小谷 和彦

Ischemic heart disease (IHD) remains one of the most important disorders associated with disability and mortality worldwide, and is one of the major causes of cardiovascular diseases in Mongolia. The objective of the current study was to determine the prevalence of IHD and its related factors in a general population in Mongolia. We conducted a nationwide cross-sectional survey between March and September, 2009. General participants were recruited from urban to rural regions in a multistage random cluster sampling method. The diagnosis of IHD was based on the Rose questionnaire (World Health Organization) and electrocardiographic findings. A total of 369 (16.2 %) subjects with IHD were diagnosed among 2,280 participants. The prevalence of subjects with IHD was significantly increased by age: from 9.9 % in individuals age 40-44 years compared to 17.7 % in those over 60 years. Smoking habits (former and current) and non-frequent intake of fruits and vegetables were significantly positively associated with IHD in men, while heavy alcohol drinking habits and lower education period of time were significantly positively associated with IHD in women. IHD was found to be prevalent, especially among people aged over 40 years, in Mongolia. Statistical factors related to IHD were found to be significantly different based on sex. The current data may provide relevant information to prevent IHD in the Mongolian population.

OBJECTIVE: Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) consist of heterogeneous particles whose subpopulations may have different atherogenic characteristics. This study investigated the associations between these subpopulations and other lipids, lipoproteins and atherosclerosis-related markers. DESIGN AND METHODS: A total of 416 subjects (124 males and 292 females, mean age: 50.8 years) were enrolled in this study. Using polyacrylamide gel electrophoresis, serum lipoproteins were separated according to their specific electrophoretic mobility based on particle size. The IDL particles were separated into three midbands (MID-A to C), and the LDL particles were separated into seven subfractions (LDL1 to 7). RESULTS: MID-B, MID-C, LDL2 and LDL3 to 6 (as a small LDL fraction) were significantly and positively correlated with very LDL (VLDL), while MID-A and LDL1 were significantly and inversely correlated with VLDL. MID-A and LDL1 were significantly and positively correlated with high-density lipoprotein (HDL). The correlation patterns between MID-A or LDL1 and triglycerides, apolipoprotein A-I, glucose, the insulin resistance index, creatinine and the mean LDL particle size had similar trends to those between HDL and these parameters. CONCLUSIONS: The respective subpopulations of IDL and LDL particles can vary in their ability to predict cardiovascular disease risks. These variations may partially explain why quantitative assessments using LDL-cholesterol concentrations, as typically performed in conventional practice, are not perfect predictors of cardiovascular disease. Further studies are required to determine the clinical relevance of analyzing the IDL and LDL subpopulations.

Prostate cancer is a common disease in modern, developed societies and has a high incidence and mortality. High-density lipoprotein cholesterol (HDL-C) has recently received much attention as a possible risk marker of prostate cancer development and prognosis. In the present article, we summarized findings from epidemiologic studies of the association between HDL-C and prostate cancer. Low HDL-C level was found to be a risk and prognostic factor of prostate cancer in several epidemiologic studies, although the overall linkage between HDL and prostate cancer has not been definitively established. The mechanisms for this association remain uncertain; however, limited data from experimental studies imply a possible role of HDL in the pathophysiology of prostate cancer. More epidemiologic research, in combination with experimental studies, is needed in this field.

While oxidized lipoprotein(a) (oxLp(a)) has been indicated to be involved in atherogenesis more than native lipoprotein(a) (Lp(a)), there is still a need to elucidate the associations among oxLp(a), hypertension, and atherosclerosis. The cardio-ankle vascular index (CAVI) is a recently developed index used to assess arterial stiffness that is independent of blood pressure components. The present study investigated the correlation between oxLp(a) and the CAVI among hypertensive subjects. Clinical data, including general atherosclerotic risk factors, in addition to Lp(a), oxLp(a), and the CAVI, were collected from 72 non-smoking, asymptomatic, and untreated female subjects (mean age: 64.3 years). Correlations between the CAVI and Lp(a) or oxLp(a) were examined in a hypertensive group (n = 34) and a non-hypertensive control group (n = 38). There was a significant and positive correlation between the CAVI and subject age in the control group, while there was a significant and positive correlation between the CAVI and subject age, systolic blood pressure, and oxLp(a) (r = 0.38, p < 0.05) in the hypertensive group. A stepwise multiple linear regression analysis identified the oxLp(a) to be correlated independently, significantly, and positively with the CAVI (β = 0.30, p < 0.05) in the hypertensive group, while this correlation was not significant in the control group. These findings suggest that the oxidative modification of Lp(a) may be associated with arterial stiffness in hypertensive, but not non-hypertensive, female subjects.

