[In the fight against atherosclerosis, statin therapy is one of the most important elements. On the basis of data from the past few years the clinical introduction of a more effective statin is not expected, however, in order to improve cardiovascular prevention further development of agents that reduce LDL-cholesterol levels more effectively than currently used statins is warranted. The need for the development of new cholesterol-lowering therapeutic options is also supported by the existence of statin intolerance. The currently available combination therapies do not provide additional mortality benefits compared with statin monotherapy. The new solutions include fourth-generation statin molecules that primarily aim to enhance the NO-donor capacity of statins, and to reduce their muscle toxicity. Certain compounds that affect cholesterol synthesis (squalene synthase inhibitors, MTP inhibitors, ACAT inhibitors) need to be further analysed because of the risk of side effects. The use of an antisense oligonucleotid that blocks the mRNA of apoB, the main protein on the LDL-particle and antibodies that inhibit the protein PCSK9 that promotes the intracellular breakdown of the LDL-receptor seems to be much more promising. Besides the lowering of LDLcholesterol level, studies have focused on the benefits of increasing HDL-cholesterol levels. Unfortunately, recently completed analyses show that new forms of the strong HDL-C increasing nicotinic acid have not provided any additional benefit when added to statin therapy. Similarly, the adverse effects associated with the promising CETP inhibitors and the lack of additional benefit when combined with statins question the significance of this drug class. The necessity for an absolute increase of HDL-cholesterol levels needs to be revised on the basis of new data, in other words, the exact role of the HDL particle in atherosclerosis needs to be further investigated.]

[Acute-onset cerebrovascular diseases are connected to a number of immunological changes. Here, we summarize immune responses participating in the evolution of atherosclerotic plaques and poststroke local immune responses in the injured CNS as well as in the systemic circulation. Ischemic injury of the CNS alters the balanced neuroimmune modulation resulting in CIDS, the central nervous system injury-induced immune deficiency syndrome. Due to the immunodepression and reduced pro-inflammatory immune responses, the susceptibility for infection is increased; indeed, poststroke infection plays a major role in stroke-related mortality. On the other hand, CIDS may protect against damaging autoimmune responses elicited by exposed CNS antigens. Investigation of immune responses related to ischemic stroke may result in novel therapies indicated by an increasing number of experimental and clinical trials altering poststroke immune responses and preventing infections.]

[Stroke is the third leading cause of death and a leading cause of major adult disability in developed countries. The annual incidence of hospitalized stroke varies between 400-500 per 100 000 inhabitants every year in Hungary. In the past decade, cholesterol lowering with 3- hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase inhibitors (statins) has proved to reduce risk of stroke in patients with and without coronary disease (CAD). In patients with CAD, statin therapy reduces the risk of first stroke by 25% to 35% versus placebo and, moreover, intensive statin therapy to LDL-C targets below 2.6 mmol/L (100 mg/dL) appears to reduce the risk further. More recently it has also been shown that intensive statin therapy can reduce risk of recurrent stroke in nondiabetic as well as diabetic patients with recent stroke or transient ischaemic attack but no CAD. The overall reduction of stroke and TIA was 23%. Evidence from retrospective studies suggests that in addition to risk reduction statin pretreatment may improve stroke outcome. It may due to their pleiotropic effects that include improvement of endothelium function, anti-inflammatory, antithrombotic, and immunomodulatory effects. As statins have both an excellent safety profile and simple administration, physicians should consider using statins, at dosages shown to have efficacy in clinical trials, in all patients whose cardiovascular risk profile puts them at high risk of stroke.]

[The incidence of coronary heart disease in women rises sharply in the years following menopause. Hormone replacement therapy involves the administration of oestrogen, which provides postmenopausal symptom relief and reverses the changes in calcium and lipid metabolism. Moreover, oestrogen is also postulated to engage multiple mechanisms that defend against hypertension. Early observations suggested that postmenopausal women treated with hormone replacement therapy have significantly reduced cardiovascular risk. However, the results of primary and secondary prevention randomized clinical trials confirmed an increased cardiovascular risk rather than a beneficial effect of hormone replacement therapy in highrisk women. Controversy between results of observational and randomized clinical trials may partly be due to the unexplored genetic background. The authors summarize the effects of oestrogen on lipids, inflammation, haemostatic parameters, blood pressure and vascular wall. Genetic factors that modulate the effect of oestrogen as well as current recommendations on hormone replacement therapy after menopause in high risk women are also presented.]

[Endothelial nitric oxide synthase enzyme is regulated through the phosphorylation of the Ser(1177) and the Thr(495) sites, which influence the biological availabilaty of nitric oxide. We examined the acute effect of cigarette smoke, which decreases nitric oxide production. Endothelial cells were treated with different concentrations and for different times with cigarette smoke buffer, then with reduced glutathione or different protein kinase inhibitors. We determined the total and the phosphorylated nitric oxide synthase levels with Western blot. Cigarette smoke increased phosphorylation in a concentration- and time dependent manner at the Ser(1177) site and more pronounced at the Thr(495) site. Besides, it also led to the dissociation of the active dimer form of the enzyme. Reduced glutathione inhibited these phosphorylations and prevented the dissociation of endothelial nitric oxide synthase enzyme. The inhibition of protein kinase A or B did not influence the effect of cigarette smoke. However, protein kinase C inhibitors increased the phosphorylation caused by cigarette smoke at Ser(1177), but decreased it at Thr(495) sites. Summarized, cigarette smoke shifts the phosphorylation of the enzyme towards an inhibitory state, further on, it leads to the dissociation of the enzymatically active form. This results in the decreased biological availabilaty of nitric oxide, in which protein kinase C may play an important role.]