Peripheral arterial disease symptoms differ between sexes, meta-analysis finds

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Cindy Porras

In future peripheral arterial disease (PAD) research, clinicians should not consider men and women as a single population and should instead report their data separately. This is the main conclusion of a systematic review and meta-analysis recently published in the European Journal of Vascular and Endovascular Surgery (EJVES), which found that symptoms of lower leg PAD present differently between men and women.

Authors Cindy Porras (Utrecht University, Utrecht, The Netherlands) and colleagues write that while PAD has traditionally been labelled as a predominantly male disease, recent studies suggest that women are affected at least as often as men. Some of these studies also describe differences in the clinical presentation of lower extremity PAD between the sexes, however the authors note that there has been no systematic review collating this information. Therefore, the present study aimed to collate and pool the available evidence in order to evaluate differences in symptoms between men and women who present with lower limb PAD.

Using PubMed, EMBASE, and the Cochrane Library, Porras et al identified all relevant studies, collecting data on study design, source of data, population characteristics, and the outcome of interest using the Newcastle–Ottawa scale and Cochrane risk of bias tool. The authors note that, using the GRADE methodology, the evidence quality was rated as high, moderate, low, or very low based on the risk of bias, inconsistency, indirectness, and imprecision. In addition, the authors detail that estimates of relative effects were pooled to generate pooled odds ratios (ORs) and the 95% confidence interval (CI) using a random-effects model.

Porras et al relay that only studies reporting on symptomatic PAD were included in their analysis. They specify that studies were eligible if they included patients over the age of 18 with a diagnosis of PAD— established either by questionnaire, ankle-brachial index at rest, treadmill, or duplex—reported symptom prevalence, and presented outcomes. The authors note that review articles and case studies were excluded from their analysis.

Out of the 2,186 studies identified, a total of 21 and 20 studies were deemed eligible for qualitative and quantitative analysis, respectively. The investigators report that, of the qualitative studies, 13 were cross-sectional, six were cohorts, one was a case-control study, and one was a randomised controlled trial. Among the eligible study populations with diagnosed PAD, women represented 43.9%.

The 21 studies eligible for qualitative analysis reported on 1,929,966 patients with diagnosed PAD. According to the authors, the data from these studies show that women presented with intermittent claudication less often than men (25.9 vs. 30.2% with OR 0.78 [95% CI 0.72–0.84]; p<0.001; very low quality of evidence). In contrast, Porras et al communicate that rest pain and atypical leg symptoms were more prevalent in women (12.8% vs. 9.2%; OR 1.4 [95% CI 1.22–1.6]; very low quality of evidence, and 22.8% vs. 19.8%; OR 1.18 [95% CI 0.96–1.45]; very low quality of evidence, respectively).

The authors acknowledge some limitations of the present study. They recognise a “substantial heterogeneity” between the studies, the fact that only studies written in English were analysed, and that not all studies reported outcomes of interest. However, Porras and colleagues express their confidence that these limitations “are unlikely to influence the results significantly” as the lower prevalence of intermittent claudication in women was consistent over several subgroups and in sensitivity analyses.

Looking ahead, Porras et al suggest that future studies are needed to understand the possible reasons for differences in clinical presentation in women and men with PAD, and how this influences diagnosis, treatment, and outcomes.


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