Archives of Medical Science最新文献

Introduction: Previous studies have reported a potential association between trimethylamine N-oxide (TMAO) and Parkinson's disease (PD). The objective of this study was to examine the potential relationship between the levels of circulating TMAO and its precursors and the risk of PD using a two-sample Mendelian randomization (MR) approach.

Material and methods: We aggregated data from three genome-wide association studies (International Parkinson's Disease Genomics Consortium, Parkinson's Research: The Organized Genetics Initiative and GenePD, and FinnGen) to extract single-nucleotide polymorphisms (SNPs) associated with circulating concentrations of TMAO, choline, carnitine, and betaine. These SNPs were employed as instrumental variables in a random-effects model to evaluate the causal relationship between circulating concentrations of TMAO and its precursors and the risk of Parkinson's disease, by estimating odds ratios with accompanying 95% confidence intervals. The primary analysis employed the inverse variance-weighted (IVW) method, which was complemented with MR-Egger regression analysis.

Results: The analysis using the IVW method, which aggregated data from the three databases, did not show any causal relationship between circulating concentrations of TMAO and its precursors, and the risk of PD (p > 0.05). This finding was further confirmed by the results of the MR-Egger analysis. A sensitivity analysis demonstrated that the results were not influenced by any biases, and a heterogeneity test indicated no significant variation among the SNPs.

Conclusions: This study did not identify any conclusive evidence of a causal association between the circulating concentrations of TMAO or its precursors and the risk of PD. Further investigation is warranted to determine whether such an association indeed exists.

Cardiovascular diseases (CVD) prevention does not only mean effective fight against the existing and well-recognized cardiovascular risk factors, but also against their complications, including micro- and macrovascular complications. Only then we might comprehensively reduce CVD burden and cardiovascular and cause-specific morbidity and mortality. In relation to obesity, prediabetes and especially diabetes, we recognize a number of potential dangerous non-cardiovascular complications, such as neuropathy, nephropathy and retinopathy. The latter's prevalence is even 30-40% and may appear in as many as 15% of patients with prediabetes. If not treated well it might result in the need for eye surgery or even vision loss. Fenofibrate has had a long history of evidence suggesting its preventive role in primary and especially secondary prevention of retinopathy, what has been investigated since the FIELD trial 19 years ago. Thus, given the obesity (the prevalence of 30% in Poland) and diabetes (10% which is predicted to be doubled in next 25 years) epidemic, we should look for the effective methods not only to optimize fasting blood glucose and haemoglobin A_1C, but also atherogenic dyslipidaemia and their complications, including retinopathy. In this Position Paper by the Polish Lipid Association (PoLA) we have reviewed the current stage of knowledge on possible mechanisms by which fenofibrate may contribute to retinopathy prevention, available data on safety and efficacy, to finally recommend administering fenofibrate in prevention of this dangerous diabetic complication, which significantly affects quality of life and disability-adjusted life-years (DALY). This intervention - well-recognized and already in common use in diabetic patients - may significantly improve population health in Poland and worldwide.

Lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle containing a highly polymorphic apolipoprotein(a) [apo(a)] homologous in > 80% to plasminogen, was identified as a genetically determined independent risk factor for cardiovascular disease. Elevated Lp(a) levels, found in about 20% of Europeans, are strongly linked to higher rates of myocardial infarction, major adverse cardiac events, accelerated plaque progression, ischemic stroke (especially in younger adults), and calcific aortic valve disease. However, its role in venous thromboembolism, including atypical locations like cerebral and retinal vein thrombosis, remains controversial despite several shared mechanisms underlying arterial and venous thromboembolism. The most robust evidence supports antifibrinolytic properties of elevated Lp(a), particularly smaller apo(a) isoforms, which inhibit plasminogen activation mainly by interacting with the tissue-type plasminogen activator, plasminogen, and fibrin. Other prothrombotic mechanisms include increased synthesis of plasminogen activator inhibitor (PAI-1), formation of denser fibrin networks composed of thinner fibers, less susceptible to lysis, increased platelet activation, enhanced oxidation of phospholipids leading to a low-grade proinflammatory state, upregulated tissue factor expression, and suppression of tissue factor pathway inhibitor. Targeted Lp(a) lowering therapies are currently being tested in randomized clinical trials and could potentially have clinically relevant antithrombotic effects, evidenced by the reduced risk of thromboembolism. This review summarizes the available data on the prothrombotic and antifibrinolytic actions of Lp(a), along with clinical evidence for the increased risk of thromboembolic events related to elevated Lp(a). It also introduces new concepts to explain discrepant clinical results regarding venous events, highlighting the impact of oxidized phospholipids on a prothrombotic state under conditions of high Lp(a).