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INTRODUCTION: Early-life determinants of middle-age cardiovascular health are poorly understood. This study examines associations of body mass index (BMI) and physical fitness in male adolescents with cardiovascular health measured by the Life's Essential 8 score in middle age.

METHODS: A population-based cohort study linked BMI and physical fitness from the Swedish Military Conscription Register (men conscripted 1972-1987) to cardiovascular health from the Swedish CArdioPulmonary bioImage Study (SCAPIS, 2013-2018). In 2025, 8930 men (mean age 18.3 years) were analyzed after 38.2 years of follow-up. Physical fitness included cardiorespiratory fitness (maximal cycle-ergometer test), and muscular strength (isometric dynamometry of knee extension, elbow flexion, and handgrip). Cardiovascular health was evaluated using the American Heart Association Life's Essential 8 score (0-100; poor health <60). Associations were assessed using linear and binomial logistic regressions and restricted cubic splines.

RESULTS: BMI and cardiorespiratory fitness exhibited J-shaped and linear associations, respectively, with cardiovascular health. Compared to normal weight (BMI: 18.5-24.9 kg/m2), adjusted odds ratios (ORs) of having poor cardiovascular health for overweight (BMI: 25.0-29.9 kg/m2) and obesity (BMI ≥30 kg/m2) were OR 2.42 (95% confidence interval [CI] 2.00-2.92) and OR 5.38 (95% CI 2.99-9.70). No statistically significant associations were observed between muscular strength and cardiovascular health.

CONCLUSIONS: Obesity and low levels of cardiorespiratory fitness in male adolescents were associated with lower cardiovascular health in middle age, after nearly four decades of follow-up. Although further studies are needed, promotion of a healthy body weight and cardiorespiratory fitness in youth may be of importance for later cardiovascular health.

IMPORTANCE: Risk stratification strategies in primary prevention of coronary events lack precision.

OBJECTIVE: To determine whether prediction of first coronary events is improved by adding information on coronary atherosclerosis from coronary computed tomography angiography (CCTA) to a model using the pooled cohort equation (PCE) risk score tool and the coronary artery calcification score (CACS).

DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study including individuals aged 50 to 64 years randomly recruited from the general population and examined at 6 university hospitals in Sweden from 2013 to 2018, with a median follow-up of 7.8 years. A sample of 30 154 individuals underwent cardiopulmonary imaging, physical examinations, routine laboratory tests, questionnaires, and/or functional tests. This study included 24 791 individuals without previous cardiovascular disease for whom high-quality CCTA images were available. Events were followed up via registers until September 2024.

EXPOSURES: The information used from the CCTA images was the extent of coronary atherosclerosis (segment involvement score), presence of noncalcified atherosclerosis, and presence of coronary obstructive disease (stenosis ≥50%).

MAIN OUTCOMES AND MEASURES: The outcome was a composite of first occurrence of nonfatal myocardial infarction or death from coronary heart disease.

RESULTS: During follow-up, 304 coronary events occurred. Segment involvement scores of 3 to 4 and greater than 4 and presence of noncalcified atherosclerosis were associated with hazard ratios of 2.71 (95% CI, 1.34-5.44), 5.27 (95% CI, 2.50-11.07), and 1.66 (95% CI, 1.23-2.22), respectively. In a model based on the PCE and CACS, CCTA-derived data improved risk discrimination (C statistic improved from 0.764 to 0.779; P = .004) and risk reclassification (net reclassification improvement of 0.133 [95% CI, 0.031-0.165]), conferred a net correct upward reclassification of 14.2% in those with events and incorrectly classified 1.6% of participants not experiencing an event into a higher-risk category. Because of the low event rate in the cohort, reclassification mainly occurred in the group classified as at low risk (<5%) according to the PCE.

CONCLUSIONS AND RELEVANCE: Information on coronary atherosclerosis from CCTA modestly improved risk prediction beyond traditional risk factors and CACS in identifying individuals at risk of coronary events and in need of primary prevention.

