Kyushu University Academic Staff Educational and Research Activities Database
Researcher information (To researchers) Need Help? How to update
Hiroaki Ikezaki Last modified date:2023.09.29

Associate Professor / Department of Comprehensive General Internal Medicine
Faculty of Medical Sciences




E-Mail *Since the e-mail address is not displayed in Internet Explorer, please use another web browser:Google Chrome, safari.
Homepage
https://kyushu-u.elsevierpure.com/en/persons/hiroaki-ikezaki
 Reseacher Profiling Tool Kyushu University Pure
Academic Degree
Ph.D.(Dr. of Medical Science): Kyushu University Graduate School of Medical Sciences
Country of degree conferring institution (Overseas)
No
Field of Specialization
Atherosclerosis, Lipid Metabolism, Infectious Disease, Liver Disease
Total Priod of education and research career in the foreign country
02years06months
Outline Activities
Clinical Research: Investigating risk factors of atherosclerotic cardiovascular disease and malignant tumors in a prospective, observational, community-dwelling cohort study.

Clinical Activity: General Internal Medicine
Research
Research Interests
  • Epidemiological research for risk factors of Atherosclerotic Cardiovascular Diseases and Malignant Tumors
    keyword : Atherosclerotic Cardiovascular Diseases, Lipid Metabolism, Malignant Tumors
    2010.04.
Academic Activities
Papers
1. Ikezaki H, Fisher VA, Lim E, Ai M, Liu CT, Cupples LA, Nakajima K, Asztalos BF, Furusyo N, Schaefer EJ, Direct versus calculated low-density lipoprotein cholesterol and C reactive protein in cardiovascular disease risk assessment in the Framingham Offspring Study, Clinical Chemistry, 10.1373/clinchem.2019.304600, 65, 9, 1102-1114, 2019.09.
2. Ikezaki H, Ai M, Schaefer EJ, Otokozawa S, Asztalos BF, Nakajima K, Zhou Y, Liu CT, Jacques PF, Cupples LA, Furusyo N, Cardiovascular Disease Prevalence and Insulin Resistance in the Kyushu-Okinawa Population Study and the Framingham Offspring Study., Journal of Clinical Lipidology, 10.1016/j.jacl.2017.01.014, 11, 2, 348-356, 2017.03.
3. Ikezaki H, Ai M, Schaefer EJ, Otokozawa S, Asztalos BF, Nakajima K, Yanhua Z, Liu CT, Jacques PF, Cupples LA, Furusyo N, Ethnic Differences in Glucose Homeostasis Markers between the Kyushu-Okinawa Population Study and the Framingham Offspring Study., Scientific Reports, 10.1038/srep36725, 6, 36725, 2016.11.
4. Ikezaki H, Nomura H, Furusyo N, Ogawa E, Kajiwara E, Takahashi K, Kawano A, Maruyama T, Tanabe Y, Satoh T, Nakamuta M, Kotoh K, Azuma K, Dohmen K, Shimoda S, Hayashi J; Kyushu University Liver Disease Study (KULDS) Group, Efficacy of interferon-beta plus ribavirin combination treatment on the development of hepatocellular., Hepatology Research, 10.1111/hepr.12555, 46, 3, E174-E180, 2016.03.
5. Ikezaki H, Furusyo N, Ihara T, Hayashi T, Ura K, Hiramine S, Mitsumoto F, Takayama K, Murata M, Kohzuma T, Ai M, Schaefer EJ, Hayashi J, Glycated Albumin as a diagnostic tool for diabetes in a general Japanese population., Metabolism – Clinical and Experimental, 10.1016/j.metabol.2015.03.003, 64, 6, 698-705, 2015.06.
6. Ikezaki H, Furusyo N, Okada K, Ihara T, Hayashi T, Ogawa E, Kainuma M, Murata M, Hayashi J, The utility of urinary myo-inositol as a marker of glucose intolerance., Diabetes Research and Clinical Practice, 10.1016/j.diabres.2013.11.018, 103, 1, 88-96, 2014.01.
