Patients with pre-existing heart failure (HF) are likely at higher risk for adverse outcomes in coronavirus disease-2019 (COVID-19), but data on this population are sparse.
This study described the ...clinical profile and associated outcomes among patients with HF hospitalized with COVID-19.
This study conducted a retrospective analysis of 6,439 patients admitted for COVID-19 at 1 of 5 Mount Sinai Health System hospitals in New York City between February 27 and June 26, 2020. Clinical characteristics and outcomes (length of stay, need for intensive care unit, mechanical ventilation, and in-hospital mortality) were captured from electronic health records. For patients identified as having a history of HF by International Classification of Diseases-9th and/or 10th Revisions codes, manual chart abstraction informed etiology, functional class, and left ventricular ejection fraction (LVEF).
Mean age was 63.5 years, and 45% were women. Compared with patients without HF, those with previous HF experienced longer length of stay (8 days vs. 6 days; p < 0.001), increased risk of mechanical ventilation (22.8% vs. 11.9%; adjusted odds ratio: 3.64; 95% confidence interval: 2.56 to 5.16; p < 0.001), and mortality (40.0% vs. 24.9%; adjusted odds ratio: 1.88; 95% confidence interval: 1.27 to 2.78; p = 0.002). Outcomes among patients with HF were similar, regardless of LVEF or renin-angiotensin-aldosterone inhibitor use.
History of HF was associated with higher risk of mechanical ventilation and mortality among patients hospitalized for COVID-19, regardless of LVEF.
Display omitted
Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has reported high efficacy ...with a favorable safety profile in various psoriatic disease manifestations. Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, patients with moderate-to-severe psoriasis received secukinumab for 40 weeks. Vascular inflammation using 18F-2-fluorodeoxyglucose–positron emission tomography/computed tomography imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52. The difference in change in aortic inflammation from baseline to week 12 for secukinumab (n = 46) versus placebo (n = 45) was –0.053 (95% confidence interval = –0.169 to 0.064; P= 0.37). Small increases in total cholesterol, low-density lipoprotein, and low-density lipoprotein particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At week 52, reductions in TNF-α (P= 0.0063) and ferritin (P= 0.0354), and an increase in fetuin-A (P= 0.0024), were observed with secukinumab treatment compared with baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared with baseline. Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment.
Inflammation is known to play a significant role in the process of atherogenesis and cardiovascular disease (CVD). Indeed, patients with chronic inflammatory diseases are at increased risk for ...cardiovascular events. However, the mechanisms linking chronic inflammation and CVD remain poorly understood. Psoriasis, a chronic inflammatory skin disease associated with a greater risk of early cardiovascular events, provides a suitable human model to study the pathophysiology of inflammatory atherogenesis in humans. Additionally, cytokines such as TNF-α, IL-17A, and other immune pathways are the common links between the pathogenesis of psoriasis and atherosclerosis, and hence the approved treatments for psoriasis, which include selective cytokine inhibition (e.g., anti-TNF, anti-IL-17A, and anti-IL-12/23) and immune modulation (e.g., methotrexate or cyclosporine), provide an opportunity to examine the effect of modulating these pathways on atherogenesis. We have been using this human model in a large, prospective cohort study, and this review summarizes our approach and results of using this human model to study inflammatory atherogenesis. Specifically, we review simultaneous multimodal imaging of several vascular beds using
fludeoxyglucose positron emission tomography/computed tomography,
fludeoxyglucose positron emission tomography/MRI, and coronary computed tomography angiography as well as cardiovascular biomarkers to better understand how modulation of inflammation may impact vascular diseases.
RATIONALE:GlycA, an emerging inflammatory biomarker, predicted cardiovascular events in population-based studies. Psoriasis, an inflammatory disease associated with increased cardiovascular risk, ...provides a model to study inflammatory biomarkers in cardiovascular disease (CVD). Whether GlycA associates with psoriasis and how it predicts subclinical CVD beyond high-sensitivity C-reactive protein in psoriasis is unknown.
OBJECTIVE:To investigate the relationships between GlycA and psoriasis and between GlycA and subclinical CVD.
