Daily Cardiology Research Analysis
Three high-impact cardiology studies advance prevention and intervention. A nationwide Danish-BMJ cohort quantifies arterial thrombotic risk across modern hormonal contraceptives, showing no excess risk with levonorgestrel IUDs. A Circulation registry study links anabolic-androgenic steroid use to markedly elevated risks of MI, cardiomyopathy, and heart failure. A large JACC registry shows that transcatheter tricuspid edge-to-edge repair improves survival only in intermediate disease stages, inf
Summary
Three high-impact cardiology studies advance prevention and intervention. A nationwide Danish-BMJ cohort quantifies arterial thrombotic risk across modern hormonal contraceptives, showing no excess risk with levonorgestrel IUDs. A Circulation registry study links anabolic-androgenic steroid use to markedly elevated risks of MI, cardiomyopathy, and heart failure. A large JACC registry shows that transcatheter tricuspid edge-to-edge repair improves survival only in intermediate disease stages, informing patient selection.
Research Themes
- Hormonal contraception and arterial thrombotic risk
- Anabolic-androgenic steroids and cardiovascular disease
- Stage-specific outcomes after transcatheter tricuspid repair
Selected Articles
1. Stroke and myocardial infarction with contemporary hormonal contraception: real-world, nationwide, prospective cohort study.
In a nationwide cohort of 2,025,691 Danish women, combined oral contraceptives doubled the risk of ischemic stroke and MI, while progestin-only pills modestly increased risk. Levonorgestrel-releasing IUDs showed no increased arterial risk. Absolute event rates were low but clinically relevant for risk–benefit counseling.
Impact: This is one of the largest real-world evaluations quantifying arterial thrombotic risks across contemporary contraceptives, isolating a method (levonorgestrel IUD) without excess risk.
Clinical Implications: Use levonorgestrel IUDs when minimizing arterial risk is paramount; discuss small but meaningful arterial risks with combined oral or progestin-only pills, particularly in patients with vascular risk factors.
Key Findings
- Combined oral contraception doubled adjusted rates of ischemic stroke and myocardial infarction versus non-use (aIRR ≈2.0).
- Progestin-only pills increased risk modestly (stroke aIRR 1.6; MI aIRR 1.5).
- Levonorgestrel-releasing intrauterine devices showed no increased risk (stroke aIRR 1.1; MI aIRR 1.1).
Methodological Strengths
- Nationwide, prospective registry design with >22 million person-years of follow-up.
- Detailed method-specific risk estimates with standardized rates and adjusted rate ratios.
Limitations
- Observational design with potential residual confounding (e.g., smoking, blood pressure).
- Generalizability may vary outside Denmark; absolute risks remain low.
Future Directions: Evaluate individualized contraceptive risk calculators integrating vascular risk factors; assess mechanisms and differential progestins’ arterial effects; extend to diverse populations.
OBJECTIVE: To evaluate the association between contemporary hormonal contraceptive use and the risk of incident ischaemic stroke and myocardial infarction. DESIGN: Real-world, nationwide, prospective cohort study. SETTING: Denmark, by use of national registries. PARTICIPANTS: All women aged 15-49 years residing in Denmark between 1996 and 2021, with no history of arterial or venous thrombosis, antipsychotics use, cancer, thrombophilia, liver disease, kidney disease, polycystic ovary syndrome, endometriosis, infertility treatment, hormone therapy use, oophorectomy, and hysterectomy. MAIN OUTCOME MEASURES: First time diagnosis of ischaemic stroke or myocardial infarction at discharge. RESULTS: Among 2 025 691 women followed up for 22 209 697 person years, 4730 ischaemic strokes