Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Department of Echocardiography, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
J Hum Hypertens. 2020 Jan;34(1):16-23. doi: 10.1038/s41371-019-0182-2. Epub 2019 Mar 7.
Aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism is an established genetic risk of hypertension, diabetes, and coronary heart diseases in Asian population. Previous experimental data showed ALDH2 regulated inflammation, a potential mechanism of heart failure with preserved ejection fraction (HFpEF). However, clinically, the association between ALDH2 polymorphism and incidence of HFpEF remains unknown. In this prospective cross-sectional study, ALDH2 genotyping was performed in 613 consecutive patients enrolled with cardiovascular diseases (CVDs), including hypertension, coronary heart diseases, and/or diabetes mellitus, with normal left ventricular ejection fraction (LVEF). HFpEF was diagnosed according to symptoms and/or signs of dyspnea, fatigue or ankle swelling, N-terminal pro-B-Type natriuretic peptide (NT pro-BNP ≥ 280 pg/mL), LVEF ≥ 50%, and at least one additional criterion: left atrial enlargement (left atrial diameter > 40 mm), diastolic dysfunction (E/E' ≥ 13 or E'/A' < 1) or concurrently with atrial fibrillation. Finally, of 613 patients with CVD, 379 patients (61.8%) were assigned to the wild-type ALDH21/1 group and 234 patients (38.2%) to the mutation-type ALDH22 group according to genotyping results. Sixty-nine patients (11.3%) were diagnosed with HFpEF. In ALDH22 group, the occurrence of HFpEF was higher (15.4% vs. 8.7%, p = 0.011) than that in ALDH21/1 group. Leukocyte count, the indicator of systemic inflammation, was significantly higher (6.9 ± 2.4 × 10/L vs. 6.5 ± 1.9 × 10/L, p = 0.010) in ALDH22 group compared to ALDH21/1 group. In conclusion, ALDH22 variant is associated with the risk of HFpEF in patients with CVD. Increased systemic inflammation probably involved in this disease process.
乙醛脱氢酶 2 (ALDH2) rs671 多态性是亚洲人群高血压、糖尿病和冠心病的既定遗传风险因素。先前的实验数据表明，ALDH2 可调节炎症，这是射血分数保留型心力衰竭（HFpEF）的潜在机制。然而，临床上，ALDH2 多态性与 HFpEF 发生率之间的关联尚不清楚。在这项前瞻性横断面研究中，对 613 例连续就诊的心血管疾病（CVD）患者进行了 ALDH2 基因分型，包括高血压、冠心病和/或糖尿病，左心室射血分数（LVEF）正常。HFpEF 根据症状和/或呼吸困难、疲劳或脚踝肿胀、N 末端 pro-B 型利钠肽（NT pro-BNP≥280pg/mL）、LVEF≥50%以及至少一个附加标准诊断：左心房扩大（左心房直径>40mm）、舒张功能障碍（E/E'≥13 或 E'/A'<1）或同时伴有心房颤动。最后，在 613 例 CVD 患者中，根据基因分型结果，379 例（61.8%）患者被分配到野生型 ALDH21/1 组，234 例（38.2%）患者被分配到突变型 ALDH22 组。69 例（11.3%）被诊断为 HFpEF。在 ALDH22 组中，HFpEF 的发生率更高（15.4%比 8.7%，p=0.011）。白细胞计数，全身性炎症的指标，在 ALDH22 组中明显高于 ALDH21/1 组（6.9±2.4×10/L 比 6.5±1.9×10/L，p=0.010）。总之，ALDH22 变体与 CVD 患者 HFpEF 的风险相关。全身性炎症的增加可能参与了这一疾病过程。
