Coronary atherosclerosis is a chronic pathological process that involves inflammation together with endothelial dysfunction and lipoprotein dysregulation. Experimental studies during the past decades ...have established the role of inflammatory cytokines in coronary artery disease, namely interleukins (ILs), tumor necrosis factor (TNF)-α, interferon-γ, and chemokines. Moreover, their value as biomarkers in disease development and progression further enhance the validity of this interaction. Recently, cytokine-targeted treatment approaches have emerged as potential tools in the management of atherosclerotic disease. IL-1β, based on the results of the CANTOS trial, remains the most validated option in reducing the residual cardiovascular risk. Along the same line, colchicine was also proven efficacious in preventing major adverse cardiovascular events in large clinical trials of patients with acute and chronic coronary syndrome. Other commercially available agents targeting IL-6 (tocilizumab), TNF-α (etanercept, adalimumab, infliximab), or IL-1 receptor antagonist (anakinra) have mostly been assessed in the setting of other inflammatory diseases and further testing in atherosclerosis is required. In the future, potential targeting of the NLRP3 inflammasome, anti-inflammatory IL-10, or atherogenic chemokines could represent appealing options, provided that patient safety is proven to be of no concern.
•Increasing prevalence of hyperuricaemia has been noted in many populations.•Uric acid is a potentially treatable predictive risk factor for cardiometabolic diseases.•Uric acid-lowering therapies ...improve outcomes in hypertension and kidney disease.•There may be benefit to lowering serum uric acid in other cardiometabolic diseases.
During the last century, there has been an increasing prevalence of hyperuricaemia noted in many populations. While uric acid is usually discussed in the context of gout, hyperuricaemia is also associated with hypertension, chronic kidney disease, hypertriglyceridaemia, obesity, atherosclerotic heart disease, metabolic syndrome, and type 2 diabetes. Here we review the connection between hyperuricaemia and cardiovascular, kidney and metabolic diseases. Contrary to the popular view that uric acid is an inert metabolite of purine metabolism, recent studies suggest serum uric acid may have a variety of pro-inflammatory, pro-oxidative and vasoconstrictive actions that may contribute to cardiometabolic diseases. Hyperuricaemia is a predictive factor for the development of hypertension, metabolic syndrome, type 2 diabetes, coronary artery disease, left ventricular hypertrophy, atrial fibrillation, myocardial infarction, stroke, heart failure and chronic kidney disease. Treatment with uric acid-lowering therapies has also been found to improve outcomes in patients with hypertension and kidney disease, in some but not all studies. In conclusion, uric acid is emerging as a potentially treatable risk factor for cardiometabolic diseases, and more clinical trials investigating the potential benefit of lowering serum uric acid are recommended in individuals with hyperuricaemia with and without deposition and concomitant hypertension, metabolic syndrome or chronic kidney disease.
To fight the COVID-19 pandemic, messenger RNA (mRNA) vaccines were the first to be adopted by vaccination programs worldwide. We sought to investigate the short-term effect of mRNA vaccine ...administration on endothelial function and arterial stiffness. Thirty-two participants (mean age 37 ± 8 years, 20 men) who received the BNT162b2 mRNA COVID-19 vaccine were studied in three sessions in a sequence-randomized, sham-controlled, assessor-blinded, crossover design. The primary outcome was endothelial function (assessed by brachial artery flow-mediated dilatation (FMD)), and the secondary outcomes were aortic stiffness (evaluated with carotid-femoral pulse wave velocity (PWV)) and inflammation (measured by high-sensitivity C-reactive protein (hsCRP) in blood samples). The outcomes were assessed prior to and at 8 h and 24 h after the 1st dose of vaccine and at 8 h, 24 h, and 48 h after the 2nd dose. There was an increase in hsCRP that was apparent at 24 h after both the 1st dose (-0.60 95% confidence intervals CI: -1.60 to -0.20, p = 0.013) and the 2nd dose (maximum median difference at 48 h -6.60 95% CI: -9.80 to -3.40, p < 0.001) compared to placebo. The vaccine did not change PWV. FMD remained unchanged during the 1st dose but decreased significantly by 1.5% (95% CI: 0.1% to 2.9%, p = 0.037) at 24 h after the 2nd dose. FMD values returned to baseline at 48 h. Our study shows that the mRNA vaccine causes a prominent increase in inflammatory markers, especially after the 2nd dose, and a transient deterioration of endothelial function at 24 h that returns to baseline at 48 h. These results confirm the short-term cardiovascular safety of the vaccine.
Atherosclerotic diseases are a leading cause of morbidity and mortality worldwide, despite the recent diagnostic and therapeutic advances. A thorough understanding of the pathophysiologic mechanisms ...is thus essential to improve the care of affected individuals. Macrophages are crucial mediators of the atherosclerotic cascade, but their role has not been fully elucidated. The two main subtypes, tissue-resident and monocyte-derived macrophages, have distinct functions that contribute to atherosclerosis development or regression. Since polarization of macrophages to an M2 phenotype and induction of macrophage autophagy have been demonstrated to be atheroprotective, targeting these pathways could represent an appealing approach. Interestingly, macrophage receptors could act as drug targets, as seen in recent experimental studies. Last but not least, macrophage-membrane-coated carriers have been investigated with encouraging results.