7. Furusyo N, Ogawa E, Sudoh M, Murata M, Ihara T, Hayashi T, Ikezaki H, Hiramine S, Mukae H, Toyoda K, Taniai H, Okada K, Kainuma M, Kajiwara E, Hayashi J, Raloxifene hydrochloride is an adjuvant antiviral treatment of postmenopausal women with chronic hepatitis C: A randomized trial., Journal of Hepatology, 10.1016/j.jhep.2012.08.003, 57, 6, 1186-1192, 2012.12, Background & Aims: Early menopause in women with chronic hepatitis C virus (HCV) infection is associated with a low likelihood of a sustained virological response (SVR) in conjunction with their antiviral treatment. This is potentially related to their reduced estrogen secretion. The study was done to determine whether selective estrogen receptor modulator administration might improve the efficacy of the current standard of care (SOC) treatment, pegylated interferon (PegIFN) α2a plus ribavirin (RBV), for postmenopausal women. Methods: One hundred and twenty-three postmenopausal women with genotype 1b chronic hepatitis C were randomly assigned to one of two treatment groups: raloxifene hydrochloride (RLX) (60 mg/day) plus SOC (PegIFNα2a 180 μg/week and RBV 600-1000 mg/day) (n = 62) or SOC only (n = 61). Genotyping was performed of the polymorphism in the interleukin-28B (IL28B) gene region (rs8099917) of DNA collected from each patient. Results: One RLX-treated patient discontinued RLX because of a systemic rash following 2 weeks of treatment. Twenty-four weeks after treatment, the SVR rate was significantly higher for RLX plus SOC patients (61.3%) than for SOC only patients (34.4%) (p = 0.0051). Further, the SVR rate was significantly higher for RLX plus SOC patients with IL28B TT (72.5%) than for SOC only patients with IL28B TT (39.2%) (p = 0.0014), but no such relationship was observed in patients carrying the minor IL28B allele. Conclusions: RLX improved the efficacy of SOC in the treatment of postmenopausal women with chronic hepatitis C. RLX shows promise as an adjuvant to the standard antiviral treatment of such patients..
8. Ogawa E, Furusyo N, Murata M, Ikezaki H, Ihara T, Hayashi T, Toyoda K, Taniai H, Okada K, Kainuma M, Hayashi J, Insulin resistance undermines the advantages of IL28B polymorphism in the pegylated interferon alpha-2b and ribavirin treatment of chronic hepatitis C patients with genotype 1., Journal of Hepatology, 10.1016/j.jhep.2012.04.027, 57, 3, 534-540, 2012.09, Background & Aims: Recent studies have suggested that insulin resistance exerts a strong influence on chronic hepatitis C virus (HCV) infection. We analyzed pretreatment factors useful for predicting sustained virological response (SVR), especially interleukin (IL) 28B polymorphism and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Methods: This cohort study consisted of 328 chronic hepatitis C patients with HCV genotype 1 who were treated for 48 weeks with pegylated interferon (PegIFN) α-2b and ribavirin (RBV). Genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on DNA collected from each patient. Results: No significant difference in IL28B genotype distribution was found according to HOMA-IR. Multivariate analysis identified the IL28B TT genotype (OR = 5.97, 95% CI 2.15-16.55, p = 0.0006) and the baseline HOMA-IR (OR = 0.65, 95% CI 0.48-0.87, p = 0.0044) as significant, independent pretreatment predictors of SVR. Receiver operating characteristic analyses to determine the optimal threshold values of HOMA-IR for predicting SVR showed that the areas under the curve (AUC) were high for both IL28B TT (AUC = 0.774, HOMA-IR cut-off value: 2.45) and IL28B TG/GG genotypes (AUC = 0.772, HOMA-IR cut-off value: 1.55). Conclusions: For HCV genotype 1, both IL28B and baseline HOMA-IR are independent pretreatment predictors of SVR in patients treated with PegIFNα-2b and RBV. Insulin resistance undermines the advantages of IL28B polymorphism to obtain SVR..
