The Decline Effect in Cardiovascular Medicine: Is the Effect of Cardiovascular Medicine and Stent on Cardiovascular Events Decline Over the Years?

이무식,Andreas J. Flammer,Amir Lerman 대한심장학회 2013 Korean Circulation Journal Vol.43 No.7

The term decline effect is referred to a diminution of scientifically discovered effects over time. Reasons for the decline effect are multi-faceted and include publication bias, selective reporting, outcomes reporting bias, regression to the mean, scientific paradigm shift, over-shadowing and habituation, among others. Such effects can be found in cardiovascular medicines through medications (e.g., aspirin, an-tithrombotics, proton pump inhibitor, beta-blockers, statins, estrogen/progestin, angiotensin converting enzyme inhibitor etc.), as well as with interventional devices (e.g., angioplasty, percutaneous coronary intervention, stents). The scientific community should understand the various dimensions of the decline effects, and effective steps should be undertaken to prevent or recognize such decline effects in cardiovascular medicines.

Serum Uric Acid is Associated with Cardiovascular Events in Patients with Coronary Artery Disease

배장호,현대우,권택근,윤현주,Amir Lerman,Charanjit S Rihal 대한심장학회 2007 Korean Circulation Journal Vol.37 No.4

Background and Objectives:Whether uric acid is a predictor of cardiovascular events remains controversial. Wesought to evaluate the effects of the serum uric acid levels on major adverse cardiovascular events (MACEs) inthe patients with coronary artery disease (CAD). Subjects and Methods:The study population consisted of 660consecutive patients with CAD, and they were followed up for a mean of 27 months (maximum: 62 months). Therecorded MACEs included acute myocardial infarction (AMI), stroke, coronary artery bypass graft, percutaneouscoronary intervention (PCI) due to de novo lesion during follow up, congestive heart failure (CHF) and suddencardiac death. Results:In the CAD patients with a uric acid level ≤3.88 mg/dL (the lowest quartile), as comparedwith those CAD patients with uric acid levels >5.74 mg/dL (the highest quartile), the MACE rate increased from7.2% to 20.1%. On univariate Cox regression analysis, the highest uric acid quartile was a predictor of AMI, CHFand MACE. The absolute serum uric acid level was predictive of PCI, CHF and MACE. Multivariate Cox regressionanalysis showed that the independent predictors of MACE were presentation with acute coronary syndrome (HR1.70, 95% CI: 1.04 to 2.78, p=0.033), multi-vessel disease (HR 2.43, 95% CI: 1.44 to 4.12, p=0.001), and the uricacid levels (HR 1.22, 95% CI: 1.05 to 1.43, p=0.010), and the highest uric acid quartile (HR 2.54, 95% CI: 1.58 to4.10, p<0.001). Conclusion:The serum uric acid level and multi-vessel disease are associated with subsequentcardiovascular events in the patients with CAD. (Korean Circulation J 2007;37:161-166)

Personalized Medicine in Cardiovascular Diseases

이무식,Andreas J. Flammer,Lilach O. Lerman,Amir Lerman 대한심장학회 2012 Korean Circulation Journal Vol.42 No.9

Personalized medicine is a novel medical model with all decisions and practices being tailored to individual patients in whatever ways possible. In the era of genomics, personalized medicine combines the genetic information for additional benefit in preventive and thera -peutic strategies. Personalized medicine may allow the physician to provide a better therapy for patients in terms of efficiency, safety and treatment length to reduce the associated costs. There was a remarkable growth in scientific publication on personalized medicine within the past few years in the cardiovascular field. However, so far, only very few cardiologists in the USA are incorporating personalized medi-cine into clinical treatment. We review the concepts, strengths, limitations and challenges of personalized medicine with a particular focus on cardiovascular diseases (CVDs). There are many challenges from both scientific and policy perspectives to personalized medicine, which can overcome them by comprehensive concept and understanding, clinical application, and evidence based practices. Individualized med-icine serves a pivotal role in the evolution of national and global healthcare reform, especially, in the CVDs fields. Ultimately, personalized medicine will affect the entire landscape of health care system in the near future.

Hypertension, a Low Ejection Fraction and Severe Angiographic Findings are Associated with Smooth Muscle Dysfunction in Patients with Coronary Atherosclerosis

배장호,Charanjit S. Rihal,현대우,박기락,권택근,윤현주,Amir Lerman 대한심장학회 2007 Korean Circulation Journal Vol.37 No.10

