Eue-Keun Choi

Coronary computed tomography angiography as a screening tool for the detection of occult coronary artery disease in asymptomatic individuals

OBJECTIVESnThe purpose of this study was to evaluate the prevalence of occult coronary artery disease (CAD) with coronary computed tomography angiography (CTA) to characterize plaque composition and to evaluate the potential of this new technology to impact risk stratification in asymptomatic middle-aged subjects.nnnBACKGROUNDnThere is a paucity of information regarding the role of CTA for the detection of occult CAD in asymptomatic individuals.nnnMETHODSnWe consecutively enrolled 1,000 middle-aged asymptomatic subjects (age 50 +/- 9 years, 63% men) who underwent CTA (64-slice multidetector row computed tomography) as part of a general health evaluation.nnnRESULTSnAtherosclerotic plaques were identified in 215 (22%, 2 +/- 1 segments/subject) individuals; 40 individuals (4%) had only noncalcified plaques. Fifty-two (5%) subjects had significant (>or=50%) diameter stenosis and 21 (2%) had severe (>or=75%) stenosis. Thirteen (25%) and 30 (58%) subjects with significant stenosis were classified into National Cholesterol Education Program low-risk and mild coronary calcification (coronary artery calcium scores <100), respectively. Midterm follow-up (17 +/- 2 months) revealed 15 cardiac events only in those with CAD on CTA: 1 unstable angina requiring hospital stay and 14 revascularization procedures. Most (87%) events occurred within 90 days of index CTA.nnnCONCLUSIONSnThe prevalence of occult CAD in apparently healthy individuals was not negligible, although their midterm prognosis was good. CTA has a potential to provide a better insight about the occult CAD in this population. However, on the basis of our results and considering present radiation exposure data, we cannot recommend that CTA be used as a screening tool for this population at this point.

Usefulness of 64-slice multidetector computed tomography as an initial diagnostic approach in patients with acute chest pain.

BACKGROUNDnRecently, multidetector computed tomography (MDCT) has been proposed as an accurate diagnostic tool to evaluate for coronary artery disease. However, the role of MDCT as part of the initial diagnostic for evaluating acute chest pain is less well established.nnnMETHODSnWe prospectively enrolled patients presenting with acute chest pain to the emergency department (ED) and risk stratified them based on the pretest probability for an acute coronary syndrome (ACS): (1) very low, (2) low, (3) intermediate, (4) high, and (5) very high or definite. After exclusion of very low and very high risk patients, 268 patients were randomized to either immediate 64-slice cardiac MDCT or a conventional diagnostic strategy. Number of admissions, ED and hospital length of stay (LOS), and major adverse cardiac events over 30 days of follow-up were compared between the strategies based on the pretest probability for ACS.nnnRESULTSnThe number of patients ultimately diagnosed with an ACS did not differ between the 2 strategies. Emergency department LOS and total admissions were not different between strategies. Patients in the MDCT-based strategy had a decreased hospital LOS (P = .049) and fewer admissions deemed unnecessary (P = .007). Reductions in unnecessary admissions were more prominent in intermediate-risk patients (P = .015). None of the patients discharged from the ED in the MDCT-based strategy experienced major adverse cardiac events at follow-up.nnnCONCLUSIONnUse of an MDCT-based strategy in the ED as part of the initial diagnostic approach for patients presenting with acute chest pain is safe and efficiently reduces avoidable admissions in patients with an intermediate pretest probability for ACS.

Detection of occult coronary artery disease in asymptomatic individuals with diabetes mellitus using non-invasive cardiac angiography

INTRODUCTION/OBJECTIVESnCardiovascular disease is the leading cause of death for individuals with diabetes mellitus. Controversy exists regarding the screening of asymptomatic diabetics for occult coronary artery disease (CAD). The purpose of this study is to describe the prevalence of occult CAD in a group of asymptomatic subjects with diabetes using non-invasive coronary angiography, as well as to investigate the predictive accuracy of current guidelines with regards to their recommended criteria for further cardiac diagnostic testing in this patient population.nnnMETHODSnWe prospectively enrolled 217 asymptomatic Korean outpatients with type 2 diabetes who had no prior history of CAD. All underwent non-invasive coronary angiography using a 64-slice multi-detector computed tomography scanner.nnnRESULTSnThe mean age of the study participants was 59+/-8 years; 66% were men. Diabetes duration was 7+/-7 years, mean Framingham risk score was 13%, and mean hemoglobin A1C level was 7%. Of the 217 outpatients, 138 (64%) had occult CAD based on cardiac computed tomography angiography (CCTA) findings. Thirty-six (36/138; 26%) had a significant stenosis on CCTA. Nearly half of the individuals (62/138; 45%) had a combination of non-calcified and calcified plaques. Only 5 out of 217 (2%) individuals with significant stenosis would have been missed using the American Diabetes Association (ADA) criteria for further cardiac testing.nnnCONCLUSIONnAlmost two thirds of asymptomatic diabetics have occult CAD, including obstructive disease. Based on CCTA findings, the ADA criteria for further cardiac diagnostic testing would identify most individuals who have a significant coronary stenosis.

