Sortilin and its potential role in cardiovascular pathology.

BACKGROUND: This comprehensive review explores the multifaceted role of sortilin, a key receptor in lipid metabolism, within the context of cardiovascular diseases (CVDs), the leading cause of global mortality. MAIN BODY: Sortilin, encoded by the SORT1 gene, is implicated in the pathogenesis of atherosclerosis, primarily through its regulation of low-density lipoprotein cholesterol (LDL-C) and very low-density lipoproteins (VLDL). The review delves into the biological functions of sortilin, emphasizing its critical role in lipid and cholesterol homeostasis and its influence on hepatic secretion of lipoproteins and atherogenesis. We highlight sortilin's pathophysiological significance in atherosclerosis, underscoring its involvement in lipid metabolism pathways and vascular inflammation, and its impact on macrophage functions in atherosclerotic plaque formation. The potential of sortilin as a therapeutic target is discussed, considering evidence that suggests its modulation could ameliorate atherosclerosis. The review also acknowledges current inconsistencies and gaps in the evidence, calling for more comprehensive patient studies and in-depth mechanistic research. Finally, the article outlines future research directions, focusing on understanding sortilin's specific cellular mechanisms in cardiovascular health, exploring its genetic variability, therapeutic implications, and its broader relevance to other diseases. CONCLUSION: This review underscores the significance of sortilin as a biomarker and a promising target for therapeutic intervention in cardiovascular pathology, while advocating for continued research to fully unravel its complex role.

International Prospective Registry of Acute Coronary Syndromes in Patients With COVID-19.

BACKGROUND: Published data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear. OBJECTIVES: The purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre-COVID-19 cohorts. METHODS: From March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re-myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre-COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019). RESULTS: In 144 ST-segment elevation myocardial infarction (STEMI) and 121 non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p < 0.001; COVID NSTE-ACS vs. MINAP: 417.0 min vs. 295.0 min; p = 0.012). Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs. 5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs. 1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 [95% confidence interval: 2.04 to 5.42]). Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001). CONCLUSIONS: In this multicenter international registry, COVID-19-positive ACS patients presented later and had increased in-hospital mortality compared with a pre-COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients.