Sex Bias Is Increasingly Prevalent in Preclinical Cardiovascular Research: Implications for Translational Medicine and Health Equity for Women

Ramirez, F. Daniel; Motazedian, Pouya; Jung, Richard G.; Santo, Pietro Di; MacDonald, Zachary; Simard, Trevor; Clancy, Aisling A.; Russo, Juan; Welch, Vivian; Wells, George; Hibbert, Benjamin

doi:10.1161/circulationaha.116.026668

Cited by 63 publications

(51 citation statements)

References 5 publications

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“…As previously described, 29 of 28 636 articles screened, 3396 met inclusion criteria and were analyzed (Figure 1). Inter-rater agreement for study inclusion before resolution was 94.5% (κ=0.72; 95% CI, 0.70–0.73).…”

Section: Resultsmentioning

confidence: 99%

“…29 After excluding studies that did not report the sex of the animals used, significant differences were noted in the proportions including animals of both sexes when stratified by CVD of interest ( P <0.0001, range 2.4%–34.7%) and by animal model used ( P <0.0001, range 6.7%–26.9%; Online Figure).…”

Section: Resultsmentioning

confidence: 99%

“…Over the past 10 years, there have been no significant changes in the proportions of studies reporting blinding or randomization (inclusion of both sexes has been reported previously 29 ). There has been a significant increase in the proportion reporting a priori sample size estimations ( P trend <0.0001), although it remains below 7% (Figure 5).…”

Section: Resultsmentioning

confidence: 99%

“…We report that, overall, these design elements are rarely implemented in studies published in leading peer-reviewed cardiovascular journals, paralleling the previously reported prevalence of sex bias. 29 Furthermore, apart from a modest increase in the proportion of studies reporting sample size calculations, there has been no improvement in these practices over the past decade, although stroke research may be a notable exception. Finally, analyses of citation counts suggest that crucial methodological aspects of preclinical studies may be overlooked by cardiovascular researchers, affording potentially biased research comparable influence on scientific research efforts as methodologically more robust studies.…”

Section: Discussionmentioning

confidence: 99%

“…As previously described, 29 all preclinical cardiovascular studies published in AHA journals with archives spanning at least 10 years were reviewed. Five journals met these criteria: Circulation ; Circulation Research ; Hypertension ; Stroke ; and Arteriosclerosis, Thrombosis, and Vascular Biology ( ATVB ).…”

Section: Methodsmentioning

confidence: 99%

See 4 more Smart Citations

Methodological Rigor in Preclinical Cardiovascular Studies

Ramirez¹,

Motazedian²,

Jung³

et al. 2017

Circulation Research

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125

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Methodological Rigor in Preclinical Cardiovascular Studies

Ramirez¹,

Motazedian²,

Jung³

et al. 2017

Circulation Research

Self Cite

125

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Organ‐on‐a‐Chip Systems for Women's Health Applications

Nawroth

Rogal

Weiß

et al. 2017

Adv Healthcare Materials

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Biomedical research, for a long time, has paid little attention to the influence of sex in many areas of study, ranging from molecular and cellular biology to animal models and clinical studies on human subjects. Many studies solely rely on male cells/tissues/animals/humans, although there are profound differences in male and female physiology, which can significantly impact disease mechanisms, toxicity of compounds, and efficacy of pharmaceuticals. In vitro systems have been traditionally very limited in their capacity to recapitulate female-specific physiology and anatomy such as dynamic sex-hormone levels and the complex interdependencies of female reproductive tract organs. However, the advent of microphysiological organ-on-a-chip systems, which attempt to recreate the 3D structure and function of human organs, now gives researchers the opportunity to integrate cells and tissues from a variety of individuals. Moreover, adding a dynamic flow environment allows mimicking endocrine signaling during the menstrual cycle and pregnancy, as well as providing a controlled microfluidic environment for pharmacokinetic modeling. This review gives an introduction into preclinical and clinical research on women's health and discusses where organ-on-a-chip systems are already utilized or have the potential to deliver new insights and enable entirely new types of studies.

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Sex‐specific in‐hospital outcomes of transcatheter aortic valve replacement with third generation transcatheter heart valves

Simard

Alqahtani

Hibbert

et al. 2021

Cathet Cardio Intervent

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Background Sex‐based differences in transcatheter aortic valve replacement (TAVR) outcomes have been previously documented. However, whether these differences persist with contemporary third generation transcatheter heart valves (THVs) is unknown. Methods We utilized Vizient's clinical database/resource manager (CDB/RM™) to identify patients who underwent TAVR between January 1, 2018 and March 31, 2020 to compare in‐hospital outcomes between males and females. The primary endpoint was in‐hospital mortality. Secondary endpoints included key in‐hospital complications, length of stay, discharge disposition, and cost. Unadjusted, propensity‐score matched and risk‐adjusted analyses of outcomes were performed. Results During the study period, 44,280 patients (24,842 males, 19,438 females) underwent TAVR. The primary endpoint of in‐hospital mortality was higher in females than in males (1.6 vs. 1.1% p < .001) in unadjusted analysis and persisted following propensity matching (1.6 vs. 0.9%, p < .001) and multivariable logistic regression with various risk‐adjustment models. In the most comprehensive model adjusting for age, race, and clinical comorbidities, female sex was associated with 34% greater odds of in‐hospital death (95% CI 20–50%, p < .001). Unadjusted and risk‐adjusted rates of post‐TAVR stroke, vascular complication, and blood transfusion were higher in females. Moreover, females demonstrated longer hospitalizations, higher costs and reduced rates of independent discharge home. Conclusion Sex‐based differences in TAVR in‐hospital outcomes persist in contemporary practice with third generation transcatheter heart valves. Further research is needed to assess the reasons for these observed disparities and to identify effective mitigation strategies.

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Sex Bias Is Increasingly Prevalent in Preclinical Cardiovascular Research: Implications for Translational Medicine and Health Equity for Women

Cited by 63 publications

References 5 publications

Methodological Rigor in Preclinical Cardiovascular Studies

Methodological Rigor in Preclinical Cardiovascular Studies

Organ‐on‐a‐Chip Systems for Women's Health Applications

Sex‐specific in‐hospital outcomes of transcatheter aortic valve replacement with third generation transcatheter heart valves

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