METHODS AND RESULTS:Patients with psoriasis and controls (n=412) participated in a 2-stage study. We measured GlycA by nuclear magnetic resonance spectroscopy. National Institutes of Health (NIH) participants underwent 18-F Fluorodeoxyglucose Positron Emission Tomography Computed Tomography (18-FDG PET/CT) scans to assess vascular inflammation (VI) and coronary computed tomographic angiography to quantify coronary artery disease burden. Psoriasis cohorts were young (mean age=47.9), with low cardiovascular risk and moderate skin disease. high-sensitivity C-reactive protein and GlycA were increased in psoriasis compared with controls (GlycAPENN408.8±75.4 versus 289.4±60.2, P<0.0001; NIH415.8±63.2 versus 346.2±46, P<0.0001) and demonstrated a dose–response with psoriasis severity. In stage 2, VI (β=0.36, P<0.001) and coronary artery disease (β=0.29, P=0.004) associated with GlycA beyond CV risk factors in psoriasis. In receiver operating characteristic analysis, GlycA added value in predicting VI (P=0.01) and coronary artery disease (P<0.01). Finally, initiating anti–tumor necrosis factor therapy (n=16) reduced psoriasis severity (P<0.001), GlycA (463.7±92.5 versus 370.1±78.5, P<0.001) and VI (1.93±0.36 versus 1.76±0.19, P<0.001), whereas GlycA remained associated with VI (β=0.56, P<0.001) post treatment.
CONCLUSIONS:GlycA associated with psoriasis severity and subclinical CVD beyond traditional CV risk and high-sensitivity C-reactive protein. Moreover, psoriasis treatment reduced GlycA and VI. These findings support the potential use of GlycA in subclinical CVD risk assessment in psoriasis and potentially other inflammatory diseases.
Chronic inflammation is a critical component of atherogenesis, however, reliable human translational models aimed at characterizing these mechanisms are lacking. Psoriasis, a chronic inflammatory ...skin disease associated with increased susceptibility to atherosclerosis, provides a clinical human model that can be utilized to investigate the links between chronic inflammation and atherosclerosis development. We sought to investigate key biological processes in psoriasis skin and human vascular tissue to identify biological components that may promote atherosclerosis in chronic inflammatory conditions. Using a bioinformatics approach of human skin and vascular tissue, we determined IFN-γ and TNF-α are the dominant pro-inflammatory signals linking atherosclerosis and psoriasis. We then stimulated primary aortic endothelial cells and ex-vivo atherosclerotic tissue with IFN-γ and TNF-α and found they synergistically increased monocyte and T-cell chemoattractants, expression of adhesion molecules on the endothelial cell surface, and decreased endothelial barrier integrity in vitro, therefore increasing permeability. Our data provide strong evidence of synergism between IFN-γ and TNF- α in inflammatory atherogenesis and provide rationale for dual cytokine antagonism in future studies.
OBJECTIVE—To understand whether directly measured psoriasis severity is associated with vascular inflammation assessed by F-fluorodeoxyglucose positron emission tomography computed tomography.
...APPROACH—In-depth cardiovascular and metabolic phenotyping was performed in adult psoriasis patients (n=60) and controls (n=20). Psoriasis severity was measured using psoriasis area severity index. Vascular inflammation was measured using average aortic target-to-background ratio using F-fluorodeoxyglucose positron emission tomography computed tomography.
RESULTS—Both the psoriasis patients (28 men and 32 women, mean age 47 years) and controls (13 men and 7 women, mean age 41 years) were young with low cardiovascular risk. Psoriasis area severity index scores (median 5.4; interquartile range 2.8–8.3) were consistent with mild-to-moderate skin disease severity. Increasing psoriasis area severity index score was associated with an increase in aortic target-to-background ratio (β=0.41, P=0.001), an association that changed little after adjustment for age, sex, and Framingham risk score. We observed evidence of increased neutrophil frequency (mean psoriasis, 3.7±1.2 versus 2.9±1.2; P=0.02) and activation by lower neutrophil surface CD16 and CD62L in blood. Serum levels of S100A8/A9 (745.1±53.3 versus 195.4±157.8 ng/mL; P<0.01) and neutrophil elastase-1 (43.0±2.4 versus 30.8±6.7 ng/mL; P<0.001) were elevated in psoriasis. Finally, S100A8/A9 protein was related to both psoriasis skin disease severity (β=0.53; P=0.02) and vascular inflammation (β=0.48; P=0.02).
