From the Department of Medicine (J.C., L.L.H., J.H.), Tulane University School of Medicine, New Orleans, LA.
Department of Epidemiology (J.C., J.D.B., L.L.H., J.H.), Tulane University School of Medicine, New Orleans, LA.
Hypertension. 2019 Apr;73(4):785-793. doi: 10.1161/HYPERTENSIONAHA.118.12358.
Apparent treatment-resistant hypertension (ATRH) is highly prevalent and associated with cardiovascular disease risk in patients with chronic kidney disease. We analyzed the association of inflammatory biomarkers with ATRH and its complications in patients with chronic kidney disease. ATRH was defined as blood pressure ≥140/90 mm Hg while taking ≥3 antihypertensive medications or blood pressure <140/90 mm Hg while taking ≥4 medications. Analyses included 1359 CRIC study (Chronic Renal Insufficiency Cohort) participants with ATRH and 2008 hypertensive participants without. Logistic regression was used to examine cross-sectional associations of inflammatory biomarkers and ATRH adjusting for demographic, lifestyle, and clinical risk factors and treatments. Cox proportional hazards models were used to assess the impact of inflammatory biomarkers on associations of ATRH with composite cardiovascular disease and mortality beyond conventional risk factors. Multivariable-adjusted odds ratio (95% CI) of ATRH for the highest tertile versus the lowest tertile of inflammatory biomarker levels was 1.29 (95% CI, 1.05-1.59) for IL (interleukin)-6, 1.49 (95% CI, 1.20-1.85) for TNF-α (tumor necrosis factor-α), and 0.77 (95% CI, 0.63-0.95) for TGF-β (transforming growth factor-β). High-sensitivity CRP (C-reactive protein), fibrinogen, IL-1β, and IL-1 receptor antagonist were not significantly associated with ATRH. Adding inflammatory biomarkers to Cox models did not attenuate the significant association of ATRH with cardiovascular disease and mortality. Our findings show higher levels of IL-6 and TNF-α and lower levels of TGF-β were independently associated with odds of ATRH. Targeting specific inflammatory pathways may improve blood pressure control in patients with chronic kidney disease.
明显的治疗抵抗性高血压（ATRH）在慢性肾脏病患者中非常普遍，并与心血管疾病风险相关。我们分析了炎症生物标志物与慢性肾脏病患者 ATRH 及其并发症的关系。ATRH 定义为服用≥3 种降压药物时血压≥140/90mmHg，或服用≥4 种药物时血压<140/90mmHg。分析包括 1359 名 CRIC 研究（慢性肾功能不全队列）中的 ATRH 患者和 2008 名无高血压的患者。使用逻辑回归检查炎症生物标志物与 ATRH 的横断面关联，调整人口统计学、生活方式和临床危险因素和治疗。使用 Cox 比例风险模型评估炎症生物标志物对 ATRH 与复合心血管疾病和死亡率的影响，超出传统危险因素。炎症生物标志物水平最高三分位与最低三分位相比，ATRH 的多变量调整比值比（95%CI）为 1.29（95%CI，1.05-1.59）为 IL-6，1.49（95%CI，1.20-1.85）为 TNF-α，0.77（95%CI，0.63-0.95）为 TGF-β。高敏 CRP（C 反应蛋白）、纤维蛋白原、IL-1β 和 IL-1 受体拮抗剂与 ATRH 无显著相关性。将炎症生物标志物添加到 Cox 模型中并没有减轻 ATRH 与心血管疾病和死亡率之间的显著关联。我们的研究结果表明，IL-6 和 TNF-α水平升高，TGF-β水平降低与 ATRH 的可能性独立相关。针对特定的炎症途径可能会改善慢性肾脏病患者的血压控制。
