著者

Shinji Koba Yuuya Yokota Tsutomu Hirano Yasuki Ito Yoshihisa Ban Fumiyoshi Tsunoda Takatoshi Sato Makoto Shoji Hiroshi Suzuki Eiichi Geshi Youichi Kobayashi Takashi Katagiri

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.15, no.5, pp.250-260, 2008 (Released:2008-11-01)

参考文献数

35

被引用文献数

63 74

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Aim: Recent evidence suggests that small dense low-density lipoprotein (sd-LDL) particles are more atherogenic than large-LDL in spite of their lower cholesterol content. This study aimed to determine whether sd-LDL-cholesterol (sd-LDL-C) is superior to LDL-C as a biomarker of coronary heart disease (CHD).Methods: LDL particle size determined by gradient gel electrophoresis and sd-LDL-C concentrations quantified by heparin-magnesium precipitation were compared between 482 stable CHD patients and 389 non-diabetic subjects without CHD who were not receiving any lipid-lowering drugs.Results: Both male and female CHD patients had significantly smaller LDL particles and lower large-LDL-C concentrations (estimated by subtracting the sd-LDL-C concentration from the LDL-C concentration), and significantly higher sd-LDL-C concentrations than the control subjects. LDL-C concentrations were modestly higher and sd-LDL-C concentrations were significantly higher in 258 patients with angiographically documented severe CHD than in the patients with mild CHD irrespective of treatment by LDL-lowering drugs and history of myocardial infarction and/or coronary revascularization. Large-LDL-C concentrations, in contrast, were similar between the two groups. Multivariate logistic regression analysis revealed that sd-LDL-C levels were significantly associated with severe CHD independently of LDL-C.Conclusion: sd-LDL-C levels are more powerful than LDL-C levels for the determination of severe stable CHD.

著者

Aya Higashiyama Ichiro Wakabayashi Tomonori Okamura Yoshihiro Kokubo Makoto Watanabe Misa Takegami Kyoko Honda-Kohmo Akira Okayama Yoshihiro Miyamoto

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.62730, (Released:2021-05-28)

参考文献数

29

被引用文献数

18

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Aim: A prospective cohort study in a Japanese urban general population was performed to investigate whether triglyceride (TG) and its related indices were associated with the risk for the incidence of ischemic cardiovascular disease (CVD) after the adjustment for low-density lipoprotein cholesterol (LDL-C) in Asian community dwellers. Methods: A 15.1-year prospective cohort study was performed in 6,684 Japanese community dwellers aged 30–79 years without a history of CVD and whose fasting TG levels were <400 mg/dL. After adjusting for covariates, including LDL-C, the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of the deciles (D) of TG and those of 1-standard deviation (SD) increment of log-transformed TG (1-SD of TG) according to LDL-C level (≥ 140 and <140 mg/dL) for ischemic CVD incidence were estimated. The multivariable-adjusted HRs and 95%CIs of the quintiles (Q) of TG, TG/HDL-C, and the cardiometabolic index (CMI) for ischemic CVD were also estimated. Results: In 101,230 person-years, 464 ischemic CVD cases occurred. For D10 of TG, the HR (95%CI) was 1.56 (1.05–2.32), and for 1-SD of TG, it was 1.30 (1.00–1.70) in participants with LDL-C <140 mg/dL and 1.07 (0.77–1.50) in those with LDL-C ≥ 140 mg/dL. For Q5 of the CMI, the multivariable-adjusted HR was higher than those of TG and TG/HDL-C. Conclusions: Fasting TG was an independent predictor for ischemic CVD incidence after adjusting for LDL-C in Japanese community dwellers with TG <400 mg/dL. Among TG, TG/HDL-C, and the CMI, the CMI could be the most powerful predictor for ischemic CVD.

著者

Masayuki Kuroda Hideaki Bujo Koutaro Yokote Takeyoshi Murano Takashi Yamaguchi Masatsune Ogura Katsunori Ikewaki Masahiro Koseki Yasuo Takeuchi Atsuko Nakatsuka Mika Hori Kota Matsuki Takashi Miida Shinji Yokoyama Jun Wada Mariko Harada-Shiba on behalf of the Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health Labour and Welfare of Japan

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.RV17051, (Released:2021-04-18)

