Endocrine Division, Unidad Asistencial Dr Cesar Milstein, Buenos Aires, Argentina.
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Front Endocrinol (Lausanne). 2023 Aug 16;14:1162626. doi: 10.3389/fendo.2023.1162626. eCollection 2023.
Hypothyroidism is associated with impaired glomerular filtration rate (GFR), a recognized cardiovascular disease (CVD), and mortality risk factor. In older adults, this association remains unexplored. We aimed to determine the relationship of elevated TSH with GFR in an elderly population at high CVD risk.
Older adults (age>65ys) with high CVD risk defined by two or more CVD risk factors: smoking (S), high blood pressure (HBP), high total cholesterol, low HDL cholesterol, diabetes (DM), metabolic syndrome or previous cardiovascular event, were prospectively included at our ambulatory Endocrine Clinic. Patients under levothyroxine or thyroid disease were excluded. TSH> 6mU/l defined subclinical hypothyroidism (ScH) with normal free T4 levels. Estimated GFR was calculated by the Berlin-Initiative Study (BIS)-1 formula for elderly population. Urinary albumin to creatinine ratio (uACR), IL-6 and TNF-α, and Carotid intima-media thickness (CIMT) were also determined. The U Mann-Whitney test, the Spearman test, and multiple linear regression were used as statistical tests.
Finally 246 patients (68% females) were included and 20 (8%) had ScH. This group, was older (median, Q1-Q3: 77,72-78; 72,68-77 years, p=0.01) and DM was less frequent than in the euthyroid group (35 vs 58%, p=0.039). Lower fasting glucose (-20%,p=0.01), GFR (-14%,p=0.01) and freeT4 (-10%,p<0.001) were found compared to euthyroid patients. A higher prevalence of Kidney failure was found in ScH (80 46%, p=0.003) vs. euthyroid individuals. Significant correlations with GFR were detected: age (r-0.482,p<0.001), TSH (r-0.172,p=0.004), IL-6 (r-0.150,p=0.047), TNF-α (r-0.274,p<0.001), uACR (r-0.170,p=0.009) and CIMT(r-0.189,p=0.004). By multiple linear regression, in a model adjusted by age, sex, BMI, uACR, S, DM, TNF-α and HBP, TSH (Bst -0.14, p=0.023, R = 0.25) was found an independent predictor of GFR.
In older adults with high CVD risk, ScH is associated with lower renal function, and this relationship is present regardless of other cardiometabolic risk factors. These results suggest that ScH could contribute to low GFR and excess CVD risk, although this hypothesis should be addressed in longitudinal studies.
甲状腺功能减退症与肾小球滤过率(GFR)降低有关,而 GFR 降低是一种公认的心血管疾病(CVD)和死亡风险因素。在老年人中,这种关联尚未得到探索。我们旨在确定高 CVD 风险的老年人群中 TSH 升高与 GFR 的关系。
在我们的门诊内分泌科,我们前瞻性地纳入了患有两种或多种 CVD 风险因素(吸烟(S)、高血压(HBP)、高总胆固醇、低 HDL 胆固醇、糖尿病(DM)、代谢综合征或既往心血管事件)的年龄>65 岁的老年人。排除正在服用左甲状腺素或患有甲状腺疾病的患者。TSH>6mU/l 定义为正常游离 T4 水平的亚临床甲状腺功能减退症(ScH)。估算的 GFR 通过柏林倡议研究(BIS)-1 公式计算,用于老年人群。还测定了尿白蛋白与肌酐比值(uACR)、IL-6 和 TNF-α 以及颈动脉内膜中层厚度(CIMT)。使用 U 曼-惠特尼检验、斯皮尔曼检验和多元线性回归作为统计检验。
最终纳入 246 名患者(68%为女性),其中 20 名(8%)患有 ScH。与甲状腺功能正常组相比,该组年龄更大(中位数,Q1-Q3:77,72-78;72,68-77 岁,p=0.01),DM 更少见(35%对 58%,p=0.039)。与甲状腺功能正常组相比,空腹血糖(-20%,p=0.01)、GFR(-14%,p=0.01)和游离 T4(-10%,p<0.001)均降低。ScH 患者(80%对 46%,p=0.003)的肾衰竭发生率更高。与 GFR 显著相关的指标有:年龄(r-0.482,p<0.001)、TSH(r-0.172,p=0.004)、IL-6(r-0.150,p=0.047)、TNF-α(r-0.274,p<0.001)、uACR(r-0.170,p=0.009)和 CIMT(r-0.189,p=0.004)。通过多元线性回归,在一个通过年龄、性别、BMI、uACR、S、DM、TNF-α 和 HBP 调整的模型中,TSH(Bst-0.14,p=0.023,R=0.25)是 GFR 的独立预测因子。
在患有高 CVD 风险的老年人中,ScH 与较低的肾功能相关,而这种关系存在于其他心血管代谢危险因素之外。这些结果表明,ScH 可能导致 GFR 降低和 CVD 风险增加,尽管这一假设应在纵向研究中得到解决。