Dyslipidemias with TG rich lipoprotein (TGRL) are regarded as powerful risk factors for atherosclerotic changes. PAGE is the usual method for detecting TGRL, especially remnant lipoprotein (RL).
The authors divided the shapes of LDL on a PAGE densitograph (Lipophor kit, Quantimetrix Co. CA, & Jokoh Co. Tokyo) into types S (symmetry), E (eminent), A (asymmetry), N (nodular) and D (disrupted) and propose the usefulness of this SEAND classification as a tool for the treatment of dyslipidemias at lipid clinics. Fenofibrate 150mg/day made a significant improvement in each lipoprotein component and changed PAGE patterns from D or N to A or S in most cases. LDL-migration index (LDL-MI), which is calculated as LDL peak distance from VLDL peak, is divided by HDL peak distance from VLDL peak, and which indicates LDL particle size, decreased (0.43-0.40) and LDL cholesterol/apoB, which also depicts LDL particle size, increased (1.03-1.20).
The effect of Fenofibrate was more potentiated in groups N and D than in S, E, A, significantly in the increment of HDL-cholesterol and decrement of apoB, C2, C3, E and LDL-MI, TG/apoB (1.86-1.25), TG/apoC2 (47.8-31.74), TG/apoC3 (17.69-13.14) and TG/apoE (40.31-27.64) which were thought to be important clinically noticeable markers for down sizing of the TGRL particle.
Levels of serum uric acid decreased in all cases which involved abnormally high levels.
In conclusion, this paper intended to clarify that for the evaluation of the effect of Fenofibrate on dyslipidemias, it would be useful to adopt the PAGE pattern classification and select cases with N, D and A as suitable indications.

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To investigate the relationship between micro- and macroangiopathy (MA) in type-2 diabetes, the prevalence and clinical characteristics of macroangiopathy were studied in subjects with peripheral and autonomic neuropathy. These complications were assessed in 829 diabetic patients on the basis of both clinical findings and non-invasive examinations. The prevalence of peripheral neuropathy (PN) and autonomic neuropathy (AN) was 45.5% and 27.6%, respectively. 21.1% of the subjects were complicated with both PN and AN. The prevalence of ischemic heart disease (IHD), cerebral infarction (CI), and arteriosclerosis obliterans (ASO) in subjects with neuropathy, especially complicated with both PN and AN, was significantly higher than in the subjects without neuropathy. Aging, duration of diabetes, HbAlc levels, high systolic blood pressure, and uremia were common risk factors for both PN and AN. In addition, smoking was associated with PN, and reduced concentrations of HDL-C with AN. These risk factors were also related with MA. Multivariate analysis indicated that AN could be an independent risk factor for all MA, on the other hand, PN was indicated for IHD and ASO. These data suggest that diabetic neuropathy is closely correlated with MA of the heart, brain and lower legs. Glycemic control, other risk factor management and evaluation of systemic MA using a non-invasive approach are important for subjects with neuropathy, especially for subjects complicated with both PN and AN.

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Practice guidelines on the prevention and management of high cholesterol in adults are now available in many countries. These guidelines are expected to have significant implications for both primary and secondary prevention of cardiovascular disease. Although HMG-CoA reductase inhibitors are frequently prescribed for patients with hypercholesterolemia, a sufficient reduction in LDL-cholesterol levels can not always be achieved by its currently recommended dosage in Japan. Therefore, we compared the efficacy and safety of two three-month treatments; i. e. doubling the dosage of the HMG-CoA reductase inhibitor, fluvastatin to 40mg/day, and combined therapy using the HMG-CoA reductase inhibitor, fluvastatin at 20mg/day and colestimide at 3g/day. A cross-over procedure of the two treatments was applied in 8 patients (men/women=2/6, mean age 71 years) with hypercholesterolemia whose total cholesterol levels were more than 220mg/dl or LDL-cholesterol levels were more than 140mg/dl, despite treatment with 20mg/day of fluvastatin.
Mean total cholesterol levels at enrollment were 246±14mg/dl (mean±SD). The combined therapy decreased them significantly to 217±27mg/dl, whereas doubling the dosage regimen did not (239±25mg/dl). The combined therapy also decreased the calculated LDL-cholesterol levels significantly from 154±14mg/dl to 118±18mg/dl. In contrast, doubling the dosage of fluvastatin did not have a significant effect (141±23mg/dl). The levels of HDL-cholesterol and triglyceride remained unchanged with both treatments. Throughout the whole study period, there were no adverse events including elevation of CK, fasting blood sugar, and liver enzymes. We conclude that a combined therapy using an HMG-CoA reductase inhibitor and colestimide is efficacious and safe to obtain a significant reduction in total and LDL-cholesterol levels in patients with hypercholesterolemia refractory to the conventional statin treatment.

