Coronary heart disease (CHD) is the single largest killer for both men and women in the US. The Japanese in Japan continue to have very low CHD rates despite increasing levels of risk factors since the end of World War II (WWII). CHD mortality has been increasing in most Asian countries except for Japan. The Electron-Beam Tomography and Risk Assessment in the Japanese and US Men in the Post World War II Birth Cohort (ERA-JUMP) (HL068200 and HL071561) was designed to test the hypothesis that levels of subclinical atherosclerosis in men in the post WWII birth cohort, i.e., men aged 40-49, in Japan exposed for long periods of time to Westernized lifestyle are lower than in age-matched US Black, White, and Japanese American men. ERA-JUMP has documented that (1) the Japanese in Japan had significantly lower levels of subclinical atherosclerosis in the coronary and carotid arteries than US populations, (2) Japanese Americans had similar or higher levels of subclinical atherosclerosis as compared to Whites, (3) the Japanese in Japan had levels of serum marine n-3 fatty acids (marine n-3) higher by >100% than US populations, and (4) serum marine n-3 had a significant inverse association with subclinical atherosclerosis. Based on these results, we propose to conduct an analysis of the relationship of marine n-3 to the progression of subclinical atherosclerosis and to extend our findings to 2 additional cohorts for validation and evaluation.
Aim 1 : to determine the association of baseline serum marine n-3 with the progression of subclinical atherosclerosis in the ERA JUMP cohort: 300 Whites, 300 Japanese Americans, 300 Japanese in Japan, and 100 Blacks. We hypothesize that the progression is slower in the Japanese in Japan than US populations, and that marine n-3 has an inverse association with the progression.
Aim 2 : to determine the association of serum marine n-3 with subclinical atherosclerosis in an expanded study in Japan, 700 Japanese men aged 50-79. The subclinical atherosclerosis measures have already been done at no cost to this study since the study was funded in Japan. Our plan is to measure serum marine n-3 in these 700 men and relate them to the extent of subclinical atherosclerosis.
Aim 3 : to examine the relationship between serum marine n-3 and food intake in 1,200 Japanese and 260 Japanese American men and women from INTERLIPID, including detailed multiple 24-hour recalls. Our plan is to measure marine n-3 in the stored blood samples of these individuals and relate them to the detailed dietary data. Our central hypothesis is that very high intake of marine n-3 has a strong anti-atherogenic effect. This hypothesis is very different from benefits of much lower doses of marine n-3 on arrhythmias or the short term benefits of high dose marine n-3 in clinical trials among individuals with extensive atherosclerosis. This hypothesis cannot be studied in a US population because of their very low intakes of marine n-3. If our hypothesis were true that marine n-3 has a strong anti-atherogenic effect, especially at high levels observed in Japan, we may be able to reduce CHD rates in the US dramatically by greatly increasing the intake of marine n-3 in the general population in the US. Our baseline study found that in men aged 40-49, the Japanese in Japan had much lower levels of subclinical atherosclerosis than US populations, that Whites and Japanese Americans had similar levels, that serum levels of n-3 fatty acids found in fish were higher by >100% in the Japanese in Japan than in US populations, and that serum n-3 fatty acids found in fish had a strong inverse association with subclinical atherosclerosis, suggesting that n-3 fatty acids found in fish, especially at higher levels found in the Japanese in Japan, have a strong anti-atherosclerotic effect. In this application we will examine the association of serum n-3 fatty acids found in fish with the progression of subclinical atherosclerosis in the US populations and the Japanese in Japan. If our hypothesis were true that n-3 fatty acids found in fish have a strong anti-atherosclerotic effect, especially at high levels observed in Japan, we may be able to reduce coronary heart disease rates in the US dramatically by greatly increasing the intake of n-3 fatty acids found in fish in the general population in the US.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL068200-09
Application #
8241129
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Nelson, Cheryl R
Project Start
2001-07-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2014-02-28
Support Year
9
Fiscal Year
2012
Total Cost
$716,997
Indirect Cost
$162,530
Name
University of Pittsburgh
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Sekikawa, Akira; Mahajan, Hemant; Kadowaki, Sayaka et al. (2018) Association of blood levels of marine omega-3 fatty acids with coronary calcification and calcium density in Japanese men. Eur J Clin Nutr :
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Okamura, Tomonori; Miura, Katsuyuki; Sawamura, Tatsuya et al. (2016) Serum level of LOX-1 ligand containing ApoB is associated with increased carotid intima-media thickness in Japanese community-dwelling men, especially those with hypercholesterolemia LOX-1 ligand and IMT in Japanese. J Clin Lipidol 10:172-80.e1
Birru, Rahel L; Ahuja, Vasudha; Vishnu, Abhishek et al. (2016) The impact of equol-producing status in modifying the effect of soya isoflavones on risk factors for CHD: a systematic review of randomised controlled trials. J Nutr Sci 5:e30

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