Comparison between valsartan and amlodipine regarding cardiovascular morbidity and mortality in hypertensive patients with glucose intolerance: NAGOYA HEART Study.

It has not been fully examined whether angiotensin II receptor blocker is superior to calcium channel blocker to reduce cardiovascular events in hypertensive patients with glucose intolerance. A prospective, open-labeled, randomized, controlled trial was conducted for Japanese hypertensive patients with type 2 diabetes mellitus or impaired glucose tolerance. A total of 1150 patients (women: 34%; mean age: 63 years; diabetes mellitus: 82%) were randomly assigned to receive either valsartan- or amlodipine-based antihypertensive treatment. Primary outcome was a composite of acute myocardial infarction, stroke, coronary revascularization, admission attributed to heart failure, or sudden cardiac death. Blood pressure was 145/82 and 144/81 mm Hg, and glycosylated hemoglobin was 7.0% and 6.9% at baseline in the valsartan group and the amlodipine group, respectively. Both of them were equally controlled between the 2 groups during the study. The median follow-up period was 3.2 years, and primary outcome had occurred in 54 patients in the valsartan group and 56 in the amlodipine group (hazard ratio: 0.97 [95% CI: 0.66-1.40]; P=0.85). Patients in the valsartan group had a significantly lower incidence of heart failure than in the amlodipine group (hazard ratio: 0.20 [95% CI: 0.06-0.69]; P=0.01). Other components and all-cause mortality were not significantly different between the 2 groups. Composite cardiovascular outcomes were comparable between the valsartan- and amlodipine-based treatments in Japanese hypertensive patients with glucose intolerance. Admission because of heart failure was significantly less in the valsartan group.

The number and function of circulating CD34(+)CD133(+) progenitor cells decreased in stable coronary artery disease but not in acute myocardial infarction.

OBJECTIVE: Circulating CD34(+)CD133(+) cells are one of the main sources of circulating endothelial progenitor cells (EPCs). Age is inversely related to the number and function of CD34(+)CD133(+) progenitor cells in stable coronary artery disease (CAD), but the relationship remains unclear in acute myocardial infarction (AMI). The authors aimed to clarify how ageing affects the number and function of mobilised CD34(+)CD133(+) progenitor cells in AMI. DESIGN AND RESULTS: Circulating CD34(+)CD133(+) progenitor cells were measured by flow cytometry. Measurements were made at admission for CAD, or on day 7 after the onset of AMI. In stable CAD (n=131), circulating CD34(+)CD133(+) cells decreased with age (r=-0.344, p<0.0001). In AMI, circulating CD34(+)CD133(+) cells did not correlate with age (n=50), and multivariate analysis revealed that the decreased number of circulating CD34(+)CD133(+) cells was associated with male sex and higher peak creatinine kinase. The ability to give rise to functional EPCs, which show good migratory and tube-forming capabilities, deteriorated among stable CAD subjects (n=10) compared with AMI subjects (N=6). CONCLUSIONS: In stable CAD, the number and function of circulating CD34(+)CD133(+) progenitor cells decreased with age, whereas those mobilised and circulating in AMI did not.

Predictors of in-hospital delay to reperfusion in patients with acute myocardial infarction in Japan.

The purpose of this study was to identify factors associated with in-hospital delay in patients with acute myocardial infarction (AMI) in Japan. In this observational study, 155 consecutive patients admitted with AMI to one of five urban hospitals were studied. The median door-to-needle time and door-to-catheterization-laboratory time was 19 min and 60 min, respectively. Three variables predicted door-to-catheterization-laboratory times >/= 60 min: failing to call an ambulance, direct admission to the hospital, and absence of diaphoresis (p < 0.05). These findings support the need for public education emphasizing the importance of calling an ambulance for AMI symptoms. Moreover, Japanese physicians should be aware that admitting patients directly to the hospital and bypassing the Emergency Department might increase delay to treatment.

Trajectory of prehospital delay in patients with acute myocardial infarction in the Japanese health care system.

OBJECTIVE: The purpose of this study was to understand the trajectory of prehospital delay in patients with acute myocardial infarction (AMI) in the Japanese health care system, which offers patients a choice between seeking treatment in a neighborhood clinic/small hospital (clinic group) or a large hospital with comprehensive cardiac services, including a cardiac catheterization laboratory (hospital group). METHODS: In this cross sectional study, 155 consecutive patients admitted with AMI to one of 5 urban hospitals in Japan were interviewed within 7 days after admission. RESULTS: The median total prehospital delay time in the clinic group (n=84) was significantly longer than the hospital group (n=71) (6 h and 48 min vs 2 h and 9 min, p<.001). Patients with severe chest pain were significantly less likely to seek treatment at a clinic/small hospital than at a large hospital compared to patients with mild or moderate symptoms (OR 0.85, 95% CI: 0.75, 0.97). Patients who did not interpret their symptoms as cardiac in origin were significantly more likely to seek treatment at a clinic/small hospital than at a large hospital compared to patients who interpreted their symptoms as cardiac in origin (OR 3.32, 95% CI: 1.56, 7.10). After controlling for demographic and medical history, patients in the clinic group were 3.69 times (95% CI: 1.28, 10.66) less likely to receive any reperfusion therapy compared to patients in the hospital group. CONCLUSIONS: Findings support the need for public education in Japan that focuses on the appropriate response to AMI symptoms. Moreover, regional AMI networks need to be instituted to provide for early transfer for PCI from clinic/small hospitals to tertiary centers.

