Takayuki Ogawa

Significance of imbalance in the ratio of serum n-3 to n-6 polyunsaturated fatty acids in patients with acute coronary syndrome.

This study aimed to assess the balance of serum n-3 to n-6 polyunsaturated fatty acids (PUFAs) in patients with acute coronary syndrome (ACS). We enrolled 1,119 patients who were treated and in whom serum PUFA level was evaluated in 5 divisions of cardiology in a metropolitan area in Japan. Serum levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA), were compared between patients with and without ACS. We also evaluated the balance of serum n-3 to n-6 PUFAs, including EPA/AA and DHA/AA ratios. EPA/AA values were 0.46 ± 0.32 and 0.50 ± 0.32 in the ACS and non-ACS groups, respectively. DHA/AA values were 0.95 ± 0.37 and 0.96 ± 0.41 in the ACS and non-ACS groups, respectively. Next, we divided the patients into 3 groups based on the tertiles of EPA/AA or tertiles of DHA/AA to determine the independent risk factors for ACS. According to multivariate logistic regression analysis, the group with the lowest EPA/AA (≤0.33) had a greater probability of ACS (odds ratio 3.14, 95% confidence interval 1.16 to 8.49), but this was not true for DHA/AA. In conclusion, an imbalance in the ratio of serum EPA to AA, but not in the ratio of DHA to AA, was significantly associated with ACS.

Difference in risk factors between acute coronary syndrome and stable angina pectoris in the Japanese: smoking as a crucial risk factor of acute coronary syndrome.

BACKGROUND AND PURPOSE Metabolic syndrome and chronic kidney disease (CKD) have received attention as new risk factors for cardiovascular disease. This study evaluated differences in key risk factors between acute coronary syndrome (ACS) and stable angina pectoris (SAP) by using traditional coronary risk factors, metabolic syndrome, and CKD. METHODS Among 1890 consecutive patients admitted to our institution, we studied 140 patients with initially diagnosed ACS and 163 patients with initially diagnosed SAP and compared risk factors between the two groups. Next, the relationship between smoking status after the initial diagnosis of coronary artery disease (CAD) and the incidence of subsequent cardiac event was examined after discharge in 284 patients. RESULTS Adjusted multivariate analysis showed that only current smoking was an independent predictor of ACS (odds ratio, 2.20; 95% CI, 1.28-3.78; p=0.004) among all risk factors we examined. Treatment with a calcium-channel blocker had a preventive effect on ACS (odds ratio, 0.44; 95% CI, 0.26-0.75; p=0.003), but treatment with a beta-blocker did not. Patients who continued to smoke after CAD was diagnosed had a risk of cardiac events about 5 times that of smokers who quit (adjusted hazard ratio, 5.05; 95% CI, 1.33-19.20; p=0.02). CONCLUSIONS The risk factors were significantly different between initially diagnosed ACS and SAP. Smoking was a more important risk factor of initially diagnosed ACS. Smoking cessation might have a preventive effect on subsequent cardiac events. Also, we found that treatment with a calcium-channel blocker would help prevent ACS in Japanese patients.

The impact of an inverse correlation between plasma B-type natriuretic peptide levels and insulin resistance on the diabetic condition in patients with heart failure

BACKGROUND A diabetic state is causally related to heart failure (HF); therefore, there should be a close correlation between the severity of diabetes and HF. However, a direct relationship between these conditions has rarely been reported and remains unclear. This study was designed to precisely examine this relationship, taking into consideration the possible association between natriuretic peptide (NP) levels and insulin resistance. MATERIAL AND METHODS We examined various hemodynamic parameters and simultaneously performed blood biochemical analyses of consecutive patients who underwent cardiac catheterization at our institution (n=840). RESULTS Simple regression analyses showed that hemoglobin A1c (HbA1c) levels were not significantly changed by the left ventricular end-diastolic pressure (LVEDP) and left ventricular ejection fraction (LVEF), which were correlated with a low cardiac index. Rather, there was a negative correlation between the HbA1c levels and plasma BNP levels as a marker of HF. A multivariate analysis showed no correlations between the HbA1c levels and cardiac functional parameters (LVEDP, LVEF or the plasma BNP levels), suggesting that the trend toward high HbA1c levels in HF cases is likely to be limited for unknown reasons. To search for an explanation of this finding, we examined the potential biological interactions between BNP and insulin resistance. A multivariate analysis revealed that the plasma BNP levels were positively correlated with age, creatinine levels and LVEDP and inversely correlated with the male gender, body mass index and HOMA-IR (homeostasis model assessment-insulin resistance) (P<0.001, respectively), but not HbA1c levels. This analysis indicated a close correlation between plasma BNP levels and insulin effectiveness in HF. CONCLUSIONS HF and diabetes tend to worsen with each other; however, the appearance of an association between them was likely blunted due to the considerable effect of NP in counteracting insulin resistance, even during the metabolically harmful condition of HF.

