Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, P. O. Box 1012, Melville, Johannesburg, 2109, South Africa,
Rheumatol Int. 2014 Mar;34(3):329-39. doi: 10.1007/s00296-013-2933-7. Epub 2014 Jan 8.
We examined the potential impact of demographic characteristics on the independent leptin-metabolic cardiovascular risk factor and leptin-endothelial activation relationships in black and white patients with RA. Leptin concentrations and those of endothelial activation molecules including soluble E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 were measured in 217 RA patients (51.6% black). We determined associations in potential confounder and mediator-adjusted mixed regression models. No independent associations between leptin concentrations and cardiovascular risk were present in all patients and either women and men or black and white patients. However, age impacted on several leptin-cardiovascular risk relations (interaction P < 0.05). In patients aged <50 years (lower quartile), after but not before adjustment for waist circumference and body mass index in addition to other confounders, leptin concentrations associated with overall endothelial activation as estimated by an SD (z) score of endothelial activation molecule concentrations (partial R = 0.341, P = 0.04). In patients aged 50-58 years (second quartile), leptin concentrations related to those of HDL cholesterol (partial R = -0.365, P = 0.01) and total cholesterol-HDL cholesterol ratio (partial R = 0.299, P = 0.04), and in those aged 59-63 years (third quartile), paradoxically related to low systolic and mean blood pressure (partial R = -0.438, P = 0.005 and partial R = -0.370, P = 0.02, respectively). Patients with RA aged <50 years experience an independent adiposity-driven leptin-endothelial activation relationship in the absence of leptin-metabolic risk factor associations. Young but not older patients with RA may sustain obesity-induced endothelial activation that is directly mediated by leptin.
我们研究了人口统计学特征对独立的瘦素代谢心血管危险因素和瘦素-内皮激活关系的潜在影响，这些特征在黑人及白人 RA 患者中有所不同。我们测量了 217 名 RA 患者（51.6%为黑人）的瘦素浓度以及内皮激活分子的浓度，包括可溶性 E-选择素、血管细胞黏附分子-1、细胞间黏附分子-1 和单核细胞趋化蛋白-1。在所有患者以及女性和男性或黑人和白人患者中，均未发现瘦素浓度与心血管风险之间存在独立关联。然而，年龄对几种瘦素-心血管风险关系有影响（交互 P < 0.05）。在年龄 <50 岁（较低四分位数）的患者中，在调整腰围和体重指数以及其他混杂因素后，但在调整之前，瘦素浓度与整体内皮激活相关，这是通过内皮激活分子浓度的标准差（z）评分来估计的（部分 R = 0.341，P = 0.04）。在年龄 50-58 岁（第二四分位数）的患者中，瘦素浓度与高密度脂蛋白胆固醇（部分 R = -0.365，P = 0.01）和总胆固醇-高密度脂蛋白胆固醇比值（部分 R = 0.299，P = 0.04）相关，在年龄 59-63 岁（第三四分位数）的患者中，瘦素浓度与低收缩压和平均血压呈相反关系（部分 R = -0.438，P = 0.005 和部分 R = -0.370，P = 0.02）。年龄 <50 岁的 RA 患者在不存在瘦素代谢危险因素关联的情况下，经历了独立的肥胖驱动的瘦素-内皮激活关系。年轻而非年长的 RA 患者可能会维持肥胖诱导的内皮激活，这种激活直接由瘦素介导。