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Anorexia nervosa is known to induce various metabolic disorders such as low T3 syndrome, high levels of GH, liver function disorder, amenorrhea, hypokalemia, hypochloremia, hypoglycemia, and lymphopenia. We experienced a 20-year-old woman with anorexia nervosa who had severe liver dysfunction and hyper HDL-cholesterolemia (140mg/dl). The level of HDL-cholesterol changed in parallel with that of serum transaminase. With the recovery of serum transaminase levels, the level of HDL-choresterol normalized to 46mg/dl. In the analysis of CETP genes, she was heterozygotic in the CETP gene with exon 15 missense mutation. CETP activity and protein concentrations were at the lowend of the normal range.
In reported cases of anorexia nervosa, the level of HDL-cholesterol is not necessarily elevated. Since the high level of HDL-cholesterol was significantly associated with her serum transaminases levels, we speculate that high serum levels of HDL-cholesterol may result from the decrease of HTGL activity due to liver dysfunction and the increase of LPL due to hyperactivity on the basis of CETP deficient heterozygotes.

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Alacepril, a sulfhydryl-containing angiotensin-converting enzyme inhibitor has been suggested to have antioxidant or free radical scavenging effects. Recently, small, dense low-density lipoprotein (LDL) has been reported to be particularly atherogenic due to its high susceptibility to oxidative modification. The effects of the oral administration of alacepril (50mg/day) on LDL particle size were examined in 12 patients with essential hypertension. The relative migratory distance (RMD) of the predominant densitometric peak of LDL from that of very low-density lipoprotein to that of high-density lipoprotein in a 3% polyacrylamide gel electrophoreis was determined as a measure of LDL particle size. RMD was shown to be inversely correlated with LDL particle diameter and RMD above 0.36 corresponded to a LDL particle diameter <25.5nm or small, dense LDL according to the preliminary experiment. Alacepril (50mg/day) was administered for 3 months. No significant alteration was observed in RMD values after administration of alacepril to the patients. However, RMD decreased in the 6 patients with small, dense LDL, suggesting that their LDL particle size had increased, and serum α-tocopherol levels increased in 5 of the 6 patients. In conclusion, the oral administration of 50mg of alacepril for 3 months enlarged LDL particle size and increased serum vitamin E levels in patients with small, dense LDL, suggesting its favorable effects on lipid metabolism by antioxidative reaction. Alacepril may be useful, especially in the treatment of hypertensive patients combined with dyslipidemia with small, dense LDL.

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In an attempt to assay native Lp (a), the anti-Lp (a) monoclonal antibody (161E2) was produced against synthetic antigen (Arg-Asn-Pro-Asp-Val-Ala-Pro). Characteristic properties of this 161E2 monoclonal antibody were identified to have reactivity to oxidative modification (treatment with CuCl2₂ and lipoxygenase), but to neither LDL, plasminogen nor native Lp (a). We developed a new ELISA method to measure Lp (a) modified by oxidative stress using this 161E2 monoclonal antibody as the capture and the labelled antibody, and conducted assay of the epitope in serum using BSA-peptide (16 peptides perl molecule of BSA) as the standard. Interestingly, hypertensive patients with complications showed a significantly higher level of oxidized Lp (a) in serum than did normotensive subjects (p<0.01), whereas there was no significant difference in native Lp (a) between normotensive and hypertensive subjects. The in vivo presence of the epitope was also confirmed with use of 161E2 monoclonal antibody-based immunostaining of arteriosclerotic tissue layer by positive response. Upon analyzing peptide homology of the epitope, it was shown to have high homology (88%) to the cytoplasmic domain of human α2A-adrenergic receptor.

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