Despite recommendations to use oral lipid-lowering therapies (LLT) in secondary prevention of atherosclerotic cardiovascular disease, numerous studies have shown substantial under-utilization. We assessed long-term persistence and dynamics of adherence to oral LLTs in patients after their first ever myocardial infarction (MI) in Sweden. A total of 83,407 patients with a MI (2010-2017) and who were dispensed an oral LLT were identified through Swedish nationwide health registries. After one, three and eight years of follow-up, persistence to lipid-lowering therapies was 90.3%, 71.1% and 50.8%, respectively. Adherence, quantified using the proportion of days covered (PDC), was a highly dynamic phenomenon with patients frequently moving between categories (high, medium, and low) of adherence. Adherence was high among persistent patients (> 70% had PDC ≥80%), but only 30% regained high adherence following non-persistence. Higher age, prescription from primary care, and higher income were associated with lower risk of non-persistence whereas higher comorbidity index, no prior statin use and concomitant use of platelet inhibitors were associated with increased risk. This study highlights the dynamic nature of adherence at the patient-level and that particular focus on adherence may be needed following non-persistence. Socioeconomic and clinical factors associated with non-persistence were identified, which in turn may help target measures to improve adherence in this high-risk patient group.

Background and aim 

Elevated lipoprotein(a) [Lp(a)] contributes to coronary artery disease (CAD). This study aimed to determine the effectiveness of cascade screening for elevated Lp(a) in patients with CAD.

Methods

Lp(a)-based cascade screening in first-degree relatives (FDR) and second-degree relatives (SDR) of index patients with CAD was performed. Index patients were recruited into pre-defined Lp(a) strata: low (<70 nmol/L), moderately elevated (70-169 nmol/L), and elevated (>= 170 nmol/L).<br /> Proportions of elevated Lp(a) in relatives were determined within each index stratum, and participation rate was evaluated.

Results

735 index patients (mean age 66.5 years, 76.9% male) participated, with 333, 149, and 253 in the low, moderately elevated, and elevated Lp(a) strata, respectively. Of 1120 invited relatives, 764 relatives (68.2%) were screened. Lp(a) was elevated in 30.2% of FDR and 19.4% of SDR of index patients with elevated Lp(a) compared with 6.2% in FDR (p < 0.001) and 5.6% in SDR (p = 0.007) of index patients with low Lp(a). The number (95%CI) of FDR needed to be screened to identify one individual with elevated Lp(a) was 3.3 (2.7-4.2) when the index patient had elevated Lp(a), compared with 16.1 (10.0-30.8) for low Lp(a) (p < 0.001). Corresponding numbers for SDR were 5.1 (3.4-8.8) and 17.8 (9.3-45.2) (p = 0.006).

Conclusions

Cascade screening for elevated Lp(a) in relatives of patients with CAD is feasible in a real-world setting. Screening was up to five times more effective when initiated from patients with elevated Lp(a) than with low.

Background: Studies comparing treatment strategies based on initiation timing-such as starting PCSK9 inhibitor (PCSK9i) therapy sooner versus later after a myocardial infarction (MI)-are prone to immortal time bias. Clone-censor-weight methods can address these issues and allow the researcher to emulate a trial in which patients are assigned to protocols dictating when PCSK9i is initiated. This study aimed to evaluate the comparability of patients in a clone-censor-weight setup who initiated a PCSK9i within 12 months post-MI versus non-initiators.

Methods: We included adult patients hospitalized for MI in Sweden (2015-2021) and followed them for 3 years. We considered two treatment strategies: initiating PCSK9i within 12 months versus not initiating PCSK9i during the same period. We applied the clone-censor-weight method to address immortal time bias and assessed remaining bias using covariate balance metrics and negative control outcomes.

Results: The primary study sample included 38 627 episodes of MI, with 561 (1.5%) initiating PCSK9i treatment within 12 months. These patients were younger, had higher baseline LDL-C levels, and were more frequently treated with ezetimibe during their post-MI follow-up compared to non-initiators. Although clone-censor-weight estimation was free of immortal time bias, it faced challenges in achieving adequate balance of covariates due to the high rates of censoring (relatively small number of people initiating a PCSK9i in the first year) and strong association between covariates and censoring. Truncation of weights provided more stable estimates but at the expense of some covariate imbalances.

Conclusions: The clone-censor-weight method is a promising approach that allows researchers to answer questions about the effect of treatment policies. But practical guidance is needed to address problems that arise from small, highly imbalanced groups, which is common with most newly introduced treatments.

Background and aims

Guidelines recommend measuring lipoprotein(a) [Lp(a)] at least once in all adults, but testing remains limited in clinical practice. We evaluated pragmatic strategies to maximize the immediate clinical impact of Lp(a) testing on the need of lipid-lowering treatment (LLT) in a primary prevention setting.

