Atrial fibrillation as risk factor for cardiovascular disease and death in women compared with men: systematic review and meta-analysis of cohort studies

Connor A Emdin, Christopher X Wong, Allan J Hsiao, Douglas G Altman, Sanne Ae Peters, Mark Woodward, Ayodele A Odutayo, Connor A Emdin, Christopher X Wong, Allan J Hsiao, Douglas G Altman, Sanne Ae Peters, Mark Woodward, Ayodele A Odutayo

Abstract

Objective: To determine whether atrial fibrillation is a stronger risk factor for cardiovascular disease and death in women compared with men.

Design: Meta-analysis of cohort studies.

Data sources: Studies published between January 1966 and March 2015, identified through a systematic search of Medline and Embase and review of references.

Eligibility for selecting studies: Cohort studies with a minimum of 50 participants with and 50 without atrial fibrillation that reported sex specific associations between atrial fibrillation and all cause mortality, cardiovascular mortality, stroke, cardiac events (cardiac death and non-fatal myocardial infarction), and heart failure.

Data extraction: Two independent reviewers extracted study characteristics and maximally adjusted sex specific relative risks. Inverse variance weighted random effects meta-analysis was used to pool sex specific relative risks and their ratio.

Results: 30 studies with 4,371,714 participants were identified. Atrial fibrillation was associated with a higher risk of all cause mortality in women (ratio of relative risks for women compared with men 1.12, 95% confidence interval 1.07 to 1.17) and a significantly stronger risk of stroke (1.99, 1.46 to 2.71), cardiovascular mortality (1.93, 1.44 to 2.60), cardiac events (1.55, 1.15 to 2.08), and heart failure (1.16, 1.07 to 1.27). Results were broadly consistent in sensitivity analyses.

Conclusion: Atrial fibrillation is a stronger risk factor for cardiovascular disease and death in women compared with men, though further research would be needed to determine any causality.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf. MW declares consultancy fees from Amgen and Novartis. All other authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5482349/bin/emdc028894.f1.jpg
Fig 1 Identification of cohort studies that reported associations between atrial fibrillation (AF) and death or cardiovascular events in men and women
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5482349/bin/emdc028894.f2.jpg
Fig 2 Maximally adjusted relative risk for all cause mortality for individuals with and without AF by sex. Area of each square is proportional to inverse variance of estimate. Horizontal lines indicate 95% confidence intervals
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5482349/bin/emdc028894.f3.jpg
Fig 3 Maximally adjusted women-to-men ratio of relative risks for any all cause mortality for individuals with and without AF. Area of each square is proportional to inverse variance of estimate. Horizontal lines indicate 95% confidence intervals
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5482349/bin/emdc028894.f4.jpg
Fig 4 Maximally adjusted relative risk for stroke for individuals with and without AF by sex. Area of each of each square is proportional to inverse variance of estimate. Horizontal lines indicate 95% confidence intervals
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5482349/bin/emdc028894.f5.jpg
Fig 5 Maximally adjusted women-to-men ratio of relative risks for stroke for individuals with and without AF. Area of each square is proportional to inverse variance of estimate. Horizontal lines indicate 95% confidence intervals
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5482349/bin/emdc028894.f6.jpg
Fig 6 Maximally adjusted pooled women-to-men ratio of relative risks for all cause mortality, CVD (cardiovascular) mortality, stroke, cardiac events, and heart failure, comparing individuals with and without AF. Area of each square is proportional to inverse variance of estimate. Horizontal lines indicate 95% confidence intervals

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