Effects of psychological stress on neutrophil phagocytosis and bactericidal activity in humans--a meta-analysis.

Several authors have reviewed the effects of psychological stress on lymphocyte activity. However the effect of psychological stress on neutrophil functions has not been reviewed. The present meta-analysis summarizes evidence of the effects of psychological stress on neutrophil phagocytosis and bactericidal activity collated from a MEDLINE search of the English literature. We searched the database to identify the relevant studies through April 30, 2013. Eleven studies met our inclusion criteria and we divided them into those addressing transient acute stress (3 studies, n=74), academic examinations (4 studies n=101) and chronic stress/life events (4 studies, n=193). We performed a meta-analysis of the data and calculated total standardized mean differences (SMD) to evaluate the effects of chronic stress. Transient acute stressors might both enhance and decrease these neutrophil functions. Academic examinations tended to elevate neutrophil functions. On the other hand, the total SMDs of neutrophil phagocytosis and bactericidal activity altered by chronic stress/life events were -0.589 (95% CI: -0.908 to -0.270, p<0.05) and -0.547 (95% CI: -0.845 to -0.248, p<0.05), respectively, indicating suppressive effects on these neutrophil functions. Further systematic review of more pooled studies is warranted to confirm that academic examinations might enhance, whereas chronic stress/life events might suppress these neutrophil functions.

Prognostic value of automated SPECT scoring system for coronary artery disease in stress myocardial perfusion and fatty acid metabolism imaging.

Quantitative SPECT analysis contributes to the diagnostic and prognostic assessment of coronary artery disease. A novel automated scoring system (heart score view) can provide identical quantitative information to that determined by expert visual analysis. The aim of the present study is to evaluate the prognostic value of the automated SPECT scoring system when applied to stress thallium and resting beta-methyl-iodophenyl pentadecanoic acid (BMIPP) SPECT images. After a preliminary validation of the automated system by comparison with expert visual analyses, outcome data from 151 consecutive patients with suspected or known coronary artery disease without prior myocardial infarction were analyzed using automated SPECT scores on stress thallium and resting BMIPP images. The software quantified abnormalities as summed stress (SSS), summed rest and summed difference scores for stress thallium and as summed BMIPP scores (SBS). Cardiac events occurred over a period of 48 months in 29 (19.2%) patients with diabetes mellitus, a lower left ventricular ejection fraction (LVEF) and more abnormal scores for thallium and BMIPP. Multivariate predictors of all cardiac events included diabetes mellitus and thallium SSS. The global Chi-square value was significantly increased when SSS was added to the clinical information (diabetes mellitus and LVEF). Negative predictive values of thallium SSS and SBS were almost identical at 84% for all cardiac events and 98% for hard cardiac events. Automatically quantified perfusion and BMIPP scores are related to cardiac events and these values can improve the risk stratification of coronary patients particularly when stress thallium imaging is combined with clinical information.

Detection of coronary artery disease using automated quantitation of myocardial perfusion on single-photon emission computed tomography images from patients with angina pectoris without prior myocardial infarction.

BACKGROUND: Whether or not automated scores obtained from myocardial single-photon emission computed tomography (SPECT) imaging using software correlate with the visual interpretations by experts remains obscure. METHODS AND RESULTS: Eighty-seven consecutive patients with known or suspected angina pectoris underwent (201)thallium stress/rest SPECT followed by coronary angiography and the summed difference scores (SDS) were calculated using Heart Score View software. The SDS was substantially associated with coronary stenosis and accurately detected culprit lesions, because the diagnostic accuracy was comparable to that of expert visual evaluation. CONCLUSIONS: Automated scores obtained from myocardial SPECT can help detect coronary artery disease.

Effects of life events and stress on neutrophil functions in elderly men.

BACKGROUND: Psychological stress or life events might significantly decrease neutrophil function in elderly individuals and lead to infectious diseases. However, relationships between these factors have not been examined in detail.We investigated the relationships between neutrophil function measured using the nitroblue tetrazolium (NBT) reduction test and measurements of psychological stress and life events among 81 men aged over 60 years. RESULTS: The numbers and scores for life events were significantly higher (p < 0.01, respectively) in a group with values reflecting phagocytosis below the median than in a control group. CONCLUSIONS: Chronic psychological stress due to life events decreases neutrophil functions among elderly men.

Coronary revascularization does not decrease cardiac events in patients with stable ischemic heart disease but might do in those who showed moderate to severe ischemia.

