Chan Joon Kim

Coronary Computed Tomographic Angiographic Findings in Asymptomatic Patients With Type 2 Diabetes Mellitus

There are limited data regarding the role of coronary computed tomographic angiography (CCTA) in asymptomatic patients with type 2 diabetes mellitus. We analyzed 557 asymptomatic type 2 diabetic patients who underwent CCTA. Cardiac event was defined as a composite of cardiac death, nonfatal myocardial infarction, acute coronary syndrome requiring hospitalization, or late revascularization. Atherosclerotic plaques were observed in 395 patients (70.9%), and 170 patients (30.5%) showed significant coronary artery disease (CAD) on CCTA. Ninety-two patients (16.5%) were associated with a significant stenosis in the left main or proximal left anterior descending artery. During the follow-up period (33.7 ± 7.8 months), although an excellent prognosis was observed in patients without significant CAD on CCTA, those with significant CAD showed more cardiac events (7.1% vs 0.5%) and lower 3-year event-free survival rates (99.2 ± 0.6% vs 90.9 ± 2.6%, p <0.001). Furthermore, in group with significant CAD, patients with significant CAD in the left main or proximal left anterior descending artery had more cardiac events (10.9% vs 2.6%) and lower 3-year event-free survival rates (97.4 ± 1.8% vs 86.1 ± 4.2%, p = 0.049). On multivariate analysis, family history of premature CAD, previous history of stroke, higher UK Prospective Diabetes Study 10-year risk scores, neuropathy, and retinopathy were independent clinical predictors of having significant CAD and left main or proximal left anterior descending artery significant CAD on CCTA. In conclusion, about 1/3 of asymptomatic type 2 diabetic patients had significant CAD on CCTA with a subsequent high risk for cardiac events. These findings suggest that CCTA may have a potential role in identifying patients with high cardiovascular risks in asymptomatic type 2 diabetes.

Comparison of Zotarolimus-Eluting Stent Versus Sirolimus-Eluting Stent for De Novo Coronary Artery DisEase in Patients With DIABETES Mellitus from the ESSENCE-DIABETES II Trial

Angiographic and clinical outcomes remain relatively unfavorable for diabetic patients even after the use of drug-eluting stent. This prospective, multicenter, randomized study compared the relative efficacy and safety of resolute zotarolimus-eluting stent (R-ZES) and sirolimus-eluting stent (SES) implantation in diabetic patients with coronary artery disease. The primary end point was noninferiority of angiographic in-segment late loss at 9 months. Clinical events were also monitored for at least 12 months. Patient recruitment was prematurely stopped after enrollment of 256 patients (127 in R-ZES group and 129 in SES) because of discontinuing production of SES. The R-ZES was noninferior to the SES for 9-month in-segment late loss (0.34 ± 0.30 vs 0.39 ± 0.43 mm; difference -0.048; 95% confidence interval -0.157 to 0.061; upper 1-sided 95% confidence interval 0.044; p <0.001 for noninferiority). In addition, in-stent late loss (0.22 ± 0.29 vs 0.21 ± 0.40 mm, p = 0.849) and the rates of in-segment (1.2% vs 6.7%, p = 0.119) and in-stent (1.2% vs 3.3%, p = 0.621) binary restenoses were similar between the 2 groups. At 12 months, there were no statistical differences between the 2 groups in the incidence of any clinical outcomes (death, myocardial infarction, stent thrombosis, ischemia-driven target lesion revascularization, ischemia-driven target vessel revascularization, and composite outcomes). In conclusion, despite having reduced power because of early study termination, our study suggests that the R-ZES has noninferior angiographic outcomes at 9 months to the SES in diabetic patients with coronary artery disease.

Impact of the CYP2C19*17 polymorphism on the clinical outcome of clopidogrel therapy in Asian patients undergoing percutaneous coronary intervention.

