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High-risk coronary plaques have certain morphological characteristics. Thus, comprehensive assessment is needed for the risk stratification of plaques in patients with coronary artery disease. Integrated backscatter intravascular ultrasound (IB-IVUS) has been used successfully used to evaluate the tissue characteristics of coronary plaques; however, the mechanical properties of plaques have been rarely assessed. Therefore, we developed Speckle-tracking IVUS (ST-IVUS) to evaluate the mechanical properties of coronary plaque. This study aimed to evaluate the relation between the tissue characteristics of coronary plaques using IB-IVUS and their mechanical properties using ST-IVUS. We evaluated 95 non-targeted plaques in 95 patients undergoing elective percutaneous coronary intervention to the left anterior descending artery. We set regions of interest (ROIs) in the cross-sectional images of coronary plaques where we divided 120 degree plaques into four quadrants (every 30 degrees), with the center at the area of maximum atheroma thickness. We measured relative calcification area (%CA, relative fibrous area (%FI) and relative lipid pool area (%LP) in a total of 380 ROIs. In ST-IVUS analysis, we measured strain in the circumferential direction of the lumen area (LA strain: %), the external elastic membrane area strain (EEM strain: %), and strain in the radial direction (radial strain: %). On global cross-sectional area IB-IVUS analysis, the %CA was 1.2 ± 1.2%; the %FI was 49.0 ± 15.9%, and the %LP was 49.7 ± 16.5%. In ST-IVUS analysis, the LA strain was 0.67 ± 0.43%; the EEM strain was 0.49 ± 0.33%, and the radial strain was 2.02 ± 1.66%. On regional analysis, the %LP was not associated with the LA strain (r = - 0.002 p = 0.97), the EEM strain (r = - 0.05 p = 0.35), or with the radial strain (r = - 0.04 p = 0.45). These trends were seen between the %FI and the LA strain (r = 0.02 p = 0.74), the %FI and the EEM strain (r = 0.05 p = 0.35), and the %FI and the radial strain (r = 0.04 p = 0.50). A significant correlation was only observed between the %CA and the LA strain (r = - 0.15 p = 0.0038). Our findings indicate that the associations between mechanical properties and tissue characteristics lacked statistical significance, more often than not, and that it is necessary to evaluate the mechanical properties as well as plaque characteristics for risk stratification of coronary plaques.

Background: The impact of real-time remote cardiac rehabilitation (CR) on health and disability-related outcomes and its correlation with physical function are unknown. We compared the effectiveness of real-time remote CR to that of hospital-based CR on the physical function improvement as well as physical functions of improvement (Δ) to clarify the relationship to health and disability for baseline.Methods: Patients with cardiovascular disease (CVD) were enrolled (n=38) in this quasi-randomized controlled trial and underwent 4 weeks of hospital-based CR, followed by 12 weeks of remote or hospital-based CR, based on quasi-randomized allocation. Patients were assessed at baseline and after 12 weeks of remote or hospital-based CR using the shortened version of the World Health Organization (WHO) Quality of Life scale (WHOQOL-BREF) for subjective satisfaction, WHO Disability Assessment Schedule (WHODAS2.0-J) for objective performance, and cardiopulmonary exercise test for physical function and peak oxygen uptake (peak VO2). The trends in measured variables from baseline to the post-CR stage were analyzed. Results: Sixteen patients (mean age, 72.2±10.4 years) completed remote CR, and 15 patients (mean age, 77.3±4.8 years) completed hospital-based CR. The post-CR physical function differed significantly between groups (Δpeak VO2, 2.8±3.0 versus 0.84±1.8 mL·min-1·kg-1; ppeak VO2 (remote CR r2=0.65, p2=0.38, ppeak VO2 (r2=0.38, pConclusions: Remote CR significantly improved physical function and objective performance in patients with CVD. Remote CR could be an effective treatment for stable patients who are unable to visit hospitals.Trial Registration: This interventional trial was registered in the UMIN-CTR registry (trial title: Development of remote program for cardiac rehabilitation using wearable electrocardiograph; trial ID: UMIN000041746; trial URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046564; registration date: 2020/09/09).

Tissue characterization plays an important role in the development of acute coronary syndromes. iMap is an intravascular ultrasound (IVUS) tissue characterization system that provides useful information by reconstructing color-coded maps. Mechanical properties due to dynamic mechanical stress during a cardiac cycle may also trigger vulnerable plaque. Speckle tracking IVUS (ST-IVUS) has been introduced to observe plaque behavior in relation to mechanical properties. We report the case of an 84-year-old woman with stable coronary artery disease who underwent percutaneous coronary intervention, at which time IVUS demonstrated mainly three low echoic areas like lipid pools with thick fibrous caps. Pathological evaluation with iMap revealed that one low echoic area was occupied with necrotic tissue and that the other two areas occupied fibrotic. Although those tissue characterizations were different, they showed similar stretching behavior at systole by ST-IVUS which depicted plaque behavior from IVUS images using a color mapping. The mechanical properties of individual coronary plaques may differ depending on the tissue disposition. It is necessary to consider mechanical properties using ST-IVUS as well as to evaluate tissue characterization in plaque risk stratification.

Background Effects of sodium‐glucose cotransporter 2 inhibitors on reducing hospitalization for heart failure have been reported in randomized controlled trials, but their effects on patients with heart failure with preserved ejection fraction ( HF p EF ) are unknown. This study aimed to evaluate the drug efficacy of luseogliflozin, a sodium‐glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus and HF p EF . Methods and Results We performed a multicenter, open‐label, randomized, controlled trial for comparing luseogliflozin 2.5 mg once daily with voglibose 0.2 mg 3 times daily in patients with type 2 diabetes mellitus suffering from HF p EF (left ventricular ejection fraction >45% and BNP [B‐type natriuretic peptide] concentrations ≥35 pg/mL) in a 1:1 randomization fashion. The primary outcome was the difference from baseline in BNP levels after 12 weeks of treatment between the 2 drugs. A total of 173 patients with diabetes mellitus and HF p EF were included. Of these, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in BNP concentrations after 12 weeks from baseline between the 2 groups. The ratio of the mean BNP value at week 12 to the baseline value was 0.79 in the luseogliflozin group and 0.87 in the voglibose group (percent change, −9.0% versus −1.9%; ratio of change with luseogliflozin versus voglibose, 0.93; 95% CI, 0.78–1.10; P =0.26). Conclusion In patients with type 2 diabetes mellitus and HF p EF , there is no significant difference in the degree of reduction in BNP concentrations after 12 weeks between luseogliflozin and voglibose. Registration URL : https://www.umin.ac.jp/ctr/index.htm ; Unique identifier: UMIN 000018395.

