研究背景

急性冠脉综合征（acute coronary syndrome，ACS）是冠状动脉粥样硬化性心脏病的一种严重表现形式。针对ACS患者，控制血脂及抗血小板是两大核心手段。前蛋白转化酶枯草溶菌素 9（preprotein converting enzyme subtilisin kexin 9，PCSK9）抑制剂的应用，可使低密度脂蛋白胆固醇（low-density lipoprotein cholesterol，LDL-C）水平降低50%~70%，在他汀类药物治疗的基础上进一步减少主要不良心血管事件（Major adverse cardiovascular events，MACEs）。迄今为止，尚无有关ACS患者接受经皮冠状动脉介入治疗（percutaneous coronary intervention，PCI）术后早期启动PCSK9抑制剂强化降脂的循证证据。

研究方法

本研究是一项单中心随机对照研究，接受PCI术后的非ST段抬高型ACS（non-ST segment elevated ACS，NSTE-ACS）患者以1：1比例随机进入依洛尤单抗组和对照组。所有入选患者在基线时均接受冠脉造影检查（coronary angiography，CAG）及光学相干断层扫描（optical coherence tomography，OCT）检查，并进行12周的随访。主要终点为术后12周OCT检查下的靶病变部位支架内皮覆盖率,定义为被内皮覆盖的支架丝数/总支架丝数。次要终点为术后12周OCT检查下的靶病变部位支架新生内皮厚度以及非靶病变部位斑块的纤维帽厚度（fibrous caps thickness，FCT）、脂质弧角度。支架新生内皮厚度通过OCT分析软件（QIVUS research edition@3.1）计算，包括支架丝距管腔最短距离（shortest distance stent lumen，SDSL）和支架丝距管腔轮廓距离（stent contour distance，SCD）。

研究结果

研究共纳入36例NSTE-ACS患者，平均年龄为57岁，其中21.6%为女性。依洛尤单抗组在基线时与对照组相比中有更高的LDL-C、载脂蛋白B（apolipoprotein B，apoB）、高敏C反应蛋白（high sensitive C-Reactive Protein， hsCRP）以及非高密度脂蛋白胆固醇（non high-density lipoprotein cholesterol，non-HDL-C）水平。在12周后，与对照组相比，依洛尤单抗组的LDL-C（-47.7% vs -3.1%，P=0.004）、hsCRP（-71.4% vs -11.5%，P=0.008）、脂蛋白a（-37.0% vs 12.9%，P=0.021）以及non-HDL-C（-44.7% vs -3.6%，P<0.001）水平均显著降低。在第12周时进行OCT检查，依洛尤单抗组与对照组支架内皮覆盖率分别为94.4%和92.9%。通过广义线性混合效应模型得出两组间支架内皮覆盖率的差值为1.7%（OR=1.36；95%CI：-1.0% ~ 4.4%；P=0.223）；在调整性别、年龄、体重指数（body mass index，BMI）、既往PCI史及糖尿病病史后，两组间支架内皮覆盖率的差值为3.3%（OR=1.51；95%CI ~ -2.1%，8.6%；P=0.285）；再进一步调整依折麦布、基线血脂谱及hsCRP水平后，两组间支架内皮覆盖率的差值为1.6%（OR=1.74；95%CI：-5.8% ~ 9.0%；P=0.382）。对靶病变部位的支架新生内皮厚度进行分析后，依洛尤单抗组的SDSL（64.0 μm vs 57.1 μm，P<0.001）以及SCD（64.4 μm vs 58.4 μm，P<0.001）相较于对照组显著升高。除此之外，在对非靶病变处斑块进行分析后，依洛尤单抗组的FCT（27.12% vs 41.28%，P=0.337）与脂质弧角度（-19.39% vs -15.53%，P=0.552）的变化百分比，与对照组相比未观察到显著性差异。

研究结论

ACS患者接受PCI术后尽早启动依洛尤单抗强化降脂3个月后，显示出改善支架内皮覆盖率的趋势，同时可一定程度增加支架新生内皮厚度。本研究可为ACS患者PCI术后尽早启动PCSK9抑制剂强化降脂提供血管内皮功能改善的腔内影像学证据。

