Berezin Alexander E, Kremzer Alexander A, Martovitskaya Yulia V, Samura Tatyana A, Berezina Tatyana A
Cardiology Unit, Internal Medicine Department, State Medical University, 26, Mayakovsky av., Zaporozhye, UA-69035, Ukraine.
Clinical Pharmacology Department, State Medical University, Zaporozhye, Ukraine.
Diabetes Metab Syndr. 2016 Jan-Mar;10(1):29-36. doi: 10.1016/j.dsx.2015.08.001. Epub 2015 Aug 21.
The study aim was to evaluate the impact of dysmetabolic comorbidities including subclinical hypothyroidism (SH) on pattern of circulating endothelial-derived microparticles (EMPs) in chronic heart failure (CHF) patients.
It was retrospectively involved a cohort of 388 patients with CHF. Fifty three CHF subjects had SH and 335 patients were free from thyroid dysfunction. Circulating levels of NT-pro brain natriuretic peptide (NT-pro-BNP), high-sensitivity C-reactive protein (hs-CRP), thyroid stimulating hormone (TSH), total and free thyroxine (T4) and triiodothyronine (T3) EMPs were measured at baseline. SH was defined per contemporary clinical guideline as state associated with elevated level of serum TSH>10 μU/L and basal normal free T3 and T4 concentration.
Circulating CD31+/annexin V+ EMPs were higher in SH patients compared with none SH subjects. In contrast, activated CD62E+ EMP numbers were not significantly different between both patient cohorts. Using C-statistics for Models with TSH, New York Heart Association (NYHA) class, dyslipidemia, and circulating biomarkers (hs-CRP, NT-proBNP, serum uric acid) as Continuous Variables we found that adding of NYHA class alone, NT-proBNP alone or their combination to the based model (TSH) improved the relative integrated discrimination improvement (IDI) for increased CD31+/annexin V+ to CD62E+ ratio by 4.9%; 9.2% and 9.6% respectively. NT-proBNP improves significantly predictive model based on TSH for increased CD31+/annexin V+ to CD62E+ ratio. Among patient study population for category-free net reclassification improvement (NRI), 4% of events (P=0.026) and 6% of non-events (P=0.012) were correctly reclassified by the addition of circulating NT-proBNP to the base model (TSH) for Increased CD31+/annexin V+ to CD62E+ ratio. Therefore, 4% of events (P=0.028) and 5% of non-events (P=0.014) were correctly reclassified using category-free NRI for increased CD31+/annexin V+ to CD62E+ ratio.
We found that SH state in CHF patients associates with impaired pattern of circulating EMPs with predominantly increased number of apoptotic-derived microparticles.
本研究旨在评估包括亚临床甲状腺功能减退（SH）在内的代谢紊乱合并症对慢性心力衰竭（CHF）患者循环内皮衍生微粒（EMPs）模式的影响。
回顾性纳入388例CHF患者队列。53例CHF患者有SH，335例患者无甲状腺功能障碍。在基线时测量NT-前脑钠肽（NT-pro-BNP）、高敏C反应蛋白（hs-CRP）、促甲状腺激素（TSH）、总甲状腺素和游离甲状腺素（T4）以及三碘甲状腺原氨酸（T3）EMPs的循环水平。根据当代临床指南，SH被定义为与血清TSH水平升高>10 μU/L以及基础游离T3和T4浓度正常相关的状态。
与无SH的受试者相比，SH患者循环中的CD31+/膜联蛋白V+ EMPs更高。相比之下，两个患者队列中活化的CD62E+ EMP数量无显著差异。将TSH、纽约心脏协会（NYHA）分级、血脂异常和循环生物标志物（hs-CRP、NT-proBNP、血清尿酸）作为连续变量用于模型的C统计分析，我们发现仅添加NYHA分级、仅添加NT-proBNP或它们的组合到基础模型（TSH）中，可使CD31+/膜联蛋白V+与CD62E+比率增加的相对综合鉴别改善（IDI）分别提高4.9%、9.2%和9.6%。NT-proBNP显著改善了基于TSH的CD31+/膜联蛋白V+与CD62E+比率增加的预测模型。在患者研究人群中，对于无类别净重新分类改善（NRI），将循环NT-proBNP添加到基础模型（TSH）中用于CD31+/膜联蛋白V+与CD62E+比率增加时，4%的事件（P = 0.026）和6%的非事件（P = 0.012）被正确重新分类。因此，使用无类别NRI用于CD31+/膜联蛋白V+与CD62E+比率增加时，4%的事件（P = 0.028）和5%的非事件（P = 0.014）被正确重新分类。
我们发现CHF患者的SH状态与循环EMPs模式受损相关，主要是凋亡衍生微粒数量增加。
