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Renal diseases have been recognized as a major cause of secondary dyslipidemia since the late 1950's. Two main pathological conditions of renal diseases, impaired renal function and severe proteinuria (nephrotic syndrome), are individually or conjointly associated with altered lipid metabolism depending on the primary diseases. An impaired renal function causes reductions in lipoprotein and hepatic TG lipase activity, the VLDL recep- tor abundance, and ApoC-II to apoC-III ratio, as well as in ApoA-I and LCAT activities. These alterations result in reduced VLDL clearance and the disturbance of HDL synthesis and maturation, leading to uremic dyslipidemia: increased levels of TG, IDL-C, and small-dense LDL-C and decreased levels of HDL-C. Lipid disorders in nephrotic syndrome (NS) are characterized by increased levels of LDL-C and/or TG. NS-induced hypoalbuminemia enhances the synthesis of cholesterol, cholesterol ester, and ApoB, leading to the increased production of LDL and VLDL. Recently, two intriguing molecules were newly identified as inhibitors of lipoprotein clearance. Pro-protein Convertase Subtilisin/Kexin type 9 (PCSK9) is upregulated in NS, and decreases LDL clearance via prompting degradation of the LDL receptor, while angiopoietin-like 4 (Angptl4) is also induced in NS and restricts VLDL clearance via inhibiting lipoprotein lipase. NS impairs HDL maturation from HDL3 to HDL2 due to a reduction of LCAT, with HDL-C levels preserved. Finally, considering that diabetic nephropathy is representative of progressive renal disease and that gluco- corticoids are an anchor drug for the treatment of NS, diabetes- or drug-associated dyslipidemia is occasional- ly superimposed on the original renal dyslipidemia. [Review].

Secondary dyslipidemia has various causes. Drug-induced dyslipidemia is classified as secondary dyslipidemia. Recent lifestyle changes and the aging of the population have resulted in an increased inci- dence of dyslipidemia, accompanying that of metabolic disorders. Thus, various medications for metabolic disorders, including diabetes, hyperlipidemia, and hypertension, have been developed. Therefore, the fre- quency of drug-induced dyslipidemia in secondary hyperlipidemia is increasing. In clinical practice, primary dyslipidemia and common secondary dyslipidemia, such as endocrine diseases, hepatic and renal diseases, and immune disorders, must be excluded. Following this exclusion, the diagnosis of drug-induced dyslipidemia can proceed. In this review, we summarize the pathogenesis, diagnosis, and treatment of drug- induced dyslipidemia. [Review].

Dyslipidemia in diabetes mellitus is a secondary change in hyperglycemia. Even if hyperlipidemia was not present, dyslipidemia will be present, especially as the increase of remnant. Usually this dyslipidemia is improved by a good control of hyperglycemia. In the pathogenesis the various factors relate to the lipid/lipoprotein metabolism, by insulin action (hyperinsulinemia or insulinopenia), adipokines, or hyperglycemia itself. The every changes of lipoprotein metabolism could be occurred in diabetes mellitus, and those are related to the increase of atherogenic lipoproteins. We should recognize the mechanism of lipids/lipoprotein metabolism in diabetes mellitus and approach to prevent the atherosclerotic diseases in diabetes.

Analysis of serum lipoprotein fractions by electrophoresis (lipoprotein electrophoresis) reveals lipid metabolism disorders, and provides various types of bio-information which lead to an accurate diagnosis and effective treatment for dyslipidemia and related diseases (e.g., coronary artery disease or chronic kidney disease). In particular, lipoprotein electrophoresis enables us to define the phenotypes of dyslipidemia, and to detect abnormal lipoproteins, which are potent biomarkers of atherosclerotic disease. In addition, lipoprotein electrophoresis is an indispensable complement to other assay methods for serum lipid component measurement that have some limitations, such as a homogeneous assay for LDL-C. However, it appears to be underestimated regarding its clinical usefulness. Indeed, the fee for lipoprotein electrophoresis tests is too low. This review specifically discusses the clinical usefulness and problems of lipoprotein electrophoresis, with a special emphasis on cost.

Dyslipidemia is one of the most important risk factors for atherosclerotic cardiovascular diseases (ASCVD), and its management is very important for the prevention of ASCVD. In addition, the management of other major risk factors, such as cigarette smoking, hypertension, and diabetes, is also important. Therefore, the comprehensive management of these major risk factors is key to prevent ASCVD. Among several types of primary dyslipidemia, familial hypercholesterolemia (FH) is a very high-risk genetic disorder which causes premature coronary artery disease (CAD). Therefore, the early diagnosis of and treatment for FH are crucial. For the treatment of dyslipidemia, lifestyle modifications are the bases of ASCVD prevention. However, when lipid management goals are not achieved with lifestyle modification, we should consider pharmacological treatments, and statins are the drugs with the most abundant evidence to support LDL-C-lowering and ASCVD prevention.

