Dietary AGEs as Exogenous Boosters of Inflammation

Most chronic modern non-transmissible diseases seem to begin as the result of low-grade inflammation extending over prolonged periods of time. The importance of diet as a source of many pro-inflammatory compounds that could create and sustain such a low-grade inflammatory state cannot be ignored, particularly since we are constantly exposed to them during the day. The focus of this review is on specific components of the diet associated with inflammation, specifically advanced glycation end products (AGEs) that form during thermal processing of food. AGEs are also generated in the body in normal physiology and are widely recognized as increased in diabetes, but many people are unaware of the potential importance of exogenous AGEs ingested in food. We review experimental models, epidemiologic data, and small clinical trials that suggest an important association between dietary intake of these compounds and development of an inflammatory and pro-oxidative state that is conducive to chronic diseases. We compare dietary intake of AGEs with other widely known dietary patterns, such as the Mediterranean and the Dietary Approaches to Stop Hypertension (DASH) diets, as well as the Dietary Inflammation Index (DII). Finally, we delineate in detail the pathophysiological mechanisms induced by dietary AGEs, both direct (i.e., non-receptor-mediated) and indirect (receptor-mediated

Industrial Use of Phosphate Food Additives: A Mechanism Linking Ultra-Processed Food Intake to Cardiorenal Disease Risk?

The consumption of ultra-processed food (UPF) keeps rising, and at the same time, an increasing number of epidemiological studies are linking high rates of consumption of UPF with serious health outcomes, such as cardiovascular disease, in the general population. Many potential mechanisms, either in isolation or in combination, can explain the negative effects of UPF. In this review, we have addressed the potential role of inorganic phosphate additives, commonly added to a wide variety of foods, as factors contributing to the negative effects of UPF on cardiorenal disease. Inorganic phosphates are rapidly and efficiently absorbed, and elevated serum phosphate can lead to negative cardiorenal effects, either directly through tissue/vessel calcification or indirectly through the release of mineral-regulating hormones, parathyroid hormone, and fibroblast growth factor-23. An association between serum phosphate and cardiovascular and bone disease among patients with chronic kidney disease is well-accepted by nephrologists. Epidemiological studies have demonstrated an association between serum phosphate and dietary phosphate intake and mortality, even in the general American population. The magnitude of the role of inorganic phosphate additives in these associations remains to be determined, and the initial step should be to determine precise estimates of population exposure to inorganic phosphate additives in the food supply

Inhibition of the Maillard reaction by phytochemicals composing an aqueous coffee silverskin extract via a mixed mechanism of action

This work aimed to evaluate the contribution of isoflavones and melatonin to the aqueous extract obtained from the coffee silverskin (CSE) antiglycative properties, which has not been previously studied. To achieve this goal, two model systems constituted by bovine serum albumin (BSA) and reactive carbonyls (glucose or methylglyoxal) in the presence or absence of pure phytochemicals (chlorogenic acid (CGA), genistein, and melatonin) and CSE were employed. Glucose was used to evaluate the effect on the formation of glycation products formed mainly in the early stage of the reaction, while methylglyoxal was employed for looking at the formation of advanced products of the reaction, also called methylglyoxal-derivative advanced glycation end products (AGE) or glycoxidation products. CGA inhibited the formation of fructosamine, while genistein and melatonin inhibited the formation of advanced glycation end products and protein glycoxidation. It was also observed that phenolic compounds from CSE inhibited protein glycation and glycoxidation by forming BSA-phytochemical complexes. CSE showed a significant antiglycative effect (p < 0.05). Variations in the UV-Vis spectrum and the antioxidant capacity of protein fractions suggested the formation of protein-phytochemical complexes. Fluorescence quenching and in silico analysis supported the formation of antioxidant-protein complexes. For the first time, we illustrate that isoflavones and melatonin may contribute to the antiglycative/antiglycoxidative properties associated with CSE. CGA, isoflavones, and melatonin composing CSE seem to act simultaneously by different mechanisms of actionM.R.H thanks the JAE Intro fellowship (JAEINT_15_00086) and the FPU predoctoral program of the Ministry of Science, Innovation, and Universities (FPU15/04238

Adverse effects of autoclaved diets on the progression of chronic kidney disease (CKD) and CKD-Mineral Bone Disorder in rats

