石井 潤一

We previously reported that serial coronary computed tomography angiography (CTA) had a potential to evaluate the interval change of plaque morphology of coronary arteries. The aim of this study was to evaluate variables associated with the plaque progression by serial CTA. We included 148 patients (age 66.3 ± 9.8 years, male 81.1 %, median scan interval 12 months) with coronary artery disease undergoing serial CTA. Each coronary artery was compared visually between baseline and follow-up CTA to detect plaque progression. Baseline characteristics between progression and nonprogression patients did not demonstrate any significant differences. Logistic analysis revealed that only low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dl at follow-up was associated with plaque progression (odds ratio 2.59, 95 % confidence interval 1.12-6.34, P = 0.0263). Cutoff value of LDL-C for plaque progression at follow-up was 103.0 mg/dl based on receiver-operator characteristic curves analyses. Of the 36 progressive lesions in 32 patients, plaque composition at baseline included 13 lesions (36.1 %) of noncalcified plaque, 1 lesion (2.8 %) of calcified plaque, 12 lesions (33.3 %) of partially calcified plaque, and the remaining 10 lesions (27.8 %) had no plaque at baseline and revealed de novo plaques at follow-up. There were 9 lesions (25 %) with high-risk plaque (HRP) characteristics at baseline and 18 lesions (50 %) with HRP at follow-up. Plaque progression of coronary arteries by serial CTA was associated with LDL-C ≥100 mg/dl at follow-up regardless of baseline LDL-C level. There was no specific finding to predict plaque progression on the baseline plaque characteristics.

Serum troponin T levels using a highly sensitive assay (hsTnT) in patients with chronic kidney disease (CKD) not on dialysis have not been examined. The aim of this prospective cohort study was to investigate the association of hsTnT with cardiac events in ambulatory CKD patients not on dialysis. The serum hsTnT level was measured in 442 ambulatory CKD patients not on dialysis whose estimated glomerular filtration rate was < 60 ml/min/1.73 m(2). Patients were divided into quartiles according to hsTnT levels, and were followed up for 3 years. Cardiac events were defined as a cardiac death, acute myocardial infarction, unstable angina pectoris that required emergency coronary revascularization, or hospitalization for worsening heart failure. During the follow-up period (median 22 months), 63 cardiac events occurred. Kaplan-Meier incidence rates of cardiac events for 3 years were 0.88 %, 11.5 %, 19.0 %, and 41.4 % among quartiles of hsTnT levels (P < 0.0001). After adjusting for other confounders, elevated hsTnT level was an independent predictor for cardiac events (hazard ratio 6.18, 95 % confidence interval 1.38-27.7, P = 0.0080 for highest quartile vs lowest quartile). In addition, C-index for receiver-operating characteristic curves for cardiac events was greater in an established risks plus hsTnT model than in the established risk alone model (0.857 vs 0.844, P = 0.026). Using a highly sensitive assay, serum hsTnT level was shown to be an independent predictor of cardiac events and a promising risk stratification tool in patients with CKD not on dialysis.

Previous studies have shown highly effective lowering of blood pressure with thiazide diuretics in combination with angiotensin receptor blockers. However, thiazide diuretics may cause the development of diabetes and abnormal lipid metabolism. Little is known as to whether dysmetabolic potential of thiazide diuretics could be neutralized when adding angiotensin receptor blockers. This study consisted of 26 patients with essential hypertension. Patients were randomized to 24 weeks of treatment with either candesartan, 12 mg monotherapy (n = 13, group A), or hydrochlorothiazide (HCTZ), 6.25 mg in combination with candesartan, 8 mg (n = 13, group B). Before and after treatment, we assessed glucose and lipid profiles including adiponectin, resistin, and active glucagon-like peptide-1 (GLP-1) levels. At baseline, there were no differences in age, body mass index, systolic blood pressure (SBP), and diastolic blood pressure (DBP), as well as plasma levels of hemoglobin A1c, insulin, low-density lipoprotein cholesterol, triglycerides, adiponectin, resistin, and active GLP-1 between the two groups. There were significant reductions in SBP (from 152 +/- 10 mmHg at baseline to 134 +/- 12 mmHg after treatment) and DBP (from 84 +/- 5 mmHg at baseline to 71 +/- 8 mmHg after treatment) in group A. There were also significant reductions in SBP (from 148 +/- 10 at baseline to 128 +/- 7 mmHg after treatment) and DBP (from 90 +/- 9 at baseline to 74 +/- 12 mmHg after treatment) in group B. There were no differences in reduction of SBP or DBP after 24 weeks of treatment between the two groups. There were no changes of the glucose and lipid profiles, including adiponectin, resistin, insulin, and active GLP-1 levels after 24 weeks of treatment in both groups. A low dose of HCTZ in combination with candesartan reduces blood pressure effectively without adverse effects on the glucose and lipid profiles. Therefore, the combination of thiazide diuretics and angiotensin receptor blockers could assist patients in achieving long-term control of blood pressure with good tolerability.