It is well known that dyslipidemia is one of the most crucial risk factors for atherosclerosis, including cardiovascular diseases (ASCVD). In order to prevent the onset of ASCVD, the Japan Atherosclerotic Society (JAS) published the JAS Guidelines in 2012 for appropriate lipid examination and treatment. However, it is unknown how the guidelines are practically used by Japanese clinicians. Therefore, we conducted a questionnaire survey to assess the present execution of and problems with clinical lipid examination and the application of the JAS Guidelines by doctors working in hospitals and clinics of Yamagata district in Japan. We found that 16% of doctors carried out clinical lipid examination every time, but some did not examine lipids at all. Fasting blood sampling for lipid examination was performed by 44% of doctors, and the items of triglycerides, HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C) were measured by more than 95%. Regarding problems with clinical lipid examination, more than 40% of doctors requested the early achievement of the standardization of LDL-C. The JAS Guidelines in 2012 were unfortunately recognized by only 55% of doctors. In addition, the rate of the clinical application of the guidelines, including the absolute risk, the flowchart of LDL-C, and non-HDL-C, was less than 30%, and more than half of the doctors measured LDL-C with the direct method, but did not use the "recommended" Friedewald method. In contrast, the cardiologists and endocrinologists generally accepted the guidelines, and their clinical application rate was higher than in other doctors. Through the questionnaire survey, it was revealed that doctors in various fields have not properly accepted the use and significance of lipid examination and the JAS Guidelines, and so further educational activities are necessary.

Obesity-associated dyslipidemia is characterized as hyper-triglyceridemia and hypo-high-density lipoproteinemia. Visceral fat accumulation results in the dysregulation of various adipocytokines as well as the elevation of portal free fatty acid and glycerol levels. The latter cause hepatic overproduction of very-low-density lipoprotein, and the adipocytokine dysregulations impair the transfer of cholesterol from extra-hepatic tissues to the liver. In addition, obesity disease associates with the elevated atherogenic remnant lipoprotein as a result of increased lipid absorption and decreased lipoprotein hydrolysis due to insulin resistance. It is important to further elucidate the regulatory mechanisms of adipocytokines on lipid metabolism for the prevention of atherosclerosis.

Low-density lipoprotein (LDL) cholesterol is the most established risk factor for atherosclerotic disease such as coronary artery disease and cerebrovascular disease. High-density lipoprotein (HDL) cholesterol and nonHDL-C as well as small dense LDL, Remnant like particles cholesterol (RLP-C) and oxidized LDL are the secondary risk factors for atherosclerosis. It is important to integrate and control these risk factors for the prevention of atherosclerosis as a real endpoint of diagnosis and treatment of dyslipidemia.

Oxidized LDL accelerates vascular endothelial damage and the progression of early arteriosclerosis, and is known as an independent risk factor for coronary artery disease. In this study, we administered pioglitazone and pitavastatin for 16 weeks to 18 patients who had type 2 diabetes complicated by dyslipidemia and then investigated the influence of these 2 drugs on MDA-LDL(i. e., oxidized LDL). As a result, a significant decrease of MDA-LDL was observed in both groups, but a significant decrease of the MDA-LDL/LDL-C ratio (an indicator of the extent of oxidation of LDL) was only observed in the pioglitazone group. Accordingly, it was demonstrated that pioglitazone improves oxidative stress, and the possibility was suggested that the MDA-LDL/LDL-C ratio is useful for the evaluation of oxidative stress in clinical practice.

Lipoprotein analysis methods employing high-performance liquid chromatography (HPLC) are divided broadly into 2 categories (HPLC with a gel-filtration column, and with an anion-exchange column), and both methods can determine lipid levels of fractionated serum lipoproteins of small amounts around 10 microl within 30 min. The former HPLC method separates lipoproteins based on the particle sizes, and larger-sized lipoproteins are eluted earlier, but this gel-filtration HPLC method determines lipid levels of lipoprotein fractions by Gaussian approximation. The latter HPLC method elutes lipoproteins based on the ion intensity of the lipoprotein particle surface and the hydrophobic properties, and determines cholesterol levels of separated lipoproteins without overlapping lipoprotein fractions. A large amount of research data on lipoprotein cholesterol levels measured using the anion-exchange HPLC method have been reported in patients with various diseases (diabetes, dyslipidemia, coronary heart disease, or chronic renal failure), and the anion-exchange HPLC method deserves a position of much greater clinical significance.