ultrasound. The associations were analysed using multinomial logistic regression, adjusted (marginal) prevalences and restricted cubic splines. RESULTS: The analysis included 8986 male adolescents (mean age 18.3 years) with a mean follow-up of 38.2 years. Physical fitness showed a reversed J-shaped association with CCTA stenosis and CAC, but no consistent association was observed for carotid plaques. After adjustments, compared with adolescents in the lowest tertile of cardiorespiratory fitness and muscular strength, those in the highest tertile had 22% (OR 0.78; 95% CI 0.61 to 0.99) and 26% (OR 0.74; 95% CI 0.58 to 0.93) lower ORs for severe (≥50%) coronary stenosis, respectively. The highest physical fitness group (high cardiorespiratory fitness and muscular strength) had 33% (OR 0.67; 95% CI 0.52 to 0.87) lower OR for severe coronary stenosis compared with those with the lowest physical fitness. CONCLUSION: This study supports that a combination of high cardiorespiratory fitness and high muscular strength in adolescence is associated with lower coronary atherosclerosis, particularly severe coronary stenosis, almost 40 years later.

Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications.

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

Cohort profile: Data standards for cardiac rehabilitation structure and processes for the SWEDEHEART cardiac rehabilitation (SWEDEHEART-CR) registry.

Data standards for quality registries should be evidence-based and follow guideline recommendations. To optimally monitor quality of care, not only patient-level variables, but also centre-level variables need to be included. Here we describe the development of variables to audit the structure and processes in cardiac rehabilitation for patients after myocardial infarction, and the resulting data standards to be implemented in the Swedish quality registry for cardiac disease, SWEDEHEART. The methodology used for the development of international clinical data standards for the European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) was followed. Based on national guidelines for secondary prevention, candidate variables were prepared, after which a multiprofessional expert group on cardiac rehabilitation selected key variables and assured face validity. An external reference group had the role of peer reviewing, ascertaining content validity and test-retest reliability. The process has resulted in 30 data standards to be introduced into the SWEDEHEART cardiac rehabilitation registry and administered on centre-level biannually. The data standards include measures of human resources, centre requirements and process-based metrics. Including registry variables which audit centre-level structure and processes is essential to improve benchmarking and standardize monitoring of quality of care, covering both services provided and patient outcomes.

Prevalence of atherosclerosis in individuals with prediabetes and diabetes compared to normoglycaemic individuals-a Swedish population-based study.

BACKGROUND: Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased atherosclerotic burden in the coronary and carotid arteries. This study will estimate the cross-sectional prevalence of atherosclerosis in the coronary and carotid arteries in individuals with prediabetes and diabetes, compared with normoglycaemic individuals in a large population-based cohort. METHODS: The 30,154 study participants, 50-64 years, were categorized according to their fasting glycaemic status or self-reported data as normoglycaemic, prediabetes, and previously undetected or known diabetes. Prevalence of affected coronary artery segments, severity of stenosis and coronary artery calcium score (CACS) were determined by coronary computed tomography angiography. Total atherosclerotic burden was assessed in the 11 clinically most relevant segments using the Segment Involvement Score and as the presence of any coronary atherosclerosis. The presence of atherosclerotic plaque in the carotid arteries was determined by ultrasound examination. RESULTS: Study participants with prediabetes (n = 4804, 16.0%) or diabetes (n = 2282, 7.6%) had greater coronary artery plaque burden, more coronary stenosis and higher CACS than normoglycaemic participants (all, p < 0.01). Among male participants with diabetes 35.3% had CACS ≥ 100 compared to 16.1% among normoglycaemic participants. For women, the corresponding figures were 8.9% vs 6.1%. The prevalence of atherosclerosis in the coronary arteries was higher in participants with previously undetected diabetes than prediabetes, but lower than in patients with known diabetes. The prevalence of any plaque in the carotid arteries was higher in participants with prediabetes or diabetes than in normoglycaemic participants. CONCLUSIONS: In this large population-based cohort of currently asymptomatic people, the atherosclerotic burden in the coronary and carotid arteries increased with increasing degree of dysglycaemia. The finding that the atherosclerotic burden in the coronary arteries in the undetected diabetes category was midway between the prediabetes category and patients with known diabetes may have implications for screening strategies and tailored prevention interventions for people with dysglycaemia in the future.