Visit-to-visit variability in systolic blood pressure (VVV-SBP) has been associated with increased cardiac events. Hence, volume analysis by two-dimensional speckle-tracking echocardiography (2-DSTE) allows physicians to easily measure phasic left atrial (LA) function. However, the relationship of VVV-SBP and functional deformation of the left atrium with patients’ clinical outcome is unclear. The aim of the study was to investigate the relationship between phasic LA function and VVV-SBP. The subjects were 70 male participants in whom 2-DSTE was performed to measure blood pressure at health check-ups every year for 5 years. The standard deviation of systolic blood pressure (SBP) was calculated to assess VVV-SBP. The average SBP (Ave-SBP) was also assessed. Total emptying function (EF) (reservoir function), passive EF (conduit function), and active EF (booster pump function) of the left atrium were calculated to evaluate phasic LA function by 2-DSTE. The Pearson correlation, simple regression analysis, and multivariate logistic regression analysis were used in data analysis. Participants’ mean age was 50 ± 10 years, and 16 participants had hypertension. VVV-SBP correlated with total EF (r = – 0.30, p = 0.014) and active EF (r = – 0.35, p = 0.003). There was no correlation between the standard deviation of SBP and passive EF (r = – 0.10, p = 0.39). Ave-SBP had no significant relationship with total EF (r = – 0.06, p = 0.62), passive EF (r = – 0.08, p = 0.50), or active EF (r = – 0.03, p = 0.78). Active EF was also associated with VVV-SBP in multiple regression analysis. The active EF was significantly decreased in the highest quartile of VVV-SBP. Despite the small sample size of our study, the VVV-SBP showed a relationship with the phasic LA function. Our findings suggest that high VVV-SBP is noted to be associated with cardiovascular risk including a deterioration of LA function in clinical practice.

著者人数: 102名（所属. 宇宙航空研究開発機構宇宙科学研究所 (JAXA)(ISAS): 松岡, 彩子; 篠原, 育; 浅村, 和史), Accepted: 2018-12-29, 資料番号: SA1180350000

The primary symptom of ischemic heart disease is typically chest pain, but in some cases, this pain may radiate to the maxillofacial region. This article describes the case of a 44-year-old man with orofacial pain of cardiac origin. The patient was suspected to be suffering from cardiac disease by the oral and maxillofacial surgeon and was referred to a cardiologist, where he received a heart examination. The patient was diagnosed by means of cardiac catheterization as having coronary spastic angina. During catheterization, intracoronary ergonovine maleate induced orofacial pain that was almost the same in character and intensity as the patient's first episode. The orofacial pain was considered to be telalgia from coronary spastic angina. The patient started medication on the same day as the diagnosis. There was no recurrence of any symptoms. These findings indicate that in such cases, the dentist may contribute to identifying ischemic heart disease and should refer the patient to a cardiologist.

Integrated backscatter intravascular ultrasound (IB-IVUS) is a useful method for analyzing coronary plaque tissue. We evaluated whether tissue composition determined using IB-IVUS is associated with the progression of stenosis in coronary angiography. Sixty-three nontarget coronary lesions in 63 patients with stable angina were evaluated using conventional IVUS and IB-IVUS. IB-IVUS images were analyzed at 1-mm intervals for a length of 10 mm. After calculating the relative areas of the tissue components using the IB-IVUS system, fibrous volume (FV) and lipid volume (LV) were calculated through integration of the slices, after which percentages of per-plaque volume (%FV/PV, %LV/PV) and per-vessel volume (%FV/VV, %LV/VV) were calculated. Progression of coronary stenosis was interpreted from the increase in percent diameter stenosis (%DS) from baseline to the follow-up period (6-9 months) using quantitative coronary angiography. %DS was 24.1 ± 12.8 % at baseline and 23.2 ± 13.7 % at follow-up. Using IB-IVUS, LV was 31.7 ± 10.5 mm(3), and %LV/PV and %LV/VV were 45.6 ± 10.3 % and 20.2 ± 6.0 %, respectively. FV, %FV/PV, and %FV/VV were 35.5 ± 12.1 mm(3), 52.1 ± 9.5 %, and 23.4 ± 7.1 %, respectively. The change in %DS was -0.88 ± 7.25 % and correlated closely with %LV/VV (r = 0.27, P = 0.03) on simple regression. Multivariate regression after adjustment for potentially confounding risk factors showed %LV/VV to be correlated independently with changes in %DS (r = 0.42, P = 0.02). Logistic regression analysis after adjusting for confounding coronary risk factors showed LV (odds ratio 1.08; 95 % confidence interval 1.01-1.16; P = 0.03) and %LV/VV (odds ratio 1.13; 95 % confidence interval 1.01-1.28; P = 0.03) to be independent predictors of the progression of angiographic coronary stenosis. Our findings suggest that angiographic luminal narrowing of the coronary artery is likely associated with tissue characteristics. IB-IVUS may provide information about the natural progression of luminal narrowing in coronary stenosis.

The aim of this retrospective case series report is to evaluate systemic methotrexate therapy in conjunction with uterine artery embolization (UAE) in the conservative management of cervical pregnancy. We examined clinical presentations, treatments, and therapeutic outcomes in fifteen patients with a cervical pregnancy who wished for preservation of fertility, treated at Okayama University Hospital between 1998 and 2012. Twelve patients received systemic methotrexate including five treated with UAE. One was treated with UAE alone. Two patients received neither UAE nor methotrexate because of a low human chorionic gonadotropin (hCG) level and poor blood flow around the gestational sac (GS). An increased GS size and the elevated hCG level during methotrexate therapy might be risk factors for emergent UAE. Two of six patients treated with UAE had subsequent confirmed viable pregnancies. In patients with a cervical pregnancy, methotrexate therapy in combination with UAE can be considered as an option before performing a hysterectomy with suitable counseling about the risk of loss of fertility. Careful observation of the GS size and hCG level during methotrexate therapy might be important for management.

Preeclampsia may be due to an excess of circulating anti-angiogenic growth factors derived from the placenta, but metabolic syndrome-like disorders may also set off a cascade of placental and systemic inflammation and oxidative stress. We present a case of severe superimposed preeclampsia with obesity, diabetes and a mild imbalance of angiogenic factors, in which diet therapy ameliorated the preeclamptic signs while improving the adiponectin level. A 41-year-old pregnant woman with obesity and diabetes was referred to our hospital because of severe proteinuria and hypertension at 22 weeks of gestation. After administration of insulin and hydralazine with diet therapy, her hypertension and proteinuria were ameliorated with a 15-kg weight loss. Her adiponectin level was low and her leptin level was high, but her angiogenic factor levels were within the normal ranges for pregnant women at admission. The diet therapy ameliorated her hypertension and proteinuria while improving her adiponectin level as she achieved weight loss. This case suggests that diet therapy for obese preeclampsia patients with a mild imbalance of anti-and pro-angiogenic factors may play an important role in managing preeclampsia. Measurements of maternal adipocytokines and angiogenic factors may be important to distinguish the main cause of preeclampsia, i.e., poor placentation or maternal constitutional factors, for managing preeclampsia in patients with obesity.

