Platelet­to­lymphocyte ratio, neutrophil­to­lymphocyte ratio and monocyte­to­HDL cholesterol ratio as helpful biomarkers for patients hospitalized for deep vein thrombosis.

There is an increased interest for novel biomarkers in order to improve the diagnostic accuracy for deep vein thrombosis (DVT). Moreover, the link between inflammation and venous thromboembolism has attracted increasing research interests. The present study aimed to evaluate the role of the platelet­to­lymphocyte ratio (PLR), neutrophil­to­lymphocyte ratio (NLR) and monocyte­to­high­density lipoprotein cholesterol ratio (MHR) as biomarkers for acute DVT. For this purpose, 300 consecutive patients who were hospitalized were considered; 33 patients out of the 300 were admitted for acute DVT of the lower limbs. The PLR, NLR and MHR, as well as the acute phase inflammation markers (leukocytes, neutrophils, C­reactive protein and fibrinogen) were measured. The patients with DVT exhibited significantly higher levels of PLR, NLR and MHR compared to those without DVT (P<0.001). Simple binary linear regression analysis (without confounding factors) between the NLR, PLR and MHR highest quartile and DVT revealed an odds ratio of 3.149 (P=0.01) for PLR, and an odds ratio of 4.191 (P=0.001) for MHR. Following the correction for the main confounding factors, PLR maintained a significant association with DVT (odds ratio, 3.379; P=0.007) and MHR maintained a stronger significant association with DVT (odds ratio, 4.378; P=0.001). It was thus hypothesized that the assessment of PLR and MHR, but not of NLR may help clinicians to improve the laboratory evaluation in elderly hospitalized patients with suspected DVT.

Evolving concepts in the pathophysiology of atherosclerosis: from endothelial dysfunction to thrombus formation through multiple shades of inflammation.

Atherosclerosis is the anatomo-pathological substrate of most cardio, cerebro and vascular diseases such as acute and chronic coronary syndromes, stroke and peripheral artery diseases. The pathophysiology of atherosclerotic plaque and its complications are under continuous investigation. In the last 2 decades our understanding on the formation, progression and complication of the atherosclerotic lesion has greatly improved and the role of immunity and inflammation is now well documented and accepted. The conventional risk factors modulate endothelial function determining the switch to a proatherosclerotic phenotype. From this point, lipid accumulation with an imbalance from cholesterol influx and efflux, foam cells formation, T-cell activation, cytokines release and matrix-degrading enzymes production occur. Lesions with high inflammatory rate become vulnerable and prone to rupture. Once complicated, the intraplaque thrombogenic material, such as the tissue factor, is exposed to the flowing blood, thus inducing coagulation cascade activation, platelets aggregation and finally intravascular thrombus formation that leads to clinical manifestations of this disease. Nonconventional risk factors, such as gut microbiome, are emerging novel markers of atherosclerosis. Several data indicate that gut microbiota may play a causative role in formation, progression and complication of atherosclerotic lesions. The gut dysbiosis-related inflammation and gut microbiota-derived metabolites have been proposed as the main working hypothesis in contributing to disease formation and progression. The current evidence suggest that the conventional and nonconventional risk factors may modulate the degree of inflammation of the atherosclerotic lesion, thus influencing its final fate. Based on this hypothesis, targeting inflammation seems to be a promising approach to further improve our management of atherosclerotic-related diseases.

Platelet­to­lymphocyte ratio, neutrophil­to­lymphocyte ratio and monocyte­to­HDL cholesterol ratio as markers of peripheral artery disease in elderly patients.

Solid evidence underlines the pivotal role played by inflammation regarding atherosclerosis. Peripheral artery disease (PAD) is one of atherosclerotic cardiovascular diseases (CVDs), it is highly frequently diagnosed in older individuals. In the present study we carried out an investigation on the association between platelet­to­lymphocytes ratio (PLR), neutrophil­to­lymphocyte ratio (NLR), monocyte­to­HDL cholesterol ratio (MHR) with PAD as favourable markers. We identified 300 subjects aged over 70 years, without any concomitant CVDs. The PLR, NLR and MHR were assessed from peripheral venous blood routinely drawn in the ward during hospitalization. Patients were divided in groups according to ankle brachial index (ABI) value (>0.9; 0.9­0.99; 1­1.4; >1.4). Higher PLR (P=0.007), NLR (P=0.0001) and MHR (P=0.0001) were associated with <0.9 ABI. Patients with a >1.4 ABI showed NLR values higher compared to >0.9l ABI (P<0.01). Univariate linear regression analysis demonstrated the direct correlation between increase in PLR (P=0.0023)and MHR (P<0.0001) with the decrease in ABI value. In multivariate linear regression analysis including main cardiovascular risk factors we found that PLR, NLR and MHR were independently associated with lower ABI (P=0.0011). Results show and suggest that the elevated PLR, NLR and MHR are related to PAD evaluated with ABI measurement. PLR and MHR seem to be more reliable markers than NLR in PAD. NLR seems to be more related to incompressibility of arterial wall. It is hypothesized that these three indexes may play a role as simple and repetitive markers of PAD.

Impact of Sex Differences and Diabetes on Coronary Atherosclerosis and Ischemic Heart Disease.

Cardiovascular diseases (CVD) including coronary artery disease (CAD) and ischemic heart disease (IHD) are the main cause of mortality in industrialized countries. Although it is well known that there is a difference in the risk of these diseases in women and men, current therapy does not consider the sexual dimorphism; i.e., differences in anatomical structures and metabolism of tissues. Here, we discuss how genetic, epigenetic, hormonal, cellular or molecular factors may explain the different CVD risk, especially in high-risk groups such as women with diabetes. We analyze whether sex may modify the effects of diabetes at risk of CAD. Finally, we discuss current diagnostic techniques in the evaluation of CAD and IHD in diabetic women.

"State-of-Art" paper of the Italian Working Group on Atherosclerosis: Preclinical assessment of early coronary atherosclerosis.

Although the early diagnosis and treatment for acute myocardial infarction have improved over the past decades, the morbidity and mortality from coronary artery disease (CAD) remain significant in Europe and worldwide. It is estimated that the majority of people in the developed countries who die suddenly from CAD, have no prior manifestation of disease, and the majority of these individuals are not considered to be at high risk. Accurate identification of individuals at risk of such events before the clinical manifestations is therefore required. This "State-of-Art" paper of the Italian Working Group on Atherosclerosis aims to i. provide an overview of both the traditional and emerging non-invasive imaging techniques used to detect early atherosclerosis in the general population with moderate cardiovascular risk; ii. identify the rationale for screening asymptomatic patients with preclinical atherosclerotic lesions and the optimal algorithm that should be used to detect them; iii. discuss the future directions of atherosclerosis research, with special focus on nanotechnology, aimed at early identification and treatment of low- and intermediate-risk patients.