25-hydroxycholesterol-induced cell death via activation of ROCK/LIMK/cofilin axis in colorectal cancer cell spheroids.

25-Hydroxycholesterol (25OHC) induces anchorage-dependent programmed cell death, or anoikis, in colorectal cancer cells but the mechanism is not fully understood. Here, we found that 25OHC induced cofilin phosphorylation and promoted rearrangement of the actin cytoskeleton in spheroids of the colorectal cancer cell lines, DLD1 and HT29/WiDr. Cell death induced by 25OHC was inhibited by the actin polymerization inhibitor, cytochalasin D, and BMS-3, an inhibitor of LIMK, which phosphorylates and inactivates cofilin. In addition, we showed that cofilin phosphorylation induced by 25OHC was associated with caspase-3 activation, which can activate ROCK. Rho GTPase was directly activated by 25OHC. These results indicate that 25OHC affects actin dynamics through activation of the Rho/ROCK/LIMK/cofilin axis, eventuating in the cell death of colorectal cancer cell spheroids.

Spermine synthesis inhibitor blocks 25-hydroxycholesterol-induced- apoptosis via SREBP2 upregulation in DLD-1 cell spheroids.

The oxysterol 25-hydroxycholesterol (25-HC) has diverse physiological activities, including the ability to inhibit anchorage-independent growth of colorectal cancer cells. Here, we found that a polyamine synthesis inhibitor, DFMO, prevented 25-HC-induced apoptosis in non-anchored colorectal cancer DLD-1 cells. Additionally, we found that the spermine synthesis inhibitor APCHA also inhibited 25-HC-induced apoptosis in DLD-1 spheroids. Inhibiting the maturation of SREBP2, a critical regulator of cholesterol synthesis, reversed the effects of APCHA. SREBP2 knockdown also abolished the ability of APCHA to counteract 25-HC activity. Furthermore, APCHA induced SREBP2 maturation and upregulated its transcriptional activity, indicating that altered polyamine metabolism can increase SREBP2 activity and block 25-HC-induced apoptosis in spheroids. These results suggest that crosstalk between polyamine metabolism and cholesterol synthetic pathways via SREBP2 governs the proliferative and malignant properties of colorectal cancer cells.

Choice reaction time and grip strength as predictors of cardiovascular mortality in middle-aged and elderly Japanese: from the Radiation Effects Research Foundation Adult Health study.

BACKGROUND: Cognitive function and physical function are important predictors of mortality. AIM: To investigate whether or not reaction time (RT) as a cognitive function and grip strength (GS) as a physical function were associated, alone or in combination, with mortality from heart disease or stroke. METHODS: The subjects included 4901 Adult Health Study participants in Hiroshima who had undergone RT and GS measurements, were 35-74 years old at baseline (1970-1972) and were followed until the end of 2007. RESULTS: After adjustment for other potential risk factors, RT was positively and GS was negatively associated with mortality from both heart disease and stroke. These associations were persistent in the model when adjusting simultaneously for RT, GS and other factors, but hazard ratios were attenuated. When we evaluated the associations by baseline age and gender, we found the greater hazard ratios for RT in the younger cohort, but no clear modification by age for GS. The interaction between RT and GS was statistically significant (P = 0.012) for stroke mortality. In the stratified analyses divided using the age-specific median value of RT or GS, the estimated hazard ratio of stroke mortality for RT was significant in participants with weak or strong GS but greater in the former, and for GS, it was only significant in participants with slow RT. CONCLUSION: RT and GS, alone and in combination, predicted heart disease and stroke mortalities. Interventions for both cognitive function and physical function may be beneficial for the prevention of cardiovascular disease mortality.

Association of N-Terminal Pro B-Type Natriuretic Peptide With Blood Pressure and Pulse Pressure in Elderly People　- A Cross-Sectional Population Study.