研究背景

2型糖尿病（Type 2 diabetes mellitus，T2DM）是导致冠心病（Coronary Heart Disease，CHD）患者心血管事件风险增加的独立危险因素。钠-葡萄糖协同转运蛋白2（Sodium-glucose cotransporter 2，SGLT2）抑制剂已被证实能够显著降低高危心血管风险患者的主要心血管不良事件（Major adverse cardiovascular events，MACEs）发生率，然而，其具体心血管保护机制仍不明确。脂代谢的影响可能是机制中的一个重要环节，但目前关于SGLT2抑制剂与冠心病患者脂代谢相关指标之间关系的真实世界研究数据仍然不足。

研究方法

本研究是一项单中心前瞻性队列研究，纳入了2020年8月至2021年8月期间在心血管代谢中心住院的550名CHD合并T2DM患者。患者按照是否使用SGLT2抑制剂治疗分为两组。此外，根据基线空腹血糖（fasting blood glucose，FBG）水平，患者被分为三个血糖控制情况类别：血糖控制良好（FBG < 6.1 mmol/L）、血糖控制中等（FBG 6.1 mmol/L~7.0 mmol/L）和血糖控制不佳（FBG > 7.0 mmol/L）。研究收集了基线人口统计学信息和生化指标，其中脂代谢相关指标包括血浆脂质谱、残余脂质谱、甘油三酯衍生指标。甘油三酯衍生指标包括血浆致动脉粥样硬化指数（atherogenic index of plasma，AIP）和甘油三酯葡萄糖指数（Triglyceride glucose index，TyG）。

研究结果

本研究共纳入550例CHD合并T2DM患者，平均年龄为60.2岁，其中女性占比21.8%。多元线性回归分析显示，接受SGLT2抑制剂治疗能显著降低AIP（β：-0.052；95% CI：-0.096，-0.009；P=0.018）和甘油三酯水平（β：-0.089；95% CI：-0.177，-0.004；P=0.039）。此外，不同血糖控制情况中SGLT2抑制剂治疗与AIP降低水平之间关系存在显著差异（交互作用P=0.041），其中血糖控制不佳的患者获益更为显著（β=-0.080，95% CI：-0.138至-0.023，P=0.007）。此外，较高的SGLT2抑制剂的使用率与AIP水平降低显著相关（Q1 vs Q4：比值比=1.887；95% CI：1.149，3.100；P=0.012），且该变化呈线性趋势（趋势P=0.035）。在高血压和高体重指数患者中进行的敏感性分析进一步证实了这些结果的稳健性。

研究结论

SGLT2抑制剂显著改善了CHD合并T2DM患者的AIP和TG水平，且不受背景降糖药物和降脂药物的影响。除此之外，亚组分析提示血糖控制不佳的CHD患者可能从SGLT2抑制剂治疗中获益更多。

Background:

Patients with acute coronary syndromes (ACS) could benefit from Proprotein Convertase Subtilisin/Kexin 9 (PCSK9)inhibitor in reducing major adverse cardiovascular events (MACEs). However, there is limited evidence on whether early post-PCI use of PCSK9 inhibitor improves stent strut coverage.

Methods:

This trial utilized optical coherence tomography (OCT) to investigate the effects of adding evolocumab to conventional lipid-lowering therapy on rate of stent struts endothelial coverage in ACS patients within 24 hours after PCI. 36 patients were randomized into receiving lipid-lowering therapy with PCSK9 inhibitor (evolocumab group) or conventional lipid-lowering therapy alone (control group) in a 1:1 ratio. OCT examinations were performed at baseline and week 12. The rate of stent strut endothelial coverage was defined as the ratio of covered struts/total struts. The stent strut neo-intimal thickness was measured by software (QIVUS research edition@3.1) and represented as the shortest distance from strut to lumen (SDSL) and the stent contour distance (SCD). The primary outcome was stent strut endothelial coverage rate 12 weeks post-randomization. Secondary outcomes included SDSL and SCD, and the changes of fibrous cap thickness (FCT) and lipid arc during follow-up in non-culprit lesion less than 70% stenosis.

