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Carotid artery disease is commonly encountered in clinical practice and accounts for approximately 30% of ischemic strokes in the general population. Numerous biomarkers have been investigated as predictors of the onset and progression of carotid disease, the occurrence of cerebrovascular complications, and overall prognosis. Among them, blood cell count (BCC) indexes of systemic inflammation might be particularly useful, from a pathophysiological and clinical point of view, given the inflammatory nature of the atherosclerotic process. The aim of this review is to discuss the available evidence regarding the role of common BCC indexes, such as the neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV), platelet distribution width (PDW), and red cell distribution width (RDW), in the diagnosis and risk stratification of carotid artery disease, and their potential clinical applications.

Patients with rheumatoid arthritis (RA), a chronic and disabling autoimmune condition that is characterized by articular and extra-articular manifestations and a pro-inflammatory and pro-oxidant state, suffer from premature atherosclerosis and excessive cardiovascular disease burden. A key step in the pathogenesis of atherosclerosis is impaired synthesis of the endogenous messenger nitric oxide (NO) by endothelial cells which, in turn, alters local homeostatic mechanisms and favors vascular damage and plaque deposition. While the exact mechanisms of endothelial dysfunction in RA remain to be established, there is good evidence that RA patients have relatively high circulating concentrations of the methylated arginine asymmetric dimethylarginine (ADMA), a potent endogenous inhibitor of endothelial NO synthase (eNOS). This review discusses the biological and pathophysiological role of ADMA, the interplay between ADMA, inflammation and oxidative stress, and the available evidence on the adverse impact of ADMA on endothelial function and atherosclerosis and potential ADMA-lowering therapies in RA patients.

Increasing age is a strong, independent risk factor for atherosclerosis and cardiovascular disease. Key abnormalities driving cardiovascular risk in old age include endothelial dysfunction, increased arterial stiffness, blood pressure, and the pro-atherosclerotic effects of chronic, low-grade, inflammation. The identification of novel therapies that comprehensively target these alterations might lead to a major breakthrough in cardiovascular risk management in the older population. Systematic reviews and meta-analyses of observational studies have shown that methotrexate, a first-line synthetic disease-modifying anti-rheumatic drug, significantly reduces cardiovascular morbidity and mortality in patients with rheumatoid arthritis, a human model of systemic inflammation, premature atherosclerosis, and vascular aging. We reviewed in vitro and in vivo studies investigating the effects of methotrexate on endothelial function, arterial stiffness, and blood pressure, and the potential mechanisms of action involved. The available evidence suggests that methotrexate might have beneficial effects on vascular homeostasis and blood pressure control by targeting specific inflammatory pathways, adenosine metabolism, and 5' adenosine monophosphate-activated protein kinase. Such effects might be biologically and clinically relevant not only in patients with rheumatoid arthritis but also in older adults with high cardiovascular risk. Therefore, methotrexate has the potential to be repurposed for cardiovascular risk management in old age because of its putative pharmacological effects on inflammation, vascular homeostasis, and blood pressure. However, further study and confirmation of these effects are essential in order to adequately design intervention studies of methotrexate in the older population.

Background:This study measured serum concentrations of vascular risk factors, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) in a representative sample of older community-dwelling adults and determined their associations with objective and subjective memory impairment. Methods: Data on clinical, lifestyle, and demographic characteristics, serum ADMA, SDMA, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. Objective memory was measured with the Audio Recorded Cognitive Screen (ARCS) neuropsychological battery and subjective memory impairment was measured using the Memory Complaint Questionnaire (MAC-Q). Results: Multivariate analysis revealed that SDMA and diabetes were significantly associated with objective memory impairment (Adjusted Odd ratio (AOR) = 3.90; 95% CI. 1.21 – 12.52 for fourth quartile (Q4) of SDMA. ADMA, SDMA, education, number of general practitioner visits and atrial fibrillation were all significantly associated with subjective memory impairment. (AOR = 1.82; 95% CI. 1.04 – 3.18 for Q4 ADMA. Conclusions: Higher serum SDMA was associated with objective and subjective memory impairment while higher serum ADMA was associated with subjective memory impairment.