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Pittsburgh, PA and Shiga, Japan - The low rate of atherosclerosis and heart disease in Japanese people may be related to their very high levels of marine-derived omega-3 fatty acids rather than genetic factors, a new study suggests [1]. The study, published in the August 5, 2008 issue of the Journal of the American College of Cardiology (available online July 28), was conducted by a group led by Dr Akira Sekikawa (University of Pittsburgh, PA, and Shiga University of Medical Science, Japan). They found that compared with white or Japanese American men living in the US, Japanese men living in Japan had twice the blood levels of omega-3 fatty acids-a finding that was independently linked to low levels of atherosclerosis. "The death rate from coronary heart disease in Japan has always been puzzlingly low. Our study suggests that the very low rates of coronary heart disease among Japanese living in Japan may be due to their lifelong high consumption of fish," Sekikawa said." Results showed that the Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar higher levels. The Japanese men also had twofold higher levels of marine-derived omega-3 fatty acids than white and Japanese Americans. In addition, the significant differences between Japanese and American men in multivariable-adjusted IMT and CAC prevalence became nonsignificant after adjustment further for marine-derived omega-3 fatty acids.

"18 645 patients with a total cholesterol of 6·5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999. Patients were randomly assigned to receive either 1800 mg of EPA daily with statin (EPA group; n=9326) or statin only (controls; n=9319) with a 5-year follow-up. The primary endpoint was any major coronary event, including sudden cardiac death, fatal and non-fatal myocardial infarction, and other non-fatal events including unstable angina pectoris, angioplasty, stenting, or coronary artery bypass grafting. Analysis was by intention-to-treat. Findings At mean follow-up of 4·6 years, we detected the primary endpoint in 262 (2·8%) patients in the EPA group and 324 (3·5%) in controls-a 19% relative reduction in major coronary events (p=0·011). Post-treatment LDL cholesterol concentrations decreased 25%, from 4·7 mmol/L in both groups. Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events. Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group. Sudden cardiac death and coronary death did not differ between groups. In patients with a history of coronary artery disease who were given EPA treatment, major coronary events were reduced by 19% (secondary prevention subgroup: 158 [8·7%] in the EPA group vs 197 [10·7%] in the control group; p=0·048). In patients with no history of coronary artery disease, EPA treatment reduced major coronary events by 18%, but this finding was not significant (104 [1·4%] in the EPA group vs 127 [1·7%] in the control group; p=0·132)."

July 29, 2008 - The low rate of atherosclerosis and heart disease in Japanese people may be related to their very high levels of marine-derived omega-3 fatty acids rather than genetic factors, a new study suggests [1]. The study, known as Electron-Beam Tomography, Risk Factor Assessment Among Japanese and US Men in the Post-World War II Birth Cohort (ERA JUMP) included 868 randomly selected men aged 40 to 49. Of these, 281 were Japanese men living in Japan; 306 were white men living in the US, and 281 were third- or fourth-generation Japanese American men from Hawaii. All study participants had a physical examination, completed a lifestyle questionnaire, and had blood tests to measure cholesterol levels and levels of omega-3 fatty acids. Atherosclerosis was assessed by measuring carotid intima-medial thickness (IMT) and coronary artery calcification (CAC). Results showed that the Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar higher levels. The Japanese men also had twofold higher levels of marine-derived omega-3 fatty acids than white and Japanese Americans. The study, published in the August 5, 2008 issue of the Journal of the American College of Cardiology (available online July 28), was conducted by a group led by Dr Akira Sekikawa (University of Pittsburgh, PA, and Shiga University of Medical Science, Japan). They found that compared with white or Japanese American men living in the US, Japanese men living in Japan had twice the blood levels of omega-3 fatty acids - a finding that was independently linked to low levels of atherosclerosis.

"The results of the uniquely-constructed ERA JUMP Study were just released, a fascinating study of the relationship of omega-3 fatty acids to coronary and carotid plaque. The study adds insight into why the Japanese experience only one third of the heart attacks of Americans, and why Japan occupies the bottom of the list for least heart attacks among all developed countries. The Electron-Beam Tomography, Risk Factor Assessment Among Japanese and U.S. Men in the Post-World War II Birth Cohort Study (ERA JUMP), a collaborative U.S.-Japanese effort, compared three groups of men: -- 281 Japanese men living in Japan -- 306 non-Japanese men living in the U.S. (Pittsburgh, Pennsylvania) -- 303 Japanese Americans (having both parents Japanese without "ethnic admixture") living in Hawaii. The last group represents a group that is genetically similar to the group in Japan, but exposed to an American diet and lifestyle. Three main measures were compared: -- Blood levels of omega-3 fatty acids, EPA and DHA) -- Carotid intimal-medial thickness (CIMT, the thickness of the carotid artery lining that can serve as an index of body-wide atherosclerosis) -- Coronary calcium (heart scan) scores."

Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; Japan EPA lipid intervention study (JELIS) Investigators. Lancet. 2007 Mar 31;369(9567):1090-8. Erratum in: Lancet. 2007 Jul 21;370(9583):220. PMID: 17398308 doi:10.1016/S0140-6736(07)60527-3 Interpretation EPA is a promising treatment for prevention of major coronary events, and especially non-fatal coronary events, in Japanese hypercholesterolaemic patients

"The Japan eicosapentaenoic acid (EPA) Lipid Intervention Study (JELIS) is a clinical trial that all Track Your Plaquers should know about. This enormous trial followed a simple design: Japanese men, between 40-75 years, and Japanese postmenopausal women aged

Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese-American, and white men: a cross-sectional study. 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; ERA JUMP (Electron-Beam Tomography, Risk Factor Assessment Among Japanese and U.S. Men in the Post-World War II Birth Cohort) Study Group. J Am Coll Cardiol. 2008 Aug 5;52(6):417-24. PMID: 18672160 Conclusions Very high levels of marine-derived n-3 FAs have anti-atherogenic properties independent of traditional cardiovascular risk factors and may contribute to lower burden of atherosclerosis in Japanese in Japan, which is unlikely due to genetic factors.

Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I. Iso H, Kobayashi M, Ishihara J, Sasaki S, Okada K, Kita Y, Kokubo Y, Tsugane S; JPHC Study Group. Circulation. 2006 Jan 17;113(2):195-202. Epub 2006 Jan 9. PMID: 16401768 doi: 10.1161/CIRCULATIONAHA.105.581355 Conclusions- Compared with a modest fish intake of once a week or &20 g/d, a higher intake was associated with substantially reduced risk of coronary heart disease, primarily nonfatal cardiac events, among middle-aged persons

The first large-scale, prospective, randomized trial of combined treatment with a statin and an omega-3 fatty acid originally derived from fish, eicosapentaenoic acid (EPA), has shown that the addition of EPA to statin therapy provides additional benefit in preventing major coronary events, apparently through lipid-independent mechanisms.[1] The Japan eicosapentaenoic acid (EPA) Lipid Intervention Study (JELIS) tested the effects of long-term use of EPA 1800 mg/day in addition to a statin in Japanese patients with hypercholesterolemia. The results add support to previous evidence of the beneficial effect of omega-3 fatty acids in patients with known coronary heart disease, and show that that effect can extend the benefit of statins, the JELIS investigators believe

Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals. Oe H, Hozumi T, Murata E, Matsuura H, Negishi K, Matsumura Y, Iwata S, Ogawa K, Sugioka K, Takemoto Y, Shimada K, Yoshiyama M, Ishikura Y, Kiso Y, Yoshikawa J. Heart. 2008 Mar;94(3):316-21. Epub 2007 Jun 25. PMID: 17591648 doi:10.1136/hrt.2006.113159

"Nov 14, 2005 | Michael O'Riordan. Dallas, TX - The addition of eicosapentaenoic acid (EPA) to low-dose statin therapy significantly reduced the incidence of major coronary events, largely driven by a reduction in unstable angina, when compared with patients taking statins alone. A subgroup analysis of the study, which involved a large number of primary-prevention patients, revealed that statin-treated secondary-prevention patients gained the most benefit from fish-oil supplementation. Dr Mitsuhiro Yokoyama Presenting the results of the Japan EPA Lipid Intervention Study (JELIS) during the late-breaking clinical-trials session at the American Heart Association Scientific Sessions 2005, Dr Mitsuhiro Yokoyama (Kobe University Graduate School of Medicine, Japan) said that the mechanism of benefit with EPA, a seafood-based, long-chain, n-3 polyunsaturated fatty acid, appears to be unrelated to the effects of cholesterol lowering. Commenting on the results of the study for heartwire, Dr Lawrence Appel (Johns Hopkins University School of Medicine, Baltimore, MD) said the findings are impressive given that the benefit of fish oil was observed on top of a regimen of statin therapy. He added that there are still some unknowns about which patient population would benefit most from fish oil."