Transient decrease in serum potassium level during ischemic attack of acute coronary syndrome: Paradoxical contribution of plasma glucose level and glycohemoglobin

BackgroundAlthough a decrease in serum potassium level has been suggested to be a fairly common observation in acute coronary syndrome (ACS), there have so far been no definitive reports directly demonstrating the transient potassium decrease (the potassium dip) during ischemic attack of ACS compared to stable phase in individual patients. To understand the pathophysiological significance of the potassium dip, we examined the changes in serum potassium level throughout ischemic attack and evaluated the clinical factors affecting it.MethodsThe degree of the potassium dip during ischemic attack (as indicated by ΔK, ΔK = K at discharge − K on admission) was examined in 311 consecutive patients with ACS who required urgent hospitalization in our institution.ResultsSerum potassium level during ischemic attack was significantly decreased compared to that during stable phase (P < 0.001). Multiple regression analysis revealed that plasma glucose level during attack was the sole factor which was positively correlated with ΔK (P < 0.01), while HbA1c level was negatively correlated (P < 0.05). The medication profiles and renal function had no impact on ΔK. A longer hospitalization period, higher incidence of myocardial infarction and higher peak creatine kinase level were observed in patients with a larger ΔK.ConclusionsWe have clearly demonstrated that there is a transient decrease in serum potassium level during ischemic attack of ACS compared to stable phase. The degree of the potassium dip was tightly correlated with glucose level, which overwhelmed the diabetic condition, and it also indicates the disease severity. The present study therefore promotes awareness of the significance of monitoring potassium level in parallel with glucose level in patients with ACS.

The plasma B-type natriuretic peptide levels are low in males with stable ischemic heart disease (IHD) compared to those observed in patients with non-IHD: a retrospective study.

Objective Although the plasma B-type natriuretic peptide (BNP) level is a marker of heart failure, it is unclear whether BNP per se plays a pivotal role for pathogenic mechanisms underlying the development of ischemic heart disease (IHD). In this study, we retrospectively examined the plasma BNP levels in stable patients with IHD and compared to stable patients with cardiovascular diseases other than IHD. Methods The study population was 2088 patients (1698 males and 390 females) who were admitted to our hospital due to IHD (n = 1,661) and non-IHD (n = 427) and underwent cardiac catheterization. Measurements of the hemodynamic parameters and blood sampling were performed. Results The plasma BNP levels were significantly lower in the IHD group than in the non-IHD group (p<0.001). The multiple regression analysis examining the logBNP values showed that age, a male gender, low left ventricular ejection fraction, low body mass index, serum creatinine, atrial fibrillation and IHD per se were significant explanatory variables. When the total study population was divided according to gender, the plasma BNP levels were found to be significantly lower in the IHD group than in the non-IHD group among males (p<0.001), but not females (p = NS). Furthermore, a multiple logistic regression analysis of IHD showed the logBNP value to be a significant explanatory variable in males (regression coefficient: −0.669, p<0.001), but not females (p = NS). Conclusions The plasma BNP levels were relatively low in stable patients with IHD compared with those observed in stable patients with non-IHD; this tendency was evident in males. Perhaps, the low reactivity of BNP is causally associated with IHD in males. We hope that this study will serve as a test of future prospective studies.

