Circulation:早绝经是克隆性造血和冠脉疾病的独立风险因素!

2021-02-02 MedSci原创 MedSci原创

早绝经,女性心血管疾病和克隆性造血风险增加!

早绝经是女性血管疾病的独立危险因素,但这种关联的潜在机制尚不清楚。不确定潜能的克隆性造血(CHIP)是一种年龄相关的具有致白血病突变但未发现恶性肿瘤的造血细胞扩增,与动脉粥样硬化加速相关。早绝经是否与CHIP相关尚不明确。

研究人员从UK生物库中筛选了11495位40-70岁的、从女性健康倡议数据库中筛选了8111位50-79岁的有全外显子测序的绝经妇女。早绝经被定义为40岁前自然或手术绝经。共主要结果是存在任何变异等位基因频率>0.1的CHIP。经年龄、种族、祖先的前10个主要成分、吸烟、糖尿病和激素治疗使用等因素调整后,用Logistic回归检验早绝经与CHIP的相关性。次要分析纳入自然 vs 手术早绝经和基因特异性CHIP亚型。

绝经后女性CHIP的发生率

本研究共纳入19606位女性,包括418位(2.1%)自然早绝经的女性和887位(4.5%)手术早绝经的女性。在队列间,有 vs 无早绝经史的绝经后女性CHIP的发生率分别为8.8% vs 5.5%(p<0.001)

早绝经与CHIP相关性

经多变量校正后,早绝经与CHIP独立相关(所有CHIP:优势比 1.36[95%CI 1.10-1.68];P=0.004; 等位基因频率>0.1的CHIP:优势比 1.40[95%CI 1.30-2.80];P<0.001),但在手术早绝经的女性中的差异很小或无显著性。

有无CHIP女性的冠脉疾病发生率

在基因特异性分析中,只有DNMT3A CHIP与早绝经明显独立相关。在绝经的中龄女性中,CHIP与偶发冠状动脉疾病独立相关(与所有CHIP相关的风险比:1.36[95%CI 1.07-1.73];P=0.012;与等位基因频率>0.1的CHIP相关的风险比 1.48[95%CI 1.13-1.94];P=0.005)。

综上,早绝经,特别是自然早绝经,与绝经后女性中的CHIP独立相关。自然早绝经可能是易患CHIP和CHIP相关心血管疾病的危险信号。

原始出处:

Michael C. Honigberg, et al. Premature Menopause, Clonal Hematopoiesis, and Coronary Artery Disease in Postmenopausal Women. Circulation. 2021;143:410–423

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    2021-12-17 aids221
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    2021-02-04 俅侠
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