参考文献数

68

被引用文献数

7

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Lecithin cholesterol acyltransferase (LCAT) is a lipid-modification enzyme that catalyzes the transfer of the acyl chain from the second position of lecithin to the hydroxyl group of cholesterol (FC) on plasma lipoproteins to form cholesteryl acylester and lysolecithin. Familial LCAT deficiency is an intractable autosomal recessive disorder caused by inherited dysfunction of the LCAT enzyme. The disease appears in two different phenotypes depending on the position of the gene mutation: familial LCAT deficiency (FLD, OMIM 245900) that lacks esterification activity on both HDL and ApoB-containing lipoproteins, and fish-eye disease (FED, OMIM 136120) that lacks activity only on HDL. Impaired metabolism of cholesterol and phospholipids due to LCAT dysfunction results in abnormal concentrations, composition and morphology of plasma lipoproteins and further causes ectopic lipid accumulation and/or abnormal lipid composition in certain tissues/cells, and serious dysfunction and complications in certain organs. Marked reduction of plasma HDL-cholesterol (HDL-C) and corneal opacity are common clinical manifestations of FLD and FED. FLD is also accompanied by anemia, proteinuria and progressive renal failure that eventually requires hemodialysis. Replacement therapy with the LCAT enzyme should prevent progression of serious complications, particularly renal dysfunction and corneal opacity. A clinical research project aiming at gene/cell therapy is currently underway.

著者

Hidenori Arai Hideaki Bujo Daisaku Masuda Toshiyuki Ishibashi Satoshi Nakagawa Kenichiro Tanabe Tatsuo Kagimura Hyun-Jae Kang Moo Hyun Kim Jidong Sung Sang-Hyun Kim Cheol-Ho Kim Jeong Euy Park Junbo Ge Byung-Hee Oh Toru Kita Yasushi Saito Masanori Fukushima Yuji Matsuzawa Shizuya Yamashita

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.62821, (Released:2021-04-18)

参考文献数

45

被引用文献数

6

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Aims: In this study, we integrated two randomized control trials, PROSPECTIVE and IMPACT, to address the effect of probucol on cerebrocardiovascular events and carotid intima-media thickness (IMT) in Japanese, Korean, and Chinese patients with coronary artery disease (CAD). Methods: A total of 1,025 patients from the PROSPECTIVE and IMPACT studies were enrolled. The time to the first major adverse cerebrocardiovascular event, in addition to carotid IMT and lipid levels, was compared between the control and probucol groups. Results: In the integrated analysis, the adjusted hazard ratio (HR) and 95% confidence interval (CI) were 0.67 and 0.44–1.03, respectively, indicating a tendency to show the effect of probucol on cerebrocardiovascular events in secondary prevention. We also found no significant differences between the control and probucol groups in the mean IMT of the carotid arteries and its changes. However, we found a significant decrease in cerebrocardiovascular events in patients with reduced levels of HDL cholesterol (HDL-C) (≥ 6.25 mg/dL) compared with those with levels <6.25 mg/dL (p=0.024), without any increase in adverse events such as severe ventricular arrhythmias. Conclusion: We demonstrated a marginal effect of probucol on cerebrocardiovascular events in Asian patients with CAD, with reasonable safety profiles. A larger study may be needed to support the effect of probucol for cardiovascular prevention.

著者

Akihiro Yoshida Masaaki Kouwaki Yasuko Matsutani Yoshiko Fukuchi Michitaka Naito

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.11, no.4, pp.215-219, 2004 (Released:2004-09-09)

参考文献数

13

被引用文献数

20 24

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Objective: We examined the usefulness of the serum total cholesterol (TC)/triglyceride (TG) and LDL-cholesterol (LDL-C)/TG ratios for predicting the presence of small, dense LDL, by comparing them with the established indicators of small, dense LDL, such as the LDL-migration index (LDL-MI) and LDL-C/Apolipoprotein B (ApoB) ratio.Materials and methods: Fasting serum lipid was analyzed in 99 Japanese hyperlipidemic and normolipidemic subjects (34 males and 65 females, 59.4 ± 11.9 years old).Results: A good negative correlation was observed between LDL-MI and log (TC/TG) (R2 = 0.473, p < 0.0001). There was a strong positive correlation between LDL-C/ApoB and log (TC/TG) (R2 = 0.665, p < 0.0001). Similar results were obtained using LDL-C instead of TC. Using LDL-MI > 0.4 as an indicator of small, dense LDL, the upper limit of TG was estimated to be 140−142 mg/dl.Conclusion: TC/TG and LDL-C/TG may offer a convenient and simple clinical tool for predicting the presence of small, dense LDL. Particularly, TC/TG could be an easy-to-use indicator of small, dense LDL for general practitioners.

