Polyvascular Disease and the Incidence of Cancer in Patients with Coronary Artery Disease.

Introduction: Based on the possible relation of atherosclerotic cardiovascular disease to the development of cancer, we examined whether polyvascular disease, as a surrogate marker of the severity of atherosclerosis, is associated with the incidence of cancer in patients with coronary artery disease (CAD). Methods: A total of 8,856 patients with CAD between January 2009 and July 2014 were eligible for this observational study. Two cohorts were established based on the presence or absence of polyvascular disease (i.e., polyvascular disease and CAD only) and tracked for the incidence of cancer and all causes of death. Polyvascular disease was defined when accompanied by diagnosed aortic and/or peripheral arterial disease or other arterial diseases at enrollment. Results: With a median follow-up of 1,095 d, the incidence of cancer was markedly higher in the cohort of 716 patients with polyvascular disease than in the cohort of 8,140 patients with CAD only (8.8% vs. 4.9%, P = 0.0001). A large difference in the incidence of cancer was also found in accordance with a number of the coexisting vascular disease with CAD. With the adjustment of shared common risks, polyvascular disease was an independent contributor to the incidence of cancer (hazard ratio, 1.362; 95% confidence interval [CI], 1.029-1.774). In a total of 548 patients (6.2% of participants) died during follow-up, and all-cause, cardiovascular, and cancer mortalities were all higher in the cohort with polyvascular disease than in the cohort with CAD only. Conclusion: The presence of polyvascular disease may be associated with the incidence of cancer in patients with CAD, implying a pivotal role of the severity of atherosclerosis in cancer development (ClinicalTrials.gov. number: NCT04198896).

Incidence of cancers in patients with atherosclerotic cardiovascular diseases.

BACKGROUND: To address a clinical impact of atherosclerotic cardiovascular diseases (CVD) on cancer developments, we investigated an issue whether any difference in an incidence of cancers is present between patients with atherosclerotic CVD and those with non-atherosclerotic CVD. METHODS: Of a total of 32,095 consecutive patients with acquired CVD enrolled in the Sakakibara Health Integrative Profile cohort study, we segregated patients based on a presence of atherosclerotic or non-atherosclerotic CVD to investigate an incidence of cancers and mortality. We also evaluated an incidence of cancers in patients with a singular presence versus a plural presence of atherosclerotic CVD. Atherosclerotic CVD included coronary artery diseases, aortic diseases and peripheral artery diseases. Non-atherosclerotic CVD were any acquired CVD except atherosclerotic CVD. RESULTS: During a median follow-up of 1020 days (interquartile range, 665-1340 days), an incidence of cancers (5% vs. 2%, p = 0.0001) and overall mortality (6% vs. 3%, p = 0.0001) were more than two-fold higher in 10,592 patients with atherosclerotic CVD than in 21,503 patients with non-atherosclerotic CVD. A presence of atherosclerotic CVD (hazard ratio 1.372 with 95% confidence interval 1.199-1.569) was independently associated with an incidence of cancers. In patients with atherosclerotic CVD, 61 of 640 patients with a plural presence and 470 of 9932 patients with a singular presence developed cancers (9% vs. 5%, p = 0.0001). An incremental risk of death was found according to a presence of atherosclerotic CVD, cancers, and both of them (all p = 0.0001). CONCLUSIONS: A presence of atherosclerotic CVD itself may have a potential risk for cancer developments. TRIAL REGISTRATION: ClinicalTrials.gov. number, NCT03005834.

Estimated glomerular filtration rate reversal by blood pressure lowering in chronic kidney disease: Japan Multicenter Investigation for Cardiovascular DiseaseB CKD study.

