Low-molecular-weight lipoprotein (a) and low relative lymphocyte concentration are significant and independent risk factors for coronary heart disease in patients with type 2 diabetes mellitus: Lp(a) phenotype, lymphocyte, and coronary heart disease.

BACKGROUND: The aim of the present prospective study was to examine whether lipoprotein (a) [Lp(a)] phenotypes and/or low relative lymphocyte concentration (LRLC) are independently associated with coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM). METHODS: Serum Lp(a) concentration, Lp(a) phenotypes, and RLC were analyzed in 214 subjects. Lp(a) phenotypes were classified into 7 subtypes according to sodium dodecyl sulfate-agarose gel electrophoresis by Western blotting. Subjects were assigned to the low-molecular-weight (LMW (number of KIV repeats: 11-22) ) and high-molecular-weight (HMW( number of KIV repeats: >22 )) Lp(a) groups according to Lp(a) phenotype and to the LRLC (RLC: <20.3%) and normal RLC (NRLC; RLC: ≥20.3%) groups according to RLC. A CHD event was defined as the occurrence of angina pectoris or myocardial infarction during the follow-up period. RESULTS: During the follow-up period, 30 cases of CHD events were verified. Neutrophil count showed no correlation with CHD, while relative neutrophil concentration and RLC showed positive and negative correlations, respectively, with CHD. The Cox proportional hazard model analysis revealed the following hazard ratios adjusted for LMW Lp(a), LRLC, and LMW Lp(a) + LRLC: (4.31; 95% confidence interval [CI], 1.99-9.32; P < 0.01, 3.621; 95% CI, 1.50-8.75; P < 0.05, and 7.15; 95% CI, 2.17-23.56; P < 0.01, respectively). CONCLUSIONS: Our results suggest that both LMW Lp(a) and LRLC are significant and independent risk factors for CHD and that the combination thereof more strongly predicts CHD in patients with T2DM.

A more detailed fatty acid composition of human lipoprotein(a)--a comparison with low density lipoprotein.

Lipoprotein(a)'s (Lp(a)'s) fatty acid composition is partially known for the cholesteryl ester (CE), triglyceride (TG) and total phospholipid (PL) fractions. Individual PLs' fatty acids are unknown. This study sought to confirm and extend existing data and elucidate the individual PLs of Lp(a). For Lp(a) versus LDL, the mole percentage saturated fatty acids comprised 11.3+/-1.3 versus 16.8+/-1.2 (CE) (P<0.05), 43.4+/-5.2 versus 39.2+/-4.0 (TG) (P<0.05), 55.7+/-6.3 versus 54.7+/-5.9 (PL) (P>0.05), 51.9+/-3.5 versus 50.2+/-4.2 (choline-containing phospholipids (PC)) (P>0.05), 40.2+/-4.6 versus 43.1+/-3.9 (ethanolamine-containing phospholipids (PE)) (P>0.05), 73.2+/-7.6 versus 81.2+/-8.2 (sphingomyelin (SPH)) (P<0.05). Linoleic acid was CE's major fatty acid and while palmitic acid was the major fatty acid in all other fractions except PE.

Reference values of plasma lipoprotein (a) in newly classified apolipoprotein(a) phenotype groups in the Japanese population.

We tried to establish the reference values of plasma lipoprotein (a) [Lp(a)] concentration in phenotype groups of apoliprotein(a) [apo A] classified by a new criterion. Lp(a) concentration was determined by latex agglutination immunoassay, and apo A was analysed by electrophoresis in sodium dodecyl sulphate-polyacrylamide gel and a Western blotting technique. According to the relative mobility to the apo B-100 band, apo A was classified into 11 isoforms, i.e. F, B, and S1-S9, and the phenotype was defined by their apparent combination. The frequency ratio of single-band versus double-band was approximately 2:1. In 382 cases of single-band, the most frequent phenotype was S5 (24.3%), followed by S4 (17.3%), S6 (15.4%) and S3 (14.4%). In 181 cases of double-band, S5/S6 phenotype was observed most frequently (12.2%). followed by S4/S5 (10.5%) and S3/S6 (7.2%). The reference value was determined between antilogs of the mean +/- 1.96 standard deviation by logarithmic transformation of all observed values for individual phenotype cases. These results suggest that the reference values shown to be variable with apo A phenotypes should be useful for evaluating Lp(a) values in diagnosis of atherosclerosis.