Severe coronary spasm occasionally detected by coronary computed tomography

Coronary spasm not only plays an important role in coronary spastic angina but also in ischae- mic heart diseases in general, and the incidence is quite high among Japanese. Coronary spasm can be reliably detected by an intracoronary injection of acetylcholine (ACh) during cardiac catheterization, but not by coronary computed tomography (CT) because coronary spasm is transient, occurs mostly between midnight and the early morning and rarely during the daytime. When a patient undergoes coronary CT at our institution, we routinely administer sublingual nitroglycerine to maximally dilate cor- onary arteries. Thus, we were totally unaware of the possibility of coronary spasm occurring during coronary CT, which did occur in a 41-year-old man and is described herein. Cardiac catheterization as an examination for chest pain at rest did not reveal any significant changes in coronary arteriograms. The patients symptoms were mild and atypical for angina pec- toris, and only nitroglycerin was prescribed. Six months later, electrocardiography in a regular outpatient clinic revealed abnormal QS mor- phology in leads V1-V4 indicating severe anterior myocardial ischaemia without specific symptoms. A second CAG was a provocative test for coronary spasm using ACh which revealed coronary spasm. Organic stenosis was also identified at Segment 6 of the left anterior descending artery (LAD). Per- cutaneous coronary intervention (PCI) using balloon angioplasty was performed. Thereafter, the patient was prescribed with medi- cation for angina pectoris. Five years later, the patient developed chest pain during exertion and was examined by coronary dual-source CT (DSCT). The results showed almost total occlusion of Segment 1 of the right coronary artery (RCA) (Panels A and B). A third CAG was planned considering PCI for the most recently identified region. No significant stenosis was evident in the LAD, but collateral arteries to the RCA via the septal branches indicated total or subtotal chronic occlusion of the RCA (Panel C). We injected nitroglycerine into the LAD to arrange PCI and then infused the RCA with contrast dye. Surprisingly, only 25% stenosis of Segment 1 was evident (Panel D) and immediate angiography of the LAD showed that the collateral arteries had dis- appeared, indicating that a severe and spontaneous coronary spasm had occurred immediately before PCI and that the total occlusion identified by DSCT was due to coronary spasm. Calcium channel blockers were then administered, which effectively treated his con- dition for now. Silent spasm frequently occurs among patients with coronary spasm, and this should be considered when analysing coronary CT images. This report is the first description of severe coronary spasm being detected by coronary CT. Panels (A and B) Arrows show significant coronary stenosis in Segment 1 of the right coronary artery detected by coronary com- puted tomography.

A randomized comparison of sirolimus- vs. paclitaxel-eluting stents for treatment of bifurcation lesions by single stent and kissing balloon: Results of the SINGLE KISS trial

BACKGROUND In the treatment of bifurcation lesions, routine stenting of both branches has thus far failed to demonstrate a clear clinical advantage over a provisional one-stent strategy. On the other hand, large scale data evaluating different stent types for clinical outcomes after one-stent treatment with final kissing inflation (FKI) of bifurcation lesions is also limited. This prospective study evaluated the clinical and angiographic outcomes of paclitaxel-eluting stents (PES) vs. sirolimus-eluting stents (SES) in single crossover main branch stenting followed by FKI in patients with bifurcation lesions. METHODS We randomized 800 patients with single bifurcation lesions to PES (n=400) and SES (n=400) groups. RESULTS Crossover rates to the two-stent strategy were low in both groups (PES 1.5%, SES 2.8%; p=0.23). At 1 year, there was no significant difference in the primary endpoint of this study, target lesion revascularization rate (PES 3.8%, SES 3.2%, hazard ratio 0.83; 95% confidence interval 0.39 to 1.76; p=0.62). Stent thrombosis occurred in only 1 case in the SES group after 282 days. At 9 months, a total of 593 patients underwent quantitative coronary measurement. The main branch restenosis rate in the PES group was significantly higher than that of the SES group (PES 12.2%, SES 5.5%; p=0.004), however both groups exhibited similar high side branch restenosis rates (PES 17.2%, SES 19.3%; p=0.6). CONCLUSIONS In patients with bifurcation lesions, a single stent strategy using PES and SES with FKI indicated similar 1 year clinical outcomes and safety profiles.

Cardiac tamponade as an independent condition affecting the relationship between the plasma B-type natriuretic peptide levels and cardiac function.