BACKGROUND: As an initial management strategy for stable ischemic heart disease (IHD), coronary revascularization therapy is thought to be equal to optimal medical therapy alone regarding prognosis. METHODS: Whether or not the effects of revascularization on the prognosis of patients with stable IHD are associated with the amount of ischemic myocardium detected by nuclear stress imaging was evaluated. This retrospective study analyzed data from 4629 patients with suspected or known IHD who underwent gated stress myocardial-perfusion SPECT at 117 hospitals in Japan. The follow-up periods were three years and the combined endpoints consisted of cardiac death, nonfatal myocardial infarction, and congestive heart failure requiring hospitalization. After matching propensity scores between patients who underwent early revascularization and those who did not (n=316 per group), we compared cardiac event rates in relation to the amount of ischemic myocardium. RESULTS: Cardiac event rates did not significantly differ between patients who underwent early revascularization and those who did not (5.4% vs. 6.4%). Among patients with ≤ 5%, 6-10%, and >10% ischemic myocardium, cardiac event rates were 8%, 3% and 0% respectively, who underwent early revascularization compared with 4.5%, 6.1%, and 12.3%, respectively, among those who did not. Cardiac event rates were significantly lower among patients with >10% ischemic myocardium who underwent early revascularization compared with those who did not (0% vs. 12.3%, p=0.0062). CONCLUSIONS: Coronary revascularization for stable IHD does not decrease major cardiac events in all patients but might do in patients with moderate to severe ischemia.

Cardiac event risk in Japanese subjects estimated using gated myocardial perfusion imaging, in conjunction with diabetes mellitus and chronic kidney disease.

BACKGROUND: Cardiac event risk is estimated using quantitative gated myocardial perfusion imaging (MPI) and clinical background in patients with ischemic heart disease. The aim of the present study was to calculate major cardiac event risk and tabulate it in the Heart Risk Table for clinical use of risk stratification. METHODS AND RESULTS: Multivariate logistic regression was performed based on a multicenter prognostic database (Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated Single-photon emission computed tomography [J-ACCESS investigation]) using MPI (n=2,395). The risk of major cardiac events (cardiac death, non-fatal myocardial infarction and heart failure requiring hospitalization) was estimated using age, ejection fraction (EF), estimated glomerular filtration rate (eGFR) and presence of diabetes mellitus (DM). Age-matched standard eGFR was determined in 77 subjects. Major cardiac event risk was calculated using the equation: risk (%/3 years)=1/(1+Exp(-(-4.699-0.0151×eGFR+0.7998×DM+0.0582×age+0.697×SSS-0.0359×EF))×100, where SSS refers to summed stress scores. Risk was determined without eGFR (the initial version) and using the present formula with eGFR (revised version), with consistent results. DM and chronic kidney disease were major determinants of cardiac events. CONCLUSIONS: Cardiac event risk was estimated using MPI defect score and left ventricular EF in conjunction with eGFR and the presence of DM. The risk table might be used for risk evaluation in Japanese patients undergoing MPI.

Estimation of cardiac event risk by gated myocardial perfusion imaging and quantitative scoring methods based on a multi-center J-ACCESS database.

BACKGROUND: Myocardial perfusion imaging (MPI) has been used to estimate cardiac event risk. The aim of the present study is to achieve stable risk estimation based on perfusion scoring and a multi-center prognostic database. METHODS AND RESULTS: Multivariate logistic regression analysis was performed to estimate cardiac event risk based on a J-ACCESS study. A stress-MPI was performed in 45 patients with coronary artery disease (CAD) and in 25 non-CAD patients. Perfusion defect scoring of summed stress score (SSS) was performed by 5 methods: (1) visual scoring; (2) automatic scoring of 3 short-axis and 1 vertical long-axis slices; (3) visual modification of Method 2; (4) automatic polar map scoring based on a Japanese multi-center database; and (5) visual modification of Method 4. Agreement of SSS between 2 observers was good (r=0.87-0.97). Agreement of estimated cardiac event risk between observers and among 5 methods was very good (r=0.99-1.00). Regarding diagnostic accuracy for CAD, Method 5 showed optimal diagnostic yields (sensitivity 84%, accuracy 77%). CONCLUSIONS: Estimation of cardiac event risk in conjunction with polar map segmentation and common normal databases resulted in stable risk values, and might be used for risk stratification in patients suspected of having CAD.

Validation of automated quantitation of myocardial perfusion and fatty acid metabolism abnormalities on SPECT images.

BACKGROUND: Myocardial perfusion and fatty acid imaging have played important roles in the risk stratification of patients with coronary artery disease (CAD). However, visual image assessment requires considerable experience and training. Therefore, an automated program has been developed that can quantify perfusion and fatty acid uptake on myocardial single emission computed tomography (SPECT). The present study aimed to validate the automated quantitative program. METHODS AND RESULTS: A total of 50 patients were studied with known or suspected CAD who underwent stress ²°¹Thallium (²°¹Tl) and resting ¹²³I-labelled ß-methyl iodophenyl pentadecanoic acid (BMIPP) SPECT. The SPECT images were quantified in 17 segments visually and using our Heart Score View software. Values were compared with those in a normal Japanese database and calculated summed stress (SSS), summed rest (SRS), summed difference (SDS), and summed BMIPP scores for each modality. Summed scores obtained using standard visual analysis and Heart Score View significantly correlated (²°¹Tl: SSS: r=0.934; SRS: r=0.827; SDS: r=0.743 summed BMIPP score: r=0.913) (each P<0.001) and Bland-Altman analysis revealed good agreement between the 2 approaches. CONCLUSIONS: Correlations between scores determined using Heart Score View software and standard visual interpretation were linear for both perfusion and fatty acid images. Thus, our new automated program might be useful for the risk stratification of patients with CAD in the clinical setting.

