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Akira Sekikawa, MD, MPH, PhD, PhD

Associate Professor, Epidemiology

Contact

130 North Bellefield Avenue, Suite 527, Pittsburgh, PA 15213
R-znvy: nxven@cvgg.rqh
Primary Phone: 967-818-6538
Fax: 967-838-6401

Assistant(s): 
Monica Love, zyyfg80@cvgg.rqh, 967-838-6340

Personal Statement

I am an MD/PhD from Japan (1983-94). I came to the US in 1994 to learn epidemiology as a basic science of disease prevention, obtained MPH then second PhD. I started epidemiological research focusing on uniquely low mortality from coronary heart disease (CHD) and chronic obstructive pulmonary disease (COPD) in Japan. 

 

Mortality from CHD and COPD and in Japan is unique for 3 reasons. First, it is >67% lower than in US despite a less favorable profile of life-time exposure to risk factors for cardiovascular and lung disease in Japan than in the US. Second, it is declining since 1970 despite a continuous and marked rise in blood levels of total cholesterol since 1960 by 50 mg/dl. Finally, studies of migrant Japanese to the US showed a dramatic increase in CHD and COPD rates, indicating that the uniquely low mortality in Japan is unlikely to be purely due to genetic susceptibility, but some environmental factors unique to Japanese in Japan. Diet and microbiome are known as our major environmental exposures,

 

Japanese in Japan have a very different diet from other developed countries, characterized by high intake of soy isoflavones (ISF) and marine omega-3 fatty acids. Observational studies in Japan showed significant inverse associations of dietary intake of ISF both with CHD and COPD. However, a recent randomized clinical trial of ISF in the US failed to show its benefit. We posit that the discrepancy is due to variations in microbiome. Equol, a metabolite of ISF by gut microbiome, is a potent anti-oxidant and 50-70% of Japanese in Japan convert ISF to equol in contrast to 20% of Americans, likely due to the difference in microbiome but not genetics. Our small study showed that equol-producers compared to non-producers had significantly lower levels of atherosclerosis independent of dietary ISFs in men in Japan. Adaptive immunity, especially pro-inflammatory type 1 helper T cell (Th1), plays a central role in atherogenesis. The higher percentages of Th1 in the circulating CD4+ T cells (%Th1) (Th1 bias) had a significant positive association with atherosclerosis in the US general population. A similar Th1 bias is reported in both the lung and peripheral blood of patients with COPD, supporting a common systemic mechanism. Preclinical studies show that omega-3 fatty acids reduces the differentiation from naive T to Th1. To further understand the effect of diet on pathobiology, we are to take nutrigenomic approach. 

 


Education

1983 | Tohoku University, Sendai, Japan | M.D.
1990 | Yamagata University, Yamagata, Japan | PhD
1996 | University of Pittsburgh, Pittsburgh, PA | MPH
1999 | University of Pittsburgh, Pittsburgh, PA | PhD


Teaching

EPI 2150 Epidemiology of Cardiovascular Disease (2005 - present) Primary instructor since 2016

Cardiovascular Training Grant. (2013- present) Co-Director

EPI2152 Workshop in Cardiovascular Epidemiology (2013-present) Associate Instructor

EPI2170 Chronic Disease Epidemiology (2014- present) Guest lecturer

 

I have trained 6 PhD students, 12 MPH students, and 6 post-doctoral fellows as a primary mentor.



Selected Publications

Selected publications in 2015-2018

Sekikawa A, Mahajan H, Kadowaki S, Hisamatsu T, Miyagawa N, Fujiyoshi A, Kadota A, Maegawa H, Murata K, Miura K, Edmundowicz D, Ueshima H. Association of blood levels of marine omega-3 fatty acids with coronary calcification and calcium density in Japanese men. Eur J Clin Nutr (ACCEPTED) 


Kadowaki S, Miura K, Kadowaki T, Fujiyoshi A, El-Saed A, Masaki KH, Okamura T, Edmundowicz D, Rodriguez BL, Nakamura Y, Barinas-Mitchell EJM, Kadota A, Willcox BJ, Abbott RD, Kuller LH, Choo J, Shin C, Ueshima H, Sekikawa A: ERA JUMP Study Group. International comparison of abdominal fat distribution among four populations: The ERA JUMP Study. Metab Syndr Relat Disord 2018; 16: 166-173


Mahajan H, Choo J, Masaki K, Fujiyoshi A, Guo J, Hisamatsu T, Evens RE, Shangguan S, Willcox B, Okamura T, Vishnu A, Barinas-Mitchell E, Ahuj V, Miura K, Kuller LH, Shin C, Ueshima H, Sekikawa A. Association of alcohol consumption and aortic calcification in healthy men aged 40-49 for the ERA JUMP Study. Atherosclerosis 2018; 268:84-91 PMID 29195109


