Cardiovascular disease is increased in patients with chronic kidney disease (CKD) and is the principle cause of morbidity and mortality in these patients. In patients with stage 5 CKD, structural changes in the myocardium have been implicated as the principle cardiovascular processes leading to this increase in morbidity and mortality, while atherosclerotic events including acute myocardial infarction and strokes are responsible for approximately 10-15% of cardiovascular deaths. Dyslipidemia is common in CKD patients and is usually not characterized by elevated cholesterol levels, except in patients with marked proteinuria. Increased triglyceride levels in conjunction with decreased high-density lipoprotein levels are the commonest qualitative abnormality. Characteristically, abnormalities in the metabolism of apolipoprotein (apo) B-containing lipoproteins have been described, including both gut derived (apoB-48) as well as those produced by hepatic synthesis (apoB-100). A decrease in enzymatic delipidation as well as reduced receptor removal of these lipoproteins both contribute to the increased levels of these apo-B-containing particles and their remnants (which are believed to be highly atherogenic). Abnormalities in the metabolism of apoA-containing lipoproteins are also present and these changes contribute to the lower levels of HDL seen. Qualitative abnormalities of these HDL particles may be associated with cellular oxidative injury and contribute to a pro-inflammatory, pro-thrombotic milieu that is frequently present in CKD patients.
Aim: Inflammation is a critical participant in mediating all stages of cardiovascular disease. Studies related with chitotriosidase that was recently found to be relevant to arterial inflammation. In this study we evaluated activity of serum chitotriosidase in acute coronary syndrome patients and its relationship with cardiovascular events, cardiac enzymes and inflammatory indicators. Methods: We prospectively analyzed consecutive 30 patients with ST-segment elevation myocardial infarction, 30 patients with non ST-segment elevation myocardial infarction, 30 patients with unstable angina pectroris who were admitted to our intensive care unit and 30 healthy people (average age 56.86±10.44 years, 81 male) between Jaunary and June 2010. Details of baseline clinical characteristics, biochemical values, receiving treatment and basal ECG findings were recorded. Data of patients with coronary angiography were evaluated. Results: Cut off value of chitotriosidase was calculated 82.00 mmol·ml-1·h-1, with 83 percent sensitivity and 72 percent spesificity. The activity of chitotriosidase in acute coronary syndrome group was 88.85±23.08 mmol·ml-1 ·h-1, where as the control group was 68.47±28.44 mmol·ml-1·h-1, respectively p=0.001).The highest activity of chitotriosidase (96.11±19.77 mmol·ml-1·h-1) was found in ST-segment elevation myocardial infarction group and the minimal activity of chitotriosidase was in the control group (68.47±28.44 mmol·ml-1·h-1) (p= 0.001). The activity of chitotriosidase in ST-segment elevation myocardial infarction and non ST-segment elevation myocardial infarction groups were significantly higher than control group (p=0.001 and p=0.045). When acute coronary syndrome groups compared to control; a positive correlation was found between chitotriosidase activity and hs-CRP (r=0.21, p= 0.046), troponin T (r=0.25, p=0.016), creatine kinase-MB (r=0.20, p=0.059). Conclusion:The activity of chitotriosidase is increased in acute coronary syndrome patients. Chitotriosidase is higher in ST-segment elevation myocardial infaction group than non ST-segment elevation myocardial infarction and unstable angina pectoris group.