BACKGROUND: N-Terminal pro B-type natriuretic peptide (NT-proBNP) is widely used as a marker of ventricular dysfunction. However, data regarding the association of NT-proBNP with blood pressure (BP) and pulse pressure (PP) in the elderly population are limited.Methods and Results:The present cross-sectional study involved 6,529 participants, aged ≥70 years, without cardiovascular disease (CVD), who underwent general health examinations. Serum NT-proBNP concentrations were determined, with high NT-proBNP concentrations defined as those ≥125 pg/mL. Subjects were divided into five groups based on PP (<50, ≥50 to <60, ≥60 to <70, ≥70 to <80, and ≥80 mmHg). NT-proBNP was positively associated with systolic BP, whereas a U-shaped association was found between diastolic BP and NT-proBNP. The odds ratios for high NT-proBNP concentrations in the PP ≥80 and ≥70 to <80 mmHg groups (OR 1.83 [P<0.001] and 1.40 [P<0.005], respectively) were significantly higher than in the PP <50 mmHg group. All data were adjusted for age, sex, body mass index, hemoglobin concentration, serum creatinine, pulse rate, smoking, alcohol intake, and antihypertensive medication intake, and the presence of diabetes and dyslipidemia. CONCLUSIONS: The results suggest that NT-proBNP concentrations may be a marker of not only ventricular dysfunction, but also arterial stiffness in the elderly population without CVD.

Association between histological features of epicardial adipose tissue and coronary plaque characteristics on computed tomography angiography.

The means by which epicardial adipose tissue (EAT) could influence coronary plaque progression biologically remain unclear. We investigated the association between the histological findings of EAT and coronary plaque characteristics assessed by coronary computed tomography angiography (CCTA). We enrolled 34 patients in whom one or more coronary plaques containing non-calcified components were detected on CCTA before cardiac surgery [coronary artery bypass graft (CABG) or non-CABG]. We evaluated visceral adipose tissue (VAT) area, EAT volume, and coronary plaque characteristics including minimum computed tomography density (CTD) and vascular Remodeling Index (RI). Lower CTD and higher RI were considered as high-risk characteristics, and coronary plaque with both CTD < 39 Hounsfield units and RI > 1.05 was defined as two-characteristic plaque (2-CP). The numbers of CD68+ macrophages and CD31+ microvessels were assessed in six random high-power fields (400×) of EAT samples obtained during cardiac surgery. The entire cohort showed a wide range of EAT volume, which were similar between patients with 2-CP and those without. Patients with 2-CP had more amounts of EAT macrophages (85 ± 38 versus 45 ± 22, p = 0.0005) and vascularity (62 ± 33 versus 37 ± 19, p = 0.013) than those without. On multivariate analyses adjusted for age, sex, coronary risk factors, statin use, type of surgery, VAT area, EAT volume, and coronary calcium score, the presence of 2-CP showed significant correlation with increased EAT macrophages (ß = 0.65, p = 0.014) and vascularity (ß = 0.74, p = 0.0053). Our findings support the hypothesis that EAT biologic activities are associated with coronary plaque vulnerability.

Tumor Necrosis Factor-α Gene Expression in Epicardial Adipose Tissue is Related to Coronary Atherosclerosis Assessed by Computed Tomography.

AIMS: Tumor necrosis factor (TNF)-α reportedly has key pro-inflammatory properties in both atherosclerosis and adipocytes. To further investigate the biologic impact of epicardial adipose tissue (EAT) on coronary atherosclerosis, we evaluated the relationship between TNF-α gene expression in EAT and clinically-assessed coronary atherosclerosis on computed tomography (CT). METHODS: We studied 47 patients before cardiac surgery (coronary artery bypass grafting [CABG], n=26; non-CABG, n=21), assessing visceral adipose tissue (VAT) area, EAT volume, coronary calcium score (CCS), and the presence of non- and/or partially-calcified coronary plaque (NCP) on CT angiography. EAT and subcutaneous adipose tissue (SAT) samples were obtained during cardiac surgery. TNF-α mRNA in EAT was measured using quantitative real-time PCR, and normalized to that of SAT as control adipose tissue. RESULTS: There was no difference in the TNF-α expression level between patients scheduled for CABG and non-CABG surgery (p=0.23), or among the subgroups based on CCS (p=0.68), while patients with NCP had the higher TNF-α expression level than those without NCP (median [interquartile range], 2.50 [1.01-5.53] versus. 1.03 [0.64-2.16], p=0.022). On multivariate analysis adjusted for age, sex, coronary risk factors, statin therapy, CABG versus non-CABG, VAT area, and EAT volume, the presence of NCP had close correlation with the elevated TNF-α expression level (ß=0.79, p=0.003). CONCLUSIONS: TNF-α expressed regionally in EAT may exert potent effects on the progression of coronary atherosclerosis, suggesting a contribution of EAT to coronary artery disease through behavior of molecule.

