Increased Levels of Circulating Fatty Acids Are Associated with Protective Effects against Future Cardiovascular Events in Nondiabetics.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide, particularly in individuals with diabetes. The current study objective was to determine the circulating metabolite profiles associated with the risk of future cardiovascular events, with emphasis on diabetes status. Nontargeted metabolomics analysis was performed by LC-HRMS in combination with targeted quantification of eicosanoids and endocannabinoids. Plasma from 375 individuals from the IMPROVE pan-European cohort was included in a case-control study design. Following data processing, the three metabolite data sets were concatenated to produce a single data set of 267 identified metabolites. Factor analysis identified six factors that described 26.6% of the variability in the given set of predictors. An association with cardiovascular events was only observed for one factor following adjustment (p = 0.026). From this factor, we identified a free fatty acid signature (n = 10 lipids, including saturated, monounsaturated, and polyunsaturated fatty acids) that was associated with lower risk of future cardiovascular events in nondiabetics only (OR = 0.65, 0.27-0.80 95% CI, p = 0.030), whereas no association was observed among diabetic individuals. These observations support the hypothesis that increased levels of circulating omega-6 and omega-3 fatty acids are associated with protective effects against future cardiovascular events. However, these effects were only observed in the nondiabetic population, further highlighting the need for patient stratification in clinical investigations.

Old and new oral anticoagulants: Food, herbal medicines and drug interactions.

The most commonly prescribed oral anticoagulants worldwide are the vitamin K antagonists (VKAs) such as warfarin. Factors affecting the pharmacokinetics of VKAs are important because deviations from their narrow therapeutic window can result in bleedings due to over-anticoagulation or thrombosis because of under-anticoagulation. In addition to pharmacodynamic interactions (e.g., augmented bleeding risk for concomitant use of NSAIDs), interactions with drugs, foods, herbs, and over-the-counter medications may affect the risk/benefit ratio of VKAs. Direct oral anticoagulants (DOACs) including Factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and thrombin inhibitor (dabigatran) are poised to replace warfarin. Phase-3 studies and real-world evaluations have established that the safety profile of DOACs is superior to those of VKAs. However, some pharmacokinetic and pharmacodynamic interactions are expected. Herein we present a critical review of VKAs and DOACs with focus on their potential for interactions with drugs, foods, herbs and over-the-counter medications.

Effect of n-3 fatty acids on carotid atherosclerosis and haemostasis in patients with combined hyperlipoproteinemia: a double-blind pilot study in primary prevention.

BACKGROUND: Intake of n-3 polyunsaturated fatty acids (n-3 PUFA) either from natural sources or dietary supplementation is inversely associated with atherothrombosis. AIM: A double-blind pilot study was designed to address the impact of n-3 PUFA on atherosclerosis, haemostasis and vascular status in patients with combined hyperlipoproteinemia. METHODS: Carotid intima-media thickness (C-IMT), texture of intima-media complex (T-IMC), lipids and platelet function were evaluated in 64 patients with combined hyperlipoproteinemia who received placebo or n-3 PUFA (6 g/day) for 2 years. C-IMT and T-IMC were assessed by B-mode ultrasound. Lipids and platelet function were determined by validated methods. RESULTS: C-IMT increased in placebo, but not in n-3 PUFA group with respect to baseline. In contrast T-IMC decreased in n-3 PUFA, but not in placebo; in both cases, however, treatment effect did not reach statistical significance. A fall of triglycerides, concomitant to a rise of high- and low-density lipoprotein cholesterol (HDL and LDL), was observed in the active treated group. Platelet function was significantly reduced by n-3 PUFA. CONCLUSIONS: Results show a favourable effectiveness of n-3 PUFA on IMT progression and T-IMC that deserves to be confirmed in larger studies. Despite the small sample size, the beneficial effect of n-3 PUFA on platelet function, triglycerides and HDL-C is clearly highlighted.