著者

Takanori Honda Yuki Ishida Masaaki Oda Kenichi Noguchi Sanmei Chen Satoko Sakata Emi Oishi Yoshihiko Furuta Daigo Yoshida Yoichiro Hirakawa Jun Hata Takanari Kitazono Toshiharu Ninomiya

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.59394, (Released:2021-01-17)

参考文献数

42

被引用文献数

6

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Aim: We investigated the influence of weight change on concurrent changes in predicted cardiovascular disease (CVD) risk and individual CVD risk factors over time. Methods: A total of 2,140 community-dwellers aged 40–74 years participated in both 2002 and 2007 health examinations. Obesity was defined as body mass index ≥ 25 kg/m2. Weight trajectories were classified as: “stable obese” (obese at both examinations), “obese to nonobese” (obese in 2002 but nonobese in 2007), “nonobese to obese” (nonobese in 2002 but obese in 2007), or “stable nonobese” (nonobese at both examinations). We compared changes in the model-predicted risk for CVD and individual CVD risk factors across weight-change categories. Results: The predicted risk for CVD increased during 5 years in all groups; the increment in the predicted risk for CVD was smallest in the obese to nonobese participants and steepest in the nonobese to obese subjects. Compared with the stable obese participants, the obese to nonobese participants had greater favorable changes in waist circumferences, blood pressure, fasting plasma glucose, serum high-density lipoprotein cholesterol, serum triglycerides, and liver enzymes. For all these parameters, opposite trends were observed when comparing the nonobese to obese participants with the stable nonobese group. Conclusions: We demonstrated the favorable association of losing weight in obese people and avoiding excessive weight gain in nonobese people with global risk of future CVD and individual CVD risk factors in a real-world setting. The findings could improve behavioral lifestyle interventions that provide information on the health consequences of weight change at health checkups.

著者

Kazutoshi Fujibayashi Hiroshi Fukuda Hirohide Yokokawa Tomomi Haniu Fukuko Oka Miki Ooike Toshiaki Gunji Noriko Sasabe Mitsue Okumura Kimiko Iijima Teruhiko Hisaoka Hiroshi Isonuma

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.19, no.10, pp.932-940, 2012 (Released:2012-10-29)

参考文献数

42

被引用文献数

22 28

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Aim: The aim was to investigate the respective associations between lifestyle and proteinuria and the estimated glomerular filtration rate (eGFR).Methods: The lifestyle habits of 25,493 middle-aged participants were investigated in a cross-sectional study to find habits that are associated with a low eGFR (<60 mL/min/1.73 m2) and/or the presence of proteinuria. The lifestyle habits of the participants were evaluated using a questionnaire. Unhealthy lifestyle habits were defined as follows: 1. obesity, 2. being a current/former smoker, 3. eating irregular meals, 4. having less than 5 hours sleep, 5. exercising less than once a week, and 6. drinking more than once a week. The associations among unhealthy habits, eGFR, and proteinuria were evaluated using multivariate analysis.Results: The following lifestyle factors were significantly and independently associated with proteinuria: obesity (odds ratio (OR): 1.18, 95%C.I: 1.04-1.34), being a current/former smoker (OR: 1.26, 95%C.I: 1.11-1.42), eating irregular meals (OR: 1.40, 95%C.I: 1.22-1.61), sleeping less than 5 hours (OR: 1.38, 95%C.I: 1.15-1.65), and exercising less than once a week (OR: 1.18, 95%C.I: 1.05-1.33). In contrast, the following unhealthy lifestyle factors were not clearly associated with a low eGFR: obesity (OR: 1.05, 95%C.I: 0.95-1.17), being a current/former smoker (OR: 0.76, 95%C.I: 0.69-0.84), eating irregular meals (OR: 0.91, 95%C.I: 0.79-1.04), sleeping less than 5 hours (OR: 1.02, 95%C.I: 0.85-1.22), and exercising less than once a week (OR: 0.91, 95%C.I: 0.83-0.99).Conclusion: Associations between proteinuria and unhealthy lifestyle habits were observed in our cross-sectional study. Unhealthy lifestyles should be monitored during the management of CKD patients with proteinuria.

