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ABSTRACT: Tissue 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.
A 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<0.01) and a negative correlation between LP(%) and FFRmyo (r=-0.52, p<0.05).
Our findings indicate that the tissue characteristics of coronary plaques in intermediate lesion affect functional stenosis.
Journal of Cardiology 02/2010; 55(3):296-302. · 1.28 Impact Factor
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ABSTRACT: 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.
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 (PeakVO(2)) 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, PeakVO(2), and AT was 0.84 +/-0.66, 17.1 +/-3.2 ml x kg(-1) x min(-1), and 11.1 +/-2.0 ml x kg(-1) x min(-1), respectively. There was no significant correlation between %DS and FFRmyo, PeakVO(2), or AT (r=0.12, 0.051, and 0.013, respectively; P=NS), but FFRmyo had a significant positive correlation with PeakVO(2) and AT (r=0.534 and 0.542, respectively; P<0.05).
Exercise capacity reflects functional stenosis in stable angina patients.
Circulation Journal 10/2009; 73(12):2308-14. · 3.77 Impact Factor
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ABSTRACT: 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, p < 0.001). 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 (p < 0.001), 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 (p < 0.001). IMT in intima in the P group significantly decreased from 3.7 +/- 0.4 to 3.3 +/- 0.4 mm (p < 0.001). 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.
Ultrasound in medicine & biology 10/2008; 35(2):193-200. · 2.02 Impact Factor
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Shinichiro Tanaka,
Sachiro Watanabe,
Hitoshi Matsuo, Tomonori Segawa,
Makoto Iwama,
Takeshi Hirose,
Haruki Takahashi,
Koji Ono,
Shunichiro Warita,
Tai Kojima,
Shinya Minatoguchi,
Hisayoshi Fujiwara
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ABSTRACT: Treatment 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.
We 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.
There 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<0.05). Class II: 24 in group A vs. 10 in group B. and class III: none in group A vs. 3 in group B (p<0.05). CBC increased the mitral valve area (Gorin formula) from 1.3+/-0.3 to 2.1+/-0.5 cm2 in patients in group A and from 1.1+/-0.2 to 1.8+/-0.4 cm2 in those in group B (p=n.s.). Among the latter, there were significantly more excessive commissurotomies than in group A and no bilateral commissurotomy. The overall or event-free survival rate during the follow-up of group B showed a lower tendency than in group A (overall: group A: 86.2% vs. group B: 84.6%, p, n.s. event-free: 56.8% vs. 46.2%, respectively, p=n.s.). Univariate predictors of all events in group B included post-CBC pulmonary arterial pressure, and the pattern of commissurotomy after CBC (p<0.05). Excessive commissurotomy increased clinical events some years later, after the procedure.
In this study, involving a small number of subjects, long-term outcomes of patients with unilateral commissural calcification receiving CBC showed no significant difference as compared to those with commissural calcification absence. However, it is necessary to perform careful follow-up of CBC patients with unilateral commissural calcium.
Journal of Cardiology 02/2008; 51(1):33-41. · 1.28 Impact Factor
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Shinichiro Tanaka,
Sachiro Watanabe,
Hitoshi Matsuo, Tomonori Segawa,
Makoto Iwama,
Takeshi Hirose,
Haruki Takahashi,
Koji Ono,
Shunichiro Warita,
Tai Kojima,
Shinya Minatoguchi,
Hisayoshi Fujiwara
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ABSTRACT: The recent SCORES trial demonstrated that lower dilatation pressures seen with self-expanding (SE) stents may be associated with lower rates of target lesion revascularization (TLR). To determine whether SE stents with low-pressure dilatation are as safe and effective as balloon expandable (BE) stents. We randomly assigned 254 patients with 279 coronary lesions to groups receiving either SE with low-pressure dilatation <12 atm (n = 143) or conventional BE stents (n = 136). Thereafter, acute results and long-term outcomes were compared. Baseline patient and angiographic characteristics were similar in two groups. The incidence of procedural complications, such as slow flow, side branch occlusion, and edge dissection were significantly lower in the SE group than in the BE group (overall: SE, 17; BE, 35; P < 0.01), and the occurrence of myocardial infarction tended to be lower in SE than in BE (SE, 1; BE, 4; not significant). Although acute gain was significantly smaller with SE than BE (SE, 2.21 +/- 0.65 mm; BE, 2.42 +/- 0.62; P < 0.01), probably due to gradual expansion of the SE stent, nearly identical minimum luminal diameters on follow-up angiography (SE, 2.14 +/- 0.92 mm vs. BE, 2.22 +/- 0.93; not significant) and similar angiographic restenosis (SE, 18.1% vs. BE, 20.5%). and TLR rates (SE, 16.1% vs. BE, 14.0%) were apparent. This prospective randomized trial demonstrates that SE stents with low-pressure dilatation is safe and effective strategy for treating coronary arterial stenosis.