Occasionally increased 18F-fluorodeoxyglucose uptake in apical hypertrophic cardiomyopathy with mid-ventricular obstruction.

We report on a 77-year-old man who was diagnosed with apical hypertrophic cardiomyopathy (HCM) with mid-ventricular obstruction. He had a cured hepatitis C infection. We detected occasionally increased 18F-fluorodeoxyglucose (18F-FDG) uptake on whole-body positron emission tomography (PET)/computed tomography (CT) performed to examine the involvement of bladder carcinoma. 18F-FDG-PET was restudied following specific preparation involving an 18-h low-carbohydrate diet and following 15-h fasting plus heparin pre-administration. Increased uptake of 18F-FDG was observed reproducibly in the hypertrophic apical to mid left ventricular myocardium, with a maximum standardized uptake value of 6.2. In contrast, relatively lower 18F-FDG-uptake areas tended to match areas of late gadolinium enhancement on cardiac magnetic resonance (CMR). Histopathological examination of myocardial biopsy showed disarried hypertrophic myocytes with cellular infiltration. Increased uptake of 18F-FDG may reflect the phenomenon of increased glucose utilization in hypertrophied myocardium. The increasing clinical utility of whole-body PET/CT for evaluating malignancies may increase the detection of occasional abnormal 18F-FDG uptake in the heart. It is necessary to clarify that 18F-FDG myocardial PET in combination with CMR may provide a more detailed risk assessment in patients with HCM. .

Identifying Small Coronary Calcification in Non-Contrast 0.5-mm Slice Reconstruction to Diagnose Coronary Artery Disease in Patients with a Conventional Zero Coronary Artery Calcium Score.

AIMS: In a new-generation computed tomography (CT) scanner, coronary artery calcium (CAC) scores were measured using 3.0-mm slice reconstruction images originally acquired with 0.5 mm thickness scans in a single beat. This study investigated the usefulness of thin-slice (0.5 mm) reconstruction for identifying small calcifications in coronary arteries and evaluated the association with coronary plaques and stenosis compared to conventional 3.0-mm reconstruction images. METHODS: We evaluated 132 patients with zero CAC scores in conventional 3.0-mm Agatston method using a 320-slice CT. Then, 0.5-mm slice reconstruction was performed to identify small calcifications. The presence of stenosis and coronary plaques was assessed using coronary CT angiography. RESULTS: In total, 22 small calcifications were identified in 18 patients. There were 28 (21%) patients with any (≥ 25%) stenosis (34 lesions). Forty-seven coronary plaques were found in 33 patients (25%), including 7 calcified plaques in 7 patients (5%), 34 noncalcified plaques in 27 patients (20%), and 6 partially calcified plaques in 5 patients (4%). Patients with small calcifications had a significantly higher prevalence of noncalcified or partially calcified plaques (83% vs 14%; p＜0.001) and obstructive stenosis (33% vs 5.2%; p＜0.001) compared to those without small calcifications. The addition of small calcifications to the coronary risk factors when diagnosing stenosis significantly improved the diagnostic value. CONCLUSION: Small calcifications detected by thin-slice 0.5-mm reconstruction are useful for distinguishing coronary atherosclerotic lesions in patients with zero CAC scores from conventional CT reconstruction.

Data set for volumetric and pathological findings of epicardial adipose tissue.

This article contains the data regarding clinically-assessed visceral adipose tissue (VAT) area and epicardial adipose tissue (EAT) volume on computed tomography (CT) images and EAT pathology, represented by inflammation and neoangiogenesis, complementing the data reported by Kitagawa et al. [1]. In 45 patients scheduled for cardiac surgery, we studied CT images obtained prior to surgery and the numbers of CD68+ individual macrophages and CD31+ neovessels in EAT samples subsequently obtained during surgery. The data revealed a moderate correlation between VAT area and EAT volume, and a strong correlation between EAT macrophage infiltration and neoangiogenesis.

