Impact of risk factors on intervened and non-intervened coronary lesions.

INTRODUCTION: In-stent restenosis (ISR) and aggravated non-intervened coronary lesions (ANL) are two pivotal aspects of disease progression in patients with coronary artery disease (CAD). Established risk factors for both include hyperlipidemia, hypertension, diabetes, chronic kidney disease, and smoking. However, there is limited research on the comparative risk factors for the progression of these two aspects of progression. The aim of this study was to analyze and compare the different impacts of identical risk factors on ISR and ANL. METHODS: This study enrolled a total of 510 patients with multiple coronary artery lesions who underwent repeated coronary angiography (CAG). All patients had previously undergone percutaneous coronary intervention (PCI) and presented non-intervened coronary lesions in addition to the previously intervened vessels. RESULTS: After data analysis, it was determined that HbA1c (OR 1.229, 95% CI 1.022-1.477, P=0.028) and UA (OR 1.003, 95% CI 1.000-1.005, P=0.024) were identified as independent risk factors for ISR. Furthermore, HbA1c (OR 1.215, 95% CI 1.010-1.460, P=0.039), Scr (OR 1.007, 95% CI 1.003-1.017, P=0.009), and ApoB (OR 1.017, 95% CI 1.006-1.029, P=0.004) were identified as independent risk factors for ANL. The distribution of multiple blood lipid levels differed between the ANL only group and the ISR only group. Non-HDL-C (2.17 mmol/L vs. 2.44 mmol/L, P=0.007) and ApoB (63.5 mg/dL vs. 71.0 mg/dL, P=0.011) exhibited significantly higher values in the ANL only group compared to the ISR only group. CONCLUSIONS: Blood glucose levels and chronic kidney disease were identified as independent risk factors for both ISR and ANL, while elevated lipid levels were only significantly associated with ANL. In patients with non-intervened coronary lesions following PCI, it is crucial to assess the concentration of non-HDL-C and ApoB as they serve as significant risk factors.

Elevated Serum Levels of Soluble ST2 Are Associated With Plaque Vulnerability in Patients With Non-ST-Elevation Acute Coronary Syndrome.

Background: Recent studies have suggested that soluble suppression of tumorigenicity-2 (sST2), an inflammation-related protein receptor, is associated with atherosclerotic diseases. This study aimed to investigate the potential predictive value of sST2 on plaque vulnerability by assessing whether elevated serum levels of sST2 are associated with vulnerable plaque features in patients with non-ST-elevation acute coronary syndrome (ACS). Methods: A total of 120 patients with non-ST-elevation ACS (167 lesions) were prospectively enrolled and evaluated by standard coronary computed tomography angiography (CCTA) and coronary angiography in this study. Serum sST2 levels were measured by ELISA (Presage® ST2 Assay Kit, Critical Diagnostics), and semiautomated software (QAngioCT, Medis) was used to quantify coronary plaques. Results: The included patients were divided into 4 groups by serum sST2 level quartiles. Volumetric analysis of the whole lesion revealed that patients with higher sST2 levels had a larger absolute necrotic core (NC) volume (Quartile 4 vs. Quartile 1, 86.16 ± 59.71 vs. 45.10 ± 45.80 mm3, P = 0.001; Quartile 4 vs. Quartile 2, 86.16 ± 59.71 vs. 50.22 ± 42.56 mm3, P = 0.002) and a higher NC percentage (Quartile 4 vs. Quartile 1, 35.16 ± 9.82 vs. 23.21 ± 16.18%, P < 0.001; Quartile 4 vs. Quartile 2, 35.16 ± 9.82% vs. 22.50 ± 14.03%, P < 0.001; Quartile 4 vs. Quartile 3, 35.16 ± 9.82% vs. 25.04 ± 14.48%, P < 0.001). Correlation analysis revealed that serum sST2 levels were positively correlated with the NC (r = 0.323, P < 0.001) but negatively correlated with dense calcium (r = -0.208, P = 0.007). Furthermore, among those with plaque calcification, patients with spotty calcification exhibited higher serum sST2 levels than those with large calcification (26.06 ± 16.54 vs. 17.55 ± 7.65 ng/mL, P = 0.002). No significant differences in plaque components at the level of the minimal lumen area (MLA) were found among the groups. Conclusions: Serum sST2 levels were correlated with different coronary plaque components in patients with non-ST-elevation ACS. A higher serum level of sST2 was correlated with plaque vulnerability. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04797819.