Ahuja V, Miura K, Vishnu A, Fujiyoshi A, Evans R, Zaid M, Miyagawa N, Hisamatsu T, Kadota A, Okamura T, Ueshima H, Sekikawa ASignificant inverse association of equol-producer status with coronary artery calcification but not dietary isoflavones in healthy Japanese men. Br J Nutr. 2017 117(2):260-266, PMID: 28205492

 

Ahuja V, Masaki K, Vishnu A, Ye L, Wilcox B, Wassel C, Fujiyoshi A, Barinas-Mitchell EJ, Miura K, Ueshima H, Rodriguez BL, Edmundowicz D, Sekikawa A; ERA JUMP Study. Progression of coronary artery calcium in Japanese American men and white men in the ERA JUMP study. Int J Cardiol. 2017; 228:672-676 PMID 27883980

 

Guo J, Fujiyoshi A, Willcox B, Choo J, Vishnu A, Hisamatsu T, Ahuja V, Takashima N, Barinas-Mitchell E, Kadota A, Evans RW, Miura K, Edmundowicz D, Masaki K, Shin C, Kuller LH, Ueshima H, Sekikawa A; ERA JUMP Study Group. Increased Aortic Calcification Is Associated With Arterial Stiffness Progression in Multiethnic Middle-Aged Men. Hypertension. 2017 Jan;69(1):102-108. Epub 2016 Nov 7. PubMed PMID: 27821619; PubMed Central PMCID: PMC5145727.

Guo J, Fujiyoshi A, Masaki K, Vishnu A, Kadota A, Barinas-Mitchell EJ, Hisamatsu T, Ahuja V, Takashima N, Evans RW, Willcox BJ, Miura K, Rodriguez B, Ueshima H, Kuller LH, Sekikawa AThe role of initial and longitudinal change in blood pressure on progression of arterial stiffness among multiethnic middle-aged men. J Hypertens. 2017 Jan;35(1):111-117. PubMed PMID: 27775956.

Miller RG, Mahajan HD, Costacou T, Sekikawa A, Anderson SJ, Orchard TJ. A Contemporary Estimate of Total Mortality and Cardiovascular Disease Risk in Young Adults With Type 1 Diabetes: The Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Care. 2016 Dec;39(12):2296-2303. Epub 2016 Sep 21. PubMed PMID: 27654986; PubMed Central PMCID: PMC5127232.

Birru RL, Ahuja V, Vishnu A, Evans RW, Miyamoto Y, Miura K, Usui T, Sekikawa A. The impact of equol producing status in modifying the effect of soy isoflavones on risk factors for coronary heart disease: a systematic review of randomized controlled trials. J Nutr Sci 2016 19;5:e30 PMCID: PMC4976117

Hisamatsu T, Miura K, Arima H, Kadota A, Kadowaki S, Torii S, Suzuki S, Miyagawa N, Sato A, Yamazoe M, Fujiyoshi A, Ohkubo T, Yamamoto T, Murata K, Abbott RD, Sekikawa A, Horie M, Ueshima H; Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) Research Group. Smoking, Smoking Cessation, and Measures of Subclinical Atherosclerosis in Multiple Vascular Beds in Japanese Men. J Am Heart Assoc. 2016 20;e003738 PubMed PMID: 27572823


Yamazoe M, Hisamatsu T, Miura K, Kadowaki S, Zaid M, Kadota A, Torii S, Miyazaki I, Fujiyoshi A, Arima H, Sekikawa A, Maegawa H, Horie M, Ueshima H.   Relationship of insulin resistance to prevalence and progression of coronary artery calcification beyond metabolic syndrome components in a general population: Shiga Epidemiological Study of Subclinical Atherosclerosis. Athero Throm Vasc Biol 2016; 36(8):1703-8  PubMed PMID: 27283744

Ahuja V, Masaki K, Barinas-Mitchell E, Rodriguez BL, Althouse AD, Ueshima H, Vishnu A, Seto TB, Kuller LH, Wilcox B, Sekikawa A. Significantly greater progression of intima-media thickness of the carotid artery in Japanese American men than white men- the ERA JUMP Study Can J Cardiol 2016, 32; 1246.e7-1246.e12 PubMed Central PMCID: PMC4912953

