Department of Medicine, University of Alabama at Birmingham.
Department of Biostatistics, University of Alabama at Birmingham.
JAMA Cardiol. 2018 Apr 1;3(4):318-325. doi: 10.1001/jamacardio.2018.0139.
Higher circulating fibroblast growth factor 23 (FGF23) concentrations are associated with cardiovascular disease events linked to heart failure, but associations of FGF23 with coronary heart disease (CHD) have been less consistent.
To determine the association of plasma FGF23 concentrations with incident CHD and whether this association differs by race, sex, or chronic kidney disease status.
DESIGN, SETTING, AND PARTICIPANTS: We examined the association of FGF23 concentrations with incident CHD risk within the Reasons for Geographic and Racial Differences in Stroke study, a prospective cohort of black and white adults 45 years and older enrolled between January 2003 and October 2007 with follow-up through December 31, 2011. Using a case-cohort design, we measured FGF23 concentrations in 829 participants who developed incident CHD and in 812 participants randomly selected from the Reasons for Geographic and Racial Differences in Stroke study cohort (cohort random sample). To account for the stratified sampling design, the cohort random sample was weighted back to the original cohort overall (n = 22 127). Cox proportional hazards models were used to examine the association of FGF23 concentration with incident CHD, adjusting for CHD risk factors and kidney function. In prespecified analyses, we examined whether race, sex, or chronic kidney disease modified the association of FGF23 concentration with incident CHD.
Plasma C-terminal FGF23 concentrations.
Investigator-adjudicated incident CHD events.
Of the 22 127 participants in the weighted cohort random sample, 13 059 (58.9%) were female and 9435 (42.6%) were black, and the mean age was 64.3 (95% CI, 63.7-64.9) years. Greater age, lower estimated glomerular filtration rate, higher urine albumin to creatinine ratio, and female sex were associated with higher FGF23 concentration at baseline. In multivariable models adjusted for established CHD risk factors and kidney function, higher FGF23 concentrations were associated with greater risk of CHD (hazard ratio [HR] comparing fourth with first quartile, 2.15; 95% CI, 1.35-3.42). The magnitude and strength of these associations differed by sex. However, these differences were no longer observed when adjusting for hormone therapy in women (men: HR comparing fourth with first quartile, 2.40; 95% CI, 1.30-4.42; women: HR comparing fourth with first quartile, 2.34; 95% CI, 1.04-5.27) or when using sex-specific FGF23 quartiles (men: HR comparing fourth with first quartile, 2.65; 95% CI, 1.43-4.90; women: HR comparing fourth with first quartile, 2.26; 95% CI, 1.02-5.03).
Higher FGF23 concentrations were associated with greater risk of CHD. Heterogeneity in the association by sex may be caused by differences in the distribution of plasma FGF23 concentrations or the use of hormone therapy in men vs women.
较高的循环成纤维细胞生长因子 23（FGF23）浓度与心力衰竭相关的心血管疾病事件有关，但 FGF23 与冠心病（CHD）的关联则不太一致。
确定血浆 FGF23 浓度与 CHD 发病的相关性，以及这种相关性是否因种族、性别或慢性肾脏病状态而不同。
设计、地点和参与者：我们在地理和种族差异中风研究（Reason for Geographic and Racial Differences in Stroke study）中，检查了 FGF23 浓度与 CHD 发病风险之间的关联。这是一项前瞻性队列研究，纳入了年龄在 45 岁及以上的黑人和白人成年人，招募时间为 2003 年 1 月至 2007 年 10 月，随访至 2011 年 12 月 31 日。我们采用病例-队列设计，在 829 名发生 CHD 的参与者和从 Reasons for Geographic and Racial Differences in Stroke 研究队列中随机选取的 812 名参与者（队列随机样本）中测量了 FGF23 浓度。为了考虑到分层抽样设计，对队列随机样本进行了加权，以恢复到原始队列的总体水平（n=22127）。我们使用 Cox 比例风险模型来检验 FGF23 浓度与 CHD 发病的相关性，调整了 CHD 危险因素和肾功能。在预设分析中，我们检查了种族、性别或慢性肾脏病是否改变了 FGF23 浓度与 CHD 发病的相关性。
血浆 C 端 FGF23 浓度。
经研究者裁定的 CHD 发病事件。
在加权的队列随机样本中，22127 名参与者中，13059 名（58.9%）为女性，9435 名（42.6%）为黑人，平均年龄为 64.3（95%置信区间，63.7-64.9）岁。年龄较大、估计肾小球滤过率较低、尿白蛋白与肌酐比值较高以及女性与基线时的 FGF23 浓度较高有关。在调整了已确立的 CHD 危险因素和肾功能的多变量模型中，较高的 FGF23 浓度与 CHD 发病风险增加相关（第四四分位数与第一四分位数比较的 HR，2.15；95%置信区间，1.35-3.42）。这些关联的程度和强度因性别而异。然而，当调整女性的激素治疗时（男性：第四四分位数与第一四分位数比较的 HR，2.40；95%置信区间，1.30-4.42；女性：第四四分位数与第一四分位数比较的 HR，2.34；95%置信区间，1.04-5.27）或使用性别特异性 FGF23 四分位数时（男性：第四四分位数与第一四分位数比较的 HR，2.65；95%置信区间，1.43-4.90；女性：第四四分位数与第一四分位数比较的 HR，2.26；95%置信区间，1.02-5.03），这些差异就不再存在了。
较高的 FGF23 浓度与 CHD 风险增加有关。性别差异的相关性可能是由血浆 FGF23 浓度的分布差异或男性与女性激素治疗的使用不同引起的。