Novel application of quantitative flow ratio for predicting microvascular dysfunction after ST-segment-elevation myocardial infarction.

OBJECTIVES: This study evaluated quantitative flow ratio (QFR) to predict microvascular dysfunction (MVD) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: QFR is a novel approach for the rapid computation of fractional flow reserve based on three-dimensional quantitative coronary angiography. We hypothesized that QFR computation could be used to predict MVD after STEMI. METHODS: Indexes such as contrast-flow QFR (cQFR), fixed-flow QFR (fQFR), and hyperemic flow velocity (HFV) were calculated in 130 STEMI patients with culprit lesion with ≥50% diameter stenosis and TIMI flow grade 2/3 in the spontaneously recanalized culprit artery on initial angiography. MVD was defined as microvascular obstruction determined by contrast-enhanced cardiac magnetic resonance at a median of 5 days after percutaneous coronary intervention. RESULTS: Patients were divided into the MVD group (76/130, 58.5%) and non-MVD group (54/130, 41.5%). Patients with MVD had higher cQFR-fQFR value (0.080 ± 0.058 vs. 0.038 ± 0.039, p < .001) and lower modeled HFV (0.096 ± 0.044 vs. 0.144 ± 0.041 m/s, p < .001). Receiver operator characteristic curve analysis revealed that both the cQFR-fQFR value (area under the curve, AUC = 0.716, p < .001) and modeled HFV (AUC = 0.805, p < .001) had high specificity and positive predictive value to predict MVD. In multivariable logistic analysis, cQFR-fQFR was identified as an independent predictor of MVD (odds ratio = 9.800, p < .001). CONCLUSIONS: This proof-of-concept study suggested that QFR computation may be a useful tool to predict MVD after STEMI (Trial Registration:NCT03780335).

Melatonin stabilizes rupture-prone vulnerable plaques via regulating macrophage polarization in a nuclear circadian receptor RORα-dependent manner.

Rupture of vulnerable plaques is the main trigger of acute cardio-cerebral vascular events, but mechanisms responsible for transforming a stable atherosclerotic into a vulnerable plaque remain largely unknown. Melatonin, an indoleamine hormone secreted by the pineal gland, plays pleiotropic roles in the cardiovascular system; however, the effect of melatonin on vulnerable plaque rupture and its underlying mechanisms remains unknown. Here, we generated a rupture-prone vulnerable carotid plaque model induced by endogenous renovascular hypertension combined with low shear stress in hypercholesterolemic ApoE-/- mice. Melatonin (10 mg/kg/d by oral administration for 9 weeks) significantly prevented vulnerable plaque rupture, with lower incidence of intraplaque hemorrhage (42.9% vs. 9.5%, P = 0.014) and of spontaneous plaque rupture with intraluminal thrombus formation (38.1% vs. 9.5%, P = 0.029). Mechanistic studies indicated that melatonin ameliorated intraplaque inflammation by suppressing the differentiation of intraplaque macrophages toward the proinflammatory M1 phenotype, and circadian nuclear receptor retinoid acid receptor-related orphan receptor-α (RORα) mediated melatonin-exerted vasoprotection against vulnerable plaque instability and intraplaque macrophage polarization. Further analysis in human monocyte-derived macrophages confirmed the role of melatonin in regulating macrophage polarization by regulating the AMPKα-STATs pathway in a RORα-dependent manner. In summary, our data provided the first evidence that melatonin-RORα axis acts as a novel endogenous protective signaling pathway in the vasculature, regulates intraplaque inflammation, and stabilizes rupture-prone vulnerable plaques.

