Effect of early use of low-dose pravastatin on major adverse cardiac events in patients with acute myocardial infarction: the OACIS-LIPID Study.

BACKGROUND: It is unclear whether early initiation of low-dose pravastatin therapy can reduce the occurrence of major adverse cardiac events after acute myocardial infarction (AMI). METHODS AND RESULTS: The study group comprised 353 patients with AMI who had plasma total cholesterol levels of 200-250 mg/dl and triglyceride levels <300 mg/dl. The patients were randomly assigned to either receive pravastatin (10 mg/daily, n=176) or not (n=177). The primary endpoint was a composite of death, nonfatal myocardial infarction (MI), unstable angina (UA), stroke, revascularization, and rehospitalization because of other cardiovascular disease. The follow-up period was 9 months. The primary endpoint occurred in 31 patients (17.9%) in the pravastatin group and 55 patients (31.4%) in the non-pravastatin group (relative risk, 0.56; 95% confidence interval, 0.36-0.87). There were no significant differences in the risk of death, nonfatal MI, UA, and stroke between the 2 groups, although the pravastatin group had a lower risk of need for revascularization. CONCLUSION: For patients with AMI, early and low-dose pravastatin therapy (10 mg/daily) reduces recurrent major adverse cardiac events, mostly the requirement for revascularization.

Impact of atherosclerosis-related gene polymorphisms on mortality and recurrent events after myocardial infarction.

Although previous epidemiologic studies have suggested an association between the onset of myocardial infarction (MI) and some genetic variations, the impact of these variants on recurrent cardiovascular events after MI has not been fully elucidated. We genotyped 87 polymorphisms of 73 atherosclerosis-related genes in consecutive acute MI patients registered in the Osaka Acute Coronary Insufficiency Study and compared the incidence of death and major adverse cardiac events (MACE) among the polymorphisms of each gene. After initial screening in 507 patients, we selected nine polymorphisms for screening in all 1586 patients. Multivariate Cox regression analysis revealed that G allele carriers at the position 252 of the lymphotoxin alpha (LTA) gene were independently associated with an increased risk of death (hazard ratio [HR]: 2.46; 95% CI: 1.24-4.86). In conclusion, a 252G allele of LTA is associated with an increased risk of death after AMI and may be a useful genetic predictor.

Influence of serotonin transporter gene polymorphism on depressive symptoms and new cardiac events after acute myocardial infarction.

BACKGROUND: In patients with acute myocardial infarction (AMI), depressive symptoms increase the risk for cardiac events. Recently, the S allele of the serotonin transporter (5-HTT) gene-linked polymorphic region was shown to reduce transcription of this gene and thus reduce serotonin reuptake, and this allele is linked with depressive symptoms as well as other psychiatric diseases. However, the influence of the S allele on depressive symptoms and cardiac events after AMI is unclear. METHODS: To investigate whether the S allele was associated with depressive symptoms and cardiac events after AMI, we prospectively examined depressive symptoms and new cardiac events in 2509 genotyped patients with AMI. RESULTS: Depressive symptoms were more common in patients with the S allele than in those without it (48.3% vs 35.0%, P = .02). Multivariate analysis revealed that the S allele was independently associated with depressive symptoms (odds ratio 2.19, 95% confidence interval [CI] 1.21-3.98, P = .01). Cardiac events (cardiac death, revascularization, heart failure, reinfarction, arrhythmia, and unstable angina) were more frequent in patients with the S allele than in those without it (31.3% vs 22.3%, P = .046). Multivariate Cox regression analysis revealed an association between the S allele and an increased risk for cardiac events (hazard ratio [HR] 1.69, 95% CI 1.03-2.78, P = .04). However, the HR became insignificant after an adjustment for depressive symptoms (HR 1.30, 95% CI 0.84-2.01, P = .24). CONCLUSIONS: The S allele in the 5-HTT gene-linked polymorphic region is associated with an increased risk for subsequent cardiac events, which is mediated, at least in part, by the depressive symptoms in patients after AMI.