Ueshima H, Kadowaki T, Hisamatsu T, Fujiyoshi A, Miura K, Ohkubo T, Sekikawa A, Kadota A, Kadowaki S, Nakamura Y, Miyagawa N, Okamura T, Kita Y, Takashima N, Kashiwagi A, MaegawaH, Hirie M, Yamamoto T, Kimura T, Kita T for the ACCESS and SESSA Research Groups. Lipoprotein-associated phospholipase A2 is related to risk of subclinical atherosclerosis but is not supported by Mendelian randomization analysis in a general Japanese population Atherosclerosis 2016; 246: 141-7 PMID 26775119


Zaid M, Miura K, Fujiyoshi A, Abbott RD, Hisamatsu T, Kadota A, Arima H, Kadowaki S, Torii S, Miyagawa N, Suzuki S, TakashimaN, Ohkubo T, Sekikawa A, Maegawa H, Horie M, Nakamura Y, Okamura T, Ueshima H for the SESSA Research Group. Associations of serum LDL particle concentration with carotid intima-media thickness and coronary artery calcification. J Clin Lipidol. 2016; 10: 1195-1202  PMID 27678437


Miller RG, Anderson SJ, Costacou T, Sekikawa A, Orchard T. Risk stratification for 25-year cardiovascular disease incidence in type 1 diabetes: tree-structured survival analysis of the Pittsburgh Epidemiology of Diabetes Complication (EDC) Study. Diabetes and Vascular Disease Research 2016; 13: 250-9 PMID: 27190081


El-Saed A, Masaki K, Okamura T, Evans RW, Nakamura Y, Willcox BJ, Lee S, Maegawa H, Seto TB, Choo J, Fujiyoshi A, Miura K, Kuller LH, Ueshima H, Sekikawa A. The associations of C-reactive protein with serum levels of polyunsaturated fatty acids and trans fatty acids among middle-aged men from three populations. J Nutr Health Aging 2016; 20: 16-21 PMID 26728928

Sekikawa A, Miyamoto Y, Miura K, Nishimura K, Willcox BJ, Masaki KH, Rodriguez B, Tracy RP,  Okamura T, Kuller LH. Continuous decline in mortality from coronary heart disease in Japan despite a continuous and marked rise in total cholesterol: Japanese experience after the Seven Country Study. Intl J Epidemiol 2015: 44: 1614-24

 

Sekikawa A, Doyle M, Kuller LH. Recent findings of long-chain n-3 polyunsaturated fatty acids (LCn-3 PUFAs) on atherosclerosis and coronary heart disease (CHD) contrasting studies in Western countries to Japan. Trends in cardiovascular medicine 2015;25:717-23 PMID:25850978   

Vishnu A, Choo J, Wilcox B, Hisamatsu T, Barinas-Mitchell EJ, Fujiyoshi A, Mackey RH, Kadota A, Ahuja V, Kadowaki T, Edmundowicz D, Miura K, Rodriguez BL, Kuller LH, Shin C, Masaki K, Ueshima H, Sekikawa A; ERA JUMP Study Group. Brachial-ankle pulse wave velocity is associated with coronary artery calcification among 1131 healthy middle-aged men. Int J Cardiol. 2015; 189: 67-72.PMID 25885874 

Zaid M, Fujiyoshi A, Miura K, Abbott RD, Okamura T, Takashima N, Torii S, Saito Y, Hisamatsu T, Miyagawa N, Ohkubo T, Kadota A, Sekikawa A, Maegawa H, Nakamura Y, Mitsunami K, Ueshima H; For the SESSA Research group. High-density lipoprotein particle concentration and subclinical atherosclerosis of the carotid arteries in Japanese men. Atherosclerosis 2015;239: 444-450. PMID 25687270.

 Ahuja V, Kadowaki T, Evans RW, Kadota A, Okamura T, El Koudary S, Fujiyoshi A, Barinas-Mitchell E, HIsamatsu T, Vishnu a, Miura K, Maegawa H, El-Saed A, Kashiwagi A, Kuller LH, Ueshima H, Sekikawa A for the ERA JUMP study. Comparison of HOMA-IR, HOMA-β and disposition index between US white men and Jpaanese men in Japan; the ERA JUMP study. Diabetologia 2015; 58: 265-71 PMID 25316435

Other selected publications from 100+ peer-reviewed articles
Sekikawa A, Miura K, Lee S, Fujiyoshi A, Edmundowicz D, Kadowaki T, Evans RW, Kadowaki S, Sutton-Tyrrell K, Okamura T, Bertolet M, Masaki KH, Nakamura Y, Barinas-Mitchell EJM, Willcox BJ, Kadota A, Seto TB, Maegawa H, Kuller LH, Ueshima H MD, PhD  for the ERA JUMP Study Group. Long-chain n-3 polyunsaturated fatty acids and incidence rate of coronary artery calcification in Japanese in Japan and United States whites – population-based prospective cohort study. Heart 100(7):569-73. PMID:24352736. PMCID:PMC3949146


