Diabetes Mellitus and Cardiovascular Prevention: The Role and the Limitations of Currently Available Antiplatelet Drugs

Diabetes mellitus (DM) is associated with macrovascular and microvascular complications. Platelets have a “key role” in atherogenesis and its thrombotic complications in subjects with DM. Moreover, the concomitant presence of multiple “classical” cardiovascular risk factors in diabetic subjects contributes to enhanced atherothrombotic risk. Antiplatelet agents are effective in primary and secondary prevention of arterial thrombosis (cardiovascular events, ischaemic stroke, and peripheral arterial occlusive disease). The role of chronic administration of antiplatelet drugs in primary prevention of arterial vascular events is known to be less clear than in secondary prevention, and, also in diabetic patients, the decision to give primary prophylaxis should be taken on an individual-patient basis, after a careful evaluation of the balance between the expected benefits and the risk of major bleedings. Although, currently, treatment has proven useful in reducing vascular events, diabetic patients continue to have a higher risk of adverse cardiovascular events compared with those in nondiabetic patients. This paper reviews the role of currently available antiplatelet drugs in primary and secondary prevention of vascular events in diabetic patients and the limitations of these drugs, and it discusses the role of novel and more potent antiplatelets and of new agents currently under clinical development

Red wine consumption and cardiovascular health

Wine is a popular alcoholic beverage that has been consumed for hundreds of years. Benefits from moderate alcohol consumption have been widely supported by the scientific literature and, in this line, red wine intake has been related to a lesser risk for coronary heart disease (CHD). Experimental studies and meta-analyses have mainly attributed this outcome to the presence in red wine of a great variety of polyphenolic compounds such as resveratrol, catechin, epicatechin, quercetin, and anthocyanin. Resveratrol is considered the most effective wine compound with respect to the prevention of CHD because of its antioxidant properties. The mechanisms responsible for its putative cardioprotective effects would include changes in lipid profiles, reduction of insulin resistance, and decrease in oxidative stress of low-density lipoprotein cholesterol (LDL-C). The aim of this review is to summarize the accumulated evidence correlating moderate red wine consumption with prevention of CHD by focusing on the different mechanisms underlying this relationship. Furthermore, the chemistry of wine as well as chemical factors that influence the composition of the bioactive components of red wine are also discussed

The progression of hemophilic arthropathy: The role of biomarkers

Background: Hemophilia A and B are X-linked congenital bleeding disorders characterized by recurrent hemarthroses leading to specific changes in the synovium and cartilage, which finally result in the destruction of the joint: this process is called hemophilic arthropathy (HA). This review highlights the most prominent molecular biomarkers found in the literature to discuss their potential use in the clinical practice to monitor bleeding, to assess the progression of the HA and the effectiveness of treatments. Methods: A review of the literature was performed on PubMed and Embase, from 3 to 7 August 2020. Study selection and data extraction were achieved independently by two authors and the following inclusion criteria were determined a priori: English language, available full text and articles published in peer-reviewed journal. In addition, further articles were identified by checking the bibliography of relevant articles and searching for the studies cited in all the articles examined. Results: Eligible studies obtained at the end of the search and screen process were seventy-three (73). Conclusions: Despite the surge of interest in the clinical use of biomarkers, current literature underlines the lack of their standardization and their potential use in the clinical practice preserving the role of physical examination and imaging in early diagnosis

Venous thromboembolism in covid-19 compared to non-covid-19 cohorts: A systematic review with meta-analysis

Background: A high incidence of venous thromboembolism (VTE) is reported in hospitalized COVID-19 patients, in particular in patients admitted to the intensive care unit (ICU). In patients with respiratory tract infections, including influenza A (H1N1), many studies have demonstrated an increased incidence of thromboses, but evidence is lacking regarding the risk difference (RD) of the occurrence of VTE between COVID-19 and non-COVID-19 patients. Methods: In this systematic review with meta-analysis, we evaluated the RD of the occurrence of VTE, pulmonary embolism (PE), and deep venous thrombosis (DVT) between COVID-19 and other pulmonary infection cohorts, in particular H1N1, and in an ICU setting. We searched for all studies comparing COVID-19 vs. non-COVID-19 regarding VTE, PE, and DVT. Results: The systematic review included 12 studies and 1,013,495 patients. The RD for VTE in COVID-19 compared to non-COVID-19 patients was 0.06 (95% CI 0.11–0.25, p = 0.011, I2 = 97%), and 0.16 in ICU (95% CI 0.045–0.27, p = 0.006, I2 = 80%). The RD for PE between COVID-19 and non-COVID-19 patients was 0.03 (95% CI, 0.006–0.045, p = 0.01, I2 = 89%). The RD for PE between COVID-19 and non-COVID-19 patients was 0.021 in retrospective studies (95% CI 0.00–0.04, p = 0.048, I2 = 92%) and 0.11 in ICU studies (95% CI 0.06–0.16, p < 0.001, I2 = 0%). Conclusions: The growing awareness and understanding of a massive inflammatory response combined with a hypercoagulable state that predisposes patients to thrombosis in COVID-19, in particular in the ICU, may contribute to a more appropriate strategy of prevention and earlier detection of the thrombotic events

Bariatric surgery and diabetes remission: Sleeve gastrectomy or mini-gastric bypass?