Identification of uncomplicated patients with acute myocardial infarction undergoing percutaneous coronary intervention: are these patients suitable for early discharge?

BACKGROUND: The hospital stay after acute myocardial infarction (AMI) is still extremely long in Japan and does not correspond with disease severity. The purpose of the present study was to identify a subgroup of AMI patients suitable for early discharge. METHODS AND RESULTS: A total of 3,739 AMI patients treated with percutaneous coronary intervention (PCI) within 24 h after onset, who enrolled Osaka Acute Coronary Insufficiency Study between April 1998 and March 2004, were studied. Patients showing no complications within the first 7 days (n=1,786) were considered to be eligible for early discharge. In these patients, multivariate logistic regression analysis selected prior myocardial infarction, left anterior descending coronary artery disease and failed PCI as independent predictors of major complications from day 8 to discharge. Patients without any predictor had significant lower rates of major complications from day 8 to 6 months after discharge than those with 1 or more predictors. Furthermore, in the present study there were no deaths in patients without any predictors. CONCLUSION: Patients who either do not have serious complications during the first 7 days or any predictor are at very low risk of major complications from day 8 to 6 months after discharge. These carefully selected patients may be suitable for early (day 8) hospital discharge after AMI.

Longitudinal study of acute myocardial infarction in the southeast Osaka district from 1988 to 2002.

BACKGROUND: Data on clinical characteristics, long-term mortality rates, and factors influencing outcome of acute myocardial infarction (AMI) based on an unselected cohort in the percutaneous coronary intervention (PCI) era are still limited in Japan. METHODS AND RESULTS: In the present study 415 consecutive patients with AMI who were admitted to hospital within 24 h of symptom onset between January 1988 and December 2002 were studied. There was a marked seasonal variation of AMI with a minimum in summer and a maximum in winter, as well as a marked circadian variation with a significant morning peak. Overall, 45.8% of patients were treated with primary PCI. Increased age and female sex were negatively associated with the probability of undergoing PCI. During the follow-up period (mean duration, 4.01+/-3.41 years), the unadjusted long-term all-cause mortality rate was 21.4%. Multivariate Cox regression analysis showed that age, prior cerebrovascular disease, renal failure, Killip > or =2, and ventricular tachycardia/fibrillation were independent predictors of worse long-term mortality after AMI. Furthermore, the use of PCI was independently associated with favorable long-term survival after AMI. CONCLUSIONS: Although PCI was associated with a favorable long-term mortality, it remains underused in subsets of patients and increased use may further reduce the long-term mortality rate in Japanese AMI patients.

Relation of C-reactive protein and one-year survival after acute myocardial infarction with versus without statin therapy.

We evaluated the interaction between inflammation and survival benefit from statin therapy in patients who had acute myocardial infarction. Although 1-year mortality did not differ between patients who used statin therapy and those who did not, among patients who had C-reactive protein (CRP) concentrations in the lower 2 tertiles (<2.9 mg/L), 1-year mortality was higher in patients who used statin therapy than in those who did not within the highest CRP-defined tertile (> or =2.9 mg/L). Statin therapy significantly decreased the hazard ratio for 1-year mortality in patients who had high CRP levels to approximately the hazard present for patients who had low CRP levels and did not receive statin therapy.

Impact of smoking status on long-term mortality in patients with acute myocardial infarction.