High prevalence of interstitial lung abnormalities in middle-aged never-smokers.

Background: Interstitial lung abnormalities (ILA) are incidental findings on chest computed tomography (CT). These patterns can present at an early stage of fibrotic lung disease. Our aim was to estimate the prevalence of ILA in the Swedish population, in particular in never-smokers, and find out its association with demographics, comorbidities and symptoms. Methods: Participants were recruited to the Swedish CArdioPulmonary BioImage Study (SCAPIS), a population-based survey including men and women aged 50-64 years performed at six university hospitals in Sweden. CT scan, spirometry and questionnaires were performed. ILA were defined as cysts, ground-glass opacities, reticular abnormality, bronchiectasis and honeycombing. Findings: Out of 29 521 participants, 14 487 were never-smokers and 14 380 were men. In the whole population, 2870 (9.7%) had ILA of which 134 (0.5%) were fibrotic. In never-smokers, the prevalence was 7.9% of which 0.3% were fibrotic. In the whole population, age, smoking history, chronic bronchitis, cancer, coronary artery calcium score and high-sensitive C-reactive protein were associated with ILA. Both ILA and fibrotic ILA were associated with restrictive spirometric pattern and impaired diffusing capacity of the lung for carbon monoxide. However, individuals with ILA did not report more symptoms compared with individuals without ILA. Interpretation: ILA are common in a middle-aged Swedish population including never-smokers. ILA may be at risk of being underdiagnosed among never-smokers since they are not a target for screening.

Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors: JACC State-of-the-Art Review.

Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed.

Design and rationale of the myocardial infarction and new treatment with metformin study (MIMET) - Study protocol for a registry-based randomised clinical trial.

AIMS: To investigate if addition of metformin to standard care (life-style advice) reduces the occurrence of cardiovascular events and death after myocardial infarction (MI) in patients with newly detected prediabetes. METHODS: The Myocardial Infarction and new treatment with Metformin study (MIMET) is a large multicentre registry-based randomised clinical trial (R-RCT) within the SWEDEHEART registry platform expected to include 5160 patients with MI and newly detected prediabetes (identified with fasting blood glucose, HbA1c or 2-h glucose on oral glucose tolerance test) at ∼20 study sites in Sweden. Patients 18-80 years, without known diabetes and naïve to glucose lowering therapy, will be randomised 1:1 to open-label metformin therapy plus standard care or standard care alone. OUTCOMES: Patients will be followed for 2 years for the primary outcome new cardiovascular event (first of death, non-fatal MI, hospitalisation for heart failure or non-fatal stroke). Secondary endpoints include individual components of the primary endpoint, diabetes diagnosis, initiation of any glucose lowering therapy, cancer, and treatment safety. Events will be collected from national healthcare registries. CONCLUSIONS: The MIMET study will investigate if metformin is superior to standard care after myocardial infarction in preventing cardiovascular events in patients with prediabetes (Clinicaltrials.gov identifier: NCT05182970; EudraCT No: 2019-001487-30).

Association between high-sensitivity C-reactive protein and coronary atherosclerosis in a general middle-aged population.

Despite abundant knowledge about the relationship between inflammation and coronary atherosclerosis, it is still unknown whether systemic inflammation measured as high-sensitivity C-reactive protein (hsCRP) is associated with coronary atherosclerosis in a general population. This study aimed to examine the association between hsCRP and coronary computed tomography angiography (CCTA)-detected coronary atherosclerosis in a population-based cohort. Out of 30,154 randomly invited men and women aged 50 to 64 years in the Swedish Cardiopulmonary Bioimage Study (SCAPIS), 25,408 had a technically acceptable CCTA and analysed hsCRP. Coronary atherosclerosis was defined as presence of plaque of any degree in any of 18 coronary segments. HsCRP values were categorised in four groups. Compared with hsCRP below the detection limit, elevated hsCRP (≥ 2.3 mg/L) was weakly associated with any coronary atherosclerosis (OR 1.15, 95% CI 1.07-1.24), coronary diameter stenosis ≥ 50% (OR 1.27, 95% CI 1.09-1.47), ≥ 4 segments involved (OR 1.13, 95% CI 1.01-1.26 ) and severe atherosclerosis (OR 1.33, 95% CI 1.05-1.69) after adjustment for age, sex and traditional risk factors. The associations were attenuated after further adjustment for body mass index (BMI), although elevated hsCRP still associated with noncalcified plaques (OR 1.16, 95% CI 1.02-1.32), proposed to be more vulnerable. In conclusion, the additional value of hsCRP to traditional risk factors in detection of coronary atherosclerosis is low. The association to high-risk noncalcified plaques, although unlikely through a causal pathway, could explain the relationship between hsCRP and clinical coronary events in numerous studies.

