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Kenji Sakata

Publications and source records attributed to Kenji Sakata.

18 recordsLinked to original sources
PubMed2026

Current and Future Perspectives of LDL-C Lowering Therapies 2026.

LDL cholesterol (LDL-C) is the central causal factor for atherosclerotic cardiovascular disease (ASCVD), and its reduction is a cornerstone of both primary and secondary prevention. Since the introduction of statins more than three decades ago, LDL-C-lowering therapy has expanded substantially, now encompassing ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9)-targeting agents, bempedoic acid, and other emerging modalities. This expanding therapeutic landscape has improved the feasibility of achieving guideline-recommended LDL-C targets, but it has also increased the complexity of clinical decision making. This review provides a contemporary and practical overview of the LDL-C-lowering strategies, beginning with the initial evaluation of patients with elevated LDL-C, including differentiation between primary and secondary causes and the identification of familial hypercholesterolemia (FH). We summarize the current treatment targets for primary and secondary prevention, highlight the optimal selection and use of statins, and discuss the assessment and management of statin intolerance, including the role of the nocebo effect. Non-statin therapies, including ezetimibe, bile acid sequestrants, PCSK9 inhibitors, inclisiran, and bempedoic acid, are reviewed with an emphasis on their mechanisms, efficacy, and clinical positioning. Advanced therapies for severe dyslipidemia, such as lipoprotein apheresis, lomitapide, and evinacumab, are also discussed in this review. Finally, we outline the future directions, including oral PCSK9 inhibitors, next-generation cholesteryl ester transfer protein (CETP) inhibitors, lipoprotein(a)-lowering agents, and genome-editing approaches. Collectively, these developments offer new opportunities to address unmet clinical needs, particularly in patients with FH, statin intolerance, and residual cardiovascular risk. A comprehensive understanding of these therapies is essential for further reducing the burden of ASCVD in the coming decades.

Humans↗
PubMed2006

A novel mutation in the cardiac myosin-binding protein C gene is responsible for hypertrophic cardiomyopathy with severe ventricular hypertrophy and sudden death.

It has been demonstrated previously that clinical phenotypes of HCM (hypertrophic cardiomyopathy) caused by mutations in the cardiac MyBP-C (myosin-binding protein C) gene show late onset, low penetrance and favourable clinical course. However, we have encountered severe phenotypes in several carriers of the MyBP-C gene mutations. The aim of the present study was to screen novel MyBP-C gene mutations in patients with HCM and to investigate the genetic differences in affected subjects with severe phenotypes. The MyBP-C gene was screened in 292 Japanese probands with HCM, and a novel c.2067+1G-->A mutation was present in 15 subjects in five families. Clinical phenotypes of carriers of the c.2067+1G-->A mutation were compared with those of a previously identified Arg820Gln (Arg820-->Gln) mutation in the MyBP-C gene. The disease penetrance in subjects aged > or =30 years was 90% in carriers of the c.2067+1G-->A mutation and 61% in carriers of the Arg820Gln mutation. Sudden death occurred in four subjects from three families with the c.2067+1G-->A mutation and in two subjects from one family with the Arg820Gln mutation. Two carriers of the c.2067+1G-->A mutation had substantial hypertrophy (maximal wall thickness > or =30 mm). In contrast, two carriers of the Arg820Gln mutation had end-stage HCM. In conclusion, the c.2067+1G-->A mutation is associated with HCM with substantial hypertrophy and moderate incidence of sudden death, whereas the Arg820Gln mutation is associated with end-stage HCM. These observations may provide important prognostic information regarding the clinical practice of HCM.

Adolescent↗
PubMed2006

Long ciliary processes with no ciliary sulcus and appositional angle closure assessed by ultrasound biomicroscopy.

