Claes Held

BACKGROUND Myocardial infarction (MI) among adults younger than 55 years is an important public health challenge. Compared with older patients, younger MI survivors experience greater psychological distress and face specific challenges related to working life, family responsibilities, and adaptation to life after MI. Cardiac distress has emerged as a clinically important patient-reported outcome encompassing the emotional, cognitive, behavioral, and social burden of heart disease, yet few psychological interventions have been developed for younger people with MI. The stress-recovery intervention Behavioral Recovery Intervention for General Health and Thriving (BRIGHT), developed for prolonged stress related to everyday stressors, has been adapted for remote delivery to younger people with MI who experience cardiac distress (MI-BRIGHT). Recruitment, adherence, and retention are recognized challenges in trials of remote psychological interventions. OBJECTIVE This study aims to evaluate the feasibility and acceptability of MI-BRIGHT and of the planned trial procedures, using prespecified progression criteria, before a full-scale randomized controlled trial. METHODS This is a prospective, single-arm feasibility study aiming to enroll approximately 30 people who had an MI before the age of 55 years within the previous 12 months and who report cardiac distress. Participants are identified through the Swedish quality registry SWEDEHEART and recruited nationwide via a digital mailbox. MI-BRIGHT comprises 6 steps described in a printed workbook, supported by 6 online sessions with a personal supervisor and digital educational videos, delivered over 13 weeks. Feasibility outcomes are recruitment, acceptability, adherence, retention, adverse events, program credibility, and program satisfaction. Exploratory outcomes include cardiac distress, recovery experiences, health-related quality of life, depression, anxiety, work ability, and health care use. RESULTS The study is funded by the Swedish Research Council (grant 2023-02220) and was approved by the Swedish Ethical Review Authority (2025-07157-01). Recruitment began on August 28, 2026, and was completed on October 9, 2026, by which time 30 participants had provided informed consent. Data collection is expected to be completed in 2027, and the results are expected to be published in 2027. CONCLUSIONS This feasibility study will provide evidence on the practicality and acceptability of MI-BRIGHT for younger MI survivors with cardiac distress and on recruitment, intervention delivery, adherence, and outcome assessment. The findings will inform refinement of the intervention and study procedures and determine whether progression to a fully powered randomized controlled trial is warranted. CLINICALTRIAL ClinicalTrials.gov NCT07706816; https://clinicaltrials.gov/study/NCT07706816

Aims: Apolipoprotein B (apoB)-containing lipoproteins contribute heterogeneously to atherosclerosis. While apoB particles are major determinants of plaque burden, Lp(a) has been linked to plaque inflammation and instability. We investigated the associations of non-Lp(a) apoB, Lp(a), and their relative balance with coronary plaque burden and vulnerability. Methods and results: Among 854 patients with recent myocardial infarction enrolled in the PROSPECT II near-infrared spectroscopy–intravascular ultrasound (NIRS-IVUS) study, total apoB was converted to nmol/L and non-Lp(a) apoB calculated by subtracting Lp(a) in nmol/L. The non-Lp(a) apoB/Lp(a) ratio was used to characterize the relative predominance of these lipoprotein classes. Higher non-Lp(a) apoB was independently associated with greater plaque burden [plaque percentage volume; β = 0.19, 95% confidence interval (CI) 0.05–0.33; P = 0.009], but not with lipid core burden index. In contrast, lower non-Lp(a) apoB/Lp(a) ratio tertile were associated with higher odds of plaque burden ≥70% [odds ratio (OR) 1.47, 95% CI 1.04–2.07; P = 0.029] and the composite vulnerability endpoint of plaque burden ≥70% and maxLCBI4mm ≥324.7 (OR 1.62, 95% CI 1.12–2.33; P = 0.011). In an exploratory external cohort from the CASABLANCA study, lower ratios identified an Lp(a)- and oxidized phospholipid-enriched phenotype and were associated with higher unadjusted cardiovascular risk. Conclusion: Non-Lp(a) apoB and Lp(a) demonstrate distinct associations with coronary plaque burden and vulnerability. Differentiating Lp(a)-associated from non-Lp(a)-associated apoB particle pools provides complementary information on coronary plaque phenotype, and the non-Lp(a) apoB/Lp(a) ratio summarizes their relative predominance. Clinical Trial Information: PROSPECT II- https://ClinicalTrial.gov Identifier: NCT02171065 CASABLANCA- https://ClinicalTrial.gov Identifier: NCT00842868. One-sentence summary: In patients with recent heart attack, the balance between conventional cholesterol-carrying particles and lipoprotein(a) identifies different types of coronary artery disease phenotypes and may help explain why some plaques are more likely to become dangerous. Key findings: Conventional apoB-containing lipoproteins (primarily LDL-related particles) were associated with greater overall coronary plaque burden, whereas a relative predominance of lipoprotein(a) was associated with plaques that had features linked to a higher risk of future cardiovascular events. A simple ratio comparing non-lipoprotein(a) apoB particles with lipoprotein(a) particles summarized these distinct biological processes and may provide complementary information for future studies evaluating cardiovascular risk and therapies targeting lipoprotein(a).

