Calf Circumference and All-Cause Mortality: A Systematic Review and Meta-Analysis Based on Trend Estimation Approaches

To perform a systematic review and meta-analysis and quantify the associations of total mortality with calf circumference (CC) in adults 18 years and older via combining various analyses based on empirical dichotomic CC, continuous CC, and dose-response CC. We conducted a systematic search of relevant studies in PubMed, EMBASE, Cochrane Library, and Web of Science published through April 12, 2022. This systematic review includes longitudinal observational studies reporting the relationships of total mortality with CC. We calculated the pooled relative risk (RR) and 95% confidence interval (CI) of total mortality with CC per 1 cm for each study and combined the values using standard meta-analysis approaches. Newcastle-Ottawa scale (NOS), Grading of Recommendations, Assessment, Development and Evaluations approach (GRADE), and the Instrument for assessing the Credibility of Effect Modification Analyses (ICEMAN) were assessed for meta-analyses. Our analysis included a total of 37 cohort studies involving 62,736 participants, across which moderate heterogeneity was observed (I2=75.7%, P<0.001), but no publication bias was found. Study quality scores ranged from 6 to 9 (mean 7.7), with only three studies awarded a score of 6 (fair quality). We observed an inverse trend between total death risk and CC per 1 cm increase (RR, 0.95, 95% CI, 0.94–0.96; P<0.001; GRADE quality=high). Only a very slight difference was found among residents of nursing homes (6.9% mortality risk reduction per one cm CC increase), community-dwellers (5.4%), and those living in hospitals (4.8%), respectively (P for meta-regression=0.617). Low credible subgroup difference was found based on the ICEMAN tool. Calf circumference is a valid anthropometric measure for mortality risk prediction in a community, nursing home, or hospital.