Methods

In 24,994 individuals aged 50-65 years from the population-based Swedish Cardiopulmonary BioImage Study (SCAPIS), we assessed: (i) whether self-reported data can identify individuals likely to have elevated Lp(a) (>= 50 mg/dL) and thus serve as a pre-screening tool, and (ii) how the clinical impact of Lp(a) testing-defined as eligibility for LLT according to ESC/EAS guidelines-varies by age and sex.

Results

Self-reported data poorly predicted elevated Lp(a) (ROC-AUC 0.54). Overall, incorporating Lp(a) levels increased eligibility for LLT from 11.3% to 19.6%. However, the clinical impact varied by age and sex. The number needed to screen (NNS) to identify one additional individual eligible for LLT was lowest in men aged 50-60 years (approximate to 10-15) and women >= 55 years (<20 at age 55 and < 10 at age 65), but substantially higher in younger women (NNS >50).

Conclusions

Elevated Lp(a) cannot be reliably identified using self-reported data. Incorporation of Lp(a) levels substantially increased eligibility for LLT. Targeting testing in men >= 50 years and women >= 55 years maximizes immediate clinical utility and may serve as a pragmatic interim strategy pending broader implementation of universal Lp(a) testing.

Purpose The primary aim of this study was to describe physical fitness in a large real-world cohort of patients entering exercise-based cardiac rehabilitation (EBCR) after first-time myocardial infarction (MI). The secondary aim was to compare the results with clinical reference values.

Methods This registry-based cohort study used data from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) post-MI registry between 2016 and 2019. Patients with first-time MI who underwent physiotherapist-led assessments of physical fitness at EBCR entry were included. Exercise capacity was evaluated by a symptom-limited cycle ergometer test and muscular endurance by a unilateral heel-rise test. Results were compared with age-stratified and sex-stratified clinical reference values. Reference values for exercise capacity were based on the Swedish Kalmar dataset, the national standard reference in Sweden since 2014, and reference values for heel-rise performance were based on a Swedish normative dataset of healthy adults.

Results A total of 15 105 patients (mean age 62.5±9.1 years, 78.4% men) were included. Exercise capacity (Watt max from the exercise test) was higher in men than women across age groups, and muscular endurance declined with age, with a steeper age-related decline in women’s heel rise performance. The mean exercise capacity of the study population corresponded to 64.7±27.4% of predicted values in men and 68.4±18.9% in women. Muscular endurance averaged 78.4%±51.0% of reference values in men and 61.7%±43.2% in women.

Conclusion At EBCR entry after a first-time MI, both exercise capacity and muscular endurance were substantially below age-specific and sex-specific reference values. These results underscore the importance of systematic baseline assessments and tailored rehabilitation interventions targeting both exercise capacity and muscular endurance.

Background

Accurate assessment of mortality, bleeding, and atherothrombotic risk in patients with cancer and acute coronary syndrome could inform novel personalised treatment strategies, but no standardised tools for this purpose exist. We aimed to develop and validate a clinically applicable risk score for mortality, bleeding, and ischaemic events in patients with cancer and acute coronary syndrome.

Methods

In this model development and validation study, we obtained data for 1 017 759 patients who presented with acute coronary syndrome in England, UK (n=815 170; 36 771 with cancer), Sweden (n=194 059; 10 262 with cancer), and Switzerland (n=8530; 203 with cancer) between Jan 1, 2004, and Aug 8, 2023. Machine learning models were developed to predict all-cause mortality, major bleeding events, and ischaemic events, defined as a composite of cardiovascular death, myocardial infarction, and ischaemic stroke, in patients with cancer and acute coronary syndrome from England in a competing risks framework with a prediction horizon of 6 months. Final models (the ONCO-ACS score) were externally validated in geographically distinct held out datasets from the English Midlands, Sweden, and Switzerland.