Background: It has been reported that the morbidity rate of vasospastic angina is higher in Japan compared to western countries, and its prognosis has already been reported. However, the prognosis of vasospastic angina in relation to coronary angiographic findings, prognostic risk factors and treatment has not yet been fully investigated. Methods and results: From January 2000 to October 2005, 1047 patients with va-sospastic angina diagnosed by coronary angiography at Gifu University Hospital and related hospitals were registered in a cohort study (follow-up rate: 91.4 %, median follow-up duration: 3.8 years). The presence of coronary artery stenosis, diabetes mellitus, total spasm, and age of more than 65 years had a negative prognostic impact on cardiovascular events. Patients were treated with calcium channel blockers such as diltiazem (CAS 33286-22-5, CAS 42399-41-7), am-lodipine (CAS 111470-99-6), nifedipine (CAS 21829-25-4), and benidipine (CAS 91599-74-5). Among these calcium channel blockers, when patient background was matched by the propensity score in patients treated with calcium channel blockers only, the cardiovascular event rate was significantly lower in the benid-ipine group than in the diltiazem group. Conclusion: The study demonstrated for the first time that total spasm is a risk factor, independent of other factors, for cardiovascular events in patients with va-sospastic angina. Treatment with benid-ipine showed a better prognosis than that with diltiazem.

SummaryBackgroundTissue characteristics of coronary plaques can be evaluated using integrated backscatter intravascular ultrasound (IB-IVUS), while fractional flow reserve (FFRmyo) is an index of functional coronary stenosis. We assessed the relation between functional stenosis and the characteristics of plaque tissue using FFRmyo and IB-IVUS.Methods and resultsA total of 17 lesions with 75%-stenosis assessed visually by coronary angiography from 17 stable angina patients (64.2±9.1 years old, 11 males) were studied. IB-IVUS was evaluated in the most stenotic cross-sectional area. Using commercially available software, coronary plaques were assessed for calcification (CA), fibrosis (F), and lipid pool (LP). Lesions were localized in the left anterior descending artery in 11 patients, the left circumflex in 3, and the right coronary artery in 3. On quantitative coronary angiography, the percent diameter stenosis (%DS) was 60.5±7.3%. Plaque burden was 71.4±9.1%, FFRmyo was 0.74±0.13. The tissue component of the plaques was: CA(%), 3.0±2.4%; F(%), 60.5±9.6%; LP(%), 37.2±11.0%. Significant correlation was not observed between %DS or plaque burden and FFRmyo, structural stenosis and plaque characterization, nor between CA(%) and FFRmyo. There was a positive correlation between F(%) and FFRmyo (r=0.62, p

Please cite this paper as: Masuyama H, Segawa T, Sumida Y, Masumoto A, Inoue S, Akahori Y, Hiramatsu Y. Different profiles of circulating angiogenic factors and adipocytokines between early- and late-onset pre-eclampsia. BJOG 2010;117:314–320. Objective Circulating angiogenic factors have been shown to be important in the pathophysiology of pre-eclampsia. Blood levels of adipocytokines differ in pre-eclampsia relative to controls and may also play an important role in disease pathogenesis. Differences in the circulating levels of these molecules were compared between matched normotensive controls and women with pre-eclampsia with onset before or at/after 32 weeks, and according to whether the women were of normal weight (18.5

SummaryObjectivesTreatment of mitral valve stenosis with catheter balloon commissurotomy (CBC) yields acceptable immediate results even when one commissure shows calcification. However, the long-term outcomes in such cases remain unclear.MethodsWe examined the immediate and long-term (mean: 11±5 years) outcomes of 57 patients who underwent 58 CBC procedures. Patients were classified into group A (no commissural calcification, n=44) or group B (unilateral commissural calcification, n=13). From the appearance of the mitral valve just after CBC, commissurotomy was judged to be bilateral, incomplete, or excessive. End points were death, recurrence of congestive heart failure necessitating hospitalization, embolism, repeat CBC, or mitral valve replacement.ResultsThere were significant numbers of unfavorable mitral valve morphologies evaluated according to Sellors classification, estimated by echocardiograms; Sellors class I: 20 patients in group A vs. none in group B (p

Because mitochondria play pivotal roles in both insulin secretion from the pancreatic beta cells and insulin resistance of skeletal muscles, we performed a large-scale association study to identify mitochondrial haplogroups that may confer resistance against or susceptibility to type 2 diabetes mellitus (T2DM). The study population comprised 2,906 unrelated Japanese individuals, including 1,289 patients with T2DM and 1,617 controls, and 1,365 unrelated Korean individuals, including 732 patients with T2DM and 633 controls. The genotypes for 25 polymorphisms in the coding region of the mitochondrial genome were determined, and the haplotypes were classified into 10 major haplogroups (i.e., F, B, A, N9a, M7a, M7b, G, D4a, D4b, and D5). Multivariate logistic-regression analysis with adjustment for age and sex revealed that the mitochondrial haplogroup N9a was significantly associated with resistance against T2DM (P=.0002) with an odds ratio of 0.55 (95% confidence interval 0.40-0.75). Even in the modern environment, which is often characterized by satiety and physical inactivity, this haplogroup might confer resistance against T2DM.

Mitochondrion-derived reactive oxygen species possibly play an important role in the pathogenesis of atherosclerosis and atherothrombotic cerebral infarction, because mitochondria in vascular endothelial cells are the major site of superoxide production. In the present study, we surveyed mitochondrial haplogroups associated with atherothrombotic cerebral infarction in 1081 Japanese subjects. Twenty-six mitochondrial single nucleotide polymorphisms of 11 major mitochondrial haplogroups (F, B, A, N9a, M7a, M7b, M7c, G1, G2, D4, and D5) were determined by use of 28-plex PCR and fluorescent beads combined with sequence-specific oligonucleotide probes. Multivariate logistic regression analysis with adjustment for conventional risk factors revealed that mitochondrial haplogroup A was associated with atherothrombotic cerebral infarction in female subjects (P

This paper reviews nonhydrostatic atmospheric models for research and NWP. Classification of nonhydrostatic atmospheric models and numerical methods to treat sound waves are described with their relative advantages. The current operational nonhydrostatic NWP models at various forecast centers and community nonhydrostatic models for research are reviewed. Brief history and development of the JMA nonhydrostatic model, a community mesoscale model for research and NWP in Japan, is introduced. Current status and near future plans of the operational nonhydrostatic mesoscale model at JMA are presented.