PURPOSE: Nonpupil block mechanisms and appositional angle closure after laser iridotomy (LI) have been reported as common findings in Asians. We evaluated the presence of these findings in a cohort of Brazilian patients using ultrasound biomicroscopy (UBM). METHODS: This observational case-control study included 22 open angle eyes and 31 eyes with occludable angles on gonioscopy (defined by 2 examiners). UBM radial scans through a typical ciliary process were obtained in both light and dark conditions, at 6 and 12-o'clock positions. Long ciliary processes with no ciliary sulcus were determined on the basis of a reference line drawn perpendicular to the iris plane passing through a point located 750 mum from scleral spur. Trabecular ciliary processes distance was measured on 6-o'clock UBM images. RESULTS: After LI, 52% of occludable angle eyes had appositional angle closure in both 6 and 12-o'clock UBM images. We also observed this finding in 14% and 23% of the control eyes (in 6 and 12-o'clock UBM images, respectively). A long ciliary process with no ciliary sulcus was observed in 61% of occludable angle eyes, and also in 32% of control eyes (6-o'clock UBM images). Control eyes had longer trabecular ciliary processes distance than occludable angle eyes (P<0.001). CONCLUSIONS: The UBM finding of long ciliary processes associated with the absence of ciliary sulcus is not necessarily related to an anterior positioning of the ciliary processes. Whether UBM appositional angle closure after LI is associated with further angle closure process and/or poor intra-ocular pressure control remains to be evaluated.

Aged↗
PubMed2006

[Passiflora edulis extract and the healing of abdominal wall of rats: morphological and tensiometric study].

INTRODUCTION: The Brazilian popular habit of using plants to treat several health conditions is ancient. Passion fruit (Passiflora edulis) is widely used to treat, usually in an empiric basis, a variety of medical conditions. Anti-inflammatory activity of Passiflora edulis extract, similar to non-steroidal anti-inflammatory drugs (NSAID's), has been described. PURPOSE: To evaluate the effect of Passiflora edulis hydroalcoholic extract on the healing of midline abdominal incisions in rats by morphological and tensiometric methods. METHODS: Forty male Wistar rats were randomly allocated into two groups to either receive Passiflora edulis extract (study group, P) or saline (control group, C) intraperitoneally, in a single isovolumetric dose, after a standardized ventral midline laparotomy had been performed. The twenty rats of the control group as well as those twenty of the study group were divided into subgroups according to the time of sacrifice, either the 3rd PO day (P3, C3) or the 7th PO day (P7, C7). On day three and on day seven after surgery, the rats were sacrificed and the wound area was excised by a standardized protocol. The healing process of the specimens was evaluated macroscopically and histologically. The tensile strength was evaluated by a constant speed computerized tensiometer to determine the breaking strength and the deformation of the healing incision. RESULTS: The macroscopic examination did not show significant differences between study and control groups. Histologically, the C3 vs. P3 comparison showed the following differences: for the variables acute inflammation (p=0.045 in favor of C3), collagenization and capillary neoformation: p=0.001 e 0.001, respectively in favor of P3. Similarly, the C7 vs. P7 comparison showed the following differences for the variables acute inflammation (p=0.002 in favor of C7), chronic inflammation and capillary neoformation: p= 0.006 e 0.001, respectively in favor of P7. Tensiometrically, maximal breaking strength (C(máx)) on day seven of the study group was higher when compared to control group, (6.91 +/- 1.36 vs. 5.05 +/- 1.63, p=0.013). Maximal deformation strength (D(máx)) on day seven of the study group was higher when compared to control group (36.49 +/- 4.61 vs. 26.19 +/-5.74, p=0.001). CONCLUSION: Passiflora edulis extract enhances the healing of midline abdominal incisions in rats, especially the histological and tensiometric aspects.

Abdominal Wall↗
PubMed2005

Changes in cardiac tissue characterization in carriers with gene mutations associated with hypertrophic cardiomyopathy.