The Potential Role of Inflammation Associated with Interaction between Osteopontin and CD44 in a Case of Pulmonary Tumor Thrombotic Microangiopathy Caused by Breast Cancer.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare and fatal cancer-related complication. We herein present a case of PTTM that diagnosed antemortem by lung scintigraphy and pulmonary microvascular cytology. The patient was treated with steroid pulse therapy. Although her symptoms temporarily improved, she died of respiratory failure. An autopsy showed PTTM, and an immunohistochemical analysis revealed the expression of osteopontin and CD44 in macrophages that had migrated into the PTTM lesions. These findings suggest that inflammation associated with the interaction between osteopontin and CD44 may play an important role in PTTM.

The relationship between inflammation and neoangiogenesis of epicardial adipose tissue and coronary atherosclerosis based on computed tomography analysis.

OBJECTIVE: Previous studies indicate that epicardial adipose tissue (EAT) biologically contributes to the progression of coronary atherosclerosis. We evaluated the relationship between EAT pathology, represented by inflammation and neoangiogenesis, and coronary atherosclerosis on computed tomography (CT) images. METHODS: We performed CT examination in 45 patients scheduled for cardiac surgery (coronary artery bypass graft [CABG], n = 21; non-CABG, n = 24) to assess visceral adipose tissue (VAT) area, EAT volume, coronary calcium score (CCS), and presence of non-calcified coronary plaque (NCP) on CT angiography. Each patient was assessed with the numbers of CD68(+) individual macrophages and CD31(+) neovessels in six random high-power fields (400×) of EAT samples subsequently obtained during cardiac surgery. RESULTS: In three groups based on CCS (mild, 0-100; moderate, 101-400; severe, >400), the moderate group had the most extensive macrophage infiltration (p = 0.0025) and neoangiogenesis (p = 0.0036) in EAT. The patients with NCP had more extensive macrophage infiltration (p = 0.010) and neoangiogenesis (p = 0.0043) in EAT than those without. On multivariate analysis adjusted for age, sex, CABG versus. non-CABG, VAT area, and EAT volume, moderate CCS and the presence of NCP showed significant correlations with increased macrophage infiltration (ß = 0.65; p < 0.0001, and ß = 0.49; p = 0.0089, respectively) and neoangiogenesis (ß = 0.55; p = 0.0011, and ß = 0.53; p = 0.012, respectively) in EAT. CONCLUSION: Inflammation and neoangiogenesis in EAT independently correlate with moderate coronary calcification and presence of NCP, suggesting that these two factors may have a role in promoting coronary atherosclerosis.

Radiation dose reduction for coronary artery calcium scoring at 320-detector CT with adaptive iterative dose reduction 3D.

To assess the possibility of reducing the radiation dose for coronary artery calcium (CAC) scoring by using adaptive iterative dose reduction 3D (AIDR 3D) on a 320-detector CT scanner. Fifty-four patients underwent routine- and low-dose CT for CAC scoring. Low-dose CT was performed at one-third of the tube current used for routine-dose CT. Routine-dose CT was reconstructed with filtered back projection (FBP) and low-dose CT was reconstructed with AIDR 3D. We compared the calculated Agatston-, volume-, and mass scores of these images. The overall percentage difference in the Agatston-, volume-, and mass scores between routine- and low-dose CT studies was 15.9, 11.6, and 12.6%, respectively. There were no significant differences in the routine- and low-dose CT studies irrespective of the scoring algorithms applied. The CAC measurements of both imaging modalities were highly correlated with respect to the Agatston- (r = 0.996), volume- (r = 0.996), and mass score (r = 0.997; p < 0.001, all); the Bland-Altman limits of agreement scores were -37.4 to 51.4, -31.2 to 36.4 and -30.3 to 40.9%, respectively, suggesting that AIDR 3D was a good alternative for FBP. The mean effective radiation dose for routine- and low-dose CT was 2.2 and 0.7 mSv, respectively. The use of AIDR 3D made it possible to reduce the radiation dose by 67% for CAC scoring without impairing the quantification of coronary calcification.