AIM: Although previous studies have shown that consumption of green tea catechins (GTC) and walking might prevent development of cardiovascular disease (CVD), the effects of GTC supplementation on CVD risk in active older people are unknown. METHODS: A total of 52 older adults (male/female 20/32, mean age 69.1 ± 5.9 years) participating in a pedometer-based walking program were randomly assigned to a GTC group with an intake of 630.9 mg GTC daily (n=26) or a control group (n=26) for 14 weeks. Cardiovascular risk markers were measured before and after this trial. RESULTS: In the GTC group, values of the following markers were significantly reduced (P<0.05) from the beginning to the end of the trial: waist circumference (from 84.2 ± 8.4 to 82.2 ± 8.5 cm), hip circumference (from 95.1 ± 6.9 to 92.2 ± 6.3 cm), total cholesterol (from 233.0 ± 46.3 to 218.8 ± 42.3 mg/dL), low-density lipoprotein cholesterol (from 130.4 ± 36.2 to 119.1 ± 33.4 mg/dL) and low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (from 2.0 ± 1.7 to 1.7 ± 0.5); only hip circumference (from 95.6 ± 8.1 to 94.1 ± 7.6 cm) was significantly reduced (P<0.05) in the control group. No significant between-group differences were found for any parameter measured. CONCLUSIONS: Although GTC might reduce cholesterol levels, the present randomized control trial suggests that GTC supplementation in active older participants did not significantly affect cardiovascular risk markers. Future studies should identify more effective combinations of GTC supplementation and physical activity.

PURPOSE: The Fukushima Health Management Survey conducted after the accident at the Fukushima Nuclear Power Plant included thyroid ultrasound examinations for children aged ≤18 years at the time of the accident. The purpose of this study was to investigate the frequency of thyroid nodular lesions detected using high-quality ultrasonography in a general population of Japanese children, in whom such data have not been previously characterized. METHODS: The current study investigated 4,365 free-living children aged between 3 and 18 years in three Japanese prefectures (Aomori, Yamanashi and Nagasaki). The same ultrasonography equipment as that used in the Fukushima Survey was employed to observe thyroid nodular lesions. The following categories of findings were used-'A', further examinations are not necessary; 'B', the presence of thyroid nodules with a diameter of ≥5.1 mm or thyroid cysts with a diameter of ≥20.1 mm; and 'C', immediate further examinations are required. As a sub-category of 'A', 'A1' was defined as the absence of nodules or cysts, and 'A2' was defined as the presence of thyroid nodules with a diameter of ≤5.0 mm or thyroid cysts with a diameter of ≤20.0 mm. RESULTS: Overall, 4,321 (99 %) of the total participants were classified with a status of 'A' and 44 (1 %) were classified with a status of 'B'. No participants were classified with a status of 'C'. A total of 56.5 % of the total participants was classified with a status of 'A2'. Thyroid nodules were identified in 1.6 % of the total participants and thyroid cysts were identified in 56.9 % of the participants. CONCLUSION: The current study provides data regarding the actual frequency of ultrasonographically detected thyroid nodular lesions among the Japanese children. These results would be useful for evaluating thyroid findings in Japanese children, although careful interpretation is required.