BACKGROUND: Cessation of smoking after a cardiovascular event has been shown in Western countries to have a beneficial effect on clinical events during long-term follow-up. However, knowledge of the effect of smoking status after acute myocardial infarction (AMI) on the long-term mortality based on a large-scale sample is still limited in Japan. METHODS AND RESULTS: In the present study 2,579 AMI patients were enrolled in the Osaka Acute Coronary Insufficiency Study (OACIS) between April 1998 and March 2003. Smoking status was assessed at baseline and 3 months after hospital discharge by mailed questionnaire. Patients were divided into nonsmokers (n=823), former smokers (those who had stopped smoking before AMI onset, n=332), quitters (those who stopped smoking after AMI onset, n=1,056), and persistent smokers (those who smoked before and after AMI, n=368). Quitters had lower long-term mortality rates than persistent smokers (3.0% vs 5.2%; log rank, p=0.032). Multivariate Cox regression analysis revealed that smoking cessation was independently associated with a reduction in risk of long-term mortality (hazard ratio, 0.39; 95% confidence interval, 0.20-0.77). CONCLUSIONS: Patients who continue to smoke after AMI are at greater risk for death than patients who quit smoking. Cessation of smoking benefits the long-term prognosis in patients with AMI.

Predictors of length of hospital stay after acute myocardial infarction in Japan.

BACKGROUND: In Western countries, the length of hospital stay after acute myocardial infarction (AMI) has decreased dramatically during the past 3 decades and is now approximately 1 week. However, epidemiological data concerning the length of hospital stay, its predictors and trends based on a large-scale sample are still limited in Japan. METHODS AND RESULTS: The study group comprised 4,113 surviving AMI patients who were enrolled in the Osaka Acute Coronary Insufficiency Study from April 1998 to March 2003. The mean length of hospital stay was 31.2 days. Clinical factors (patient characteristics, severity of infarction, therapy, and in-hospital complications) only explained 26% of the variation in hospital stay. The mean hospital stay was significantly longer in 1998 than in 2002. In 2002, occupational status and admission to a high-volume hospital were independent predictors of a shorter hospital stay, but this association was not observed in 1998. CONCLUSIONS: The hospital stay is still extremely long in Japan and clinical factors do not provide an explanation. The findings of the present study suggest that the hospital stay could be reduced in some patients with AMI, but randomized studies are needed to examine the feasibility of early discharge.

Reduced collateral circulation to the infarct-related artery in elderly patients with acute myocardial infarction.

OBJECTIVES: The purpose of this study was to investigate the hypothesis that circulation via collateral vessels to an infarct-related artery (IRA) is impaired with aging in patients with acute myocardial infarction (AMI). BACKGROUND: Animal experiments have shown that advanced age blunts the development of new vessels in response to angiogenic cytokines. METHODS: Of 3,573 consecutive patients with AMI, 1,934 patients who fulfilled the following criteria were enrolled in this study: 1) coronary angiograms were obtained within 72 h after the onset of AMI; and 2) IRA showed complete occlusion (Thrombolysis In Myocardial Infarction [TIMI] flow grade 0 or 1). Collaterals to the IRA were angiographically evaluated using the Rentrop score. Rentrop scores 1 to 3 were defined as demonstrating significant collaterals. RESULTS: The prevalence of collaterals decreased with age, from 47.9%, 45.8%, 43.4%, to 34.0% in patients <50 years, 50 to 59 years, 60 to 69 years, > or =70 years, respectively (p < 0.001). Advanced age was an independent factor predicting the absence of collateral circulation to the IRA. In contrast, time to catheterization, history of angina pectoris, and preinfarction angina were independent predictors for the presence of collaterals. Multivariate analysis showed that the absence of collaterals was an independent predictor of in-hospital mortality in elderly patients > or =70 years (odds ratio, 15.6; 95% confidence interval, 3.5 to 69.6), although this finding was not significant in patients <70 years. CONCLUSIONS: Advanced age is associated with decreased angiographic presence of collaterals to the IRA in patients with AMI. This abnormality may contribute to the poor prognosis of elderly patients with AMI.

[Effect of successful late reperfusion by primary coronary angioplasty on mechanical complications of acute myocardial infarction].

