Chronic Airflow Limitation, Emphysema and Impaired Diffusing Capacity in Relation to Smoking Habits in a Swedish Middle-Aged Population.

RATIONALE: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure. OBJECTIVES: To study the prevalence of CAL, emphysema and impaired DLCO in relation to smoking and respiratory symptoms in a middle-aged population. METHODS: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DLCO, high-resolution computed tomography (HRCT) and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced expiratory volume (FEV1/FVC)<0.7. RESULTS: The overall prevalence was for CAL 8.8%, for impaired DLCO (DLCO

Associations between psychosocial burden and prognostic biomarkers in patients with chronic coronary syndrome: a STABILITY substudy.

AIM: To investigate associations between psychosocial burden and biomarkers reflecting pathophysiological pathways in patients with chronic coronary syndrome. METHODS: Psychosocial (PS) factors were collected from self-assessed questionnaires and biomarkers representing inflammation (high-sensitivity [hs]-C-reactive protein [CRP], interleukin-6 [IL-6], lipoprotein-associated phospholipase A2 [Lp-PLA2]) and cardiac injury/stress (hs-troponin T [hs-TnT], N-terminal pro-B type natriuretic peptide [NT-proBNP]) were measured in 12,492 patients with chronic coronary syndrome in the STABILITY trial. Associations between level of each psychosocial factor (never-rarely (reference), sometimes, often-always) and biomarkers were evaluated using linear models with adjusted geometric mean ratios (GMR). A score comprising four factors ('feeling down', 'loss of interest', financial stress', 'living alone') that previously demonstrated association with cardiovascular (CV) outcome was created, and categorized into three levels: low, moderate and high PS burden. Associations between PS score and biomarkers were evaluated similarly. RESULTS: Greater PS burden was significantly associated with a gradual increase in inflammatory biomarkers (GMR [95% CI] for moderate vs low PS burden; and high vs low PS burden): hs-CRP (1.09 [1.04-1.14]; 1.12 [1.06-1.17]), IL-6 (1.05 [1.02-1.07]; 1.08 [1.05-1.11]), LpPLA2 (1.01 [1.00 - 1.02]; 1.02 [1.01-1.04]) and cardiac biomarkers hs-TnT (1.03 [1.01-1.06]; 1.06 [1.03-1.09]) and NT-proBNP (1.09 [1.04-1.13]; 1.21 [1.15-1.27]). CONCLUSIONS: In patients with chronic coronary syndrome, greater psychosocial burden was associated with increased levels of inflammatory and cardiac biomarkers. While this observational study does not establish causal nature of these associations, the findings suggest inflammation and cardiac injury/stress as plausible pathways linking psychosocial burden to an elevated CV risk, that needs to be further explored.

We studied the association between psychosocial factors and various circulating protein biomarkers, reflecting different underlying mechanisms of disease, with the hope of shedding light on the link between psychological factors like depression and stress and the risk of cardiovascular events in patients with chronic coronary syndrome. We analysed data from the global large-scale STABILITY trial, which included more than 12,000 patients with chronic coronary syndrome. Participants filled out a questionnaire assessing their level of psychosocial burden, including experiences of depressive symptoms, stress at home, at work and financial stress. Additionally, blood samples were collected in which biomarkers (NTproBNP, high-sensitive Troponin-T, Interleukin-6, CRP and LpPLA2) were analysed. Our findings revealed a significant association between higher psychosocial burden and increased concentrations of biomarkers in patients with chronic coronary syndrome. These biomarkers reflect both inflammatory processes and cardiac damage or dysfunction which could be potential disease mechanisms explaining the increased risk of adverse events in patients with chronic coronary syndrome and high psychosocial burden. Although causal relationships cannot be determined from this study, the findings suggest that inflammation and cardiac stress may play crucial roles in linking psychosocial factors to heightened cardiovascular risk in this patient population. These insights could pave the way for better understanding and managing cardiovascular health in individuals with chronic coronary syndrome, offering hope for more targeted interventions in the future.

Self-Report Tool for Identification of Individuals With Coronary Atherosclerosis: The Swedish CardioPulmonary BioImage Study.

BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis. METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly. CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.

Life's Essential 8 is inversely associated with high-sensitivity C-reactive protein.

Life's Essential 8 (LE8) is a score that includes modifiable risk factors for cardiovascular disease. Four health behaviors (diet, physical activity, nicotine exposure and sleep health) and four health factors (non-HDL cholesterol, blood glucose, blood pressure and body mass index) are included. These modifiable risk factors promote inflammation, and inflammation is one of the biological mechanisms of cardiovascular disease development. Thus, we examined the relationship between cardiovascular health measured by LE8 and low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) in the cross-sectional population-based Swedish CArdioPulmonary bioImage Study (SCAPIS). The study consisted of 28,010 participants between 50 and 64 years (51.5% women, mean age 57.5 years). All individual LE8 components were assigned a score between 0 (unhealthy) and 100 (healthy) points, and a global score was calculated. The association between LE8 scores and high-risk hs-CRP (defined as > 3.0 mg/L) was analyzed using adjusted logistic regression with spline analyses. There was a strong, dose response and inverse association between LE8 scores and levels of hs-CRP. Thus, those with a low LE8 score (= 50.0 points) had 5.8 higher (95% confidence interval [CI] 5.2-6.4) odds ratio (OR) of having high hs-CRP as compared to those with a high LE8 score (= 80.0 points). In conclusion, our findings show strong inverse associations between LE8 scores and levels of hs-CRP.

