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Diabetes is an important poor prognostic factor for ischemic heart disease and other cardiovascular diseases. Various study results have previously shown that new diabetes therapeutic agents including GLP-1 agonists and DPP-4 inhibitors have been suggested to be able to not only improve the pathology of diabetes, but also improve cardiovascular risk and be useful in prognosis. This report describes the effects of incretin on the cardiovascular system and its expected efficacy in reducing cardiovascular risk.

Fibrates and eicosapentaenoic acid (EPA) are effective in lowering elevated plasma triglycerides(TG) and low density lipoprotein cholesterol(LDL-C). These drugs have shown to reduce the risk of major cardiovascular events by several studies. Fibrates activate peroxisome proliferator-activated receptors(PPAR), especially PPARa. EPA and its metabolites act in the body by their interactions with the metabolites of arachidonic acid. Fibrates and EPA have nonlipid peliotropic effects such as anti-inflammation, endothelial-dependent smooth muscle relaxation and anti-thrombus in vascular wall. Thus it is suggested that peliotropic effects of these drugs contribute to the reduction of atherosclerosis progression.

Peroxisome proliferator-activated receptor (PPAR) gamma is a nuclear receptor and ligand-activated transcription factor which plays important roles in the control of energy balance. The thiazolidinediones (TZDs), in use as an insulin-sensitizing agent, are well known as the PPARgamma agonist. Recent studies reported that PPARgamma agonists involve in lipid metabolism through regulating genes including lipoprotein lipase, CD36, and ABCA1. Some clinical trials have been shown that TZD decreased serum levels of LDL-cholesterol and triglycerides and increased serum levels of HDL-cholesterol in type 2 diabetes. In addition, activation of PPARgamma is implicated in the regulation of endothelial function, proliferation and migration of vascular smooth muscle cells, and activation of macrophages.

The endothelium modulates vascular tone, blood coagulation, cell growth, and inflammation throughout the circulatory system. Endothelial dysfunction has been proposed to be one of the initiating events of atherosclerosis and is characterized by unbalanced concentrations of vasodilating and vasoconstricting factors, the most important being nitric oxide (NO) and angiotensin II (AII), respectively. In endothelial cells, AII, the key effector of the renin-angiotensin system (RAS), stimulates the production of reactive oxygen species (ROS) and negatively regulates the NO signaling pathway and thereby induces endothelial dysfunction. RAS blockade with an angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers(ARBs) provides a rational approach to reverse endothelial dysfunction. In this review, attention has been specifically focused on recent findings and putative mechanisms of the beneficial effects of RAS blockade on endothelial function.

Chronic kidney disease (CKD) is characterized by proteinuria and kidney dysfunction caused by multiple factors. Metabolic disorders such as diabetes, dyslipidemia and hypertension are involved in the underlying pathological mechanisms of CKD and cardiovascular disease (CVD). In patients with CKD, CVD is a major cause of morbidity and mortality. Recent clinical studies have revealed that intervention by angiotensin II blockade with ARB and ACEI reduces CKD and CVD. Accordingly, earlier intervention to metabolic disorders with blockers for angiotensin II and aldosterone may prevent CKD as well as CVD associated with CKD.

When the vascular endothelial function fails, arterial atherosclerosis is developed. Furthermore, if the endothelial dysfunction progresses, it is known to cause angina pectoris, myocardial infarction, cerebrovascular accident. By medical therapy and replacement therapy, correction of the life style, the endothelial dysfunction is understood that it could be improved reversibly. Therefore, it is very important to evaluate the vascular endothelial function for arteriosclerotic severity and the prediction of the cardiovascular disease onset and the effect of medical therapy. In the 1990s, high-frequency ultrasonographic imaging of the brachial artery to assess endothelium-dependent flow-mediated vasodilation (FMD) was developed. This technique is attractive because it is noninvasive and allows repeated measurements. However, despite its widespread use, there are technical and interpretive limitations. Therefore, for clinical application of the endothelial function test, its problems must be understood well.

Atherosclerotic vascular diseases are expected to remain the major cause of mortality and morbidity globally well. Preventive measures by lifestyle changes(diet, exercise) will play an important role in retarding the onset of these diseases. The 4S, CARE and LIPID study demonstrated the efficacy of a statin on cardiovascular morbidity and mortality and on total mortality. The cardioprotective effect of statin is partially due to the cholesterol independent effect. Fibrate also decrease the mortality of patients with ischemic heart disease by improving the fiblolytic state. The association of a statin and a fibrate is reserved to specialized centers, however we should not forget the usefulness of diet.