Article Text

Download PDFPDF

Rationale and tutorial for analysing and reporting sex differences in cardiovascular associations
  1. Mark Woodward1,2,3
  1. 1 The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
  2. 2 The George Institute for Global Health, University of Oxford, Oxford, UK
  3. 3 Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA
  1. Correspondence to Professor Mark Woodward, The George Institute for Global Health, Hayes House, 75 George Street, Oxford OX1 2BQ, UK; markw{at}


Cardiovascular disease (CVD) is the leading cause of death in women and men. Yet biological and social factors differ between the sexes, while the importance of CVD in women may be underestimated due to the higher age-specific rates in men and the historical bias towards the male model of CVD. Consequently, sex differences in risk factor associations with CVD occur, but these are not always recognised. This article argues that sex disaggregation should be the norm in CVD research, for both humanitarian and clinical reasons. A tutorial on how to design and analyse sex comparisons is provided, including ways of reducing bias and increasing efficiency. This is presented both in the context of analysing individual participant data from a single study and a meta-analysis of sex-specific summary data. Worked examples are provided for both types of research. Fifteen key recommendations are included, which should be considered when undertaking sex comparisons of CVD associations. Paramount among these is the need to estimate sex differences, as ratios of relative risks or differences in risk differences, rather than merely test them for statistical significance. Conversely, when there is no evidence of statistical or clinical significance of a sex difference, the conclusions from the research should not be sex-specific.

  • epidemiology
  • medical education
  • statistics and study design
  • meta-analysis

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

View Full Text

Statistics from


  • Contributors MW wrote the entire paper.

  • Funding MW is supported by a National Health and Medical Research Council Fellowship (APP108026) and Program Grant (APP1149987). The funding sources had no role in the design or conduct of the study; collection, management, analysis and interpretation of the data; or preparation, review or approval of the manuscript.

  • Competing interests MW does consultancy for Amgen and Kyowa Hakko Kirin outside the submitted work.

  • Ethics approval UK Biobank has obtained research tissue bank approval from its governing research ethics committee, as recommended by the National Research Ethics Service. No separate ethical approval was required. The study was conducted in accordance with the principles of the Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Researchers can apply to use the UK Biobank resource and access the data used. No additional data are available.

  • Patient consent for publication Not required.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.