Patients are diagnosed as having chronic kidney disease (CKD) if estimated glomerular filtration rate (eGFR) is <60 mL/min/1.73 m(2) . Low eGFR is likely to increase the incidence of cardiovascular events and lead to dialysis. Therefore, it is important to prevent eGFR from decreasing eGFR. However, it still remains unknown whether antihypertensive therapy can prevent low eGFR from becoming even lower and improve eGFR in hypertensive patients with CKD. The authors analyzed the results of the Japan Multicenter Investigation for Cardiovascular DiseaseB (JMIC-B) and investigated the effects of antihypertensive therapy on eGFR. In hypertensive patients with CKD (eGFR <60), eGFR was significantly increased from 51.87±6.21 (n=98) to 57.55±19.00 (P<.001) after 3 years of antihypertensive therapy. In patients without CKD (eGFR ≥60), eGFR was significantly decreased from 91.84±23.27 (n=682) to 88.95±23.67 (P<.001). Regardless of the type of antihypertensive drugs used, eGFR was significantly increased in patients with CKD and was significantly decreased in patients without CKD. This paper shows that antihypertensive therapy can improve eGFR in hypertensive patients with CKD. J Clin Hypertens (Greenwich). 2012;00:00-00. ©2012 Wiley Periodicals, Inc.

Landiolol, an ultra-short-acting ß1-blocker, more effectively terminates atrial fibrillation than diltiazem after open heart surgery: prospective, multicenter, randomized, open-label study (JL-KNIGHT study).

BACKGROUND: Recent studies have suggested that esmolol is the first choice for rate control in patients with postoperative atrial fibrillation (AF) after coronary artery bypass surgery, but side-effects of esmolol such as hypotension are problematic. To overcome this problem, landiolol, an ultra-short-acting ß(1)-blocker with a less negative inotropic effect than esmolol, has been developed. The aim of the present study was to investigate whether landiolol was effective for both rate control and conversion to normal sinus rhythm (NSR). METHODS AND RESULTS: A prospective, randomized, open-label comparison between i.v. landiolol and diltiazem in patients with postoperative AF was undertaken between January 2008 and June 2009 in Japan. Of 335 patients included in the analysis, 71 patients went into AF. Among these 71 patients, conversion to NSR within 8h after onset of AF occurred in 19 of 35 patients (54.3%) in the landiolol group vs. 11 of 36 patients (30.6%) in the diltiazem group (P<0.05). The incidence of hypotension was lower in the landiolol group (4/35, 11.4%) compared with the diltiazem group (11/36, 30.6%; P<0.05). The incidence of bradycardia was also lower in the landiolol group (0%) compared with the diltiazem group (4/36, 11.1%; P<0.05). CONCLUSIONS: Landiolol is more effective and safer than diltiazem for patients with postoperative AF after open heart surgery.

Reverse remodeling and improved function by antihypertensive treatment in hypertensive patients with coronary artery disease.

BACKGROUND: Although antihypertensive therapy reduces cardiovascular events, it is unclear whether there are differences in cardiac remodeling and function between treatments with nifedipine retard and angiotensin-converting enzyme inhibitors (ACE-Is). It is also not clear how antihypertensive therapy influences cardiac remodeling and function. METHODS: Hypertensive patients with coronary artery disease were randomly assigned to the nifedipine retard (n = 108) or ACE inhibitors groups (n = 102) and treated for 3 years. The primary endpoints were changes in end-diastolic volume index (EDVI) and end-systolic volume index (ESVI) as indices of cardiac remodeling, whereas the secondary endpoints were changes in ejection fraction (EF), stroke volume index (SVI), cardiac index (CI) and regional wall motion as indices of cardiac function. Left ventriculography was performed at baseline and after 3 years of treatment. Fifty-eight and 61 patients, respectively, were subjected to the final analysis. RESULTS: Comparable changes in remodeling and function were obtained in the nifedipine retard group and the ACE-Is group. Both groups showed a significant reduction of EDVI and ESVI, and a significant increase in EF, SVI, and CI, whereas the decreased regional wall motion significantly improved. In both groups, weak but significant correlations were noted between treatment-induced changes of systolic blood pressure and those of primary and secondary endpoints. CONCLUSION: The above findings show that treatments with nifedipine retard or ACE-Is cause a comparable change in remodeling and cardiac function. Lowering of the blood pressure by either drug leads to reverse remodeling or improvement of cardiac function. In addition to alleviation of coronary artery damage by reducing blood pressure, there is a favorable effect on the left ventricular structure and function. Reducing the blood pressure is critically important for hypertensive patients with coronary artery disease.

