Cardiac rehabilitation (CR) following acute myocardial infarction (AMI) improves physical capacities and decreases hospitalizations and cardiovascular mortality. L-arginine is the substrate used by nitric oxide (NO) synthase to generate NO and it has been shown to exert its beneficial effects on endothelium driving vasodilatation, reducing inflammation, and ameliorating physical function. We hypothesized that L-arginine could enhance physical capacities in patients who underwent CR after AMI. We designed a study aimed to assess the effects of L-arginine administration on the physical capacity of patients who underwent coronary revascularization after AMI. The trial was carried out amid the COVID-19 pandemic. Patients were assigned, with a 2:1 ratio, to add to their standard therapy one bottle containing 1.66 g of L-arginine or one bottle of identical aspect apart from not containing L-arginine, twice a day orally for 3 weeks. Patients performed a 6-minute walking test (6MWT), and their Borg modified 0–10 rating of perceived exertion (BRPE) was assessed before starting and at the end of the treatment. Seventy-five patients receiving L-arginine, and 35 receiving placebo successfully completed the study. The 6MWT distance increased significantly in the L-arginine group compared with both baseline and placebo (P < 0.0001). Additionally, we observed a significant improvement in the BRPE in patients treated with L-arginine but not in the placebo group. Taken together, our data indicate that L-arginine potentiates the response to CR independently of age, sex, baseline functional capacity, and comorbid conditions. SIGNIFICANCE STATEMENT This study shows for the first time that oral supplementation of L-arginine potentiates the response to cardiac rehabilitation after myocardial infarction and cardiac revascularization. Indeed, we observed a significant improvement in two fundamental parameters, namely, the 6-minute walking test and the Borg modified 0–10 rating of perceived exertion. Strikingly, the beneficial effects of L-arginine were independent of age, sex, comorbid conditions, and baseline functional capacity.

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L-Arginine Enhances the Effects of Cardiac Rehabilitation on Physical Performance: New Insights for Managing Cardiovascular Patients During the COVID-19 Pandemic

Peripheral biomarkers are increasingly vital non-invasive methods for monitoring coronary artery disease (CAD) progression. Their superiority in early detection, prognosis evaluation and classified diagnosis is becoming irreplaceable. Nevertheless, they are still less explored. This study aimed to determine and validate the diagnostic and therapeutic values of differentially expressed immune-related genes (DE-IRGs) in CAD.We downloaded clinical information and RNA sequence data from the GEO database. We used R software, GO, KEGG and Cytoscape to analyze and visualize the data. A LASSO method was conducted to identify key genes for diagnostic model construction. The ssGSEA analysis was used to investigate the differential immune cell infiltration. Besides, we constructed CAD mouse model (low-density lipoprotein receptor deficient mice with high fat diet) to discover the correlation between the screened genes and severe CAD progress. We further uncovered the role of IL13RA1 might play in atherosclerosis.A total of 762 differential genes were identified between the peripheral blood of 218 controls and 199 CAD patients, which were significantly associated with infection, immune response and neural activity. 58 DE-IRGs were obtained by overlapping the differentially expressed genes(DEGs) and immune-related genes downloaded from ImmpDb database. Through LASSO regression, CCR9, CER1, CSF2, IL13RA1, INSL5, MBL2, MMP9, MSR1, NTS, TNFRSF19, CXCL2, HTR3C, IL1A, and NR4A2 were distinguished as peripheral biomarkers of CAD with eligible diagnostic capabilities in the training set (AUC = 0.968) and test set (AUC = 0.859). The ssGSEA analysis showed that the peripheral immune cells had characteristic distribution in CAD and also close relationship with specific DE-IRGs. RT-qPCR test showed that CCR9, CSF2, IL13RA1, and NTS had a significant correlation with LDLR-/- mice. IL13RA1 knocked down in RAW264.7 cell lines decreased SCARB1 and ox-LDL-stimulated CD36 mRNA expression, TGF-β, VEGF-C and α-SMA protein levels and increased the production of IL-6, with downregulation of JAK1/STAT3 signal pathway.We constructed a diagnostic model of advanced-stage CAD based on the screened 14 DE-IRGs. We verified 4 genes of them to have a strong correlation with CAD, and IL13RA1 might participate in the inflammation, fibrosis, and cholesterol efflux process of atherosclerosis by regulating JAK1/STAT3 pathway. 

