Oxidized low-density lipoprotein (OxLDL) has been shown to exist in human circulating plasma. Several groups including ours have developed methods for immunologically measuring OxLDL, which have been applied to several clinical, both cross-sectional and prospective, studies. These data clearly show that OxLDL levels correlate well with the severity of cardiovascular diseases. In particular, recent observations suggest that plasma OxLDL levels could be a useful marker for predicting future cardiovascular events; however, substantial differences exist among the different methods of OxLDL measurement. To evaluate the clinical data on circulating OxLDL, a proper understanding of the similarity, differences, and limitation of the methods is needed. This paper summarizes the characteristics of the methods used and recent clinical findings.
Aim: The objective of the present study was to propose plasmalogens as a beneficial factor in human plasma by showing a highly positive correlation with high-density lipoprotein (HDL) and a significant reduction with aging. Methods: For 148 elderly subjects suspected of coronary artery disease (CAD), clinical characteristics such as coronary stenosis, hyperlipidemia, abnormal glucose tolerance, and hypertension were investigated, and serum biochemical markers including plasmalogens were determined. Results: Serum plasmalogens levels tended to fall in significant coronary stenosis and abnormal glucose tolerance. Correlative analyses among serum biochemical markers revealed that plasmalogens positively correlate with HDL-related values, particularly apolipoprotein A-I (apo A-I), and that the molar ratio of choline plasmalogen (ChoPlas) to ethanolamine plasmalogen (EtnPlas) correlates positively with low-density lipoprotein (LDL) particle size, and negatively with apo A-II and fasting triglyceride (TG) levels. Comparison of plasmalogens in elderly subjects with those of 119 healthy young subjects showed a marked decrease in serum plasmalogens levels by aging. Conclusion: These results suggest that serum plasmalogens, antioxidant phospholipids, function as a beneficial factor as well as HDL, and that the measurement of serum plasmalogens is useful in clinical diagnosis.
Aim: The aim of this study was to investigate the effect of SNP45 of the adiponectin gene on body fat distribution and carotid atherosclerosis in Japanese obese subjects. Methods: A total of 64 obese subjects were investigated. Genotypes of SNP45 were assayed by polymerase chain reaction-restriction fragment length polymorphism. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured using computed tomography. The progression of atherosclerosis was evaluated by plaque score (PS) of carotid artery using B-mode ultrasonography. Results: Men carrying the G allele of SNP45 showed higher VFA (172.8±50.8 vs. 147.1±58.7, p=0.005), lower SFA (209.9±101.8 vs. 273.4±142.2, p=0.007), higher VFA/SFA (V/S) ratio (1.00±0.46 vs. 0.60±0.26, p <0.001) and higher PS (9.5±3.7 vs. 6.8±4.2, p=0.012) than those with TT genotype. Multivariate analysis showed that SNP45 was an independent determinant of V/S ratio and PS in men. In subgroup analysis, PS tended to be associated with V/S ratio only in the carrier of 45G allele. Conclusion: These results suggest that the G allele could be a risk factor of metabolic syndrome and the development of atherosclerosis in Japanese obese subjects.
Aim: The prevalence of metabolic syndrome, as defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (ATPIII) modified for age (≥3 of the following abnormalities): waist circumference of at least 80 cm; serum glucose level of at least 110 mg/dL; triglyceride level of at least 110 mg/dL; high density lipoprotein (HDL) cholesterol level of 40 mg/dL or less; and blood pressure (BP) of at least 130/75 mmHg, was estimated in male high school students who attended an annual school health examination. Methods: The subjects were divided into three body mass index (BMI) categories (obese: ≥25; mildly obese: 23-24.9: and normal weight: <23 kg/m²). Of the 1446 students (mean age 15 years), 96 (6.6%) were obese and 158 (10.9%) were mildly obese. Results: The overall prevalence of metabolic syndrome was 1.4%, being present in; 15.6% of obese subjects. Overall, elevated systolic BP was most common (19.9%). In obese subjects, 51% had an elevated systolic BP. Conclusion: Our study suggests that metabolic syndrome is present in more than 1% of male adolescents and 15% of obese male adolescents in Japan.
Aim: Cardiovascular events associated with hypertension often involve thrombosis. Increased platelet activity is one of the risk factors of cardiovascular diseases. Antithrombotic properties of antihypertensive agents are not fully characterized. Angiotensin II type 1 receptor blockers (ARBs) are widely used for the treatment of hypertension. Some ARBs can provoke antiaggregatory effects on platelets in vitro. Whether ARBs can inhibit platelet aggregation was tested in hypertensive patients in vivo. Methods: Platelet aggregation was assessed by the highly sensitive particle counting method using laser-light scattering. Results: Large platelet aggregation induced by adenosine diphosphate (ADP, 3 µM) was 2.6±0.4 (×10&sup7;) (SE) in hypertensive patients treated with losartan (72±3 years old, n=10) while it was 3.9±0.6 in hypertensive patients treated with candesartan (70±5 years old, n=6; p=0.056). Large platelet aggregation induced by thromboxane A2 receptor agonist, U46619 (10 µM), was 2.8±0.5 (×10&sup7;) in hypertensive patients treated with losartan while it was 5.1±0.9 in hypertensive patients treated with candesartan (p=0.033). Clinical characteristics including the control of blood pressure did not differ between the two groups (losartan 136±5/73±3 mmHg vs. candesartan 135±4/76±5). Conclusion: Thus, losartan may have the possibility to inhibit platelet activation in patients with hypertension independent of blood pressure reduction. Antiaggregatory properties may be independent of angiotensin II type 1 receptor or of antihypertensive actions. The favorable effects of losartan on reduction of adverse cardiovascular events among hypertensive patients may be at least partly mediated by inhibition of platelet activation.
Aim: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities and a predictor of both type 2 diabetes mellitus and adverse cardiovascular events. Whether there are gender differences in the association between early atherosclerosis and MetS has not yet been thoroughly elucidated. Methods: The subjects consisted of 388 men aged 64±16 years and 480 women aged 70±13 years. Early atherosclerosis was assessed by carotid intima-media thickness (IMT) on B-mode ultrasonography. Results: Carotid IMT values were significantly greater in both male (p=0.007) and female (p=0.002) subjects with MetS. After adjusting for established risk factors, the difference persisted on a significant level in women (p=0.003), but was weak in men (p=0.013). Multiple regression analysis using IMT as an objective variable, with adjustment for various risk factors as explanatory variables, showed that MetS (p=0.016) was a significant independent contributing factor along with known risk factors only in women. Among the components of MetS, hypertension (p=0.036) and dyslipidemia (p=0.008) had a strong impact on carotid IMT in men, whereas hypertension (p=0.003) ranked first in women. Conclusion: The effect of MetS in early carotid atherosclerosis is more pronounced in women than in men, and the impact of MetS components on carotid IMT differs between men and women.