Association of traditional cardiovascular risk factors with coronary plaque sub-types assessed by 64-slice computed tomography angiography in a large cohort of asymptomatic subjects.

OBJECTIVEnAlthough prior studies have shown that traditional cardiovascular (CV) risk factors are associated with the burden of coronary atherosclerosis, less is known about the relationship of risk factors with coronary plaque sub-types. Coronary computed tomography angiography (CCTA) allows an assessment of both, total disease burden and plaque characteristics. In this study, we investigate the relationship between traditional CV risk factors and the presence and extent of coronary plaque sub-types in a large group of asymptomatic individuals.nnnMETHODSnThe study population consisted of 1015 asymptomatic Korean subjects (53+/-10 years; 64% were males) free of known CV disease who underwent 64-slice CCTA as part of a health screening evaluation. We analyzed plaque characteristics on a per-segment basis according to the modified American Heart Association classification. Plaques in which calcified tissue occupied more than 50% of the plaque area were classified as calcified (CAP), <50% calcified area as mixed (MCAP), and plaques without any calcium as non-calcified (NCAP).nnnRESULTSnA total of 215 (21%) subjects had coronary plaque while 800 (79%) had no identifiable disease. Multivariate regression analysis demonstrated that increased age (per decade) and gender are the strongest predictors for the presence of any coronary plaque or the presence of at least one segment of CAP and MCAP (any plaque-age: OR 2.89; 95% CI 2.34, 3.56; male gender: OR 5.21; 95% CI 3.20, 8.49; CAP-age: OR 2.75; 95% CI 2.12, 3.58; male gender: 4.78; 95% CI 2.48, 9.23; MCAP-age: OR 2.62; 95% CI 2.02, 3.39; male gender: OR 4.15; 95% CI 2.17, 7.94). The strongest predictors for the presence of any NCAP were gender (OR 3.56; 95% CI 1.96-6.55) and diabetes mellitus (OR 2.87; 95% CI 1.63-5.08). When looking at the multivariate association between the presence of >/=2 coronary segments with a plaque sub-type and CV risk factors, male gender was the strongest predictor for CAP (OR 7.31; 95% CI 2.12, 25.20) and MCAP (OR 5.54; 95% CI 1.84, 16.68). Alternatively, smoking was the strongest predictor for the presence of >/=2 coronary segments with NCAP (OR 4.86; 95% CI 1.68, 14.07). Low-density lipoprotein cholesterol (LDL-C) was only a predictor for the presence and extent of mixed coronary plaque.nnnCONCLUSIONnAge and gender are overall the strongest predictors of atherosclerosis as assessed by CCTA in this large asymptomatic Korean population and these two risk factors are not particularly associated with a specific coronary plaque sub-type. Smoking is a strong predictor of NCAP, which has been suggested by previous reports as a more vulnerable lesion. Whether a specific plaque sub-type is associated with a worse prognosis is yet to be determined by future prospective studies.

Impact of Coronary Computed Tomographic Angiography Results on Patient and Physician Behavior in a Low-Risk Population

BACKGROUNDnThe impact of screening coronary computed tomographic angiography (CCTA) on physician and patient behavior is unclear.nnnMETHODSnWe studied asymptomatic patients from a health-screening program. Our study population comprised 1000 patients who underwent CCTA as part of a prior study and a matched control group of 1000 patients who did not. We assessed medication use, secondary test referrals, revascularizations, and cardiovascular events at 90 days and 18 months.nnnRESULTSnA total of 215 patients in the CCTA group had coronary atherosclerosis (CCTA positive). Medication use was increased in the CCTA-positive group compared with both the CCTA-negative (no atherosclerosis) and control groups at 90 days (statin use, 34% vs 5% vs 8%, respectively; aspirin use, 40% vs 5% vs 8%, respectively), and 18 months (statin use, 20% vs 3% vs 6%, respectively; aspirin use, 26% vs 3% vs 6%, respectively). After multivariable risk adjustment, the odds ratios for statin and aspirin use in the CCTA-positive group at 18 months were 3.3 (95% confidence interval [CI], 1.3-8.3) and 4.2 (95% CI, 1.8-9.6), respectively. At 90 days, in the total CCTA group vs controls, there were more secondary tests (55 [5%] vs 22 [2%]; P < .001) and revascularizations (13 [1%] vs 1 [0.1%]; P < .001). One cardiovascular event occurred in each group over 18 months.nnnCONCLUSIONSnAn abnormal screening CCTA result was predictive of increased aspirin and statin use at 90 days and 18 months, although medication use lessened over time. Screening CCTA was associated with increased invasive testing, without any difference in events at 18 months. Screening CCTA should not be considered a justifiable test at this time.