Heart and Vessels 01/2008; 23(1):1-8. · 2.05 Impact Factor
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Hitoshi Matsuo,
Sachiro Watanabe,
Takatomo Watanabe,
Shunichiro Warita,
Tai Kojima,
Takeshi Hirose,
Makoto Iwama,
Koji Ono,
Haruki Takahashi, Tomonori Segawa,
Shinya Minatoguchi,
Hisayoshi Fujiwara
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ABSTRACT: The potential exists for microcirculatory impairment during rotational coronary atherectomy (RA) due to embolization of plaque debris, platelet aggregation, or vasospasm. This prospective randomized pilot study aimed to confirm favorable effects of nicorandil during RA compared with verapamil.
We randomly assigned 200 patients with 219 coronary lesions planned to undergo RA with intracoronary infusion of nicorandil cocktail (100 patients, 109 lesions), which contained nicorandil 24 mg, nitroglycerin 5 mg, and heparin 10,000 U in 1000 mL saline, or verapamil cocktail (100 patients, 110 lesions), which contained verapamil 10 mg instead of nicorandil. Drug cocktails were infused through a 4F Teflon sheath of the rotablator system during RA. The primary end point was incidence of no-reflow/slow-flow phenomenon; secondary end points were those of continuous ST elevation, Q-wave myocardial infarction (MI), and non-Q-wave MI.
Group baseline and coronary angiographic characteristics were similar. Rotational atherectomy was performed successfully, and no patients died or required emergency coronary artery bypass grafting. Incidence of no-reflow/slow-flow phenomenon was significantly lower in the nicorandil group (nicorandil 5/109 lesions, verapamil 13/110 lesions, P < .005). Incidences of persistent ST-segment elevation and non-Q-wave MI were significantly lower in the nicorandil group (ST-segment elevation: nicorandil 3/100 patients, verapamil 10/100 patients, P < .05; non-Q-wave MI: nicorandil 2/100, verapamil 9/100 patients, P < .05). One patient each in the 2 groups experienced Q-wave MI.
Our findings suggest that continuous intracoronary infusion of nicorandil during RA prevents acute periprocedural complications. Nicorandil should be used as adjunctive treatment during RA.
American heart journal 11/2007; 154(5):994.e1-6. · 4.65 Impact Factor
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ABSTRACT: The purpose of the present study was to identify gene polymorphisms that confer susceptibility to recurrent restenosis after bare-metal stenting of coronary arteries, and thereby to assess the genetic risk for this condition. The study population comprised 527 unrelated Japanese individuals, including 28 subjects who developed in-stent restenosis two or more times and 499 subjects without restenosis. The genotypes for 142 polymorphisms of 121 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Eleven polymorphisms were related (P<0.05) to the prevalence of recurrent in-stent restenosis as determined by the Chi-square test. 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 -55Cright curved arrow T polymorphism of the uncoupling protein 3 gene (UCP3) was significantly (P=0.0006 in a recessive model) associated with the prevalence of recurrent in-stent restenosis, with the T allele representing a risk factor for this condition. A stepwise forward selection procedure showed that the UCP3 genotype significantly (P=0.0014, recessive model) affected the prevalence of recurrent in-stent restenosis. Determination of the genotype for UCP3 may thus contribute to assessment of the genetic risk for recurrent in-stent restenosis.