Blood flows out of microvessels in the dermis when pressure higher than arterial blood pressure is applied to the fingertip, and subsequently re-flows into the microcirculation when pressure is released. Both the blood outflow and the reflow characteristics of microcirculation under pressurization are associated with microvasculature, blood and blood pressure. This study describes a novel method of measuring blood inflow and outflow characteristics of dermis microcirculation. An optical sensor, which is furnished with a 571 nm wavelength light source and a photodetector, is pressed to the skin surface using a pressure higher than the human subject's systolic arterial pressure. Hemoglobin concentration by change of the blood flow amount is estimated by the Beer-Lambert law. This method is applied to the measurement of blood inflow and outflow characteristics of microcirculation caused by reactive hyperemia after ischemia with duration of 5 min. Among three parameters evaluated, the one relating to the amplitude of pulsation shows a close correlation with conventional plethysmography, while the other two show varying time responses. Our method provides a new and useful insight into pathophysiology in health and disease conditions and may help researchers better understand the underlying mechanisms of numerous microcirculation-influenced diseases and medical conditions.

BACKGROUND & OBJECTIVES: Oxidative stress plays important roles in the pathophysiology of type 2 diabetes mellitus (T2DM). The diacron reactive oxygen metabolites (d-ROMs) test has been used in the clinics. The present study was aimed to investigate the correlation of the oxidative stress status, as evaluated by the d-ROMs, with atherosclerotic risk factors in T2DM patients, in comparison to controls. METHODS: The study included 200 subjects (100 patients with T2DM and 100 controls; 86 males/114 females; mean age 59.0 yr). Clinical variables including the body mass index, blood pressure (BP), glucose and lipid panels, in addition to the d-ROMs, were measured. RESULTS: Patients with T2DM showed significantly higher d-ROMs levels than controls (322 ± 60 vs. 345 ± 64 U. Carr., P<0.05). A multiple linear regression analysis revealed that systolic BP (β=0.26, P<0.05) and high-density lipoprotein cholesterol (HDL-C: β= -0.30, P<0.05) were independently and significantly correlated with the d-ROMs levels in patients with T2DM, although these correlations were not significant in the controls. The gender-based analysis showed that systolic BP (β = 0.44, P<0.05) and HDL-C (β = -0.36, P<0.05) were independently and significantly correlated with the d-ROMs levels in females with T2DM, while there was a marginally significant correlation between HDL-C and the d-ROMs levels (β = -0.36, P=0.06) in males with T2DM. INTERPRETATION & CONCLUSIONS: The present findings may reinforce the importance of BP control in female patients with T2DM, as well as the management of HDL-C in male and female patients with T2DM, under the linkage between oxidative stress and atherosclerosis.

Ultrasound probes are usually in a direct contact with the skin when used for detecting pathologic abnormalities. The probe could be a vector of bacterial transmission, but there have been few studies on this topic.We have made such studies, briefly reviewing 1)the conditions governing a possible bacterial transmission by probe, 2) the deterioration of an ultrasound probe by alcohol disinfection, 3) a suitable method for evaluating bacterial contamination of an ultrasound probe, and 4) the best procedure for decontaminating such probes. This paper ,may lead to a formal consideration of the relationship between ultrasound probes and their roles in bacterial transmission in clinical practice.

