Tomas Jernberg

Background: Socioeconomic status (SES) is a major risk factor for coronary heart disease, but the life‐course mechanisms and causal pathways remain poorly understood. Therefore, we investigated whether low childhood SES was associated with midlife coronary atherosclerosis and if any association could be explained by established risk factors in adulthood. Methods: This observational cohort study included 15 640 participants, aged 50 to 64 years, from the population‐based SCAPIS (Swedish Cardiopulmonary Bioimage Study) who underwent coronary computed tomography angiography. Coronary atherosclerosis was assessed by segment involvement score and coronary artery calcification score. Childhood SES was defined by parental disposable income at participant age 10 to 12 years retrieved from national registers. Associations between moderate–severe coronary atherosclerosis (segment involvement score ≥4 or coronary artery calcification >100) and childhood SES were estimated using multivariable logistic regression adjusting for adult lifestyle habits, adult SES, and traditional cardiovascular risk factors. Results: Participants in the lowest versus highest parental income quintile were more likely to have moderate–severe coronary atherosclerosis (segment involvement score ≥4; odds ratio [OR], 1.43 [95% CI, 1.20–1.71], P P 100. Conclusions: Low childhood SES was associated with moderate–severe coronary atherosclerosis in midlife only partially explained by established risk factors in adulthood. Our findings suggest that childhood SES is a social determinant of long‐term cardiovascular health that cannot be fully explained by established adult risk factors.

To evaluate the clinical implementation of long-read genome sequencing (lrGS) and establish the population reference resources needed to support its use in diagnostics, we integrate two complementary initiatives: Genome of Sweden (GoS), Sweden’s contribution to Genome of Europe (GoE), and the Genomic Medicine Sweden – Rare Diseases (GMS-RD) long-read sequencing pilot. The initial GoS release of 576 individuals provides population-scale maps of genetic and epigenetic variation. Among 485 GMS-RD probands, 161 (33.2%) receive a molecular diagnosis, with lrGS providing added clinical value in 40 (24.8%). As a first-line test, lrGS could have avoided at least 42 follow-up analyses and an additional testing cycle in 7.2% of probands, reducing costs and the burden on patients. By integrating population and clinical long-read genomics, Sweden establishes a national ecosystem for genomic research and clinical diagnostics. Our findings support the clinical implementation of lrGS and offer a scalable model for national collaboration.

Aims: Invasive management and intensive antithrombotic regimens have decreased ischemic risk after myocardial infarction (MI) at the cost of more bleeding. Of particular concern is upper gastrointestinal bleeding (UGIB), which is both common and preventable, yet not well characterized over time. We aimed to describe trends of UGIB hospitalization in relation to other bleeding and ischaemic outcomes and explore associated clinical factors. Methods and results: We included patients with acute MI who were enrolled in the SWEDEHEART registry, discharged alive on antithrombotic treatment between 1999 and 2020. Patients were followed for hospitalization for adverse events at 1 year. Trends were analysed in 2-year intervals for the overall cohort and subgroups. Standardized event rates for UGIB were calculated to assess the association of changes in demographics, comorbidities, in-hospital procedures, and pharmacotherapy. Bleeding hospitalizations increased from 2.4% to 4.5%, peaking at 4.7% in 2013–14, while 1 year major adverse cardiovascular and cerebral events decreased from 20.1% to 9.4%. The gastrointestinal tract was the most common bleeding site across all time intervals, with the majority of cases being UGIBs. Percutaneous coronary intervention, dual antiplatelet therapy, potent antiplatelet agents, and direct oral anticoagulants increased over time. Standardized event rates for UGIB suggest that changes in incidence were associated with evolving management strategies. Conclusion: Bleeding hospitalizations after MI increased until 2013–14, with UGIB the most common source, while ischaemic outcomes declined. These opposing trends were associated with the adoption of invasive management and intensified antithrombotic therapy. Routine tailoring of antithrombotic intensity and systematic gastroprotective measures should be considered as part of post-MI care.

Aims: Investigate sex-specific associations between exercise capacity and the risk of all-cause mortality and major adverse cardiovascular events (MACE) after myocardial infarction (MI), using nationwide real-world data. Methods and results: A prospective cohort study using the SWEDEHEART registry. Patients with an MI (2016–20) were included. Exercise capacity (maximal workload in W) was assessed using bicycle ergometer testing performed before exercise-based cardiac rehabilitation, 2–8 weeks after hospital discharge. Outcomes were all-cause mortality and MACE (MI, stroke, and cardiovascular death), identified in national cause-of-death and patient registries (2016–23). Associations between exercise capacity and outcomes were evaluated using adjusted Cox proportional hazard models. The functional form of the association was assessed using restricted cubic splines. There were 15 945 patients (78% men), with a median age of 64 (IQR: 56–70) years, included. During a median follow-up of 3.2 (2.3–4.3) years, 420 deaths and 948 MACE occurred. Higher exercise capacity (per 10-W increase) was associated with an 18% lower hazard of death in men and a 33% lower hazard in women, with a linear association for both sexes. Similarly, MACE hazard decreased by 8% in men and 18% in women per 10-W increase in exercise capacity, with a curvilinear association for men and a linear association for women. Conclusion: Higher exercise capacity measured by routine clinical exercise testing was associated with lower risk of all-cause mortality and recurrent MACE, with stronger associations in women. These findings support the use of exercise capacity testing to identify patients at the highest risk.

