The striking link of Cushing's syndrome with the metabolic syndrome (MetS) and cardiovascular disease (CVD) suggests that long-term exposure to extremely high cortisol levels catalyzes cardiometabolic deterioration. However, it remained unclear whether the findings from the extreme glucocorticoid overabundance observed in Cushing's syndrome could be translated into more subtle variations in long-term glucocorticoid levels among the general population, for example, due to chronic stress. Here, we performed a systematic review (PROSPERO: CRD42023425541) of evidence regarding the role of subtle variations in long-term biological stress, measured as levels of scalp hair cortisol (HairF) and cortisone (HairE), in the context of MetS and CVD in adults. We also performed a meta-analysis on the cross-sectional difference in HairF levels between individuals with versus without CVD. Seven studies were included regarding MetS, sixteen regarding CVD, and one regarding both. Most articles indicated a strong, consistent cross-sectional association of higher HairF and HairE levels with CVD, which was confirmed by our meta-analysis for HairF (eight studies, SMD = 0.48, 95% confidence intervals [CIs]: 0.16–0.79, p = 0.0095). Moreover, these relationships appear largely independent of standard risk factors. Age seems relevant as the effect seems stronger in younger individuals. Results regarding the associations of HairF and HairE with MetS were inconsistent. Altogether, long-term biological stress, measured as HairF and HairE, is associated with the presence of CVD, and less consistently with MetS. Prospective studies need to evaluate the directionality of this relationship and determine whether HairF and HairE can be used in addition to standard risk factors in predicting future cardiometabolic deterioration.

中文翻译：

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长期糖皮质激素与代谢综合征和心血管疾病的关系：系统评价和荟萃分析

库欣综合征与代谢综合征 (MetS) 和心血管疾病 (CVD) 之间的显着联系表明，长期暴露于极高的皮质醇水平会催化心脏代谢恶化。然而，目前尚不清楚库欣综合征中观察到的糖皮质激素极度过量的结果是否可以转化为普通人群中长期糖皮质激素水平的更微妙的变化，例如由于慢性压力所致。在这里，我们对关于长期生物应激中细微变化的作用的证据进行了系统回顾（PROSPERO：CRD42023425541），在 MetS 和 CVD 的背景下，以头皮头发皮质醇 (HairF) 和可的松 (HairE) 的水平来衡量在成人中。我们还对患有 CVD 和未患有 CVD 的个体之间 HairF 水平的横截面差异进行了荟萃分析。纳入了七项关于 MetS 的研究，十六项关于 CVD 的研究，一项关于两者的研究。大多数文章表明，较高的 HairF 和 HairE 水平与 CVD 存在强烈、一致的横截面关联，这一点已被我们对 HairF 的荟萃分析所证实（八项研究，SMD = 0.48，95% 置信区间 [CI]：0.16–0.79，p  = 0.0095）。此外，这些关系似乎很大程度上独立于标准风险因素。年龄似乎与年龄有关，因为这种效应在年轻人中似乎更强。关于 HairF 和 HairE 与 MetS 关联的结果不一致。总而言之，以 HairF 和 HairE 测量的长期生物应激与 CVD 的存在相关，而与 MetS 的一致性较差。前瞻性研究需要评估这种关系的方向性，并确定除了标准风险因素之外，HairF 和 HairE 是否可以用于预测未来心脏代谢恶化。