Development of new risk score for pre-test probability of obstructive coronary artery disease based on coronary CT angiography.

Existing methods to calculate pre-test probability of obstructive coronary artery disease (CAD) have been established using selected high-risk patients who were referred to conventional coronary angiography. The purpose of this study is to develop and validate our new method for pre-test probability of obstructive CAD using patients who underwent coronary CT angiography (CTA), which could be applicable to a wider range of patient population. Using consecutive 4137 patients with suspected CAD who underwent coronary CTA at our institution, a multivariate logistic regression model including clinical factors as covariates calculated the pre-test probability (K-score) of obstructive CAD determined by coronary CTA. The K-score was compared with the Duke clinical score using the area under the curve (AUC) for the receiver-operating characteristic curve. External validation was performed by an independent sample of 319 patients. The final model included eight significant predictors: age, gender, coronary risk factor (hypertension, diabetes mellitus, dyslipidemia, smoking), history of cerebral infarction, and chest symptom. The AUC of the K-score was significantly greater than that of the Duke clinical score for both derivation (0.736 vs. 0.699) and validation (0.714 vs. 0.688) data sets. Among patients who underwent coronary CTA, newly developed K-score had better pre-test prediction ability of obstructive CAD compared to Duke clinical score in Japanese population.

Clinical implications of the coronary artery calcium score in Japanese patients.

Coronary artery calcification (CAC) is a well-established surrogate marker of the total burden of coronary atherosclerosis. The CAC score, as measured on coronary computed tomography (CT), is associated with the prevalence of coronary artery disease (CAD) as well as cardiovascular morbidity and mortality. The CAC score is used to reclassify coronary risks in asymptomatic individuals with intermediate risks. However, there are few clinical data regarding the usefulness of the CAC score for identifying high-risk Japanese patients. In this review article, we describe our previous studies of the prognostic value of the CAC score in patients with proven or suspected CAD. In addition, we reanalyzed our previous data for 723 patients with suspected CAD and found both all-cause and cardiovascular disease mortality to be significantly higher among the patients with a CAC score of ≥100 than among those with a CAC score of ＜100. Several studies from Japan have also shown that the CAC score is associated with the prevalence of obstructive CAD, as demonstrated on invasive coronary angiography or stress myocardial perfusion imaging. Furthermore, the CAC score provides useful information for performing coronary CT angiography, as asymptomatic patients without CAC are expected to have favorable outcomes. In contrast, the diagnostic accuracy is decreased in patients with a high CAC score (＞400 or 600). In conclusion, the CAC score may have useful clinical applications in symptomatic and asymptomatic Japanese individuals. However, further studies are required to evaluate the prognostic value of this parameter for predicting cardiovascular morbidity and mortality in population-based analyses of asymptomatic Japanese subjects.

Insulin resistance and subclinical abnormalities of global and regional left ventricular function in patients with aortic valve sclerosis.

