Central obesity is independently associated with an elevated risk of cardiovascular disease, particularly thrombotic complications. Increasing data supports a link between excess body weight and the risk to suffer acute myocardial infarction, stent thrombosis after percutaneous interventions, ischemic stroke and vein thrombosis. Experimental and in vitro data have provided insights as to the mechanisms currently presumed to increase the thrombotic risk in obese subjects. Obesity is characterized by a chronic low grade inflammation and systemic oxidative stress that eventually damage the endothelium losing its antithrombotic properties. Obesity also stimulates the expression of leptin and attenuates adiponectin release, a protective adipokine. Although the contribution of adipokines to thrombosis has been questioned, recent work has suggested that they enhance platelet activation and, although to a lesser extent, induce the coagulation cascade through tissue factor (TF) expression. Increased body weight also impairs platelet sensitivity to insulin signaling and enhances the production of bioactive isoprostanes further promoting platelet reactivity. Finally, obese subjects have shown elevated circulating levels of von Willebrand factor, TF, factor VII and VIII, and fibrinogen, favoring a mild-to-moderate hypercoagulable state, and, on the other hand, increased secretion of plasminogen activator inhibitor (PAI)-1 and thrombin activatable fibrinolysis inhibitor (TAFI) contributing to impair the fibrinolytic system. In the present review, we provide an overview of the impact of excess body weight on thrombosis. We will focus on the link between dysfunctional adipose tissue and endothelial damage, platelet reactivity, enhanced coagulation and impaired fibrinolysis; mechanisms currently recognized to increase arterial thrombotic risk in obese subjects.

High Density Lipoprotein (HDL) particles, beyond serving as lipid transporters and playing a key role in reverse cholesterol transport, carry a highly variable number of proteins, micro-RNAs, vitamins, and hormones, which endow them with the ability to mediate a plethora of cellular and molecular mechanisms that promote cardiovascular health. It is becoming increasingly evident, however, that the presence of cardiovascular risk factors and co-morbidities alters HDLs cargo and protective functions. This concept has led to the notion that metrics other than HDL-cholesterol levels, such as HDL functionality and composition, may better capture HDL cardiovascular protection. On the other hand, the potential of HDL as natural delivery carriers has also fostered the design of engineered HDL-mimetics aiming to improve HDL efficacy or as drug-delivery agents with therapeutic potential. In this paper, we first provide an overview of the molecules known to be transported by HDL particles and mainly discuss their functions in the cardiovascular system. Second, we describe the impact of cardiovascular risk factors and co-morbidities on HDL remodeling. Finally, we review the currently developed HDL-based approaches.

Besides the well-characterized effect of foods and supplements enriched with plant sterols/stanols on serum LDL-C concentrations, evidence is now emerging that phytosterols exert beneficial effects on non-lipid variables such as inflammatory and oxidative stress markers, coagulation parameters and endothelial function. This makes sterols and stanols an attractive alternative for dietary interventions in cardiovascular disease prevention, particularly in populations at low or medium risk. This review aims to summarize the current knowledge derived from experimental studies and human data on the anti-inflammatory effects of phytosterols/stanols and their relevance in promoting atheroprotection and preventing cardiovascular disease. The anti-inflammatory effects induced by plant sterols/stanols have been demonstrated in in vitro studies and in experimental animal models. However, not all the beneficial effects seen at an experimental level have translated into clinical benefit. Indeed, clinical studies that evaluate the association between phytosterols consumption and inflammatory variables (CRP and cytokines) are inconsistent and have not yet provided a solid answer. Plant sterols have been proposed as useful adjuncts to statin therapy to further reduce the risk of cardiovascular disease. However, there is limited available data and more research needs to be done.

Beyond lipid-lowering, statins exert cardioprotective effects. High-dose statin treatment seems to reduce cardiovascular complications in high-risk patients. The ideal timing and administration regime remain unknown. This study compared the cardioprotective effects of intravenous statin administration during myocardial infarction (MI) with oral administration immediately post-MI. Hypercholesterolemic pigs underwent MI induction (90 min of ischemia) and were kept for 42 days. Animals were distributed in 3 arms (A): A1 received an intravenous bolus of atorvastatin during MI; A2 received an intravenous bolus of vehicle during MI; and A3 received oral atorvastatin within 2 h post-MI. A1 and A3 remained on daily oral atorvastatin for the following 42 days. Cardiac magnetic resonance analysis (days 3 and 42 post-MI) and molecular/histological studies were performed. At day 3, A1 showed a 10% reduction in infarct size compared with A3 and A2 and a 50% increase in myocardial salvage. At day 42, both A1 and A3 showed a significant decrease in scar size versus A2; however, A1 showed a further 24% reduction versus A3. Functional analyses revealed improved systolic performance in A1 compared with A2 and less wall motion abnormalities in the jeopardized myocardium versus both groups at day 42. A1 showed enhanced collagen content and AMP-activated protein kinase activation in the scar, increased vessel density in the penumbra, higher tumor necrosis factor α plasma levels and lower peripheral blood mononuclear cell activation versus both groups. Intravenous administration of atorvastatin during MI limits cardiac damage, improves cardiac function, and mitigates remodeling to a larger extent than when administered orally shortly after reperfusion. This therapeutic approach deserves to be investigated in ST-segment elevation MI patients.