International Journal of Molecular Medicine 10/2007; 20(4):533-8. · 1.98 Impact Factor
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ABSTRACT: The purpose of the present study was to identify gene polymorphisms that confer susceptibility to restenosis after bare-metal stenting of coronary arteries, and thereby to predict the genetic risk for this condition.
The study population comprised 461 unrelated Japanese individuals (350 men, 111 women) who underwent stent implantation, including 107 subjects who developed in-stent restenosis and 354 subjects without this condition. The genotypes for 142 polymorphisms of 121 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariate logistic regression analysis with adjustment for the prevalence of diabetes mellitus revealed that the 1615G-->A polymorphism of BCHE, the 7,067,365C-->A polymorphism of INSR, the C-->T polymorphism of GPX1, the G-->A polymorphism of ROS1, and the G-->A polymorphism of MMP9 were associated (P<0.05) with in-stent restenosis. Further analysis with adjustment both for the prevalence of diabetes mellitus and for quantitative coronary angiographic measurements revealed that the BCHE, GPX1, and ROS1 genotypes were independently associated (P<0.05) with in-stent restenosis.
Determination of the genotypes for BCHE, GPX1, and ROS1 may prove informative for assessment of the genetic risk for in-stent restenosis.
Atherosclerosis 10/2007; 194(2):e172-8. · 3.79 Impact Factor
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Tetsuro Yoshida,
Kazuhiro Yajima,
Takeshi Hibino,
Kimihiko Kato,
Hitoshi Matsuo, Tomonori Segawa,
Sachiro Watanabe,
Mitsutoshi Oguri,
Kiyoshi Yokoi,
Yoshinori Nozawa,
Genjiro Kimura,
Yoshiji Yamada
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ABSTRACT: 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 (P<0.005) 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.
International Journal of Molecular Medicine 10/2007; 20(4):581-90. · 1.98 Impact Factor
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Kimihiko Kato,
Mitsutoshi Oguri,
Takeshi Hibino,
Kazuhiro Yajima,
Hitoshi Matsuo, Tomonori Segawa,
Sachiro Watanabe,
Hidemi Yoshida,
Kei Satoh,
Yoshinori Nozawa,
Kiyoshi Yokoi,
Yoshiji Yamada
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ABSTRACT: Atrial fibrillation (AF) may result from an electric conduction disturbance, increased hemodynamic stress, ischemia, inflammation, or remodeling in atria. Although genetic epidemiological studies have identified several genetic variants as risk factors for AF, the genetic determinants of this condition remain largely unknown. The purpose of the present study was to identify gene polymorphisms that confer susceptibility to lone AF. The study population comprised 1069 unrelated Japanese individuals, including 196 subjects with chronic lone AF and 873 controls. The genotypes for 40 polymorphisms of 32 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 analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hyperchole-sterolemia as well as a stepwise forward selection procedure revealed that the -1306C-->T polymorphism of the matrix metalloproteinase 2 gene (MMP2) and the -592A-->C polymorphism of the interleukin 10 gene (IL10) were significantly (false discovery rate of <0.05) associated with the prevalence of AF. The T allele of the MMP2 polymorphism and the C allele of the IL10 polymorphism were a risk factor for and protective factor against AF, respectively. Determination of the genotypes for these polymorphisms may thus prove informative for assessment of the genetic component of AF.
International Journal of Molecular Medicine 07/2007; 19(6):933-9. · 1.98 Impact Factor
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Yoshiji Yamada,
Kimihiko Kato,
Takeshi Hibino,
Kiyoshi Yokoi,
Hitoshi Matsuo, Tomonori Segawa,
Sachiro Watanabe,
Sahoko Ichihara,
Hidemi Yoshida,
Kei Satoh,
Yoshinori Nozawa
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ABSTRACT: The aim of the study was to identify gene polymorphisms that confer susceptibility to metabolic syndrome in order to allow reliable assessment of genetic risk for this condition.