Assessment of Subclinical Coronary Atherosclerosis in Asymptomatic Patients With Type 2 Diabetes Mellitus With Single Photon Emission Computed Tomography and Coronary Computed Tomography Angiography

We evaluated the characteristics of coronary artery disease in asymptomatic patients with type 2 diabetes mellitus (DM) using single photon emission computed tomography (SPECT) and coronary computed tomographic angiography (CCTA). A total of 116 patients with DM without abnormal electrocardiographic findings or evidence of peripheral arterial disease (number of risk factors > or =2; 62 +/- 7 years, 59% men) underwent CCTA and SPECT. Of the 116 patients with DM, 88 (76%) had a normal single photon emission computed tomographic findings, and 28 (24%) had abnormal perfusion defects. Of the 116 patients, 92 (79%) had atherosclerotic plaques (2 +/- 2 segments per subject), and 20 (17%) had significant stenosis seen on CCTA. Patients with DM and normal findings on SPECT had a similar prevalence of atherosclerotic plaque (78% vs 82%), significant stenosis (15% vs 25%), severe stenosis (7% vs 7%), and calcified (40% vs 43%), mixed (49% vs 57%), and noncalcified plaques (26% vs 29%) and a high (>100) coronary artery calcium score (32% vs 29%; all p >0.05) compared to those with abnormal findings on SPECT. During the mid-term follow-up (24 +/- 4 months), 5 cardiac events occurred in patients with DM and normal findings on SPECT, only in those with occult CAD on CCTA: 1 sudden cardiac death and 4 revascularization procedures. In conclusion, a significant percentage of patients with DM and normal eletrocardiographic findings, no peripheral arterial disease, and normal findings on SPECT have evidence of occult CAD on CCTA. Furthermore, a small percentage had had a cardiac event by mid-term follow-up. SPECT showed limited capability to differentiate the coronary risks between patients with DM and no coronary plaque and from those with a certain degree of disease; 2 circumstances that represent different coronary risks.

N-cadherin Determines Individual Variations in the Therapeutic Efficacy of Human Umbilical Cord Blood-derived Mesenchymal Stem Cells in a Rat Model of Myocardial Infarction

In this study, we established and characterized human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) from four different donors. However, the hUCB-MSCs showed remarkable variations in their therapeutic efficacy for repairing rat infarcted myocardium (including the process of angiogenesis) 8 weeks after transplantation. In addition, we observed that the level of vascular endothelial growth factor (VEGF) is correlated with the therapeutic efficacy of the four hUCB-MSCs. Next, to investigate the practical application of hUCB-MSCs, we searched for surface signature molecules that could serve as indicators of therapeutic efficacy. The gene for N-cadherin was the only cell surface gene that was highly expressed in the most effective hUCB-MSCs, both at the transcriptional and translational levels. We observed downregulation and upregulation of VEGF in response to N-cadherin blocking and N-cadherin overexpression, respectively. Activation of extracellular signal-regulated kinase (ERK), but not protein kinase B, was increased when N-cadherin expression was increased, whereas disruption of N-cadherin-mediated cell-cell contact induced suppression of ERK activation and led to VEGF downregulation. Moreover, by investigating hUCB-MSCs overexpressing N-cadherin or N-cadherin knockdown hUCB-MSCs, we confirmed the in vivo function of N-cadherin. In addition, we observed that DiI-labeled hUCB-MSCs express N-cadherin in the peri-infarct area and interact with cardiomyocytes.