Although genetic epidemiologic studies have suggested that several genetic variants increase the risk for hypertension, the genes that underlie genetic susceptibility to this condition remain to be identified definitively. We have now performed a large-scale association study to identify gene polymorphisms for reliable assessment of the genetic component of hypertension.The study population comprised 4853 unrelated Japanese individuals, including 2818 subjects with hypertension (1677 men, 1141 women) and 2035 controls (1011 men, 1024 women). The genotypes for 150 polymorphisms of 128 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology.Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking revealed that four polymorphisms (1648G--A in ITGA2, -30G--A in GCK, A--G in SAH, and 1117C--A in PTGIS) were significantly (P.01) associated with hypertension. A stepwise forward selection procedure demonstrated that ITGA2, GCK, and PTGIS genotypes significantly affected the prevalence of hypertension. Combined genotype analysis of these polymorphisms yielded a lowest odds ratio of 0.47 for the genotypes of AA or AG for ITGA2, GA or AA for GCK, and CC for PTGIS, which were present in 1.1% and 2.0% of hypertensive and control individuals, respectively.These results suggest that the genotypes for ITGA2, GCK, and PTGIS may prove reliable for the assessment of the genetic component of hypertension. Determination of the combined genotypes for these genes may contribute to personalized prevention of this condition.

Superoxide, which mitochondria mainly produce in vascular endothelial cells, plays an important role in the pathogenesis of atherosclerosis and coronary artery disease. Accordingly, mitochondrial functional differences are thought to be one of the most important factors for the risk of myocardial infarction among various individuals. In the present study, we surveyed mitochondrial haplogroups associated with myocardial infarction in Japanese subjects. The study population comprised 2,137 unrelated Japanese individuals, including 1,181 subjects with a first myocardial infarction (920 males, 261 females) and the control subjects (522 males, 434 females). Twenty-eight mitochondrial single nucleotide polymorphisms of 12 major mitochondrial haplogroups (A, B, D4, D5, F, G1, G2, M7a, M7b, M7c, N9a, and N9b) were determined by use of 28-plex PCR and fluorescent beads combined with sequence-specific oligonucleotide probes. After adjustment for age, sex, body mass index, and prevalence of smoking, hypertension, hypercholesterolemia, and type 2 diabetes, a significantly (P = 0.0019) lower prevalence of haplogroup N9b was detected in subjects with myocardial infarction than in the controls. Especially, the prevalence of this haplogroup was significantly lower (P = 0.0007) in the male subjects with the disease than in the male controls. In contrast, there were trends towards higher prevalence of the disease in haplogroup G1 for males (P < 0.05). No significant haplogroup-related associations were detected for females. Our data suggest that haplogroup N9b confers resistance against myocardial infarction in Japanese males.

Objective— We performed an association study to identify gene polymorphisms for assessing the genetic risk of ischemic or hemorrhagic stroke. Methods and Results— The study population comprised 3151 unrelated Japanese individuals: 1141 stroke patients (636 with atherothrombotic cerebral infarction, 282 with intracerebral hemorrhage, and 223 with subarachnoid hemorrhage) and 2010 controls. The genotypes for 202 polymorphisms of 152 genes were determined by suspension array technology. Multivariable logistic regression analysis with adjustment for conventional risk factors revealed that the –572G→C polymorphism of the interleukin-6 (IL-6) gene ( IL6 ) was significantly ( P UCP3 ), the –863C→A polymorphism of the tumor necrosis factor (TNF) gene ( TNF ), and the G→A (Gly243Asp) polymorphism of the polycystic kidney disease 1–like gene ( PKD1-like ) were significantly associated with subarachnoid hemorrhage. Conclusions— IL6 genotype may be useful in assessing the genetic risk for atherothrombotic cerebral infarction and intracerebral hemorrhage, and genotypes for UCP3 , TNF , and PKD1-like may be similarly beneficial in assessment of the risk for subarachnoid hemorrhage. Validation of our findings will require additional studies with independent subject panels.

SummaryAlthough lifestyle and environmental factors influence the prevalence of myocardial infarction, genetic epidemiological studies have suggested that several genetic variants increase the risk for this condition. We have performeda large-scale association study to identify gene polymorphisms for reliable assessment of the genetic risk of myocardial infarction. The study population comprised 3,483 unrelated Japanese individuals (1,913 men; 1,570 women), including 1,192 subjects with myocardial infarction and 2,291 controls. The genotypes for 164 polymorphisms of 137 candidate genes were determined with an oligonucleotide ligation assay based on analysis of fluorescent microspheres with suspension array technology. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hypercholesterolemia revealed that the 677C→T (Ala222Val) polymorphism of MTHFR, the 1595C→G (Ser447Stop) polymorphism of LPL, and the –108/3G→4G polymorphism of IPF1 were significantly associated with the prevalence of myocardial infarction. A stepwise forward selection procedure demonstrated that IPF1, MTHFR, and LPL genotypes significantly affected the prevalence of myocardial infarction. Combined genotype analysis of these polymorphisms yieldeda maximum odds ratio of 2.54 for the combined genotype of TT for MTHFR,CC for LPL,and 3G3G for IPF1.The genotypes for MTHFR, LPL, and IPF1 may prove reliable for assessment of genetic risk for myocardial infarction. Determination of the combined genotype for these genes may contribute to primary, personalized prevention of this condition.

Simulations of the Northern Hemisphere ice sheet at the Last Glacial Maximum (LGM; 21 kyr BP) are performed using a high-resolution atmospheric general circulation model (AGCM) in order to re-evaluate the conventional surface temperature- or elevation-based parameterization. The influence of precipitation change on the steady-state topography of the Laurentide ice sheet at the LGM is estimated using an AGCM with a horizontal resolution of ∼1° and a three-dimensional thermomechanically coupled ice-sheet model. The ice volume estimated by the AGCM simulation is much larger than that indicated by the conventional parameterization. Through sensitivity analysis of the AGCM and ice-sheet model, it is found that the rate of precipitation change depends on the location of the ice sheet, and that the rate of precipitation change due to surface elevation change is higher than the rate unrelated to surface elevation change on the Laurentide ice sheet. The rate of precipitation is also shown to exhibit seasonality and regionality due to effects such as interior desertification and the concentration of storm tracks.

A patient with distal slow-flow after stenting in the old vein graft intervention was reported. This case is a first in whom guidewire-based serial measurement of pressure-derived fractional flow reserve (FFRmyo) and thermodilution-based coronary flow reserve (CFRthermo) clearly demonstrated the serial change of microvascular circulation. During slow-flow, CFRthermo remained in low value despite significant improvement of FFRmyo from 0.61 to 0.90. After thrombus aspiration and nicorandil injection, coronary flow reestablished immediately. CFRthermo improved significantly from 1.3 during slow-flow to 3.6 after restoration of flow. Catheter Cardiovasc Interv 2003;60:392–398. © 2003 Wiley-Liss, Inc.