Melatonin differentially regulates pathological and physiological cardiac hypertrophy: Crucial role of circadian nuclear receptor RORα signaling.

Exercise-induced physiological hypertrophy provides protection against cardiovascular disease, whereas disease-induced pathological hypertrophy leads to heart failure. Emerging evidence suggests pleiotropic roles of melatonin in cardiac disease; however, the effects of melatonin on physiological vs pathological cardiac hypertrophy remain unknown. Using swimming-induced physiological hypertrophy and pressure overload-induced pathological hypertrophy models, we found that melatonin treatment significantly improved pathological hypertrophic responses accompanied by alleviated oxidative stress in myocardium but did not affect physiological cardiac hypertrophy and oxidative stress levels. As an important mediator of melatonin, the retinoid-related orphan nuclear receptor-α (RORα) was significantly decreased in human and murine pathological hypertrophic cardiomyocytes, but not in swimming-induced physiological hypertrophic murine hearts. In vivo and in vitro loss-of-function experiments indicated that RORα deficiency significantly aggravated pathological cardiac hypertrophy, and notably weakened the anti-hypertrophic effects of melatonin. Mechanistically, RORα mediated the cardioprotection of melatonin in pathological hypertrophy mainly by transactivation of manganese-dependent superoxide dismutase (MnSOD) via binding to the RORα response element located in the promoter region of the MnSOD gene. Furthermore, MnSOD overexpression reversed the pro-hypertrophic effects of RORα deficiency, while MnSOD silencing abolished the anti-hypertrophic effects of RORα overexpression in pathological cardiac hypertrophy. Collectively, our findings provide the first evidence that melatonin exerts an anti-hypertrophic effect on pathological but not physiological cardiac hypertrophy via alleviating oxidative stress through transactivation of the antioxidant enzyme MnSOD in a RORα-dependent manner.

Intracoronary infusion of alprostadil and nitroglycerin with targeted perfusion microcatheter in STEMI patients with coronary slow flow phenomenon.

BACKGROUND: The treating aims of ST-segment elevation myocardial infarction (STEMI) are vessels recanalization and coronary flow restoration. Coronary slow flow phenomenon (CSFP) is one of the common complications in STEMI patients after percutaneous coronary intervention (PCI) and leads to a higher incidence of adverse clinical outcomes. Alprostadil is a kind of liposomal prostaglandin E1 with beneficial effects on vasodilation, platelet disaggregation and fibrinolysis. But it still remains unclear that whether alprostadil can improve the coronary perfusion in STEMI patients with CSFP after PCI. METHODS: In this study, a total of 57 STEMI cases with CSFP were included, 28 of which received 2 µg alprostadil by intracoronary infusion with targeted perfusion microcatheter while the others received 200 µg nitroglycerin. Coronary angiograms were analyzed by two experienced interventional cardiologists who were blinded to the medicine administration. RESULTS: We found that compared with nitroglycerin, alprostadil treatment was significantly more effective in increasing the incidence of TFG 3(78.6% vs. 48.3%, P = 0.021), MBG 3(46.4% vs. 20.7%, P = 0.039), TMPG 3(53.6% vs. 24.1%, P = 0.022) and complete STR (42.8% vs. 17.2%, P = 0.035) and reducing cTFC (28.71 frames vs. 46.03 frames, P = 0.001). Furthermore, in this study, intracoronary infusion of alprostadil with targeted perfusion microcatheter hardly affected the blood pressure and heart rate of patients, and no threaten complication were observed. CONCLUSIONS: Alprostadil can effectively alleviate CSFP, which is at the same time secure even for STEMI patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03296670.