Yoshifumi Okura

Serum Lipoprotein (a) Levels in Maintenance Hemodialysis Patients

To further understand lipoprotein (a) [Lp(a)] and atherosclerosis, we measured serum Lp(a), lipoprotein, and apolipoprotein levels in 55 patients (males, 24-73 years old) on maintenance hemodialysis, and compared them with those of 82 controls (males, 21-81 years old). The serum Lp(a) levels in patients on maintenance hemodialysis were significantly higher than those of the normal controls, while serum total cholesterol (TC), high-density lipoprotein-cholesterol, (HDL-C), HDL2-C, HDL3-C, apolipoprotein (apo) Al, apo All levels, and lecithin-cholesterol acyltransferase (LCAT) activities were significantly (p < 0.05) reduced in the patient group. The frequency distribution of serum Lp(a) levels in the patients was different from that in the control group, and no prognostic tendency of serum Lp(a) levels was noted by the etiology of renal failure as histologically determined by the renal biopsies. In the patient group, we also found that serum Lp(a) levels negatively correlated with serum triglycerides (TG) and total protein (TP) concentrations (p < 0.05), but no correlation was found between the duration of hemodialysis therapy or patient age and the serum levels of TC, TG, apo B and Lp(a) levels when tested for simple regression. Significant (p < 0.05) positive correlations were also found between TP and serum TG, apo B, and LCAT activities. These opposing tendencies of Lp(a) and serum TG, apo B, when measured against TP concentrations, indicate that serum TP levels may not affect serum lipoprotein and Lp(a) levels in the same direction. These data suggest that hemodialysis or end-stage renal disease itself, rather than hypoproteinemia, may hold the key to high serum Lp(a) levels in hemodialysis patients.

Combined therapy with probucol and pravastatin in hypercholesterolaemia. One year follow-up study.

SummaryThe effect of co-administration of low doses of pravastatin to hypercholesterolaemic patients already receiving long-term probucol treatment (mean 500–1,000 mg/day for 350 days) were investigated. Pravastatin 5 mg/day (Group 1; 12m, 13f; mean age 59.1 y) or 10 mg/day (Group 2; 8m, 11f; mean age 60.8 y) was administered, and blood was taken after 0, 3, 6, and 12 months.Both groups showed a significant reduction in serum total cholesterol (TC), phospholipid (PL), low density lipoprotein-cholesterol (LDL-C), LDL-triglyceride (TG), LDL-PL, apolipoprotein (apo) B, and apo E after the combined therapy. These levels were reduced more in Group 2 than in Group 1 subjects. In Group 2, significant falls in serum TG and apo CII were also observed. The changes in TC, PL, LDL-C, apo B, apo CII and apo E were dependent upon the dose of pravastatin, as assessed by two-way analysis of variance. Serum high density lipoprotein (HDL)3-C, apo AI and apo AII were slightly but significantly increased in both groups after 12 months of combined therapy, but the increase was not sufficient to reverse the probucol-induced lowering of the HDL level. We conclude that combined therapy resulted in a significant reduction in atherogenic lipoproteins and apolipoproteins, and an increasing dose of pravastatin (5 mg to 10 mg daily) made the lipid lowering effect more prominent. The reduction in serum HDL-C due to long-term probucol administration was not reversed by the addition of pravastatin.

Angiotensin-converting enzyme insertion/deletion genotype is associated with the activities of plasma coagulation factor VII and X independent of triglyceride metabolism

Background The D allele of angiotensin‐converting enzyme (ACE) insertion/deletion (I/D) polymorphism and coagulation activity play important roles in cardiovascular events, however, the precise association between these two risk factors remains unclear. Methods We identified the ACE I/D genotype and measured the plasma coagulation factor VII and X (FVII and FX) activities and serum lipids in 172 patients (110 men and 62 women, mean age 56.7 ± 13.3 years) undergoing coronary angiography. Results The frequency of the D allele was significantly higher in those with a history of myocardial infarction (MI) than in those with normal coronary arteries, but there was no significant association between FVII and FX activities and the stage of coronary disease. Plasma coagulation factor VII and FX activities were significantly lower in the DD genotype (n=42) than in the II genotype (n=67, P<0.001 and P<0.001, respectively) or the ID genotype (n=63, P<0.01 and P<0.05, respectively). The association of the ACE D allele with lower activities of FVII and FX was also seen in patients with coronary artery disease (CAD). There was a significant association between serum triglyceride levels with FVII and FX, but not with the ACE I/D genotype. Conclusion We concluded that the ACE I/D polymorphism may contribute more to the onset of MI than the activities of FVII and FX and that the ACE D allele might be associated with lower plasma activities of FVII and FX. The potential link between ACE I/D polymorphism and the plasma activities of FVII and FX is probably independent of triglyceride metabolism. Coron Artery Dis 14:285‐291 • 2003 Lippincott Williams & Wilkins.