The main aim of this study was to elucidate whether the beneficial effect of antecedent angina is a cellular protective effect or the result of an increase of collateral flow. Of 42 patients with angina who underwent percutaneous transluminal coronary angioplasty (PTCA) for proximal left anterior descending artery (LAD) stenosis, 22 had experienced antecedent anginal pain (AP) within 7 days prior to PTCA. 99mTc-sestamibi was injected during balloon inflation, and quantitative analysis of ischemic severity during coronary occlusion was calculated (SS). An electrocardiogram was recorded during ballooning to calculate the sum of ST elevation (ΣST). ΣST was significantly reduced in patients with AP compared with patients without AP (1.88±0.89 mV vs 1.18±0.74 mV, p=0.0088); however, no difference was observed in defect severity. A close correlation was observed between SS and ΣST in both groups. The multivariate regression model demonstrated that both a large SS (p

Background/aimsAge, proteinuria, metabolic syndrome, and hyperuricemia are the reported risk factors for chronic kidney disease (CKD) and cardiovascular disease (CVD). However, the best predictor of changes in renal function in the early stages of renal disease in a healthy middle-aged population is still unknown. Our study evaluated the correlation between changes in renal function and common risk factors to determine such a predictor.MethodsIn total, 2,853 healthy persons aged ≤50 years participated in the study. They had no proteinuria and were not on medications for hypertension, diabetes mellitus, hyperlipidemia, or hyperuricemia. Over 2 years, participants underwent annual health screening. The relationship between changes in estimated glomerular filtration rate (eGFR) and changes in risk factors for CKD was evaluated using univariate and multivariate linear regression analyses.ResultsOver 2 years, eGFR showed a significant decrease. Univariate regression analysis revealed that changes in fasting plasma glucose (FPG), total cholesterol, LDL-cholesterol, serum uric acid levels, and hemoglobin showed a significant negative correlation with changes in eGFR. Multiple regression analysis confirmed that changes in FPG, serum uric acid levels, in particular, and hemoglobin had a significant negative correlation with changes in eGFR.ConclusionThe changes in eGFR and other variables over 2 years were small and could be within expected biologic variation. A longer observational study is needed to elucidate whether FPG, serum uric acid and hemoglobin represent the earliest markers of eGFR decline.

OBJECTIVES This study focused on 1) the determination of the optimal preconditioning (PC) duration, and 2) the protective effect of nicorandil (NC), a hybrid nitrate with a K atp channel opening effect, during a percutaneous transluminal coronary angioplasty (PTCA) model in humans. BACKGROUND The ischemic PC effect is induced in 180 s ischemia, but not in 120 s ischemia in rabbit hearts. However, the duration of ischemia that induces PC effect and the role of the K atp channel in the PC effect in humans are still unclear. METHODS Forty-six patients with stable angina were randomly allocated to four groups: the duration of the first inflation as PC ischemia was 60 s in the PC60 group (n = 12), and 180 s in the PC180 group (n = 12). In the other groups, NC (80 μg/kg) was intravenously given for 1 min in the NC group (n = 12), and isosorbide dinitrate (ISDN) (40 μg/kg) was given in the ISDN group (n = 10). Five minutes after first inflation or drug administration, a second inflation was conducted for 120 s in each group. In the ECG, the lead with the largest shift in ST segment (deltaST max), and the sum of elevated ST levels in all leads (sigmaST) were determined. RESULTS In the PC60 group, no significant difference was observed in either deltaST max or sigmaST between the first and second inflation. However, the second inflation in the PC180 group showed significantly lower levels of deltaST max and sigmaST compared with those of the first inflation. In the NC group, both deltaST max and sigmaST measured at 30 s and 60 s after balloon inflation were significantly lower than those of the first inflation in the PC60 and PC180 control groups. In the ISDN group, no significant difference was observed in deltaST max or sigmaST. CONCLUSION In human PTCA models, a PC effect is observed in 180 s ischemia, but not in 60 s ischemia. A pharmacological PC effect is induced by NC, a K atp channel opener with a nitrate-like effect but not ISDN. This suggests that the opening of K atp channels plays an important role in the protecting effect of NC.

Background: Hemolytic disease of the fetus/newborn due to Jra immunization is very rare and considered to be mild, and only routine obstetrical care is recommended for pregnant women sensitized to the Jra antigen. Case Report: A 20-year-old nulliparous woman was referred to our hospital for perinatal management. Her indirect Coombs test was positive for anti-Jra antibody (1:64). At 33 weeks’ gestational age, we observed that fetal growth was mildly restricted and the peak systolic velocity of the fetal middle cerebral artery (PSV-MCA) was above the upper limit of the reference range (1.55 multiples of the median). Amniocentesis was also carried out and the ΔOD450 value was in the lower mid-zone of the Liley curve. We continued to carefully observe the patient because we observed PSV-MCA values within 1.50–1.60 multiples of the median and no other findings of fetal anemia. She vaginally delivered a female infant weighing 2,136 g at 37 weeks’ gestational age. The infant received treatment with both iron and recombinant erythropoietin without developing hyperbilirubinemia and blood transfusion. Conclusion: PSV-MCA should be monitored for the detection of fetal anemia, even in pregnant women sensitized to some antigens for which only routine obstetrical care is recommended.

Pregnancies after orthotropic liver transplantation (OLT) have demonstrated favorable perinatal outcomes. However, obstetrical complications in OLT recipients are more common than those in a normal population. In countries where the number of cadaveric donors is limited, living-related liver transplantation (LRLT) is a valuable procedure, but few pregnancies after LRLT have been reported.We present a case of a pregnant woman after LRLT who developed severe preeclampsia with fetal growth restriction (FGR), and a review of literature.A 34-year-old nulliparous woman was referred to our hospital as a LRLT recipient. She was admitted to our hospital at 25 weeks' gestational age as she had developed severe preeclampsia, although her liver function was stable and there were no episodes for rejection or cholestasis. Emergency cesarean section was performed at 28 weeks' gestational age because of FGR and non-reassuring fetal status. Although there is no Medline available report in English of a successful pregnancy after LRLT, there are 11 cases of successful pregnancies after LRLT in the Japanese literature. These cases suggested that the incidences of preeclampsia, FGR, preterm delivery and cesarean delivery in pregnancies after LRLT are similar to those after OLT, but liver dysfunction and/or cholestasis in pregnancies after LRTL might be more common compared with those after OLT.Careful observation is needed after LRLT and the potential for differences in risk with LRLT recipients in comparison to OLT recipients should be considered.

The Energization and Radiation in Geospace (ERG) project for solar cycle 24 will explore how relativistic electrons in the radiation belts are generated during space storms. This geospace exploration project consists of three research teams: the ERG satellite observation team, the ground-based network observation team, and the integrated data analysis/simulation team. Satellite observation will provide in situ measurements of features such as the plasma distribution function, electric and magnetic fields, and plasma waves, whereas remote sensing by ground-based observations using, for example, HF radars, magnetometers, optical instruments, and radio wave receivers will provide the global state of the geospace. Various kinds of data will be integrated and compared with numerical simulations for quantitative understanding. Such a synergetic approach is essential for comprehensive understanding of relativistic electron generation/loss processes through crossenergy and cross-regional coupling in which different plasma populations and regions are dynamically coupled with each other. In addition, the ERG satellite will utilize a new and innovative measurement technique for wave-particle interactions that can directly measure the energy exchange process between particles and plasma waves. In this paper, we briefly review some of the profound problems regarding relativistic electron accelerations and losses that will be solved by the ERG project, and we provide an overview of the project.