The impact of the CYP2C19*17 polymorphism on the clinical outcome in Asians undergoing percutaneous coronary intervention (PCI) is unknown. We sought to assess the long-term impact of CYP2C19*17 on the risk for adverse clinical events in 2188 Korean patients taking clopidogrel after PCI. The prevalence of the CYP2C19*17 allele [*wt/*17: 2.4% (n=53), *17/*17: 0%] was very low. The 2-year cumulative event rates for bleeding [*wt/*17 vs. *wt/*wt: 2 vs. 2.3%; adjusted hazard ratio (HR), 1.23; 95% confidence interval (CI), 0.16–9.45], stent thrombosis (2 vs. 1.1%; HR, 3.98; 95% CI, 0.49–31.6) or composite of any death, and myocardial infarction or stroke (5.4 vs. 7.1%; HR, 1.37; 95% CI, 0.32–5.73) did not differ on the basis of the presence of CYP2C19*17. In conclusion, in our study population of Asian patients, the CYP2C19*17 polymorphism was not associated with adverse clinical outcomes after PCI because of its low prevalence, the rarity of homozygotes, and the relatively low rate of adverse clinical events.

Impact of Percutaneous Coronary Intervention for Chronic Total Occlusion in Non–Infarct-Related Arteries in Patients With Acute Myocardial Infarction (from the COREA-AMI Registry)

Chronic total occlusion (CTO) in a non-infarct-related artery (IRA) is an independent predictor of clinical outcomes in patients with acute myocardial infarction (AMI). This study evaluated the impact of successful percutaneous coronary intervention (PCI) for CTO of a non-IRA on the long-term clinical outcomes in patients with AMI. A total of 4,748 patients with AMI were consecutively enrolled in the Convergent Registry of Catholic and Chonnam University for AMI registry from January 2004 to December 2009. We enrolled 324 patients with CTO in a non-IRA. To adjust for baseline differences, propensity matching (96 matched pairs) was used to compare successful PCI and occluded CTO for the treatment of CTO in non-IRA. The primary clinical end points were all-cause mortality and a composite of the major adverse cardiac events, including cardiac death, MI, stroke, and any revascularization during the 5-year follow-up. Patients who received successful PCI for CTO of non-IRA had lower rates of all-cause mortality (16.7% vs 32.3%, hazard ratio 0.459, 95% CI 0.251 to 0.841, p = 0.012) and major adverse cardiac events (21.9% vs 55.2%, hazard ratio 0.311, 95% CI 0.187 to 0.516, p <0.001) compared with occluded CTO group. Subgroup analyses revealed that successful PCI resulted in a better mortality rate in patients with normal renal function compared to patients with chronic kidney disease (p = 0.010). In conclusion, successful PCI for CTO of non-IRA is associated with improved long-term clinical outcomes in patients with AMI.

Obstructive Sleep Apnea Using Watch-PAT 200 Is Independently Associated With an Increase in Morning Blood Pressure Surge in Never-Treated Hypertensive Patients.

This study aimed to examine the association between obstructive sleep apnea (OSA) and morning blood pressure surge in never‐treated patients with essential hypertension. This prospective study included a total of 58 patients (mean age, 51.7 years; 55.2% men) with never‐treated essential hypertension. The patients were divided into non‐OSA (n=23, 49.3±12.7 years) and OSA (n=35, 53.2±9.8 years) groups. The OSA group was defined as having an apnea‐hypopnea index level >5 as measured by the Watch‐PAT 200. The authors collected 24‐hour ambulatory BP, plasma aldosterone concentration, and plasma renin activity data from all of the patients. The measured sleep‐trough morning systolic blood pressure (SBP) increases were higher in the OSA group than in the non‐OSA group (28.7±11.8 mm Hg vs 19.6±12.8 mm Hg, P=.008). The sleep‐trough morning SBP increase was inversely correlated with the lowest oxygen saturation (r=−0.272, P=.039). OSA known to be associated with increased daytime and nocturnal sympathetic activity was associated with significantly higher sleep‐trough morning SBP levels in this study.