著者

Meng-Huan Lei Yu-Lin Wu Sheng-Liang Chung Chao-Chin Chen Wei-Cheng Chen Yu-Chen Hsu

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.59386, (Released:2020-11-07)

参考文献数

43

被引用文献数

10

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Aims: Type 2 diabetes mellitus (T2DM) is no longer regarded as a coronary risk equivalent, and heterogeneity of cardiovascular risk exists, suggesting that further risk stratification should be mandatory. This study aimed to determine the prevalence and clinical predictors of coronary artery calcium (CAC) score, and evaluate the CAC score as a predictor of cardiovascular outcome in a large asymptomatic T2DM cohort. Methods: A total of 2,162 T2DM patients were recruited from a Diabetes Shared Care Network and the CAC score was measured. Cardiovascular outcomes were obtained for 1,928 patients after a follow-up of 8.4 years. Multiple regression analysis and Cox proportional hazard regression were applied to identify clinical predictors of CAC and calculate the incidence and hazard ratios (HRs) for all-cause mortality and cardiovascular events by CAC category. Results: Of the recruited patients, 96.8% had one or more risk factors. The distribution of CAC scores was as follows: CAC=0 in 24.2% of the patients, 0 <CAC ≤ 100 in 41.5%, 100 <CAC ≤ 400 in 20.3%, CAC >400 in 14.7%. The multivariable predictor of increased CAC included age (years) (odds ratio, 1.07; 95% confidence interval, 1.06–1.08), male sex (1.82; 1.54–2.17), duration (years) of T2DM (1.07; 1.05–1.09), and multiple risk factors (1.94; 1.28–2.95). Increasing severity of CAC was associated with higher all-cause or cardiac mortality and higher incident cardiovascular events. The HRs for cardiac death or major cardiac events in CAC >400 vs CAC=0 were 8.67 and 10.52, respectively (p<0.001) Conclusion: CAC scoring provides better prognostication of cardiovascular outcome than traditional risk factors in asymptomatic T2DM patients, and may allow identifying a high-risk subset for enhancing primary prevention.

著者

Sy Rody G Cutiongco Eva Maria C Punzalan1 Felix Eduardo R Santos Ronald S Geronimo Francis Ruel B Tangco Rogelio V

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.14, no.3, pp.116-121, 2007

被引用文献数

9

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Aim: Background: HDL-C has emerged as an important independent predictor of cardiovascular disease. The FNRI-HDL and NNHes Study Group in the Philippines reported that there was a high prevalence of low HDL among Filipinos. Most cases of low HDL-C are associated with secondary causes like Metabolic Syndrome. A primary cause of reduced HDL-C such as increase Cholesteryl Ester Transfer Protein activity has been identified. Objectives: 1. To determine the phenotype and frequency of Cholesteryl Ester Transfer Protein (TaqIB) polymorphism among Filipinos with cardiovascular risk factors. 2. To determine the association of TaqIB polymorphism with HDL-C levels among Filipinos with cardiovascular risk factors. Design: Cross-sectional Study. Setting: University of the Philippines-Philippine General Hospital. Statistical Analysis: Descriptive statistics, Chi square test and Fisher's correlation test using Stata version 6.<BR>Methods: Fifty patients were included in this pilot study and were examined with respect to genotype, lipid profiles, blood sugar and other cardiovascular risk factors. Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphism (RFLP) and Agarose Gel Electrophoresis techniques were used to determine the CETP TaqIB Polymorphism.<BR>Results: Out of 50 patients, 66% were females and 34% were males with a mean age of 55 y/o and a BMI of 27 kg/m&sup2;. The following risk factors were identified: hypertension (92%), dyslipidemia (88%), obesity (68%), smoking (50%), diabetes mellitus type 2 (18%) and family history of premature CAD (14%). The genotype frequencies of B1B1; B1B2; B2B2 were 40%; 50% 10% respectively. The B1B1 homozygote was associated with lower HDL-C levels (45.35 &plusmn; 8.82 mg/dL) compared to B1B2 (48.96 &plusmn; 10.10 mg/dL) and B2B2 (48.99 &plusmn; 10.13 mg/dL)). <BR>Conclusions: Cholesteryl Ester Transfer Protein (TaqIB) Polymorphisms exist among Filipinos with cardiovascular risk factors. The frequency of TaqIB polymorphism among Filipinos with cardiovascular risk factors were B1B1 (40%), B1B2 (50%) and B2B2 (10%). B1B1 polymorphism is more common than B2B2 and associated with low HDL-C.