Association between high-sensitivity C-reactive protein and coronary plaque subtypes assessed by 64-slice coronary computed tomography angiography in an asymptomatic population

Background— Elevated levels of C-reactive protein (CRP) are associated with poor cardiovascular outcomes, even after accounting for traditional cardiovascular risk factors. We sought to analyze the relationship between levels of CRP and coronary plaque subtypes as assessed by coronary computed tomography angiography. Methods and Results— We evaluated 1004 asymptomatic South Korean subjects (mean age, 49±9.3 years) who underwent coronary computed tomography angiography as part of a health screening evaluation. We examined the association between increasing CRP levels and plaque subtypes using multivariable linear and logistic regression analysis. Coronary plaque was observed in 211 of 1004 individuals (21%). Subjects with high CRP (≥2 mg/L) had an increased prevalence of any plaque type (30.7% versus 16.7% P<0.001) and mixed calcified arterial plaque (MCAP) (19.3% versus 6.3% P<0.001) as compared with subjects with low-normal CRP. Multivariable logistic regression analysis demonstrated that elevated CRP predicted the presence of any MCAP (high versus low-normal CRP group; odds ratio, 2.81; 95% confidence interval, 1.62 to 4.89). When examining the multivariable logistic regression analysis between the presence of ≥2 plaques and CRP, subjects with high CRP were more likely to have MCAP than those with low-normal CRP levels (odds ratio, 3.78; 95% confidence interval, 1.49 to 9.55). Conclusions Elevated levels of CRP are associated with an increased prevalence of MCAP as assessed by coronary computed tomography angiography. Longitudinal studies will determine if the excess risk observed in persons with elevated CRP may be mediated, at least in part, by an increased burden of MCAP.

Association between increasing levels of hemoglobin A1c and coronary atherosclerosis in asymptomatic individuals without diabetes mellitus.

BackgroundEarlier studies have shown an association between high-normal glucose and increasing glycosylated hemoglobin (HbA1c) levels and cardiovascular events. The objective of this investigation was to study the association between increasing levels of HbA1c in asymptomatic individuals without diabetes mellitus (DM) and coronary plaque characteristics. MethodsThe study population consisted of 1043 asymptomatic Korean individuals without DM who underwent 64-slice cardiac computed tomography angiography as part of a health screening evaluation. We excluded 147 individuals with known history of DM and/or fasting glucose of at least 126u2009mg/dl, no HbA1c data, or missing risk factor information. The associations between coronary atherosclerosis and plaque subtype burden with increasing HbA1c levels were assessed using multivariable regression analyses. ResultsThe final study population consisted of 906 individuals without DM (mean age: 49±9 years, 62% males); 19 and 9% of the population had any and two or more segments with coronary plaque, respectively. Unadjusted analysis showed a positive association between increasing levels of HbA1c and the number of coronary segments with any (P<0.001) and with mixed coronary plaques (P<0.0001). The association persisted even when traditional risk factors were taken into account. No significant relationship was found between increasing HbA1c levels and the burden of noncalcified or calcified plaque. ConclusionIncreasing levels of HbA1c in asymptomatic individuals without DM are associated with the presence of coronary atherosclerosis, but more specifically with the presence and burden of mixed coronary plaques. Elements of plaque instability have been associated with mixed coronary plaques.

Comprehensive evaluation of coronary arteries by multidetector-row cardiac computed tomography according to the glucose level of asymptomatic individuals.

BACKGROUNDnEarly detection of atherosclerosis in individuals with diabetes is important because of high cardiovascular mortality in this population. We performed multidetector-row computed tomography (MDCT) in asymptomatic individuals to investigate the status of coronary artery stenosis and plaque characteristics depending on the glucose level.nnnMETHODS AND RESULTSnThe plaque burden (number of diseased coronary segments), severity of stenosis, plaques characteristics, and coronary artery calcium score (CACS) were assessed by MDCT in 1043 asymptomatic individuals. Anthropometric parameters and metabolic profiles were also acquired. Twenty-one percents of subjects had plaques and 5% had significant stenosis. Mean (+/-S.D.) CACS of study population was 17+/-81. Subjects with impaired fasting glucose (IFG, n=215, 21%) or diabetes (n=112, 11%) had a greater plaque burden, more coronary stenosis (>50% of diameter stenosis) and higher CACS than normal subjects (all, p<0.01). Noncalcified and mixed plaques were observed more in subjects with diabetes (19%) and IFG (11%) than normal (7%). After adjustment for confounding factors, higher fasting glucose was strongly associated with significant coronary stenosis and a greater plaque burden.nnnCONCLUSIONSnMore significant coronary stenosis and multivessel involvement, higher CACS, and greater plaque burden were observed in subjects with IFG or diabetes by MDCT, even they are asymptomatic. Proactive screening, irrespective of the imaging modalities used, in asymptomatic subjects with prediabetes and diabetes is helpful to identify those who have a higher cardiovascular morbidity and mortality. Further studies will guide us with respect to which imaging modality is more appropriate.