Aim: Serum gamma-glutamyltransferase (GGT) levels, which are associated with insulin resistance, may predict the incidence of cardiovascular disease and mortality. Here, the relationship was analyzed between changes in obesity parameters and those in serum GGT over a one-year period. Methods: Data were analyzed from individuals who underwent general health screening two years running. Results: Among 3086 individuals (1954 men, 1132 women), percent changes in both waist circumference (%dWC) and body mass index (BMI) (%dBMI) were significantly correlated with percent changes in GGT (%dGGT) in men (r=0.17 and r=0.31, respectively). On the other hand, in women, %dBMI, but not %dWC, had a significant association with %dGGT. When age, %dWC, %dBMI, smoking status, and alcohol intake were all included as independent variables, %dBMI, but not %dWC, showed a graded association with the highest %dGGT quartile in both genders. Furthermore, incorporation of %dWC as an additional independent variable to age, gender, and %dBMI did not show an incremental improvement in prediction for the highest %dGGT quartile (C statistic, 0.643 to 0.648; p= 0.380), suggesting that taking WC changes into account does not significantly improve the prediction of GGT changes when BMI has already been taken into consideration. Conclusion: Changes in BMI are dose-dependently associated with GGT changes in both genders; however, the additional consideration of changes in WC does not show a significant statistical improvement in the prediction of GGT changes.
Aim: Adiponectin is a key molecule involved in metabolic syndrome. Single nucleotide polymorphisms (SNPs) in the ADIPOQ gene encoding adiponectin correlate with various diseases, such as diabetes mellitus; however, there is insufficient information about ADIPOQ SNPs and the onset of cardiovascular events. Methods: This hospital-based cohort study included 353 patients with essential hypertension (mean age, 62.9±0.6; mean follow-up period. 7.9±0.2 years) in whom ADIPOQ SNPs encoding G276T, I164T, A349G, and/or G967A amino acid changes were detected. We analyzed the correlation between ADIPOQ SNPs and various parameters, including pulse wave velocity (PWV), and assessed whether these SNPs could be risk factors for the onset of stroke, cardiovascular disease, and mortality. Results: Subjects with the T allele of G276T showed significantly lower HDL cholesterol, and significantly higher HbA1c and brachial-ankle PWV (baPWV). Kaplan-Meier analysis revealed that subjects with the T allele of G276T had a significantly higher frequency of stroke (p= 0.0489). The Cox proportional hazard model showed that the T allele of G276T was an independent and significant risk factor for stroke after adjusting for traditional risk factors (relative risk: 1.879, p= 0.0479); however, when adjusted for traditional risk factors and baPWV, the relative risk was significantly diminished (relative risk: 0.710, p= 0.4937). G276T was significantly correlated with dyslipidemia and glucose metabolism. Conclusion: The T allele of G276T was a significant and independent risk for the onset of stroke, and mediated the incidence of stroke through increased arterial stiffness.
Aim: Menopause is considered a cardiovascular risk factor (CRF), but age at menopause (AAM) varies considerably and could affect the risk among post-menopausal women. The aim of the study was to clarify whether AAM is associated with hypertension, diabetes mellitus (DM) and hypercholesterolemia, independent of chronological age, lifestyle and hormone replacement therapy (HRT), in a sizeable number of Japanese women. Methods: A retrospective study was conducted using the baseline survey of the ongoing large prospective Japan Nurses’ Health Study. The prevalence of hypertension, DM, and hypercholesterolemia of pre-menopausal and three post-menopausal AAM groups (early: <45 years, intermediate: 45-53 years, late: >53 years) was compared among 22,426 women aged 40-59 years. Daily lifestyle such as smoking, alcohol consumption, and physical activity were included. Results: The estimated risk (odds ratio: OR) was significantly higher in post-menopausal women and linearly elevated according to the AAM groups, and the late AAM group was more likely to have hypertension, DM, or hypercholesterolemia; however, after adjustment for age, BMI (kg/m2), HRT and lifestyle, menopause and AAM showed a significant association with only hypercholesterolemia and the early AAM group had the highest OR (2.72 (1.93-3.82)). Menopause and AAM did not show any independent association with the risk of hypertension and DM in the fully adjusted model. Conclusions: Among the post-menopausal women, early menopause increased the risk for hypercholesterolemia independently. AAM can be a useful screening tool to identify women at high risk for adverse post-menopausal lipid profiles in the Japanese.