冠動脈石灰化と虚血性心疾患の関係は以前より報告がなされている. 今回, 我々は虚血性心疾患が疑われ冠動脈造影を施行した40名の維持透析患者と100名の非透析患者につき冠動脈石灰化と有意狭窄病変の関係につき検討した.維持透析患者群の72.5%が冠動脈石灰化を認め非透析患者群の37.5%に比して有意に頻度が高く (p

Emergency percutaneous cardiopulmonary bypass support (PCPS) was instituted in 3 patients with acute myocardial infarction in cardiac arrest refractory to conventional resuscitation measures. All had severe double or triple vessel disease. Percutaneous transluminal coronary angioplasty (PTCA) was performed in 1 patient, and PTCA and directional coronary atherectomy (DCA) were performed in the other 2 patients on combined intraaortic balloon pumping (IABP) and PCPS. Flow rates of 2 to 5 L/min were achieved, with restoration of mean arterial pressure to more than 60 mm Hg during PCPS. The status of all patients was improved hemodynamically with PCPS. One patient died of hemorrhage during PCPS. DCA was successfully performed in the other 2 patients, and PCPS and IABP was discontinued. Time on PCPS ranged from 10 h to 8 days. Time on IABP ranged from 10 days to 2 weeks. These 2 patients died of pneumonia or multiorgan failure after 1. 5 months. In conclusion, emergency PCPS is a powerful resuscitative tool that may stabilize the condition of patients in cardiac arrest to allow for definitive intervention.

血液透析患者のLp(a) リポタンパク (Lp(a)) は高値であることが知られており, Lp(a) のプラスミノーゲンとの構造的相同性から, 血液凝固・線溶系に対する影響が示唆されている. しかし透析患者における凝固・線溶系とLp(a) との関連性についての報告はほとんどみられない.我々は人間ドック受診コントロール群 (C群, n=40), 慢性糸球体腎炎による透析導入患者 (A1群, n=25), 糖尿病性腎症による透析導入患者 (A2群, n=15), さらに血液透析歴10年以上の維持透析患者 (B群, n=21) のそれぞれにおける血清Lp(a) および凝固・線溶系因子を測定し, その関連性について検討を加えた.C群に比較してLp(a) はA1群 (p

当院における維持血液透析患者59名 (男性32名, 女性27名, 平均年齢60.7歳, 平均透析期間4.9年) のHCV-RNAおよびそのgenotype, HCV抗体 (第二世代抗体, C100-3抗体, N14抗体, GOR抗体) を測定し, 年齢, 性, 基礎疾患, 透析歴, 輸血歴, 手術歴, 家族歴, 肝疾患の既往, 肝障害の有無, HBc抗体との関連について多変量解析を用いて検討した. HCV-RNA陽性率は初回測定では20.3% (12/59), 第二世代抗体陽性率は45.8% (27/59), C100-3抗体陽性率は16.9% (10/59), N14抗体陽性率は30.5% (18/59), GOR抗体陽性率は25.4% (15/59) であった. HCV-RNA陽性者はすべて第二世代抗体陽性であったが, その他の抗体は必ずしも陽性を示さなかったことより, HCV感染のスクリーニングには第二世代抗体が最も適切であると考えられた.また, このうち37名において6か月後に第二世代抗体とHCV-RNAの再検査を行ったところ, 第二世代抗体陽性, HCV-RNA陰性であった5名のHCV-RNAが陽性化し, HCV-RNAは時期をおいて複数回測定することが望ましいと考えられた. さらに, 第二世代抗体, HCV-RNAともに陰性より両指標とも陽性化を認め, 新規感染を疑わせる1例を経験した. この時点におけるHCV-RNA陽性者は17名であり, このうち測定し得たgenotypeはII型が12例, II+III型が1例, III型が2例であった.第二世代抗体陽性者は90%以上に輸血歴を認め, 透析期間も抗体陰性者に比して有意に長期であったが過去6か月間のGPT異常の頻度には有意差を認めなかった. 第二世代抗体陽性に関する多重ロジスチックモデルを用いた多変量解析では第一に透析歴が, 第二に輸血歴が有意に関与していた.以上から, 第二世代抗体によるスクリーニングおよびより注意深い観血的操作により, 水平感染を予防する必要があると考えられた.

Aim: To evaluate whether pregnant women with chronic kidney disease (CKD) adapt poorly to increases in renal blood flow. This can exacerbate renal function and impair perinatal outcome, as there is a major interplay between CKD and preeclampsia (PE). Methods: We analyzed the outcomes of 90 pregnant women with preexisting CKD. The estimated glomerular filtration rate (eGFR) was measured along with the levels of angiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor, which might act in the pathophysiology of PE. Results: In pregnancies with CKD, PE and preterm delivery were increased and the increased blood pressure worsened the perinatal outcomes much more than the increased proteinuria. All pregnancies with severe renal insufficiency were delivered preterm because of impaired renal function. The eGFR was correlated significantly with 24-hour creatinine clearance (r = 0.830). Significant differences in sFlt-1 and placental growth factor levels were found between severe PE without any complications and severe superimposed PE (p < 0.05), and between women with and without declining renal function in superimposed PE (p < 0.01). Conclusion: Pregnancies with CKD have a high risk of obstetrical complications. The eGFR might serve for evaluating renal function during pregnancy. Angiogenic factors might be potential markers for a differential diagnosis between PE and worsening renal function.

In anesthetized open-chest dogs, an intravenous bolus injection of endothelin-1 (ET-1, 400 pmol/kg) caused transient hypotension (initial hypotensive phase; phase 1), followed by a continuous elevation of blood pressure (late hypertensive phase; phase 2). The constriction and dilation of the systemic capacitance and resistance vessels were evaluated from the change in mean circulatory pressure (MCP) and in total peripheral resistance (TPR) in phases 1 and 2. To examine the modification of the action of ET-1 on the blood vessels by the baroceptor reflex or by the endothelium-derived relaxing factor (EDRF) released by ET-1 in phase 1, we performed experiments in dogs under total spinal anesthesia (TSA group), methylene blue-treated dogs (MB group) as well as in the untreated dogs (control group). ET-1 decreased the TPR significantly, and increased the MCP significantly in phase 1 in the control (n = 8) and TSA (n = 8) groups; there was no difference between the groups. ET-1 had no significant effect on TPR but increased the MCP significantly in MB group (n = 8) during phase 1. The percentage increase of MCP in the MB group significantly exceeded that of the control group. ET-1 increased both the TPR and MCP significantly in phase 2 in the control group (n = 8). This study indicated that the vasoconstrictor action of ET-1 on the systemic capacitance vessels in phase 1 did not result from a baroceptor reflex, and that the vasodilator action of ET-1 on the systemic resistance vessels may be at least in part mediated via EDRF released by ET-1. We suggest that the vasoconstrictor action of ET-1 on the systemic capacitance vessels is strong, but the vasodilator action of EDRF on the systemic capacitance vessels is weak.