著者

Yuanying Li Hiroshi Yatsuya Sachiko Tanaka Hiroyasu Iso Akira Okayama Ichiro Tsuji Kiyomi Sakata Yoshihiro Miyamoto Hirotsugu Ueshima Katsuyuki Miura Yoshitaka Murakami Tomonori Okamura EPOCH-JAPAN Research Group

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.58958, (Released:2020-10-10)

参考文献数

44

被引用文献数

9

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Aims: We aimed to develop and validate risk prediction models to estimate the absolute 10-year risk of death from coronary heart disease (CHD), stroke, and cardiovascular disease (CVD). Methods: We evaluated a total of 44,869 individuals aged 40–79 years from eight Japanese prospective cohorts to derive coefficients of risk equations using cohort-stratified Cox proportional hazard regression models. Discrimination (C-index) of the equation was examined in each cohort and summarised using random-effect meta-analyses. Calibration of the equation was assessed using Hosmer-Lemeshow chi-squared statistic. Results: Within a median follow-up of 12.7 years, we observed 765 deaths due to CVD (276 CHDs and 489 strokes). After backward selection, age, sex, current smoking, systolic blood pressure (SBP), proteinuria, prevalent diabetes mellitus, the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDLC), interaction terms of age by SBP, and age by current smoking were retained as predictors for CHD. Sex was excluded in the stroke equation. We did not consider TC/HDLC as a risk factor for the stroke and CVD equations. The pooled C-indices for CHD, stroke, and CVD were 0.83, 0.80, and 0.81, respectively, and the corresponding p-values of the Hosmer-Lemeshow tests were 0.18, 0.003, and 0.25, respectively. Conclusions: Risk equations in the present study can adequately estimate the absolute 10-year risk of death from CHD, stroke, and CVD. Future work will evaluate the system as an education and risk communication tool for primary prevention of CHD and stroke.

著者

Takashi Nomiyama

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.ED130, (Released:2020-06-05)

参考文献数

10

著者

Shinichiro Uchiyama Takao Hoshino Hugo Charles Kenji Kamiyama Taizen Nakase Kazuo Kitagawa Kazuo Minematsu Kenichi Todo Yasushi Okada Jyoji Nakagawara Ken Nagata Hiroshi Yamagami Takenori Yamaguchi Pierre Amarenco

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.58552, (Released:2020-09-17)

参考文献数

22

被引用文献数

4

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Aims: We have previously reported 5-year follow-up data on the TIAregistry.org, an international prospective cohort in patients with transient ischemic attack (TIA) or minor stroke. We conducted a Japanese subgroup analysis because outcomes and predictors might differ according to ethnicities and regions. In this study, we compared the baseline and 5-year follow-up data of Japanese and non-Japanese patients with TIA or minor stroke.Methods: Patients with TIA or minor ischemic stroke within 7 days after the onset were classified into two groups based on ethnicity, Japanese (n=345) and non-Japanese (n=3502); further, 5-year event rates were compared between the two groups. We also determined predictors of 5-year stroke for both groups. Results: Vascular death and death from any cause were identified to be less prevalent, unlike stroke and intracranial hemorrhage, which was determined to be more prevalent in Japanese than in non-Japanese patients. Five-year rate of stroke was significantly higher in Japanese patients. Cumulative stroke and major cardiovascular event rates did not decline but instead linearly increased from 1 to 5 years in both groups. Baseline risk factors for 5-year stroke were as follows: age, diabetes, history of stroke or TIA, and congestive heart failure in Japanese patients. Independent predictors of 5-year stroke were large artery atherosclerosis, congestive heart failure, diabetes, and age in Japanese patients. Conclusions: Recurrent stroke and intracranial hemorrhage were determined to be more prevalent at 5 years after TIA or minor stroke in Japanese patients than in non-Japanese patients. Strategies to mitigate the long-term risks of stroke, aside from adherence to current guidelines, should take Japanese-patient-specific residual risks into account.

著者

Hitoshi Hamamura Hisashi Adachi Mika Enomoto Ako Fukami Sachiko Nakamura Yume Nohara Nagisa Morikawa Akiko Sakaue Kenta Toyomasu Maki Yamamoto Yoshihiro Fukumoto

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.56390, (Released:2020-07-04)