Yokoyama Y, Nishimura K, Barnard N, Takegami M, Sekikawa A, Okamura T, Miyamoto Y. Vegetarian diets and blood pressure: A meta-analysis. JAMA Internal Medicine 2014;174(4):577-87. PMID:24566947


Sekikawa A, Willcox BJ, Usui T, Carr JJ, Barinas-Mitchell EJM, Masaki KH,  Watanabe M, Tracy RP, Bertolet M, Evans RW, Nishimura K, Sutton-Tyrrell K, Kuller LH, Miyamoto Y. Do differences in risk factors explain the lower rates of coronary heart disease in Japanese versus U.S. women? J Women’s Health 2013; 22: 966-977

Miyagawa N, Miura K, Okuda N, Kadowaki T, Takashima N, Nagasawa S, Nakamura Y, Matsumura Y, Hozawa A, Fujiyoshi A, Hisamatsu T, Yoshita K, Sekikawa A, Ohkubo T, Abbott RD, Okamura T, Okayama A, Ueshima H for the NIPPON DATA80 Research Group. Long-chain n-3 polyunsaturated fatty acids intake and cardiovascular disease mortality risk in Japanese: a 24-year follow-up of NIPPON DATA80. Atherosclerosis 2014;232(2):384-9. PMID:24468152

 

Sekikawa A, Willcox BJ, Usui T, Carr JJ, Barinas-Mitchell EJM, Masaki KH,  Watanabe M, Tracy RP, Bertolet M, Evans RW, Nishimura K, Sutton-Tyrrell K, Kuller LH, Miyamoto Y. Do differences in risk factors explain the lower rates of coronary heart disease in Japanese versus U.S. women? J Women’s Health 2013; 22: 966-977

Sekikawa A, Shin C, Masaki K, Barinas Mitchell EJ, Hirooka N, Willcox BJ, Choo J, White J, Evans RW, Fijiyoshi A, Okamura T, Miura K, Muldoon MF, Ueshima H, Kuller LH, Sutton-Tyrrell K. Association of Total Marine Fatty Acids, Eicosapentaenoic and Docosahexaenoic Acids, With Aortic Stiffness in Koreans, Whites, and Japanese Americans.  Am J Hypertens. 2013; 26: 1321-7

El Khoudary SR, Barinas-Mitchell E, Curb JD, Shin C, Ueshima H, Masaki K, Evans RW, Miura K, Edmundowicz D, Kuller LH, Sutton-Tyrrell K, Sekikawa A for the ERA JUMP Study Group. Adiponectin, Systolic Blood Pressure and Drinking Alcohol Are Associated with More Aortic Stiffness Progression among Apparently Healthy Men. Atherosclerosis 2012; 225: 275-80. 

Sekikawa A, Steingrimsdottir L, Ueshima H, Shin C, Curb JD, Evans RW, Hauksdottir AM, Kadota A, Choo J, Masaki K,  Thorsson B, Launer LJ, Garcia ME, Maegawa H, Willcox BJ, Eiriksdottir G, Fujiyoshi A, Miura K, Harris TB, Kuller LH, Gudnason V. Serum levels of marine-derived n-3 fatty acids in Icelanders, Japanese, Koreans, and Americans - A descriptive epidemiologic study. Prostaglandins, Leukotrienes & Essential Fatty Acids 2012; 87: 11-6

Sekikawa A, Shin C, Curb JD, Barinas-Mitchell E, Masaki K, El-Saed A, Seto TB, Mackey RH, Choo J, Fujiyoshi A, Miura K, Edmundowicz D, Kuller LH, Ueshima H, Sutton-Tyrrell K, for the ERA JUMP Study group. Aortic stiffness and calcification in men in a population-based international study. Atherosclerosis 2012; 222:473-7.