The study population comprised 1788 unrelated Japanese individuals (1033 men, 755 women), including 1017 subjects with metabolic syndrome (634 men, 383 women) and 771 controls (399 men, 372 women). The genotypes for 158 polymorphisms of 133 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, and the prevalence of smoking revealed that the -1131T-->C polymorphism of the apolipoprotein A-V gene (APOA5) was significantly associated with the prevalence of metabolic syndrome, with the C allele representing a risk factor for this condition. A stepwise forward selection procedure demonstrated that APOA5 genotype (CC+TC versus TT) significantly affected the prevalence of metabolic syndrome. The C allele of this polymorphism was associated with an increased serum concentration of triglycerides and a decreased concentration of HDL-cholesterol.
Genotype for APOA5 may prove reliable for assessment of genetic risk for metabolic syndrome.
Atherosclerosis 05/2007; 191(2):298-304. · 3.79 Impact Factor
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Noriyuki Fuku,
Kyong Soo Park,
Yoshiji Yamada,
Yutaka Nishigaki,
Young Min Cho,
Hitoshi Matsuo, Tomonori Segawa,
Sachiro Watanabe,
Kimihiko Kato,
Kiyoshi Yokoi,
Yoshinori Nozawa,
Hong Kyu Lee,
Masashi Tanaka
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ABSTRACT: 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.
The American Journal of Human Genetics 04/2007; 80(3):407-15. · 10.60 Impact Factor
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Sachiyo Yamaguchi,
Yoshiji Yamada,
Hitoshi Matsuo, Tomonori Segawa,
Sachiro Watanabe,
Kimihiko Kato,
Kiyoshi Yokoi,
Sahoko Ichihara,
Norifumi Metoki,
Hidemi Yoshida,
Kei Satoh,
Yoshinori Nozawa
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ABSTRACT: Type 2 diabetes mellitus is a complex metabolic disorder in which endogenous sex hormones may contribute to sex-dependent etiologies. We hypothesized that genetic variants related to type 2 diabetes mellitus might differ between men and women. We thus performed a large-scale association study to identify gene polymorphisms associated with type 2 diabetes mellitus in men and women separately. The study population comprised 4854 unrelated Japanese individuals (2688 men, 2166 women), including 1490 subjects with type 2 diabetes mellitus (969 men, 521 women). The genotypes for 16 gene polymorphisms 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, body mass index, and smoking status revealed that the T-->G (3' UTR) polymorphism of the thrombospondin 2 gene (THBS2), the -603A-->G polymorphism of the coagulation factor III gene (F3), and the G-->T (intron 2) polymorphism of the adipocyte, C1Q, and collagen domain containing (adiponectin) gene (ADIPOQ) were significantly associated with the prevalence of type 2 diabetes mellitus in men, and that the A-->G (Arg160Gly) polymorphism of the paraoxonase 1 gene (PON1) was significantly associated with this condition in women. A stepwise forward selection procedure demonstrated that genotypes of THBS2, F3, and ADIPOQ were significant determinants of type 2 diabetes mellitus in men, and that genotype of PON1 significantly affected this condition in women. Genotyping of these polymorphisms may prove informative for assessment of the genetic component of type 2 diabetes mellitus for men and women separately.
International Journal of Molecular Medicine 04/2007; 19(4):631-7. · 1.98 Impact Factor
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Yutaka Nishigaki,
Yoshiji Yamada,
Noriyuki Fuku,
Hitoshi Matsuo, Tomonori Segawa,
Sachiro Watanabe,
Kimihiko Kato,
Kiyoshi Yokoi,
Sachiyo Yamaguchi,
Yoshinori Nozawa,
Masashi Tanaka
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ABSTRACT: 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.
