FGF23 改变了维生素 D 与心脏重构之间的关系。
FGF23 modifies the relationship between vitamin D and cardiac remodeling.
机构信息
Renal Division, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
出版信息
Circ Heart Fail. 2013 Jul;6(4):817-24. doi: 10.1161/CIRCHEARTFAILURE.112.000105. Epub 2013 Jun 7.
BACKGROUND
There is growing evidence to support an important role for vitamin D and related hormones, parathyroid hormone and fibroblast growth factor 23 (FGF23), on cardiac remodeling in chronic kidney disease. Our objective was to determine the relationships between vitamin D and cardiac remodeling in chronic kidney disease and the effects of parathyroid hormone and FGF23 on these associations.
METHODS AND RESULTS
In 1431 participants from the Chronic Renal Insufficiency Cohort study, we measured 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), FGF23, and parathyroid hormone and performed quantitative echocardiography. Using linear regression methods, we determined significant negative interactions between 25(OH)D and FGF23 on left ventricular (LV) mass (P=0.016), end-diastolic volume (P=0.029), and end-systolic volumes (P=0.021). In participants with an FGF23 level greater than the median of 123.5 RU/mL, each doubling of 25(OH)D was associated with a 2.5% (95% confidence interval, -4.8, -0.2) lower LV mass. This association was less pronounced with FGF23 levels less than the median (0.4%; 95% confidence interval, -1.9, 2.7). Conversely, in participants with deficient 25(OH)D levels <20 ng/mL, each doubling of FGF23 was associated with a 3.4% (95% confidence interval, 1.2, 5.6) greater LV mass compared with only a 1.6% (95% confidence interval, -0.2, 3.5) difference in participants with sufficient 25(OH)D. Similar findings were observed with 25(OH)D and volumes (P<0.05), and 1,25(OH)2D and LV mass and volumes (P<0.005). There was no effect modification by parathyroid hormone.
CONCLUSIONS
We identified significant interactions among 25(OH)D, 1,25(OH)2D, and FGF23 on cardiac remodeling. Increased LV mass and cavity dilatation were observed with low 25(OH)D and high FGF23. Our findings suggest that consideration of both hormones is crucial to understanding the role of either in cardiac remodeling, and may have important therapeutic implications.
背景
越来越多的证据表明，维生素 D 和相关激素、甲状旁腺激素和成纤维细胞生长因子 23（FGF23）在慢性肾脏病的心脏重构中起着重要作用。我们的目的是确定维生素 D 与慢性肾脏病中心脏重构的关系，以及甲状旁腺激素和 FGF23 对这些关联的影响。
方法和结果
在慢性肾功能不全队列研究的 1431 名参与者中，我们测量了 25-羟维生素 D（25（OH）D）、1,25-二羟维生素 D（1,25（OH）2D）、FGF23 和甲状旁腺激素，并进行了定量超声心动图检查。我们使用线性回归方法确定了 25（OH）D 和 FGF23 之间在左心室（LV）质量（P=0.016）、舒张末期容积（P=0.029）和收缩末期容积（P=0.021）上的显著负交互作用。在 FGF23 水平高于中位数 123.5 RU/mL 的参与者中，25（OH）D 加倍与 LV 质量降低 2.5%（95%置信区间，-4.8，-0.2）相关。在 FGF23 水平低于中位数的参与者中，这种关联不那么明显（0.4%；95%置信区间，-1.9，2.7）。相反，在 25（OH）D 水平<20 ng/mL 的参与者中，与 FGF23 加倍相关的 LV 质量增加了 3.4%（95%置信区间，1.2，5.6），而在 25（OH）D 水平充足的参与者中，FGF23 加倍仅导致 LV 质量增加 1.6%（95%置信区间，-0.2，3.5）。在 25（OH）D 和容量（P<0.05）以及 1,25（OH）2D 和 LV 质量和容量（P<0.005）方面也观察到了类似的发现。甲状旁腺激素没有改变这种相互作用。
结论
我们发现 25（OH）D、1,25（OH）2D 和 FGF23 之间存在显著的相互作用，对心脏重构有影响。低 25（OH）D 和高 FGF23 与 LV 质量增加和腔室扩张有关。我们的研究结果表明，考虑到这两种激素对于理解它们在心脏重构中的作用至关重要，这可能具有重要的治疗意义。
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