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CLINICAL RESEARCH: ATHEROSCLEROSIS

Marine-Derived n-3 Fatty Acids and Atherosclerosis in Japanese, Japanese-American, and White Men

A Cross-Sectional Study

Akira Sekikawa, MD, PhD^_*,,_*, J. David Curb, MD, MPH^,, Hirotsugu Ueshima, MD, PhD, Aiman El-Saed, MD, PhD^_*, Takashi Kadowaki, MD, PhD^,_*, Robert D. Abbott, PhD^,,, Rhobert W. Evans, PhD^_*, Beatriz L. Rodriguez, MD, PhD, Tomonori Okamura, MD, PhD^,||, Kim Sutton-Tyrrell, DrPH^_*, Yasuyuki Nakamura, MD, PhD, FACC^¶, Kamal Masaki, MD, Daniel Edmundowicz, MD, MPH, FACC^_*, Atsunori Kashiwagi, MD, PhD, Bradley J. Willcox, MD, Tomoko Takamiya, MD, PhD^_*, Ken-ichi Mitsunami, MD, PhD, Todd B. Seto, MD, MPH^#, Kiyoshi Murata, MD, PhD, Roger L. White, MD^_**, Lewis H. Kuller, MD, DrPH^_* for the ERA JUMP (Electron-Beam Tomography, Risk Factor Assessment Among Japanese and U.S. Men in the Post-World War II Birth Cohort) Study Group

^_* University of Pittsburgh, Pittsburgh, Pennsylvania
Shiga University of Medical Science, Otsu, Shiga, Japan
Pacific Health Research Institute, Honolulu, Hawaii
University of Virginia, Charlottesville, Virginia
^|| National Cardiovascular Center, Suita, Osaka, Japan
^¶ Kyoto Women's University, Kyoto, Japan
^# Queen's Medical Center, Honolulu, Hawaii
^_** Holistica Health Center, Honolulu, Hawaii.

Manuscript received November 14, 2007; revised manuscript received March 7, 2008, accepted March 11, 2008.

^_* Reprint requests and correspondence: Dr. Akira Sekikawa, Assistant Professor of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 North Bellefield Avenue, Suite 546, Pittsburgh, Pennsylvania 15213. (Email: akira{at}pitt.edu).

Objectives: We sought to examine whether marine-derived n-3 fatty acids are associated with less atherosclerosis in Japanese versus white populations in the U.S.

Background: Marine-derived n-3 fatty acids at low levels are cardioprotective through their antiarrhythmic effect.

Methods: A population-based cross-sectional study in 281 Japanese (defined as born and living in Japan), 306 white (defined as white men born and living in the U.S.), and 281 Japanese-American men (defined as Japanese men born and living in the U.S.) ages 40 to 49 years was conducted to assess intima-media thickness (IMT) of the carotid artery, coronary artery calcification (CAC), and serum fatty acids.

Results: Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar levels. Japanese had 2-fold higher levels of marine-derived n-3 fatty acids than whites and Japanese Americans in the U.S. Japanese had significant and nonsignificant inverse associations of marine-derived n-3 fatty acids with IMT and CAC prevalence, respectively. The significant inverse association with IMT remained after adjusting for traditional cardiovascular risk factors. Neither whites nor Japanese Americans had such associations. Significant differences between Japanese and whites in multivariable-adjusted IMT (mean difference 39 µm, 95% confidence interval [CI]: 21 to 57µm, p < 0.001) and CAC prevalence (mean difference 10.7%, 95% CI: 2.9% to 18.4%, p = 0.007) became nonsignificant after we adjusted further for marine-derived n-3 fatty acids (22 µm, 95% CI: –1 to 46 µm, p = 0.065 and 5.0%, 95% CI: –5.3% to 15.4%, p = 0.341, respectively).

Conclusions: Very high levels of marine-derived n-3 fatty acids have antiatherogenic properties that are independent of traditional cardiovascular risk factors and may contribute to lower the burden of atherosclerosis in Japanese, a lower burden that is unlikely the result of genetic factors.

Key Words: atherosclerosis • epidemiology • n-3 fatty acids • coronary artery calcification • intima-media thickness • Japanese

Abbreviations and Acronyms   CAC = coronary artery calcification   CCA = common carotid artery   CCS = coronary calcium score   CHD = coronary heart disease   CI = confidence interval   HDL = high-density lipoprotein   IMT = Intima-media thickness

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