Background: Autoclaving rodent diets is common in laboratory animals, but autoclaving increases the formation of dietary advanced glycation end-products (AGE). We studied the effect of autoclaved (AC) diet alone or in combination with a diet high in bioavailable phosphorus on biochemistries of chronic kidney disease-mineral and bone disorder (CKD-MBD), intestinal gene expression, and oxidative stress. Methods: Male CKD rats (Cy/+) and normal littermates were fed 1 of 3 diets: AC 0.7% phosphorus grain-based diet for 28 weeks (AC); AC diet for 17 weeks followed by non-autoclaved (Non-AC) 0.7% phosphorus casein diet until 28 weeks (AC + Casein); or Non-AC diet for 16 weeks followed by a Non-AC purified diet until 30 weeks (Non-AC + Casein). Results: AC diets contained ~3× higher AGEs and levels varied depending on the location within the autoclave. Rats fed the AC and AC + Casein diets had higher total AGEs and oxidative stress, irrespective of kidney function. Kidney function was more severely compromised in CKD rats fed AC or AC + Casein compared to Non-AC + Casein. There was a disease-by-diet interaction for plasma phosphorus, parathyroid hormone, and c-terminal fibroblast growth factor-23, driven by high values in the CKD rats fed the AC + Casein diet. Compared to Non-AC + Casein, AC and AC + Casein-fed groups had increased expression of receptor of AGEs and intestinal NADPH oxidase dual oxidase-2, independent of kidney function. Conclusions: Autoclaving rodent diets impacts the progression of CKD and CKD-MBD, highlighting the critical importance of standardizing diets in experiments

Elevated Troponins after COVID-19 Hospitalization and Long-Term COVID-19 Symptoms: Incidence, Prognosis, and Clinical Outcomes—Results from a Multi-Center International Prospective Registry (HOPE-2)

Background: Acute cardiac injury (ACI) after COVID-19 has been linked with unfavorable clinical outcomes, but data on the clinical impact of elevated cardiac troponin on discharge during follow-up are scarce. Our objective is to elucidate the clinical outcome of patients with elevated troponin on discharge after surviving a COVID-19 hospitalization. Methods: We conducted an analysis in the prospective registry HOPE-2 (NCT04778020). Only patients discharged alive were selected for analysis, and all-cause death on follow-up was considered as the primary endpoint. As a secondary endpoint, we established any long-term COVID-19 symptoms. HOPE-2 stopped enrolling patients on 31 December 2021, with 9299 patients hospitalized with COVID-19, of which 1805 were deceased during the acute phase. Finally, 2382 patients alive on discharge underwent propensity score matching by relevant baseline variables in a 1:3 fashion, from 56 centers in 8 countries. Results: Patients with elevated troponin experienced significantly higher all-cause death during follow-up (log-rank = 27.23, p < 0.001), and had a higher chance of experiencing long-term COVID-19 cardiovascular symptoms. Specifically, fatigue and dyspnea (57.7% and 62.8%, with p-values of 0.009 and <0.001, respectively) are among the most common. Conclusions: After surviving the acute phase, patients with elevated troponin on discharge present increased mortality and long-term COVID-19 symptoms over time, which is clinically relevant in follow-up visits

Clinical Profile and Determinants of Mortality in Patients with Interstitial Lung Disease Admitted for COVID-19.

BACKGROUND Concern has risen about the effects of COVID-19 in interstitial lung disease (ILD) patients. The aim of our study was to determine clinical characteristics and prognostic factors of ILD patients admitted for COVID-19. METHODS Ancillary analysis of an international, multicenter COVID-19 registry (HOPE: Health Outcome Predictive Evaluation) was performed. The subgroup of ILD patients was selected and compared with the rest of the cohort. RESULTS A total of 114 patients with ILDs were evaluated. Mean ± SD age was 72.4 ± 13.6 years, and 65.8% were men. ILD patients were older, had more comorbidities, received more home oxygen therapy and more frequently had respiratory failure upon admission than non-ILD patients (all p < 0.05). In laboratory findings, ILD patients more frequently had elevated LDH, C-reactive protein, and D-dimer levels (all p < 0.05). A multivariate analysis showed that chronic kidney disease and respiratory insufficiency on admission were predictors of ventilatory support, and that older age, kidney disease and elevated LDH were predictors of death. CONCLUSIONS Our data show that ILD patients admitted for COVID-19 are older, have more comorbidities, more frequently require ventilatory support and have higher mortality than those without ILDs. Older age, kidney disease and LDH were independent predictors of mortality in this population.S

Chronic Oral Anticoagulation Therapy and Prognosis of Patients Admitted to Hospital for COVID-19: Insights from the HOPE COVID-19 Registry

