An interventional study of Arm 1: wCAR-CARE - Precision Prevention (Arm A) and Guideline-directed standard of care in Cardiovascular Diseases (CVD), Coronary Artery Disease and Atheroscleroses, sponsored by Women's Heart Austria. Not yet recruiting at 1 site in Austria. Open to female participants aged 40 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-30.
Sponsored by Women's Heart Austria · Not applicable, Interventional, and Prevention
The wCAR-Austria Study is a multicentre, prospective, interventional study evaluating a novel women-specific cardiovascular risk score (wCAR) in 800 women aged 40-65 years across Austria. The wCAR score integrates conventional and women-specific cardiovascular risk factors - including hypertensive disorders of pregnancy, gestational diabetes, premature ovarian insufficiency, autoimmune disease, and menopause stage - into a three-axis, multiplicatively modular architecture.
The study consists of two phases:
A randomised, controlled interventional substudy (wCAR-CARE, PROBE design) allocates all participants with wCAR ≥ 11 points 1:1 to a structured precision-prevention arm (arm A, including tailored lifestyle intervention, structured statin evaluation, and menopausal hormone therapy counselling within the "window of opportunity") versus guideline-directed standard of care (arm B) for 24 months.
Co-primary endpoints of Phase A are the area under the receiver-operating-characteristic curve (AUC) of the wCAR score for any coronary plaque (including non-calcified soft plaque on CCTA) in the intermediate stratum (E1a, n=100) and in the combined intermediate + high strata (E1b, n=200), analysed under a Bonferroni-Holm closed-testing procedure. The co-primary endpoint of wCAR-CARE is a composite risk-factor endpoint at month 24. The primary Phase B endpoint is time to first MACE.
Secondary endpoints include reclassification improvement of wCAR versus SCORE2 and PREVENT, convergence validation against age-adjusted NT-proBNP percentiles, and convergence validation against high-sensitivity troponin-T using sex-specific thresholds per the Fifth Universal Definition of Myocardial Infarction (Mills et al., 2026).
Background. Cardiovascular disease is the leading cause of death in women in Austria and worldwide, yet women are systematically under-recognised in cardiovascular risk assessment. Established risk scores such as SCORE2 and PREVENT do not adequately incorporate women-specific risk factors including hypertensive disorders of pregnancy, gestational diabetes, premature ovarian insufficiency (POI), autoimmune disease, elevated lipoprotein(a), or menopausal status. The women-specific cardiovascular risk score wCAR was developed to address this gap and integrates conventional and women-specific risk factors in a three-axis, multiplicatively modular architecture. In a monocentric pilot study of 107 women, wCAR showed an AUC of 0.66 for coronary artery calcium (CAC > 0) versus 0.52 for PREVENT-ASCVD.
Design. Multicentre, prospective, interventional two-phase study enrolling 800 women aged 40-65 across six Austrian centres.
Phase A - cross-sectional validation (12 months). All participants undergo clinical examination (blood pressure, height, weight, waist circumference - WHtR as primary adiposity indicator, BMI as secondary covariate), extended laboratory testing (lipid profile including Lp[a], HbA1c, fasting glucose for TyG-Index, creatinine/eGFR, hs-CRP, NT-proBNP with age- and sex-adjusted percentile referencing, hs-troponin-T with sex-specific thresholds per Fifth UDMI 2026, uric acid), validated questionnaires (Menopause Rating Scale, WHO-5, PHQ-9, Food Frequency Questionnaire), and calculation of wCAR, SCORE2, and PREVENT scores.
Coronary photon-counting CT angiography (CCTA) is performed in a stratified randomised subset of 250 participants:
This stratified sampling minimises cumulative radiation exposure while providing sufficient statistical power for the primary endpoints. Photon-counting CCTA delivers 1-3 mSv effective dose, comparable to natural annual background radiation. All images are centrally analysed by a core laboratory using CE-marked Siemens Healthineers software.
Phase B - prospective follow-up (3-5 years). Annual structured contact with all 800 participants; MACE ascertainment and adjudication by an independent endpoint committee blinded to treatment allocation.
wCAR-CARE interventional substudy. All Phase A participants with wCAR ≥ 11 points are randomised 1:1 to arm A (structured precision-prevention intervention including tailored lifestyle intervention with defined behaviour targets - 7,000 steps per day on at least 5 days per week, at least two structured strength-training sessions per week, at least 30 vegetable portions per week, added sugar less than 25 g per day, alcohol less than 100 g per week, 7-9 hours of sleep, non-smoking - structured statin evaluation, and MHT counselling within the "window of opportunity") versus arm B (guideline-directed standard of care). Intervention duration: 24 months. Co-primary endpoint E2: composite risk-factor endpoint at month 24 (achievement of at least one of: ≥ 1 wCAR class improvement, LDL-C reduction ≥ 15%, systolic blood pressure reduction ≥ 10 mmHg, TyG-Index reduction ≥ 10%, HbA1c reduction ≥ 0.3 percentage points in participants with pre-diabetes or T2DM).
EDC × Sugar substudy. In a stratified subsample of 200 participants, an exploratory analysis examines the association between endocrine-disrupting chemical exposure (urinary phthalate and bisphenol metabolites, optionally serum PFAS) and sugar consumption with coronary plaque status.
Statistical analysis. ROC analyses using DeLong's method for AUC comparisons; NRI and IDI with bootstrap confidence intervals; Cox proportional hazards regression; mixed models for longitudinal data. Convergence validation of wCAR against age-adjusted NT-proBNP percentiles and against sex-specific hs-troponin-T (Fifth UDMI 2026) across the entire cohort (n=800).
