Background. Cardiovascular disease is the leading cause of mortality in women. Most
cardiovascular biomarker research, however, has been conducted in male-predominant
cohorts, and traditional risk-stratification tools systematically underestimate cardiovascular
burden in postmenopausal women.
Current work. We have completed a multi-omic characterization of subclinical
cardiovascular disease in a Spanish Mediterranean cohort of men and postmenopausal
women, combining proteomics (Olink Inflammation and Cardiovascular III panels) and
metabolomics. Our primary focus is the molecular signature of menopausal status and
postmenopausal cardiovascular risk. Our secondary focus is sex differences in circulating
protein and metabolite patterns. In both analyses, we assess the added value of these
signatures over traditional risk scores, with particular interest in features relevant to women
currently under-detected.
Why external data are needed. Our study lacks independent external validation. Replication
in cohorts with different geographic, dietary and metabolic backgrounds is needed to
determine whether the patterns observed in a Mediterranean population generalise to
other settings, and is also expected by high-impact cardiovascular journals.
Specific aims:
1. Test whether the proteomic and metabolomic signatures associated with
menopausal status and postmenopausal cardiovascular risk replicate in an
independent cohort.
2. Test whether the sex-stratified protein and metabolite patterns identified in our
cohort also replicate externally.
3. Assess the generalisability of these signatures across populations with distinct
cardiovascular risk profiles.
4. Validate, where the data allow, the most consistent proteomic and metabolomic
features from our analyses.
5. Use the requested data as a comparative reference for ongoing work, including a
complementary study based on capillary blood biomarkers in women.
Translational rationale. A validated, sex- and menopause-aware multi-omic layer would
complement current cardiovascular risk scores, particularly in postmenopausal women,
where existing tools perform suboptimally. External validation is a prerequisite to translate
these biomarkers into accessible clinical formats, such as capillary-blood-based screening for
primary prevention.
Analytical framework. Analyses are stratified by menopausal status and sex, using standard
biostatistical methods: differential expression and abundance adjusted for age and BMI,
association with available cardiovascular phenotypes, and discrimination metrics for
selected features. Adjustment for established cardiovascular confounders is applied
throughout. Proteomic and metabolomic layers are analysed both independently and in
integrated models.
Expected outcome. Cross-cohort confirmation of menopause- and sex-related proteomic
and metabolomic features linked to cardiovascular risk in women, supporting a clinically
useful, sex- and menopause-aware complement to traditional risk assessment.