BACKGROUND: Lifestyle modifications are considered the most effective means of delaying or preventing the development of type 2 diabetes (T2DM). To contain the growing population of T2DM, it is critical to clarify effective and efficient settings for intervention and modalities for intervention delivery with a wide population reach.The Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1) is a cluster randomized controlled trial to test whether goal-focused lifestyle coaching delivered by telephone can prevent the development of T2DM in high-risk individuals in a real-world setting. This paper describes the study design and recruitment of the study subjects. METHODS: For the recruitment of study subjects and their follow-up annually over 3 years, we employed health checkups conducted annually at communities and worksites. Health care divisions recruited from communities and companies across Japan formed groups as a cluster randomization unit. Candidates for the study, aged 20-65 years with fasting plasma glucose (FPG) of 5.6-6.9 mmol/l, were recruited from each group using health checkups results in 2006. Goal-focused lifestyle support is delivered by healthcare providers via telephone over a one-year period. Study subjects will be followed-up for three years by annual health checkups. Primary outcome is the development of diabetes defined as FPG≥7.0 mmol/l on annual health checkup or based on self-report, which is confirmed by referring to medical cards. RESULTS: Forty-three groups (clusters), formed from 17 health care divisions, were randomly assigned to an intervention arm (22 groups) or control arm (21 clusters) between March 2007 and February 2008. A total of 2840 participants, 1336 from the intervention and 1504 from the control arm, were recruited. Consent rate was about 20%, with no difference between the intervention and control arms. There were no differences in cluster size and characteristics of cluster between the groups. There were no differences in individual characteristics between the study arms. CONCLUSION: We have launched J-DOIT1, a nation-wide trial to prevent the development of T2DM in high-risk individuals using telephone-delivered intervention. This trial is expected to contribute to evidence-based real-world preventive practices. TRIAL REGISTRATION: UMIN000000662.

BACKGROUND: We developed a practical method for analysis of PON-1 enzymatic activity in HDL subclasses. METHODS: The assay uses 4-12% polyacrylamide gradient gels, phenylacetate as substrate coupled with densitometric phenol detection using 4-aminoantipyrine. The measurement PON-1 activity in situ across the HDL subclasses has a strong correlation with the kinetic microplate assay for total PON-1 activity, r=0.91, p<0.001. RESULTS: The same HDL-C level, healthy subjects (n=33) display a large difference in the ratio of PON-1 activity in small vs. large HDL. Since PON-1 activity is larger in HDL(3) we propose that this difference has a potent predictive value for clinical risk assessment and therapeutic choice. Our method also offers the advantage of assessing the distribution of up to six different HDL apolipoproteins in the same gel after transfer. CONCLUSIONS: We seek to further dissect the cause of a different distribution of PON-1 activity in HDL subclasses by employing this method that permits practical, inexpensive analysis of antioxidant function of HDL subclasses and has the potential for application in clinical chemistry and to shed some light on the importance of PON-1 distribution.

OBJECTIVE: To investigate the correlation between gamma-glutamyltransferase (GGT) and remnant-like particle cholesterol (RLP-C) in dyslipidemic patients. SUBJECTS AND METHODS: General cardiometabolic variables, plus serum GGT and RLP-C levels, were measured in 118 dyslipidemic patients (59 males, mean age 58 ± 13 years). Correlation analyses of GGT with other variables, including RLP-C, were performed. RESULTS: The median levels (interquartile ranges) of RLP-C and GGT were 0.21 mmol/l (0.14-0.35) and 26 IU/l (17-39), respectively. A stepwise multiple regression analysis revealed an independent, significant and positive correlation between GGT and RLP-C (β = 0.351, p < 0.001), followed by male gender and BMI. CONCLUSION: There was a significant positive association between GGT and RLP-C, thereby indicating that the association between GGT and cardiovascular disease may be partly due to the interaction with RLP-C in dyslipidemic patients. Further research is therefore warranted to confirm the observed relationship.

OBJECTIVE: This study investigated the relationship between sleep adequacy and small dense low-density lipoprotein (sdLDL) in a Japanese population. SUBJECTS AND METHODS: Clinical data, including atherosclerotic risk factors, in addition to the mean LDL particle size (LDL-PS) measured by gel electrophoresis, were evaluated in 136 community-dwelling female subjects (40-80 years old). The sleep status was self-reported and the subjects were divided into those who had inadequate sleep (≤ 6 or ≥ 9 h of sleep) and had adequate sleep (7-8 h). RESULTS: The mean LDL-PS was significantly smaller in subjects with inadequate sleep [n = 68, 26.4 ± 0.4 (SD) nm] than in those with adequate sleep (n = 68, 26.6 ± 0.4 nm, p < 0.05). This difference remained significant and independent after adjusting for confounders (β = 0.15-0.19, p < 0.05). CONCLUSION: Sleep adequacy was associated with the presence of sdLDL, while the influence of the sleep status on LDL-PS was minor in this population. Further research on the associations among sleep, sdLDL and cardiovascular disease prevention is warranted.