BACKGROUND: The role of combined evaluation of myocardial perfusion imaging (MPI; by single-photon emission computed tomography) and computed tomography angiography (CTA) for risk stratification of coronary artery disease was evaluated. For CTA, the extent of luminal stenosis, and also the features of high-risk plaques (HRP, including positive remodeling and low attenuation) were evaluated. METHODS AND RESULTS: A total of 304 patients (65 ± 11 years, male 72%, median follow-up: 24 months) who underwent CTA and MPI were enrolled in the study. Summed stress scores and summed difference scores (SDS) for MPI, stenosis, and HRP were evaluated, and event rates were compared. Cardiac events were defined as acute coronary event including cardiac death or non-fatal acute myocardial infarction, and unstable angina requiring revascularization. Of 304 patients, 51 (16.8%) underwent early revascularization. In the remaining 253 patients, an event occurred in 11 (4.3%). HRP (hazard ratio [HR], 4.75, P=0.00171) and stenosis (+) with SDS >0 (HR, 4.58, P=0.0461) were significant independent predictors of cardiac event. The event rate for stenosis (+) with SDS >0 was significantly higher than others (log-rank P=0.0490). The event rates were significantly different between HRP(+) and HRP(-) (16.1% vs. 2.7%, log-rank P=0.0013). CONCLUSIONS: HRP on CTA was an independent predictor of acute coronary events, as was stenosis (+) with SDS >0, and HRP had increased prognostic value over stenosis and abnormal MPI findings.

Background: Several epidemiologic studies have reported an inverse association between serum levels of carotenoids and cardiovascular disease risk. However, no studies have reported an association between serum carotenoids and N-terminal pro-brain-type natriuretic peptide (NT-proBNP) in the general population. Methods: In this cross-sectional study,we investigated whether serum carotenoids were associated with serum NTproBNP in 1056 Japanese subjects (390 men, 666 women) who attended a health examination. Serum levels of carotenoids were separately determined by high-performance liquid chromatography. Serum NT-proBNP level was measured by electrochemiluminescence immunoassay. Results: Serum NT-proBNP was elevated (≥55 pg/ml) in 31.8% of men and 48.2% of women. Multivariate logistic regression analyses adjusted for confounding factors showed a significant association between the highest quartile of serum a-carotene and elevated NT-proBNP in men (odds ratio [OR]= 0.40, 95% CI = 0.19-0.82, P for trend = 0.005) and women (OR = 0.62, 95% CI = 0.39-0.99, P for trend = 0.047). In women, moreover, elevated serum NTproBNP was significantly associated with serum canthaxanthin (OR = 0.57, 95% CI = 0.36-0.90 for highest quartile, P for trend = 0.026) and ß-cryptoxanthin (OR = 0.53, 95% CI = 0.32-0.85 for highest quartile, P for trend = 0.026), after adjusting for potential confounders. Conclusions: Higher levels of serum carotenoids were associated with lower risk of elevated serum NT-proBNP levels after adjusting for possible confounders, which suggests that a diet rich in carotenoids could help prevent cardiac overload in the Japanese population. © 2013 Japan Epidemiological Association.

Objective To study the usefulness of combined risk stratification of coronary CT angiography (CTA) and myocardial perfusion imaging (MPI) in patients with previous coronary-artery-bypass grafting (CABG). Design A retrospective, observational, single centre study. Setting and patients 204 patients (84.3% men, mean age 68.77.6) undergoing CTA and MPI. Main outcome measures CTA defined unprotected coronary territories (UCT; 0, 1, 2 or 3) by evaluating the number of significant stenoses which were defined as the left main trunk 50% diameter stenosis, other native vessel stenosis 70% or graft stenosis 70%. Using a cut-off value with receiver-operating characteristics analysis, all patients were divided into four groups: group A (UCT=0, summed stress score (SSS)<4), group B (UCT1, SSS<4), group C (UCT=0, SSS4) and group D (UCT1, SSS4). Results Cardiac events, as a composite end point including cardiac death, non-fatal myocardial infarction, unstable angina requiring revascularisation and heart-failure hospitalisation, were observed in 27 patients for a median follow-up of 27.5months. The annual event rates were 1.1%, 2%, 5.7% and 12.9% of patients in groups A, B, C and D, respectively (log rank p value <0.0001). Adding UCT or SSS to a model with significant clinical factors including left ventricular ejection fraction, time since CABG and Euro SCORE II improved the prediction of events, while adding UCT and SSS to the model improved it greatly with increasing C-index, net reclassification improvement and integrated discrimination improvement. Conclusions The combination of anatomical and functional evaluations non-invasively enhances the predictive accuracy of cardiac events in patients with CABG.

OBJECTIVES: The clinical benefit of ezetimibe, an intestinal cholesterol transporter inhibitor, for treatment of postprandial hyperlipidemia was assessed in subjects who ingested a high-fat and high-glucose test meal to mimic westernized diet. METHODS: We enrolled 20 male volunteers who had at least one of the following: waist circumference ≥ 85 cm, body mass index ≥ 25 kg/m(2), or triglycerides (TG) from 150 to 400mg/dL. After 4 weeks of treatment with ezetimibe (10mg/day), the subjects ingested a high-fat and high-glucose meal. Then changes in serum lipid and glucose levels were monitored after 0, 2, 4, and 6h, and the area under the curve (AUC) was calculated for the change in each parameter. RESULTS AND CONCLUSION: At 4 and 6h postprandially, TG levels were decreased (p<0.01) after 4 weeks of ezetimibe treatment, and the AUC for TG was also decreased (p<0.01). Apolipoprotein B48 (apo-B48) levels at 4 and 6h postprandially were significantly decreased after ezetimibe treatment (p<0.01 and p<0.001, respectively), and the AUC for apo-B48 was also significantly decreased (p<0.01). Blood glucose and insulin levels at 2h postprandially were significantly decreased by ezetimibe (p<0.05). The AUCs for blood glucose and insulin were also significantly decreased (p<0.05 and p<0.01, respectively). Since ezetimibe improved postprandial lipid and glucose metabolism, this drug is likely to be beneficial for dyslipidemia in patients with postprandial metabolic abnormalities.