参考文献数

38

被引用文献数

16

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Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been identified as an important regulator of low-density lipoprotein (LDL) receptor processing. Evolocumab and alirocumab are PCSK9 inhibitors; however, little is known about the association between PCSK9 levels and lipid profiles in a general population. Because PCSK9 inhibitors have LDL-C lowering effects, we investigated whether there is a positive correlation between serum PCSK9 levels and LDL-C or lipoprotein(a) [Lp(a)]. Methods: In Uku town, 674 residents (mean age; 69.2±8.3 years) received health check-ups. The participants underwent a physical examination and blood tests, including PCSK9 and Lp(a). Serum PCSK9 and Lp(a) were measured by ELISA and Latex methods, respectively. HOMA-IR was calculated by fasting plasma glucose×insulin levels/405. Results: The mean (range) of PCSK9 and Lp(a) were 211.2 (49-601) ng/mL and 60 (1-107) mg/dL, respectively. Because of a skewed distribution, the log-transformed values were used. With univariate linear regression analysis, PCSK9 levels were associated with Lp(a) (p=0.028), triglycerides (p<0.001), and HOMA-IR (p<0.001), but not with LDL-C (p=0.138) levels. Multiple stepwise regression analysis revealed that serum PCSK9 levels were independently associated with triglycerides (p<0.001), Lp(a) (p=0.033) and HOMA-IR (p=0.041). Conclusions: PCSK-9 is independently associated with triglycerides, Lp(a) levels, and HOMA-IR, but not LDL-C, in a relatively large general population sample.

著者

Mari Tanaka Hironori Imano Yasuhiko Kubota Kazumasa Yamagishi Mitsumasa Umesawa Isao Muraki Renzhe Cui Mina Hayama-Terada Yuji Shimizu Takeo Okada Tetsuya Ohira Tomoko Sankai Takeshi Tanigawa Shinichi Sato Akihiko Kitamura Masahiko Kiyama Hiroyasu Iso and the CIRCS Investigators

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.54064, (Released:2020-06-10)

参考文献数

30

被引用文献数

11

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Aim: This study aimed to investigate the association between the serum high-sensitivity C-reactive protein (hs-CRP) levels and incident atrial fibrillation risk in the general Japanese population, who have lower hs-CRP levels than the Western population, and assess whether the association is modified by sex, overweight, hypertension, and smoking status. Methods: We conducted a prospective study in 6517 Japanese men and women aged 40–79 years without atrial fibrillation at baseline and enrolled in the Circulatory Risk in Communities Study (2002–2008). The hs-CRP levels were measured using the latex particle-enhanced immunonephelometric assay. Atrial fibrillation was identified using standard 12-lead electrocardiograms and information on physician-diagnosed atrial fibrillation history from the follow-up surveys. We used a Cox proportional hazard regression stratified by community. Results: During a median follow-up of 11 years, 127 new cases of atrial fibrillation (74 and 53 cases among men and women, respectively) were found. Compared to the lowest quintile of hs-CRP levels, the multivariable hazard ratios (95% confidence intervals) were 2.54 (1.17–5.50), 2.28 (1.06–4.93), 2.92 (1.37–6.23), and 2.77 (1.30–5.91) for the second, third, fourth, and fifth (highest) quintiles, respectively. There was no significant effect modification by sex, overweight, hypertension, and smoking status (P for interaction >0.05). Conclusions: Elevated hs-CRP levels were significantly associated with increased risk of atrial fibrillation in the Japanese population. The association of hs-CRP levels with incident atrial fibrillation did not vary according to sex, overweight, hypertension status, or smoking status.

著者

Shuaibo Huang Ru Ding Yi Lin Zhiqing He Feng Wu Xianliang Dai Yihong Chen Yanping Gui Zhigang Huang Zonggui Wu Chun Liang

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.23, no.5, pp.632-643, 2016-05-02 (Released:2016-05-02)

参考文献数

59

被引用文献数

5 13

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Aim: Immunologic dysfunction was recently found to be one of the most important mechanisms underlying the initiation and development of atherosclerosis. Thymus involution can contribute to immune disturbance and disequilibrium of T-cell subsets. This study aimed to explore whether recent thymic emigration (RTE) is impaired in patients with coronary artery disease (CAD).Methods: Content of signal-joint T cell receptor excision circles (sj-TREC) in T lymphocytes, a molecular marker of RTE, was assessed among CAD patients and age-matched controls. Monochrome multiplex quantitative PCR method was used to assess the samples' telomere length in order to exclude the potential influence of T cell proliferation on the dilution of sj-TREC. Patients were grouped according to Gensini score (GS) (low, GS <18; intermediate, GS 18–41; high, GS >41). Ordinary logistic regression models were used to determine potential risk factors for CAD and GS tertiles.Results: Average copy numbers of sj-TREC per 106 T lymphocytes among patients with unstable angina, stable angina, and controls were 726±429, 1213±465, and 1795±838, respectively (P<0.001). However, there was no significant difference in telomere length among groups. Moreover, the content of sj-TREC in the high GS group was most significantly reduced than the low GS group (P<0.001). Multivariate logistic regression analysis revealed that lower sj-TREC was independently associated with the progression of CAD (OR=0.44, P<0.001) and higher GS (OR=0.4, P<0.001).Conclusion: Impaired RTE could be partly responsible for CAD development. Mechanisms may be involved in the disturbance of T lymphocyte compartment and interruption of maintained immune tolerance resulting from thymus involution.

