压力相关神经生物学途径将社会经济差距与心血管疾病联系起来。
Stress-Associated Neurobiological Pathway Linking Socioeconomic Disparities to Cardiovascular Disease.
机构信息
Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
出版信息
J Am Coll Cardiol. 2019 Jul 2;73(25):3243-3255. doi: 10.1016/j.jacc.2019.04.042.
BACKGROUND
Lower socioeconomic status (SES) associates with a higher risk of major adverse cardiac events (MACE) via mechanisms that are not well understood.
OBJECTIVES
Because psychosocial stress is more prevalent among those with low SES, this study tested the hypothesis that stress-associated neurobiological pathways involving up-regulated inflammation in part mediate the link between lower SES and MACE.
METHODS
A total of 509 individuals, median age 55 years (interquartile range: 45 to 66 years), underwent clinically indicated whole-body F-fluorodeoxyglucose positron emission tomography/computed tomography imaging and met pre-defined inclusion criteria, including absence of known cardiovascular disease or active cancer. Baseline hematopoietic tissue activity, arterial inflammation, and in a subset of 289, resting amygdalar metabolism (a measure of stress-associated neural activity) were quantified using validated F-fluorodeoxyglucose positron emission tomography/computed tomography methods. SES was captured by neighborhood SES factors (e.g., median household income and crime). MACE within 5 years of imaging was adjudicated.
RESULTS
Over a median 4.0 years, 40 individuals experienced MACE. Baseline income inversely associated with amygdalar activity (standardized β: -0.157 [95% confidence interval (CI): -0.266 to -0.041]; p = 0.007) and arterial inflammation (β: -0.10 [95% CI: -0.18 to -0.14]; p = 0.022). Further, income associated with subsequent MACE (standardized hazard ratio: 0.67 [95% CI: 0.47 to 0.96]; p = 0.029) after multivariable adjustments. Mediation analysis demonstrated that the path of: ↓ neighborhood income to ↑ amygdalar activity to ↑ bone marrow activity to ↑ arterial inflammation to ↑ MACE was significant (β: -0.01 [95% CI: -0.06 to -0.001]; p < 0.05).
CONCLUSIONS
Lower SES: 1) associates with higher amygdalar activity; and 2) independently predicts MACE via a serial pathway that includes higher amygdalar activity, bone marrow activity, and arterial inflammation. These findings illuminate a stress-associated neurobiological mechanism by which SES disparities may potentiate adverse health outcomes.
背景
较低的社会经济地位（SES）与主要不良心脏事件（MACE）的风险增加有关，但具体机制尚不清楚。
目的
由于社会心理压力在 SES 较低的人群中更为普遍，因此本研究假设，涉及炎症上调的与应激相关的神经生物学途径部分介导了 SES 较低与 MACE 之间的联系。
方法
共纳入 509 名中位年龄 55 岁（四分位距：45 至 66 岁）的个体，这些个体接受了临床指征明确的全身 F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描成像，并符合预先确定的纳入标准，包括无已知心血管疾病或活动性癌症。使用经过验证的 F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描方法，量化基线造血组织活性、动脉炎症以及 289 名个体的静息杏仁核代谢（应激相关神经活动的一种测量方法）。SES 通过社区 SES 因素（例如，家庭收入中位数和犯罪）来捕获。在成像后 5 年内判定 MACE。
结果
在中位时间为 4.0 年的随访期间，有 40 名个体发生了 MACE。基线收入与杏仁核活性呈负相关（标准化β：-0.157[95%置信区间（CI）：-0.266 至-0.041]；p=0.007）和动脉炎症（β：-0.10[95%CI：-0.18 至-0.14]；p=0.022）。此外，在多变量调整后，收入与随后的 MACE 相关（标准化风险比：0.67[95%CI：0.47 至 0.96]；p=0.029）。中介分析表明，从↓社区收入到↑杏仁核活性，再到↑骨髓活性，再到↑动脉炎症，再到↑MACE 的路径具有统计学意义（β：-0.01[95%CI：-0.06 至-0.001]；p<0.05）。
结论
较低的 SES：1）与较高的杏仁核活性相关；2）通过包括较高的杏仁核活性、骨髓活性和动脉炎症在内的连续途径独立预测 MACE。这些发现阐明了 SES 差异可能增强不良健康结果的应激相关神经生物学机制。
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