Clinical Significance of Chronic Kidney Disease and Atrial Fibrillation on Morbidity and Mortality in Patients with Acute Myocardial Infarction

Background/Aims: Atrial fibrillation (AF) often coexists with acute myocardial infarction (AMI), and chronic kidney disease (CKD) is a major risk for AMI. However, the combined impact of CKD and AF on the mortality and morbidity in AMI population has not been determined. Methods: Between January 2004 and December 2009, a total of 4,738 AMI patients were enrolled prospectively. Patients were divided into four groups according to the combined status of CKD and AF. The primary endpoint was a combination of 5-year major adverse cardiac and cerebrovascular events (MACCE). Results: The prevalence of AF was significantly higher in CKD patients than in non-CKD patients (6.76 vs. 3.31%, p < 0.001). The highest cumulative event rate of MACCE and death was observed in patients with both CKD and AF (68.5 and 64.0%), respectively. In multivariable analyses, compared with patients with neither AF nor CKD, hazard ratios (HR) for composite of MACCE were 1.66 (95% CI, 1.14-2.41), 1.24 (95% CI, 1.06-1.46), and 2.10 (95% CI, 1.42-3.13) for patients with AF only, those with CKD only, and those with both CKD and AF, respectively (p for interaction = 0.935). Patients with both CKD and AF had a greatest risk for all-cause mortality (HR 2.54; 95% CI, 1.60-4.53), and the significant synergistic interaction was observed between CKD and AF (p for interaction = 0.015). Conclusion: The combined effect of AF and CKD on the risk of MACCE after an AMI is stronger than any separate condition, and it confers a synergistic effect on the all-cause mortality risk.

Evaluation of the incremental prognostic value of the combination of CYP2C19 poor metabolizer status and ABCB1 3435 TT polymorphism over conventional risk factors for cardiovascular events after drug-eluting stent implantation in East Asians

Purpose:We evaluated the incremental prognostic value of combining the CYP2C19 poor metabolizer (PM) and ABCB1 3435 TT for adverse clinical outcomes over conventional risk factors in a percutaneous coronary intervention (PCI) cohort.Methods:We enrolled 2,188 patients. The primary end point was a composite of death from any cause, nonfatal myocardial infarction (MI), and stroke during 1-year follow-up. The population was stratified into the following four groups: CYP2C19 EM/IM+ABCB1 3435 CC/CT, CYP2C19 EM/IM+ABCB1 3435 TT, CYP2C19 PM+ABCB1 3435 CC/CT, and CYP2C19 PM+ABCB1 3435 TT.Results:A total of 87 (3.97%) primary end-point events occurred (64 deaths, 8 non-fatal MIs and 15 strokes). Multivariate Cox analysis indicated that CYP2C19 PM+ABCB1 3435 TT status was a significant predictor of the primary end point (hazard ratio = 4.51, 95% confidence interval (CI) = 1.92–10.58). However, addition of combined genetic status to the clinical risk model did not improve the model discrimination (C-statistic = 0.786 (95% CI = 0.734–0.837) to 0.785 (95% CI = 0.733–0.838)) or risk reclassification (categorical net reclassification improvement (0.040, P = 0.32), integrated discrimination improvement (0.021, P = 0.026)).Conclusions:In a real-world East Asian PCI population taking clopidogrel, although the concurrent presence of CYP2C19 PM and ABCB1 TT is a strong independent predictor of adverse outcomes, the combined status of two at-risk variants does not have an incremental prognostic value beyond that of the conventional clinical risk factors.Genet Med 18 8, 833–841.

The Prognostic Value of the Left Ventricular Ejection Fraction Is Dependent upon the Severity of Mitral Regurgitation in Patients with Acute Myocardial Infarction.