Results:

Apart from higher baseline levels of low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), high-sensitivity C-reactive protein (hsCRP), non-high-density lipoprotein cholesterol (non-HDL-C), and small dense LDL in the evolocumab group, there were no significant differences between the two groups in other baseline characteristics, medication use, or biomarkers. During the follow-up period, in the evolocumab group, greater percent reductions in LDL-C (-47.7% vs -3.1%, P=0.004), lipoprotein(a) (-37.0% vs 12.9%, P=0.021), and high-sensitivity C-reactive protein (-71.4% vs -11.5%, P=0.008) was found when compared with the control group. Serial OCT evaluation was performed on 29 PCI-targeted lesions. The rate of stent strut endothelial coverage was 94.4% in the evolocumab group and 92.9% in the control group. Logistic regression analysis indicated an unadjusted difference of 1.7% (OR 1.36, 95%CI -1.0% to 4.4%, P=0.223). After adjusting for gender, age, BMI, prior PCI, and diabetes, the difference was 3.3% (OR 1.51, 95%CI -2.1% to 8.6%, P=0.285). Further adjustment for medication and laboratory results showed a difference of 1.6% (OR 1.74, 95%CI -5.8% to 9.0%, P=0.382). For the key secondary outcomes, SDSL (64.0 μm vs. 57.1 μm, P<0.001) and SCD (64.4 μm vs. 58.4 μm, P<0.001) were significantly higher in the evolocumab group after 12 weeks. Additionally, both groups showed improvement trends in the percent change of FCT (evolocumab: 27.12% vs. control: 41.28%, P=0.337) and lipid arc (evolocumab: -19.39% vs. -15.53%, P=0.552) in non-culprit lesion, although these differences between groups were not statistically significant.

Conclusions:

Early initiation of intensive lipid-lowering therapy with evolocumab within 3 months after PCI in ACS patients demonstrated a trend toward improved stent endothelial coverage while moderately increasing neointimal thickness. This study provides intravascular imaging evidence supporting the early use of PCSK9 inhibitors for intensive lipid lowering to enhance vascular endothelial function in post-PCI ACS patients.

Background:

Coronary heart disease (CHD) is a major cause of mortality in individuals with glycemic metabolism disorders. Researches have shown that sodium-dependent glucose transporter 2 inhibitors (SGLT2i) provide benefits to diabetic patients with elevated cardiovascular risk.

Methods:

This prospective study analyzed data from 550 CHD patients from August 2020 to August 2021. Of these, 223 patients received SGLT2i, while 327 did not. Patients were stratified into three categories by glycemic control status based on fasting blood glucose (FBG) levels: well-controlled diabetes (FBG<6.1mmol/L), moderately controlled diabetes (FBG between 6.1 mmol/L to 7.0 mmol/L) and poorly controlled diabetes (FBG>7.0mmol/L). We collected baseline demographic information and biochemical markers, including plasma lipid profiles and triglyceride (TG)-derived markers, such as the atherogenic index of plasma (AIP) and triglyceride-glucose (TyG) index. The AIP was calculated as Lg [TG (mg/dL)/HDL (mg/dL)], and the TyG index as Ln[TG(mg/dL)×FBG(mg/dL)/2]. Associations among biochemical markers, SGLT2i use, and glycemic control status were examined using multiple linear and logistic regression, subgroup analysis, and sensitivity analysis.

Results:

The study included 550 CHD patients with an average age of 60.2 years, 21.8% of whom were female. Multiple linear regression indicated a significant positive effect of SGLT2i on changing AIP (β=-0.052, 95% CI, -0.096 to -0.009, P=0.018) and TG levels (β=-0.089, 95% CI, -0.177 to -0.004, P=0.039). The interaction between SGLT2i use and glycemic control status was statistically significant for AIP changes (P for interaction = 0.041), with greater benefits observed in patients with poorly controlled diabetes (β=-0.080, 95% CI, -0.138 to -0.023, P=0.007). Logistic regression revealed higher SGLT2i prescription rates linked to significant AIP reduction (Q1 vs Q4: odds ratio, 1.887, 95% CI, 1.149 to 3.100, P=0.012; P for trend = 0.035). Sensitivity analysis confirmed these findings in patients with hypertension and high BMI.

Conclusions:

SGLT2i significantly improved AIP and TG levels in CHD patients with comorbid diabetes, regardless of background hypoglycemic and lipid-lowering drugs. Subgroup analysis suggests that CHD patients with poorly controlled diabetes might benefit more from SGLT2i treatment.