It has been suggested that early treatment decreases, but late treatment increases, the risk of mechanical complications for a thrombolytic strategy. However, few studies have evaluated whether late reperfusion by primary coronary angioplasty decreases the risk of mechanical complications. A total of 2,209 patients with acute myocardial infarction treated with primary coronary angioplasty within 24 hr after the onset of symptoms were divided into three groups: early reperfusion (ER; <- 12 hr, n = 1,647), late reperfusion (LR; > 12 hr, n = 219), and failed reperfusion (RF; n = 343). We evaluated the incidence, risk ratio, and predictors of mechanical complication. The overall incidence of mechanical complications was 2.0%. The incidence of mechanical complications was highest in the FR group (ER 1.4%, LR 1.8%, FR 5.0%, p <0.01). After adjusting for clinical variables, the risk ratio for mechanical complications increased in the FR group compared with LR group [risk ratio 7.34, 95% confidence interval (CI) 1.02 - 52.80, p = 0.04]. Predictors of an increased risk of mechanical complications by multivariate analysis were age >- 70 years (odds ratio 3.68, 95% CI 1.56-8.64, p < 0.01), Killip class >- II (odds ratio 3.73, 95% CI 1.52-9.12, p >- 0.01), absence of collateral vessels (odds ratio 4.09, 95% CI 1.17-14.26, p = 0.03), and FR (odds ratio 2.68, 95% CI 1.01-6.61, p = 0.03). In conclusion, successful late reperfusion by primary coronary angioplasty is associated with the reduced risk of mechanical complications in patients with acute myocardial infarction.

Prognostic significance of atrial fibrillation/atrial flutter in patients with acute myocardial infarction treated with percutaneous coronary intervention.

Atrial fibrillation (AF) is a frequent complication after acute myocardial infarction (AMI) that has been associated with increased in-hospital and long-term mortality rates in the prethrombolytic and thrombolytic eras. Current therapies, including percutaneous coronary intervention (PCI), are effective in reducing mortality in patients with AMI. However, little is known concerning the incidence and prognostic significance of AF in patients with AMI who are treated with PCI. We evaluated 2,475 consecutive patients with AMI who underwent PCI within 24 hours after onset and who were enrolled in the Osaka Acute Coronary Insufficiency Study. Patients were categorized into 2 groups according to the presence of AF or atrial flutter. The incidence of AF was 12.0%. Patients with AF were older, were in higher Killip classes, had higher rates of previous myocardial infarction and previous cerebrovascular disease, had systolic blood pressure of <100 mm Hg and heart rates of > or =100 beats/min, multivessel disease, and had poorer reperfusion of the infarct-related artery than those without AF. Patients with AF had higher in-hospital (16.0% vs 6.7%, p <0.001) and 1-year (18.9% vs 7.9%, p <0.001) mortality than those without AF. Multivariate Cox regression analysis revealed that AF was an independent predictor of 1-year mortality (hazard ratio 1.64, 95% confidence interval 1.05 to 2.55) but was not a predictor of in-hospital mortality. AF is a common complication in patients with AMI who are treated with PCI and independently influences 1-year mortality.

Effect of successful late reperfusion by primary coronary angioplasty on mechanical complications of acute myocardial infarction.

It has been suggested that early treatment decreases, but late treatment increases, the risk of mechanical complications for a thrombolytic strategy. However, few studies have evaluated whether late reperfusion (LR) by primary coronary angioplasty decreases the risk of mechanical complications. A total of 2,209 patients with acute myocardial infarction treated with primary coronary angioplasty within 24 hours after the onset of symptoms were divided into 3 groups: early reperfusion (ER; < or =12 hours, n = 1,647), LR (>12 hours, n = 219), and failed reperfusion (FR; n = 343). We evaluated the incidence, risk ratio, and predictors of mechanical complications. The overall incidence of mechanical complications was 2.0%. The incidence of mechanical complications was highest in the FR group (ER 1.4%, LR 1.8%, FR 5.0%; p <0.01). After adjusting for clinical variables, the risk ratio for mechanical complications increased in the FR group compared with the LR group (risk ratio 7.34, 95% confidence interval [CI] 1.02 to 52.80; p = 0.04). Predictors of an increased risk of mechanical complications by multivariate analysis were age > or =70 years (odds ratio [OR] 3.68, 95% CI 1.56 to 8.64; p <0.01), Killip class > or =II (OR 3.73, 95% CI 1.53 to 9.12; p <0.01), absence of collateral vessels (OR 4.09, 95% CI 1.17 to 14.26; p = 0.03), and FR (OR 2.68, 95% CI 1.09 to 6.61; p = 0.03). In conclusion, successful LR by primary coronary angioplasty is associated with the reduced risk of mechanical complications in patients with acute myocardial infarction.