CONCLUSIONS—Psoriasis severity is associated with vascular inflammation beyond cardiovascular risk factors. Psoriasis increased neutrophil activation and neutrophil markers, and S100A8/A9 was related to both skin disease severity and vascular inflammation.
Preclinical and clinical research provide strong evidence that chronic, systemic inflammation plays a key role in development and progression of atherosclerosis. Indeed, chronic inflammatory ...diseases, such as psoriasis, are associated with accelerated atherosclerosis and increased risk of cardiovascular events. Contemporary research has demonstrated plausible mechanistic links between immune cell dysfunction and cardiometabolic disease in psoriasis. In this review, we describe the role of potential common immunological mechanisms underlying both psoriasis and atherogenesis. We primarily discuss innate and adaptive immune cell subsets and their contributions to psoriatic disease and cardiovascular morbidity. Emerging efforts should focus on understanding the interplay among immune cells, adipose tissue, and various biomarkers of immune dysfunction to provide direction for future targeted therapy.
Objective
To assess the effect of tumor necrosis factor inhibitors (TNFi) on subclinical cardiovascular disease in patients with psoriatic disease.
Methods
We performed a 2‐stage study. In stage 1, ...carotid total plaque area was assessed in patients with psoriasis or psoriatic arthritis (PsA) (n = 319) by ultrasound at baseline and after 2–3 years. The annual progression rate of atherosclerosis was the outcome of interest. In stage 2, PsA patients receiving TNFi (n = 21) and age‐ and sex‐matched PsA patients not receiving any biologic agent (n = 13) underwent 18F‐fluorodeoxyglucose–positron emission tomography/computed tomography at baseline and 1 year to assess vascular inflammation, measured as target‐to‐background ratio (TBR). In both stages, multivariable regression analyses adjusted for cardiovascular risk factors and use of statins were performed.
Results
In stage 1, men had significantly higher atherosclerosis progression than women (P < 0.001). TNFi was associated with reduced atherosclerosis progression in men after controlling for cardiovascular risk and use of statins (adjusted β = −2.20 95% confidence interval −3.41, −1.00, P < 0.001). There was no association between TNFi and atherosclerosis progression in women (P = 0.74). In stage 2, patients receiving TNFi had reduced TBR at 1 year (P = 0.03). Those not receiving TNFi had no significant change in TBR (P = 0.32). The improvement in aortic vascular inflammation in the TNFi group was independent of cardiovascular risk factors (adjusted β = −0.41 95% confidence interval −0.74, −0.08, P = 0.02).
Conclusion
Our findings indicate that TNFi treatment is associated with reduced progression of carotid plaques in men and improvement in vascular inflammation in both men and women with psoriatic disease.
A detailed review to analyze the anti ulcer proton pump inhibitor (PPI) drugs, particularly for determination of their concentration percentage (assay) by analytical methods developed on analytical ...instruments i.e., UV visible Spectrophotometer, High Performance Liquid Chromatography, Ultra Performance Liquid Chromatography, and Hyphenated techniques. The review includes literature survey of PPI drugs namely omeprazole (OPZ), lansoprazole (LPZ), pantoprazole (PPZ) rabeprazole (RPZ), dexlansoprazole (DLPZ), esomeprazole (EPZ), dexrabeprazole (DRPZ), ilaprazole (IPZ), and tenatoprazole (TPZ). The examined literature survey addressed chromatographic (HPLC and UPLC) and UV visible spectrophotometric methods with LC-MS/MS methods used in pure forms, pharmaceutical formulations, and human plasma and other biological fluids for their estimation. In case of validation parameters mostly Linearity, Recovery study, LOD and LOQ was considered and mentioned.
PDF