Symptom severity as a predictor of reported differences of prehospital delay between medical records and structured interviews among patients with AMI.

BACKGROUND: The time interval from symptom onset to hospital arrival can guide the decision to start reperfusion for patients with acute myocardial infarction (AMI). AIMS: The aims of the study were 1) to examine the consistency and agreement of prehospital delay time between medical record review and structured patient interview and 2) to identify whether symptom severity is an independent predictor of differences in reported prehospital delay between these two data sources. METHODS: In this cross-sectional study, a convenience sample of 155 patients with AMI in Japan was recruited. The time and date of symptom onset were obtained from medical record review and a structured patient interview. The interviewer asked about severity of symptoms, using a scale on 0 to 10 scale, with 0 being "no symptom" and 10 being "the most severe symptoms imaginable". RESULTS: The prehospital delay time from the medical record was significantly shorter than from the structured interview. Perfect agreement of reported prehospital delay time between two data sources was found in 46% of patients. Patients with symptom severity scores of greater than 8 on a 10-point scale were 2.2 times (95% CI: Odds Ratio 1.1 to 5.1) more likely to report different symptom onset time. CONCLUSIONS: Prehospital delay time documented in the medical record was shorter than that identified from a structured interview. In addition, the discrepancy between the two data sources may be larger in those patients with severe AMI symptoms.

Do Japanese workers who experience an acute myocardial infarction believe their prolonged working hours are a cause?

BACKGROUND: Cardiovascular disease related to excessive work/job stress has been a significant social concern for the Japanese public. Therefore, we conducted a cross-sectional study to (1) compare job stress levels between patients with acute myocardial infarction (AMI) patients and healthy workers, and (2) examine the types of stresses associated with patients' causal belief of AMI among patients with AMI. METHODS: Forty-seven patients admitted to the hospital with AMI and 47 healthy workers visiting a hospital for their annual physical examination were recruited in Japan. Both groups were employed full time and matched on age and gender. Job stress was assessed by the Brief Job Stress Questionnaire, which consists of four subscales: job demand, job control, support from supervisors, and support from coworkers. Causal belief was assessed by a semi-structured interview. RESULTS: Compared with healthy workers (50.7+/-8.6 h), AMI patients worked significantly longer hours per week (58.3+/-15.0 h) prior to their AMI. Among AMI patients, 38% reported that job stress might have contributed to their AMI. AMI patients who reported acute stressful events at work during the month prior to AMI were 6.88 times (95% CI: 1.84, 25.75) more likely to believe that job stress/overwork caused their AMI after controlling for working hours per week and age. CONCLUSIONS: Like other known cardiac risk factors, it is important for clinicians to assess patient's excessive working hours. The education and counseling of patients following AMI must take into consideration long working hours, acute stressful events at work, and the patient's perceived view of job stress.

Prehospital delay and independent/interdependent construal of self among Japanese patients with acute myocardial infarction.

Reducing the time from symptom onset to reperfusion therapy is an important approach to minimizing myocardial damage and to preventing death from acute myocardial infarction (AMI). Previous studies suggest that certain ethnic or national groups, such as the Japanese, are more likely to delay in accessing care than other groups. The aims of this paper were the following; (1) to examine whether culture (defined as independent and interdependent construal of self) is associated with delay in accessing medical care in Japanese patients experiencing symptoms of AMI; (2) to determine if the relationship between independent and interdependent construal of self and prehospital delay time is mediated by cognitive responses and/or emotional responses; and (3) to determine if independent and interdependent construal of self independently predicts choice of treatment site (clinic vs. hospital). A cross-sectional study was conducted at hospitals in urban areas in Japan. One hundred and forty-five consecutive patients who were admitted with AMI within 72 h of the onset of symptoms were interviewed using the modified response to symptoms questionnaire and the independent and interdependent construal of self scale. The interdependent construal of self scores were significantly associated with prehospital delay time, controlling for demographics, medical history, and symptoms (p<.001). However, the relationship between independent and interdependent self and prehospital delay times was not mediated by cognitive or emotional responses. In multiple logistic regression analysis, patients with high independent construal of self were more likely to seek care at a hospital rather than a clinic compared to those with lower independent construal of self. In conclusion, cultural variation within this Japanese group was observed and was associated with prehospital delay time.

Illness attribution among Japanese patients with acute myocardial infarction.