Background. Most evidence regarding anticoagulation and COVID-19 refers to the hospitalization setting, but the role of oral anticoagulation (OAC) before hospital admission has not been well explored. We compared clinical outcomes and short-term prognosis between patients with and without prior OAC therapy who were hospitalized for COVID-19. Methods. Analysis of the whole cohort of the HOPE COVID-19 Registry which included patients discharged (deceased or alive) after hospital admission for COVID-19 in 9 countries. All-cause mortality was the primary endpoint. Study outcomes were compared after adjusting variables using propensity score matching (PSM) analyses. Results. 7698 patients were suitable for the present analysis (675 (8.8%) on OAC at admission: 427 (5.6%) on VKAs and 248 (3.2%) on DOACs). After PSM, 1276 patients were analyzed (638 with OAC; 638 without OAC), without significant differences regarding the risk of thromboembolic events (OR 1.11, 95% CI 0.59-2.08). The risk of clinically relevant bleeding (OR 3.04, 95% CI 1.92-4.83), as well as the risk of mortality (HR 1.22, 95% CI 1.01-1.47; log-rank p value = 0.041), was significantly increased in previous OAC users. Amongst patients on prior OAC only, there were no differences in the risk of clinically relevant bleeding, thromboembolic events, or mortality when comparing previous VKA or DOAC users, after PSM. Conclusion. Hospitalized COVID-19 patients on prior OAC therapy had a higher risk of mortality and worse clinical outcomes compared to patients without prior OAC therapy, even after adjusting for comorbidities using a PSM. There were no differences in clinical outcomes in patients previously taking VKAs or DOACs. This trial is registered with NCT04334291/EUPAS34399

Underlying heart diseases and acute COVID-19 outcomes

Background: The presence of any underlying heart condition could influence outcomes during the coronavirus disease 2019 (COVID-19). Methods: The registry HOPE-COVID-19 (Health Outcome Predictive Evaluation for COVID-19, NCT04334291) is an international ambispective study, enrolling COVID-19 patients discharged from hospital, dead or alive. Results: HOPE enrolled 2798 patients from 35 centers in 7 countries. Median age was 67 years (IQR: 53.0–78.0), and most were male (59.5%). A relevant heart disease was present in 682 (24%) cases. These were older, more frequently male, with higher overall burden of cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, smoking habit, obesity) and other comorbidities such renal failure, lung, cerebrovascular disease and oncologic antecedents (p &lt; 0.01, for all). The heart cohort received more corticoids (28.9% vs. 20.4%, p &lt; 0.001), antibiotics, but less hydroxychloroquine, antivirals or tocilizumab. Considering the epidemiologic profile, a previous heart condition was independently related with shortterm mortality in the Cox multivariate analysis (1.62; 95% CI 1.29–2.03; p &lt; 0.001). Moreover, heart patients needed more respiratory, circulatory support, and presented more in-hospital events, such heart failure, renal failure, respiratory insufficiency, sepsis, systemic infammatory response syndrome and clinically relevant bleedings (all, p &lt; 0.001), and mortality (39.7% vs. 15.5%; p &lt; 0.001).Conclusions: An underlying heart disease is an adverse prognostic factor for patients suffering COVID-19. Its presence could be related with different clinical drug management and would benefit from maintaining treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers during in-hospital stay

Chronic Oral Anticoagulation Therapy and Prognosis of Patients Admitted to Hospital for COVID-19: Insights from the HOPE COVID-19 Registry

BackgroundMost evidence regarding anticoagulation and COVID-19 refers to the hospitalization setting, but the role of oral anticoagulation (OAC) before hospital admission has not been well explored. We compared clinical outcomes and short-term prognosis between patients with and without prior OAC therapy who were hospitalized for COVID-19.MethodsAnalysis of the whole cohort of the HOPE COVID-19 Registry which included patients discharged (deceased or alive) after hospital admission for COVID-19 in 9 countries. All-cause mortality was the primary endpoint. Study outcomes were compared after adjusting variables using propensity score matching (PSM) analyses.Results7698 patients were suitable for the present analysis (675 (8.8%) on OAC at admission: 427 (5.6%) on VKAs and 248 (3.2%) on DOACs). After PSM, 1276 patients were analyzed (638 with OAC; 638 without OAC), without significant differences regarding the risk of thromboembolic events (OR 1.11, 95% CI 0.59-2.08). The risk of clinically relevant bleeding (OR 3.04, 95% CI 1.92-4.83), as well as the risk of mortality (HR 1.22, 95% CI 1.01-1.47; log-rank p value = 0.041), was significantly increased in previous OAC users. Amongst patients on prior OAC only, there were no differences in the risk of clinically relevant bleeding, thromboembolic events, or mortality when comparing previous VKA or DOAC users, after PSM.ConclusionHospitalized COVID-19 patients on prior OAC therapy had a higher risk of mortality and worse clinical outcomes compared to patients without prior OAC therapy, even after adjusting for comorbidities using a PSM. There were no differences in clinical outcomes in patients previously taking VKAs or DOACs. This trial is registered with NCT04334291/EUPAS34399