Postprandial hyperglycemia and/or hyperlipidemia can contribute to development of atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to compare the effects of miglitol and sitagliptin on postprandial glucose and lipid metabolism in patients with T2DM. Thirty-five patients with T2DM were randomized to 2 groups receiving miglitol (150 mg/day) or sitagliptin (50 mg/day). Serum variables related to glucose and lipid metabolism were measured before and after treatment for 10 weeks and at 0, 60, and 120 min using a cookie-loading test (CLT). After 10 weeks of treatment, miglitol (n = 16) and sitagliptin (n = 18) caused a similarly significant decrease in hemoglobin A1c (mean: 7.6% to 7.3% versus 8.0% to 7.6%) and a significant increase in fasting insulin levels, with a greater increase observed in the miglitol group than in the sitagliptin group (p=0.03). In addition, a significant decrease in the change in glucose levels after the CLT was observed in both groups, with a greater decrease observed in the miglitol group than in the sitagliptin group (p=0.02). The miglitol group also showed a greater decrease in the change in insulin levels after the CLT than the sitagliptin group (p<0.01). The lipid and lipoprotein levels did not show any significant differences between the groups after the CLT. Our results suggested that miglitol and sitagliptin treatment resulted in similar glycemic control but that a greater decrease in postprandial glucose and insulin levels was observed with miglitol compared with sitagliptin in patients with T2DM.

AIM: The aim of this study was to investigate the relationship between atherosclerotic manifestations and brachial and radial arterial wall elasticity (AWE) measured using the phased tracking method in patients with type 2 diabetes mellitus (T2DM). METHODS: This study included T2DM patients (n= 220, mean age 59 years) without a history of stroke or coronary artery disease. The brachial AWE, radial AWE, carotid mean intima-media thickness (IMT), max-IMT and flow-mediated vasodilation (FMD) were measured. The patients were classified according to the number of atherosclerotic risk factors, including obesity, dyslipidemia and hypertension. Group 1 included T2DM patients only, group 2 included patients with two risk factors, group 3 included patients with three risk factors and group 4 included patients with four risk factors. The patients were also divided into two groups according to microangiopathic complications, including retinopathy and nephropathy. The between-group differences were analyzed. RESULTS: The brachial AWE (548, 697, 755 and 771 kPa for groups 1, 2, 3 and 4, respectively) and radial AWE (532, 637, 717 and 782 kPa for groups 1, 2, 3 and 4, respectively) significantly increased in association with an increasing number of risk factors. The brachial AWE and radial AWE were significantly higher in the patients with microangiopathic complications than in those without microangiopathic complications (brachial AWE 797 and 694 kPa and radial AWE 780 and 660 kPa, respectively). Receiver operating characteristic curve analyses revealed that, for brachial AWE and radial AWE, the area under the curve was equal to the max-IMT and higher than the mean-IMT and FMD. CONCLUSIONS: Upper limb AWE measurement can reflect the degree of atherosclerosis risk overload and may be useful for evaluating vascular complications in T2DM patients.

OBJECTIVES: Although hypertension is the primary cause of morbidity and mortality from cardiovascular diseases in Mongolia, reviews about hypertension in this country have not been reported, to our knowledge. Information on the overview of this disease may be useful to establish measures and policy to prevent hypertension and its related complications. The aim of our article is to summarize the current situation vis-à-vis hypertension in Mongolia. METHODS: Population-based studies that provided relevant information on hypertension in Mongolia were searched through PubMed, abstract books of the Mongolian Medical University resources from cardiologists, epidemiological databases and reliable websites of national organizations. Available articles from 1970 to present were selected. RESULTS: A high prevalence of hypertension, which varied according to geographic location, exists among Mongolian people. The prevalence of hypertension may be influenced by nutritional factors, sedentary lifestyle, socioeconomic status and environmental factors in particular. CONCLUSIONS: The high prevalence of hypertension among Mongolian people can be a serious health problem in this country. Defining ethnic features of hypertension and related conditions will be the initial step that may lead to prevention of this disease. Further research and positive efforts to prevent hypertension appear necessary for Mongolians.