Background and Objectives: Nitroglycerin-mediated arterial dilation (NMD) was shown to be preserved in mostprevious studies, and this is possibly due to using a single high dose of nitroglycerin (NTG), which causes maximalarterial dilation. We sought to evaluate the clinical factors of flow-mediated dilation (FMD) and NMD atdifferent doses of NTG in the patients with coronary artery disease (CAD). Subjects and Methods: Thirty-twoconsecutive patients (mean age: 61 years old, 18 males) with angiographically proven CAD underwent FMD andNMD at total cumulative doses of 25μg, 175μg and 325μg with using high-resolution ultrasound for the imaging.Results: The FMD, NMD (25μg), NMD (175μg) and NMD (325μg) were 4.72±1.82%, 7.08±3.02%,13.33±6.14% and 15.89±7.24%, respectively (p<0.001 compared with each other). Univariate analysis showedthat the FMD is associated with the serum homocysteine level, the NMD (25μg) is associated with the bodymass index, the NMD (175μg) is associated with the fasting blood sugar and the ejection fraction, and the NMD(325μg) is associated with the fasting blood sugar, while there was no significant difference of the FMD andNMD according to the presence of CAD risk factors. Multivariate analysis disclosed that the independent factorsof FMD were the serum homocysteine and triglyceride levels, and those of NMD (25μg) were hypertension, a lowejection fraction and severe coronary angiographic findings, while there was no independent factor for NMD(175μg) and NMD (325μg). Conclusion: This study suggests that hypertension, a low ejection fraction and significantstenotic coronary lesion may be associated with endothelium-independent smooth muscle dysfunction atlow dose NTG, while the serum homocysteine and triglyceride levels are associated with endothelium-dependentendothelial dysfunction in the patients with CAD. Using low-dose NTG is important when measuring the NMD.

The Prevalence of Cardiovascular Disease Risk Factors and the Framingham Risk Score in Patients Undergoing Percutaneous Intervention Over the Last 17 Years by Gender: Time-trend Analysis From the Mayo Clinic PCI Registry

이무식,Andreas J. Flammer,김현수,홍지영,Jing Li,Ryan J. Lennon,Amir Lerman 대한예방의학회 2014 Journal of Preventive Medicine and Public Health Vol.47 No.4

Objectives: This study aims to investigate trends of cardiovascular disease (CVD) risk factor profiles over 17 years in percutaneous coronary intervention (PCI) patients at the Mayo Clinic. Methods: We performed a time-trend analysis within the Mayo Clinic PCI Registry from 1994 to 2010. Results were the incidence and prevalence of CVD risk factors as estimate by the Framingham risk score. Results: Between 1994 and 2010, 25 519 patients underwent a PCI. During the time assessed, the mean age at PCI became older, but the gender distribution did not change. A significant trend towards higher body mass index and more prevalent hypercholesterolemia, hypertension, and diabetes was found over time. The prevalence of current smokers remained unchanged. The prevalence of ever-smokers decreased among males, but increased among females. However, overall CVD risk according to the Framingham risk score (FRS) and 10-year CVD risk significantly decreased. The use of most of medications elevated from 1994 to 2010, except for β-blockers and angiotensin converting enzyme inhibitors decreased after 2007 and 2006 in both baseline and discharge, respectively. Conclusions: Most of the major risk factors improved and the FRS and 10-year CVD risk declined in this population of PCI patients. However, obesity, history of hypercholesterolemia, hypertension, diabetes, and medication use increased substantially. Improvements to blood pressure and lipid profile management because of medication use may have influenced the positive trends.

Individual Measurement and Significance of Carotid Intima, Media, and Intima-Media Thickness by B-Mode Ultrasonographic Image Processing

Bae, Jang-Ho,Kim, Wuon-Shik,Rihal, Charanjit S.,Lerman, Amir American Heart Association 2006 Arteriosclerosis, thrombosis, and vascular biology Vol.26 No.10

<P>OBJECTIVE: We assessed the clinical significance of intima (IT), media (MT), and intima-media (IMT) thickness of the common carotid artery using B-mode ultrasonographic image processing. METHODS AND RESULTS: One hundred seventy consecutive patients underwent common carotid artery scanning using high-resolution ultrasonography. A total of 150 patients could be analyzed off-line using ultrasonographic image processing, devised for individual measurement of IT, MT, and IMT. By univariate analysis, IT (range, 0.27 to 0.41 mm) was associated with age, whereas MT (range, 0.27 to 0.74 mm) and IMT (range, 0.49 to 1.12 mm) were associated with age, fibrinogen, and creatinine. Among atherosclerosis risk factors, hypertension was associated with thickness of all 3 layers, whereas smoking was associated with IT only. By multivariate analysis, IT was associated with age, hypertension, and smoking, whereas MT and IMT were associated with age, hypertension, and blood urea nitrogen level. CONCLUSIONS: Carotid IT is associated with smoking, whereas age and hypertension are associated with thickness of all 3 arterial layers. Our results suggest a differential response of the vasculature to systemic risk factors.</P>

The Prevalence of Cardiovascular Disease Risk Factors and the Framingham Risk Score in Patients Undergoing Percutaneous Intervention Over the Last 17 Years by Gender: Time-trend Analysis From the Mayo Clinic PCI Registry

Lee, Moo-Sik,Flammer, Andreas J.,Kim, Hyun-Soo,Hong, Jee-Young,Li, Jing,Lennon, Ryan J.,Lerman, Amir The Korean Society for Preventive Medicine 2014 Journal of Preventive Medicine and Public Health Vol.47 No.4

