Leukocyte Telomere Length in Relation to 17 Biomarkers of Cardiovascular Disease Risk: A Cross-Sectional Study of US Adults.
Leukocyte Telomere Length in Relation to 17 Biomarkers of Cardiovascular Disease Risk: A Cross-Sectional Study of US Adults.
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DOI：
10.1371/journal.pmed.1002188
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发表时间：
2016-11
期刊：
影响因子：
15.8
通讯作者：
Epel ES
中科院分区：
文献类型：
--
作者：
Rehkopf DH;Needham BL;Lin J;Blackburn EH;Zota AR;Wojcicki JM;Epel ES
白细胞端粒长度（LTL）是一个公认的免疫系统年龄的生物学标志，并且已经证明LTL与心血管疾病之间存在关联。这可能部分是由于LTL与其他与心血管疾病风险相关的生物标志物的关系。然而，LTL与肥胖、代谢、促炎和心血管生物标志物之间的关联强度尚未在美国全国代表性人群中进行系统评估。我们研究了LTL和17种心血管生物标志物之间的关系，包括脂蛋白、血糖、循环压、促炎标志物、肾功能和肥胖指标，这些指标来自1999-2002年美国全国健康和营养调查（NHANES）的20 - 84岁成人。（n = 7，252），统计学调整免疫细胞类型分布。我们还研究了这些协会是否因年龄、种族/民族、性别、教育和收入而系统地不同。我们发现，以下生物标志物中的一个单位差异与LTL中的酶对差异相关：体重指数-0.00478（95% CI -0.00749--0.00206），腰围-0.00211（95% CI -0.00325--0.000969），体脂百分比-0.00516（95%CI-0.00761--0.0027），高密度脂蛋白胆固醇0.00179（95% CI 0.000571-0.00301），甘油三酯-0.000285（95% CI -0.000555--0.0000158），脉率-0.00194 C反应蛋白-0.0363（95% CI 0.0601- 0.0124），胱抑素C -0.0391（95% CI -0.0772- 0.00107）。当使用临床临界点时，我们还发现LTL与胰岛素抵抗-0.0412（95%CI-0.0685--0.0139）、收缩压0.0455（95%CI 0.00137-0.0897）和舒张压-0.0674（95%CI-0.126--0.00889）之间存在相关性。在不控制白细胞类型的情况下，这些相关性高出10%-15%。在年龄、种族/民族、性别、教育或收入方面的关联差异很小。我们的研究结果与一般人群中这些心血管生物标志物之间的关系有关，但与作为临床结局的心血管疾病无关。LTL与肥胖最密切相关，但也与几个生理系统的生物标志物相关。因此，LTL可能是心血管疾病的预测因子，通过其与多种危险因素的关联，这些危险因素在生理上与心血管疾病的发展风险相关。我们的研究结果是一致的LTL是心血管衰老的生物标志物，通过建立生理机制。大卫Kupkopf和同事分析了白细胞端粒长度与心血管疾病风险生物标志物的关联。白细胞端粒长度（LTL）是白色血细胞分裂的生物标志物，与年龄密切相关。关于LTL如何与不同类型的死亡率相关，仍有不同的发现。观察证据和准实验研究表明，LTL较短与心血管疾病死亡率之间存在关联。然而，目前尚不清楚LTL是否完全独立于已知的心血管疾病的生物学途径。我们研究了美国25至84岁参与者的全国代表性数据，这些参与者的LTL与其他17种心血管风险生物标志物一起进行了沿着测量。我们发现LTL与肥胖指标（BMI、腰围、体脂百分比）、C反应蛋白、胱抑素C、高密度脂蛋白（HDL）胆固醇、甘油三酯、胰岛素抵抗、收缩压、舒张压和脉率之间存在沿着关系。我们没有发现这些关系在年龄，种族/民族或社会经济地位方面存在有意义的差异，这表明我们发现的关联在不同人群中通常是一致的。我们的研究结果表明，LTL与不同生理系统的心血管危险因素有关。研究结果对LTL是否是心血管疾病的原因没有任何影响。
Leukocyte telomere length (LTL) is a putative biological marker of immune system age, and there are demonstrated associations between LTL and cardiovascular disease. This may be due in part to the relationship of LTL with other biomarkers associated with cardiovascular disease risk. However, the strength of associations between LTL and adiposity, metabolic, proinflammatory, and cardiovascular biomarkers has not been systematically evaluated in a United States nationally representative population. We examined associations between LTL and 17 cardiovascular biomarkers, including lipoproteins, blood sugar, circulatory pressure, proinflammatory markers, kidney function, and adiposity measures, in adults ages 20 to 84 from the cross-sectional US nationally representative 1999–2002 National Health and Nutrition Examination Survey (NHANES) (n = 7,252), statistically adjusting for immune cell type distributions. We also examine whether these associations differed systematically by age, race/ethnicity, gender, education, and income. We found that a one unit difference in the following biomarkers were associated with kilobase pair differences in LTL: BMI -0.00478 (95% CI -0.00749–-0.00206), waist circumference -0.00211 (95% CI -0.00325–-0.000969), percentage of body fat -0.00516 (95% CI -0.00761–-0.0027), high density lipoprotein (HDL) cholesterol 0.00179 (95% CI 0.000571–0.00301), triglycerides -0.000285 (95% CI -0.000555–-0.0000158), pulse rate -0.00194 (95% CI -0.00317–-0.000705), C-reactive protein -0.0363 (95% CI 0.0601–-0.0124), cystatin C -0.0391 (95% CI -0.0772–-0.00107). When using clinical cut-points we additionally found associations between LTL and insulin resistance -0.0412 (95% CI -0.0685–-0.0139), systolic blood pressure 0.0455 (95% CI 0.00137–0.0897), and diastolic blood pressure -0.0674 (95% CI -0.126–-0.00889). These associations were 10%–15% greater without controlling for leukocyte cell types. There were very few differences in the associations by age, race/ethnicity, gender, education, or income. Our findings are relevant to the relationships between these cardiovascular biomarkers in the general population but not to cardiovascular disease as a clinical outcome. LTL is most strongly associated with adiposity, but is also associated with biomarkers across several physiological systems. LTL may thus be a predictor of cardiovascular disease through its association with multiple risk factors that are physiologically correlated with risk for development of cardiovascular disease. Our results are consistent with LTL being a biomarker of cardiovascular aging through established physiological mechanisms. David Rehkopf and colleagues analyze the association of leukocyte telomere length with cardiovascular disease risk biomarkers. Leukocyte telomere length (LTL) is a biomarker of white blood cell division and is strongly associated with age. There are still mixed findings on how LTL is related to different types of mortality. Observational evidence and quasi-experimental studies suggest that there is an association between shorter LTL and cardiovascular disease mortality. It is unclear, however, whether or not LTL is completely independent of already known biological pathways of cardiovascular disease. We examined US nationally representative data on participants ages 25 to 84 that had LTL measured along with 17 other cardiovascular risk biomarkers. We found associations between LTL and measures of adiposity (BMI, waist circumference, percentage of body fat), along with C-reactive protein, cystatin C, high-density lipoprotein (HDL) cholesterol, triglycerides, insulin resistance, systolic blood pressure, diastolic blood pressure, and pulse rate. We did not find that there were a meaningful number of differences in these relationships by age, race/ethnicity, or socioeconomic position, suggesting that the associations we find are generally consistent across different population groups. Our findings suggest that LTL is associated with cardiovascular risk factors across different physiological systems. The study findings do not have any implications for whether LTL is a cause of cardiovascular disease.
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