Epidemiology of CHD of men aged 40+ in US, Hawaii, Japan

描述（由申请人提供）：冠心病（CHD）是美国男性和女性的单一最大杀手。尽管自第二次世界大战（二战）结束以来危险因素水平不断增加，但日本人的CHD发病率仍然很低。除日本外，大多数亚洲国家的冠心病死亡率一直在上升。二战后出生队列中日本和美国男性的电子束断层扫描和风险评估（ERA-JUMP）（HL 068200和HL 071561）旨在检验二战后出生队列中男性亚临床动脉粥样硬化水平的假设，即，在日本，40-49岁的男性长期暴露于西方化的生活方式中，低于年龄匹配的美国黑人、白色和日裔美国男性。ERA-JUMP记录了（1）在日本的日本人冠状动脉和颈动脉的亚临床动脉粥样硬化水平显著低于美国人群，（2）日裔美国人的亚临床动脉粥样硬化水平与白人相似或更高，（3）在日本的日本人血清海洋n-3脂肪酸水平（4）血清marine n-3与亚临床动脉粥样硬化呈显著负相关。基于这些结果，我们建议进行海洋n-3的亚临床动脉粥样硬化的进展的关系进行分析，并将我们的研究结果扩展到2个额外的队列进行验证和评估。目标1：确定ERA JUMP队列中基线血清marine n-3与亚临床动脉粥样硬化进展的相关性：300名白人，300名日裔美国人，300名日本人和100名黑人。我们假设，在日本的进展是缓慢的日本人比美国人口，海洋N-3与进展呈负相关。目的2：在日本对700名年龄在50-79岁的日本男性进行的一项扩大研究中，确定血清marine n-3与亚临床动脉粥样硬化的相关性。自从日本资助这项研究以来，亚临床动脉粥样硬化的测量已经在这项研究中免费完成。我们的计划是测量这700名男性的血清marine n-3，并将其与亚临床动脉粥样硬化的程度联系起来。目标3：在来自INTERLIPID的1，200名日本人和260名日裔美国人男性和女性中检查血清marine n-3与食物摄入量之间的关系，包括详细的多次24小时召回。我们的计划是测量这些人储存的血液样本中的海洋氮-3，并将其与详细的饮食数据联系起来。我们的中心假设是，非常高的海洋n-3摄入量具有很强的抗动脉粥样硬化作用。这一假设与低剂量的海洋n-3对心律失常的益处或在广泛动脉粥样硬化个体中的临床试验中高剂量海洋n-3的短期益处非常不同。这一假设无法在美国人群中进行研究，因为他们的海洋N-3摄入量非常低。如果我们的假设是真的，海洋n-3具有很强的抗动脉粥样硬化作用，特别是在日本观察到的高水平，我们可能能够通过大幅增加美国普通人群中海洋n-3的摄入量来大幅降低美国的冠心病发病率。我们的基线研究发现，在40-49岁的男性中，在日本的日本人的亚临床动脉粥样硬化水平比美国人群低得多，白人和日裔美国人的水平相似，在日本的日本人的鱼类中发现的n-3脂肪酸的血清水平比美国人群高>100%，并且在鱼中发现的血清n-3脂肪酸与亚临床动脉粥样硬化有很强的负相关性，这表明在鱼中发现的n-3脂肪酸，特别是在日本的日本人中发现的较高水平的n-3脂肪酸，具有很强的抗动脉粥样硬化作用。在本申请中，我们将研究在美国人群和日本人群中发现的鱼类血清n-3脂肪酸与亚临床动脉粥样硬化进展的关系。如果我们的假设是正确的，即在鱼类中发现的n-3脂肪酸具有很强的抗动脉粥样硬化作用，特别是在日本观察到的高水平，我们可能能够通过大幅增加美国普通人群中鱼类中发现的n-3脂肪酸的摄入量来大幅降低美国的冠心病发病率。

DESCRIPTION (provided by applicant): 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.