著者

Shizuya Yamashita Hidenori Arai Hideaki Bujo Daisaku Masuda Tohru Ohama Toshiyuki Ishibashi Koji Yanagi Yasuji Doi Satoshi Nakagawa Koichi Yamashiro Kenichiro Tanabe Toru Kita Masunori Matsuzaki Yasushi Saito Masanori Fukushima Yuji Matsuzawa on Behalf of the PROSPECTIVE Study Group

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.55327, (Released:2020-04-24)

参考文献数

50

被引用文献数

26

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Aims: Although intensive statin therapy reduced cardiovascular risks, cardiovascular events have not been completely prevented. Probucol is a potent antioxidant and reduces tendon xanthomas in familial hypercholesterolemia patients despite reduction of high-density lipoprotein (HDL)-cholesterol (HDL-C). We investigated whether probucol can reduce cardiovascular events on top of conventional lipid-lowering therapy in patients with coronary heart disease (CHD). Methods: PROSPECTIVE is a multicenter, randomized, prospective study that recruited 876 Japanese patients with CHD and dyslipidemia with an low-density lipoprotein (LDL)-cholesterol (HDL-C) level of ≥ 140 mg/dL without medication or those treated with lipid-lowering drugs. Lipid-lowering agents were administered during the study period in the control group (n=438), and probucol 500 mg/day was added to lipid-lowering therapy in the probucol group (n=438). Patients were randomly assigned to two treatment groups by adjusting the LDL-C level and presence of diabetes and hypertension and followed up for more than 3 years. The primary end point was a composite of cerebrovascular and cardiovascular events (cardiovascular disease death including sudden death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, hospitalization for heart failure, or coronary revascularization). The secondary end point was carotid intima–media thickness in a subset of patients. Results: The incidence of the primary end point showed a trend to be lower in the probucol group compared with that in the control group despite reduced HDL-C without serious adverse events. Anti-atherogenic effects of probucol may be attributed to its potent antioxidative function and enhancement of reverse cholesterol transport. Conclusion: Since there was no statistical significance between the probucol and control groups despite a marked reduction of HDL-C, further studies on the clinical outcomes of probucol on top of conventional therapy may be necessary in the future (UMIN000003307).

著者

Hiroaki Ikezaki Norihiro Furusyo Yuya Yokota Masumi Ai Bela F Asztalos Masayuki Murata Jun Hayashi Ernst J Schaefer

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.54130, (Released:2020-04-10)

参考文献数

46

被引用文献数

14

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Aim: The association between small dense low-density lipoprotein cholesterol (sdLDL-C) levels and carotid intimal medial thickness (cIMT) progression has not been evaluated fully. We assessed specialized lipoproteins, including sdLDL-C, with regard to cIMT progression in a prospective observational study in Japan. Methods: Plasma total cholesterol, direct LDL-C, sdLDL-C, LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, Lp(a), and adiponectin were measured in 2,030 men and women (median age 59 years, free of cardiovascular disease (CVD) and off cholesterol lowering medication). At both baseline and after a five-year follow-up, cIMT was assessed. Univariate, multivariate regression, and least square analyses were performed to examine the relationships between direct LDL-C, sdLDL-C, and other lipoproteins with cIMT progression. Results: The median cIMT at baseline was 0.63 mm and five-year progression was 0.18 mm. After adjustment for standard CVD risk factors, including age, gender, systolic blood pressure, total cholesterol, HDL-C, smoking, diabetes, and hypertension treatment, only direct LDL-C, sdLDL-C, and the sdLDL-C/LDL-C ratio were associated with cIMT progression. Even in subjects with direct LDL-C <100 mg/dL, who were considered at low CVD risk, elevated sdLDL-C were associated with cIMT progression (P for trend=0.009) in a model with established CVD risk factors, although the sdLDL-C/LDL-C ratio did not. Those correlations did not change by including triglycerides as a controlling factor or excluding premenopausal women from the analyzed population. Conclusions: Small dense LDL-C has a stronger relationship with cIMT progression than LDL-C does; therefore, measuring sdLDL-C may allow for the formulation of optimal therapy for CVD prevention.