BACKGROUND: Insulin resistance, as a key mediator of metabolic syndrome, is thought to be associated with pathogenesis of calcific aortic valve disease and altered left ventricular (LV) function and structure. However, in patients with aortic valve sclerosis (AVS), the association between insulin resistance and subclinical impairment of LV function is not fully elucidated. METHODS: We studied 57 patients (mean age 70 ± 8 years, 22 women) with asymptomatic AVS but normal LV ejection fraction in echocardiography. LV longitudinal and circumferential strain and strain rate was analyzed using two-dimensional speckle tracking echocardiography. Patients with uncontrolled hypertension and diabetes mellitus, chronic kidney disease, and concomitant coronary artery disease were excluded. They were divided into the insulin-resistant group (AVS+IR; N = 28) and no insulin-resistant group (AVS-IR; N = 29) according to the median value of homeostatic model assessment index. Computed tomography scans were also performed to measure the aortic valve calcium score and the visceral adipose tissue (VAT) area. In addition, age- and sex- adjusted 28 control subjects were recruited for the comparison. RESULTS: There were no significant differences in LV ejection fraction or mass index among the groups. The AVS+IR group had a higher aortic valve calcium score (median 94 versus 21, P = 0.022) and a larger VAT area (113 ± 42 cm2 versus 77 ± 38 cm2, P = 0.001) than the AVS-IR group. Notably, LV global longitudinal strain, strain rate (SR), and early diastolic SR were significantly lower in the AVS+IR group than in the AVS-IR group and in control subjects (strain: -16.2 ± 1.6% versus -17.2 ± 1.2% and -18.9 ± 0.8%; SR: -1.18 ± 0.26 s(-1) versus -1.32 ± 0.21 s(-1) and -1.52 ± 0.08 s(-1); early diastolic SR: -1.09 ± 0.23 s(-1) versus -1.23 ± 0.18 s(-1) and -1.35 ± 0.12 s(-1); P < 0.05 for all comparison), whereas circumferential function were not significantly different. Multiple linear regression analyses revealed insulin resistance as an independent determinant of LV longitudinal strain (P = 0.017), SR (P = 0.047), and early diastolic SR (P = 0.049) regardless of LV mass index or VAT area. CONCLUSIONS: Insulin resistance is a powerful independent predictor of subclinical LV dysfunction regardless of concomitant visceral obesity and LV hypertrophy. Thus, it may be a novel therapeutic target to prevent subsequent heart failure in patients with AVS.

Impact of aldosterone-producing adenoma on cardiac structures in echocardiography.

BACKGROUND: Primary aldosteronism (PA) is a most common cause of secondary hypertension. In PA, left ventricular hypertrophy (LVH) is more progressive than in any other cause of hypertension. Aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) are major subtypes of PA. However there is little information concerned with differences of cardiac structures between these two subtypes. METHODS: We reviewed echocardiographic findings in 46 patients with PA. All patients had a positive screen test and subtypes of PA were confirmed by adrenal vein sampling. Subjects consisted of 20 patients with APA (APA group, 52.4 ± 10.8 years) and 26 patients with IHA (IHA group, 56.2 ± 9.5 years). We investigated differences of cardiac structures and functions in the left atrium and ventricle between the APA group and IHA group. RESULTS: In terms of clinical characteristics, the height and duration of hypertension were greater and serum potassium concentration and BMI were lower in the APA group than in the IHA group. Plasma aldosterone concentration (PAC) and PAC to plasma renin activity ratio were higher in the APA group than in the IHA group. In echocardiographic assessment, the left atrial volume, left ventricular end-diastolic and end-systolic diameters, left ventricular mass (LVM), and prevalence of LVH were greater in the APA group than in the IHA group. Multiple linear regression analysis revealed that the diagnosis of APA independently correlated with left atrial volume, left ventricular end-diastolic diameter, and LVM. CONCLUSIONS: We demonstrated that differences of cardiac structures between the APA group and IHA group existed. In APA, left atrial enlargement and LVH were more prominent than in IHA.

Incremental prognostic value of cardiac computed tomography angiography in asymptomatic aortic stenosis: significance of aortic valve calcium score.

BACKGROUND: Cardiac computed tomography angiography (CCTA) provides the simultaneous evaluation of the aortic valve, myocardium, and coronary arteries. In particular, aortic valve calcium score (AVCS) can be accurately measured on the same scanning sequence used to measure coronary artery calcification, with no additional cost or radiation exposure. We sought to evaluate the prognostic value of CCTA measures, including AVCS, in asymptomatic aortic stenosis (AS). METHODS AND RESULTS: Sixty-four initially asymptomatic patients with AS with a normal ejection fraction were prospectively enrolled and followed for median 29 (IQR=18-50) months. During follow-up, 27 (42%) patients experienced cardiac events, including five cardiac deaths, eleven aortic valve replacements. Multivariate Cox proportional hazards analysis identified three CCTA measures as significant predictors of cardiac events: aortic valve area (per 0.1cm(2) decrease; hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.05-1.34); multi-vessel obstructive coronary artery disease (HR: 2.84, 95% CI: 1.10-7.32); and AVCS (per 100; HR: 1.09, 95% CI: 1.04-1.15). Kaplan-Meier analysis showed that patients with AVCS greater than or equal to the median value of 723 had significantly worse outcomes than those with AVCS less than 723 (p<0.0001). The C-statistic value for cardiac events substantially increased when these CCTA measures were added to clinical characteristics plus echocardiographic peak transaortic velocity (0.913 vs. 0.702, p<0.001). CONCLUSIONS: In patients with asymptomatic AS, CCTA measures of valve area, coronary stenosis, and calcification severity provide independent and incremental prognostic value after accounting for the echocardiographic severity of stenosis.