OBJECTIVE: The purpose of this study was to describe causal attribution of acute myocardial infarction (AMI) in Japanese patients. DESIGN: A cross-sectional study design was used. SETTING: The setting for this study was 5 hospitals in urban areas in Japan. SAMPLE: A convenience sample of 155 patients admitted with AMI was used. MEASURES: Causal attribution was assessed by a semi-structured interview. Known risk factors were assessed by medical record review and patient interview. RESULTS: Twenty-two different primary causes for AMI were identified. Patients most commonly cited smoking, stress, and diet as risk factors. Except for smoking, Japanese patients did not identify their cardiac risk factors as a cause of their AMI. Controlling for sociodemographic characteristics, patients with a recorded history of coronary heart disease were significantly less likely to attribute their cardiac risk factors to their AMI (P <.05). CONCLUSIONS: Effective education and counseling of patients after an AMI must be coupled with their view of what factors put them at risk for future AMIs.

Risk stratification and survival in post myocardial infarction patients: a large prospective and multicenter study in Japan.

BACKGROUND: Recent clinical trials suggest that the mortality in high-risk patients with ischemic heart disease can be significantly reduced with the use of implantable cardioverter-defibrillator (ICD). Given the high cost and invasiveness of the procedure, it is important to apply it to the patients after myocardial infarction (MI) highly susceptible to sudden arrhythmic death. OBJECTIVE: The purpose of this study was to assess clinical predictors of mortality in post-MI patients in Japan. METHODS AND RESULTS: In 495 consecutive MI survivors, 350 (71%) received acute-reperfusion therapy, whereas 145 (29%) did not. Nonsustained ventricular tachycardia (NSVT) was present in 136 patients (28%) in 24-h ambulatory ECGs at 7+/-6 in-hospital days. Left ventricular dysfunction (LVEF< or =35%) was present in 20/347 patients (5.7%) at 13+/-8 days. Forty-eight patients (9.7%) died during the follow-up period (48+/-13 months); 23 from cardiac and 25 from noncardiac causes. Kaplan-Meier survival analyses showed that mortality rates were higher among patients who were > or =70 years old (log-rank test, P<0.0001); had heart failure at admission (Killip scale> or =2, P=0.001); did not receive acute-reperfusion (P=0.004); and had left ventricular dysfunction with LVEF< or =35% (P=0.02). The presence of NSVT was a significant predictor of death (P=0.036) only in the patients who did not receive acute-reperfusion. Multivariate Cox regression analysis revealed that an independent predictor of total mortality was an age> or =70 (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P<0.00001). CONCLUSIONS: High-risk patients after acute MI can be identified on the basis of age, ventricular dysfunction, heart failure and acute-reperfusion therapy. The presence of NSVT before discharge has a prognostic value only in the patients without acute-reperfusion.

Association of gene polymorphisms with coronary artery disease in individuals with or without nonfamilial hypercholesterolemia.

A substantial proportion of individuals with coronary artery disease (CAD) has concomitant hypercholesterolemia. A large-scale association study was performed to identify separately genes that confer susceptibility to CAD in the absence or presence of nonfamilial hypercholesterolemia. The study population comprised 5248 unrelated Japanese individuals, including 3085 subjects with CAD (2350 men, 735 women) and 2163 controls (1329 men, 834 women). Among all study subjects, 2541 individuals (1688 men, 853 women) had nonfamilial hypercholesterolemia, and 2707 individuals (1991 men, 716 women) did not have this condition. The genotypes for 33 polymorphisms of 27 candidate genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hyperuricemia revealed that three polymorphisms [994G --> T (Val279Phe) in the platelet-activating factor acetylhydrolase gene, 242C --> T (His72Tyr) in the NADH/NADPH oxidase p22 phox gene, and 1100C --> T in the apolipoprotein C-III gene] were significantly associated with CAD in men with hypercholesterolemia. Genotyping of these three polymorphisms may prove informative for prediction of the genetic risk for CAD in men with nonfamilial hypercholesterolemia.

Effects of coagulation Factor VII polymorphisms on the coronary artery disease in Japanese: Factor VII polymorphism and coronary disease.

We investigated the relationships among Factor VII coagulant activity (FVIIc), genetic polymorphisms of Factor VII (FVII) and coronary artery disease (CAD) in 380 unrelated Japanese individuals (mean 64 years) who underwent coronary angiography and whose cholesterol levels were within normal range. CAD subjects were defined as those in whom one of the three major coronary arteries showed >50% narrowing after nitroglycerin administration. FVIIc was measured and the following polymorphisms of FVII were determined: R353Q polymorphism (M1, M2 alleles), -323 0/10 bp polymorphism (0, 10 alleles), hypervariable region 4 of intron 7 (HVR4; H5, H6, H7 alleles). FVIIc was slightly lower in M1M2/M2M2 than M1M1 (89.5+/-8.9%, 93.4+/-17.8%). Those with M2 and/or 10 allele have less chance of developing CAD (M2: OR 0.36, 95% CI 0.18-0.69, 10: OR 0.50, 95% CI 0.26-0.97). However, both alleles did not associate with myocardial infarction (MI). HVR4 was unrelated with CAD, nor with MI. In conclusion, M2 and/or 10 allele has protective effects on the developing CAD in individuals with a normal cholesterol level.