Aim: The purpose of this study was to determine the effects of lutein supplement on serum cytokines, apoE and lipoprotein profiles in early atherosclerosis population. Methods: Early atherosclerosis patients (n= 65) were randomized to receive placebo (A+P, n= 31) or 20 mg/d lutein (A+L, n= 34) for 3 months. Results: Serum lutein increased significantly compared to baseline after lutein supplements in A+L group (p<0.001). Lutein supplements resulted in a significant decrease in serum interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) at 3 month in A+L group (p<0.05). Intragroup comparison revealed a significant difference in the changes of serum MCP-1 between A+L and A+P groups (p= 0.021). The serum low-density lipoprotein (LDL) and triglyceride (TG) significantly decreased in A+L group (p<0.05). The changes in serum lutein were negatively associated with those in serum LDL in A+L group (r=−0.384, p=0.043), while no such relationship was observed in A+P group (r= 0.087, p= 0.685). Conclusion: An increase in serum lutein after supplementation can reduce inflammatory cytokines and regulate serum lipids, which may pay important roles in early atherosclerosis.
Aim: The cardio-ankle vascular index (CAVI) reflects overall arterial stiffness from the aorta to the ankle, independent of blood pressure. Cerebral small vessel diseases (SVDs), including white matter lesions (WML), silent lacunar infarction (SLI) and cerebral microbleeds (CMB), are considered to increase the risk of stroke and cognitive impairment further. We aimed to investigate the association of cerebral SVD with CAVI in asymptomatic young and middle-aged subjects. Methods: Asymptomatic Korean individuals aged 30 to 59 years old without neurologic disease who had CAVI and brain magnetic resonance imaging (MRI) were evaluated retrospectively. Results: Among 484 subjects, cerebral SVDs (advanced WML, SLI and CMB) were found in 20 (4.1%). Subjects with SVDs tended to be older and to have higher systolic blood pressure (SBP) and higher CAVI. From multivariate regression analysis, including pulse pressure (PP) or SBP, CAVI showed a significant association with SVD [adjusted OR (95% CI): 1.889 (1.094-3.263), p= 0.002 and 1.793 (1.020-3.153), p= 0.043, for PP and SBP, respectively]. When CAVI was assessed by quartiles, the highest quartile of CAVI (CAVI >7.65) showed a significant association with SVD, after adjustment for PP [adjusted OR (95% CI): 2.766 (1.115-6.866), p= 0.028]. Conclusion: In young and middle-aged subjects, cerebral SVD was significantly associated with arterial stiffness measured by CAVI after adjusting for PP or SBP.
Aim: The adipocyte-derived hormone leptin plays a key role in the regulation of food intake and energy expenditure. Recent studies have suggested that leptin is also involved in the pathogenesis of obesity-associated atherosclerosis and cardiovascular disease. In this study, we investigated the associations of leptin and the soluble leptin receptor (sOb-R) with atherosclerosis in patients with type 2 diabetes. Methods: Three hundred seventeen type 2 diabetic subjects were enrolled in this cross-sectional study. Fasting plasma leptin and sOb-R concentrations were measured by enzyme-linked immunosorbent assays. The intima-media thickness (IMT) of the common carotid artery was measured by ultrasound. Results: The IMT was significantly associated with sOb-R concentrations, age, diabetes duration, serum creatinine (sCre) levels, and systolic blood pressure (SBP), but not with leptin concentrations or the leptin/sOb-R ratio. The concentrations of leptin (r=0.478, p<0.001) and the sOb-R (r= −0.404, p<0.001) and the leptin/sOb-R ratio (r=0.501, p<0.001) were strongly correlated with IMT in subjects treated with insulin for glycemic control, but not in those treated with diet alone or oral hypoglycemic agents. Multiple regression analysis, including age, sex, diabetes duration, body mass index, SBP, HbA1c, triglycerides, LDL-cholesterol, sCre, smoking, and insulin therapy, revealed that plasma leptin and the leptin/sOb-R ratio were independently associated with IMT in subjects treated with insulin. Conclusions: Plasma leptin and the leptin/sOb-R ratio are associated with atherosclerosis in patients with type 2 diabetes on insulin therapy, and these associations were independent of obesity and other cardiovascular risk factors.
