Doctor of Medicine, Yokohama City University (2003)
Peter Fitzgerald, Postdoctoral Faculty Sponsor
This study investigated the association between arterial remodeling and geographic distribution of cardiac allograft vasculopathy (CAV), and outcomes after heart transplantation.CAV is characterized by a combination of coronary intimal thickening and pathological vessel remodeling, which varies at different locations in coronary arteries.In 100 transplant recipients, serial volumetric intravascular ultrasonography (IVUS) was performed at baseline and 1 year post-transplantation in the first 50 mm of the left anterior descending artery (LAD). IVUS indices were evaluated in the entire segment and 3 equally divided LAD segments. Paradoxical vessel remodeling was defined as [Δvessel volume/Δintimal volume <0].After 1 year, death or re-transplantation occurred in 20 patients over a median follow-up period of 4.7 years. Paradoxical vessel remodeling was observed in 57%, 41%, 50%, and 40% for the entire vessel, proximal, middle, and distal LAD segments, respectively. Kaplan-Meier analysis revealed a significantly lower event-free rate of survival in patients with paradoxical vessel remodeling involving the proximal LAD segment, which was not present when involving the entire LAD or mid and distal LAD segments. In multivariate analysis, paradoxical vessel remodeling of the proximal LAD segment was independently associated with death or re-transplantation (hazard ratio [HR]: 11.18; 95% confidence interval [CI]: 2.39 to 83.23; p = 0.0015).Despite the diffuse nature of CAV, paradoxical vessel remodeling of the proximal LAD segment at 1 year was the primary determinant of long-term mortality or re-transplantation. Assessment of arterial remodeling combined with coronary intimal thickening may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.
View details for DOI 10.1016/j.jchf.2015.07.013
View details for PubMedID 26577615
Blood glucose variability is receiving considerable attention as a new risk factor for coronary artery disease. This study aimed to investigate the association between blood glucose variability and coronary plaque tissue characteristics.In 57 patients with acute coronary syndrome, integrated backscatter intravascular ultrasound (IB-IVUS) and gray-scale IVUS were performed before balloon dilatation or stent implantation in the culprit vessels. Standard IVUS indices were evaluated for volume index (volume/length), and plaque components were measured by IB-IVUS for percent tissue volume. In addition to conventional glucose indicators, blood glucose variability in a stable state was determined by calculating the mean amplitude of glycemic excursions (MAGE) using a continuous glucose monitoring system.Higher MAGE values were significantly correlated with larger percent plaque volumes (r = 0.32, p = 0.015), and increased lipid (r = 0.44, p = 0.0006) and decreased fibrous (r = -0.45, p = 0.0005) plaque components. In contrast, HbA1c or fasting plasma glucose values were not significantly correlated with plaque volumes and percent plaque components. Homeostasis model assessment of insulin resistance values were positively correlated with vessel (r = 0.35, p = 0.007) and plaque (r = 0.27, p = 0.046) volumes, but not with percent plaque components. In multiple regression analysis, higher MAGE values were independently associated with increased lipid (β = 0.80, p = 0.0035) and decreased fibrous (β = -0.79, p = 0.0034) contents in coronary plaques.Among all glucose indicators studied, only higher blood glucose variability was an independent determinant of increased lipid and decreased fibrous contents with larger plaque burden, suggesting blood glucose variability as one of the important factors related to coronary plaque vulnerability.