BACKGROUND: The long-term outcomes of Kawasaki disease (KD) are unknown. METHODS: Fifty-two collaborating hospitals collected data on all patients who had received a new definite diagnosis of KD between July 1982 and December 1992. Patients were followed until December 31, 2009 or death. Standardized mortality ratios (SMRs) were calculated based on Japanese vital statistics data. RESULTS: Of the 6576 patients enrolled, 46 (35 males and 11 females) died (SMR: 1.00; 95% CI: 0.73-1.34). Among persons without cardiac sequelae, SMRs were not high after the acute phase of KD (SMR: 0.65; 95% CI: 0.41-0.96). Among persons with cardiac sequelae, 13 males and 1 female died during the observation period (SMR: 1.86; 95% CI: 1.02-3.13). CONCLUSIONS: In this cohort, the mortality rate among Japanese with cardiac sequelae due to KD was significantly higher than that of the general population. In contrast, the rates for males and females without sequelae were not elevated.

Paraoxonase 1 (PON1) and serum amyloid A (SAA) are proteins carried by high-density lipoprotein (HDL) particles. Among the HDL-associated protein molecules, SAA, an inflammation-related marker, and PON1, an antioxidant marker, tend to change in relatively clear opposite directions in physiological situations. In clinical chemistry, paired measurements of both markers may provide useful information to understand dysfunctional HDL in diseases with inflammation and oxidative stress conditions. Actually, limited clinical studies have suggested that the combined use of PON1 and SAA may be a tool for observing the pathophysiology of some disease entities. From the findings of experimental studies, PON1 appears to be cooperatively regulated by inflammation- and oxidative stress-related molecules linked with SAA regulation in humans. More studies remain to be performed to ascertain the value of paired measurements of both promising markers in clinical practice.

Due to the likelihood of physical and mental health impacts following the unprecedented accident at the Fukushima Dai-ichi Nuclear Power Plant, the Fukushima prefectural government decided to conduct the Fukushima Health Management Survey to assist in the long-term health management of residents. This included thyroid ultrasound examination for all children in Fukushima. For appropriate evaluation of ultrasound screening of the thyroid, it is important to understand its reference data of thyroid findings in children in general. In order to analyze the frequencies of specific thyroid findings, we conducted ultrasound screening of the thyroid by the same procedures as used in Fukushima in 4,365 children, aged 3 to 18 years, from three Japanese prefectures. Overall, thyroid cysts were identified in 56.88% and thyroid nodules in 1.65% of the participants. Thyroid cysts and nodules with a maximum diameter of more than 5 mm were identified in 4.58% and 1.01%, respectively, and age-adjusted prevalences were 3.82% and 0.99%, respectively. Although the prevalence of cysts and nodules varied among the examination areas, no significant differences were observed among the three examination areas in the prevalence of cysts and nodules with a maximum diameter of more than 5 mm. Also, the prevalence of thyroid cysts and nodules, especially those with a maximum diameter of more than 5 mm, significantly increased with age, and showed a female predominance. We also identified ectopic thymus (1.95%), diffuse goiter (1.40%), ultimobranchial body (0.73%), lymph node swelling (0.21%) and thyroid agenesis (0.05%). This is the first ultrasound description of the age-adjusted prevalence of thyroid cysts and nodules, or of the prevalence of abnormalities other than cysts and nodules, such as ectopic thymus, in relation to age, in the general Japanese child population. We contend that this can provide relevant information for the Fukushima Health Management Survey and future population studies.