Sekikawa A, Kadowaki T, El-Saed E, Okamura T, Sutton-Tyrrell K, Nakamura Y, Evans EW, Mitsunami K, Edmundowicz D, Nihio Y, Nkata K, Kadota A, Otake T, Miura K, Choo, J, Abbott RD, Kuller LH, Ueshima H.  Differential association of docosahexaenoic and eicosapentaenoic acids with carotid intima-media thickness. Stroke 2011; 42:2538-43

Sekikawa A, Kadowaki T, Curb JD, Evans RW, Maegawa H, Abbott RD, Kim Sutton-Tyrrell K, Okamura T, Shin C, Edmundowicz D, Kadota A, Choo J, El-Saed A, Ueshima H, Kuller LHfor the ERA JUMP Study group, Circulating levels of eight cytokines and marine n-3 fatty acids and indices of obesity and in Japanese, white and Japanese American middle-aged men. Cytokine Research 2010; 30: 541-8

Sekikawa A, Curb JD, Ueshima H, El-Saed A, Kadowaki T, Abbott RD, Evans RW, Rodriguez BL,  Okamura T, Sutton-Tyrrell K, Nakamura Y, Masaki K, Edmundowicz D, Kashiwagi A, Willcox BJ, Takamiya T, Mitsunami K, Seto TB, Murata K, White RL, Kuller LH. Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese Americans, and Whites. J Am Coll Cardiol 2008; 52: 417-24 

Sekikawa A, Ueshima H, Sutton-Tyrrell K, Kadowaki T, El-Saed A, Okamura T, Takamiya T, Ueno Y, Evans RW, Nakamura Y, Edmundowicz D, Kashiwagi A, Maegawa H, Kuller LH. Intima-media thickness of the carotid artery and the distribution of lipoprotein subclasses in men aged 40-49 between whites in the U.S. and the Japanese in Japan for the ERA JUMP Study. Metabolism 2008;57:177-82 

Sekikawa A, Ueshima H, Kadowaki T, El-Saed A, Okamura T, Takamiya T, Kashiwagi A, Edmundowicz D, Murata K, Sutton-Tyrrell K, Maegawa H, Evans R, Kita Y, Kuller L. Less subclinical atherosclerosis in Japanese men in Japan than in white men in the United States in the post World-War-II birth cohort  Am J Epidemiol 2007; 165: 617-24

Kadowaki T, Sekikawa A, Okamura T, Takamiya T, Kashiwagi A, Zaky WR, Maegawa H, El-Saed A, Nakamura Y, Evans RW, Edmundowicz D, Kita Y, Kuller L. Ueshima H. Higher levels of adiponectin in American than in Japanese men despite obesity. Metabolism 2006; 55:1561-3

Kadowaki T, Sekikawa A, Murata K, Maegawa H, Takamiya T, Okamura T, El-Saed, A, Miyamatsu N, Edmundowicz D, Kita Y, Sutton-Tyrrell K, Kuller LH, Ueshima H. Large visceral visceral fat in Japanese than Caucasian men. International Journal of Obesity 2006; 7:1163-5 


Sekikawa A, Horiuchi BY, Edmundowicz D, Ueshima H, Curb JD, Sutton-Tyrrell K, Okamura T, Kadowaki T, Kashiwagi A, Mitsunami K, Murata K, Nakamura Y, Rodriguez BL, Kuller LH. A "natural experiment" in cardiovascular epidemiology in the early 21st century. Heart 2003;89: 255-7 

Sekikawa A, Satoh T, Hayawaka T, Ueshima H, Kuller LH. Coronary heart disease mortality among men aged 35-44 by prefecture in Japan in 1995-1999 and its comparison with that among white men aged 35-44 by state in the United States in 1995-1998: Vital statistics data in recent birth cohorts. Jpn Circ J 2001;65:887-892 

Sekikawa A,Eguchi H, Tominaga M, Igarashi K, Abe T,Manaka H,Sasaki H,Fukuyama H,Kato T,Kihohara Y, Fujishima M. Prevalence of type 2 diabetes mellitus and impaired glucose tolerance in a rural area of Japan, the Funagata diabetes study. J Diab Complications 14: 78-83; 2000 

Sekikawa A, Kuller LH, Ueshima H, Park JE, Suh I, Jee SH, Lee HK, Pan WH. Coronary heart disease trends in the post World War II birth cohorts aged 35-44 in men in Japan, South Korea, and Taiwan, and a comparison with the United States. Intl J Epidemol 28: 1044-49; 1999 

Sekikawa A, Eguchi H, Tominaga M, Manaka H, Sasaki H, Chang YF, Kato T. Evaluating the prevalence of type 2 diabetes reported by the Oguni registry, using a two-sample model of capture-recapture methods. Intl J Epidemiol 28: 498-501, 1999

Sekikawa A, Tominaga M, Takahashi K, Eguchi H, Igarashi M, Ohnuma H, Sugiyama K, Manaka H, Sasaki H, Fukuyama H, Miyazawa K. Prevalence of Diabetes and Impaired Glucose Tolera nce in Funagata area, Japan. Diabetes Care 16 570-574, 1993

Akira  Sekikawa
© 2018 by University of Pittsburgh Graduate School of Public Health

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