9. Furusyo N, Koga T, Ai M, Otokozawa S, Kohzuma T, Ikezaki H, Schaefer EJ, Hayashi J, Utility of glycated albumin for the diagnosis of diabetes mellitus in a Japanese population study
Results from the Kyushu and Okinawa Population Study (KOPS)., Diabetologia, 10.1007/s00125-011-2310-6, 54, 12, 3028-3036, 2011.12, Aims/hypothesis: Glycated albumin is a measure of the mean plasma glucose concentration over approximately 2-3 weeks. We determined reference values for glycated albumin, and assessed its utility for the diagnosis of type 2 diabetes mellitus in the general population. Methods: We studied 1,575 men and women (mean age, 49.9 years; range, 26-78 years) who participated in a periodic health examination in a suburban Japanese town. HbA 1c and fasting plasma concentrations of glucose (FPG) and glycated albumin were measured. Participants with FPG ≥7.0 mmol/l or HbA 1c ≥6.5% (48 mmol/mol) were diagnosed as having diabetes. In our laboratory, the glycated albumin assay had intra-assay and inter-assay CVs of 1.1% and 1.6%, respectively. Results: Glycated albumin levels were significantly correlated with HbA 1c levels (r=0.766, p16% (58 of 207, 28.0%). Receiver operating characteristic curve analysis indicated that a glycated albumin level of ≥15.5% was optimal for predicting diabetes, with a sensitivity of 83.3% and a specificity of 83.3%. Conclusions/interpretation: There is merit to further investigating the potential for glycated albumin to be used as an alternative measure of dysglycaemia for future research and clinical practice..
10. Hiroaki Ikezaki, Elise Lim, L Adrienne Cupples, Ching-Ti Liu, Bela F Asztalos, Ernst J Schaefer, Small Dense Low-Density Lipoprotein Cholesterol Is the Most Atherogenic Lipoprotein Parameter in the Prospective Framingham Offspring Study., Journal of the American Heart Association, 10.1161/JAHA.120.019140, 10, 5, e019140, 2021.02, Background Elevated plasma levels of direct low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), low-density lipoprotein (LDL) triglycerides, triglycerides, triglyceride-rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and lipoprotein(a) have all been associated with incident atherosclerotic cardiovascular disease (ASCVD). Our goal was to assess which parameters were most strongly associated with ASCVD risk. Methods and Results Plasma total cholesterol, triglycerides, high-density lipoprotein cholesterol, direct LDL-C, sdLDL-C, LDL triglycerides, remnant lipoprotein particle cholesterol, triglyceride-rich lipoprotein cholesterol, and lipoprotein(a) were measured using standardized automated analysis (coefficients of variation,
11. Hiroaki Ikezaki, Norihiro Furusyo, Yuya Yokota, Masumi Ai, Bela F Asztalos, Masayuki Murata, Jun Hayashi, Ernst J Schaefer, Small Dense Low-Density Lipoprotein Cholesterol and Carotid Intimal Medial Thickness Progression., Journal of atherosclerosis and thrombosis, 10.5551/jat.54130, 27, 10, 1108-1122, 2020.10, 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..