Aim: Several lines of evidence indicate that small dense low-density lipoproteins (sd-LDL) are more atherogenic than large buoyant LDL; however, few prospective studies have addressed the role of sd-LDL in cardiovascular disease (CVD). We therefore examined the association between sd-LDL cholesterol (sd-LDL-C) and CVD in a Japanese cohort. Methods: An 11.7-year prospective study was performed using a general population aged 30-79 without a history of cardiovascular disease. Direct LDL-C and sd-LDL-C were measured in samples from 2034 participants (968 men and 1066 women). Results: During the follow-up period, there were 116 incident cases of CVD. The multivariable-adjusted hazard ratios (HRs) of sd-LDL-C for CVD were calculated using a proportional hazards regression model after adjusting for age, hypertension, diabetes, use of lipid-lowering drugs, body mass index, and current smoking and alcohol drinking, and found that increasing quartiles of sd-LDL-C were associated with increased risk of CVD. We also determined that age and sex-adjusted HRs per 10 mg/dL of sd-LDL-C and HRs for CVD, stroke, cerebral infarction, and coronary artery disease were 1.21 (95% CI: 1.12-1.31), 1.17 (95% CI: 1.05-1.30), 1.15 (95% CI: 1.00-1.33), and 1.29 (95% CI: 1.14-1.45), respectively. Conclusions: It was demonstrated that sd-LDL-C was significantly associated with CVD in a Japanese population, providing evidence of sd-LDL-C as an important biomarker to predict CVD.
Aim: To investigate the acute effects of postprandial exercise on glucose and lipoprotein metabolism after the intake of glucose with or without fat cream in healthy but sedentary young women. Methods: Healthy young Japanese women with a sedentary lifestyle, normal weight (18.5≤BMI<25), normal ovarian cycle, and apolipoprotein (apo) E3/3 were enrolled as participants. They ingested 1 g/kg body weight of glucose only or glucose supplemented with 1 g/kg oral fat tolerance test (OFTT) cream 4 (0.35 g/kg as fat) with or without postprandial walking exercise on a motorized treadmill (ca. 50%V·o2max for 30 min) 20 min after intake of the beverage. Each subject performed 4 trials in a randomized, cross-over design. Venous blood was drawn before (0 h), and 20 min, 1, 2, 4, and 6 h after ingestion. Results: Postprandial exercise alleviated the sharp rise of serum glucose and insulin, and transiently mitigated the decrease of free fatty acids (FFA) after ingestion of the glucose-only beverage. Although no fat was contained in the glucose beverage, transient apoB48 secretion was observed without the rise of serum triglyceride (TG) and remnant-like particle (RLP)-TG, suggesting that apoB48-containing lipoprotein particles with little TG were released by the exercise. Serum apoB48 concentrations at 6 h had decreased to levels lower than the baseline (0 h, after 12-h overnight fast) with or without exercise, suggesting that the 12-h overnight fast may not have been a ‘true’ fast. Similarly, postprandial exercise suppressed the sharp rise of serum glucose and insulin, and transiently mitigated the decrease of FFA after the ingestion of glucose with OFTT cream. Postprandial exercise stimulated the transient secretion of apoB48-containing TG-rich lipoproteins (TRL) with a rapid rise of serum apoB48, TG, and RLP-TG; however, the subsequent course of lipemia was not significantly changed. Serum apoB48 and RLP-TG values did not return to the baseline even after 6 h, suggesting that postprandial lipoprotein metabolism was not finished at the end of the experiment. Conclusion: Postprandial aerobic exercise alleviated the glycemic peak at 1 h associated with insulin ‘sparing’. The effect of exercise on fat metabolism was transient, enhancing the secretion of intestinal TRL at an early phase, but no further significant effects were observed. Postprandial exercise transiently stimulated the secretion of apoB48 after glucose intake without a fat load.