Shinichi Sakai

Impact of pitavastatin on high-sensitivity C-reactive protein and adiponectin in hypercholesterolemic patients with the metabolic syndrome: The PREMIUM Study

BACKGROUND Inflammatory reactions and oxidative stress, which are important in progression of atherosclerosis, are reported to be increased in individuals with metabolic syndrome (MetS). On the other hand, adiponectin levels are lowered. Since effects of pitavastatin on these parameters have not been reported in hypercholesterolemic patients with MetS, the present study was conducted. PURPOSE To evaluate the effects of pitavastatin on inflammatory reaction, oxidative stress, and plasma adiponectin levels in hypercholesterolemic MetS patients in a multicenter trial. METHODS This open-label, single group study was performed at 7 hospitals in Japan. Pitavastatin (2mg/day) was administered to 103 consecutive patients with hypercholesterolemia, subdivided into MetS and non-MetS for 12 weeks. Blood samples were collected after overnight fasting at the start of treatment (baseline) and after 12 weeks. RESULTS In the patients with MetS (n=69), mean values of plasma high-sensitivity C-reactive protein (hs-CRP) were significantly higher and mean values of plasma high-molecular-weight (HMW)-adiponectin significantly lower than in their counterparts without MetS (n=34). The baseline HMW-adiponectin and high-density lipoprotein cholesterol (HDL-C) values significantly correlated only in the MetS patients (r=0.318; p=0.01). In an effectiveness analysis including 94 patients (62 with MetS, 32 without MetS), the level of hs-CRP was significantly decreased in patients with MetS during the drug treatment, whereas HMW-adiponectin did not change. When patients with MetS were divided into two subgroups according to the percent changes in HDL-C, significantly greater increase in HMW-adiponectin by pitavastatin treatment was observed in the HDL-C ≥10% increase subgroup than in the HDL-C <10% increase subgroup (p=0.009). CONCLUSION Twelve weeks administration of pitavastatin, in addition to the antihyperlipidemic effects, may be beneficial as an anti-atherosclerotic therapy in hypercholesterolemic patients with MetS, taking changes in hs-CRP and HMW-adiponectin into consideration. ClinicalTrials.gov identifier: NCT00444717.

Impact of Admission Anemia on Coronary Microcirculation and Clinical Outcomes in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Microvascular dysfunction after primary percutaneous coronary intervention (PCI) augments myocardial damage and prognosis in acute myocardial infarction. However, the relationship between baseline anemia and coronary microcirculation in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear. We performed primary PCI in 337 consecutive patients with STEMI. Anemia was defined as a hemoglobin level < 13 g/dL in men and < 12 g/dL in women. Admission anemia was present in 17.5% of the patients enrolled. Data on epicardial coronary flow, STsegment resolution (STR) on electrocardiography, myocardial injury, and the incidence of adverse cardiac events defined as cardiac death or hospitalization for congestive heart failure were analyzed. The median follow-up period was 54.8 months. Despite comparable epicardial coronary flow, the rate of STR ≥ 50% was lower in anemic patients compared with non-anemic patients (55.9% versus 71.2%, P = 0.02). On multivariate logistic regression analysis, baseline anemia was an independent negative predictor of STR ≥ 50% (odds ratio, 0.53; 95% confidence interval: 0.31-0.92, P = 0.03). Moreover, anemic patients had higher maximum creatine kinase levels normalized for body surface area (2,215 ± 1,318 IU/L/m(2) versus 1,797 ± 1,199 IU/L/m(2), P = 0.047). Anemia remained an independent significant predictor of adverse events on multivariate Cox proportional hazard analysis (hazard ratio, 2.34; 95% confidence interval: 1.01-5.64, P = 0.048). In conclusion, admission anemia was related to microcirculatory dysfunction and poor prognosis in patients with STEMI. The decreased oxygen delivery might exacerbate microvascular function.

