Department of Cardiology, Cardiology Clinic, Gaziantep City Hospital, Gaziantep, Turkey.
Eur Rev Med Pharmacol Sci. 2024 Aug;28(16):4121-4135. doi: 10.26355/eurrev_202408_36665.
Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are a new class of drugs that lower blood glucose and reduce mortality in heart failure patients with reduced ejection fraction (HFrEF). They also have antioxidant effects. The exact mechanism of SGLT-2i is unknown. This study investigated the effects of SGLT-2i on asprosin, matrix metalloproteinase (MMP), and tissue inhibitor of MMP (TIMP-1) concentrations and echocardiographic measurements of strain in the left heart chamber.
This prospective follow-up study included 56 patients with HFrEF and diabetes mellitus (DM) who did not initially receive SGLT-2 inhibitors. The control group consisted of 30 healthy individuals. Patients with HFrEF were administered either empagliflozin (n=28) or dapagliflozin (n=28) in addition to their treatment. The patient group was evaluated for left ventricular global longitudinal strain (LVGLS), left atrial (LA) strain, and LA volumes at the beginning and third month of the study. The control group had blood collected once, while the patient group had it twice: at the start of the trial, on the same day as the echocardiographic evaluation, and at the end of the third month after starting an SGLT-2i. Serum levels of asprosin, MMP-1 and TIMP-1 were assessed.
LVGLS increased significantly in HFrEF patients at the third-month assessment compared to baseline (-8.6±2.3% vs. -9±2.5%, respectively; p<0.001), but there was no significant difference in LVEF (p=0.593). A substantial increase was observed in the left atrial ejection fraction (LAEF) compared to baseline values (36.3±9.4% vs. 42.1±8.7%, respectively; p<0.001), driven by a reduction in minimal LA volume [32.5 (19-96) ml vs. 32 (20-86) ml, respectively; p=0.018]. Compared to baseline evaluation, LA reservoir [13 (6-25) vs. 16.5 (2-26), respectively; p<0.001] and contraction strain (7.7±4.3 vs. 9.4±5.6, respectively; p=0.014) values were also enhanced at the third month. Between the baseline and the 3rd month, the patient group's LA conduit strain (p=0.122) and LA maximum volume (p=0.716) remained unchanged. Serum asprosin significantly increased (11.7±5.1 ng/mL vs. 14±9.4 ng/mL, respectively; p=0.032); however, no statistically significant alteration was detected in MMP (p=0.278) and TIMP-1 levels (p=0.401).
SGLT-2i are associated with elevated levels of LVGLS, LAEF, LA contraction strain, and LA reservoir strain. SGLT-2i medications may improve plasma asprosin levels to boost energy metabolism, reduce oxidative stress and reactive oxygen radicals.
钠-葡萄糖协同转运蛋白-2 抑制剂（SGLT-2i）是一类新型药物，可降低射血分数降低的心力衰竭（HFrEF）患者的血糖并降低死亡率。它们还具有抗氧化作用。SGLT-2i 的确切机制尚不清楚。本研究旨在探讨 SGLT-2i 对天冬氨酸蛋白酶原（asprosin）、基质金属蛋白酶（MMP）和基质金属蛋白酶组织抑制剂 1（TIMP-1）浓度以及左心室内应变的超声心动图测量值的影响。
这项前瞻性随访研究纳入了 56 名未初始接受 SGLT-2i 治疗的 HFrEF 和糖尿病（DM）患者。对照组由 30 名健康个体组成。在 HFrEF 患者中，除了常规治疗外，还给予恩格列净（n=28）或达格列净（n=28）。在研究开始和第 3 个月评估患者的左心室整体纵向应变（LVGLS）、左心房（LA）应变和 LA 容积。对照组仅采血一次，而患者组采血两次：在试验开始时、与超声心动图评估同日，以及开始使用 SGLT-2i 后的第 3 个月末。评估血清中天冬氨酸蛋白酶原、MMP-1 和 TIMP-1 水平。
与基线相比，HFrEF 患者在第 3 个月的评估中 LVGLS 显著增加（-8.6±2.3%比-9±2.5%；p<0.001），但左心室射血分数（LVEF）无显著差异（p=0.593）。与基线相比，左心房射血分数（LAEF）显著增加（36.3±9.4%比 42.1±8.7%；p<0.001），这主要归因于最小左房容积的减少[32.5（19-96）ml 比 32（20-86）ml；p=0.018]。与基线评估相比，LA 储备[13（6-25）比 16.5（2-26）；p<0.001]和收缩应变（7.7±4.3 比 9.4±5.6；p=0.014）在第 3 个月也增强。在基线和第 3 个月之间，患者组的 LA 传导应变（p=0.122）和 LA 最大容积（p=0.716）保持不变。血清天冬氨酸蛋白酶原水平显著升高（11.7±5.1 ng/ml 比 14±9.4 ng/ml；p=0.032）；然而，MMP（p=0.278）和 TIMP-1 水平（p=0.401）无统计学显著变化。
SGLT-2i 与 LVGLS、LAEF、LA 收缩应变和 LA 储备应变的升高有关。SGLT-2i 药物可能会提高血浆天冬氨酸蛋白酶原水平，以促进能量代谢，减少氧化应激和活性氧自由基。
