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Tada, Hayato ; Kawashiri, Masa-aki ; Yamagishi, Masakazu ; 多田, 隼人 ; 川尻, 剛照 ; 山岸, 正和
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金沢大学附属病院循環器内科<br />We have learned that low-density lipoprotein (LDL) cholesterol is the cause of atherosclerosis from v
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arious aspects, including a single case with familial hypercholesterolemia, other cases with different types of Mendelian dyslipidemias, large-scale randomized controlled trials using LDL cholesterol lowering therapies, and Mendelian randomization studies using common as well as rare variants associated with LDL cholesterol levels. There is no doubt that determinations of genotypes in lipid-associated genes have contributed not only to the genetic diagnosis for Mendelian dyslipidemias but also to the discoveries of novel therapeutic targets. Furthermore, recent studies have shown that such genetic information could provide useful clues for the risk prediction as well as risk stratification in general and in particular population. We provide the current understanding of genetic analyses relating to plasma lipids and coronary artery disease.<br />This article distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.
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Uchiyama, K. ; Ino, H. ; Hayashi, Kenshi ; Fujioka, K. ; Takabatake, S. ; Yokawa, J. ; Namura, M. ; Mizuno S. ; Tatami, R. ; Kanaya, H. ; Nitta, Y. ; Michishita, I. ; Hirase, H. ; Ueda, K. ; Aoyama, T. ; Okeie, K. ; Haraki, T. ; Mori, K. ; Araki, T. ; Minamoto, M. ; Oiwake, H. ; Konno, Tetsuo ; Sakata, Kenji ; Kawashiri, Masa-aki ; Yamagishi, Masakazu ; 林, 研至 ; 山岸, 正和
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金沢大学医薬保健研究域医学系<br />Percutaneous coronary intervention (PCI) using a drug-eluting stent (DES) leads to less re-stenosis
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than PCI using a bare metal stent (BMS), however there is still controversy whether use of a DES for severe coronary disease leads to an acceptable outcome in patients with diabetes mellitus (DM). In this study 8159 lesions were treated in 6739 patients (mean age 68.9 years) with coronary artery disease. Use of a DES significantly decreased the re-stenosis rate compared with BMS in both DM (9.6% versus 21.3%) and non-DM (9.5% versus 17.1%) patients. The re-stenosis rate was significantly higher in DM than in non-DM patients in the BMS group but not in the DES group. There was no statistically significant difference in event-free survival after stenting of patients with left main coronary artery (LMCA) disease between the BMS and DES groups. It was concluded that, compared with BMS, DES reduced re-stenosis in patients with DM, however, we advise careful treatment after using DES for severe coronary disease, including LMCA lesions, in patients with DM. © 2011 Field House Publishing LLP.
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Nitta, Y. ; Yamamoto, R. ; Yamaguchi, Y. ; Katsuda, S. ; Kaku, B. ; Taguchi, T. ; Takabatake, S. ; Nakahama, K. ; Yamagishi, Masakazu ; 山岸, 正和
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金沢大学医薬保健研究域医学系<br />Calcium channel blockers (CCBs) can prevent cardiovascular events in patients with coronary artery d
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isease (CAD). This study looked retrospectively at the prognosis of CAD in hypertensive patients with CAD who had undergone a coronary angiograph, had been given a CCB (benidipine [n = 66], amlodipine [n = 45], or long-acting nifedipine [n = 31]) on hospital discharge and were then followed up for a mean ± SD of 5.2 ± 2.9 years. Systolic/diastolic blood pressure for all 142 patients decreased significantly from a mean ± SD of 137 ± 20/74 ± 15 mmHg to 129 ± 20/71 ± 12 mmHg. Major adverse cardiovascular events (MACE) occurred in 15 patients. Chronic kidney disease (CKD) was a significant risk factor for MACE (hazard ratio 2.35, 95%confidence intervals 1.45, 3.80). Benidipine was superior to nifedipine in preventing MACE in patients both with and without CKD. In conclusion, benidipine and amlodipine reduced the frequency of MACE in hypertensive patients with CAD, particularly in those with complicating CKD. © 2010 Field House Publishing LLP.