BACKGROUND: Early detection in patients with hypertrophic cardiomyopathy (HCM) is very important. Integrated backscatter (IB) provides a useful noninvasive measure of the acoustic properties of the myocardium, and may detect early myocardial changes. METHODS: Thirty-four carriers who had gene mutations causing HCM were studied. The patients were divided into three groups as follows: (1) 21 patients with wall hypertrophy (Group A), (2) 7 patients with ECG abnormalities but without wall hypertrophy (Group B), and (3) 6 carriers with neither ECG abnormalities nor wall hypertrophy (Group C). All subjects underwent ECG, conventional echocardiography and acoustic densitometry. In addition, we studied subjects < or =20 years old from Groups B and C (Group B-2 and Group C-2, respectively), and compared them with control subjects with no cardiac disorders who were < or =20 years old. RESULTS: In Group A, cyclic variations of integrated backscatter (CV-IB) in the interventricular septum and left ventricular posterior wall were significantly smaller than in Group C. The amplitude of IB in the interventricular septum and left ventricular posterior wall in Group A was significantly higher than those in Group C. Even in Group B, CV-IB in the interventricular septum was significantly smaller than those in Group C. Among patients < or =20 years old, CV-IB in the interventricular septum was significantly smaller in Group B-2 than in control subjects, while that in Group C-2 did not differ from that in control subjects. CONCLUSIONS: Changes in tissue characterization were found in the hearts of HCM gene carriers even in the absence of wall hypertrophy. These results suggest that tissue changes detectable by the acoustic densitometry methods may occur in the hearts of HCM gene carriers without wall hypertrophy, and that they may be detectable at the time of appearance of ECG abnormalities.

Adolescent↗
PubMed2005

High incidence of sudden cardiac death with conduction disturbances and atrial cardiomyopathy caused by a nonsense mutation in the STA gene.

BACKGROUND: The STA gene encodes emerin and is one of the genes that is affected in Emery-Dreifuss muscular dystrophy (EDMD). Although it has been reported that EDMD caused by the STA gene mutation is associated with X-linked recessive inheritance, the genotype-phenotype correlations, with special reference to cardiac manifestations, are not well defined. METHODS AND RESULTS: We identified 16 carriers (7 male and 9 female) with a nonsense mutation in exon 6 of the STA gene in 2 EDMD families. Pacemakers were required for treatment of bradyarrhythmias in all 7 male carriers and in 2 of the 9 female carriers. In addition, 2 of the 9 female carriers displayed atrial fibrillation. In these 2 families, 3 males without pacemaker implantation, who were not tested genetically, had died suddenly. In these family members, the majority of carriers with the mutation had not been clinically diagnosed as having EDMD before genetic testing because of extremely mild or nonexistent skeletal myopathy. CONCLUSIONS: EDMD caused by this mutation is characterized by atypical clinical features and incomplete penetrance of the clinical phenotype and may result in serious cardiac complications, including sudden death. Approaches to preventing possible sudden death in carriers with the STA gene mutation require further study.

Adolescent↗
PubMed2005

Abnormal sympathetic innervation of the heart in a patient with Emery-Dreifuss muscular dystrophy.

A 33-year-old man was admitted for general malaise and vomiting. An electrocardiogram showed a complete atrioventricular block and an echocardiogram showed right atrial dilatation and normal wall motion of left ventricle (LV). Gene analysis showed nonsense mutation in the STA gene, which codes for emerin, and Emery-Dreifuss muscular dystrophy was diagnosed. An endomyocardial biopsy of right ventricle showed mild hypertrophy of myocytes. Myocardial scintigraphic studies with Tc-99m methoxyisobutylisonitrile (MIBI) and I-123-betamethyl-p-iodophenylpentadecanoic acid (BMIPP) scintigrams showed no abnormalities. In contrast, I-123 metaiodobenzylguanidine (MIBG) scintigrams showed a diffuse and severe decrease in accumulation of MIBG in the heart. Six months later, his LV wall motion on echocardiograms developed diffuse hypokinesis. These results suggest that the abnormality on I-123 MIBG myocardial scintigrams may predict LV dysfunction in Emery-Dreifuss muscular dystrophy.

3-Iodobenzylguanidine↗
PubMed2005

Differentiation between patients with takotsubo cardiomyopathy and those with anterior acute myocardial infarction.