Angiotensin II receptor blocker-based vs. non-angiotensin II receptor blocker-based therapy in patients with angiographically documented coronary artery disease and hypertension: the Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease (HIJ-CREATE).

AIMS: To test whether angiotensin II receptor blockers (ARBs) therapy can reduce the incidence of cardiovascular events compared with non-ARB-based standard pharmacotherapy in coronary artery disease (CAD) patients with hypertension. METHODS AND RESULTS: Angiographically documented CAD patients with hypertension were randomly assigned to receive either candesartan-based (n= 1024) or non-ARB-based pharmacotherapy including angiotensin-converting enzyme-inhibitors (n = 1025). The primary endpoint was the occurrence of a first major adverse cardiovascular event (MACE). There were 552 primary events during a median follow-up of 4.2 years: 264 (25.8%) in the candesartan group and 288 (28.1%) in the non-ARB group (hazard ratio, 0.89; 95% confidence interval, 0.76-1.06). No significant differences existed between groups in terms of cardiovascular death (2.7 vs. 2.4%, 1.14; 0.66-1.95), non-fatal myocardial infarction (2.8 vs. 2.5%, 1.12; 0.66-1.88), or heart failure (3.9 vs. 4.3%, 0.91; 0.59-1.40). New-onset diabetes was diagnosed significantly less frequently with candesartan than with non-ARBs (0.37; 0.16-0.89). Incidence of study drug discontinuation due to adverse events was lower with candesartan than with non-ARBs (5.7 vs. 12.2%, P < 0.001). CONCLUSION: Although candesartan showed no significant differences in MACE compared with the non-ARB treatment group, the drug significantly reduced the incidence of new-onset diabetes and was better tolerated. This study is registered as International Standard Randomised Controlled Trial No. UMIN000000790.

Efficacy of abciximab for patients undergoing balloon angioplasty: data from Japanese evaluation of c7E3 Fab for elective and primary PCI organization in randomized trial (JEPPORT).

BACKGROUND: The efficacy and safety of abciximab were investigated in Japanese patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) or unstable angina. METHODS AND RESULTS: The 973 patients were randomized into 3 groups: the low-dose group (L group) received bolus injection of 0.20 mg/kg followed by 12-h infusion; the high-dose group (H group) received bolus injection of 0.25 mg/kg followed by 12-h infusion; the placebo group (P group) received bolus and infusion of placebo. The incidence of the primary endpoint (30-day post-PCI coronary events: death, MI or urgent revascularization) was 3.6%, 1.6%, and 4.1% in the P, L, and H groups, respectively, with no significant difference between the P and L groups (P=0.104) or between the P and H groups (P=0.772). The incidence of bleeding tended to increase in a dose-dependent manner. CONCLUSION: No significant difference in the incidence of coronary events was found between the placebo and abciximab groups, so the efficacy of abciximab in preventing post-PCI coronary events in Japanese patients was not confirmed.

Nifedipine retard prevents hospitalization for angina pectoris better than angiotensin-converting enzyme inhibitors in hypertensive Japanese patients with previous myocardial infarction (JMIC-B substudy).