and 2072 myocardial infarctions occurred. Standardised ischaemic stroke rate per 100 000 person years were 18 (95% confidence interval 18 to 19) for no use, 39 (36 to 42) for combined oral contraception, 33 (25 to 44) for progestin-only pills, and 23 (17 to 29) for intrauterine device. Standardised myocardial infarction rate per 100 000 person years were 8 (8 to 9) for no use, 18 (16 to 20) for combined oral contraception, 13 (8 to 19) for progestin-only pills, and 11 (7 to 16) for intrauterine device. Compared with no use, current use of combined oral contraception was associated with an adjusted rate ratio of 2.0 (1.9 to 2.2) for ischaemic stroke and 2.0 (1.7 to 2.2) for myocardial infarction. These corresponded to standardised rate differences of 21 (18 to 24) extra ischaemic strokes and 10 (7 to 12) extra myocardial infarctions per 100 000 person years. Compared with no use, current use of progestin-only pills was associated with an adjusted rate ratio of 1.6 (95% CI 1.3 to 2.0) for ischaemic stroke and 1.5 (1.1 to 2.1) for myocardial infarction, equating to 15 (6 to 24) extra ischaemic strokes and four (-1 to 9) extra myocardial infarctions per 100 000 person years. Increased arterial thrombotic risk was also observed with use of the combined vaginal ring (adjusted incidence rate ratio of 2.4 (1.5 to 3.7) for ischaemic stroke and 3.8 (2.0 to 7.3) for myocardial infarction), patch (3.4 (1.3 to 9.1) and no myocardial infarctions), and progestin-only implant (2.1 (1.2 to 3.8) and ≤3 myocardial infarctions), whereas no increased risk was observed with progestin-only intrauterine device (1.1 (1.0 to 1.3) for ischaemic stroke and 1.1 (0.9 to 1.3) for myocardial infarction). CONCLUSIONS: Use of contemporary oestrogen-progestin and progestin-only contraceptives was associated with an increased risk of ischaemic stroke and, in some cases, myocardial infarction except for the levonorgestrel-releasing intrauterine device, which was not associated with either. Although absolute risks were low, clinicians should include the potential risk of arterial thrombosis in their assessment of the benefits and risks when prescribing a hormonal contraceptive method.
2. Cardiovascular Disease in Anabolic Androgenic Steroid Users.
In a matched nationwide cohort, anabolic-androgenic steroid users had markedly elevated risks of MI, revascularization, VTE, arrhythmias, cardiomyopathy (aHR ~9), and heart failure over ~11 years. These robust associations quantify the cardiovascular burden of AAS use.
Impact: Provides definitive population-level evidence linking AAS use to a spectrum of major cardiovascular outcomes, informing public health, sports medicine, and clinical screening strategies.
Clinical Implications: Clinicians should screen for AAS exposure in young/middle-aged men with cardiomyopathy, arrhythmias, or premature ASCVD; counsel cessation and monitor cardiac function.
Key Findings
- AAS users had a threefold higher risk of acute MI (aHR 3.00) and nearly threefold higher need for PCI/CABG (aHR 2.95).
- Cardiomyopathy risk was profoundly increased (aHR 8.90), with elevated risks of HF (aHR 3.63) and arrhythmias (aHR 2.26).
- Venous thromboembolism risk was also higher (aHR 2.42), underscoring systemic thromboinflammatory effects.
Methodological Strengths
- Nationwide registry linkage with long-term follow-up and large matched control cohort (1:50).
- Comprehensive endpoint ascertainment across multiple cardiovascular outcomes.
Limitations
- Selection limited to sanctioned users; exposure misclassification (dose/duration) possible.
- Residual confounding cannot be excluded; stroke/cardiac arrest underpowered.
Future Directions: Prospective mechanistic studies on AAS cardiotoxicity, dose-response, and reversibility; evaluate screening pathways and cessation interventions to reduce CVD burden.