Clinical Characteristics and Long-Term Outcomes of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) has various morphological and clinical features. A decade has passed since the previous survey of the epidemiological and clinical characteristics of Japanese HCM patients. The Aichi Hypertrophic Cardiomyopathy (AHC) Registry is based on a prospective multicenter observational study of HCM patients. The clinical characteristics of 42 ambulant HCM patients followed up for up to 5 years were investigated. The primary endpoint was major adverse cardiac events (MACE), defined as death, non-fatal stroke, admission due to congestive heart failure (CHF), or episodes of sustained ventricular tachycardia/fibrillation. The MACE-free survival during the 5-year follow-up period was 76% according to Kaplan-Meier analysis. HCM-related death occurred in 3 (7%) patients and SCD occurred in 2 (5%) patients. Additionally, 3 (7%) patients were admitted to the hospital due to CHF. Meanwhile, sustained VT was detected in one (2%) of the patients who received ICD implantation and subsequently terminated with antitachycardia pacing using an ICD. The patients with HCM exhibiting left ventricular outflow obstruction (HOCM) had a slightly lower MACE-free survival rate than those with neither HOCM nor dilated-HCM (dHCM) (71% versus 81%, log-rank P = 0.581). Furthermore, the patients with dHCM demonstrated a significantly lower MACE-free survival rate than those with neither HOCM nor dHCM (33% versus 81%, log-rank P = 0.029). In the AHC Registry targeting current Japanese HCM patients, we demonstrated that many HCM patients continue to suffer from MACE despite the development of various treatments for HCM.

Relationship between QRS score and microvascular obstruction after acute anterior myocardial infarction

BACKGROUND The QRS score on electrocardiogram (ECG) in patients with myocardial infarction (MI) reportedly reflects the severity of myocardial damage. The presence of microvascular obstruction (MO) assessed by cardiac magnetic resonance (CMR) imaging is associated with irreversible myocardial damage. MO assessed by CMR is known to be a predictor for adverse clinical outcome after ST-elevation MI. The aim of the present study was to examine the relationship between QRS score and MO in acute anterior MI patients. METHODS Sixty-two patients with first acute anterior MI who successfully underwent primary percutaneous coronary intervention (PCI) were enrolled. The QRS score after PCI on admission ECG was calculated by a Selvester-Wagner QRS scoring system. CMR imaging was performed at 11.4±3.9 days after MI. MO was defined as delayed enhancement with contrast-devoid core. Patients were divided into two groups as follows: 37 patients who showed MO (MO group) and 25 patients who did not show it (non-MO group). RESULTS The QRS score was significantly greater in the MO group than in the non-MO group. The QRS score significantly correlated with MO volume (r=0.418, p=0.010). Multivariate analysis showed that the QRS score (odds ratio 1.362, 95% CI: 1.038-1.951, p=0.024) and the peak creatine kinase levels (odds ratio 1.001, 95% CI: 1.000-1.002, p<0.001) were independent predictors for MO. CONCLUSIONS Our results indicate that the QRS score derived from simple and widely available ECG may be a useful parameter for assuring the presence of MO.

Impact of Plaque Burden in the Left Main Coronary Artery Determined by Intravascular Ultrasound on Cardiovascular Events in a Japanese Population Undergoing Percutaneous Coronary Intervention

The left main coronary artery (LMCA) is a particularly important target of atherosclerotic plaque accumulation. The aim of this study was to investigate the connection between subclinical plaque burden in the LMCA measured by intravascular ultrasound and future cardiovascular events. Two hundred eighteen consecutive patients underwent percutaneous coronary intervention for the left anterior descending coronary artery or the left circumflex coronary artery under intravascular ultrasound guidance. Plaque burden in the LMCA was analyzed for these patients, and major adverse cardiac events were also evaluated. Data were analyzed by grouping the patients into tertiles according to plaque burden values; tertile 1, <32% area stenosis; tertile 2, 32% to 45% area stenosis; and tertile 3, >45% area stenosis. During a 3-year follow-up period (average 16.1 months), 12% of tertile 1, 18% of tertile 2, and 40% of tertile 3 experienced major adverse cardiac events, mostly due to repeat revascularization (p <0.001). On Cox multivariate analysis, plaque burden in the LMCA (per percentage) detected by intravascular ultrasound remained an independent significant predictor of major adverse cardiac events (hazard ratio 1.04, 95% confidence interval 1.02 to 1.07) and future revascularization (hazard ratio 1.05, 95% confidence interval 1.02 to 1.07) (p <0.001). In conclusion, plaque burden in the LMCA is useful as an indicator of coronary atherosclerosis and may be a significant predictor of cardiovascular events, especially revascularization.