OBJECTIVES AND BACKGROUND: We previously reported that nifedipine retard showed comparable efficacy to angiotensin-converting enzyme (ACE) inhibitors for the prevention of cardiac events in hypertensive patients with coronary artery disease during the Japan Multicenter Investigation for Cardiovascular Diseases B study. In the nifedipine group, patients with a history of myocardial infarction (MI) showed a significant reduction in hospitalization for angina pectoris compared with the ACE inhibitor group. We investigated whether this difference was related to the progression of coronary arteriosclerosis. METHODS: To evaluate coronary arteriosclerosis, we performed coronary angiography (CAG) and a quantitative analysis of coronary angiograms. RESULTS: The cumulative incidence of hospitalization for angina was significantly lower in the nifedipine group (log-rank test P = 0.013). The etiology of angina requiring hospitalization was determined on the basis of CAG findings. Its incidence secondary to the development of new lesions or the progression of existing lesions was significantly lower in the nifedipine group than in the ACE inhibitor group (log-rank test P = 0.042 and P = 0.028, respectively). Using quantitative coronary analysis, changes in the coronary artery luminal diameter were compared between the nifedipine and ACE inhibitor groups. The minimum coronary lumen diameter did not show a significant change in the nifedipine group, whereas it decreased significantly in the ACE inhibitor group (paired t-test P = 0.002), and there was a significant difference between the two groups by analysis of covariance (P = 0.047). CONCLUSION: These results indicate that nifedipine more effectively prevented admission for angina pectoris by inhibiting the progression of coronary artery disease in patients with a history of MI.

Unstable angina and non-ST elevation acute coronary syndrome: epidemiology and current management in Japan (Japan Multicenter Investigation for Cardiovascular Disease-D (JMIC-D) Committee).

BACKGROUND: A multicenter study was conducted to assess the current medical management of unstable angina (UA) and non-ST-elevation acute coronary syndrome in Japan. METHODS AND RESULTS: This study presents the results of a nationwide questionnaire survey of 770 sites and a case report investigation performed at 20 sites. The questionnaire survey revealed that the number of acute myocardial infarction (AMI) patients treated annually was 1.56-fold greater than the number of UA patients. Non-ST-elevation AMI accounted for 17% of all patients with AMI. Analysis of case reports for 885 UA patients showed extensive use of invasive treatment. In the UA patients, the cumulative incidence of a composite endpoint (all-cause mortality, AMI, and urgent coronary revascularization) was 2% at 1 month and 9% at 6 months. Stratified analysis with respect to the composite endpoint through 6 months showed a significantly lower incidence in patients treated with a calcium-channel blocker than in patients not treated with a calcium-channel blocker. CONCLUSIONS: In Japan, fewer patients are hospitalized annually for treatment of UA than for AMI. The largest percentage of UA patients had Braunwald class III disease. Non-ST-elevation AMI is managed in Japan according to the principle of early invasive treatment, resembling the treatment for ST-elevation AMI. The outcome of treatment is better for Japanese UA patients than for Japanese AMI patients.

Effects of nifedipine on systemic and pulmonary vascular impedance in subjects undergoing cardiac catheterization.

Nifedipine 10 mg, administered sublingually to 12 patients following diagnostic cardiac catheterization, caused reduction in systemic resistance, and change of impedance together with alteration in contour of the ascending aortic and left ventricular pressure waves. The substantial reduction in ascending aortic and left ventricular systolic pressure with nifedipine occurred despite an increase in stroke volume and cardiac output, and was associated with similar reductions in mean pressure and indices of wave reflection. In the same patients, there were no significant changes in pulmonary vascular resistance or impedance, nor in pulmonary artery or right ventricular pressure pulse contour. For the systemic circulation, as with nitroglycerin and nitroprusside, reduction in wave reflection appears to be an important factor in the drug's action and for its beneficial effects on cardiac load in the treatment of angina pectoris, systemic hypertension and left ventricular failure. Thus the observed effects of nifedipine were attributed to vasodilatation of the systemic arteries and arterioles.

The echocardiographic determinants of functional mitral regurgitation differ in ischemic and non-ischemic cardiomyopathy.