Aims: The ‘obesity paradox’ suggests lower cardiovascular risk at higher body mass index (BMI) after myocardial infarction (MI), but whether it reflects true protection or methodological bias is unclear. Methods and results: From the nationwide SWEDEHEART registry, patients hospitalized with MI from 2010 to 2021 were included. BMI at admission was modelled both as a continuous variable using restricted cubic splines and categorized into six groups, with 20 to <25 kg/m2 as reference. The primary outcome was major adverse cardiovascular events (MACE), a composite of recurrent MI, stroke, heart failure hospitalization, or cardiovascular death. Cox regression models estimated the BMI associated with lowest risk and HRs for categorical BMI groups. Adjustments included sociodemographic factors, smoking, and comorbidities not attributed to obesity. Mediation analyses assessed the roles of diabetes, hypertension, and prior cardiovascular disease. In 173 617 patients, the mean age was 71.0 years, 66.7% were men, and mean BMI was 27.1 kg/m2. During a median follow-up of 3.3 years, 36.5% experienced MACE. BMI had a U-shaped association with MACE, with the lowest risk at BMI 25.1 kg/m2. The adjusted HR (95% CI) for MACE was 0.99 (0.97–1.01) for overweight and 1.17 (1.14–1.20) for obesity class I, increasing across higher obesity classes. Excess risk was largely mediated by diabetes, hypertension, and prior cardiovascular disease. Conclusion: Obesity was associated with increased risk of MACE, partly mediated by obesity-related risk factors. The findings suggest that previously reported ‘obesity paradoxes’ may reflect differences in confounder adjustment, handling of mediators, patient populations, and survivor bias.

Background and Aims: The 2021 ESC guidelines on cardiovascular (CV) disease prevention recommend the SMART-REACH lifetime risk model to guide treatment decisions in patients with established atherosclerotic CV disease. The aim was to develop the SMART-REACH2 model for estimating lifetime risk of recurrent CV events and treatment benefits in patients with established atherosclerotic CV disease, with systematic recalibration to the four European and other global risk regions. Methods: SMART-REACH2 was derived in 8708 individuals aged 40–90 years with coronary, cerebrovascular, peripheral artery disease and/or abdominal aortic aneurysm from the UCC-SMART cohort. Sex-stratified, cause-specific Cox models for recurrent CV events and non-CV death were fitted using age as timescale and routinely available predictors. Recurrent CV events were defined as a composite of myocardial infarction, stroke, or CV death. Recalibration was based on representative cohorts per risk region. External validation was performed in 2 085 780 patients from 54 countries; model performance was assessed by calibration plots and Harrell's C-statistic. Results: In the derivation cohort, 2057 recurrent CV events occurred over a median follow-up of 8.5 years (25th–75th: 4.3–13.0). In external validation, 307 706 events occurred. The pooled C-statistic was 0.68 (95% confidence interval 0.66–0.69) and ranged from 0.66 (0.64–0.69) for European low-risk region up to 0.72 (0.66–0.78) for Latin America, with adequate calibration across risk regions. Performance was consistent across sexes and CV disease subtypes. Using SMART-REACH2, estimated potential gains in CV disease-free life expectancy for a 50-year-old example patient receiving intensified preventive treatment (15 mmHg systolic blood pressure and 1.0 mmol/L low-density lipoprotein cholesterol reduction) ranged from 2 years in the low-risk region to 4.4 years in the very-high-risk region. Conclusions: The updated SMART-REACH2 model accounts for geographical and sex-specific variations and allows estimation of short-term and lifetime risk of recurrent CV events and treatment benefits, facilitating shared decision-making as recommended by guidelines.