12. Hiroaki Ikezaki, Norihiro Furusyo, Paul F Jacques, Motohiro Shimizu, Masayuki Murata, Ernst J Schaefer, Yoshihisa Urita, Jun Hayashi, Higher dietary cholesterol and ω-3 fatty acid intakes are associated with a lower success rate of Helicobacter pylori eradication therapy in Japan., The American journal of clinical nutrition, 10.3945/ajcn.116.144873, 106, 2, 581-588, 2017.08, Background:Helicobacter pylori infection is a known risk factor for duodenal ulcers, gastritis, and gastric cancer. The eradication of H. pylori is successful in treating these disorders; however, the success rate of eradication therapy is declining. There may be an interaction with nutrient intake to account for this decline.Objective: We investigated the influence of food and nutrient intake on H. pylori eradication therapy.Design: In this study, 4014 subjects underwent endoscopy, were tested for serum antibodies to H. pylori (2046 positive; 51.0%), and had their food intake assessed with the use of a food-frequency questionnaire (FFQ). Of the positive subjects, endoscopies showed that 389 (19.0%) had gastritis and/or duodenal ulcers and were also positive for a 13C-urea breath test (UBT). These 389 subjects received 1-wk H. pylori eradication therapy with lansoprazole, amoxicillin, and clarithromycin and a second UBT 8 wk after treatment. Complete demographic characteristics, serum lipid, insulin, glycated hemoglobin, C-reactive protein (CRP), and creatinine concentrations as well as complete FFQs were available for 352 subjects. Multivariate logistic regression analyses were performed to determine factors that were associated with successful H. pylori eradication therapy.Results: The success rate of eradication therapy was 60.4% (235 of 389). Factors associated with the failure of eradication therapy included increased age (P = 0.02), higher CRP concentrations (P
13. Hiroaki Ikezaki, Norihiro Furusyo, Ryoko Nakashima, Makiko Umemoto, Ken Yamamoto, Yuji Matsumoto, Azusa Ohta, Sho Yamasaki, Satoshi Hiramine, Koji Takayama, Eiichi Ogawa, Kazuhiro Toyoda, Masayuki Murata, Nobuyuki Shimono, Jun Hayashi, Kyushu and Okinawa Population Study (KOPS): a large prospective cohort study in Japan., BMJ open, 10.1136/bmjopen-2021-053763, 11, 12, e053763, 2021.12, PURPOSE: The Kyushu and Okinawa Population Study (KOPS) was established to investigate gene-environmental interactions in non-communicable diseases in Japan. Besides collecting blood samples and anthropometric measurements, we also obtained medical histories, psychological status and lifestyle habits, including physical activities and dietary patterns. PARTICIPANTS: KOPS is a community-based prospective cohort study and consists of participants from four southwestern areas in Japan. Baseline surveys were conducted between 2004 and 2007 (wave 1), and 2009 and 2012 (wave 2) at the sites of municipality-based health check-ups. A total of 17 077 participants were included, comprising 10 697 participants of wave 1 and 6380 participants of wave 2; the median age in both groups was 61 years. Among them, 3006 individuals participated in both wave 1 and wave 2 surveys. FINDINGS TO DATE: We have focused on either risk or confounding factors for non-communicable diseases. We have assessed the clinical utility of the newly developed biomarkers for impaired glucose tolerance, such as urinary myo-inositol and glycated albumin, and atherosclerosis, such as small dense low-density lipoprotein cholesterol. We have conducted an international collaborative study with Framingham Offspring Study to investigate ethnic differences in impaired glucose tolerance and cardiovascular diseases. We have found that insulin resistance and deficiency might account for the ethnic differences in impaired glucose tolerance and cardiovascular disease risks. As gene-environmental interaction analyses, we found a synergic effect of interleukin 28B single nucleotide polymorphisms (SNPs) and gender on the spontaneous elimination of hepatitis C, and a beneficial interaction of SNPs of high-density lipoprotein cholesterol and gender on the impact of physical activity. In addition, we reported eight novel loci contributing to the development and severity of coronary artery disease from a large genome-wide association study. FUTURE PLANS: We plan to investigate further the clinical utility of the newly developed biomarkers and the gene-environmental interactions using prospective data..
14. Ikezaki H, Nomura H, Shimono N, Impact of peripheral mitochondrial DNA level on immune response after COVID-19 vaccination. , iScience, 10.1016/j.isci.2023.107094, 26, 107094, 2023.07.
