Cardiac injury and mortality in patients with Coronavirus disease 2019 (COVID-19): insights from a mediation analysis

Patients at greatest risk of severe clinical conditions from coronavirus disease 2019 (COVID-19) and death are elderly and comorbid patients. Increased levels of cardiac troponins identify patients with poor outcome. The present study aimed to describe the clinical characteristics and outcomes of a cohort of Italian inpatients, admitted to a medical COVID-19 Unit, and to investigate the relative role of cardiac injury on in-hospital mortality

I farmaci che riducono la mortalit\ue0: gli ipolipemizzanti

Cardiovascular disease (CVD) is the leading cause of death in Italy and in the 28 countries of the European Union. Low-density lipoprotein cholesterol (LDL-C) is a key CVD risk factor. Results from the randomized intervention clinical trials with lipid-lowering agents strongly suggest that the reduction of fatal and non-fatal CVD events is associated with the absolute LDL-C reduction, in mg/dl or mmol/L, regardless of the lipid-lowering agent studied. Statins, by decreasing cholesterol synthesis in the liver, are associated with a large LDL-C reduction and with robust and convincing evidence of a significant reduction of all-cause, CVD and coronary heart disease (CHD) mortality. An LDL-C reduction by 39 mg/dl (1 mmol/L) on statin therapy is associated with a decrease by 10% (p<0.0001) in all-cause mortality, by 20% (p<0.0001) in CHD deaths and by 24% (p<0.0001) in major cardiovascular events. These results were often observed in secondary CVD prevention patients (4S, HPS and LIPID trials), independently of patients\u2019 gender and age, in patients on primary CVD prevention at high CV risk and in patients with type two diabetes. In patients with diabetes a 39 mg/dl (1 mmol/L) LDL-C reduction is associated with a decrease by 9% (p=0.02) in all-cause mortality, by 12% (p=0.03) and 13% (p=0.008) in deaths due to CHD and CVD causes respectively, and by 21% (p<0.0001) in major cardiovascular events. Data on CVD and CHD mortality regarding ezetimibe, fibrates and PCSK9 inhibitors are not nearly as robust as those with statin therapy: a significant reduction with these lipid-lowering agents has been observed in combined clinical endpoints including fatal and non-fatal CVD events while no significant reduction in all-cause, CVD or CHD mortality has been reported. This lack of positive results on CVD and CHD mortality should be interpreted in the light of remarkable changes in the background therapy to prevent CVD events seen in patients enrolled in the more recent trials where aggressive antihypertensive, antiplatelet and lipid-lowering therapy are common enrollment criteria for both control and active treatment groups

HDL Cholesterol Efflux and Serum Cholesterol Loading Capacity Alterations Associate to Macrophage Cholesterol Accumulation in FH Patients with Achilles Tendon Xanthoma

Achilles tendon xanthoma (ATX) formation involves macrophage cholesterol accumulation within the tendon, similar to that occurring in atheroma. Macrophage cholesterol homeostasis depends on serum lipoprotein functions, namely the high-density lipoprotein (HDL) capacity to promote cell cholesterol efflux (cholesterol efflux capacity, CEC) and the serum cholesterol loading capacity (CLC). We explored the HDL-CEC and serum CLC, comparing 16 FH patients with ATX to 29 FH patients without ATX. HDL-CEC through the main efflux mechanisms mediated by the transporters ATP binding cassette G1 (ABCG1) and A1 (ABCA1) and the aqueous diffusion (AD) process was determined by a cell-based radioisotopic technique and serum CLC fluorimetrically. Between the two groups, no significant differences were found in terms of plasma lipid profile. A trend toward reduction of cholesterol efflux via AD and a significant increase in ABCA1-mediated HDL-CEC (+18.6%) was observed in ATX compared to no ATX patients. In ATX-presenting patients, ABCG1-mediated HDL-CEC was lower (−11%) and serum CLC was higher (+14%) compared to patients without ATX. Considering all the patients together, ABCG1 HDL-CEC and serum CLC correlated with ATX thickness inversely (p = 0.013) and directly (p < 0.0001), respectively. In conclusion, lipoprotein dysfunctions seem to be involved in ATX physiopathology and progression in FH patients

