Table 2.
Future directions: proposed focus areas for future CV biomarker research and future clinical applications
| Proposed Focus Areas of Future CV Biomarker Research | |
|---|---|
| Recruitment & Enrollment | ● Increase recruitment and retention of female subjects in research studies including animal studies, human observational studies, and human clinical trials.144, 145 ● Consider sex-specific biomarker thresholds when biomarker cut-points are used as eligibility criteria for inclusion into research studies. ● Enroll specialized populations historically excluded from research studies, such as pregnant women.147 |
| Study Design | ● Adopt sex-specific thresholds when biomarkers are used as disease or endpoint surrogates in research studies. ● Consider single sex research studies and trials when further investigating a sex-specific signal.148 ● Interrogate sex-based differences using deep phenotyping approaches (e.g. large scale multi -omic studies, clonal hematopoiesis of indeterminate potential [CHIP], and deep sequencing). ● Investigate the role of X-linked genes and X chromosome inactivation in cardiovascular disease pathogenesis.149 ● Incorporate ascertainment of female-specific factors (e.g. menopause, adverse pregnancy outcomes, parity, menses, hormone therapy, oral contraceptive use, etc.) in research study design. Female-specific factors, however, should not be conflated with biologic sex differences.29 ● Identify and adjust for relevant confounders that influence the association between sex and biomarker. |
| Reporting | ● For all biomarker research studies, report sex-stratified analyses when possible.146 ● When reporting sex-specific results of biomarker analyses, include sex-specific plasma concentrations, cut-points, risk ratios, and prediction models.7, 146 |
| Future Clinical Applications | |
| Diagnosis | ● For biomarkers that display clinically relevant sex differences, consider sex-specific thresholds.146 |
| Therapy | ● Do not use underpowered sex-specific biomarker analyses as support for withholding evidence-based therapies for women.150 |