著者

Kazuyuki Ozaki Takaaki Kubo Ryuta Imaki Hisahito Shinagawa Hidehira Fukaya Keita Ohtaki Seiga Ozaki Tohru Izumi Yoshifusa Aizawa

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.13, no.4, pp.216-219, 2006 (Released:2006-08-15)

参考文献数

22

被引用文献数

32 39

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We investigated the lipid lowering and anti-atherosclerotic effects of atorvastatin in patients with hypercholesterolemia. Thirty patients were given atorvastatin 10 mg daily, and assessed for serum lipids, intima-media thickness (IMT), and brachial-ankle pulse wave velocity (ba-PWV) at the baseline, 6 months, and 12 months. Remnant-like particle-cholesterol (RLP-C), lipoprotein (a)(Lp(a)), and high-sensitivity C-reactive protein (hs-CRP) were measured in some patients at the baseline and at 6 months. Total cholesterol, triglyceride and low-density lipoprotein cholesterol were significantly decreased by 32%, 23% and 44% at 6 months, respectively, and these effects were sustained at 12 months. There was no change in high-density lipoprotein cholesterol. IMT at the baseline was 0.88 ± 0.16 mm and decreased to 0.76 ± 0.13 mm at 6 months, remaining at 0.75 ± 0.12 mm at 12 months. We did not observe any significant changes in ba-PWV. RLP-C and hs-CRP were significantly reduced from 7.3 ± 10.8 mg/dL to 4.3 ± 5.3 mg/dL and 0.075 ± 0.065 mg/dL to 0.039 ± 0.043 mg/dL at 6 months, respectively. There was no change in Lp(a). The observed decrease in IMT suggests that atorvastatin possibly improves atherosclerosis, in addition to the significant reduction of serum lipids.

著者

Yuya Nakano

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.RV17039, (Released:2019-12-20)

参考文献数

84

被引用文献数

30

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Low birth weight (LBW) infants have higher risk of developing insulin resistance and its comorbidities later in life. The concept of “developmental origins of health and disease” suggests that intrauterine and postnatal environments have an important role in increasing these risks. The risk of such adult-onset diseases in LBW infants might be associated with adipose tissue maldevelopment including altered body composition and increased amount of visceral fat, which is the same mechanism as that in children and adults with metabolic syndrome. However, LBW infants often have different characteristics: they are not always overweight or obese over their life course. The inconsistency might be associated with the thrifty phenotype, which is produced in response to impaired growth potential and decreased lean body mass. LBW infants tend to be obese within the limits of impaired growth potential. Through our previous investigations evaluating longitudinal changes in adiponectin levels at an early stage of life, we speculated that probably, the intrauterine life of term infants or the period up to term-equivalent age in preterm infants might be the key age for the development of adipose tissues including fat cells. Because of that, we hypothesized that the smaller number of adipocytes in LBW infants might be associated with overloading of single adipocytes and impaired adipose tissue expandability. The possible mechanisms are discussed from the perspective of adipose tissue maldevelopment in LBW infants.

著者

Kazuo Omori Naoto Katakami Shoya Arakawa Yuichi Yamamoto Hiroyo Ninomiya Mitsuyoshi Takahara Taka-aki Matsuoka Hiroshi Tsugawa Masahiro Furuno Takeshi Bamba Eiichiro Fukusaki Iichiro Shimomura

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.52506, (Released:2020-01-25)

参考文献数

32

被引用文献数

15

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Aim: An identification of the high-risk group of atherosclerotic cardiovascular disease (CVD) is important in the management of patients with diabetes. Metabolomics is a potential tool for the discovery of new biomarkers. With this background, we aimed to identify metabolites associated with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 176 patients with T2DM who have never had a CVD event and 40 who were survivors of coronary artery disease (CAD) events were enrolled. Non-targeted metabolome analysis of fasting plasma samples was performed using gas chromatography coupled with mass spectrometry (GC/MS) highly optimized for multiple measurement of blood samples. First, metabolites were screened by analyzing the association with the established markers of subclinical atherosclerosis (i.e., carotid maximal intima-media thickness (max-IMT) and flow-mediated vasodilation (FMD)) in the non-CVD subjects. Then, the associations between the metabolites detected and the history of CAD were investigated. Result: A total of 65 annotated metabolites were detected. Non-parametric univariate analysis identified inositol and indoxyl sulfate as significantly (p<0.05) associated with both max-IMT and FMD. These metabolites were also significantly associated with CAD. Moreover, inositol remained to be associated with CAD even after adjustments for traditional coronary risk factors. Conclusions: We identified novel biomarker candidates for atherosclerosis in Japanese patients with T2DM using GC/MS-based non-targeted metabolomics.