Diabetes as a risk factor for heart failure in women and men: a systematic review and meta-analysis of 47 cohorts including 12 million individuals

Abstract

Aims/hypothesis: The prevalence of diabetes and heart failure is increasing, and diabetes has been associated with an increased risk of heart failure. However, whether diabetes confers the same excess risk of heart failure in women and men is unknown. The aim of this study was to conduct a comprehensive systematic review with meta-analysis of possible sex differences in the excess risk of heart failure consequent to diabetes. Our null hypothesis was that there is no such sex difference.

Methods: A systematic search was conducted in PubMed for population-based cohort studies published between January 1966 and November 2018. Studies were selected if they reported sex-specific estimates of RRs for heart failure associated with diabetes, and its associated variability, which were adjusted at least for age. Random-effects meta-analyses with inverse variance weighting were used to obtain pooled sex-specific RRs and women-to-men ratio of RRs (RRRs) for heart failure associated with diabetes.

Results: Data from 47 cohorts, involving 12,142,998 individuals and 253,260 heart failure events, were included. The pooled multiple-adjusted RR for heart failure associated with type 1 diabetes was 5.15 (95% CI 3.43, 7.74) in women and 3.47 (2.57, 4.69) in men, leading to an RRR of 1.47 (1.44, 1.90). Corresponding pooled RRs for heart failure associated with type 2 diabetes were 1.95 (1.70, 2.22) in women and 1.74 (1.55, 1.95) in men, with a pooled RRR of 1.09 (1.05, 1.13).

Conclusions/interpretation: The excess risk of heart failure associated with diabetes is significantly greater in women with diabetes than in men with diabetes. PROSPERO registration: CRD42019135246.

Keywords: Diabetes; Heart failure; Meta-analysis; Sex differences; Systematic review.

Fig. 1

Flow chart of study selection

Fig. 2

Multiple-adjusted RR for heart failure, comparing individuals with type 1 and type 2 diabetes with those without diabetes for (a) women and (b) men. APCSC, Asia Pacific Cohort Studies Collaboration; CALIBER, Cardiovascular disease research using LInked Bespoke studies and Electronic health Records; CHS, Cardiovascular Health Study; KPMCP, Northern California Kaiser Permanente Medical Care Program; LRPP, Cardiovascular Disease Lifetime Risk Pooling Project (Framingham Heart, Framingham Offspring, Atherosclerosis Risk In Communities [ARIC], Chicago Heart Association Detection Project in Industry Study [CHA]); NDR, National Diabetes Registry; NHANES I, First National Health and Nutrition Examination Survey; NHI, National Health Insurance; NHS, National Health Service

Fig. 3

Multiple-adjusted women-to-men RRR for heart failure, comparing individuals with type 1 and type 2 diabetes with those without diabetes. APCSC, Asia Pacific Cohort Studies Collaboration; CALIBER, Cardiovascular disease research using LInked Bespoke studies and Electronic health Records; CHS, Cardiovascular Health Study; KPMCP, Northern California Kaiser Permanente Medical Care Program; LRPP, Cardiovascular Disease Lifetime Risk Pooling Project (Framingham Heart, Framingham Offspring, Atherosclerosis Risk In Communities [ARIC], Chicago Heart Association Detection Project in Industry Study [CHA]); NDR, National Diabetes Registry; NHANES I, First National Health and Nutrition Examination Survey; NHI, National Health Insurance; NHS, National Health Service

Fig. 4

Subgroup analyses of multiple-adjusted women-to-men RRR for heart failure, comparing individuals with type 2 diabetes with those without. ^aYear of baseline: two studies were excluded because baseline year bridged pre-1985 and 1986 onwards. ^bAbsolute risk of heart failure: absolute risk was derived using data from individuals with and without diabetes combined. Four studies were excluded because absolute risk was not available for both sexes