Background: Increased epicardial adipose tissue volume (EATV) is a potentially important risk marker for coronary artery disease (CAD) available from cardiac computed tomography (CT) images. Sex-differences and effects of age and body size on EATV have been insufficiently explored, and no reliable reference values exist. Consequently, EATV has yet to find its deserved use in clinical practice. Objectives: To define normal values by sex and age, the best normalization procedure for EATV to neutralize effects of body-size, explore the relationship between normalized EATV and cardiac risk, and propose a clinically meaningful cut-off. Methods: AI-based automated EATV data from the general population (n=25,155) and a clinical cohort (n=2,482) with suspected CAD was normalized to height, BSA and heart volumes. Correlation between EATV and EAT attenuation was tested with Spearman?s rank correlation and linear regression to find the optimal normalization. Normalized EATV was compared to high-risk by SCORE2 and obstructive CAD in the population cohort. A cut-off including 95% of cases with obstructive CAD was defined in the general population and tested in the clinical cohort. Results: EATV varied with sex and age across cohorts. Normalization of EATV to total heart volume (EATVh) was superior by all metrics and neutralized the effects of sex. High-risk by SCORE2 and the prevalence of obstructive CAD increased over quartiles of EATVh in the population cohort, and significantly higher EATVh was seen with obstructive CAD in both cohorts. A cut-off of 0.1 in EATVh had a negative predictive value for obstructive CAD of 97.1% in the general population and 88.9% in the clinical cohort. Conclusions: EATV varies considerably with sex, age and body size. Normalization to heart volume outperformed other procedures, and EATVh is a useful marker of obstructive CAD in both the general population and symptomatic patients.

Aims: Patients with acute myocardial infarction (MI) and atrial fibrillation (AF) present challenges in antithrombotic treatment. Effects of newer treatment strategies on outcomes remain uncertain. We assessed implementation of antithrombotic treatment and occurrence of cardiovascular (CV) events and major bleeding in patients with MI and AF. Methods and results: Nationwide data from SWEDEHEART and national health registries were used to identify 71 513 survivors of an acute MI with AF between 2000 and 2021. Changes in antithrombotic therapies over time in 2-year cohorts were analysed, and associations with 1-year outcomes were assessed. The outcomes were ischaemic stroke or systemic embolism, MI, major bleeding, CV mortality and all-cause mortality. Logistic regression was used to standardize for changes in patient characteristics and treatment over time. Oral anticoagulant use increased from 21% in 2000–2001 to 75% in 2020–2021, largely due to adoption of direct oral anticoagulants (DOACs) after the first DOAC approval in 2011, most often combined with a single antiplatelet. Over time, particularly in the last decade, 1-year risk of ischaemic stroke or systemic embolism declined from 6.0% to 2.1%, and CV mortality decreased from 19.8% to 10.5%. Major bleeding increased from 3.9% to 7.6% in 2014–2015, then declined to 6.4% in 2020–2021, simultaneously with adoption of single rather than dual antiplatelet therapy in combination with DOAC. Conclusion: Between 2000 and 2021, among patients with MI and AF, we observed reductions in 1-year risks of ischaemic stroke or systemic embolism and CV mortality, occurring during a period of increased prescription of oral anticoagulants, particularly DOACs. Key question and findings: Key Question Have recent clinical trial findings on antithrombotic therapy in patients with myocardial infarction and concomitant atrial fibrillation been implemented, and have they resulted in any improvement in 1-year outcomes? Key Finding In patients with myocardial infarction and atrial fibrillation, we observed substantial reductions in 1-year risks of ischaemic stroke or systemic embolism and cardiovascular mortality, associated with increased prescribing of oral anticoagulants, particularly DOACs.

Aims: This study aimed to estimate consequences of myocardial infarction (MI) on long-term outcomes and resource needs by comparing outcomes, healthcare resource use, and associated costs between first-time MI patients and matched controls. Methods and results: First-time MI patients from the nationwide SWEDEHEART registry, along with matched controls without prior MI (matched by sex, age, and region) 2012–2022, were included. Follow-up continued through November 2024 and assessed major adverse cardiovascular events (MACE), defined as cardiovascular death, MI, ischaemic stroke, acute limb ischaemia, or urgent arterial revascularization, as well as, healthcare resource use and associated costs. Among 118 810 first-time MI patients and 588 687 matched controls, followed for a median (IQR) of 6.6 (4.2–9.4) years, the 10-year MACE probability was 48.5% vs. 21.1% (HR [95% CI] 3.65 [3.61–3.69]), mainly due to higher rate of cardiovascular death (21.7% vs. 11.1%), MI (18.4% vs. 5.9%), and arterial revascularization (22.9% vs. 4.2%). Associations attenuated after adjustment for baseline characteristics but remained significant (MACE: adjHR[95%CI]: 3.18[3.15–3.22]). Cases had twice as many inpatient visits (0.65 vs. 0.32/patient year) and inpatient days (3.05 vs. 1.67/patient year), with nearly double the mean annual total costs (€7266 vs. €3934) when outpatient visits and medication also were included. Differences were greatest in the first year but persisted, especially among females and those with risk factors such as hypertension or diabetes. Conclusion: First-time MI patients have persistently higher risks of cardiovascular death, MI, and ischaemic stroke, along with greater healthcare use and costs, underscoring the need for effective prevention.