The prognostic value of the left ventricle ejection fraction (LVEF) after acute myocardial infarction (AMI) has been questioned even though it is an accurate marker of left ventricle (LV) systolic dysfunction. This study aimed to examine the prognostic impact of LVEF in patients with AMI with or without high-grade mitral regurgitation (MR). A total of 15,097 patients with AMI who received echocardiography were registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between January 2005 and July 2011. Patients with low-grade MR (grades 0-2) and high-grade MR (grades 3-4) were divided into the following two sub-groups according to LVEF: LVEF ≤ 40% (n = 2,422 and 197, respectively) and LVEF > 40% (n = 12,252 and 226, respectively). The primary endpoints were major adverse cardiac events (MACE), cardiac death, and all-cause death during the first year after registration. Independent predictors of mortality in the multivariate analysis in AMI patients with low-grade MR were age ≥ 75 yr, Killip class ≥ III, N-terminal pro-B-type natriuretic peptide > 4,000 pg/mL, high-sensitivity C-reactive protein ≥ 2.59 mg/L, LVEF ≤ 40%, estimated glomerular filtration rate (eGFR), and percutaneous coronary intervention (PCI). However, PCI was an independent predictor in AMI patients with high-grade MR. No differences in primary endpoints between AMI patients with high-grade MR (grades 3-4) and EF ≤ 40% or EF > 40% were noted. MR is a predictor of a poor outcome regardless of ejection fraction. LVEF is an inadequate method to evaluate contractile function of the ischemic heart in the face of significant MR.

Contrast Volume/Raw eGFR Ratio for Predicting Contrast-Induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Intervention for Myocardial Infarction

Background: Considering that contrast medium is excreted through the whole kidney in a similar manner to drug excretion, the use of raw estimated glomerular filtration rate (eGFR) rather than body surface area (BSA)-normalized eGFR is thought to be more appropriate for evaluating the risk of contrast-induced acute kidney injury (CI-AKI). Methods: This study included 2,189 myocardial infarction patients treated with percutaneous coronary intervention. Logistic regression analysis was performed to identify the independent risk factors. We used receiver-operating characteristic (ROC) curves to compare the ratios of contrast volume (CV) to eGFR with and without BSA normalization in predicting CI-AKI. Results: The area under the curve (AUC) of the ROC curve for the model including all the significant variables such as diabetes mellitus, left ventricular ejection fraction, preprocedural glucose, and the CV/raw modification of diet in renal disease (MDRD) eGFR ratio was 0.768 [95% confidence interval (CI), 0.720-0.816; p < 0.001]. When the CV/raw MDRD eGFR ratio was used as a single risk value, the AUC of the ROC curve was 0.650 (95% CI, 0.590-0.711; p < 0.001). When the CV/MDRD eGFR ratio with BSA normalization ratio was used, the AUC of the ROC curve further decreased to 0.635 (95% CI, 0.574-0.696; p < 0.001). The difference between the two AUCs was significant (p = 0.002). Conclusions: Raw eGFR is a better predictor for CI-AKI than BSA-normalized eGFR.

Family history of diabetes and the risk of subclinical atherosclerosis.

AIM This study investigated the influence of a family history of diabetes on the risk of subclinical coronary atherosclerosis according to coronary computed tomography angiography (CCTA) in asymptomatic individuals. METHODS A total of 6434 consecutive asymptomatic individuals with no prior history of coronary artery disease voluntarily underwent CCTA evaluation as part of a general health examination. Coronary atherosclerotic plaque and significant coronary artery stenosis (degree of stenosis ≥50%) on CCTA were assessed. Logistic regression analysis was used to determine the association between a family history of diabetes and atherosclerotic plaque or significant coronary artery stenosis according to the degree of diabetes (normal, prediabetic and diabetic). RESULTS Mean age of study participants was 53.7±7.6 years, and 4694 (73.0%) were male. A total of 1593 (24.8%) participants had a family history of diabetes in a first-degree relative. Among the study participants, 1115 (17.3%), 3122 (48.5%) and 2197 (34.1%) were categorized as diabetic, prediabetic and normal, respectively. In diabetic participants, after stepwise adjustments for clinical and laboratory variables, a family history of diabetes was significantly associated with non-calcified plaque (P<0.05 for all), but did not appear to be associated with either calcified or mixed plaques or with significant coronary artery stenosis (P>0.05 for all). In prediabetic and normal participants, a family history of diabetes was not associated with either atherosclerotic plaque or significant coronary artery stenosis (P>0.05 for all). CONCLUSION In asymptomatic diabetic individuals, a family history of diabetes is consistently associated with non-calcified coronary plaque after adjusting for risk factors.