Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans.
Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans.
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DOI：
10.1186/s13148-021-01035-3
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发表时间：
2021-03-16
影响因子：
5.7
通讯作者：
Smith JA
中科院分区：
文献类型：
--
作者：
Ammous F;Zhao W;Ratliff SM;Mosley TH;Bielak LF;Zhou X;Peyser PA;Kardia SLR;Smith JA
心血管疾病（CVD）是美国成年人死亡的主要原因。与其他种族相比，非裔美国人的CVD发病率和死亡率更高。确定用于CVD临床风险预测的生物标志物为精确预防和早期干预提供了机会。使用线性混合模型，我们调查了表观遗传年龄加速（内在（IEAA），外在（EEAA），PhenoAge（PhenoAA）和GrimAge（GrimAA））和高血压，胰岛素抵抗和血脂异常的1，100名主要高血压非洲裔美国人兄弟姐妹之间的横截面关联。然后，我们使用虚弱风险模型评估了表观遗传年龄加速与自我报告的CVD事件时间之间的关联，并研究了与临床风险评分（Frachial风险评分（FRS）和动脉粥样硬化性心血管疾病（ASCVD）风险方程）模型相比CVD风险预测的改善。在调整性别和实际年龄后，表观遗传年龄加速增加与较高的收缩压（IEAA），较高的脉压（EEAA和GrimAA），较高的空腹血糖（PhenoAA和GrimAA），较高的空腹胰岛素（EEAA），较低的低密度胆固醇（GrimAA）和较高的甘油三酯（GrimAA）相关。GrimAA的5年增加与CVD发病率相关，风险比为1.54（95% CI 1.22-2.01），在调整CVD风险因素后仍显着。在风险评分模型中添加GrimAA改善了使用似然比检验的模型拟合（FRS P = 0.013，ASCVD P = 0.008），但没有改善C统计量（P > 0.05）。净重新分类指数（NRI）显示，在FRS（NRI：0.055，95% CI 0.040-0.071）和ASCVD方程（NRI：0.029，95% CI 0.006-0.064）中添加GrimAA后，风险类别重新分配略有显著改善。表观遗传年龄加速测量与高血压患病率非洲裔美国人队列中传统CVD危险因素相关。GrimAA与CVD发病率相关，并且与临床风险评分相比，CVD事件的预测略有改善。在线版本包含补充材料，可通过10.1186/s13148-021-01035-3获得。
Cardiovascular disease (CVD) is the leading cause of mortality among US adults. African Americans have higher burden of CVD morbidity and mortality compared to any other racial group. Identifying biomarkers for clinical risk prediction of CVD offers an opportunity for precision prevention and earlier intervention. Using linear mixed models, we investigated the cross-sectional association between four measures of epigenetic age acceleration (intrinsic (IEAA), extrinsic (EEAA), PhenoAge (PhenoAA), and GrimAge (GrimAA)) and ten cardiometabolic markers of hypertension, insulin resistance, and dyslipidemia in 1,100 primarily hypertensive African Americans from sibships in the Genetic Epidemiology Network of Arteriopathy (GENOA). We then assessed the association between epigenetic age acceleration and time to self-reported incident CVD using frailty hazard models and investigated CVD risk prediction improvement compared to models with clinical risk scores (Framingham risk score (FRS) and the atherosclerotic cardiovascular disease (ASCVD) risk equation). After adjusting for sex and chronological age, increased epigenetic age acceleration was associated with higher systolic blood pressure (IEAA), higher pulse pressure (EEAA and GrimAA), higher fasting glucose (PhenoAA and GrimAA), higher fasting insulin (EEAA), lower low density cholesterol (GrimAA), and higher triglycerides (GrimAA). A five-year increase in GrimAA was associated with CVD incidence with a hazard ratio of 1.54 (95% CI 1.22–2.01) and remained significant after adjusting for CVD risk factors. The addition of GrimAA to risk score models improved model fit using likelihood ratio tests (P = 0.013 for FRS and P = 0.008 for ASCVD), but did not improve C statistics (P > 0.05). Net reclassification index (NRI) showed small but significant improvement in reassignment of risk categories with the addition of GrimAA to FRS (NRI: 0.055, 95% CI 0.040–0.071) and the ASCVD equation (NRI: 0.029, 95% CI 0.006–0.064). Epigenetic age acceleration measures are associated with traditional CVD risk factors in an African-American cohort with a high prevalence of hypertension. GrimAA was associated with CVD incidence and slightly improved prediction of CVD events over clinical risk scores. The online version contains supplementary material available at 10.1186/s13148-021-01035-3.
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全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
5.7
作者：
Hillary, Robert F.;Stevenson, Anna J.;Marioni, Riccardo E.
通讯作者：
Marioni, Riccardo E.
影响因子：
--
作者：
Fortin, Jean-Philippe;Fertig, Elana;Hansen, Kasper
通讯作者：
Hansen, Kasper
影响因子：
5.6
作者：
Grant, Crystal D.;Jafari, Nadereh;Conneely, Karen N.
通讯作者：
Conneely, Karen N.
影响因子：
12.3
作者：
Horvath S
通讯作者：
Horvath S