Department of Emergency Medicine, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong, 250012, People's Republic of China.
Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China.
Cardiovasc Diabetol. 2024 Feb 24;23(1):83. doi: 10.1186/s12933-023-02092-z.
Whether distributions and prognostic values of high-sensitivity cardiac troponin (hs-cTn) T and I are different across normoglycemic, prediabetic, and diabetic populations is unknown.
10127 adult participants from the National Health and Nutrition Examination Survey 1999-2004 with determined glycemic status and measurement of at least one of hs-cTn assays were included, from whom healthy participants and presumably healthy diabetic and prediabetic participants were selected to investigate pure impacts of glycemic status on distributions of hs-cTn. The nonparametric method and bootstrapping were used to derive the 99th upper reference limits of hs-cTn and 95% CI. Participants with available follow-up and hs-cTn concentrations of all 4 assays were included in prognostic analyses. Associations of hs-cTn with all-cause and cardiac-specific mortality were modeled by Cox proportional hazard regression under the complex survey design. The incremental value of hs-cTn to an established risk score in predicting cardiac-specific mortality was assessed by the 10-year area under time-dependent receiver operating characteristic curve (AUC) using the Fine-Grey competing risk model.
Among 9714 participants included in prognostic analyses, 5946 (61.2%) were normoglycemic, 2172 (22.4%) prediabetic, and 1596 (16.4%) diabetic. Hyperglycemic populations were older than the normoglycemic population but sex and race/ethnicity were similar. During the median follow-up of 16.8 years, hs-cTnT and hs-cTnI were independently associated with all-cause and cardiac-specific mortality across glycemic status. In the diabetic population, adjusted hazard ratios per 1-standard deviation increase of log-transformed hs-cTnT and hs-cTnI (Abbott) concentrations were 1.77 (95% CI 1.48-2.12; P < .001) and 1.83 (95% CI 1.33-2.53; P < .001), respectively, regarding cardiac-specific mortality. In the diabetic but not the normoglycemic population, adding either hs-cTnT (difference in AUC: 0.062; 95% CI 0.038-0.086; P < 0.001) or hs-cTnI (Abbott) (difference in AUC: 0.071; 95% CI 0.046-0.097; P < 0.001) would significantly increase the discriminative ability of the risk score; AUC of the score combined with hs-cTnT would be further improved by incorporating hs-cTnI (0.018; 95%CI 0.006-0.029; P = 0.002). The 99th percentile of hs-cTnT of the presumably healthy diabetic population was higher than the healthy population and had no overlap in 95% CIs, however, for hs-cTnI 99th percentiles of the two populations were very close and 95% CIs extensively overlapped.
Hs-cTnT and hs-cTnI demonstrated consistent prognostic associations across glycemic status but incremental predictive values in hyperglycemic populations only. The susceptibility of hs-cTnT 99th percentiles to diabetes plus the additive value of hs-cTnI to hs-cTnT in diabetic cardiovascular risk stratification suggested hs-cTnI and hs-cTnT may be differentially associated with glycemic status, but further research is needed to illustrate the interaction between hyperglycemia and hs-cTn.
目前尚不清楚高敏心肌肌钙蛋白（hs-cTn）T 和 I 在血糖正常、糖尿病前期和糖尿病人群中的分布和预后价值是否不同。
本研究纳入了 1999-2004 年全国健康和营养调查（National Health and Nutrition Examination Survey，NHANES）中至少有一项 hs-cTn 检测的 10127 名成年参与者，其中包括健康参与者和推测为健康的糖尿病和糖尿病前期参与者，以研究血糖状态对 hs-cTn 分布的纯影响。采用非参数方法和自举法得出 hs-cTn 的第 99 个上限参考值和 95%CI。将有可用随访和所有 4 项 hs-cTn 检测结果的参与者纳入预后分析。采用复杂抽样设计下的 Cox 比例风险回归模型，对 hs-cTn 与全因和心脏特异性死亡率的相关性进行建模。使用 Fine-Grey 竞争风险模型评估 hs-cTn 对既定风险评分在预测心脏特异性死亡率方面的增量价值，通过时间依赖性接收器工作特征曲线（receiver operating characteristic curve，ROC）下面积（area under the curve，AUC）的 10 年评估。
在预后分析中纳入的 9714 名参与者中，5946 名（61.2%）血糖正常，2172 名（22.4%）为糖尿病前期，1596 名（16.4%）为糖尿病。高血糖人群比血糖正常人群年龄更大，但性别和种族/民族相似。在中位随访 16.8 年期间，hs-cTnT 和 hs-cTnI 在血糖状态下均与全因和心脏特异性死亡率独立相关。在糖尿病人群中，hs-cTnT 和 hs-cTnI（雅培）浓度每增加 1 个标准差的校正风险比分别为 1.77（95%CI 1.48-2.12；P<0.001）和 1.83（95%CI 1.33-2.53；P<0.001），与心脏特异性死亡率相关。仅在糖尿病人群中，添加 hs-cTnT（AUC 差异：0.062；95%CI 0.038-0.086；P<0.001）或 hs-cTnI（雅培）（AUC 差异：0.071；95%CI 0.046-0.097；P<0.001）均可显著提高风险评分的区分能力；将 hs-cTnI 纳入评分后，评分结合 hs-cTnT 的 AUC 将进一步提高（0.018；95%CI 0.006-0.029；P=0.002）。推测为健康的糖尿病人群的 hs-cTnT 第 99 百分位数高于健康人群，且 95%CI 无重叠，但两人群的 hs-cTnI 第 99 百分位数非常接近，95%CI 广泛重叠。
hs-cTnT 和 hs-cTnI 在血糖状态下均具有一致的预后相关性，但仅在高血糖人群中具有增量预测价值。hs-cTnT 第 99 百分位数对糖尿病的敏感性以及 hs-cTnI 对糖尿病心血管风险分层中 hs-cTnT 的附加价值表明，hs-cTnT 和 hs-cTnI 可能与血糖状态存在不同的相关性，但需要进一步的研究来阐明高血糖与 hs-cTn 之间的相互作用。