Plasma B-type natriuretic peptide (BNP) is finely regulated by the cardiac function and several extracardiac factors. Therefore, the relationship between the plasma BNP levels and the severity of heart failure sometimes seems inconsistent. The purpose of the present study was to investigate the plasma BNP levels in patients with cardiac tamponade and their changes after pericardial drainage. This study included 14 patients with cardiac tamponade who underwent pericardiocentesis. The cardiac tamponade was due to malignant diseases in 13 patients and uremia in 1 patient. The plasma BNP levels were measured before and 24–48 h after drainage. Although the patients reported severe symptoms of heart failure, their plasma BNP levels were only 71.2 ± 11.1 pg/ml before drainage. After appropriate drainage, the plasma BNP levels increased to 186.0 ± 22.5 pg/ml, which was significantly higher than that before drainage (P = 0.0002). In patients with cardiac tamponade, the plasma BNP levels were low, probably because of impaired ventricular stretching, and the levels significantly increased in response to the primary condition after drainage. This study demonstrates an additional condition that affects the relationship between the plasma BNP levels and cardiac function. If inconsistency is seen in the relationship between the plasma BNP levels and clinical signs of heart failure, the presence of cardiac tamponade should therefore be considered.

Biphasic action of aldosterone on Akt signaling in cardiomyocytes.

Both aldosterone and Akt signaling play pivotal roles in the pathogenesis of heart failure. However, little is known about the correlation between them. We herein investigated whether aldosterone interacts with Akt signaling in a coordinated manner in cardiomyocytes. Neonatal rat cardiomyocytes were stimulated with aldosterone for either a short (10-min) or long (24-h) time. The phosphorylation of Akt and its downstream effector, GSK3β, were transiently increased after short-term stimulation, which was blocked by either PI3K or Na(+)/H(+) exchanger inhibitors, but not by the mineralocorticoid receptor antagonist, eplerenone. Long-term stimulation also significantly increased Akt-GSK3β phosphorylation and this effect was reduced by eplerenone. Thus, these results suggest that aldosterone activates Akt signaling via a biphasic reaction that occurs through different cascades. To understand the significance of the rapid action of aldosterone, cardiomyocytes were exposed to hydrogen peroxide for from 10 to 60 min. A short-term aldosterone stimulation (for up to 30 min) significantly protected cardiomyocytes from oxidative stress-induced cellular damage. Eplerenone did not abrogate this beneficial effect, while a PI3K inhibitor did. Therefore, during the early phase, aldosterone has favorable effects on cardiomyocytes, partly by acute activation of a mineralocorticoid receptor-independent cascade through the Na(+)/H(+) exchanger, PI3K, and Akt. In contrast, its persistent activity produces pathological effects partly by chronic Akt activation in a mineralocorticoid receptor-dependent manner.

Severe lasting coronary spasm detected by multi-detector row computed tomography

A 41-year-old male without overt risk factors (non-smoker) suddenly complained of severe chest pain during desk work at Ota General Hospital. His chest pain lasted for 20 min and he was able to meet with a physician when his chest symptom was still present. On physical examination, he suffered from chest pain of 5 on a scale of 10 and dyspnea. His pulse rate was 55 bpm and regular, and his systolic and diastolic blood pressures were 130 mm Hg and 84 mm Hg, respectively. On auscultation, normal heart sounds were detected, and no extra heart sounds or murmur were detected. The patients respiratory sounds were clear and no rale was detected. Laboratory examinations revealednoabnormalities except for amild elevation of the white blood cell count (9960/μl). Blood biochemical tests also showed no abnormalities, including creatine kinase (57 mg/ dl) and MB isoform (9 mg/dl). The brain natriuretic peptide level was within the normal range (6.8 pg/ml). A chest X-ray film showed a normal cardiothoracic ratio (48.6%) without any congestion. An electrocardiogram showed a sinus rhythm of 63 bpm with an inverted T wave in lead III and flattened T wave in lead aVF. Echocardiography revealed normal left ventricular contraction (EF=68%) without any wall motion abnormalities. From these observations and symptoms, we suspected angina pectoris and performed 64 multi-detector row computed tomography (MDCT) (Aquilion CX, Toshiba Medical Systems Corp., Otawara, Japan) using a contrast medium (Fig. 1A–C). We