1,720,979 research outputs found
Physical activity to reduce PCSK9 levels
No full textThe amount of physical activity (PA) people practice everyday has been reducing in the last decades. Sedentary subjects tend to have an impaired lipid plasma profile with a higher risk of atherosclerosis and related cardio- and cerebrovascular events. Regular PA helps in both primary and secondary cardiovascular prevention because of its beneficial effect on the whole metabolism. Several studies reported lower levels of plasma lipids in trained subjects, but the precise mechanisms by which PA modulates lipoproteins remain only partially described. Thereupon, proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serin protease whose main function is to reduce the amount of low-density lipoprotein cholesterol (LDL-C) receptors, with the direct consequence of reducing LDL-C uptake by the liver and increasing its circulating pool. Accordingly, recently developed PCSK9 inhibitors improved cardiovascular prevention and are increasingly used to reach LDL-C goals in patients at high CV risk. Whether PA can modulate the levels of PCSK9 remains partially explored. Recent studies suggest PA as a negative modulator of such a deleterious CV mediator. Yet the level of evidence is limited. The aim of this review is to summarize the recent reports concerning the regulatory role of PA on PCSK9 plasma levels, highlighting the beneficial role of regular exercise on the prevention of atherosclerosis and overall CV health
Inflammatory biomarkers of ischemic stroke
No full textIschemic stroke remains the second leading cause of death and among the major causes of morbidity worldwide. Therapeutic options are currently limited to early reperfusion strategies, while pharmacological neuroprotective strategies despite showing promising results in the experimental setting constantly failed to enter the clinical arena. Inflammation plays an important role in the pathophysiology of ischemic stroke and mediators of inflammation have been longtime investigated as possible prognostic marker and therapeutic target for stroke patients. Here, we summarized available evidence on the role of cytokines, soluble adhesion molecules and adipokines in the pathophysiology, prognosis and therapy of ischemic stroke
Obesity, cardiovascular and cerebrovascular disease: the role of GLP-1 receptor agonists
No full textObesity prevalence is increasing dramatically worldwide, representing an important economic burden for our society. The treatment of obesity is quite challenging, potentially due to the fact that different phenotypes of the disease exist. Considering "obesities" rather than "obesity" and therefore considering different metabolism pathophysiology might help to better identify more tailored treatments. Glucagon-like peptide-1 receptor agonists (GLP-1RA), such as dulaglutide and semaglutide, are routinely prescribed for the treatment of type 2 diabetes mellitus (T2DM) in obese patients or those at high cardiovascular (CV) risk. Indeed, despite being developed for T2DM, GLP-1RA are increasingly recognized as anti-obesity treatments due to their weight loss effects. Furthermore, recent evidence showed that the CV prevention exerted by these molecules goes beyond that due to the weight loss and pleiotropic effects are reported. For instance, these drugs hold anti-inflammatory properties on vessels, enhance atherosclerotic plaque stability, reduce local advanced glycated end products receptor expression, lower monocyte-macrophages adhesion, and antagonize the effect of angiotensin-II. On the heart, GLP-1RA ameliorate cardiomyocyte survival and myocardial contractility, reduce cardiac hypertrophy, and are one of the few drugs that can reduce epicardial fat thickness. In this review, we summarize recent evidence concerning obesity/dysmetabolism and cardio-/cerebrovascular health. We further highlight the possible role of GLP-1RA as a treatment for obesity-related cardiovascular diseases by describing the principal molecular mechanisms known from current literature
Evaluating inflammatory status to predict atrial fibrillation recurrence following ablation: The role of systemic immune-inflammation index
