Diabetes as a risk factor for incident peripheral arterial disease in women compared to men: a systematic review and meta-analysis

Abstract

Aims/hypothesis Previous meta-analyses have suggested that diabetes confers a greater excess risk of coronary heart disease, stroke, vascular dementia, and heart failure in women compared to men. While the underlying mechanism that explains such greater excess risk is unknown, in the current meta-analysis we hypothesized that we would find a similar sex difference in the relationship between diabetes and peripheral arterial disease (PAD). Methods PubMed MEDLINE, the Cochrane Database of Systematic Reviews, and Embase were systematically searched for prospective population-based cohort studies, with no restriction on publication date, language, or country. We included studies that reported the relative risk (RR), and its variability, for incident PAD associated with diabetes in both sexes. We excluded studies that did not adjust at least for age, and in which participants had pre-existing PAD. In cases where sex-specific results were not reported, study authors were contacted. Random-effects meta-analyses with inverse variance weighting were used to obtain summary sex-specific RRs and the women: men ratio of RRs for PAD. The Newcastle–Ottawa scale was used to assess study quality. Results Data from seven cohorts, totalling 2071,260 participants (49.8% women), were included. The relative risk for incident PAD associated with diabetes compared with no diabetes was 1.96 (95% CI 1.29–2.63) in women and 1.84 (95% CI 1.29–2.86) in men, after adjusting for potential confounders. The multiple-adjusted RR ratio was 1.05 (95% CI 0.90–1.22), with virtually no heterogeneity between studies (I2 = 0%). All studies scored 6–8, on the Newcastle–Ottawa scale of 0–9, indicating good quality. Eleven of the 12 studies that met review inclusion criteria did not report sex-specific relative risk, and these data were collected through direct correspondence with the study authors. Conclusion/interpretation Consistent with other studies, we found evidence that diabetes is an independent risk factor for PAD. However, in contrast to similar studies of other types of cardiovascular disease, we did not find evidence that diabetes confers a greater excess risk in women compared to men for PAD. More research is needed to explain this sex differential between PAD and other forms of CVD, in the sequelae of diabetes. In addition, we found that very few studies reported the sex-specific relative risk for the association between diabetes and PAD, adding to existing evidence for the need for improved reporting of sex-disaggregated results in cardiovascular disease research.

Are there sex differences in the effect of type 2 diabetes in the incidence and outcomes of myocardial infarction? A matched-pair analysis using hospital discharge data

“…Additionally, in the UK, as in Spain, women with diabetes are less likely than men with diabetes to meet all recommended care requirements and might be less likely to achieve target values for treated CVRFs [ 15 , 42 ]. However, in contrast to other types of CVD, one large meta-analysis did not find evidence that diabetes confers a greater excess risk for peripheral arterial disease in women than in men [ 43 ]. More research is needed to determine possible unknown mechanisms responsible for sex differences in diabetes-related cardiovascular risk, and this should also take into account hormonal factors [ 44 ].…”

The relation of anatomical distribution of symptomatic peripheral arterial disease (PAD) with HbA1c level in patients with type 2 diabetes mellitus

“…Mechanisms for atherosclerosis include endothelial and vascular smooth muscle cell derangement and platelets activation that promote slow inflammatory process and thrombosis. 21 , 22 Several inflammatory markers are found in patient with diabetes, such as CRP, that are associated with PAD development and abnormal glucose metabolism. 23 Platelets are essential in the process of inflammation and thrombus formation.…”

Sex related differences in therapy and outcome of patients with intermittent claudication in a real-world cohort

“…Amongst others, CCS and DM have previously been highlighted to increase long-term mortality (CCS alone: HR 1.234; DM alone: HR 1.260; CCS and DM: HR 1.76) and amputation risk (DM alone: HR 2.238; DM and CCS: HR 2.199 [26]) in patients with low-stage LEAD. While DM has been rated as a particular risk factor in female patients to develop cardiovascular arteriosclerosis [27], sex differences may be overestimated in regard to LEAD [28]. In our cohort, both DM and CCS were significantly higher co-prevalent in male IC patients, affecting almost every second patient.…”