Admission criteria for a cardiovascular short stay unit: a retrospective analysis on a pilot unit

Rapid intensive observation (RIO) units have been created to guarantee high standards of care in a sustainable health-care system. Within short stay units (SSUs), which are a subgroup of RIOs, only rapidly manageable patients should be admitted. Physicians are unable to predict the length of stay (LOS) as objective criteria to make such a prediction are missing. A retrospective observational study was carried out to identify the objective criteria for admission within a cardiovascular care-oriented SSU. Over a period of 317days, 340 patients (age 69.4±14.7years) were admitted to a pilot SSU within our internal medicine department. The most frequent diagnoses were chest pain (45.9%), syncope (12.9%), and supraventricular arrhythmias (11.2%). The median LOS was 4days (quartile 1:3; quartile 3:7). Predictors of LOS≤96h were age115g/L, estimated glomerular filtration rate>45mL/min/1.73m2, Charlson Comorbidity Index40, diagnosis of chest pain, syncope, supraventricular arrhythmias, or acute heart failure. The HEART (history, ECG, age, risk factors, troponin) score was found to be excellent in risk stratification of patients admitted for chest pain. Blood tests and anamnestic variables can be used to predict the LOS and thus SSU admission. The HEART score may help in the classification of patients with chest pain admitted to an SSU

Pro-inflammatory monocyte-macrophage polarization imbalance in human hypercholesterolemia and atherosclerosis.

Monocyte-macrophages (MoMas) play a major role in atherosclerosis. In mice, hypercholesterolemia increases pro-inflammatory monocytes that promote plaque growth, but whether this is true also in humans in unknown. We herein analyzed monocyte subsets and MoMa phenotypes in familiar (FH, n = 22) and non-familiar (NFH, n = 20) hypercholesterolemic compared with normocholesterolemic (CTRL, n = 20) patients. We found that FH and NFH had higher circulating pro-inflammatory CD68(+)CCR2(+) M1 MoMas than CTRL, while anti-inflammatory CX3CR1(+)CD163(+)/CD206(+) M2 MoMas were reduced only in NFH. As a result, the M1/M2 polarization balance was increased in FH and, more markedly in NFH. M1 MoMas and the M1/M2 polarization ratio were directly correlated to pre-treatment LDL cholesterol levels and strongly associated with the presence of atherosclerotic plaques. In conclusion, we show for the first time that human hypercholesterolemia is associated with a pro-inflammatory imbalance of circulating monocytic cells, which can predispose to the development of atherosclerosis

Lung Ultrasound Patterns and Clinical-Laboratory Correlates during COVID-19 Pneumonia: A Retrospective Study from North East Italy

BACKGROUND AND AIM: Lung ultrasound (LUS) is a convenient imaging modality in the setting of coronavirus disease-19 (COVID-19) because it is easily available, can be performed bedside and repeated over time. We herein examined LUS patterns in relation to disease severity and disease stage among patients with COVID-19 pneumonia.METHODS: We performed a retrospective case series analysis of patients with confirmed SARS-CoV-2 infection who were admitted to the hospital because of pneumonia. We recorded history, clinical parameters and medications. LUS was performed and scored in a standardized fashion by experienced operators, with evaluation of up to 12 lung fields, reporting especially on B-lines and consolidations.RESULTS: We included 96 patients, 58.3% men, with a mean age of 65.9 years. Patients with a high-risk quick COVID-19 severity index (qCSI) were older and had worse outcomes, especially for the need for high-flow oxygen. B-lines and consolidations were located mainly in the lower posterior lung fields. LUS patterns for B-lines and consolidations were significantly worse in all lung fields among patients with high versus low qCSI. B-lines and consolidations were worse in the intermediate disease stage, from day 7 to 13 after onset of symptoms. While consolidations correlated more with inflammatory biomarkers, B-lines correlated more with end-organ damage, including extrapulmonary involvement.CONCLUSIONS: LUS patterns provide a comprehensive evaluation of patients with COVID-19 pneumonia that correlated with severity and dynamically reflect disease stage. LUS patterns may reflect different pathophysiological processes related to inflammation or tissue damage; consolidations may represent a more specific sign of localized disease, whereas B-lines seem to be also dependent upon generalized illness due to SARS-CoV-2 infection