Trends in physiological coagulation factors in Japanese patients receiving novel oral anticoagulants

Little is known about physiological anticoagulation effects via antithrombin III (AT III) and protein C/S (PC/PS) in patients using new oral anticoagulants (NOACs).

Clinical Characteristics of Nonobese Patients with Acute Coronary Syndrome and Increased Epicardial Fat Volume

Aim: Increased epicardial fat volume (EFV) is an independent risk factor for acute coronary syndrome (ACS). Although EFV increases with body mass index (BMI), some ACS patients have an increased EFV but normal BMI. We here investigated the clinical characteristics of nonobese ACS patients with an increased EFV. Methods: A total of 197 Japanese patients hospitalized for ACS was evaluated for EFV, abdominal visceral fat area (VFA), and lipid and glucose profiles. Control subjects comprised 141 individuals who were suspected of having ACS but whose coronary computed tomography findings were normal. Results: EFV was increased in ACS patients compared with control subjects (120 ± 47 versus 95 ± 45 mL, P < 0.01). ACS patients were divided into four groups based on average EFV (120 mL) and a BMI obesity cutoff of 25 kg/m2. For the 30 nonobese ACS patients with an above-average EFV, EFV was positively correlated with VFA (r = 0.23, P = 0.031). These individuals were significantly older (74 ± 10 years) and tended to have a higher homeostasis model assessment–insulin resistance value (5.5 ± 3.8) compared with other ACS patients. Among nonobese study subjects, EFV was independently associated with ACS (odds ratio= 2.01, P = 0.021) and correlated with abdominal circumference (r = 0.26, P = 0.017). Conclusion: Nonobese ACS patients with an increased EFV were elderly and tended to manifest insulin resistance. Measurement of EFV may prove informative for evaluation of ACS risk among elderly nonobese individuals with an increased abdominal girth.

Microvascular obstruction on delayed enhancement cardiac magnetic resonance imaging after acute myocardial infarction, compared with myocardial 201Tl and 123I-BMIPP dual SPECT findings

BACKGROUND The hypo-enhanced regions within the hyper-enhanced infarct areas detected by cardiac magnetic resonance (CMR) imaging reflect microvascular obstruction (MO) after acute myocardial infarction (AMI). The combined myocardial thallium-201 ((201)Tl)/iodine-123-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid ((123)I-BMIPP) dual single-photon emission computed tomography (SPECT) is a useful tool for detecting myocardial reversibility after AMI. We evaluated whether MO could be an early predictor of irreversible myocardial damage in comparison with (201)Tl and (123)I-BMIPP dual SPECT findings in AMI patients. METHODS Sixty-two patients with initial AMI who successfully underwent coronary revascularization were enrolled. MO was defined by CMR imaging. Patients were divided into 2 groups as follows: MO group (n=32) and non-MO group (n=30). Scintigraphic defect scores were calculated using a 17-segment model with a 5-point scoring system. The mismatch score (MMS) was calculated as follows: the total sum of (Σ) (123)I-BMIPP defect score minus Σ(201)Tl defect score. The percentage mismatch score (%MMS) was calculated as follows: MMS/(Σ(123)I-BMIPP score)×100 (%). RESULTS The percentage infarct size (%IS) was significantly greater in the MO group than in the non-MO group (32.2±13.8% vs. 18.3±12.1%, p<0.001). The %MMS significantly correlated with the %IS and the percentage MO (r=-0.26, p=0.03; r=-0.45, p<0.001, respectively). The %MMS was significantly greater in the non-MO group than in the MO group (45.4±42.4% vs. 13.3±28.0%, p=0.001), and was an independent predictor for MO (OR 0.97, 95%CI 0.94-0.99, p=0.02). CONCLUSIONS Our results reconfirm that, in comparison with myocardial dual scintigraphy, MO is an important structural abnormality. CMR imaging is useful for the early detection of irreversible myocardial damage after AMI.