Risk stratification for cardiac death in hemodialysis patients without obstructive coronary artery disease.

The incidence of cardiac death is higher among patients receiving dialysis compared with the general population. Although obstructive coronary artery disease is involved in cardiac deaths in the general population, deaths in hemodialysis patients occur in the apparent absence of obstructive coronary artery disease. To study this further, we prospectively enrolled 155 patients receiving hemodialysis after angiography had confirmed the absence of obstructive coronary lesions. All patients were examined by single-photon emission computed tomography using the iodinated fatty acid analog, BMIPP, the uptake of which was graded in 17 standard myocardial segments and assessed as summed scores. Insulin resistance was determined using the homeostasis model assessment index of insulin resistance (HOMA-IR). During a mean follow-up of 5.1 years, 42 patients died of cardiac events. Stepwise Cox hazard analysis associated cardiac death with reduced BMIPP uptake and increased insulin resistance. Patients were assigned to subgroups based on BMIPP summed scores and HOMA-IR cutoff values for cardiac death of 12 and 5.1, respectively, determined by receiver operating characteristic analysis. Cardiac death-free survival rates at 5 years were the lowest (32.2%) in the subgroup with both a summed score and assessment equal to or above the cutoff values compared with any other combination (52.9-98.7%) above, equal to, or below the thresholds. Thus, impaired myocardial fatty acid metabolism and insulin resistance may be associated with cardiac death among hemodialysis patients without obstructive coronary artery disease.

Prediction of cardiac death in hemodialysis patients by myocardial fatty acid imaging.

OBJECTIVES: The aim was to evaluate the potential of single-photon emission computed tomography (SPECT) to predict cardiac death in chronic hemodialysis patients using the iodinated fatty acid analogue iodine-123 123I-beta-methyl iodophenyl-pentadecanoic acid (BMIPP). BACKGROUND: We previously reported that BMIPP SPECT could detect asymptomatic coronary artery disease with high sensitivity in hemodialysis patients. METHODS: We prospectively enrolled 375 asymptomatic hemodialysis patients who had undergone dual SPECT using 123I-BMIPP and 201thallium (Tl) chloride. Patients who had a clinical history of myocardial infarction and/or coronary revascularization were excluded from the study. Uptake on SPECT images was graded in 17 segments on a 5-point scale (0 normal, 4 absent) and assessed as summed BMIPP or Tl scores. RESULTS: During a 3.6 +/- 1.0-year follow-up, 57 patients who had undergone coronary revascularization within 60 days of SPECT were excluded from the analysis. Among the remaining 318 patients (male/female: 170/148; 64 +/- 12 years of age), 50 died of cardiac events (acute myocardial infarction 22, congestive heart failure 17, cardiac sudden death 11). Stepwise Cox hazard analysis associated cardiac death with age (> or =70 years) and with severely abnormal BMIPP SPECT images (BMIPP summed scores > or =12: hazard ratio 21.894; p < 0.0001). Kaplan-Meier analysis showed that the cardiac death-free survival rates at 3 years were 61% and 98% in patients with BMIPP summed scores of > or =12 and <12, respectively. CONCLUSIONS: Severely impaired myocardial fatty acid metabolism, which might mainly reflect repetitive myocardial ischemia, can identify a high-risk group of cardiac death among hemodialysis patients.

Relationships between lifestyle factors and neutrophil functions in the elderly.

We investigated the relationships between neutrophil functions and lifestyle factors in the elderly. The subjects (84 males, 73.9+/-5.8 years old; and 63 females, 70.0+/-4.6 years old) belonged to a recreational seniors club in Japan. Investigations of the subjects' stress, exercise habits, smoking habits, and alcohol-drinking habits were performed. The phagocytosis and superoxide productivity of the neutrophils were measured with a nitroblue tetrazolium (NBT) reduction test. In addition, leukocyte counts and serum total protein (TP) levels were determined. The results revealed that aging, high serum levels, and stress-coping factors (e.g., having hobbies, keeping pets, and close links with friends or family) significantly correlated with preferable neutrophil functions. In addition, significant effects of lifestyle factors on the balance between phagocytosis and subsequent superoxide production were observed. Thus, the results of the present study suggest that there are correlations between neutrophil functions and lifestyle factors in the elderly.