Joint effects of Chlamydia pneumoniae infection and classic coronary risk factors on risk of acute myocardial infarction.

BACKGROUND: Although not in itself strongly predictive of coronary heart disease, Chlamydia pneumoniae infection could interact with classic risk factors in determining risk of acute myocardial infarction (AMI). METHODS: We assessed C pneumoniae immunoglobulin (Ig) G and IgA titers and classic risk factors in 618 patients with AMI and in 967 controls. RESULTS: IgG titers were not related to AMI, but a significant association was seen between IgA titers and AMI. Excess risk of AMI was noted mainly among patients with the highest IgA titers, such as those beyond 2.88 (the 95th percentile cutoff point in control subjects), showing a 1.8-fold increase in risk (odds ratio 1.75, 95% CI 1.04-2.92). Classic risk factors did not differ between subjects with IgA titers above and below the 95th percentile cutoff. However, in multivariate analyses, models incorporating both IgA titers and a classic risk factor such as obesity, hypercholesterolemia, or smoking predicted risk more effectively than single-parameter models. For example, the odds ratio for AMI among subjects with the highest IgA titers plus hypercholesterolemia was greater than the product of individual risks associated with these high IgA titers and with hypercholesterolemia. CONCLUSIONS: Interactions with classic risk factors (ie, obesity, hypercholesterolemia, and smoking), increased the predictive value of C pneumoniae IgA antibody titers in determining risk of AMI.

Impact of high-sensitivity C-reactive protein on predicting long-term mortality of acute myocardial infarction.

Although the C-reactive protein (CRP) concentration measured shortly after acute myocardial infarction (AMI) is associated with infarct size, its prognostic value is controversial. The reduction of CRP is accelerated by reperfusion. Therefore, the CRP concentration, measured during the stable phase of AMI in patients treated predominantly with reperfusion therapies, may be independent of infarct size and may predict long-term mortality. We studied 1,309 patients with AMI enrolled in the Osaka Acute Coronary Insufficiency Study between April 1999 and June 2001. CRP was measured during the stable phase (mean 25 days after AMI onset). The patients were followed for an average of 522 days. Reperfusion therapies were performed in 90% of the patients. Patients in the highest quartile of CRP values (> or =0.38 mg/dl) were older, had higher prevalences of diabetes mellitus, and had higher Killip classes than patients in the lower 3 quartiles (<0.38 mg/dl). Multivariate logistic regression analysis revealed that CRP was independently associated with age and the absence of revascularization therapies. Patients in the highest quartile had a higher long-term mortality rate than patients in the lower 3 quartiles (8.9% vs 2.0%; p <0.001). Multivariate Cox regression analysis revealed that the highest quartile of CRP values was an independent predictor of long-term mortality (hazard ratio 4.94, 95% confidence interval 1.13 to 21.6). We conclude that CRP measured during the stable phase of AMI is not associated with infarct size in the reperfusion era but is significantly associated with long-term mortality of AMI.

Prevalence of Helicobacter pylori infection and its link to coronary risk factors in Japanese patients with acute myocardial infarction.