Background: Some stable angina patients with significant coronary function have low exercise capacity, whereas some have high exercise capacity. The aim of the present study was to determine whether coronary pressure-derived fractional flow reserve (FFRmyo), a functional index of coronary stenosis, is a better indicator of exercise capacity than angiographic stenosis. Methods and Results: The 15 male (65.8 ±8.9 years old) subjects with stable angina and 75% angiographic stenosis underwent a cardiopulmonary exercise test (CPX), and peak oxygen uptake (PeakVO2) and oxygen uptake at anaerobic threshold (AT) were measured. The relationship between FFRmyo and CPX values was assessed. The left anterior descending artery was affected in 8 patients, the left circumflex artery in 5, and the right coronary artery in 2. Percent diameter stenosis (%DS) was 61.7 ±9.1% by quantitative coronary angiography. Mean FFRmyo, PeakVO2, and AT was 0.84 ±0.66, 17.1 ±3.2 ml · kg-1 · min-1, and 11.1 ±2.0 ml · kg-1 · min-1, respectively. There was no significant correlation between %DS and FFRmyo, PeakVO2, or AT (r=0.12, 0.051, and 0.013, respectively; P=NS), but FFRmyo had a significant positive correlation with PeakVO2 and AT (r=0.534 and 0.542, respectively; P

Hemolytic disease of the fetus/newborn due to Jr(a) immunization is very rare and considered to be mild, and only routine obstetrical care is recommended for pregnant women sensitized to the Jr(a) antigen.A 20-year-old nulliparous woman was referred to our hospital for perinatal management. Her indirect Coombs test was positive for anti-Jr(a) antibody (1:64). At 33 weeks' gestational age, we observed that fetal growth was mildly restricted and the peak systolic velocity of the fetal middle cerebral artery (PSV-MCA) was above the upper limit of the reference range (1.55 multiples of the median). Amniocentesis was also carried out and the DeltaOD450 value was in the lower mid-zone of the Liley curve. We continued to carefully observe the patient because we observed PSV-MCA values within 1.50-1.60 multiples of the median and no other findings of fetal anemia. She vaginally delivered a female infant weighing 2,136 g at 37 weeks' gestational age. The infant received treatment with both iron and recombinant erythropoietin without developing hyperbilirubinemia and blood transfusion.PSV-MCA should be monitored for the detection of fetal anemia, even in pregnant women sensitized to some antigens for which only routine obstetrical care is recommended.

[1] Orbital forcing is a major driver of climate variability on timescales of 10,000 to 100,000 years. Changes in the orbital parameters cause variations in the length of the seasons by several days. Consequently, models using a fixed present-day calendar result in biased paleoseasons, especially in boreal autumn when the vernal equinox is used as an anchor point. The bias is estimated for temperatures and precipitation in a transient model simulation over the last 21,000 years and an accelerated simulation over the last 129,000 years. The largest differences of up to 4 K occur over the continents in high latitudes. Precipitation estimates are mostly affected in the low latitudes. The time-dependent bias is large enough to modify the temporal characteristics of temperature and precipitation indices. It is discussed to what extent the bias in one season is distorting comparisons between models and paleoproxies. The bias has minor implications for proxy-model comparisons in general. However, proxies of monsoon activity should be compared with fixed angular seasons. For process studies and climate sensitivity studies the use of fixed angular seasons is imperative.

The effect of a strong, lipophilic statin (pitavastatin) on the thoracic aorta has not yet been elucidated. The purpose of the present study was to evaluate the effects of pitavastatin (P) therapy on plaque components and morphology in the thoracic aorta by transesophageal echocardiography (TEE) and clarify the impact of the therapy on media and intima in patients with hypercholesterolemia. Sixty-four media and 64 intima of the thoracic aorta were investigated in 32 patients with hypercholesterolemia. The corrected integrated backscatter (c-IBS) values in the thoracic aortic wall and intima-media thickness (IMT) at the same site were measured before and after P therapy or diet (D) for 7 mo. Moreover, c-IBS values in media were measured in 168 patients without hypercholesterolemia to estimate age-dependent changes. C-IBS values in media were correlated with age (r = 0.84, p0.001). C-IBS and IMT of media in the P group significantly decreased from -17.8 +/- 2.4 to -20.1 +/- 3.7 dB and from 1.7 +/- 0.3 to 1.5 +/- 0.3 mm, respectively (p0.001), whereas those in the D group significantly increased from -18.3 +/- 2.0 to -16.7 +/- 2.1 dB and from 1.6 +/- 0.3 to 1.7 +/- 0.2 mm, respectively (p0.001). IMT in intima in the P group significantly decreased from 3.7 +/- 0.4 to 3.3 +/- 0.4 mm (p0.001). C-IBS in intima in the P group significantly increased from -10.2 +/- 2.2 to -6.9 +/- 1.7 dB, which indicated plaque stabilization. Pitavastatin improved the atherosis measured by IMT and sclerosis measured by c-IBS values in the media and induced stabilization and regression of plaques in the intima of the thoracic aorta.

It has been reported that the morbidity rate of vasospastic angina is higher in Japan compared to western countries, and its prognosis has already been reported. However, the prognosis of vasospastic angina in relation to coronary angiographic findings, prognostic risk factors and treatment has not yet been fully investigated.From January 2000 to October 2005, 1047 patients with vasospastic angina diagnosed by coronary angiography at Gifu University Hospital and related hospitals were registered in a cohort study (follow-up rate: 91.4%, median follow-up duration: 3.8 years). The presence of coronary artery stenosis, diabetes mellitus, total spasm, and age of more than 65 years had a negative prognostic impact on cardiovascular events. Patients were treated with calcium channel blockers such as diltiazem (CAS 33286-22-5, CAS 42399-41-7), amlodipine (CAS 111470-99-6), nifedipine (CAS 21829-25-4), and benidipine (CAS 91599-74-5). Among these calcium channel blockers, when patient background was matched by the propensity score in patients treated with calcium channel blockers only, the cardiovascular event rate was significantly lower in the benidipine group than in the diltiazem group.The study demonstrated for the first time that total spasm is a risk factor, independent of other factors, for cardiovascular events in patients with vasospastic angina. Treatment with benidipine showed a better prognosis than that with diltiazem.