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Nakajima, Kenichi ; Nishimura, Tsunehiko
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The multicenter Japanese-Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS), which involved 117 institutions and 4,629 patients, was the first attempt to quantify cardiac events and survival using
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stress-rest-gated single-photon emission computed tomography myocardial perfusion images (MPI) and QGS software in Japan. A 3-year follow-up study showed a relatively lower incidence of hard events than in the USA and some European countries, but a similar role of perfusion and left ventricular (LV) function. A low event risk with normal MPI and a higher incidence of major cardiac events in patients with large perfusion defects and LV dysfunction were defined. MPI was useful even among patients with proven coronary artery stenosis. The association between diabetes and chronic kidney disease (CKD) was an important predictor of cardiac events and the risk was evaluated using new software and risk charts. Additional studies were extended to include asymptomatic diabetes (J-ACCESS 2) and CKD (J-ACCESS 3). Because risk estimation is linked to the national healthcare system and clinical practice, optimal risk stratification and guidance for therapeutic strategies are recommended. (Circ J 2012; 76: 1313-1321)
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Yamaguchi, Masato ; Shimizu, Masami ; Ino, Hidekazu ; Okeie, Kazuyasu ; Yasuda, Toshihiko ; Fujino, Noboru ; Fujii, Hiroyuki ; Mabuchi, Tomohito ; Mabuchi, Hiroshi
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金沢大学大学院医学系研究科<br />Patients with diabetes mellitus (DM) often have a positive result on exercise testing despite a norma
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l coronary arteriogram, which indicates that exercise-induced ST depression is not always an accurate indicator of the presence of coronary artery disease (CAD) in such patients. The present study evaluated the usefulness of the post-exercise systolic blood pressure (SBP) response for the detection of CAD in 47 consecutive patients with DM. Significant stenotic lesions were detected by angiography in 25 patients; 18 of these had true positive (TP) exercise testing results, and 7 had false negative (FN) results. No significant stenotic lesions were detected in the remaining 22 patients and of these 10 had true negative (TN) exercise testing results, and 12 had false positive (FP) results. The SBP ratio (SBP after 3 min of recovery divided by the SBP at peak exercise) was significantly higher in patients with coronary stenoses than in those without. Analysis of the relative cumulative frequency revealed that a SBP ratio greater than 0.87 was associated with significant stenoses. The sensitivity, specificity, and accuracy of ST change combined with a SBP ratio greater than 0.87 for detecting stenoses in patients with DM were 68%, 82%, and 74%, respectively. These results suggest that calculating the SBP ratio, in combination with monitoring for ST depression, improves the accuracy of treadmill exercise testing for the detection of CAD in patients with DM.
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Yagi, Kunimasa ; Hifumi, Senshu ; Nohara, Atsushi ; Higashikata, Toshinori ; Inazu, Akihiro ; Mizuno, Kiyoo ; Namura, Masanobu ; Ueda, Kosei ; Kobayashi, Junji ; Shimizu, Masami ; Mabuchi, Hiroshi
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金沢大学大学院医学系研究科 <br />Background: The aim of the present study was to clarify the risk factors of several types of arterio
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sclerosis lesions in Japanese individuals with heterozygous familial hypercholesterolemia (FH): renal arteriosclerosis (RAS), abdominal aortic sclerosis (AOS), iliac arteriosclerosis (IAS) and coronary artery disease (CAD). Methods and Results: Coronary angiography (CAG) and abdominal aortic angiography (AAA) were performed in 117 consecutive heterozygous FH subjects (79 men, 38 women; age 22-76). RAS (stenotic lesion or aneurysm) was observed in 39 cases (33%), predominantly in the proximal portion (74%) and both sides equally (right/left=27/23). Most cases of RAS (64%) presented with <25% stenosis. The differences in the contributing risk factors for the progression and development of RAS, AOS, IAS and CAD in FH were then analyzed. Multiple logistic regression analyses showed independent risk factors for formation of atherosclerosis in each artery were: age alone for RAS; age and plasma low-density lipoprotein cholesterol (LDL-C) for AOS; age, LDL-C and high-density lipoprotein cholesterol (HDL-C) for IAS; and HDL-C and diabetes mellitus for CAD. Conclusion: In Japanese subjects with heterozygous FH, there are distinct risk factors for the development and progression of atherosclerosis in the renal, iliac, abdominal aorta, and coronary arteries.
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Nakajima, Kenichi ; Matsuo, Shinro ; Kawano, Masaya ; Matsumoto, Naoya ; Hashimoto, Jun ; Yoshinaga, Keiichiro ; Taki, Junichi ; Okuda, Koichi
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金沢大学医薬保健研究域医学系<br />Purpose The Japanese Society of Nuclear Medicine (JSNM) working group has created a myocardial perfu
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sion imaging database applicable to standard acquisition protocol. The aim of this study is to validate the diagnostic accuracy of the common normal database compared with the expert interpretation of each institute. Methods Five institutions participated in this study and used different acquisition settings which included 360°/ 180° rotation, camera configuration and camera orbits. The software and its version used in each institution also varied. The working group database was applied to detect the culprit coronary territory from a total of 166 patients with coronary artery disease (CAD) and 145 patients with lowlikelihood of CAD. Results When summed stress score C4 was defined as significant abnormality, overall sensitivity, specificity and accuracy of patient-based analysis were 77, 72 and 75%, respectively, based on quantitative analysis using the common database, whereas those by institutional visual expert reading were 72, 79 and 75%, respectively. Conclusion The common database, which was created by a multi-center working group and separated between male/ female with 180/360° acquisitions, demonstrated comparable diagnostic accuracy to expert interpretation by each institute, and it may be applicable to multi-center studies.