The association between Helicobacter pylori (H. pylori) infection and coronary artery disease, as well as the association between H. pylori infection and classic coronary risk factors, is controversial in patients from Western countries. The high prevalence of H. pylori infection in Japanese subjects enables an examination of these associations in a large population, especially in young patients, because coronary risk factors may be more strongly associated with younger individuals than with older individuals. The IgG seropositivity to H. pylori was assessed in 618 cases with acute myocardial infarction (AMI) and in 967 controls. The prevalence of seropositivity to H. pylori was similar between cases and controls, but in subjects younger than 55 years, the rate was significantly higher in cases than in controls (58.7% vs 43.3%, p = 0.009). After adjustment for age, gender, diabetes mellitus, hypertension, smoking, body mass index, total cholesterol, and high density lipoprotein cholesterol, the odds ratio for acute myocardial infarction was 2.97 (95% confidence interval, 1.37-6.41; p = 0.006). Worsening of classic coronary risk factors was not associated with H. pylori infection in subjects younger than 55 years. These results suggest that in younger individuals in Japan, H. pylori infection is significantly associated with AMI independent of the classic coronary risk factors.

Depressive symptoms predict 12-month prognosis in elderly patients with acute myocardial infarction.

BACKGROUND: Several studies have associated depressive symptoms with an increased risk for cardiac events after the onset of acute myocardial infarction (AMI). The aim of the present study is to investigate the impact of the depressive symptoms on prognosis of the elderly patients with AMI. METHOD: Depression was assessed in consecutive patients with AMI (n = 1042; mean age 63 +/- 11 years) using the Zung Self-Rating Depression Scale (SDS). Patient with a score > or = 40 was classified as having depressive symptoms. Cardiac events (cardiac death, nonfatal re-MI, coronary angioplasty or bypass surgery, readmission for heart failure, unstable angina, or uncontrolled arrhythmia) were examined during 12 months follow-up period. RESULTS: Depressive symptoms were observed in 438 patients (42.0%). Prevalence of depression was not dependent of age (P = 0.60) and gender (P = 0.91). The rate of cardiac events was 31.2% per year in patients with depressive symptoms whereas 23.9% per year in patients without depressive symptoms. Multiple logistic regression analyses showed that depression was significantly associated with 1-year cardiac events (odds ratio 1.41, 95% CI 1.03 to 1.92, P = 0.03) after controlling for age, gender, severity of myocardial infarction, coronary risk factors, e.g. hypertension, diabetes mellitus and smoking habits. Depression was a significant risk factor for the cardiac events (log rank, P = 0.02) in the elderly patients (> or = 65 years old, 501 patients). However, the association of depression with cardiac events in the young patients (< 65 years old, 541 patients) was not statistically significant (P = 0.11). CONCLUSION: Depression after AMI is a significant predictor of 1-year cardiac events for Japanese population, and its presence augments the risk especially in the elderly patients.

Muscle pump-dependent self-perfusion mechanism in legs in normal subjects and patients with heart failure.

Leg venous pressure markedly falls during upright exercise via a muscle pump effect, creating de novo perfusion pressure. We examined physiological roles of this mechanism in increasing femoral artery blood flow (FABF) and its alterations in chronic heart failure (CHF). In 10 normal subjects and 10 patients with CHF, standard hemodynamic variables, mean ankle vein pressure (MAVP), and FABF with Doppler techniques were obtained during graded upright bicycle exercise. To evaluate a nonspecific blood flow response, normal subjects also performed supine exercise. In normal subjects, MAVP rapidly declined by 45 mmHg and FABF correspondingly increased 5.3-fold without a systemic pressor response during 10 s of light upright exercise at 5 W. Approximately 67% of the blood flow response was attributed to the venous pressure drop-dependent mechanism. In CHF patients, MAVP declined by only 36 mmHg and FABF increased only 1.7-fold during the same upright exercise. The muscle venous pump has an ability to increase FABF at least threefold via the venous pressure drop-dependent mechanism. This mechanism is impaired in CHF patients.