Introduction. Hypertriglyceridemia is an important risk factor for coronary heart disease. The purpose of the present study was to identify gene polymorphisms associated with hypertriglyceridemia (serum triglyceride concentration, ≥1.65 mmol/L) for assessment of the genetic risk for this condition. Methods. A total of 5206 individuals from two independent populations was examined: Subject panel A comprised 3787 individuals who either visited outpatient clinics of or were admitted to the participating hospitals because of various symptoms or for a health checkup; subject panel B comprised 1419 community-dwelling elderly individuals. The genotypes for 100 polymorphisms of 65 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Given the multiple comparisons of genotypes with hypertriglyceridemia, we adopted the criterion of a false discovery rate (FDR) of Results. Evaluation of genotype distributions by the chi-square test and subsequent multivariable logistic regression analysis with adjustment for age and sex revealed that seven polymorphisms [−1131T→ C, −3A→G, and 553G→T (Gly185Cys) of APOA5 ; 1100C→T of APOC3 ; 85T→C of APOA1 ; 41A→G (Glu14Gly) of ACAT2 ; C→G (Ser47Stop) of LPL ] were significantly (FDR < 0.05) associated with hypertriglyceridemia in subject panel A. To validate these associations, we examined the same polymorphisms in subject panel B. The six polymorphisms of APOA5 , APOC3 , APOA1 , and LPL , but not that of ACAT2 , were again significantly associated with hypertriglyceridemia. Serum triglyceride concentrations differed significantly ( P< 0.05, ANOVA) among genotypes of each of these six polymorphisms in both subject panels. The three polymorphisms of APOA5 were in linkage disequilibrium. Conclusions. Polymorphisms of APOA5 , APOC3 , APOA1 , and LPL are determinants of hypertriglyceridemia. Genotyping of these polymorphisms may prove informative for assessment of the genetic risk for hypertriglyceridemia and may contribute to the personalized prevention of this condition.

Introduction. A low serum concentration of HDL-cholesterol and a high serum concentration of LDL-cholesterol are risk factors for atherosclerosis. Our goal was to identify genetic variants that confer susceptibility to a low serum concentration of HDL-cholesterol ( Methods. A total of 5213 individuals from two independent populations was examined: Subject panel A comprised 3794 individuals who either visited outpatient clinics of or were admitted to the participating hospitals because of various symptoms or for a health checkup; subject panel B comprised 1419 community-dwelling elderly individuals. The genotypes for 100 polymorphisms of 65 candidate genes were determined. Given the multiple comparisons of genotypes with these conditions, we adopted the criterion of a false discovery rate (FDR) of Results. Examination of genotype distributions by the chi-square test and subsequent multivariable logistic regression analysis with adjustment for age and sex revealed that six [−1131T→C, −3A→G, and 553G→T (Gly185Cys) of APOA5 ; −250G→A and −515C→T of LIPC ; 13989A→G (Ile119Val) of CYP3A4 ] and three [4070C→T (Arg158Cys) and 3932T→C (Cys112Arg) of APOE ; 190G→A (Val64Ile) of CCR2 ] polymorphisms were significantly (FDR < 0.05) associated with low HDL-cholesterol and high LDL-cholesterol, respectively, in subject panel A. To validate these associations, we examined the same polymorphisms in subject panel B. The three polymorphisms of APOA5 and two polymorphisms of APOE were significantly associated with low HDL-cholesterol and high LDL-cholesterol, respectively. The serum concentrations of HDL-cholesterol and LDL-cholesterol differed significantly ( P < 0.01, ANOVA) among genotypes of the corresponding polymorphisms in both subject panels. The polymorphisms of APOA5 and APOE were each in linkage disequilibrium. Conclusions. Polymorphisms of APOA5 and APOE are determinants of low HDL-cholesterol and high LDL-cholesterol, respectively. Genotyping of these polymorphisms may prove informative for prediction of the genetic risk for these conditions.

Introduction: Aneurysms and dissections at the thoracic aorta (TAA) are the leading causes of mortality and morbidity in the United States and Japan. Although hypertension is a major risk for TAA, several studies have indicated that genetic factors also influence the structural formation of TAA. The purpose of the present study was to identify gene polymorphisms associated with TAA among hypertensive patients for assessment of the genetic risk for this condition. Methods: This case-control study comprised 1351 hypertensive individuals, including 88 subjects with TAA and 1263 without any cardiovascular complications. The genotypes for 142 polymorphisms of 121 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Results: Evaluation of genotype distributions by the chi-square test and subsequent multivariable logistic regression analysis with adjustment for age, sex, body mass index, and prevalence of smoking, diabetes mellitus, hypercholesterolemia, and metabolic syndrome revealed that the T→G (3′ UTR) polymorphism of the thrombospondin 2 gene ( THBS2 ; odds ratio, 4.7) is significantly (P < 0.05) associated with TAA in hypertensive subjects, with the variant G allele representing a risk factor for this condition. Furthermore, the -110A→C polymorphism of heat-shock 70-kD protein 8 gene ( HSPA8 ; odd ratio, 0.3), the C→T (Pro198Leu) polymorphism of the glutathione peroxidase gene ( GPX1 ; odds ratio, 0.3), the -6G→A polymorphism of angiotensin 1 gene ( AGT ; odds ratio, 0.3), and the -850C→T polymorphism of tumor necrosis factor gene ( TNF ; odds ratio, 0.5) were significantly associated with this condition, with the variant allele of each polymorphism being protective against this condition. A stepwise forward selection procedure revealed that polymorphisms of THBS2 , HSPA8 , GPX1 , AGT , and TNF significantly affected the prevalence of TAA. Conclusions: Genetic variant of THBS2 may be a risk factor for TAA in hypertensive patients, whereas variants of HSPA8 , GPX1 , AGT , and TNF may be protective against this condition. Determination of genotypes for these polymorphisms may prove informative for assessment of the genetic risk for TAA.

Hyperlipidemia or dyslipidemia is one of the most important risk factors for coronary heart disease. The purpose of the present study was to identify gene polymorphisms for assessment of the genetic risk for myocardial infarction (MI) in individuals with low or high serum concentrations of high- density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, or triglyceride (TG), thereby contributing to the personalized prevention of MI in such individuals. The study population comprised 2682 unrelated Japanese individuals (1796 men, 886 women), including 1113 subjects (869 men, 244 women) with MI and 1569 controls (927 men, 642 women). The genotypes for 164 polymorphisms of 137 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analyses and stepwise forward selection procedures revealed that seven different polymorphisms were significantly (P0.005) associated with MI in individuals with low or high serum concentrations of HDL- or LDL-cholesterol or of TG: the 190T --C (Trp64Arg) polymorphism of ADRB3 in individuals with low HDL-cholesterol; the 1018C --T (Thr145Met) polymorphism of GP1BA, the A --G (Ile646Val) polymorphism of AKAP10, and the -55C --T polymorphism of UCP3 in individuals with high HDL-cholesterol; the -603A --G polymorphism of F3 and the -11377C --G polymorphism of ADIPOQ in individuals with low LDL-cholesterol; the 1018C --T polymorphism of GP1BA in individuals with low TG; and the 4G --5G polymorphism of PAI1 in individuals with high TG. No polymorphism was associated with MI in individuals with high LDL-cholesterol. These results suggest that polymorphisms associated with MI may differ among individuals with different lipid profiles. Stratification of subjects according to lipid profiles may thus be important for personalized prevention of MI based on genetic information.