Temporal trends in cardiovascular risk factors, lifestyle and secondary preventive medication for patients with myocardial infarction attending cardiac rehabilitation in Sweden 2006-2019: a registry-based cohort study.

OBJECTIVES: Registries have been highlighted as means to improve quality of care. Here, we describe temporal trends in risk factors, lifestyle and preventive medication for patients after myocardial infarction (MI) registered in the quality registry Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART). DESIGN: A registry-based cohort study. SETTING: All coronary care units and cardiac rehabilitation (CR) centres in Sweden. PARTICIPANTS: Patients attending a CR visit at 1-year post-MI 2006-2019 were included (n=81 363, 18-74 years, 74.7% men). OUTCOME MEASURES: Outcome measures at 1-year follow-up included blood pressure (BP) <140/90 mm Hg, low-density lipoprotein-cholesterol (LDL-C)<1.8 mmol/L, persistent smoking, overweight/obesity, central obesity, diabetes prevalence, inadequate physical activity, and prescription of secondary preventive medication. Descriptive statistics and testing for trends were applied. RESULTS: The proportion of patients attaining the targets for BP<140/90 mmHg increased from 65.2% (2006) to 86.0% (2019), and LDL-C<1.8 mmol/L from 29.8% (2006) to 66.9% (2019, p<0.0001 both). While smoking at the time of MI decreased (32.0% to 26.5%, p<0.0001), persistent smoking at 1 year was unchanged (42.8% to 43.2%, p=0.672) as was the prevalence of overweight/obesity (71.9% to 72.9%, p=0.559). Central obesity (50.5% to 57.0%), diabetes (18.2% to 27.2%) and patients reporting inadequate levels of physical activity (57.0% to 61.5%) increased (p<0.0001 for all). From 2007, >90.0% of patients were prescribed statins and approximately 98% antiplatelet and/or anticoagulant therapy. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription increased from 68.7% (2006) to 80.2% (2019, p<0.0001). CONCLUSIONS: While little change was observed for persistent smoking and overweight/obesity, large improvements were observed for LDL-C and BP target achievements and prescription of preventive medication for Swedish patients after MI 2006-2019. Compared with published results from patients with coronary artery disease in Europe during the same period, these improvements were considerably larger. Continuous auditing and open comparisons of CR outcomes might possibly explain some of the observed improvements and differences.

Elevated low-density lipoprotein cholesterol: An inverse marker of morbidity and mortality in patients with myocardial infarction.

BACKGROUND: The incidence of atherosclerotic cardiovascular disease increases with levels of low-density lipoprotein cholesterol (LDL-C). Yet, a paradox may exist where lower LDL-C levels at myocardial infarction (MI) are associated with poorer prognoses. OBJECTIVE: To assess the association between LDL-C levels at MI with risk factor burden and cause-specific outcomes. METHODS: Statin-naive patients hospitalized for a first MI and registered in SWEDEHEART were included. Data were linked to Swedish registers. Primary outcomes were all-cause mortality and nonfatal MI. Associations between LDL-C and outcomes were assessed using adjusted proportional hazards models. RESULTS: Among 63,168 patients (median age, 66 years), the median LDL-C level was 3.0 mmol/L (interquartile range 2.4-3.6). Patient age and comorbidities increased as LDL-C decreased. During a median follow-up of 4.5 years, 10,236 patients died, and 4973 had nonfatal MI. Patients with the highest LDL-C had a lower risk of mortality (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.71-0.80). The risk of hospitalization for pneumonia, hip fracture, chronic obstructive pulmonary disease, and new cancer diagnosis was lower with higher LDL-C (HR range, 0.40-0.81). Patients with the highest LDL-C had a greater risk of recurrent MI (HR 1.16; 95% CI 1.07-1.26). CONCLUSIONS: Patients with the highest LDL-C levels at MI had the lowest incidence of mortality and morbidity. This seems to reflect lower age at MI, less underlying morbidities, paired with the modifiability of LDL-C. However, supporting the causal association between LDL-C and ischemic heart disease, elevated LDL-C was simultaneously associated with an increased risk of nonfatal MI.

