Risk Factors of Arterial Events in Patients with Venous Thromboembolism: A Systematic Review and Meta-Analysis

Background If recent studies suggested that arterial ischemic events in patients with venous thromboembolism (VTE) are more frequent than in the general population without VTE, whether patients with VTE have different risk factors of arterial events than classic known cardiovascular risk factors remain undefined. Through this systematic review and meta-analysis, we aimed to identify risk factors of arterial ischemic events in patients with VTE. Methods We searched PubMed, EMBASE, and Cochrane databases to identify cohort studies published between January 1, 2000, and December 31, 2020, reporting risk factors of arterials ischemic events in patients with VTE. Random-effect models meta-analysis served to get the pooled hazard ratio (HR) and 95% confidence interval (CI) of each risk factor identified. Results We screened 1,467 records of which 18 were finally included in systematic review and 10 in meta-analyses. Adjusted HR for 9 factors were included in meta-analysis. Male gender (HR: 1.38; 95% CI: 1.28–1.49), diabetes (HR: 1.65; 95% CI: 1.28–2.12), hypertension (HR: 1.38; 95% CI: 1.04–1.84), previous atherothrombotic event (HR: 3.22; 95% CI: 1.12–9.23), chronic kidney disease (HR: 1.41; 95% CI: 1.05–1.88), cancer (HR: 1.72; 95% CI: 1.41–2.09), and unprovoked VTE (HR: 1.88; 95% CI: 1.37–2.57) were the identified risk factors of arterial events in VTE population after meta-analysis. Conclusion Risk factors of arterial events in patients with VTE include usual cardiovascular risk factors and other risk factors that are related to VTE such as cancer and unprovoked VTE.

Anti-platelet drug loaded targeted technologies for the effective treatment of Atherothrombosis

: Atherothrombosis is the result of direct interaction between atherosclerotic plaque and arterial thrombosis and is the most common type of cardiovascular disease. As a long term progressive disease, atherosclerosis frequently results in an acute atherothrombotic event through plaque rupture and platelet-rich thrombus formation. The pathophysiology of atherothrombosis involves cholesterol accumulation endothelial dysfunction, dyslipidemia, immuno-inflammatory and apoptotic aspects. Platelet activation and aggregation is the major cause for stroke because of its roles including thrombus, contributing to atherosclerotic plaque, and sealing off bleeding vessel. Platelet aggregates are associated with arterial blood pressure and cardiovascular ischemic events. Under normal physiological conditions when a blood vessel is damaged, the task of platelets within the circulation is to arrest the blood loss. Antiplatelet inhibit platelet function thereby decrease thrombus formation with complementary modes of action to prevent atherothrombosis. In the present scientific scenario, researchers throughout the world are focusing towards the development of novel drug delivery systems to enhance patient’s compliance. Immediate responding pharmaceutical formulations become an emerging trend in the pharmaceutical industries with better patient compliance. Here in the proposed review will focused towards the understanding on the molecular pathogenesis of atherothrombosis and recent novel formulation approaches for the treatment of atherothrombosis with special emphasis on commercial formulation and upcoming technologies.

Is Plaque Rupture Always Responsible in Acute Coronary Syndrome?

The majority cause of myocardial infarction is the atherothrombotic event, mainly cause by plaque rupture. Since the 20th century, it was found that the plaque rupture was not the solely condition responsible for the acute coronary syndrome. With the invention of more sensitive myocardial biomarker, a series of guideline was written as guideline for the definition of myocardial infarction. This review discuss about the consensus in the Universal Definition of Myocardial Infarction.