BACKGROUND: Functional mitral regurgitation (MR) is one of the common and severe complications in patients with dilated cardiomyopathy. The detailed mechanisms that cause functional MR remain to be elucidated. Using two-dimensional transthoracic echocardiography, we investigated the differences in major determinants of MR severity between ischemic cardiomyopathy (ICM) and non-ICM patients. METHODS: We enrolled 103 patients (91 males; age 64+/-12 years) with significant left ventricular (LV) dilatation. They were divided into ICM group (n=69) with significant coronary disease, and non-ICM (n=34) group without coronary disease. We devised a novel and simple parameter; the short-axis sphericity index (SI), to evaluate global LV remodeling, and used coaptation depth (CD) and tenting area (TA) to evaluate mitral deformity. RESULTS: In all cases, CD, TA and left atrium diameter (LAD) correlated positively with maximum regurgitation area (MRA) (r=0.54, 0.57, 0.57; P<0.0001). A negative correlation was observed between MRA and SI (r=-0.33, P=0.0008). There was no significant relationship between MRA and LV ejection fraction (EF). In non-ICM cases, SI tended to be lower with reduced EF. Multivariate stepwise linear regression analysis showed the following equations; ICM: MRA=-9.4+0.81CD+0.21LAD (r2=0.47, P<0.0001), non-ICM: MRA=-7.2+0.17LVDs (LV end systolic diameter) -8.7SI+0.27LAD (r2=0.63, P<0.0001). CONCLUSIONS: The strongest determinants of functional MR severity differ in ICM and non-ICM. While LV diameter and SI (global LV remodeling index) mainly determine the severity in non-ICM, CD that reflects mitral deformity is the major determinant in ICM.

Catecholamine analysis with microcolumn LC-peroxyoxalate chemiluminescence reaction detection.

BACKGROUND: Plasma catecholamines (CAs) are widely used as an index of sympathetic nervous system activity. In addition, CAs are known to be metabolized by catechol-O-methyltransferase (COMT) to produce their 3-O-methyl metabolites. We previously established a sensitive determination method of CAs and their 3-O-methyl metabolites using HPLC-peroxyoxalate chemiluminescence (POCL) reaction detection system. In this study, a microcolumn (100 x 1.0 mm I.D.) was used for separation to obtain higher sensitivity and shorter analysis time. METHODS: The system included automated precolumn ion-exchange extraction of amines, followed by separation on an ODS column, coulometric oxidation, fluorescence derivatization with ethylenediamine, and finally POCL reaction detection. RESULTS: The detection limits for CAs and their 3-O-methyl metabolites were 0.3-2.0 fmol. The analysis time was about 35 min, about half that of previously reported results. The method developed was used in monitoring changes in CAs and 3-O-methyl metabolite concentrations in human plasma during exercise. CONCLUSION: The simultaneous determination method for concentrations of CAs and their 3-O-methyl metabolites in human plasma was developed using micro LC-peroxyoxalate chemiluminescence detection. We were successful in quantitating the changes in plasma CAs and their 3-O-methyl metabolites during exercise.

[Clinical experience with nifedipine in the treatment of angina pectoris in Japan].

Developed by Bayer in Germany, nifedipine was shown to be effective in the treatment of patients with angina pectoris by Japanese investigators. Professor Kimura first reported the efficacy of nifedipine in patients with angina pectoris and those findings have been replicated in numerous trials conducted since then. Clinical trials found a low incidence of fixed coronary artery stenosis in Japanese patients with variant angina pectoris, and a complete antianginal response with Ca2+ channel antagonist such as nifedipine. It was hypothesised that the mechanism of this benefit with nifedipine was because of a strong coronary vasodilating action along with an inhibitory effect on coronary spasm. Recent evidence has established the tolerability and efficacy of once-daily dosage forms, which provide stable plasma nifedipine concentrations, in the management of coronary artery disorders.

Effect of pravastatin on progression of coronary atherosclerosis in patients after coronary artery bypass surgery.

BACKGROUND: Although the anti-atherosclerotic effects of HMG-CoA reductase inhibitors are well known, their specific effect on saphenous vein grafts after coronary artery bypass graft (CABG) operation is not well documented and has not been studied in Japan, so the aim of the present prospective randomized controlled study involving 27 Japanese institutions was to investigate the effects of pravastatin on the progression of atherosclerosis in such grafts and native coronary arteries after CABG. METHODS AND RESULTS: A total of 303 patients who had undergone CABG were randomly assigned to either the pravastatin group (n =168) or the control group (n = 167). Paired coronary angiograms were obtained at baseline and at the end of 5-year follow-up in 182 (60%) patients. The low-density lipoprotein cholesterol concentration significantly decreased in the pravastatin group from 141.4 mg/dl to 113.7 mg/dl (-19.6%), compared with 141.1 mg/dl to 133.7 mg/dl (-5.2%) in the control group (p < 0.001). Although there was no significant difference in the quantitative coronary angiography measurements between the 2 groups, the global change score indicated a significant pravastatin-mediated reduction in plaque progression (p < 0.01). CONCLUSIONS: Pravastatin can potentially reduce atherosclerotic progression in both the bypass graft and native coronary arteries of patients after CABG.