Ethics. Approved by the Ethics Committee of Carinthia (M2026-15, valid until 27 August 2027). Local ethics approvals for additional participating centres are pending.
Funding. Investigator-initiated trial funded through the Association's own resources and in-kind contributions from Siemens Healthcare Diagnostics GmbH (imaging equipment, analysis software, participant insurance). No public or private project funding in the form of monetary grants.
Exclusion Criteria:
• Intervention: Behavioural / Drug
Behavioral: Arm 1: wCAR-CARE - Precision Prevention (Arm A)
* Description: Guideline-directed cardiovascular prevention care delivered by the participant's regular treating physicians without structured additional intervention. Study-related follow-up contacts at M0, M3, M6, M12, M18, M24 for structured E2 component ascertainment. * Intervention: Standard of Care
Behavioral: Guideline-directed standard of care
• Description: Structured, phenotype-adapted precision prevention including tailored lifestyle intervention (defined behaviour targets: 7,000 steps/day on ≥ 5 days/week, ≥ 2 structured strength-training sessions/week, ≥ 30 vegetable portions/week, added sugar \< 25 g/day, alcohol \< 100 g/week, 7-9 hours of sleep, non-smoking), structured statin evaluation per ESC 2021 guidelines, and menopausal hormone therapy counselling per EMAS 2021 / NAMS 2022 within the "window of opportunity" (\< 10 years post-menopause). Follow-up contacts at M0, M1, M3, M6, M12, M18, M24.
Guideline-directed cardiovascular prevention care delivered by the participant's regular treating physicians without structured additional intervention. Participants continue their usual care pathway as clinically indicated by their treating physician, without protocol-mandated lifestyle coaching, structured statin evaluation, or menopausal hormone therapy counselling. Study-related follow-up contacts occur at Month 0, 3, 6, 12, 18, and 24 for structured ascertainment of the co-primary composite risk-factor endpoint (E2) and its components, without influencing clinical management decisions.
Area Under the ROC Curve (AUC) of the wCAR Score for Detecting Any Coronary Plaque on Photon-Counting CCTA in Women With Intermediate wCAR Risk (6-10 Points)
Discriminative performance of the women's cardiovascular risk (wCAR) total score for the presence of any coronary plaque (calcified, mixed or non-calcified) on photon-counting coronary computed tomography angiography (CCTA), with central core-lab image evaluation blinded to the wCAR score. Analysis population: study-mandated CCTA participants randomly sampled from the intermediate wCAR stratum (6-10 points, n=100). Reported as AUC with 95% confidence interval (ROC analysis, DeLong method; bootstrap confidence intervals). Co-primary with E1b; multiplicity controlled by Bonferroni-Holm closed testing. Protocol endpoint E1a.
Time frame: At baseline (Phase A cross-sectional assessment)
Time to First Major Adverse Cardiovascular Event (MACE: Cardiovascular Death, Non-Fatal Myocardial Infarction, Non-Fatal Stroke or Coronary Revascularisation) by wCAR Risk Category
Prognostic value of the wCAR score for MACE in the total cohort (n=800). MACE is defined as the first occurrence of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or coronary revascularisation, adjudicated by an independent endpoint committee blinded to participant identity using pseudonymised clinical records. Reported as hazard ratio with 95% CI for wCAR categories R3/R4 versus R1/R2 (Cox proportional hazards regression) and Harrell's C-statistic; Kaplan-Meier estimates by wCAR risk category. Protocol endpoint Phase B.
Time frame: Up to 5 years after baseline (minimum follow-up 3 years)
Percentage of Participants Achieving the Composite Risk-Factor Endpoint at Month 24 (wCAR Class Improvement or Reduction in LDL-C, Systolic Blood Pressure, TyG Index or HbA1c)
Binary composite endpoint, achieved if at least one of the following criteria is met at month 24 compared with baseline: (a) improvement by at least one wCAR risk class (e.g., very high to high); (b) LDL-C reduction of at least 15%; (c) systolic blood pressure reduction of at least 10 mmHg; (d) TyG index reduction of at least 10%; (e) HbA1c reduction of at least 0.3 percentage points (participants with prediabetes or type 2 diabetes only). Population: participants with wCAR score of 11 points or higher randomised 1:1 to Arm A (wCAR-guided precision prevention) or Arm B (guideline-based standard care). Endpoint assessment blinded to arm allocation (PROBE design). Reported as number and percentage of participants achieving the endpoint per arm; primary analysis by intention-to-treat using logistic regression adjusted for centre and wCAR stratum (risk difference and odds ratio with 95% CI). Protocol endpoint E2 (wCAR-CARE substudy).
Time frame: 24 months after randomisation
Area Under the ROC Curve (AUC) of the wCAR Score for Detecting Any Coronary Plaque on Photon-Counting CCTA in Women With Intermediate or High wCAR Risk (6-15 Points)
Discriminative performance of the women's cardiovascular risk (wCAR) total score for the presence of any coronary plaque (calcified, mixed or non-calcified) on photon-counting coronary computed tomography angiography (CCTA), with central core-lab image evaluation blinded to the wCAR score. Analysis population: study-mandated CCTA participants randomly sampled from the intermediate (6-10 points, n=100) and high (11-15 points, n=100) wCAR strata (combined n=200). Reported as AUC with 95% confidence interval (ROC analysis, DeLong method; bootstrap confidence intervals). Co-primary with E1a; multiplicity controlled by Bonferroni-Holm closed testing. Protocol endpoint E1b.
Time frame: At baseline (Phase A cross-sectional CCTA assessment)
This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.