15. Schaefer EJ*, Ikezaki H*, Diffenderfer MR, Lim E, Liu CT, Hoogeveen RC, Guan W, Tsai MY, Ballantyne CM * joint first authorship, Atherosclerotic Cardiovascular Disease Risk and Small Dense Low-Density Lipoprotein Cholesterol in Men, Women, African Americans and Non-African Americans: The Pooling Project. , Atherosclerosis, 10.1016/j.atherosclerosis.2023.01.015., 367, 15-23, 2023.02.
Presentations
1. Ikezaki H, Schaefer EJ, Murata M, Shimono N, Association between Nonalcoholic Fatty Liver Disease Risk Alleles and Atherosclerosis, AHA Scientific Sessions 2022, 2022.11.
2. Hiroaki Ikezaki、Ernst J Schaefer、Elise Lim、L Adrienne Cupples、Ching-Ti Liu、Ron C Hoogeveen、Weihua Guan、Michael Tsai、Christie M Ballantyne, Atherosclerotic cardiovascular disease risk and small dense low-density lipoprotein cholesterol in men, women, African Americans and non-African Americans, 第54回 日本動脈硬化学会総会, 2022.07.
3. Ikezaki H, Furusyo N, Ai M, Okazaki M, Hayashi J, Schaefer EJ, Relationship Between the Cholesterol and Triglyceride Content of Lipoprotein Subclasses and Carotid Intima-Media Thickness: Results from the Kyushu and Okinawa Population Study, AHA Scientific Sessions 2021, 2021.11.
4. Ikezaki H, Nakashima R, Furusyo N, Ai M, Okazaki M, Hayashi J, Schaefer EJ, Relationship between dietary vitamin D intake, obesity, and twenty lipoprotein subclasses: results from the Kyushu and Okinawa Population Study (KOPS), AHA Scientific Sessions 2021, 2021.11.
5. Ikezaki H, Lim E, Liu CT, Cupples LA, Asztalos BF, Murata M, Furusyo N, Schaefer EJ, Gender Differences in Lipoprotein Parameters in Cardiovascular Disease Risk; The Framingham Offspring Study, AHA Scientific Sessions 2020, 2020.11.
6. Ikezaki H, Yokota Y, Ai M, Asztalos BF, Murata M, Hayashi J, Schaefer EJ, Atherogenic Lipoproteins and Carotid Intimal Medial Thickness Progression over 5 years, 88th EAS Congress, 2020.10.
7. Ikezaki H, Lim E, Liu CT, Cupples LA, Asztalos BF, Schaefer EJ, Atherogenic Lipoproteins and Atherosclerotic Cardiovascular Disease in the Framingham Offspring Study, 88th EAS Congress, 2020.10.
8. Ikezaki H, Lim E, Liu CT, Cupples LA, Asztalos BF, Schaefer EJ, Atherogenic Lipoproteins and Incident Atherosclerotic Cardiovascular Disease in the Framingham Offspring Study, EPI|LIFESTYLE 2020, 2020.03.
9. Ikezaki H, Yokota Y, Ai M, Asztalos BF, Murata M, Hayashi J, Schaefer EJ, Small Dense Low-Density Lipoprotein Cholesterol and Carotid Intimal Medial Thickness Progression, EPI|LIFESTYLE 2020, 2020.03.
10. Ikezaki H, Lim E, Liu CT, Cupples LA, Nakajima K, Asztalos BF, Murata M, Furusyo N, Schaefer EJ, Small dense LDL cholesterol as a cardiovascular risk assessment; results from Framingham Offspring Study, AHA Scientific Sessions 2019, 2019.11.
11. Ikezaki H, Furusyo N, Yokota Y, Ai M, Asztalos BF, Murata M, Hayashi J, Schaefer EJ, Small Dense Low Density Lipoprotein Cholesterol Level Predicts Carotid Intimal Medial Thickness Progression over 5 years, AHA Scientific Sessions 2019, 2019.11.
