Epigenetic age acceleration mediates the association between low-grade systemic inflammation and cardiovascular diseases: insight from the NHANES 1999-2002.

IF 4.8 2区 医学 Q1 GENETICS & HEREDITY
Xiaolang Chen, Jin Zhong, Yingnan Lv, Lancheng Wei, Huijiao Zhou, Yongmei Yang, Jinfan Chi, Zhen Lee, Huabei Wu, Haiying Zhang
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引用次数: 0

Abstract

Background: Currently, with the global aging of the population, inflammation, recognized as a hallmark in age-related diseases, has been studied and linked to cardiovascular diseases (CVD). However, limited evidence on whether inflammation modifies epigenetic aging and affects CVD risk.

Methods: This study included 404 CVD patients and 1941 non-CVD individuals from the 1999-2002 National Health and Nutrition Examination Survey cross-sectional data. Low-grade systemic inflammation was assessed using C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and systemic inflammation response index (SIRI). Epigenetic age accelerations (EAAs) were calculated as the residuals between chronological and epigenetic ages: Horvath age acceleration (AgeAccel), AgeAccelHannum, and AgeAccelPheno. Weighted linear and logistic regression analyzed the associations between exposures and outcomes, with mediating effects assessed using the Sobel test.

Results: After adjusting confoundings, the log-transformed NLR and SIRI were positively associated with CVD risk, and the odds ratio (OR) ranges from 1.260 to 1.354 (all P < 0.05). Furthermore, the ln-transformed CRP was positively associated with AgeAccelHannum and AgeAccelPheno, and the coefficient (β) ranges from 0.505 to 1.304 (all P < 0.05); the ln-transformed NLR and SIRI were positively associated with all three EAAs, and the β ranges from 0.392 to 2.212 (all P < 0.005). Additionally, 1-unit increase in AgeAccelHannum and AgeAccelPheno was associated with 2.8% (OR: 1.028, 95% CI 1.007-1.049, P = 0.011) and 3.5% (OR: 1.035, 95% CI 1.014-1.056, P = 0.002) increase in CVD risk, respectively. After adjusting confoundings, mediation analysis showed that AgeAccelHannum mediates 10.44% (P = 0.046) of the association between NLR and CVD risk; and AgeAccelPheno mediates 24.03% (P = 0.009) and 18.16% (P = 0.015) of the NLR-CVD and SIRI-CVD risk associations, respectively.

Conclusion: Our results demonstrate that EAAs mediate the association between systemic inflammation and CVD risk, highlighting the potential of a multi-target approach to inflammation and epigenetic modifications for personalized management to reduce CVD risk.

表观遗传年龄加速介导低级别全身性炎症和心血管疾病之间的关联:来自NHANES 1999-2002的见解
背景:目前,随着全球人口老龄化,炎症作为年龄相关疾病的标志,已被研究并与心血管疾病(CVD)联系起来。然而,关于炎症是否改变表观遗传衰老并影响心血管疾病风险的证据有限。方法:本研究纳入了1999-2002年全国健康与营养调查中404例心血管疾病患者和1941例非心血管疾病个体的横断面数据。采用c反应蛋白(CRP)、中性粒细胞与淋巴细胞比值(NLR)和全身炎症反应指数(SIRI)评估低级别全身性炎症。表观遗传年龄加速(EAAs)计算为实足年龄和表观遗传年龄之间的残差:Horvath年龄加速(AgeAccel), AgeAccelHannum和AgeAccelPheno。加权线性和逻辑回归分析了暴露与结果之间的关系,并使用Sobel检验评估了中介效应。结果:在调整混杂因素后,对数转换后的NLR和SIRI与心血管疾病风险呈正相关,比值比(OR)范围为1.260 ~ 1.354(均为P)。结论:我们的研究结果表明,EAAs介导了全身炎症和心血管疾病风险之间的关联,强调了多靶点炎症治疗和表观遗传修饰的潜力,以实现个性化管理,降低心血管疾病风险。
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来源期刊
自引率
5.30%
发文量
150
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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