No full textAtrial fibrillation (AF) is the most common arrhythmia in humans, affecting more than 40 million people worldwide. Radiofrequency catheter ablation (RFCA) was first introduced as a treatment for AF by Haïssaguerre M in the late 1990s. This procedure quickly became the treatment of choice, especially for symptomatic patients with AF refractory to medication. However, up to 45% of patients may experience AF recurrence within 12 months after RFCA. In this setting, AF recurrence is likely multifactorial, including atrial remodeling, local fibrosis or incomplete ablation due to failure in locating the trigger. Additionally, patients with obesity, sleep apnea, hypertension, or diabetes are at an increased risk of AF recurrence after RFCA. Inflammation is increasingly recognized as a potential key factor in AF recurrence and may arise both from the healing response of heart tissue post-ablation or from chronic low-grade inflammation, as observed in many risk factors. Here, we present an original study by Wang et al, which investigated the combination of the systemic immune-inflammation index—a marker developed to assess overall inflammatory status—and the APPLE score, designed to predict AF recurrence following RFCA. The study found that using both indicators together improved the accuracy of AF recurrence prediction. These findings underscore the significant role of inflammation in cardiovascular disease and demonstrated its impact on AF recurrence after RFCA. Further research is warranted to validate the combined use of these two scores in clinical settings for predicting AF recurrence following catheter ablation
Inflammation as a cause of acute myocardial infarction in patients with myeloproliferative neoplasm
No full textMyeloproliferative neoplasms (MPN) are a group of diseases characterized by the clonal proliferation of hematopoietic progenitor or stem cells. They are clinically classifiable into four main diseases: chronic myeloid leukemia, essential thrombocythemia, polycythemia vera, and primary myelofibrosis. These pathologies are closely related to cardio- and cerebrovascular diseases due to the increased risk of arterial thrombosis, the most common underlying cause of acute myocardial infarction. Recent evidence shows that the classical Virchow triad (hypercoagulability, blood stasis, endothelial injury) might offer an explanation for such association. Indeed, patients with MPN might have a higher number and more reactive circulating platelets and leukocytes, a tendency toward blood stasis because of a high number of circulating red blood cells, endothelial injury or overactivation as a consequence of sustained inflammation caused by the neoplastic clonal cell. These abnormal cancer cells, especially when associated with the JAK2V617F mutation, tend to proliferate and secrete several inflammatory cytokines. This sustains a pro-inflammatory state throughout the body. The direct consequence is the induction of a pro-thrombotic state that acts as a determinant in favoring both venous and arterial thrombus formation. Clinically, MPN patients need to be carefully evaluated to be treated not only with cytoreductive treatments but also with cardiovascular protective strategies
Sepsis in elderly patients: the role of neutrophils in pathophysiology and therapy
No full textSepsis is among the most important causes of mortality, particularly within the elderly population. Sepsis prevalence is on the rise due to different factors, including increasing average population age and the concomitant rise in the prevalence of frailty and chronic morbidities. Recent investigations have unveiled a "trimodal" trajectory for sepsis-related mortality, with the ultimate zenith occurring from 60 to 90 days until several years after the original insult. This prolonged temporal course ostensibly emanates from the sustained perturbation of immune responses, persevering beyond the phase of clinical convalescence. This phenomenon is particularly associated with the aging immune system, characterized by a broad dysregulation commonly known as "inflammaging." Inflammaging associates with a chronic low-grade activation of the innate immune system preventing an appropriate response to infective agents. Notably, during the initial phases of sepsis, neutrophils-essential in combating pathogens-may exhibit compromised activity. Paradoxically, an overly zealous neutrophilic reaction has been observed to underlie multi-organ dysfunction during the later stages of sepsis. Given this scenario, discovering treatments that can enhance neutrophil activity during the early phases of sepsis while curbing their overactivity in the later phases could prove beneficial in fighting pathogens and reducing the detrimental effects caused by an overactive immune system. This narrative review delves into the potential key role of neutrophils in the pathological process of sepsis, focusing on how the aging process impacts their functions, and highlighting possible targets for developing immune-modulatory therapies. Additionally, the review includes tables that outline the principal potential targets for immunomodulating agents
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