Prevalence of angina pectoris and association with coronary atherosclerosis in a general population.

OBJECTIVE: To assess the contemporary prevalence of, and factors associated with angina pectoris symptoms, and to examine the relationship to coronary atherosclerosis in a middle-aged, general population. METHODS: Data were based on the Swedish CArdioPulmonary bioImage Study (SCAPIS), in which 30 154 individuals were randomly recruited from the general population between 2013 and 2018. Participants that completed the Rose Angina Questionnaire were included and categorised as angina or no angina. Subjects with a valid coronary CT angiography (CCTA) were categorised by degree of coronary atherosclerosis; ≥50% obstruction (obstructive coronary atherosclerosis), <50% obstruction or any atheromatosis (non-obstructive coronary atherosclerosis) or none (no coronary atherosclerosis). RESULTS: The study population consisted of 28 974 questionnaire responders (median age 57.4 years, female 51.6%, hypertension 19.9%, hyperlipidaemia 7.9%, diabetes mellitus 3.7%), of which 1025 (3.5%) fulfilled the criteria of angina. Coronary atherosclerosis was more common in individuals having angina compared with those with no angina (n=24 602, obstructive coronary atherosclerosis 11.8% vs 5.4%, non-obstructive coronary atherosclerosis 38.9% vs 37.0%, no coronary atherosclerosis 49.4% vs 57.7%, all p<0.001). Factors independently associated with angina were birthplace outside of Sweden (OR 2.58 (95% CI 2.10 to 2.92)), low educational level (OR 1.41 (1.10 to 1.79)), unemployment (OR 1.51 (1.27 to 1.81)), poor economic status (OR 1.85 (1.38 to 2.47)), symptoms of depression (OR 1.63 (1.38 to 1.92)) and high degree of stress (OR 2.92 (1.80 to 4.73)). CONCLUSION: Angina pectoris symptoms are common (3.5%) among middle-aged individuals of the general population of Sweden, though with low association to obstructive coronary atherosclerosis. Sociodemographic and psychological factors are highly associated with angina symptoms, irrespective of degree of coronary atherosclerosis.

Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs: A Randomized Clinical Trial.

Importance: Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure-lowering therapies are available but the potential for maximizing benefit by personalized targeting of drug classes is unknown. Objective: To investigate and quantify the potential for targeting specific drugs to specific individuals to maximize blood pressure effects. Design, Setting, and Participants: A randomized, double-blind, repeated crossover trial in men and women with grade 1 hypertension at low risk for cardiovascular events at an outpatient research clinic in Sweden. Mixed-effects models were used to assess the extent to which individuals responded better to one treatment than another and to estimate the additional blood pressure lowering achievable by personalized treatment. Interventions: Each participant was scheduled for treatment in random order with 4 different classes of blood pressure-lowering drugs (lisinopril [angiotensin-converting enzyme inhibitor], candesartan [angiotensin-receptor blocker], hydrochlorothiazide [thiazide], and amlodipine [calcium channel blocker]), with repeated treatments for 2 classes. Main Outcomes and Measures: Ambulatory daytime systolic blood pressure, measured at the end of each treatment period. Results: There were 1468 completed treatment periods (median length, 56 days) recorded in 270 of the 280 randomized participants (54% men; mean age, 64 years). The blood pressure response to different treatments varied considerably between individuals (P < .001), specifically for the choices of lisinopril vs hydrochlorothiazide, lisinopril vs amlodipine, candesartan vs hydrochlorothiazide, and candesartan vs amlodipine. Large differences were excluded for the choices of lisinopril vs candesartan and hydrochlorothiazide vs amlodipine. On average, personalized treatment had the potential to provide an additional 4.4 mm Hg-lower systolic blood pressure. Conclusions and Relevance: These data reveal substantial heterogeneity in blood pressure response to drug therapy for hypertension, findings that may have implications for personalized therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02774460.

Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS.

BACKGROUND AND AIMS: Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change. METHODS: We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomography angiography (CCTA) and expressed as segment involvement score (SIS). RESULTS: The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p < 0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women. CONCLUSIONS: Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.

Association between atherogenic lipids and GnRH agonists for prostate cancer in men with T2DM: a nationwide, population-based cohort study in Sweden.

BACKGROUND: Gonadotropin-releasing hormone agonists (GnRH) used in prostate cancer (PCa) are associated with atherogenic dyslipidaemia. It can be assumed that GnRH need to be used with greater caution in men with type 2 diabetes mellitus (T2DM). This study investigated association of GnRH with atherogenic lipids (AL) in PCa men with T2DM. METHODS: Two cohorts including 38,311 men with 11 years follow-up based on Swedish national registers were defined (PCa-Exposure cohort and GnRH-Exposure cohort). Based on European guidelines on cardiovascular diseases (CVD), primary outcomes were defined as: 1.0 mmol/L increase in AL and lipid-lowering therapy (LLT) intensification. We used Cox proportional-hazards models and Kaplan-Meier curves to assess the association. RESULTS: There was an association between GnRH and increased AL (i.e., triglyceride, PCa-Exposure cohort: HR 1.77, 95% CI 1.48-2.10; GnRH-Exposure cohort: HR 1.88, 95% CI 1.38-2.57). There was also an association between PCa diagnosis and increased AL. In contrast, no association between LLT intensification and GnRH was found. CONCLUSION: In this large population-based study, men with T2DM on GnRH for PCa had an increased risk of increased atherogenic lipids. These results highlight the need to closely monitor lipids and to be ready to intensify lipid-lowering therapy in men with T2DM on GnRH for PCa.

Organizational and patient-level predictors for attaining key risk factor targets in cardiac rehabilitation after myocardial infarction: The Perfect-CR study.

BACKGROUND: Benefits of cardiac rehabilitation (CR) programme components on attaining risk factor targets post-myocardial infarction (MI) and their predictive strength relative to patient characteristics remain unclear. We aimed to identify organizational and patient-level predictors of risk factor target attainment at one-year post-MI. METHODS: In this observational study data on CR organization at 78 Swedish CR centres was collected and merged with patient-level registry data (n = 7549). Orthogonal partial least squares discriminant analysis identified predictors (Variables of Importance for the Projection (VIP) values >0.8) of attaining low-density lipoprotein-cholesterol (LDL-C) <1.8 mmol/L, blood pressure (BP) <140/90 mmHg and smoking abstinence. RESULTS: The strongest predictors (VIP [95% CI]) for attaining LDL-C and BP targets were offering psychosocial management (2.14 [1.78-2.50]; 2.45 [1.91-2.99]), having a psychologist in the CR team (1.62 [1.36-1.87]; 2.05 [1.67-2.44]), extended opening hours (2.13 [2.00-2.27]; 1.50 [0.91-2.10]), adequate facilities (1.54 [0.91-2.18]; 1.89 [1.38-2.40]), and having a medical director (1.70 [0.91-2.48]; 1.46 [1.04-1.88]). The strongest patient-level predictors of attaining LDL-C and/or BP targets were low baseline LDL-C (3.95 [3.39-4.51]) and having no history of hypertension (2.93 [2.60-3.26]), respectively, followed by exercise-based CR participation (1.38 [0.66-2.10]; 1.46 [1.14-1.78]). For smoking abstinence, the strongest organizational predictor was varenicline being prescribed by CR physicians (1.88 [0.95-2.80]) and patient-level predictors were participation in exercise-based CR (2.47 [2.07-2.88]) and group education (1.92 [1.43-2-42]), and no cardiovascular disease history (2.13 [1.78-2.48]). CONCLUSIONS: We identified multiple CR organizational and patient-level predictors of attaining risk factor targets post-MI. These results may influence the future design of comprehensive CR programmes.