Bergan Natalie, Prachee Ishika, Curran Lara, McGurk Kathryn A, Lu Chang, de Marvao Antonio, Bai Wenjia, Halliday Brian P, Gregson John, O'Regan Declan P, Ware James S, Tayal Upasana
National Heart Lung Institute, Imperial College London, UK (N.B., L.C., K.A.M., B.P.H., J.S.W., U.T.).
Royal Brompton & Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, UK (I.P., B.P.H., J.S.W., U.T.).
Circulation. 2025 Feb 18;151(7):442-459. doi: 10.1161/CIRCULATIONAHA.124.070872. Epub 2025 Feb 3.
Dilated cardiomyopathy (DCM) appears to be diagnosed twice as often in male than in female patients. This could be attributed to underdiagnosis in female patients or sex differences in susceptibility. Up to 30% of cases have an autosomal dominant monogenic cause, where equal sex prevalence would be expected. The aim of this systematic review, meta-analysis, and population study was to assess the sex ratio in patients with DCM, stratified by genetic status, and evaluate whether this is influenced by diagnostic bias.
A literature search identified DCM patient cohorts with discernible sex ratios. Exclusion criteria were studies with a small (n<100), pediatric, or peripartum population. Meta-analysis and metaregression compared the proportion of female participants for an overall DCM cohort and the following subtypes: all genetic DCM, individual selected DCM genes ( and ), and gene-elusive DCM. Population DCM sex ratios generated from diagnostic codes were also compared with those from sex-specific means using the UK Biobank imaging cohort; this established ICD coded, novel imaging-first, and genotype first determined sex ratios.
A total of 99 studies, with 37 525 participants, were included. The overall DCM cohort had a 0.30 female proportion (95% CI, 0.28-0.32), corresponding to a male:female ratio (M:F) of 2.38:1. This was similar to patients with an identified DCM variant (0.31 [95% CI, 0.26-0.36]; M:F 2.22:1; =0.56). There was also no significant difference when compared with patients with gene-elusive DCM (0.30 [95% CI, 0.24-0.37]; M:F 2.29:1; =0.81). Furthermore, the ratio within autosomal dominant gene variants was not significantly different for (0.28 [95% CI, 0.22-0.36]; M:F 2.51:1; =0.82) or (0.35 [95% CI, 0.27-0.44]; M:F 1.84:1; =0.41). Overall, the sex ratio for DCM in people with disease attributed to autosomal dominant gene variants was similar to the all-cause group (0.34 [95% CI, 0.28-0.40]; M:F 1.98:1; =0.19). In the UK Biobank (n=47 549), DCM defined by International Classification of Diseases, 10th revision, coding had 4.5:1 M:F. However, implementing sex-specific imaging-first and genotype-first diagnostic approaches changed this to 1.7:1 and 2.3:1, respectively.
This study demonstrates that DCM is twice as prevalent in male patients. This was partially mitigated by implementing sex-specific DCM diagnostic criteria. The persistent male excess in genotype-positive patients with an equally prevalent genetic risk suggests additional genetic or environmental drivers for sex-biased penetrance.
URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42023451944.
扩张型心肌病（DCM）在男性患者中的诊断率似乎是女性患者的两倍。这可能归因于女性患者的诊断不足或易感性的性别差异。高达30%的病例有常染色体显性单基因病因，预期性别患病率相同。本系统评价、荟萃分析和人群研究的目的是评估按遗传状态分层的DCM患者的性别比，并评估其是否受诊断偏倚的影响。
文献检索确定了具有可识别性别比的DCM患者队列。排除标准为样本量小（n<100）、儿科或围产期人群的研究。荟萃分析和元回归比较了总体DCM队列以及以下亚型中女性参与者的比例：所有遗传性DCM、个别选定的DCM基因（和）以及基因未明确的DCM。还将根据诊断编码生成的人群DCM性别比与使用英国生物银行成像队列中按性别特定均值得出的性别比进行比较；这确定了国际疾病分类第10版编码、新型影像优先和基因型优先确定的性别比。
共纳入99项研究，37525名参与者。总体DCM队列中女性比例为0.30（95%CI，0.28 - 0.32），对应男女比例（M:F）为2.38:1。这与已确定DCM变异的患者相似（0.31 [95%CI，0.26 - 0.36]；M:F 2.22:1；=0.56）。与基因未明确的DCM患者相比也无显著差异（0.30 [95%CI，0.24 - 0.37]；M:F 2.29:1；=0.81）。此外，常染色体显性基因变异中的比例在（0.28 [95%CI，0.22 - 0.36]；M:F 2.51:1；=0.82）或（0.35 [95%CI，0.27 - 0.44]；M:F 1.84:1；=0.41）时无显著差异。总体而言，归因于常染色体显性基因变异的疾病患者中DCM的性别比与全病因组相似（0.34 [95%CI，0.28 - 0.40]；M:F 1.98:1；=0.