Suppression of endogenous testosterone in young men increases serum levels of high density lipoprotein subclass lipoprotein A-I and lipoprotein(a).

We investigated the effect of testosterone suppression on lipoprotein metabolism in men. After a baseline period of 14 days, 12 healthy young men received over a period of 3 weeks daily s.c. injections of Cetrorelix, an antagonist of GnRH. The volunteers were then followed-up for 10 additional weeks. Administration of Cetrorelix suppressed testosterone significantly up to day 35, after which values returned to baseline. Suppression of testosterone was associated with significant and consistent increases in mean serum levels of high density lipoprotein (HDL) cholesterol by 20% (P < 0.0001), apolipoprotein A-I (apoA-I) by 10% (P = 0.0032), apoA-II by 7% (P = 0.0112), HDL subclass lipoprotein A-I (LpA-I) by 23% (P = 0.002), and plasma lecithin:cholesterol acyltransferase by 7% (P < 0.001). Serum levels of HDL subclass LpA-I/LpA-II changed insignificantly. Moreover, suppression of testosterone significantly increased the median of lipoprotein(a) [Lp(a)] levels from 5.5 to 8.5 mg/dL (P < 0.0001). The increase in Lp(a) levels was positively correlated with baseline levels of Lp(a) (r = 0.91; P < 0.001) and amounted to 40-60% in individuals with baseline levels of Lp(a) higher than 3 mg/dL. We conclude that endogenous testosterone is involved in the regulation of HDL cholesterol and Lp(a) levels and may thereby influence cardiovascular risk.

Lipoprotein(a) phenotypes in Japanese children: a cohort study.

BACKGROUND: Elevated serum lipoprotein(a) [Lp(a)] concentrations have been demonstrated to be associated with cardiovascular diseases due to premature atherosclerosis. However, the association of Lp(a) phenotypes with the development of these diseases remains largely unexplored. METHODS: We analyzed the population-based frequencies of serum Lp(a) phenotypes in 269 Japanese children aged 8-13 years in one community. According to the different apolipoprotein(a) [apo(a)] electrophoretic mobilities, Lp(a) was classified into seven single-band and respective double-band phenotypes. Each individual expressed a single (homozygotic) or a double band (heterozygotic). RESULTS: The serum Lp(a) concentration frequency distribution was skewed toward lower levels with a mean +/- SD of 15.5 +/- 18.0 mg/dl and a median of 11.0 mg/dl. The Lp(a) phenotype frequencies revealed that the frequency of double-band phenotype expression (55%) was higher than that of single bands (44%) and that the frequency of phenotypes representative of low molecular weight apo(a) was very low (2%). The mean serum Lp(a) concentration of the double-band-expressing subjects was higher than that of subjects with the single-band phenotype (20.1 +/- 19.9 vs. 10.5 +/- 15.9 mg/dl, p < 0.01). CONCLUSIONS: These findings of Lp(a) phenotypes in children seemed to differ from those in Japanese adults in another study; contrary to expectation, the predominant Lp(a) phenotypes found in children were those frequently associated with cardiovascular diseases in adults. Thus, it is speculated that children whose Lp(a) phenotypes remain unchanged during the transition to adulthood may show an increased susceptibility to cardiovascular disease, although the nutritional effects on the Lp(a) phenotypes cannot be neglected.

Arterial thrombosis: putative role of lipoprotein(a).

Lipoprotein(a) has been associated with several arterial thrombotic disorders. This article presents evolving concepts of Lp(a) and its potential role in coagulation. An overview of lipoprotein structure and function provides background information for further understanding of the pathophysiologic role of Lp(a) in atherosclerosis and thrombosis. Further research is needed to clarify the function of Lp(a) in humans and its role in arterial thrombosis.