Harada Paulo H N, Buring Julie E, Cook Nancy R, Cobble Michael E, Kulkarni Krishnaji R, Mora Samia
Center for Lipid Metabolomics, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
J Endocr Soc. 2017 Feb 1;1(2):113-123. doi: 10.1210/js.2016-1085. Epub 2017 Jan 13.
CONTEXT: Whether subclinical hypothyroidism (SCH) is associated with cardiometabolic abnormalities is uncertain. OBJECTIVE: To examine diverse cardiometabolic biomarkers across euthyroid, SCH, and overt hypothyroidism (HT) in women free of cardiovascular disease (CVD). DESIGN: Cross-sectional adjusted associations for lipids, lipoprotein subclasses, lipoprotein insulin resistance score, inflammatory, coagulation, and glycemic biomarkers by ANCOVA for thyroid categories or TSH quintiles on a Women's Health Study subcohort. SETTING: Outpatient. PATIENTS OR OTHER PARTICIPANTS: Randomly sampled 3,914 middle-aged and older women for thyroid function analysis (thyroid-stimulating hormone [TSH], free T4), of whom 3,321 were not on lipid lowering therapy. INTERVENTION: None. MAIN OUTCOME MEASURE: Associations of SCH and HT with cardiometabolic markers. RESULTS: Going from euthyroid to HT, the lipoprotein subclasse profiles were indicative of insulin resistance [respective values and p for trend]: larger VLDL size (nm)[51.5 (95%CI51.2, 51.8) to 52.9 (51.8, 54.1) p=0.001]; higher LDL particles concentration (nmol/L)[1283 (95%CI1267, 1299) to 1358 (1298, 1418) p=0.004] and smaller LDL size. There was worsening lipoprotein insulin resistance score from euthyroid 49.2 (95%CI 48.3, 50.2) to SCH 52.1 (95%CI 50.1, 54.0), and HT 52.1 (95%CI 48.6, 55.6), p for trend 0.008. Of the other biomarkers, SCH and HT were associated with higher hs-CRP and HbA1c. For increasing TSH quintiles results were overall similar. CONCLUSIONS: In apparently healthy women, SCH cardiometabolic profiles indicated worsening insulin resistance and higher CVD risk markers compared with euthyroid individuals, despite similar LDL and total cholesterol. These findings suggest that cardiometabolic risk may increase early in the progression towards SCH and OH.
背景:亚临床甲状腺功能减退(SCH)是否与心脏代谢异常相关尚不确定。 目的:在无心血管疾病(CVD)的女性中,研究甲状腺功能正常、SCH和显性甲状腺功能减退(HT)患者的多种心脏代谢生物标志物。 设计:在女性健康研究亚队列中,通过协方差分析(ANCOVA)对甲状腺类别或促甲状腺激素(TSH)五分位数进行血脂、脂蛋白亚类、脂蛋白胰岛素抵抗评分、炎症、凝血和血糖生物标志物的横断面校正关联分析。 地点:门诊。 患者或其他参与者:随机抽取3914名中老年女性进行甲状腺功能分析(促甲状腺激素[TSH]、游离T4),其中3321名未接受降脂治疗。 干预措施:无。 主要观察指标:SCH和HT与心脏代谢标志物的关联。 结果:从甲状腺功能正常到HT,脂蛋白亚类谱显示出胰岛素抵抗[各自的值和趋势p值]:极低密度脂蛋白(VLDL)大小增加(nm)[从51.5(95%CI 51.2,51.8)到52.9(51.8,54.1),p = 0.001];低密度脂蛋白(LDL)颗粒浓度升高(nmol/L)[从1283(95%CI 1267,1299)到1358(1298,1418),p = 0.004]且LDL大小减小。脂蛋白胰岛素抵抗评分从甲状腺功能正常时的49.2(95%CI 48.3,50.2)恶化至SCH时的52.1(95%CI 50.1,54.0),以及HT时的52.1(95%CI 48.6,55.6),趋势p值为0.008。在其他生物标志物中,SCH和HT与较高的高敏C反应蛋白(hs-CRP)和糖化血红蛋白(HbA1c)相关。对于TSH五分位数增加的情况,结果总体相似。 结论:在看似健康的女性中,与甲状腺功能正常的个体相比,SCH的心脏代谢谱显示胰岛素抵抗恶化且心血管疾病风险标志物更高,尽管低密度脂蛋白和总胆固醇水平相似。这些发现表明,在向SCH和显性甲状腺功能减退进展的早期,心脏代谢风险可能会增加。
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