Association between aortic valve calcification and myocardial ischemia, especially in asymptomatic patients.

UNLABELLED: Aortic valve calcification (AVC) is recognized as a manifestation of systemic arteriosclerosis. However, it is unclear whether AVC is associated with myocardial ischemia. Stress myocardial perfusion SPECT (MPS) is widely used for the diagnosis of myocardial ischemia. However, routine MPS is not recommended, particularly in asymptomatic patients. Accordingly, we investigated the hypothesis that the presence of AVC is strongly associated with inducible myocardial ischemia, even among asymptomatic patients. METHODS: We investigated 669 consecutive patients who underwent both adenosine stress (201)Tl MPS and echocardiography. We evaluated the extent and severity of myocardial ischemia by the summed difference score (SDS). We defined the presence of myocardial ischemia as SDS ≥ 3 and moderate to severe ischemia as SDS ≥ 8. We classified the severity of AVC according to the number of affected aortic leaflets. We also compared the mean SDS and the prevalence of SDS ≥ 3 and SDS ≥ 8 among patients stratified by the severity of AVC. RESULTS: The presence of AVC was significantly associated with myocardial ischemia (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.10-2.23; P = 0.013) and moderate to severe ischemia (OR, 2.16; 95% CI, 1.26-3.80; P = 0.0061). In 311 asymptomatic patients, AVC was strongly associated with moderate to severe ischemia (OR, 4.31; 95% CI, 1.67-12.8; P = 0.0043). However, the SDS value and the prevalence of SDS ≥ 3 and SDS ≥ 8 did not increase with increasing number of affected aortic leaflets. CONCLUSION: The presence of AVC may be associated with the presence of myocardial ischemia, particularly in asymptomatic patients. However, we found no association between the extent of AVC and inducible myocardial ischemia. The presence of AVC may be a useful anatomic marker to help identify patients at high risk of myocardial ischemia, particularly asymptomatic patients.

Effects of statin therapy on non-calcified coronary plaque assessed by 64-slice computed tomography.

UNLABELLED: Computed tomography angiography (CTA) enables characterization of non-calcified coronary atherosclerotic lesions (NCALs) and assessment of plaque vulnerability. We investigated whether the characteristics of NCALs detected by 64-slice CTA were influenced by preceding statin therapy and serum lipid profiles. METHODS: Among 493 consecutive patients who underwent coronary CTA, we enrolled 114 patients with NCALs. We divided the patients into three groups according to preceding statin therapy: intensive statins (IS, n=24), moderate statins (MS, n = 26), and no statin (NS, n = 64). The vulnerability of each NCAL was evaluated by density (low-density plaque defined as CT density ≤ 38 HU), positive remodeling (remodeling index > 1.05), and the presence of adjacent spotty calcification. RESULTS: Percentages of patients in the IS, MS, and NS groups with low-density NCALs were 46%, 58%, and 80%, respectively (p = 0.009) and positive remodeling NCALs were 54%, 58%, and 75%, respectively (p = 0.10). We also found an inverse correlation between serum LDL-C level and the minimum plaque CT density. According to the regression equation, a CT density of 38 HU corresponded with LDL-C of 100 mg/dl. The number of low-density plaques was positively correlated with low-density to high-density lipoprotein cholesterol ratio (LDL-C/HDL-C). An LDL-C/HDL-C > 2.5 independently predicted multiple low-density plaques (OR 2.39 [95%CI: 1.28-4.86], p < 0.001). CONCLUSIONS: Our CTA findings demonstrate that low-density NCALs occur less frequently in patients with intensive statin pre-treatment. A high LDL-C/HDL-C ratio is also associated with larger numbers of low-density NCALs.