Migaku Kikuchi

Prognostic impact of spontaneous coronary artery dissection in young female patients with acute myocardial infarction: A report from the Angina Pectoris–Myocardial Infarction Multicenter Investigators in Japan

BACKGROUND We sought to compare the prognosis of patients with spontaneous coronary artery dissection (SCAD) and atherosclerosis as the cause of acute myocardial infarction (AMI), especially in young females. METHODS AND RESULTS A total of 20,195 patients with AMI at 20 institutions between 2000 and 2013 were retrospectively studied. Major adverse cardiac event (MACE: cardiac death, AMI or urgent revascularization) was the endpoint. The overall prevalence of SCAD was 0.31% (n=63; female, 94%). SCAD developed following emotional stress in 29% of patients. Revascularization was performed in 56% (35 of 63 patients), and SCAD recurrence developed in the originally involved vessel in 6 of 35 patients with revascularization, compared to none among 28 patients after conservative therapy (p=0.002). We compared the clinical characteristics of young female AMI patients aged ≤50years in the SCAD (n=45) and no-SCAD groups (atherosclerotic AMI, n=55). During a median follow-up of 50months, SCAD recurred in 27% of patients, of which 42% was in the first 30days. Kaplan-Meier analysis showed a significantly higher incidence of MACE in the SCAD group compared to the no-SCAD group (hazard ratio, 6.91; 95% confidence interval, 2.5 to 24.3; p<0.001), although the rate of successful percutaneous coronary intervention for SCAD was as high as 92%. CONCLUSIONS Young female patients with SCAD represent a high-risk subgroup of patients with AMI and require close follow-up.

Irbesartan, an angiotensin receptor blocker, exhibits metabolic, anti-inflammatory and antioxidative effects in patients with high-risk hypertension

Irbesartan, an angiotensin II receptor blocker (ARB), acts as a selective PPAR-γ (peroxisome proliferator-activated receptor-γ) modulator, and thus may have anti-inflammatory and antioxidative effects, as well as beneficial effects on glucose and lipid metabolism. We enrolled 118 high-risk hypertensive outpatients, defined as those with the presence of at least one complication such as coronary artery disease, cerebrovascular disease or diabetes, and who were receiving any ARB except for irbesartan (67±10 years, 80% male subjects). After a 4-week control period, all ARBs were switched to an equivalent dose of irbesartan. We evaluated changes in lipid parameters, inflammatory markers and derivatives of reactive oxygen metabolites (d-ROMs) as an oxidative stress index. After 12 weeks of irbesartan, there were significant decreases in triglycerides (138±73 versus 123±65 mg dl−1, P<0.05), high-sensitivity C-reactive protein (hs-CRP) (2.80±0.53 versus 2.66±0.50, log (ng ml−1), P<0.05) and d-ROMs (338±74 versus 305±62 U.CARR, P<0.001). There were significant increases in high-density lipoprotein cholesterol (50±13 versus 52±14 mg dl−1, P<0.01) and adiponectin (9.4±6.2 versus 16.6±13.4 ng ml−1, P<0.05). There were no significant changes in systolic and diastolic blood pressure. The change in d-ROMs from baseline to 12 weeks was positively correlated with the change in hs-CRP (R=0.34, P<0.01). Irbesartan appears to exert beneficial effects on oxidative stress, inflammation, lipid metabolism and metabolic syndrome, indicating that it may be useful in high-risk hypertensive patients.

Regional cerebral oxygen saturation monitoring for predicting interventional outcomes in patients following out-of-hospital cardiac arrest of presumed cardiac cause: A prospective, observational, multicentre study

AIM This study investigated the value of regional cerebral oxygen saturation (rSO2) monitoring upon arrival at the hospital for predicting post-cardiac arrest intervention outcomes. METHODS We enrolled 1195 patients with out-of-hospital cardiac arrest of presumed cardiac cause from the Japan-Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry. The primary endpoint was a good neurologic outcome (cerebral performance categories 1 or 2 [CPC1/2]) 90 days post-event. RESULTS A total of 68 patients (6%) had good neurologic outcomes. We found a mean rSO2 of 21%±13%. A receiver operating characteristic curve analysis indicated an optimal rSO2 cut-off of ≥40% for good neurologic outcomes (area under the curve 0.92, sensitivity 0.81, specificity 0.96). Good neurologic outcomes were observed in 53% (55/103) and 1% (13/1092) of patients with high (≥40%) and low (<40%) rSO2, respectively. Even without return of spontaneous circulation (ROSC) upon arrival at the hospital, 30% (9/30) of patients with high rSO2 had good neurologic outcomes. Furthermore, 16 patients demonstrating ROSC upon arrival at the hospital and low rSO2 had poor neurologic outcomes. Multivariate analyses indicated that high rSO2 was independently associated with good neurologic outcomes (odds ratio=14.07, P<0.001). Patients with high rSO2 showed favourable neurologic prognoses if they had undergone therapeutic hypothermia or coronary angiography (CPC1/2, 69% [54/78]). However, 24% (25/103) of those with high rSO2 did not undergo these procedures and exhibited unfavourable neurologic prognoses (CPC1/2, 4% [1/25]). CONCLUSION rSO2 is a good indicator of 90-day neurologic outcomes for post-cardiac arrest intervention patients.

Cardioprotective effects of low-dose combination therapy with a statin and an angiotensin receptor blocker in a rat myocardial infarction model

PURPOSE Statins attenuate angiotensin II-induced myocyte hypertrophy and this might increase the cardioprotective effects of renin-angiotensin system inhibition in the ischemic heart. In this study, we investigated the cardioprotective effects of combination therapy with low-dose simvastatin and low-dose losartan using a rat myocardial infarction model. METHODS Myocardial infarction was created in rats by left anterior descending artery ligation, and the animals were randomly allocated to one of four groups: control (n=8), losartan 3 mg/kg/day (n=8), simvastatin 2 mg/kg/day (n=8), and losartan 3 mg/kg/day plus simvastatin 2 mg/kg/day (n=8). Each treatment was started on the day of coronary ligation, and hemodynamics, myocardial blood flow, and infarct size were measured after 28 days. RESULTS Blood pressure, heart rate, and left ventricular systolic and end-diastolic pressures were not significantly different comparing the control group with the 3 other treatment groups. The peak positive first derivative of left ventricular pressure (peak LV dP/dt) was equivalent comparing the control group with the losartan and simvastatin groups. However, the peak LV dP/dt was greater in the losartan plus simvastatin group than in the control group (p<0.05). Myocardial blood flow, left ventricular weight, and infarct size were not significantly altered by the 3 treatments. CONCLUSIONS Treatment with 3 mg/kg/day losartan plus 2 mg/kg/day simvastatin but not losartan or simvastatin alone improved left ventricular systolic function in a rat myocardial infarction model. The result suggests that statins given in combination with angiotensin receptor blockers might have beneficial cardioprotective effects, even at low-doses for each agent.

Impact of irbesartan, an angiotensin receptor blocker, on uric acid level and oxidative stress in high-risk hypertension patients

Hyperuricemia is a known cardiovascular risk factor. The angiotensin II receptor blocker (ARB) losartan is known to decrease serum uric acid (UA) level. A recent in vitro study demonstrated a strong interaction between irbesartan and UA transporters that exceeded that of losartan. The purpose of the present study was to evaluate the hypouricemic effect of irbesartan in a clinical setting. A total of 40 high-risk hypertensive outpatients with coronary artery disease, cerebrovascular disease and/or diabetes complications who were taking ARBs other than irbesartan and losartan were enrolled in this study. After a 4-week control period, the patients’ prescribed ARBs were exchanged for an equivalent dose of irbesartan. We assessed blood pressure, heart rate, serum UA level, parameters of lipid and glucose metabolism, cardiac and renal function and inflammatory and oxidative stress markers in blood samples taken immediately before the initiation of irbesartan treatment and again after 12 weeks of treatment. All 40 recruited patients were followed (31 men and 9 women, mean age: 68 years) without any dropouts. During the 12 weeks of irbesartan treatment, no significant changes in blood pressure, heart rate, parameters of lipid or glucose metabolism or other biomarkers of cardiac function, renal function, or inflammation were observed. However, UA level (5.9±1.6 to 5.5±1.6 mg ml−1, P=0.028) and the oxidative stress marker derivative reactive oxygen metabolites (dROMs) (354±83 to 310±65 U.CARR, P<0.001) were significantly lower at 12 weeks of treatment compared with before treatment. These results suggest that irbesartan has beneficial effects on hyperuricemia and oxidative stress.

Pleiotropic effects of ARB on dyslipidemia.

Angiotensin II type 1 (AT1) receptor blockers (ARBs), widely used in the treatment of hypertension, have cardiovascular, cerebral, and renal protective effects beyond blood pressure control. In addition to direct end-organ protection, some ARBs have been suggested to improve abnormalities of glucose and lipid metabolisms, resulting in an anti-atherosclerotic effect in patients with hypertension. In several clinical trials, the effects of ARBs on lipid metabolism have been emerged, although the effects are heterogeneous. Certain subgroups of ARBs such as telmisartan have been identified as partial agonists for the peroxisome proliferators activated receptor (PPAR)-γ, and thus, this class of ARBs has been mostly focused on their effects on lipid metabolism. Based on the pleiotropic effects on lipid metabolism, we can envision that ARBs would provide the promising outcome for hypertensive patients aggregating metabolic risk factors, including dyslipidemia.