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Identification of diagnostic biomarkers and therapeutic targets in peripheral immune landscape from coronary artery disease

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Multiple sclerosis is a central nervous system inflammatory demyelinating disease with a wide range of clinical symptoms, ocular involvement being frequently marked by the presence of optic neuritis (ON). The emergence and progression of ON in multiple sclerosis is based on various pathophysiological mechanisms, disease progression being secondary to inflammation, demyelination, or axonal degeneration. Early identification of changes associated with axonal degeneration or further investigation of the molecular processes underlying remyelination are current concerns of researchers in the field in view of the associated therapeutic potential. This article aims to review and summarize the scientific literature related to the main molecular mechanisms involved in defining ON as well as to analyze existing data in the literature on remyelination strategies in ON and their impact on long-term prognosis.

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Optic Neuritis in Multiple Sclerosis—A Review of Molecular Mechanisms Involved in the Degenerative Process

(1) Background: Currently, limited data are available regarding the relationship between epicardial fat and plaque composition. The aim of this study was to assess the relationship between visceral fat surrounding the heart and the lipid core burden in patients with coronary artery diseases; (2) Methods: Overall, 331 patients undergoing coronary angiography with combined near-infrared spectroscopy and intravascular ultrasound imaging were evaluated for epicardial adipose tissue (EAT) thickness using transthoracic echocardiography. Patients were divided into thick EAT and thin EAT groups according to the median value; (3) Results: There was a positive correlation between EAT thickness and maxLCBI4mm, and maxLCBI4mm was significantly higher in the thick EAT group compared to the thin EAT group (437 vs. 293, p < 0.001). EAT thickness was an independent predictor of maxLCBI4mm ≥ 400 along with age, low-density lipoprotein-cholesterol level, acute coronary syndrome presentation, and plaque burden in a multiple linear regression model. Receiver operating characteristic curve analysis showed that EAT thickness was a predictor for maxLCBI4mm ≥ 400; (4) Conclusions: In the present study, EAT thickness is related to the lipid core burden assessed by NIRS-IVUS in patients with CAD which suggests that EAT may affect the stability of the plaques in coronary arteries.

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Epicardial Adipose Tissue Thickness Is Related to Plaque Composition in Coronary Artery Disease

The atherosclerotic vascular disease is a cardiovascular continuum in which the main role is attributed to atherosclerosis, from its appearance to its associated complications. The increasing prevalence of cardiovascular risk factors, population ageing, and burden on both the economy and the healthcare system have led to the development of new diagnostic and therapeutic strategies in the field. The better understanding or discovery of new pathophysiological mechanisms and molecules modulating various signaling pathways involved in atherosclerosis have led to the development of potential new biomarkers, with key role in early, subclinical diagnosis. The evolution of technological processes in medicine has shifted the attention of researchers from the profiling of classical risk factors to the identification of new biomarkers such as midregional pro-adrenomedullin, midkine, stromelysin-2, pentraxin 3, inflammasomes, or endothelial cell-derived extracellular vesicles. These molecules are seen as future therapeutic targets associated with decreased morbidity and mortality through early diagnosis of atherosclerotic lesions and future research directions.

https://www.mdpi.com/1422-0067/23/9/4998/pdf?version=1651825665

Novel Biomarkers of Atherosclerotic Vascular Disease—Latest Insights in the Research Field

Atherosclerosis is the basis of the cardiovascular continuum in peripheral artery disease (PAD) patients. Limiting functional decline and increasing quality of life are the main objectives for these patients. We conducted a prospective cohort study on 101 patients with PAD admitted to a single center in Northeast Romania. We used an index score to evaluate the 10-year mortality risk assessment and based on the scores we divided the patients into two groups: a low and low-intermediate risk mortality group (49 cases, 48.5%) and a high-intermediate and high-risk mortality group (52 cases, 51.5%). We analyzed demographics, comorbidities, clinical and paraclinical parameters and we aimed to identify the parameters associated with an unfavorable prognosis. Patients in the high-intermediate and high-risk mortality group were associated more with cardiovascular risk factors. Hypertension (p = 0.046), dyslipidemia (p < 0.001), diabetes mellitus (p < 0.001), and tobacco use (p = 0.018) were statistically significant factors. Lipid profile (low-density lipoprotein cholesterol, p = 0.005) and fasting blood glucose (p = 0.013) had higher mean serum values in the high-intermediate and high-risk mortality group, with a positive correlation between them and the ankle-brachial index value (p = 0.003). A multidisciplinary assessment and, especially, correction of associated cardiovascular risk factors prevent complications, and thus, improve the prognosis in the medium and long term.