BACKGROUND: There has not been a comparison of the electrocardiographic (ECG) finding of ST-segment elevation in the precordial leads in patients with takotsubo cardiomyopathy (TC) and those with anterior acute myocardial infarction (AMI), with regard to the location of the culprit lesion. METHODS AND RESULTS: The present study evaluated 18 patients with TC, and 85 with anterior AMI who were divided into 3 groups: group A had the culprit lesion proximal to both the first septal branch (S1) and the first diagonal branch (D1), group B had the culprit lesion proximal to either S1 or D1, and group C had the culprit lesion distal to both S1 and D1. In patients with TC, reciprocal ST-segment depression in the inferior leads was observed less frequently than in patients in groups A (p<0.0001) and B (p=0.0002), and abnormal Q waves and ST-segment elevation in the inferior leads were observed more frequently than in group A (p=0.0007, p=0.0057, respectively). The ECG findings in TC did not differ from those in group C. CONCLUSION: Electrocardiographic findings may differentiate TC from AMI with a proximal lesion of left anterior descending coronary artery, but not those with distal lesions.

Aged↗
PubMed2003

A novel missense mutation in the myosin binding protein-C gene is responsible for hypertrophic cardiomyopathy with left ventricular dysfunction and dilation in elderly patients.

OBJECTIVES: We studied the clinical features of hypertrophic cardiomyopathy (HCM) caused by a novel mutation in the myosin binding protein-C (MyBP-C) gene in patients and family members of Japanese descent. BACKGROUND: Previous reports have demonstrated that the clinical features of HCM associated with mutations in the MyBP-C gene include late onset and a favorable clinical course. Recently, some mutations in genes encoding sarcomeric proteins have been reported to be a cause of dilated cardiomyopathy (DCM), as well as HCM. However, mutations of the MyBP-C gene have not been reported as a cause of DCM up to now. METHODS: We analyzed MyBP-C gene mutations in 250 unrelated probands with HCM and in 90 with DCM. We used electrocardiography (ECG) and echocardiography to determine clinical phenotypes. RESULTS: We identified 17 individuals in 8 families (7 HCM, 1 DCM) with an Arg820Gln mutation in the MyBP-C gene. Overall, 2 (40%) of 5 carriers age >70 years displayed "burnt-out" phase HCM, and one of them had been diagnosed as having DCM before genetic identification. The disease penetrance in subjects age >50 years was 70% by echocardiography and 100% by ECG, and that in those age <50 years was 40% and 50%, respectively. CONCLUSIONS: Elderly patients with Arg820Gln mutation may show "burnt-out" phase HCM, and patients with this mutation may be included among those diagnosed as having DCM. Screening of patients with DCM, as well as HCM, for this mutation is of significant importance because patients with this mutation may be diagnosed clinically as having DCM.

Adolescent↗
PubMed2003

Q-T peak dispersion in congenital long QT syndrome: possible marker of mutation of HERG.

Congenital long QT syndrome (LQTS) is caused by mutations in various cardiac potassium or sodium channel genes, with 6 different genotypes thus far identified. However, it is unknown whether these genotypes can be differentiated by QT variables. The electrocardiograms obtained from 16 patients with a mutation in KCNQ1 (LQT1), 7 patients with a mutation in HERG (LQT2) and 20 control subjects were analyzed. The corrected QT interval (QTc), Q-T peak interval (QTpc) and dispersion of QTc or QTpc were measured in 6 precordial leads. The corrected interval from T peak to T end (Tpec) was measured in lead V(5). The maximum QTc, QTc dispersion, and Tpec were significantly increased in the LQT1 and LQT2 patients than in the controls. However, there were no significant differences in these indices between the LQT1 and LQT2 patients. In contrast, QTpc dispersion was significantly increased in the LQT2 patients (78+/-25 ms) compared with the LQT1 patients (29+/-15 ms) and controls (26+/-19 ms). These results suggest that increased lag of the peak of the T wave in each precordial lead (QTpc dispersion) may be a possible index to differentiate LQTS patients with HERG mutation from those with KCNQ1 mutation.

Adult↗
PubMed2003

In-hospital outcome in octogenarians with acute coronary syndrome undergoing emergent coronary angiography.