Objectives: This study aims to investigate trends of cardiovascular disease (CVD) risk factor profiles over 17 years in percutaneous coronary intervention (PCI) patients at the Mayo Clinic. Methods: We performed a time-trend analysis within the Mayo Clinic PCI Registry from 1994 to 2010. Results were the incidence and prevalence of CVD risk factors as estimate by the Framingham risk score. Results: Between 1994 and 2010, 25 519 patients underwent a PCI. During the time assessed, the mean age at PCI became older, but the gender distribution did not change. A significant trend towards higher body mass index and more prevalent hypercholesterolemia, hypertension, and diabetes was found over time. The prevalence of current smokers remained unchanged. The prevalence of ever-smokers decreased among males, but increased among females. However, overall CVD risk according to the Framingham risk score (FRS) and 10-year CVD risk significantly decreased. The use of most of medications elevated from 1994 to 2010, except for ${\beta}$-blockers and angiotensin converting enzyme inhibitors decreased after 2007 and 2006 in both baseline and discharge, respectively. Conclusions: Most of the major risk factors improved and the FRS and 10-year CVD risk declined in this population of PCI patients. However, obesity, history of hypercholesterolemia, hypertension, diabetes, and medication use increased substantially. Improvements to blood pressure and lipid profile management because of medication use may have influenced the positive trends.

Impact of Plaque Composition on Long-Term Clinical Outcomes in Patients with Coronary Artery Occlusive Disease

김기홍,Wan Ho Kim,Hyun Woong Park,In Girl Song,Dong Ju Yang,서영훈,Hyung Bin Yuk,Yo Han Park,Taek-Geun Kwon,Charanjit S Rihal,Amir Lerman,이무식,Jang-Ho Bae 대한심장학회 2013 Korean Circulation Journal Vol.43 No.6

Background and Objectives: It is unclear which plaque component is related with long-term clinical outcomes in patients with coronary artery occlusive disease (CAOD). We assessed the relationship between plaque compositions and long-term clinical outcomes in those patients. Subjects and Methods: The study subjects consisted of 339 consecutive patients (mean 61.7±12.2 years old, 239 males) who underwent coronary angiogram and a virtual histology-intravascular ultrasound examination. Major adverse cardiac and cerebrovascular events (MACCE), including all-cause death, non-fatal myocardial infarction, cerebrovascular events, and target vessel revascularization were evaluated during a mean 28-month follow-up period. Results: Patients with high fibrofatty volume (FFV, >8.90 mm 3 , n=169) had a higher incidence of MACCE (25.4% vs. 14.7%, p=0.015), male sex (75.7% vs. 65.3%, p=0.043), acute coronary syndrome (53.3% vs. 35.9%, p=0.002), multivessel disease (62.7% vs. 41.8%, p<0.001) and post-stent slow flow (10.7% vs. 2.4%, p=0.002) than those with low FFV (FFV ≤8.90 mm 3 , n=170). Other plaque composition factors such as fibrous area/volume, dense calcified area/volume, and necrotic core area/volume did not show any impact on MACCE. Cardiogenic shock {hazard ratio (HR)=8.44; 95% confidence interval (CI)=3.00-23.79; p<0.001 } and FFV (HR=1.85; 95% CI=1.12-3.07; p=0.016) were the independent predictors of MACCE by Cox regression analysis. Thin-cap fibroatheroma, necrotic core area, and necrotic core volume were not associated with MACCE. Conclusion: FFV of a culprit lesion was associated with unfavorable long-term clinical outcomes in patients with CAOD.

Three Dimensional Quantitative Coronary Angiography Can Detect Reliably Ischemic Coronary Lesions Based on Fractional Flow Reserve

정우영,최병주,임성훈,Yoshiki Matsuo,Ryan J Lennon,Rajiv Gulati,Gurpreet S. Sandhu,David R Holmes Jr,Charanjit S Rihal,Amir Lerman 대한의학회 2015 Journal of Korean medical science Vol.30 No.6

Conventional coronary angiography (CAG) has limitations in evaluating lesions producing ischemia. Three dimensional quantitative coronary angiography (3D-QCA) shows reconstructed images of CAG using computer based algorithm, the Cardio-op B system (Paieon Medical, Rosh Ha’ayin, Israel). The aim of this study was to evaluate whether 3D-QCA can reliably predict ischemia assessed by myocardial fractional flow reserve (FFR) < 0.80. 3D-QCA images were reconstructed from CAG which also were evaluated with FFR to assess ischemia. Minimal luminal diameter (MLD), percent diameter stenosis (%DS), minimal luminal area (MLA), and percent area stenosis (%AS) were obtained. The results of 3D-QCA and FFR were compared. A total of 266 patients was enrolled for the present study. FFR for all lesions ranged from 0.57 to 1.00 (0.85 ± 0.09). Measurement of MLD, %DS, MLA, and %AS all were significantly correlated with FFR (r = 0.569, 0609, 0.569, 0.670, respectively, all P < 0.001). In lesions with MLA < 4.0 mm2, %AS of more than 65.5% had a 80% sensitivity and a 83% specificity to predict FFR < 0.80 (area under curve, AUC was 0.878). 3D-QCA can reliably predict coronary lesions producing ischemia and may be used to guide therapeutic approach for coronary artery disease.