Pre-operative atrial fibrillation as the key determinant of outcome of mitral valve repair for degenerative mitral regurgitation.

AIMS: To examine the impact of pre-operative atrial fibrillation (AF) on the outcome of mitral valve repair (MVR) for degenerative mitral regurgitation (MR). METHODS AND RESULTS: Among 392 patients with moderate to severe MR who underwent MVR between 1991 and 2002, 283 patients with isolated degenerative MR were followed for 4.7+/-3.3 years. Of 27 deaths, nine were due to cardioembolic events and four were due to left ventricular (LV) dysfunction. When compared with patients with pre-operative AF, those with sinus rhythm (SR) had better survival (96+/-2.1 vs. 87+/-3.2% at 5 years, P=0.002) and higher cardiac event-free rates (96+/-2.0 vs. 75+/-4.4% at 5 years, P<0.001). In patients with pre-operative SR, observed and expected survival were similar (P=0.811). Cox multivariable regression analysis confirmed AF [P=0.027, adjusted hazard ratio (AHR) 2.9] and age as independently predictive of survival, and AF (P=0.002, AHR 3.1), New York Heart Association Class, and LV fractional shortening as independently predictive of cardiac event. CONCLUSION: Death due to LV dysfunction was not frequent and cardioembolic events due to AF were the leading cause for cardiac death. Pre-operative AF became a strong independent predictor of survival and morbidity. Patients with pre-operative SR had excellent prognosis. The benefits of preventing cardioembolic events due to AF validate the indication of MVR for patients with high risk for AF.

Quantitative coronary angiogram analysis: nifedipine retard versus angiotensin-converting enzyme inhibitors (JMIC-B side arm study).

This study was performed to compare the effects of nifedipine retard and angiotensin-converting enzyme (ACE) inhibitors on the progression of coronary atherosclerosis by means of quantitative coronary angiogram. Coronary angiogram was performed before the start of the study and during the 3-year treatment period. This study was conducted on the assumption that possible coronary vasodilation, which may be caused by nifedipine, was excluded by administration of sufficient isosorbide dinitrate. The changes from the baseline in the minimum lumen diameter of the coronary artery in all measured segments were negligible in the nifedipine group (+0.02+/-0.27 mm; P=0.543), whereas they were significantly reduced in the ACE inhibitor group (-0.12+/-0.27 mm; P<0.001), with a significant difference observed between the groups (P=0.002). The number of progressors in the nifedipine group was significantly lower than that in the ACE inhibitor group (P=0.019), and there was also a significant difference between the groups in the number of patients in whom > or =1 lesion developed after treatment (P=0.040). However, the changes of minimum lumen diameter stratified by baseline percent diameter stenosis demonstrated that progression of coronary atherosclerosis was suppressed in the nifedipine group for lesions with a percent diameter stenosis of < or =40 but was suppressed in both groups for those with a percent diameter stenosis of > or =41. This study suggests that nifedipine retard and ACE inhibitors may be effective in suppression of progression of coronary atherosclerosis, and that nifedipine in particular may be effective for mild to moderate stenosis.

Nifedipine retard was as effective as angiotensin converting enzyme inhibitors in preventing cardiac events in high-risk hypertensive patients with diabetes and coronary artery disease: the Japan Multicenter Investigation for Cardiovascular Diseases-B (JMIC-B) subgroup analysis.