BACKGROUND Cardiovascular (CV) events such as a myocardial infarction with non-obstructive coronary arteries (MINOCA) or takotsubo syndrome (TS) are associated with heightened levels of stress and anxiety. There are currently no established treatment guidelines for these conditions, but emerging research indicates that internet-based cognitive behavior therapy (ICBT) is effective in the short-term for reducing these symptoms. However, the long-term stability of effects is unknown, as well as the importance of timing of the intervention. OBJECTIVE This paper aims to investigate the stability of effects achieved by ICBT after MINOCA or TS for common mental health symptoms, as well as to compare the difference in effect between early and late initiation of the intervention. METHODS This was a parallel, multicenter, randomized controlled trial of ICBT on symptoms of stress and anxiety. The ICBT intervention was a guided, 7–9-week written program, where completion of at least 5/9 steps was considered a minimum dose. Participants were included if they reported elevated stress (Perceived stress scale, 14 items [PSS-14] > 24) or anxiety (Hospital anxiety and depression scale, anxiety subscale [HADS-A] > 7) and were randomized (1:1) to either early intervention group (EIG; immediately after randomization) or late intervention group (LIG; 10-12 weeks after randomization). Mental health outcomes were assessed using PSS-14, HADS, cardiac anxiety questionnaire [CAQ], and impact of event scale [IES]. Outcome data was collected at three follow-up time points: 10-12 (1), 20-22 (2), and 50-52 (3) weeks after randomization. This paper reports results from follow-up 2 and 3. Data was analyzed by the intention-to-treat principle, using linear mixed models, assuming data missing at random. RESULTS Eighty-eight participants were randomized (EIG: 45; LIG: 43). The response rate at follow-up 2 was 81% and at follow-up 3 was 73%. Eighty-seven percent completed the minimum dose in the EIG, and 51% in the LIG. Intervention effects achieved in the EIG at follow-up 1 remained stable over time. The average trend was lower levels of stress and anxiety in the EIG compared with the LIG, but no differences were statistically significant. Regarding symptoms of post-traumatic stress, the EIG reported significantly lower levels than the LIG, at follow-up 2 (-2.32, 95% CI: -4.42, -0.21, p=0.03). CONCLUSIONS Short-term effects achieved by ICBT after MINOCA or TS for symptoms of stress and anxiety were stable over time and there was little evidence suggesting a difference in effect between early or late initiation of treatment. However, patients in the EIG completed the treatment to a higher degree and reported superior treatment effects on symptoms of post-traumatic stress. These novel findings are important for informing care after a MINOCA or TS, but more research is needed before firm conclusions can be drawn. CLINICALTRIAL clinicaltrials.gov NCT04178434 INTERNATIONAL REGISTERED REPORT RR2-https://doi.org/10.1186/s13063-022-06530-3

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.