BACKGROUND: Small dense low-density lipoprotein (sdLDL), which has a small LDL particle size with a greater susceptibility to oxidation, is considered a risk marker for cardiovascular disease (CVD). The diacron reactive oxygen metabolites (d-ROMs) have recently been introduced as a clinically useful oxidative stress-related marker. Physical activity can reduce the CVD risk. The present study investigated the correlation between the changes of the mean LDL particle size and the oxidative stress status, as assessed by the d-ROMs, in a physical activity intervention in hyperlipidemic subjects. METHODS: We performed a 6-month intervention study of 30 hyperlipidemic subjects (12 male/18 female, mean age 64 years), focusing on a moderate physical activity increase. The clinical data, including the atherosclerotic risk factors besides the mean LDL particle size measured with the gel electrophoresis and the d-ROMs, were evaluated pre- and post-intervention. RESULTS: The mean LDL particle size was significantly larger in the post-intervention than in the pre-intervention evaluation (26.9 ± 0.3 (SD) vs. 27.1 ± 0.4 nm, P < 0.01), while the d-ROMs levels were significantly reduced in the post-intervention period compared to those at pre-intervention (319 ± 77 vs. 290 ± 73 U. Carr., P < 0.05). A stepwise multiple regression analysis revealed that there was an independent, significant and inverse correlation between the pre- and post-intervention changes of the d-ROMs and the mean LDL particle size (β = -0.55, P < 0.01). CONCLUSIONS: The intervention study suggests that sdLDL and oxidative stress can concomitantly affect the risk of developing CVD and that both factors can improve by even a moderate increase in physical activity among hyperlipidemic subjects.

OBJECTIVES: Chronic inflammation and oxidative stress are associated with health and the disease status. The objective of the present study was to investigate the association among white blood cell (WBC) counts, neutrophil counts as a WBC subpopulation, and diacron reactive oxygen metabolites (d-ROMs) levels in an asymptomatic population. METHODS: The clinical data, including general cardiovascular risk variables and high-sensitivity C-reactive protein (hs-CRP), were collected from 100 female subjects (mean age, 62 years) in outpatient clinics. The correlation of the d-ROMs with hs-CRP, WBC, and neutrophil counts was examined. RESULTS: The mean/median levels were WBC counts 5.9 × 10(9)/L, neutrophil counts 3.6 × 10(9)/L, hs-CRP 0.06 mg/dL, and d-ROMs 359 CURR U. A simple correlation analysis showed a significant positive correlation of the d-ROMs with the WBC counts, neutrophil counts, or hs-CRP levels. The correlation between d-ROMs and neutrophil counts (β = 0.22, P < 0.05), as well as that between d-ROMs and hs-CRP (β = 0.28, P < 0.01), remained significant and independent in a multiple linear regression analysis adjusted for other variables. A multiple linear regression analysis showed that WBC counts had only a positive correlation tendency to the d-ROMs. CONCLUSIONS: Neutrophils may be slightly but more involved in the oxidative stress status, as assessed by d-ROMs, in comparison to the overall WBC. Further studies are needed to clarify the biologic mechanism(s) of the observed relationship.

BACKGROUND: Elevated and extreme circulating levels of lipoprotein(a) (Lp(a)) are considered to be an atherosclerotic risk factor, although additional studies on the low levels of Lp(a) are necessary to provide confirmation. The carotid intima-media thickness (CIMT) is known as a surrogate index of atherosclerosis. The aim of the present study was to investigate the correlation between the serum Lp(a) and CIMT in asymptomatic subjects with a relatively low Lp(a) level. METHODS: The study included 65 asymptomatic female Japanese subjects (mean age: 60 years) with a serum Lp(a) level < 30 mg/dL. Clinical data including the serum Lp(a) and CIMT were measured, and their correlations were examined. RESULTS: The median Lp(a) level was 18.6 mg/dL and the mean CIMT level was 0.8 mm. There was a significant and inverse correlation between the CIMT and Lp(a) (r = - 0.24, P ≤ 0.05), in addition to a significant and positive correlation between the CIMT and subject age and systolic blood pressure. A stepwise multiple linear regression analysis identified the Lp(a) to be correlated independently, significantly and inversely with the CIMT. CONCLUSIONS: The Lp(a) levels were inversely correlated with the CIMT in this population, suggesting that subjects with a low Lp(a) level may have a predisposition to carotid atherosclerosis. This finding was preliminary and should be investigated further in larger studies and in additional settings. KEYWORDS: Lp(a); Carotid artery; IMT; Atherosclerosis.