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Nakajima, Kenichi ; Yamasaki, Yoshimitsu ; Kusuoka, Hideo ; Izumi, Tohru ; Kashiwagi, Atsunori ; Kawamori, Ryuzo ; Shimamoto, Kazuaki ; Yamada, Nobuhiro ; Nishimura, Tsunehiko
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金沢大学医薬保健研究域医学系<br />Purpose Diabetic patients have a high risk for cardiovascular events. The role of myocardial perfusi
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on imaging was investigated in asymptomatic diabetic patients to evaluate short-term prognosis in a Japanese population. Methods A total of 506 asymptomatic patients ≥50 years of age who had carotid artery maximum intima-media thickness ≥1.1 mm, urinary albumin excretion of ≥30 mg/g creatinine, with additional criteria of abdominal obesity, low HDL cholesterol, high triglyceride level, and hypertension were enrolled and followed up over a 3-year period. Gated SPECT with stress-rest protocol was performed and analyzed by summed defect scores and QGS software. One-year cardiovascular events were analyzed. Results Myocardial ischemia was observed in 17% of patients, and abnormal perfusion findings of ischemia and/or scar were observed in 32% of patients. By the end of the 1-year follow-up, 33 (6.5%) cardiovascular events occurred including 6 all-cause deaths. Patients with summed stress score (SSS) >8 had a higher incidence of either death or cardiovascular events. Event-free survival rates for SSS 0–3, 4–8, 9–13, and ≥14 were 0.96, 0.95, 0.82, and 0.76, respectively. Multivariate Cox regression analysis showed that significant variables were SSS, history of cerebrovascular accident, and electrocardiographic abnormality at rest. Conclusion The 1-year interim summary showed that cardiovascular events were significantly higher in patients with SPECT abnormality, although hard cardiac event rate was relatively low. Targeted treatment strategy is required for asymptomatic but potentially high-risk diabetic patients.
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Nakajima, Kenichi ; Yamasaki, Yoshimitsu ; Kusuoka, Hideo ; Izumi, Tohru ; Kashiwagi, Atsunori ; Kawamori, Ryuzo ; Shimamoto, Kazuaki ; Yamada, Nobuhiro ; Nishimura, Tsunehiko
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金沢大学医薬保健研究域医学系<br />Purpose: Diabetic patients have a high risk for cardiovascular events. The role of myocardial perfus
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ion imaging was investigated in asymptomatic diabetic patients to evaluate short-term prognosis in a Japanese population. Methods: A total of 506 asymptomatic patients ≥50 years of age who had carotid artery maximum intima-media thickness ≥1.1 mm, urinary albumin excretion of ≥30 mg/g creatinine, with additional criteria of abdominal obesity, low HDL cholesterol, high triglyceride level, and hypertension were enrolled and followed up over a 3-year period. Gated SPECT with stress-rest protocol was performed and analyzed by summed defect scores and QGS software. One-year cardiovascular events were analyzed. Results: Myocardial ischemia was observed in 17% of patients, and abnormal perfusion findings of ischemia and/or scar were observed in 32% of patients. By the end of the 1-year follow-up, 33 (6.5%) cardiovascular events occurred including 6 all-cause deaths. Patients with summed stress score (SSS) >8 had a higher incidence of either death or cardiovascular events. Event-free survival rates for SSS 0-3, 4-8, 9-13, and ≥14 were 0.96, 0.95, 0.82, and 0.76, respectively. Multivariate Cox regression analysis showed that significant variables were SSS, history of cerebrovascular accident, and electrocardiographic abnormality at rest. Conclusion: The 1-year interim summary showed that cardiovascular events were significantly higher in patients with SPECT abnormality, although hard cardiac event rate was relatively low. Targeted treatment strategy is required for asymptomatic but potentially high-risk diabetic patients. © 2009 Springer-Verlag.
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Nakajima, Kenichi ; Matsuo, Shinro ; Okuda, Koichi ; Wakabayashi, Hiroshi ; Tsukamoto, Kazumasa ; Nishimura, Tsunehiko
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Background:Myocardial perfusion imaging (MPI) has been used to estimate cardiac event risk. The aim of the present study
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is to achieve stable risk estimation based on perfusion scoring and a multi-center prognostic database. Methods and Results:Multivariate logistic regression analysis was performed to estimate cardiac event risk based on a J-ACCESS study. A stress-MPI was performed in 45 patients with coronary artery disease (CAD) and in 25 non-CAD patients. Perfusion defect scoring of summed stress score (SSS) was performed by 5 methods: (1) visual scoring; (2) automatic scoring of 3 short-axis and 1 vertical long-axis slices; (3) visual modification of Method 2; (4) automatic polar map scoring based on a Japanese multi-center database; and (5) visual modification of Method 4. Agreement of SSS between 2 observers was good (r=0.87-0.97). Agreement of estimated cardiac event risk between observers and among 5 methods was very good (r=0.99-1.00). Regarding diagnostic accuracy for CAD, Method 5 showed optimal diagnostic yields (sensitivity 84%, accuracy 77%). Conclusions:Estimation of cardiac event risk in conjunction with polar map segmentation and common normal databases resulted in stable risk values, and might be used for risk stratification in patients suspected of having CAD. © All rights are reserved to the Japanese Circulation Society.
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