The Nurses' Role in the Cardiac Rehabilitation Team: Data From the Perfect-CR Study.

BACKGROUND: Nurses constitute a central profession in the cardiac rehabilitation (CR) team delivering comprehensive CR to individuals with cardiovascular disease. We aimed to identify specific components reflecting the nurses' role in the CR team associated with attainment of risk factor targets post myocardial infarction. METHODS: Center-level data (n = 78) was used from the Perfect-CR study, in which structure and processes applied at CR centers in Sweden (including details on the nurses' role) were surveyed. Patient-level data (n = 6755) was retrieved from the SWEDEHEART registry. Associations between structure/processes and target achievement for systolic blood pressure (BP) (<140 mm Hg) and low-density lipoprotein cholesterol (LDL-C, <1.8 mmol/L) at 1 year post myocardial infarction were assessed using logistic regression. RESULTS: Structure and processes reflecting nurses' autonomy and role in the CR team associated with patients achieving systolic BP and/or LDL-C targets included the following: nurses having treatment algorithms to adjust BP medication (odds ratio [95% confidence interval]: systolic BP, 1.22 [1.05-1.42]; LDL-C, 1.17 [1.03-1.34]) and lipid-lowering medication (systolic BP, 1.14 [1.00-1.29]; LDL-C, 1.17 [1.05-1.30]), patients having the same nurse throughout follow-up (systolic BP, 1.07 [1.03-1.11]; LDL-C, 1.10 [1.06-1.14]), number of follow-up hours with a nurse (systolic BP, 1.13 [1.07-1.19]), having regular case rounds to discuss patient cases during follow-up (LDL-C, 1.22 [1.09-1.35]), and nurses having training in counseling methods (systolic BP, 1.06 [1.03-1.10]). CONCLUSION: Components reflecting CR nurses' autonomy and role in the team are of importance for patients attaining risk factor targets post myocardial infarction. The results could provide guidance for optimizing nurses' competence and responsibilities within the CR team to improve patient care.

Eligibility for lipid-lowering therapy when applying systemic coronary risk estimation 2 (SCORE2) according to guidelines on apparently healthy middle-aged individuals.

AIMS: To estimate the proportion eligible for lipid-lowering therapy (LLT) when using the systemic coronary risk estimation 2 (SCORE2) on apparently healthy individuals. METHODS: Individuals aged 50-64 years were randomly invited to the Swedish cardiopulmonary bioimage study (SCAPIS, n=30,154). Participants with previous atherosclerotic cardiovascular disease (CVD), diabetes mellitus, or chronic kidney disease were excluded. The 10-year risk of CVD was estimated using the SCORE2 equation and the multicell chart. Eligibility for LLT was estimated according to the 2021 European Society of Cardiology CVD prevention guidelines. Presence of coronary atherosclerosis was determined using coronary computed tomography angiography (CCTA). RESULTS: Among 26,570 apparently healthy individuals, 32% had high, and 4% had very-high 10-year CVD risk, according to the SCORE2 equation. Among high and very-high risk individuals, 99% had LDL-C levels above guideline goals making 35% of the total population eligible for LLT. Of those eligible, undergoing imaging, 38% had no signs of coronary atherosclerosis according to CCTA. Using the SCORE2 chart, 52% of the population were eligible for LLT, of which 44% had no signs of coronary atherosclerosis. In those with high or very-high risk, ongoing LLT was reported in 7% and another 11% received LLT within six months after study participation. CONCLUSIONS: Nearly all apparently healthy individuals with high and very-high CVD risk, or 35% of the total population, were eligible for LLT according to guidelines, and a large proportion had no signs of atherosclerosis. Compared with the SCORE2 equation, the SCORE2 chart resulted in more individuals being eligible for LLT.

KEY QUESTIONS: What proportion of an apparently healthy middle-aged population would be eligible for lipid-lowering therapy (LLT) according to the 2021 ESC guidelines when using SCORE2? What proportion of those eligible for LLT have atherosclerosis according to coronary imaging? KEY FINDING: According to the guidelines, nearly all individuals categorized as high and very-high risk according to the SCORE2 equation, or 35% of the total population, were eligible for LLT, of which 38% had no signs of coronary atherosclerosis. These proportions increased when the SCORE2 multicell chart was used. TAKE-HOME MESSAGE: Implementing SCORE2 and the ESC guidelines would result in more than one in three apparently healthy middle-aged individuals being eligible for LLT. A significant proportion would have no signs of coronary atherosclerosis.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.