Findings

Patients with cancer and with acute coronary syndrome were characterised by high rates of mortality (cumulative incidence 27·8% [95% CI 27·3–28·3]), major bleeding (7·3% [7·0–7·5]), and ischaemic events (16·1% [15·7–16·4]) and had a distinct risk profile. The ONCO-ACS score was informed by a single set of variables: tumour type, time since cancer diagnosis, metastatic disease, age, haemoglobin, heart rate, estimated glomerular filtration rate, BMI, Killip class, cardiac arrest, and major bleed within 6 months. Accounting for traditional and cancer-related risk factors, ONCO-ACS showed a time-dependent area under the receiver operating characteristic curve (tAUC) at 6 months of 0·84 (0·83–0·85) for all-cause mortality, 0·70 (0·68–0·73) for major bleeding, and 0·79 (0·78–0·81) for ischaemic events on internal validation. On external validation, ONCO-ACS achieved similar performance for all-cause mortality (tAUC at 6 months 0·84 [0·82–0·85] for the English Midlands, 0·80 [0·79–0·82] for Sweden, and 0·83 [0·76–0·91] for Switzerland), major bleeding events (0·70 [0·67–0·74] for the English Midlands, 0·67 [0·65–0·70] for Sweden, and 0·74 [0·57–0·91] for Switzerland), and ischaemic events (0·76 [0·74–0·78] for the English Midlands, 0·70 [0·69–0·72] for Sweden, and 0·73 [0·61–0·86] for Switzerland). ONCO-ACS was well calibrated and decision curve analyses suggested favourable clinical utility. Applying ONCO-ACS to current guidelines suggests that most patients with cancer and acute coronary syndrome qualify for invasive management and long dual antiplatelet therapy using clopidogrel.

Interpretation

The ONCO-ACS score provides a validated practical tool for predicting mortality, bleeding, and ischaemic risk in patients with cancer and acute coronary syndrome. Combined assessment of competing outcome risks could facilitate balancing treatment benefits and harms.

Objectives: To describe the rationale, design and data collection procedures of the Swedish CArdioPulmonary bioImage Study (SCAPIS) re-examination, which, in its further scope, aims to quantify and explain the development of atherosclerosis, pathological cardiovascular ageing, longitudinal decline in lung function and the malignant transformation of pulmonary nodules among middle-aged Swedes in the longitudinal SCAPIS.

Methods: SCAPIS re-examination is a prospective observational study reassessing approximately 15,000 participants (50% of the original SCAPIS cohort) from six university hospitals. Participants were aged 55-75 years at follow-up, occurring a median of 8.1 years after the baseline investigation. Standardized protocols replicated baseline imaging and functional assessments, including questionnaires, clinical assessments and extensive computer tomography imaging.

Results: Interim analyses of the first 5000 participants (50% women; median age 65.5 [61.8-69.1] years) indicated an expected age-related increase in the prevalence and treatment of hypertension (from 22% to 37%) and diabetes (from 4% to 8%), together with a modest rise in central adiposity. Body mass index (median 26.6 kg/m2) and the proportion of obesity (22%) remained largely stable, whereas current smoking decreased from 7.5% to 3.4%. The observed patterns were consistent in men and women.

Conclusion: Here we present the rationale, design, methods and management of incidental findings in the SCAPIS re-examination. By integrating serial imaging, functional testing and biomarker profiling, the re-examination will furnish unprecedented insight into cardiopulmonary disease dynamics in an ageing population. These data will underpin personalized risk prediction and inform preventive strategies, while serving as a benchmark for future population-based imaging cohorts.

AIM: To analyze utilization and discontinuation of secondary preventive medications after acute myocardial infarction (MI).

METHODS: In separate analyses for each drug (statins, beta-blockers, aspirin, and renin-angiotensin-aldosterone system [RAAS] inhibitors), patients with a first-time MI (2006-2021) registered in the nationwide Swedish MI register SWEDEHEART, surviving >30 days, and discharged with a new prescription of the drug were included. Based on filled prescriptions, treatment initiation, discontinuation (defined as ≥90-day period of non-treatment after the end of previous prescriptions), reinitiation (restarting treatment after discontinuation) and the proportion of patients with ongoing treatment at various time points after the MI were assessed.

RESULTS: The analyses included 159,155 patients: 122,288 patients discharged with a statin, 79,968 with a RAAS inhibitor, 105,095 with a beta-blocker, and 127,463 with aspirin: 95-97% of the patients filled their first prescription for the drug. Treatment discontinuation ranged from 12-14% at 1 year, 27-37% at 5 years, and 36-51% at 12 years across drugs. Among those who discontinued treatment, the proportion who reinitiated treatment was 28-46% at 1 year, 42-62% at 5 years, and 47-67% at 12 years after discontinuation across drugs. The proportion of patients who were alive with ongoing treatment (regardless of previous discontinuation/reinitiation episodes) was 91-92% at 1 year, 79-82% at 5 years, and 74-79% at 12 years after the index MI.

CONCLUSIONS: Discontinuation of secondary preventive medications was common, but so was reinitiation. Thus, the proportion of patients with ongoing treatment was 91-92% at 1 year and 74-79% at 12 years after the MI. This study, which did not assess reasons for drug discontinuation, indicates that long-term utilization of secondary preventive medication after MI may not be as low as previously thought.