Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri.
Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, District of Columbia.
J Am Geriatr Soc. 2019 Nov;67(11):2353-2361. doi: 10.1111/jgs.16092. Epub 2019 Jul 30.
Cardiac troponin T, measured using a high-sensitive assay (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with increased stroke risk and perhaps with cognitive decline. However, few well-designed prospective studies with extended follow-up have been conducted. We aimed to estimate the association of hs-cTnT and NT-proBNP with 15-year cognitive change in the Atherosclerosis Risk in Communities (ARIC) study.
Prospective cohort study.
Four US communities.
A total of 9114 and 9108 participants from the Atherosclerosis Risk in Communities study for analyses of hs-cTnT and NT-proBNP, respectively.
We examined association of hs-cTnT and NT-proBNP with 15-year change (1996-1998 to 2011-2013) in three cognitive tests of executive function (Digit Symbol Substitution Test), verbal learning memory (Delayed Word Recall Test), and semantic fluency (Word Fluency Test), and an overall score combining the three tests using multivariable linear mixed effect models. We conducted several sensitivity analyses including multiple imputations to address bias due to missing data and attrition, and we compared associations within groups combining hs-cTnT and NT-proBNP into a three-level categorical variable.
At baseline (1996-1998), mean age was 63.4 (standard deviation [SD] = 5.7) years; 56.4% were women, and 17.5% were black. The hs-cTnT at baseline was not associated with cognitive change in any measure. Some evidence indicated accelerated decline in verbal learning and memory when comparing those in the highest with the lowest NT-proBNP quintiles; however, this association was not replicated when considering clinically relevant cutoffs or deciles of exposure in survivors. Sensitivity analyses were consistent with our primary analyses. There was little evidence to support effect modification by any considered factors. People with highest levels of both biomarkers had excessive decline in global z scores vs people with lowest levels (-.34; 95% confidence interval = -.63 to -.04).
Markers of myocardial injury and stretch were not associated with cognitive decline following 15 years among survivors, but when combined together they were suggestive in post hoc analysis. Whether this represents targets of intervention should be examined in the future. J Am Geriatr Soc 67:2353-2361, 2019.
使用高敏检测法(hs-cTnT)测量心肌钙蛋白 T 和 N 末端脑钠肽前体(NT-proBNP)与卒中风险增加相关,或许与认知能力下降相关。然而,很少有经过精心设计且随访时间较长的前瞻性研究。我们旨在评估 hs-cTnT 和 NT-proBNP 与动脉粥样硬化风险社区研究(ARIC)中 15 年认知变化的相关性。
前瞻性队列研究。
美国四个社区。
分别对来自 ARIC 研究的 9114 名和 9108 名参与者进行 hs-cTnT 和 NT-proBNP 分析。
我们使用多变量线性混合效应模型,检测 hs-cTnT 和 NT-proBNP 与执行功能(数字符号替换测试)、语言学习记忆(延迟单词回忆测试)和语义流畅性(单词流畅性测试)三个认知测试的 15 年变化(1996-1998 年至 2011-2013 年)之间的关联,以及将这三个测试组合成一个综合分数。我们进行了几项敏感性分析,包括多重插补,以解决因数据缺失和流失引起的偏差,并在结合 hs-cTnT 和 NT-proBNP 为三水平分类变量的情况下比较了组内的关联。
在基线(1996-1998 年)时,平均年龄为 63.4 岁(标准差[SD] = 5.7);56.4%为女性,17.5%为黑人。基线时的 hs-cTnT 与任何测量的认知变化均无关。有一些证据表明,与 NT-proBNP 五分位最低的人相比,最高的人在语言学习和记忆方面的认知下降速度更快;然而,当考虑幸存者的临床相关临界点或暴露的十分位数时,这种关联并未得到复制。敏感性分析与我们的主要分析一致。几乎没有证据支持任何考虑因素的效应修饰。与最低水平生物标志物的人相比,最高水平的两种生物标志物的人整体 z 评分下降过多(-0.34;95%置信区间=-0.63 至-0.04)。
心肌损伤和拉伸标志物与幸存者 15 年后的认知下降无关,但在事后分析中结合在一起时具有提示性。这是否代表干预的目标,未来应加以检验。