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Mortality Risk Assessment in Peripheral Arterial Disease—The Burden of Cardiovascular Risk Factors over the Years: A Single Center’s Experience

Vascular aging, early vascular aging or supernormal vascular aging are concepts used for estimating the cardiovascular risk at a certain age. From the famous line of Thomas Sydenham that “a man is as old as his arteries” to the present day, clinical studies in the field of molecular biology of the vasculature have demonstrated the active role of vascular endothelium in the onset of cardiovascular diseases. Arterial stiffness is an important cardiovascular risk factor associated with the occurrence of cardiovascular events and a high risk of morbidity and mortality, especially in the presence of diabetes. Sodium–glucose cotransporter 2 inhibitors decrease arterial stiffness and vascular resistance by decreasing endothelial cell activation, stimulating direct vasorelaxation and ameliorating endothelial dysfunction or expression of pro-atherogenic cells and molecules.

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Impact of Sodium–Glucose Cotransporter 2 (SGLT2) Inhibitors on Arterial Stiffness and Vascular Aging—What Do We Know So Far? (A Narrative Review)

Cardiac rehabilitation (CR) is an integral part of the management of various cardiovascular disease such as coronary artery disease (CAD), peripheral artery disease (PAD), or chronic heart failure (CHF), with proven morbidity and mortality benefits. This article aims to review and summarize the scientific literature related to cardiac rehabilitation programs for patients with PAD and how they were adapted during the COVID-19 pandemic. The implementation of CR programs has been problematic since the COVID-19 pandemic due to social distancing and work-related restrictions. One of the main challenges for physicians and health systems alike has been the management of PAD patients. COVID-19 predisposes to coagulation disorders that can lead to severe thrombotic events. Home-based walking exercises are more accessible and easier to accept than supervised exercise programs. Cycling or other forms of exercise are more entertaining or challenging alternatives to exercise therapy. Besides treadmill exercises, upper- and lower-extremity ergometry also has great functional benefits, especially regarding walking endurance. Supervised exercise therapy has a positive impact on both functional capacity and also on the quality of life of such patients. The most effective manner to acquire this seems to be by combining revascularization therapy and supervised exercise. Rehabilitation programs proved to be a mandatory part of the integrative approach in these cases, increasing quality of life, and decreasing stress levels, depression, and anxiety.

https://www.mdpi.com/2077-0383/11/2/416/pdf?version=1642154231

Cardiac Rehabilitation in Patients with Peripheral Artery Disease—A Literature Review in COVID-19 Era

Background and Objectives: Cardiac rehabilitation (CR) plays an essential role in peripheral artery disease (PAD), leading to improved functional status, increased quality of life, and reduced arterial stiffness. We aimed to assess factors associated with clinical improvement 6 months after enrolment in a rehabilitation program at an academic medical center in north-eastern Europe. Materials and Methods: We conducted a prospective cohort study on 97 patients with PAD admitted to a single tertiary referral center. At the 6-months follow-up, 75 patients (77.3%) showed improved clinical status. We analyzed demographics and clinical and paraclinical parameters in order to explore factors associated with a favorable outcome. Results: Hypertension (p = 0.002), diabetes mellitus (p = 0.002), dyslipidemia (p = 0.045), and obesity (p = 0.564) were associated with no clinical improvement. Smoking cessation (p < 0.001), changing sedentary lifestyle (p = 0.032), and improvement of lipid and carbohydrate profile as well as functional status parameters and ambulatory arterial stiffness index (p = 0.008) were factors associated with clinical improvement at the 6-months follow-up. Conclusions: PAD patients require an integrative, multidisciplinary management to maintain functional status and increase quality of life. Improving carbohydrate and lipid profile, adopting a healthy lifestyle, quitting smoking and increasing exercise capacity are predictors for clinical improvement 6 months after enrolment in a CR program.

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Cristina Adam

Papers

Novel Biomarkers of Atherosclerotic Vascular Disease—Latest Insights in the Research Field

Mortality Risk Assessment in Peripheral Arterial Disease—The Burden of Cardiovascular Risk Factors over the Years: A Single Center’s Experience

Impact of Sodium–Glucose Cotransporter 2 (SGLT2) Inhibitors on Arterial Stiffness and Vascular Aging—What Do We Know So Far? (A Narrative Review)

Cardiac Rehabilitation in Patients with Peripheral Artery Disease—A Literature Review in COVID-19 Era

Cardiac Rehabilitation in Peripheral Artery Disease in a Tertiary Center—Impact on Arterial Stiffness and Functional Status after 6 Months