AIM: To investigate the weight loss and glycemic control status [blood glucose, hemoglobin A1c (HbA1c) and hypoglycaemic treatment]. METHODS: The primary risk factor for type 2 diabetes is obesity, and 90% of all patients with type 2 diabetes are overweight or obese. Although a remarkable effect of bariatric surgery is the profound and durable resolution of type 2 diabetes clinical manifestations, little is known about the difference among various weight loss surgical procedures on diabetes remission. Data from patients referred during a 3-year period (from January 2009 to December 2011) to the University of Naples "Federico II" diagnosed with obesity and diabetes were retrieved from a prospective database. The patients were split into two groups according to the surgical intervention performed [sleeve gastrectomy (SG) and mini-gastric bypass (MGB)]. Weight loss and glycemic control status (blood glucose, HbA1c and hypoglycaemic treatment) were evaluated. RESULTS: A total of 53 subjects who underwent sleeve gastrectomy or mini-gastric bypass for obesity and diabetes were screened for the inclusion in this study. Of these, 4 subjects were excluded because of surgical complications, 7 subjects were omitted because young surgeons conducted the operations and 11 subjects were removed because of the lack of follow-up. Thirty-one obese patients were recruited for this study. A total of 15 subjects underwent SG (48.4%), and 16 underwent MGB (51.6%). After adjusting for various clinical and demographic characteristics in a multivariate logistic regression analysis, high hemoglobin A1c was determined to be a negative predictor of diabetes remission at 12 mo (OR = 0.366, 95%CI: 0.152-0.884). Using the same regression model, MGB showed a clear trend toward higher diabetes remission rates relative to SG (OR = 3.780, 95%CI: 0.961-14.872). CONCLUSION: Although our results are encouraging regarding the effectiveness of mini-gastric bypass on diabetes remission, further studies are needed to provide definitive conclusions in selecting the ideal procedure for diabetes remission

Effects of Bisphosphonate Treatment on Circulating Lipid and Glucose Levels in Patients with Metabolic Bone Disorders

Bisphosphonates are the first-choice treatment of osteoporosis and Paget’s disease of bone. Among the bisphosphonates, the non-amino-bisphosphonates, such as clodronic acid, are intracellular converted into toxic analogues of ATP and induce cellular apoptosis whereas the amino-bisphosphonates, such as zoledronic acid, inhibit the farnesyl-diphosphate-synthase, an enzyme of the mevalonate pathway. This pathway regulates cholesterol and glucose homeostasis and is a target for statins. In this retrospective cohort study, we evaluated the effects of an intravenous infusion of zoledronic acid (5&nbsp;mg) or clodronic acid (1500&nbsp;mg) on blood lipid (i.e. total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglycerides) and glucose levels in patients with osteoporosis and Paget’s disease of bone. All patients were evaluated before, 1 and 6&nbsp;months after bisphosphonate treatment. Pagetic and osteoporotic patients treated with zoledronic acid showed a significant reduction in glucose and atherogenic lipids during follow-up whereas these phenomena were not observed after clodronic treatment. The effect on circulating lipid levels was similar in naïve and re-treated Pagetic patients. Zoledronic acid treatment was associated with a reduction in blood glucose and atherogenic lipids in patients with metabolic bone disorders. The extent of change was similar to that obtained with the regular assumption of a low-intensity statin. Further studies are warranted to better evaluate the clinical implications of these observations

Markers of subclinical atherosclerosis in patients with aortic valve sclerosis : A meta-analysis of literature studies

Objective: Growing evidence suggested an association between aortic valve sclerosis (AVSc) and cardiovascular (CV) events. However, little is known about the association of AVSc with major markers of subclinical atherosclerosis. We performed a meta-analysis of literature studies to address this issue. Approach and Results: Studies on the relationship between AVSc and common carotid artery intima-media thickness (IMT), prevalence of carotid plaques (CPs), flow-mediated dilation (FMD), aortic pulse wave velocity (PWV) and augmentation index (AIx) were systematically searched in electronic databases. Thirteen studies enrolling 1086 AVSc patients and 2124 controls were included. Compared to controls, AVSc patients showed higher IMT (MD: 0.32 mm; 95%CI: 0.07, 0.58; p=0.014), and higher prevalence of CPs (OR: 4.06; 95%CI: 2.38, 6.93; p<0.001). Moreover, lower FMD (MD: -4.48%; 95%CI: -7.23, -1.74; p=0.001) and higher PWV (MD: 0.96%; 95%CI: 0.11, 1.81; p=0.027) were found in AVSc subjects than in controls, with no differences in AIx (MD: 0.76%; 95%CI: -0.97, 2.49; p=0.389). In Meta-regression analyses body mass index and triglycerides levels have an impact on the difference in IMT between cases and controls, while male gender and smoking habit were associated with the difference in the prevalence of CPs between the two groups. Conclusion: AVSc is significantly associated with altered markers of subclinical atherosclerosis, thus supporting the concept that AVSc and atherosclerosis share common etiopathological mechanism and/or risk factors. On this basis, an echocardiogram carried out to assess the state of the aortic valve would be desirable whenever an altered subclinical marker of atherosclerosis is found

Novel whole blood assay for phenotyping platelet reactivity in mice identifies ICAM-1 as a mediator of platelet-monocyte interaction

British Heart Foundation (PG/12/68/29779 and PG/14/48/30916) and the Wellcome Trust (101604/Z/13/Z to SN and TW, and 098291/Z/12/Z to S.N)