Division of Cardiology, Department of Internal Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, Taiwan.
Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, No.7, Chung-Chan South Road, Taipei, 100, Taiwan.
Cardiovasc Diabetol. 2023 Feb 20;22(1):35. doi: 10.1186/s12933-023-01767-x.
The glycemic continuum often indicates a gradual decline in insulin sensitivity leading to an increase in glucose levels. Although prediabetes is an established risk factor for both macrovascular and microvascular diseases, whether prediabetes is independently associated with the risk of developing atrial fibrillation (AF), particularly the occurrence time, has not been well studied using a high-quality research design in combination with statistical machine-learning algorithms.
Using data available from electronic medical records collected from the National Taiwan University Hospital, a tertiary medical center in Taiwan, we conducted a retrospective cohort study consisting 174,835 adult patients between 2014 and 2019 to investigate the relationship between prediabetes and AF. To render patients with prediabetes as comparable to those with normal glucose test, a propensity-score matching design was used to select the matched pairs of two groups with a 1:1 ratio. The Kaplan-Meier method was used to compare the cumulative risk of AF between prediabetes and normal glucose test using log-rank test. The multivariable Cox regression model was employed to estimate adjusted hazard ratio (HR) for prediabetes versus normal glucose test by stratifying three levels of glycosylated hemoglobin (HbA1c). The machine-learning algorithm using the random survival forest (RSF) method was further used to identify the importance of clinical factors associated with AF in patients with prediabetes.
A sample of 14,309 pairs of patients with prediabetes and normal glucose test result were selected. The incidence of AF was 11.6 cases per 1000 person-years during a median follow-up period of 47.1 months. The Kaplan-Meier analysis revealed that the risk of AF was significantly higher in patients with prediabetes (log-rank p < 0.001). The multivariable Cox regression model indicated that prediabetes was independently associated with a significant increased risk of AF (HR 1.24, 95% confidence interval 1.11-1.39, p < 0.001), particularly for patients with HbA1c above 5.5%. The RSF method identified elevated N-terminal natriuretic peptide and altered left heart structure as the two most important risk factors for AF among patients with prediabetes.
Our study found that prediabetes is independently associated with a higher risk of AF. Furthermore, alterations in left heart structure make a significant contribution to this elevated risk, and these structural changes may begin during the prediabetes stage.
血糖连续体通常表明胰岛素敏感性逐渐下降，导致血糖水平升高。尽管糖尿病前期是大血管和微血管疾病的既定危险因素，但糖尿病前期是否与心房颤动 (AF) 的发病风险独立相关，特别是发病时间，尚未使用高质量的研究设计和统计机器学习算法进行很好的研究。
我们使用来自台湾国立台湾大学医院电子病历中收集的数据进行了一项回顾性队列研究，该研究纳入了 2014 年至 2019 年间的 174835 名成年患者，以调查糖尿病前期与 AF 之间的关系。为了使糖尿病前期患者与血糖正常的患者具有可比性，我们使用倾向评分匹配设计选择两组的匹配对，比例为 1:1。使用对数秩检验比较糖尿病前期和血糖正常组的累积 AF 风险。使用多变量 Cox 回归模型通过糖化血红蛋白 (HbA1c) 的三个水平分层来估计糖尿病前期与血糖正常组的调整后的危险比 (HR)。进一步使用随机生存森林 (RSF) 方法的机器学习算法来确定与糖尿病前期患者 AF 相关的临床因素的重要性。
选择了 14309 对糖尿病前期和血糖正常的患者。在中位随访 47.1 个月期间，AF 的发生率为每 1000 人年 11.6 例。Kaplan-Meier 分析显示，糖尿病前期患者的 AF 风险显著更高 (对数秩 p<0.001)。多变量 Cox 回归模型表明，糖尿病前期与 AF 发生的显著风险增加相关 (HR 1.24，95%置信区间 1.11-1.39，p<0.001)，尤其是 HbA1c 高于 5.5%的患者。RSF 方法确定升高的 N 末端脑钠肽和改变的左心结构是糖尿病前期患者 AF 的两个最重要的危险因素。
我们的研究发现，糖尿病前期与 AF 风险增加独立相关。此外，左心结构的改变对这种升高的风险有重要贡献，并且这些结构变化可能在糖尿病前期阶段就开始了。