BACKGROUND: Use of anabolic androgenic steroids (AASs) is associated with increased mortality, and case reports have suggested that some of these deaths are due to cardiovascular disease. However, the epidemiology of cardiovascular disease in AAS users is still relatively unexplored. This study aimed to measure the incidence of cardiovascular disease in male AAS users and to compare these rates with those of a cohort from the general population matched by age and sex. METHODS: Men sanctioned in an antidoping program for AAS use in Danish fitness centers between 2006 and 2018 were included and matched for age and sex with 50 times as many controls from the general Danish population. The cohort was followed until June 30, 2023. Using the nationwide registries, we obtained information on admissions, prescriptions, educational length, and occupational status for both the AAS users and controls. This study investigated the incidence of acute myocardial infarction, percutaneous coronary intervention, or coronary artery bypass graft, venous thromboembolism, ischemic stroke, arrhythmia, cardiomyopathy, heart failure, and cardiac arrest during the follow-up period. RESULTS: During an average of 11 years of follow-up, AAS users (n=1189) demonstrated a significantly higher incidence of several cardiovascular events compared with controls (n=59 450). Correspondingly, AASs were associated with an increased risk of acute myocardial infarction (adjusted hazard ratio [aHR] 3.00 [95% CI, 1.67-5.39]), percutaneous coronary intervention or coronary artery bypass graft (aHR 2.95 [95% CI, 1.68-5.18]), venous thromboembolism (aHR 2.42 [95% CI, 1.54-3.80]), arrhythmias (aHR 2.26 [95% CI, 1.53-3.32]), cardiomyopathy (aHR 8.90 [95% CI, 4.99-15.88]), and heart failure (aHR 3.63 [95% CI, 2.01-6.55]). Due to the limited number of ischemic stroke and cardiac arrest cases among AAS users, these outcomes were not reportable. CONCLUSIONS: AAS use is associated with a substantially increased risk of cardiovascular disease in a large cohort with a long follow-up period.
3. Tricuspid Regurgitation Disease Stages and Treatment Outcomes After Transcatheter Tricuspid Valve Repair.
In EuroTR (n=1,885), T-TEER conferred a 1-year survival benefit only in intermediate-stage TR (HR 0.73), with no benefit in early or advanced stages. Stage stratification by biventricular function, renal function, and natriuretic peptides guided selection and was externally validated.
Impact: Provides actionable, stage-based selection criteria to optimize T-TEER benefits, potentially reconciling trial-neutral survival results by timing of intervention.
Clinical Implications: Prioritize T-TEER referral for intermediate-stage TR based on integrated ventricular-renal-biomarker staging; reconsider intervention in very early or advanced stages where survival benefit is not demonstrated.
Key Findings
- Among 1,885 TR patients, only the intermediate-stage subgroup had lower 1-year mortality with T-TEER versus conservative therapy (HR 0.73).
- No mortality difference with T-TEER in early-stage (HR 0.78) or advanced-stage (HR 1.06) disease.
- Disease staging incorporated LV/RV function, renal function, and natriuretic peptides and was externally validated.
Methodological Strengths
- Large prospective multicenter registry with comparative conservative cohort.
- Externally validated staging framework and clinically relevant endpoint (1-year mortality).
Limitations
- Nonrandomized design with potential selection/residual confounding.
- Staging thresholds and generalizability beyond registry settings require further validation.
Future Directions: Prospective randomized trials stratified by disease stage; refine thresholds and integrate right ventricular-pulmonary coupling metrics to optimize timing.
BACKGROUND: Tricuspid transcatheter edge-to-edge repair (T-TEER) has emerged as a treatment option for patients with severe tricuspid regurgitation (TR). However, randomized trials have not shown a survival benefit, possibly because of the inclusion of patients in an early or too advanced disease stage. OBJECTIVES: The authors sought to investigate the association between disease stage and outcomes following T-TEER. METHODS: In total, 1,885 patients with significant TR were analyzed, including 585 conservatively treated individuals and 1,300 patients who received T-TEER. Patients were evaluated as part of the prospective EuroTR (European Registry of Transcatheter Repair for Tricuspid Regurgitation) registry and grouped into early, intermediate, and advanced disease stage. Disease stage was based on left and right ventricular function, renal function, and natriuretic peptide levels. The stratification was validated in an external cohort. The primary endpoint was 1-year mortality. RESULTS: Overall, 395 patients (21% [395/1,885]) were categorized as early, 1,173 patients (62% [1,173/1,885]) as intermediate, and 317 patients (17% [317/1,885]) as advanced disease stage. In patients with early and advanced disease, mortality did not differ between interventional and conservative treatment (early-stage HR: 0.78; 95% CI: 0.34-1.80; P = 0.54; advanced stage HR: 1.06; 95% CI: 0.71-1.60; P = 0.78). However, mortality was significantly lower in patients undergoing percutaneous treatment with intermediate disease stage (HR: 0.73; 95% CI: 0.52-0.99; P = 0.03). CONCLUSIONS: Compared to medically treated controls, T-TEER was associated with 1-year survival at intermediate stage disease but not at early or advanced disease stages. The timing of T-TEER with regard to disease stages might be crucial to optimize treatment benefits.