Human Genetics 03/2007; 120(6):827-36. · 5.07 Impact Factor
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Masashi Tanaka,
Noriyuki Fuku,
Yutaka Nishigaki,
Hitoshi Matsuo, Tomonori Segawa,
Sachiro Watanabe,
Kimihiko Kato,
Kiyoshi Yokoi,
Kiyoshi Yoko,
Masafumi Ito,
Yoshinori Nozawa,
Yoshiji Yamada
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ABSTRACT: To identify mitochondrial haplogroups that confer resistance against or susceptibility to metabolic syndrome, we performed a large-scale association study on 1,337 unrelated Japanese individuals, including 871 subjects with metabolic syndrome and 466 control subjects. Metabolic syndrome was diagnosed according to modified National Cholesterol Education Program Adult Treatment Panel III guidelines, using the cutoff point for obesity as a BMI of >/=25 kg/m(2) instead of waist circumference. 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, G1, G2, D5, and D4. Multivariate logistic regression analysis revealed that the haplogroup N9a was significantly associated with resistance against metabolic syndrome in women with an odds ratio (OR) of 0.21 (95% CI 0.07-0.58, P = 0.0042). Women with haplogroups G1 and D5 tended to be resistant against metabolic syndrome with an OR of 0.22 (0.06-0.68, P = 0.0129) for G1 and with an OR of 0.32 (0.10-0.96, P = 0.0469) for D5, respectively. These results indicate that mitochondrial haplogroup N9a may be a protective factor against metabolic syndrome in Japanese women.
Diabetes 02/2007; 56(2):518-21. · 8.29 Impact Factor
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Kensuke Io,
Shinya Minatoguchi,
Kazuhiko Nishigaki,
Shinsuke Ojio,
Tsutomu Tanaka, Tomonori Segawa,
Hitoshi Matsuo,
Sachiro Watanabe,
Arihiro Hattori,
Katsumi Ueno,
Hiroyoshi Ono,
Kunihiko Hiei,
Hironobu Sato,
Norihiko Morita,
Toshiyuki Noda,
Toshihiko Kato,
Masanori Kawasaki,
Genzou Takemura,
Hisayoshi Fujiwara
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ABSTRACT: 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.
Arzneimittel-Forschung 02/2007; 57(9):573-81. · 0.72 Impact Factor
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Kohta Nishihama,
Yoshiji Yamada,
Hitoshi Matsuo, Tomonori Segawa,
Sachiro Watanabe,
Kimihiko Kato,
Kazuhiro Yajima,
Takeshi Hibino,
Kiyoshi Yokoi,
Sahoko Ichihara,
Norifumi Metoki,
Hidemi Yoshida,
Kei Satoh,
Yoshinori Nozawa
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ABSTRACT: The purpose of the present study was to assess the genetic risk for myocardial infarction (MI) in individuals with or without conventional coronary risk factors and thereby to contribute to the personalized prevention of MI in such individuals. The study population comprised 3483 unrelated Japanese individuals (1913 men, 1570 women). The 1192 subjects with MI (926 men, 266 women) and 2291 controls (987 men, 1304 women) either had or did not have conventional coronary risk factors, including hypertension, hypercholesterolemia, and diabetes mellitus. 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 analysis and a stepwise forward selection procedure revealed that nine different polymorphisms were significantly (P<0.005) associated with MI among individuals with or without hypertension, hypercholesterolemia, or diabetes mellitus: 1018Cright curved arrow T of GP1BA, -108/3Gright curved arrow 4G of IPF1, 677Cright curved arrow T of MTHFR, and Gright curved arrow A of UTS2 in hypertensive individuals; 2445Gright curved arrow A of FABP2, -108/3Gright curved arrow 4G of IPF1, 677Cright curved arrow T of MTHFR, -11,377Cright curved arrow G of ACDC, Aright curved arrow G of AKAP10, 11,496Gright curved arrow A of F7, and 46Cright curved arrow T of F12 in individuals without hypercholesterolemia; 2445Gright curved arrow A of FABP2 in diabetic individuals; and -108/3Gright curved arrow 4G of IPF1 in nondiabetic individuals. Polymorphisms associated with MI may thus differ among individuals with different conventional coronary risk factors. Stratification of subjects on the basis of such risk factors may thus be important in order to achieve personalized prevention of MI with the use of genetic information.