Very elderly patients have higher mortality rates than younger patients after acute coronary syndrome (ACS). However, the mechanism by which increasing age contributes to such mortality remains unclear. In addition, the efficacy and safety of invasive coronary procedures for octogenarians with ACS have not been well established. We compared the clinical characteristics and in-hospital outcome of 193 octogenarians (mean age, 83 years) with those of 1,462 younger patients (mean age, 64 years) with ACS who underwent emergent coronary angiography. Octogenarians included a greater number of females, had higher rates of cerebrovascular disease and multivessel disease, a higher Killip class, a higher Forrester class, and lower rates of smoking, diabetes, and hypercholesterolemia than the younger subjects. Interventions, including percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG), were performed less frequently in octogenarians than in younger patients (88.0% versus 90.8%). The procedural success rate in octogenarians did not differ from that in younger patients. However, the in-hospital mortality rate for the octogenarians was about three times higher than for the younger patients (19.2% versus 6.9%). Multivariate analysis revealed that the predictors of in-hospital mortality in the octogenarians were a higher Killip class and a higher Forrester class. Octogenarians with ACS had fewer coronary risk factors and a similar success rate for the intervention, but had more greatly impaired hemodynamics and higher in-hospital mortality than the younger patients. Therefore, impaired myocardial reserve may contribute to a large portion of in-hospital deaths in octogenarians with ACS.

Aged↗
PubMed2003

[Clinical evaluation of continuous isoproterenol inhalation in adult patients with severe acute asthma].

The clinical efficacy and safety of continuous inhalation therapy using l-isoproterenol in adult acute severe asthma were retrospectively evaluated. Fifty adult patients (34 men and 16 women, mean age 47.5) with severe acute asthma, which was not improved by conventional therapy including intermittent inhalation of salbutamol, intravenous aminophylline, and corticosteroid, were given continuous l-isoproterenol inhalation treatment. Both the lowered PaO2/FiO2 and the elevated PaCO2 improved significantly within 4 hours later. Forty-seven patients (94.0%) showed clinical improvement whereas two (4.0%) did not respond and received mechanical ventilation. No obvious side effects were noted in 49 patients (98.0%), while an 81-year-old man showed an elevation of blood pressure, which recovered promptly after discontinuation of the treatment. Based on these observations, we conclude that continuous inhalation therapy using l-isoproterenol is a safe and possibly useful option in the treatment of severe adult acute asthma, especially in patients who do not respond to conventional therapy.

Acute Disease↗
PubMed2002

Chronologic electrocardiographic changes in patients with hypertrophic cardiomyopathy associated with cardiac troponin 1 mutation.

BACKGROUND: Deletion of lysine 183 (K183del) in the cardiac troponin I (cTnI) gene is one of the mutations that causes hypertrophic cardiomyopathy (HCM). However, the phenotypic expression of this mutation has not been well established. METHODS AND RESULTS: We analyzed 10 probands with HCM associated with a K183del in the cTnI gene, as well as their family members. Forty-seven of these 80 subjects were found to be carriers and 33 were noncarriers. In the carrier subjects, electrocardiogram (ECG) abnormalities were initially noted during the early teenage years preceding echocardiographic abnormalities. Abnormal Q waves were found first and most frequently compared with other ECG abnormalities. Abnormal Q waves were frequently observed in leads II, III, aVF, V5, and V6 in teenage patients, whereas they were observed in many leads in patients >20 years old. The youngest of the 11 patients who had sudden cardiac death among studied pedigrees was a 14-year-old boy. CONCLUSIONS: These results suggest that the first phenotypic manifestation in patients with HCM associated with a K183del mutation in the cTnI gene is abnormal Q waves in leads II, III, aVF, V5, and V6 during the early teenage years. To prevent sudden death in family members of patients with this mutation, it may be necessary to genetically diagnose it before age 10 years and to pay careful attention to any development of abnormal Q waves.

Adolescent↗
PubMed2002

Effects of gender on the number of diseased vessels and clinical outcome in Japanese patients with acute coronary syndrome.