View details for DOI 10.1186/s12933-015-0275-3
View details for PubMedID 26289581
This study sought to determine the additional clinical value of gait speed to Framingham risk score (FRS), cardiac function, and comorbid conditions in predicting cardiovascular events in patients with ST-segment elevation myocardial infarction.There is growing evidence that gait speed is inversely associated with all-cause mortality, particularly cardiovascular mortality, among the elderly.We undertook a single-center prospective observational study of gait speed in 472 patients with ST-segment elevation myocardial infarction in Japan, between 2001 and 2008. Gait speeds were measured using a 200-m course before discharge in all patients, and we followed up cardiovascular events, which consist of cardiovascular deaths, nonfatal myocardial infarctions, and nonfatal ischemic strokes.During the 2,596 person-years of follow-up, 83 patients (17.6%) experienced cardiovascular events. Cardiovascular events increased across decreasing tertiles of gait speed (fastest tertile: n = 5, 3.2%; middle tertile: n = 20, 12.6%; slowest tertile, n = 58, 36.7%). By multiple adjusted Cox proportional hazards analysis, gait speed was a significant and independent predictor of cardiovascular events (hazard ratio for increasing 0.1 m/s of gait speed: 0.71, 95% confidence interval [CI]: 0.63 to 0.81, p < 0.001). The addition of gait speed to the model incorporating FRS, B-type natriuretic peptide levels, and comorbidity index improved reclassification (net reclassification index: 32.8%, 95% CI: 17.4 to 48.3, p < 0.001) and the C-statistics with a reasonable global fit and calibration (C-statistics: from 0.703 [95% CI: 0.636 to 0.763] to 0.786 [95% CI: 0.738 to 0.829]).Among patients with ST-segment elevation myocardial infarction, slow gait speed was significantly associated with an increased risk of cardiovascular events. (Gait Speed for Predicting Cardiovascular Events After Myocardial Infarction; NCT01484158).
View details for DOI 10.1016/j.jacc.2013.02.020
View details for Web of Science ID 000318910300006
View details for PubMedID 23500222
To assess the mechanism of long-term LDL-C-lowering effect of ezetimibe-plus-statin.Coronary artery disease patients whose LDL-C ≥ 70 mg/dL after treatment with atorvastatin 10 mg/day or rosuvastatin 2.5 mg/day were randomly assigned to receive ezetimibe 10 mg/day + statin (n = 78) or double-dose statin (n = 72) for 52 weeks.Greater LDL-C reduction was observed and maintained until 52 weeks in ezetimibe-plus-statin, while LDL-C levels re-increased after 12 weeks in double-dose statin. Although lathosterol/TC increased, campesterol/TC decreased more in ezetimibe-plus-statin. In contrast, lathosterol/TC unchanged and campesterol/TC increased, increasing campesterol/lathosterol ratio for 52 weeks in double-dose statin. Plasma PCSK9 levels were higher in double-dose statin than in ezetimibe-plus-statin at 12 weeks, but similar at 52 weeks.Although the difference in PCSK9 between 2 groups was transient, that in both campesterol and lathosterol persisted until 52 weeks. These results demonstrated simultaneous inhibition of cholesterol absorption and synthesis provides stable and greater decrease in LDL-C levels.
View details for DOI 10.1016/j.atherosclerosis.2012.07.036
View details for Web of Science ID 000309261400028
View details for PubMedID 22892323
Ezetimibe-plus-statin therapy has been reported to provide greater reduction in low-density lipoprotein cholesterol (LDL-C) level than statin monotherapy. The aim of the present study was to evaluate the relationship between LDL-C lowering effect and baseline cholesterol absorption and synthesis markers in patients with coronary artery disease (CAD).A total of 171 patients with CAD whose LDL-C level was ≥ 100 mg/dl after treatment with atorvastatin (10mg/day) or rosuvastatin (2.5 mg/day) for 4 weeks were assigned to additionally receive ezetimibe (10mg/day) plus a statin or a double dose of statin for 12 weeks. The decreases in LDL-C (-30.0 ± 15.6 mg/dl vs. -19.2 ± 14.2 mg/dl) and the ratio of campesterol, an absorption marker, to total cholesterol levels (-1.35 ± 0.90 µg/mg vs. 0.33 ± 0.74 µg/mg) were greater in the ezetimibe-plus-statin group (P<0.05, respectively). The decrease in LDL-C level in the ezetimibe-plus-statin group was greatest in patients with baseline levels of higher absorption and lower synthesis markers and smallest in patients with baseline levels of lower absorption and higher synthesis markers (-34.3 ± 15.6 mg/dl vs. -21.5 ± 16.7 mg/dl, P<0.05). The decrease in LDL-C did not differ, irrespective of baseline levels of cholesterol absorption and synthesis markers, in the double-dose statin group, and was similar to that in patients with lower absorption and higher synthesis markers in the ezetimibe-plus-statin group.Ezetimibe-plus-statin therapy may be useful for lowering LDL-C level, irrespective of baseline levels of cholesterol absorption and synthesis markers.
View details for DOI 10.1253/circj.CJ-11-0391
View details for Web of Science ID 000295428200034
View details for PubMedID 21817821