12. Ikezaki H, Fisher VA, Liu Ct, Cupples LA, Nakajima K, Murata M, Furusyo N, Asztalos BF, Schaefer EJ, Direct Lipoprotein Measurements and Cardiovascular Disease Risk Assessment in the Framingham Offspring Study, Vascular Discovery Scientific Sessions 2019, 2019.05.
13. Ikezaki H, Furusyo N, Yokota Y, Ai M, Asztalos BF, Murata M, Hayashi J, Schaefer EJ, Small Dense Low Density Lipoprotein Cholesterol Predict Carotid Intimal Medial Thickness Progression, Vascular Discovery Scientific Sessions 2019, 2019.05.
14. Ikezaki H, Fisher VA, Liu Ct, Cupples LA, Nakajima K, Asztalos BF, Schaefer EJ, Low Density Lipoprotein Subfractions, Lipoprotein(a), and Cardiovascular Disease Risk Assessment in the Framingham Offspring Study, AHA Scientific Sessions 2018, 2018.11.
15. Ikezaki H, Yokota Y, Schaefer EJ, Horvath KV, Asztalos BF, Furusyo N, Lipoprotein(a) and Carotid Intimal Medial Thickness, ATVB/PVD 2017, 2017.05.
16. Ikezaki H, Fisher VA, Cupples LA, Minagawa A, Ito Y, Schaefer EJ, Remnant Lipoprotein Cholesterol and Other Lipoprotein Levels in Coronary Heart Disease Cases and Controls: Results from the Framingham Offspring Study, 5th International Symposium on Chylomicrons in Diseases, 2016.11.
17. Ikezaki H, Ai M, Schaefer EJ, Otokozawa S, Asztalos BF, Nakajima K, Yanhua Z, Liu CT, Jacques PF, Cupples LA, Furusyo N, Hyperinsulinemia and Cardiovascular Disease in Japan and the United States, AHA Scientific Session 2016, 2016.11.
18. Ikezaki H, Furusyo N, Jacques PF, Murata M, Schaefer EJ, Urita Y, Hayashi J, Impact of food consumption on Helicobacter pylori eradication therapy: a Japanese community-based observational study, ID Week 2016, 2016.10.
19. Ikezaki H, Ai M, Schaefer EJ, Otokozawa S, Asztalos BF, Nakajima K, Yanhua Z, Liu CT, Jacques PF, Cupples LA, Furusyo N, Cardiovascular Disease Prevalence and Risk Factors in Japanese and American Populations, ATVB/PVD 2016, 2016.05.
20. Ikezaki H, Furusyo N, Hiramine S, Ogawa E, Murata M, Hayashi J, Natural human interferon-beta plus ribavirin treatment toleration by chronic hepatitis C patients with depression or thrombocytopenia, ID Week 2013, 2013.10.
Membership in Academic Society
  • American Heart Association, Council on Epidemiology and Prevention, and Arteriosclerosis, Thrombosis & Vascular Biology
  • European Atherosclerosis Society
  • The Japanese Society of Internal Medicine
  • The Japanese Society of Hepatology
  • The Japanese Association of Infectious Diseases
  • Japan Atherosclerosis Society
  • The Japan Geriatrics Society
  • The Japan Diabetes Society
  • The Japanese Society of Hospital General Medicine
  • The Japanese Society for Helicobacter Research
Awards
  • ATVB Council Travel Awards for Young Investigators, AHA Scientific Sessions 2018
  • Young Investigator Award, the Japanese Association for Infectious Diseases, West Japan Council
  • Encourage award in 10th Scientific Meeting, The Fukuoka Association of Medical Sciences
  • Research Grant in 2017, Kaibara Morikazu Medical Science Promotion Foundation
  • Research Grant in 2017, The Japanese Society of Hospital General Medicine
  • Society’s award in 2017, The Japanese Society of Hospital General Medicine
  • 27th Japan Heart Foundation / Bayer Yakuhin Research Grant Abroad
  • Chairman’s award in 6th Scientific Meeting, The Japanese Society of Hospital General Medicine