It has been reported that women with acute myocardial infarction (AMI) have a higher short-term mortality rate than men, but the reason is unclear and it is not known if it also applies to unstable angina pectoris (UAP). In addition, most previous studies have not presented angiographic findings. In the present study, the findings from 1,408 patients with AMI (group A: 361 women, 1,047 men) and 332 patients with UAP (group B: 103 women, 229 men) who underwent coronary angiography within 30 days of onset were analyzed. In both groups, the women were older and had a higher rate of hypertension and a lower rate of smoking than the men. There was no significant difference in Killip class or the number of diseased vessels between the women and men in both groups. Interventions (coronary angioplasty and coronary artery bypass grafting) were performed less frequently in the women than in the men (87.2% vs 91.8%, p=0.04) in group A, but not in group B (80.6% vs 81.2%, NS). In both groups, the overall mortality rate during hospitalization was higher in women than in men (group A: 14.4% vs 7.4%, p<0.0001, group B: 7.8% vs 1.7%, p=0.007). Multivariate analysis revealed that female gender was an independent predictor of in-hospital mortality in group B (odds ratio (OR): 6.4, 95% confidence interval (CI) 1.1-37.0, p=0.04), but not in group A (OR: 1.7, 95%CI 0.98-2.9, p=0.06). The independent predictors of in-hospital mortality, other than female gender were age, prior congestive heart failure, prior cerebrovascular disease and a higher Killip class in group A, and in both groups a higher number of diseased vessels. In conclusion, Japanese women with acute coronary syndromes present with similar angiographic findings and hemodynamics, but have a higher in-hospital mortality than male patients. Our results suggest that older age may be a potential explanation for the higher in-hospital mortality in women with AMI, but female gender itself may be an important predictor for it among those with UAP.

Acute Disease↗
PubMed2002

ETS proteins and MMPs: partners in invasion and metastasis.

Binding sites for the ETS domain family of transcription factors are found in the promoters of the matrix metalloproteinase (MMP) family of matrix degrading enzymes. Evidence is accumulating that both these groups of molecules are important in the process of angiogenesis in addition to matrix degradation. Furthermore, they are both expressed in tumor tissue as well as in the normal surrounding stroma. These factors along with various sites at which they may be regulated collectively makes them attractive targets to consider for therapeutic intervention in the processes of invasion and metastasis.

Binding Sites↗
PubMed2002

[Minute pulmonary meningothelial-like nodules: a case report].

The presence of multiple small nodular shadows on a routine chest radiograph was noticed in a 56-year-old woman who had undergone a left mastectomy on the diagnosis of breast cancer 8 years before. Chest CT films revealed small nodules scattered beneath the pleura mainly in both lower lobes. A biopsy was performed during video-assisted thoracoscopy to rule out metastasis from breast cancer. Biopsy specimens showed spindle--or oval-shaped cells arranged in nests associated with a dedicated network of capillaries. These findings were compatible with minute meningothelium-like nodules (MN). The pathogenesis of MN is still unknown. It is common in elderly women, and the prognosis is excellent without any treatment. MN is an important disease in the differential diagnosis of multiple nodular shadows found on chest CT.

Breast Neoplasms↗
PubMedDate not supplied

Cardiac sympathetic nerve activity in patients with hypertrophic cardiomyopathy with malignant ventricular tachyarrhythmias.

BACKGROUND: Malignant ventricular tachyarrhythmia (VT) and sudden death are serious events in hypertrophic cardiomyopathy (HCM). However, the pathophysiology of this condition is not well understood. The objective of this study was to evaluate the relationship between cardiac sympathetic nerve activity and the occurrence of VT in HCM patients. Methods and results We studied iodine 123 metaiodobenzylguanidine scintigraphy and 24-hour ambulatory electrocardiographic monitoring in 44 HCM patients, 15 with VT (group A) and 29 without VT (group B). With planar I-123 metaiodobenzylguanidine imaging, the heart-to-mediastinum ratio for early and delayed acquisition and washout rate were calculated. Polar maps of left ventricular myocardium were divided into 20 segments, and the SD of uptake and washout rate in 20 segments were calculated as indices of regional variation. The global washout rate was significantly higher in group A than in group B (26.8 +/- 6.4% vs 17.4 +/- 5.7%, P <.0001), although other parameters including heterogeneity indices did not differ. The logistic multiple regression analysis also determined that washout rate was the most powerful predictor of VT in patients with HCM. CONCLUSIONS: The occurrence of malignant VT in HCM may be associated with global cardiac sympathetic nerve activity rather than with the heterogeneity of this activity.

3-Iodobenzylguanidine↗