Myocardial Infarction Type 2 and Myocardial Injury

BACKGROUND The development and implementation of sensitive and high-sensitivity cardiac troponin assays has not only expedited the early ruling in and ruling out of acute myocardial infarction, but has also contributed to the identification of patients at risk for myocardial injury with necrosis, as confirmed by the presence of cardiac troponin concentrations above the 99th percentile. Myocardial injury with necrosis may occur either in the presence of overt ischemia from myocardial infarction, or in the absence of overt ischemia from myocardial injury accompanying other conditions. Myocardial infarction type 2 (T2MI) has been a focus of attention; conceptually T2MI occurs in a clinical setting with overt myocardial ischemia where a condition other than an acute atherothrombotic event is the major contributor to a significant imbalance between myocardial oxygen supply and/or demand. Much debate has surrounded T2MI and its interrelationship with myocardial injury. CONTENT We provide a detailed overview of the current concepts and challenges regarding the definition, diagnosis, management, and outcomes of T2MI, as well as the interrelationship to myocardial injury, and emphasize several critical clinical concepts for both clinicians and researchers moving forward. SUMMARY T2MI and myocardial injury are frequently encountered in clinical practice and are associated with poor outcomes in both the short term and long term. Diagnostic strategies to facilitate the clinical distinction between ischemic myocardial injury with or without an acute atheroma-thrombotic event vs non–ischemic-mediated myocardial injury conditions are urgently needed, as well as evidence-based therapies tailored toward improving outcomes for patients with T2MI.

Peri-operative platelet function testing: The potential for reducing ischaemic and bleeding risks

SummaryThe pivotal role of platelet activation and reactivity during atherothrombotic event occurrence associated with acute coronary syndromes (ACS) or percutaneous coronary interventions (PCI) is well established. Numerous translational research studies have established a threshold level of platelet reactivity during dual antiplatelet therapy above which a higher risk for ischaemic event occurrence has been observed. The clinical validity of these threshold values in reducing ischemic event occurrence with modified P2Y12 receptor therapy is currently under investigation in large-scale clinical trials. The association between on-treatment platelet reactivity measured by an ex vivo assay and the occurrence of bleeding events is less established. Currently, there is limited evidence of an association between platelet inhibition and coronary artery bypass grafting (CABG)- related bleeding in patients on clopidogrel therapy indicating that preoperative platelet function monitoring may guide both the timing of elective CABG and the administration of blood products in patients needing surgery. However, in the absence of a large-scale prospective clinical trial, routine platelet function monitoring and modification of timing of surgery based on platelet function monitoring are currently not recommended.

Abstract 2655: Polymorphisms in the Gene Encoding for Cyclooxygenase-2 and the Risk of Recurrent Atherothrombotic Events

Multiple single nucleotide polymorphisms (SNP’s) in the gene encoding for cyclooxygenase-2 (COX-2) have been identified. These SNP’s may modify risk of atherothrombotic events. The COX-2 -765G->C SNP has been associated with decreased COX-2 activity and with significantly lower odds of a first atherothrombotic event. The − 1195G->A SNP on the other hand seems to be correlated with increased COX-2 activity, but has not been investigated in relation to atherothrombotic events. Our aim is to investigate whether these two functional COX-2 SNP’s are associated with the risk of recurrent atherothrombotic events. Patients hospitalized between Apr 2002 and Jan 2004 with acute coronary syndrome were genotyped for the COX-2 − 765G->C and − 1195G->A SNP’s and followed up to July 2008. The primary endpoint was a composite of cardiovascular death, myocardial infarction and/or stroke. Multivariate analysis was performed. We included a cohort of 379 consecutive patients (median age 66 y (IQR 55–73), 66% were males). Genotyping for the − 765G->C showed frequencies of 72% GG, 27% GC and 1% CC. For the − 1195G->A frequencies were 5% GG, 35% GA and 60% AA. There was strong linkage disequilibrium (D’=−1.0) between both SNP’s. The primary endpoint occurred in 82 patients (22%). The unadjusted hazard ratio for the − 765GC/CC genotypes was 1.33 (95% confidence intervals [CI] 0.84 –2.10, p= 0.22) compared with − 765GG , the adjusted hazard ratio was 1.16 (95% CI 0.72–1.88, p=0.54). Haplotype analysis of the combination of −1195- and −765-genotypes, revealed no genetic subgroup at significantly increased risk either. Previously, the COX-2 − 765G->C SNP was associated with a reduced risk for first atherothrombotic event. For the risk of recurrent events we found no effect for this SNP. In addition we studied the combination with the functional − 1195G->A SNP of COX-2, which did not show a significant effect on recurrent events either.