How individual components of cardiac rehabilitation (CR) programmes predict attainment of risk factor targets after 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 1-year post-MI. Organizational structure and processes followed at all 78 CR centres in Sweden were surveyed and merged with patient-level registry data (n = 6755). Predictors of attaining low-density lipoprotein-cholesterol (LDL-C) and blood pressure (BP) targets and smoking abstinence were identified using orthogonal partial least squares discriminant analysis, generating variables of importance for the projection (VIP) values. Variables with VIP > 0.8 were considered meaningful. The strongest predictors for attaining LDL-C and BP targets included availability of psychosocial management, medication adjustment protocols for nurses, continuity in nurse-patient contact, extended opening hours and adequate facilities, and having a medical director at the CR centre. The strongest patient-level predictors of attaining LDL-C and/or BP targets included low baseline LDL-C and having no history of hypertension, respectively, and the patient having participated in exercise-based CR. For smoking abstinence, the strongest organizational predictors were availability of psychosocial management, having a medical director, prescribing nicotine replacement therapy and varenicline, and self-reported team spirit. Patient-level predictors included having participated in exercise-based CR and group education. We identified multiple CR organizational predictors of attaining key risk factor targets after MI. These results may influence the future design of comprehensive CR programmes.

Background: Patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) or Takotsubo syndrome (TS) often suffer from poor mental health and low quality‐of‐life post event, with no current evidence‐based treatments available. This study aimed to evaluate the effects of an internet‐delivered cognitive behavioral therapy program on stress and anxiety symptoms in patients diagnosed with myocardial infarction with nonobstructive coronary arteries or TS. Methods: A parallel, multicenter, randomized controlled trial with a wait‐list control group was conducted. Patients with elevated symptoms of stress or anxiety were included (the 14‐item perceived stress scale ≥25 or hospital anxiety and depression scale, anxiety subscale ≥8). The primary outcome was normalized stress and anxiety levels 10 to 12 weeks after randomization. Secondary outcomes included normalized stress and anxiety separately and symptoms as continuous measures. Results: A total of 88 patients were randomized (treatment: 45, control: 43). The treatment group showed a greater, though not statistically significant proportion of normalized patients (odds ratio, 2.37 [95% CI, 0.88–6.38], P =0.09). Secondary analyses indicated treatment effects on anxiety normalization and on symptoms as continuous measures (effect sizes: d=0.44–0.67). There was also an interaction between treatment and diagnosis (TS versus non‐TS), favoring a treatment effect in TS patients ( P =0.016). Conclusions: The patient‐tailored internet‐delivered cognitive behavioral therapy program reduced stress and anxiety symptoms in patients with myocardial infarction with nonobstructive coronary arteries or TS and normalized anxiety symptoms in a greater proportion of treated patients than controls. Exploratory analyses indicated that patients with TS may experience greater benefit from the internet‐delivered cognitive behavioral therapy intervention, but this warrants further research.

