wCAR-Austria: A Women-Specific Score to Assess Cardiovascular Risk in Women Aged 40 to 65

NCT07849127 | Not Yet Recruiting DMC

• 1 other identifier: M2026-15
• Study Type: interventional
• Target: 800
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Cardiovascular Diseases (CVD); Coronary Artery Disease; Atheroscleroses

Keywords

coronary artery calcium; NT-proBNP; menopause; sex-specific risk stratification; women's cardiovascular health; midlife; coronary artery calium; NT-proBNP; Menopause; sex-specific risk stratification; coronary artery calcium; women's cardiovascular health; midlife

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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).

  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.

  At baseline (Phase A cross-sectional CCTA assessment)

Study Arms (3)

Structured, phenotype-adapted precision prevention including tailored lifestyle intervention (define

EXPERIMENTAL

• Intervention: Behavioural / Drug

Behavioral: Arm 1: wCAR-CARE - Precision Prevention (Arm A)

Phase A cross-sectional characterisation without study-related intervention; participants with wCAR

NO INTERVENTION

wCAR-CARE - Guideline-Directed Standard of Care (Arm B)

ACTIVE COMPARATOR

* 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

Interventions

Arm 1: wCAR-CARE - Precision Prevention (Arm A) BEHAVIORAL

• 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.

Structured, phenotype-adapted precision prevention including tailored lifestyle intervention (define

Guideline-directed standard of care BEHAVIORAL

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.

wCAR-CARE - Guideline-Directed Standard of Care (Arm B)

Eligibility Criteria

• Age: 40 Years - 65 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women aged 40-65 years
• Pre-, peri-, or postmenopausal (including women with premature ovarian insufficiency and early menopause)
• Ability to provide written informed consent after thorough information

You may not qualify if:

• Known manifest atherosclerotic cardiovascular disease (prior myocardial infarction, coronary revascularisation, stroke)
• Pregnancy at the time of baseline visit
• eGFR \< 30 ml/min/1.73 m² (KDIGO G4-G5)
• Advanced oncological disease with life expectancy \< 3 years
• Known contrast agent allergy with anaphylactic reaction
• Inability to provide informed consent

Sponsors & Collaborators

• Women's Heart Austria: lead

Study Sites (1)

Anna Rab

Klagenfurt, 9020, Austria

Location

MeSH Terms

Conditions

Cardiovascular Diseases; Coronary Artery Disease; Atherosclerosis

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Central Study Contacts

Anna Rab, MD

CONTACT

+43 676 3610516; anna.rab@icloud.com

Steringer

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2026
• First Posted: September 30, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2034
• Last Updated: September 30, 2026

Record last verified: 2026-09

Locations

AU (1)