Sex as a Biological Variable SABV Clinical Perspectives

Sex as a Biological Variable SABV: Clinical Perspectives Nanette K. Wenger, MD, MACC, MACP, FAHA Professor of Medicine (Cardiology) Emory University School of Medicine Consultant, Emory Heart & Vascular Center Founding Consultant, Emory Women’s Heart Center Atlanta, Georgia 1

DISCLOSURE STATEMENT Nanette Kass Wenger, M. D. Name of Commitment Name of Organization Research Grants/Contracts/Trial Astra. Zeneca, Boehringer Ingelheim, Steering Committee/Trial Data Department of Defense (Do. D), Duke Safety and Monitoring Board Clinical Research Institute, NHLBI, Zoll Medical Consultantship Amarin Pharma, Inc. , Astra. Zeneca, Janssen Pharmaceuticals 2

Sex as a Biological Variable In the Cardiology World • Substantial disparities in prevention, diagnostic methodology, recognition, management, clinical outcomes of CVD in women • Underrepresentation of women in CV clinical trials, data registries + lack of sex-specific analyses → constrained evidence based for clinical decision-making • Addition of sex-specific strategies, methods for study of CVD in women across lifespan → improved CVD clinical outcomes, ↓ disparities in women Wenger, J Am Coll Cardiol 67: 2186, 2016 3

Sex as a Biological Variables Related to Reproductive Health • Hormone levels • Oral contraceptive use • Hormonal fertility therapy • Pregnancy history and complications • Polycystic ovary syndrome • Measures of menopause • Menopausal hormone therapy 4

Sex as a Biological Variable Risk-Enhancing Factors • Diabetes mellitus • Autoimmune inflammatory disorders • Vasomotor dysfunction • Metabolic syndrome • High-risk race/ethnicity Arnett, J Am Coll Cardiol 74: e 177, 2019 5

Sex as a Biological Variable Psychosocial Variables • Depression • Stress • Abuse and domestic violence • Post-traumatic stress disorders • Aging 6

Sex as a Biological Variable Population Research • In addition to commonly collected demographic variables • Hormonal level status • Pregnancy-related disorders • Polycystic ovary syndrome • Depression • Abuse • Domestic violence • Post-traumatic stress disorders • Other social determinants of health 7

Sex as a Biological Variable Physiologic Research • Implications for outcomes and therapies – physiologic/pathophysiologic differences • Coronary microvascular dysfunction • Heart failure with preserved ejection fraction • Takotsubo cardiomyopathy • Adverse digoxin, QT prolonging medication mortality • Post-MI depression • Sex differences in pharmacology of CV drugs, chemotherapeutic agents with CV toxicity 8

Sex as a Biological Variable Clinical Trial Research • Cohort of women sufficiently powered to enable comparative analysis of primary trial outcome • How to analyze in a sex-specific fashion, how to analyze for interaction by sex 9

Sex as a Biological Variable Key Components to Improve Quality Cardiovascular Care for Women • Enhance quantity, quality evidence-based medicine by improving trial design, enrollment, retention of women subjects; improve result analysis and reporting; provide better incentives to perform research in women • Mandate changes in drug and device development and approval processes to develop better data for women • Incorporate specific recommendations for women into guidelines when data sufficient • Apply proven sex-based differences in risk stratification, diagnostic testing, drug usage and dosing in clinical care Wenger, J Am Coll Cardiol 67: 2186, 2016 10

Sex as a Biological Variable Resource • From Cardiovascular Network of Society for Women’s Health Research • Ouyang P, et al. Strategies and Methods to Study Sex-Specific Cardiovascular Health and Disease in Women: A Guide for Clinical Scientists. Biol Sex Differ 2016. doi. org/10. 1186/s 13293 -016 -0073 -y. 11