BACKGROUND: Clinical guidelines recommend different revascularization strategies for nonculprit lesions in patients with ST-segment–elevation myocardial infarction (STEMI) versus non-STEMI (NSTEMI). Whether the prevalence of untreated high-risk vulnerable plaques differs in STEMI and NSTEMI and affects their outcomes is unknown. METHODS: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree II), a multicenter, prospective natural history study, patients with recent myocardial infarction underwent 3-vessel coronary angiography with coregistered near-infrared spectroscopy and intravascular ultrasound after successful percutaneous coronary intervention of obstructive lesions from 2014 through 2017. Two-feature high-risk plaques were defined as those with both plaque burden ≥70% and maximum lipid core burden index over any 4-mm segment ≥324.7. The primary end point was major adverse cardiovascular events arising from untreated nonculprit lesions during a median 3.7-year follow-up. RESULTS: Of 898 patients, 199 (22.2%) with 849 nonculprit lesions had STEMI and 699 (77.8%) with 2784 nonculprit lesions had NSTEMI. By intravascular ultrasound, the median nonculprit lesion length was 17.4 mm (interquartile range, 16.3–18.5) in STEMI and 17.7 mm (interquartile range, 17.1–18.4) in NSTEMI ( P =0.63), and the median minimal lumen area was 5.5 mm ² (interquartile range, 5.3–5.7 mm ² ) in STEMI and 5.5 mm ² (interquartile range, 5.3–5.6 mm ² ) in NSTEMI ( P =0.99). At the lesion level, the prevalence of 2-feature high-risk nonobstructive nonculprit plaques was slightly higher in patients with STEMI than in patients with NSTEMI (12.8% versus 10.1%; P =0.03). At the patient level, however, the prevalence of 2-feature high-risk plaques was similar in STEMI versus NSTEMI (38.8% versus 32.7%; P =0.11). The prevalence of patients with 1 or more lesions meeting at least 1 high-risk plaque criterion was also similar (plaque burden ≥70%, 63.3% versus 57.8% [ P =0.16]; maximum lipid core burden index over any 4-mm segment ≥324.7, 63.3% versus 57.6% [ P =0.15]). The 4-year rates of nonculprit lesion–related major adverse cardiovascular events were similar in STEMI versus NSTEMI (8.6% versus 7.8%; hazard ratio, 1.02 [95% CI, 0.57–1.81]; P =0.95), as were the rates of all major adverse cardiovascular events (14.2% versus 13.0%; hazard ratio, 1.06 [95% CI, 0.68–1.64]; P =0.80). CONCLUSIONS: In the PROSPECT II study, the per-patient prevalence of high-risk vulnerable plaques was comparable in STEMI versus NSTEMI, as was the overall long-term incidence of nonculprit lesion–related and all major adverse cardiovascular events. These results support a similar revascularization strategy for nonculprit lesions in patients with STEMI or NSTEMI after culprit lesion management. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02171065.

Aims: Myocardial infarction with non-obstructive coronary arteries (MINOCA) and takotsubo syndrome (TS) are both characterized by lack of significant coronary artery stenoses and a higher prevalence of mental health disorders preceding the event. Currently, little is known about their pathological aetiologies and subsequent treatment plans, giving cause for concern among those affected. The objective of this review is to provide a comprehensive overview of mental health status and quality of life (QoL) in MINOCA and TS patients after the acute event, compared with both cardiac and non-cardiac populations, and over time. Methods and results: A systematic search was conducted via Cochrane Library, CINAHL, PsycINFO, PubMed, ASSIA, Web of Science, Scopus, and Embase from inception to May 2024. The review was registered in PROSPERO and methods, and results were reported in accordance with the PRISMA guidelines. Quality assessment and risk of bias were evaluated using the Newcastle–Ottawa Scale for cross-sectional and cohort studies. Sample sizes ranged from 13 to 5322 participants. The risk of bias was high in 18/28, medium in 7/28, and low in 3/28 studies. Across the symptoms assessed, MINOCA and TS patients reported worse mental health status or QoL than non-cardiac groups in 10/13 studies and cardiac groups in 10/20 studies. Investigating change over time, 1/5 studies found deteriorating mental health status, 3/5 reported improved mental health status or QoL, and 1/5 reported no change in MINOCA and TS patients. Conclusion: Patients with MINOCA or TS seem to have worse mental health status and QoL after the acute event than non-cardiac individuals, but it is yet difficult to conclude whether mental distress and QoL are equal or worse compared with coronary heart disease patients. There is no convincing evidence that mental health status or QoL of MINOCA and TS patients naturally improve over time after the acute event. Among the studies evaluated, risk of bias was high. More high-quality studies are needed, investigating mental health status and QoL among MINOCA and TS patients.