The involvement of cardiovascular disease in cancer onset and development represents a contemporary interest in basic science. It has been recognized, from the most recent research, that metabolic ...syndrome-related conditions, ranging from atherosclerosis to diabetes, elicit many pathways regulating lipid metabolism and lipid signaling that are also linked to the same framework of multiple potential mechanisms for inducing cancer. Otherwise, dyslipidemia and endothelial cell dysfunction in atherosclerosis may present common or even interdependent changes, similar to oncogenic molecules elevated in many forms of cancer. However, whether endothelial cell dysfunction in atherosclerotic disease provides signals that promote the pre-clinical onset and proliferation of malignant cells is an issue that requires further understanding, even though more questions are presented with every answer. Here, we highlight the molecular mechanisms that point to a causal link between lipid metabolism and glucose homeostasis in metabolic syndrome-related atherosclerotic disease with the development of cancer. The knowledge of these breakthrough mechanisms may pave the way for the application of new therapeutic targets and for implementing interventions in clinical practice.
Objective
Emerging data indicate an increased risk of cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and highlight the potential impact of coronavirus ...disease (COVID‐19) on the management and outcomes of acute stroke. We conducted a systematic review and meta‐analysis to evaluate the aforementioned considerations.
Methods
We performed a meta‐analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS‐CoV‐2 infection status. We used a random‐effects model. Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (CIs).
Results
We identified 18 cohort studies including 67,845 patients. Among patients with SARS‐CoV‐2, 1.3% (95% CI = 0.9–1.6%, I2 = 87%) were hospitalized for cerebrovascular events, 1.1% (95% CI = 0.8–1.3%, I2 = 85%) for ischemic stroke, and 0.2% (95% CI = 0.1–0.3%, I2 = 64%) for hemorrhagic stroke. Compared to noninfected contemporary or historical controls, patients with SARS‐CoV‐2 infection had increased odds of ischemic stroke (OR = 3.58, 95% CI = 1.43–8.92, I2 = 43%) and cryptogenic stroke (OR = 3.98, 95% CI = 1.62–9.77, I2 = 0%). Diabetes mellitus was found to be more prevalent among SARS‐CoV‐2 stroke patients compared to noninfected historical controls (OR = 1.39, 95% CI = 1.00–1.94, I2 = 0%). SARS‐CoV‐2 infection status was not associated with the likelihood of receiving intravenous thrombolysis (OR = 1.42, 95% CI = 0.65–3.10, I2 = 0%) or endovascular thrombectomy (OR = 0.78, 95% CI = 0.35–1.74, I2 = 0%) among hospitalized ischemic stroke patients during the COVID‐19 pandemic. Odds of in‐hospital mortality were higher among SARS‐CoV‐2 stroke patients compared to noninfected contemporary or historical stroke patients (OR = 5.60, 95% CI = 3.19–9.80, I2 = 45%).
Interpretation
SARS‐CoV‐2 appears to be associated with an increased risk of ischemic stroke, and potentially cryptogenic stroke in particular. It may also be related to an increased mortality risk. ANN NEUROL 2021;89:380–388
PurposePatients suffering from cardiovascular autonomic failure often develop neurogenic supine hypertension (nSH), i.e., high blood pressure (BP) in the supine position, which falls in the upright ...position owing to impaired autonomic regulation. A committee was formed to reach consensus among experts on the definition and diagnosis of nSH in the context of cardiovascular autonomic failure.MethodsAs a first and preparatory step, a systematic search of PubMed-indexed literature on nSH up to January 2017 was performed. Available evidence derived from this search was discussed in a consensus expert round table meeting in Innsbruck on February 16, 2017. Statements originating from this meeting were further discussed by representatives of the American Autonomic Society and the European Federation of Autonomic Societies and are summarized in the document presented here. The final version received the endorsement of the European Academy of Neurology and the European Society of Hypertension.ResultsIn patients with neurogenic orthostatic hypotension, nSH is defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, measured after at least 5 min of rest in the supine position. Three severity degrees are recommended: mild, moderate and severe. nSH may also be present during nocturnal sleep, with reduced-dipping, non-dipping or rising nocturnal BP profiles with respect to mean daytime BP values. Home BP monitoring and 24-h-ambulatory BP monitoring provide relevant information for a customized clinical management.ConclusionsThe establishment of expert-based criteria to define nSH should standardize diagnosis and allow a better understanding of its epidemiology, prognosis and, ultimately, treatment.
Aim
To investigate the associations of blood pressure variability (BPV), expressed as long‐term (visit‐to‐visit) and short‐term (ambulatory blood pressure monitoring ABPM and home blood pressure ...monitoring HBPM) and all‐cause mortality, major adverse cardiovascular events (MACEs), extended MACEs, microvascular complications (MiCs) and hypertension‐mediated organ damage (HMOD) in adult patients with type 2 diabetes.
Materials and methods
PubMed, Medline, Embase, Cinahl, Web of Science, ClinicalTrials.gov and grey literature databases were searched for studies including patients with type 2 diabetes, at least one variable of BPV (visit‐to‐visit, HBPM, ABPM) and evaluation of the incidence of at least one of the following outcomes: all‐cause mortality, MACEs, extended MACEs and/or MiCs and/or HMOD. The extracted information was analyzed using random effects meta‐analysis and meta‐regression.
Results
Data from a total of 377 305 patients were analyzed. Systolic blood pressure (SBP) variability was associated with a significantly increased risk of all‐cause mortality (HR 1.12, 95% CI 1.04–1.21), MACEs (HR 1.01, 95% CI 1.04–1.17), extended MACEs (HR 1.07, 95% CI 1.03–1.11) and MiCs (HR 1. 12, 95% CI 1.01–1.24), while diastolic blood pressure was not. Associations were mainly driven from studies on long‐term SBP variability. Qualitative analysis showed that BPV was associated with the presence of HMOD expressed as carotid intima‐media thickness, pulse wave velocity and left ventricular hypertrophy. Results were independent of mean blood pressure, glycaemic control and serum creatinine levels.
Conclusions
Our results suggest that BPV might provide additional information rather than mean blood pressure on the risk of cardiovascular disease in patients with type 2 diabetes.
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