We stratified findings from the Japan Multicenter Investigation for Cardiovascular Diseases-B according to whether or not the patients had diabetes and compared the incidence of cardiac events occurring over a 3-year period between treatment with nifedipine retard and angiotensin converting enzyme (ACE) inhibitor. The primary endpoint was the overall incidence of cardiac events (cardiac death or sudden death, myocardial infarction, hospitalization for angina pectoris or heart failure, serious arrhythmia, and coronary interventions), and the secondary endpoints were a composite of other events (cerebrovascular accidents, worsening of renal dysfunction, non-cardiovascular events, and total mortality). The results showed no significant difference in the incidence of the primary endpoint between the nifedipine group (n=199) and the ACE inhibitor group (n=173) in diabetic patients: 15.08% vs. 15.03%, relative risk 1.06, p=0.838. Also in nondiabetic patients, no significant difference was observed between the former (n=629) and the latter (n=649): 13.67% vs. 12.33%, relative risk 1.04, p=0.792. Similar results were obtained for the incidence of the secondary endpoints: in diabetic patients, 5.03% vs. 5.20%, relative risk 0.89, p=0.799; in nondiabetic patients, 2.70% vs. 2.47%, relative risk 1.07, p=0.842. Achieved blood pressure levels were 138/76 and 136/77 mmHg in the nifedipine group and 140/78 and 138/79 mmHg in the ACE inhibitor group in diabetic and nondiabetic patients, respectively. This study showed that nifedipine retard was as effective as ACE inhibitors in reducing the incidence of cardiac events in extremely high-risk hypertensive patients with complications of diabetes and coronary artery disease.

Is angiotensin-converting enzyme inhibitor useful in a Japanese population for secondary prevention after acute myocardial infarction? A final report of the Japanese Acute Myocardial Infarction Prospective (JAMP) study.

BACKGROUND: Although angiotensin-converting enzyme (ACE) inhibitors have appeared to be useful for secondary prevention after acute myocardial infarction (AMI) in Western countries, that has not been confirmed in non-western countries. We investigated whether ACE inhibitors improve survival rates in patients who have survived an AMI in Japan. METHODS: A randomized controlled trial, the first non-pharmaceutical company-supported multicenter trial of a medication in Japan, was carried out in 48 institutions from 1993 to 2000. A total of 888 of 1163 patients with AMI were eligible for the full analysis set (FAS). The mean patient age was 62 years, and 78% of patients were men. Subjects were randomized to 2 groups; 422 received ACE inhibitors and 466 did not receive ACE inhibitors. The primary end point was combined cardiac events, which was defined as cardiac or non-cardiac death, recurrent non-fatal myocardial infarction, coronary revascularization, and hospitalization because of worsening angina or congestive heart failure. The mean follow-up period was 5.8 years. RESULTS: There were no significant differences in the 2 groups in baseline data. During the follow-up period, 3 patients were lost to follow-up. With Kaplan-Meier analysis, the annual rate of total cardiac events was 32% in both groups. After adjustment for clinical baseline data, ACE inhibitor administration was not revealed with Cox regression analysis to have a significant prognostic effect in our study. CONCLUSION: We did not show a significant improvement in outcome with ACE inhibitor administration in subjects who survived after AMI in a Japanese study population. Further evaluations with a larger population or in subjects who are at a higher risk for AMI are necessary to confirm our findings.

A randomized, open-label, comparative study of simvastatin plus diet versus diet alone on angiographic retardation of coronary atherosclerosis in adult Japanese patients: Japanese utilization of simvastatin therapy (JUST) study.