International Journal of Molecular Medicine 02/2007; 19(1):129-41. · 1.98 Impact Factor
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Sachiyo Yamaguchi,
Yoshiji Yamada,
Norifumi Metoki,
Hidemi Yoshida,
Kei Satoh,
Sahoko Ichihara,
Kimihiko Kato,
Takashi Kameyama,
Kiyoshi Yokoi,
Hitoshi Matsuo, Tomonori Segawa,
Sachiro Watanabe,
Yoshinori Nozawa
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ABSTRACT: The aim of the present study was to assess the genetic risk for atherothrombotic cerebral infarction (ACI) in men and women separately as well as in individuals with or without conventional risk factors for atherosclerosis and thereby to contribute to the personalized prevention of ACI. The study population comprised 2705 unrelated Japanese individuals (1244 men, 1461 women), including 636 subjects (372 men, 264 women) with ACI. Subjects with ACI and controls either had or did not have conventional risk factors for atherosclerosis, including hypertension, hypercholesterolemia, and diabetes mellitus. The genotypes for 202 polymorphisms of 152 candidate genes were determined by a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis and a stepwise forward selection procedure revealed that 11 different polymorphisms were significantly (P < 0.005) associated with ACI in women or men or in individuals with or without hyper-tension, hypercholesterolemia, or diabetes mellitus: the 584C-->T polymorphism of LIPG, 5665G-->T of EDN1, and G-->A of CCL11 in women; 677C-->T of MTHFR, 1323C-->T of ITGB2, 3932T-->C of APOE, and -231A-->G of EDNRA in men; -572 G -->C of IL6 in hypertensive individuals; -403G-->A of CCL5 and G-->A of COMT in individuals with hypercholesterolemia; and 3932T--> C of APOE and A-->G of TNFSF4 in diabetic individuals. Polymorphisms associated with ACI may thus differ between women and men as well as among individuals with different risk factors. Stratification of subjects on the basis of sex or conventional risk factors for atherosclerosis may therefore be important in order to achieve the personalized prevention of ACI with the use of genetic information.
International Journal of Molecular Medicine 12/2006; 18(5):871-83. · 1.98 Impact Factor
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Yoshiji Yamada,
Hitoshi Matsuo, Tomonori Segawa,
Sachiro Watanabe,
Kimihiko Kato,
Takeshi Hibino,
Kiyoshi Yokoi,
Sahoko Ichihara,
Norifumi Metoki,
Hidemi Yoshida,
Kei Satoh,
Yoshinori Nozawa
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ABSTRACT: 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.
American Journal of Hypertension 11/2006; 19(11):1158-65. · 3.18 Impact Factor
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Yoshiji Yamada,
Kimihiko Kato,
Takashi Kameyama,
Kiyoshi Yokoi,
Hitoshi Matsuo, Tomonori Segawa,
Sachiro Watanabe,
Sahoko Ichihara,
Hidemi Yoshida,
Kei Satoh,
Yoshinori Nozawa
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ABSTRACT: The purpose of the present study was to identify gene polymorphisms for the reliable assessment of genetic factors for obesity. The study population comprised 3906 unrelated Japanese individuals (2286 men, 1620 women), including 1196 subjects (677 men, 519 women) with obesity (body mass index of > or = 25 kg/m2) and 2710 controls (1609 men, 1101 women). The genotypes for 147 polymorphisms of 124 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, and the prevalence of smoking revealed that the -30Gright curved arrow A polymorphism of GCK, the -240Aright curved arrow T polymorphism of ACE, and the -482Cright curved arrow T polymorphism of APOC3 were significantly (P < 0.01) associated with the prevalence of obesity, and the -1989Tright curved arrow G polymorphism of ESR1 was almost significantly associated. A stepwise forward selection procedure demonstrated that ACE, GCK, and ESR1 genotypes significantly (P < 0.01) and independently affected the prevalence of obesity. Combined genotype analysis for these three polymorphisms yielded a lowest odds ratio of 0.45 for the combined genotypes of AT or TT for ACE, GG for GCK, and GG for ESR1 in comparison with the combined genotypes of AA for ACE, GG for GCK, and TT or TG for ESR1. Genotypes for ACE, GCK, and ESR1 may prove reliable for the assessment of genetic factors for obesity. Determination of the combined genotypes for these genes may contribute to the personalized prevention of this condition.
International Journal of Molecular Medicine 11/2006; 18(5):843-51. · 1.98 Impact Factor