OBJECTIVES: Small dense low-density lipoprotein (sdLDL) which has a small LDL particle size with greater susceptibility to oxidation is regarded as a risk marker for cardiovascular disease. The diacron reactive oxygen metabolites (d-ROMs) test has recently been introduced as an oxidative stress-related marker in the clinic. The aim of the present study was to investigate the correlation between the mean LDL particle size and the oxidative stress status as evaluated by the d-ROMs in dyslipidemic patients. METHODS: The study included 278 dyslipidemic patients (121 male and 157 female, mean age, 60 years). Clinical data including the conventional atherosclerotic risk factors in addition to the mean LDL particle size measured with the gel electrophoresis and the d-ROMs were collected. RESULTS: Male patients had a significantly smaller mean LDL particle size than females (262.2 ± 7.5 [SD] vs. 264.3 ± 6.7 Å, P<0.05), while female patients had a significantly higher d-ROMs level than males (318 ± 68 vs. 350 ± 72 U. Carr., P<0.01). A multiple regression analysis revealed that there was an independent, significant, and inverse correlation between the mean LDL particle size and the d-ROMs (β=-0.19, P<0.05). CONCLUSIONS: These findings of the co-existence of both markers suggest that sdLDL and oxidative stress can be cooperative in atherogenesis, possibly leading to the incidence of CVD, in dyslipidemic patients.

BACKGROUND: Inflammation and oxidative stress are associated with human health and the disease status. The present study aimed to investigate the longitudinal correlation between the diacron reactive oxygen metabolites (d-ROMs) level, as an oxidative stress-related marker, and high-sensitivity C-reactive protein (hsCRP), as an inflammatory marker, during a one-year period among asymptomatic subjects. METHODS: The data, including anthropometric and biochemical markers, were collected at baseline and after the one-year period from 71 participants (male/female = 41/30, mean age 50 years). The correlation between the changes of the d-ROMs and hsCRP levels during the study period was examined. RESULTS: A simple correlation analysis showed a significant and positive correlation to exist between the changes of the d-ROMs and hsCRP levels (r = 0.40, P < 0.01). This significant correlation remained independent in a multiple linear regression analysis adjusted for confounding factors. CONCLUSIONS: The present findings suggest that the relationship between the d-ROMs and hsCRP levels could be prospectively followed, and that monitoring both markers may help to better understand the cooperation of inflammation and oxidative stress in association with health and disease. Further studies are necessary to clarify the biological mechanism(s) responsible for the observed relationship. KEYWORDS: Oxidative stress; Oxygen reactive species; Inflammation; CRP.

In this review we summarize the findings from the literature and our own laboratory on the decreased PON1 activity in renal failure, the mechanisms proposed and the effect of interventions. In addition to profound alterations in lipoproteins, reduced serum PON1 activity has been clearly established in the past decade and could contribute to accelerated development of atherosclerosis in ESRD and in HD. PON1 lactonase activity is lower in ESRD patients. Hemodialysis partially restores PON1 lactonase and the other activities. PON1 activity recovery after dialysis suggests that uremic toxins may play a mechanistic role in PON1 inactivation. Lower PON1 activity in CRF patients is associated with low thiol concentration, high CRP, and is beneficially enhanced with vitamin C and flavonoids. Changes in HDL subclasses, namely lower HDL(3) in these patients may also play a role in PON1 lower activity. Future research should focus on: (1) mechanistic studies on causes for low PON1 activity and mass; (2) prospective studies focusing on whether there is an added predictive value in measuring PON1 activity (and PON1 activity in HDL(3)) in this patient population; (3) intervention studies attempting to increase PON1 activity.