BACKGROUND: Cholesterol-lowering therapy reduces the risk of cardiovascular events by slowing the progression or enhancing the regression of coronary atherosclerosis. OBJECTIVE: This study assessed the effects of simvastatin 10 mg/d on progressive coronary atherosclerosis in Japanese patients with coronary artery disease and mild to moderate hypercholesterolemia. METHODS: In a 2-year, open-label comparative study, patients with coronary atherosclerotic lesions (> or =50% diameter stenosis) and serum total cholesterol levels > or =200 and < or =280 mg/dL were randomly assigned to 2 groups: 1 group received simvastatin 10 mg/d taken orally with diet (S-D) and the other group was assigned to diet alone (D). Atherosclerotic progression in coronary segments was compared in the 2 groups using quantitative coronary angiography (QCA). QCA measurements were done under blinded conditions. The study's primary end point was the comparison of mean changes in each segment's minimum obstruction diameter (MOD) or mean segment diameter (MSD) between the S-D group and the D group. RESULTS: A total of 299 patients were randomized, 146 to the S-D group and 153 to the D group. Mean (SD) age was 58.7 (8.0) years and mean (SD) total cholesterol level was 232.6 (21.6) mg/dL at baseline. After 2 years, serum low-density lipoprotein cholesterol levels decreased by 31.9% in the S-D group and by 2.0% in the D group. QCA showed significant stenotic progression in the D group, with reductions in MOD and MSD both by per-segment-based (P < 0.001 and P = 0.004, respectively) and per-patient-based (both P = 0.004) analyses. Although simvastatin treatment suppressed atherosclerotic progression in both per-segment- and per-patient-based analyses, significant reductions were found only in MOD values with per-segment-based analyses (P = 0.034). In a categorical approach, progression was found in significantly fewer segments in the S-D group compared with the D group (MOD, P = 0.014; MSD, P = 0.003), with odds ratios (S-D) group/D group) of 0.571 for MOD and 0.390 for MSD. Significantly fewer patients with angiographic progression were observed in the S-D group (23.3%) compared with the D group (39.4%) with respect to MSD (P = 0.02). CONCLUSION: Two years of treatment with simvastatin 10 mg/d improved patients' lipid profile and retarded coronary atherosclerotic progression in Japanese patients with coronary artery disease and mild to moderate hypercholesterolemia

Impact of mitral regurgitation on long-term survival in patients with ischemic cardiomyopathy: efficacy of combined mitral valve repair and revascularization.

Ischemic cardiomyopathy complicated by severe mitral regurgitation (MR) has a poor prognosis. In such cases, whether mitral valve repair for MR improves the prognosis of survival remains unclear. In this study, 50 patients diagnosed with ischemic cardiomyopathy at our hospital between August 1991 and August 1996 were studied to examine the long-term prognosis and factors determining the prognosis. Among 17 patients with the complication of severe MR, 11 underwent mitral valve repair (repair group) and 6 did not (nonrepair group). Among the 33 patients without MR, 15 underwent revascularization (revascularization group) and 18 received medical treatment alone (medical group). Patients with MR showed significantly poorer baseline activities of daily living (ADL) [New York Heart Association (NYHA) class III or above: MR(+) vs MR(-) = 14 vs 8; P = 0.0001] and survival rate [MR(+) vs MR(-); log rank = 3.8, P = 0.05]. In contrast, patients in whom mitral valve repair was actively performed to resolve MR had favorable outcomes for both ADL (NYHA class improved from 3.9 +/- 0.3 to 2.7 +/- 1.0; P = 0.0004) and survival rate (MV repair vs nonrepair: long rank = 10.1, P = 0.0015). In addition, among patients without MR, the revascularization group showed more favorable results in terms of ADL (NYHA class improved from 3.5 +/- 0.7 to 2.5 +/- 0.8; P = 0.0059) and survival rate (revascularization vs medical: log rank = 3.7, P = 0.05), irrespective of improvement of left ventricular function. When the factors determining the prognosis for ischemic cardiomyopathy were examined by multivariate analysis, whether or not revascularization was conducted, the presence or absence of mitral regurgitation, and if present, whether or not mitral valve repair was performed were identified as independent factors determining the prognosis (revascularization: hazard ratio = 0.121, P = 0.012; absence of MR: hazard ratio = 0.104, P = 0.050; mitral valve repair: hazard ratio = 0.018, P = 0.005). These results showed that revascularization should be conducted as actively as possible in patients with ischemic cardiomyopathy; in addition, for those patients with mitral regurgitation, mitral valve repair should be conducted actively to relieve it.