Role of fatty acid metabolism for the prevention of sudden cardiac death

脂肪酸代谢在预防心源性猝死中的作用

• 批准号: 8133955
• 负责人: Stephanie Elizabeth Chiuve
• 金额: $ 11.73万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2013-01-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8133955
• 关键词: Accounting; Age; Alcohols; American Heart Association; Anti-Arrhythmia Agents; Antioxidants; Arachidonic Acids; Area; Arrhythmia; Award; Behavior Therapy; Biological Markers; Biological Markers; Biology; Biometry; Blood; Body mass index; Cardiac; Cardiovascular system; Cell membrane; Cessation of life; Cohort Studies; Communication; Conflict (Psychology); Congestive Heart Failure; Coronary heart disease; Data; Data Collection; Death Rate; Development; Diet; Diet Modification; Dietary Assessment; Dietary Fats; Dietary Fatty Acid; Dietary Questionnaires; Dietary intake; Disease; Enzymes; Epidemiologist; Erythrocytes; Experimental Models; Fatty Acid Desaturases; Fatty Acids; Functional disorder; Funding; Gender; Genes; Genetic; Genetic Variation; Goals; Grant; Health; Health Professional; Heart Arrest; Heart Diseases; Hospitals; Incidence; Individual; Intake; K-Series Research Career Programs; Knowledge; Linoleic Acids; Measurement; Measures; Mentored Clinical Scientist Development Award (K08); Mentors; Mentorship; Methods; Myocardial; Nurses' Health Study; Nutritional; Observational Study; Omega-3 Fatty Acids; Participant; Pathway interactions; Patients; Phase; Physical activity; Physicians; Plasma; Polyunsaturated Fatty Acids; Population; Population Characteristics; Prevention; Preventive Intervention; Primary Prevention; Property; Recording of previous events; Records; Research; Research Design; Research Personnel; Risk; Risk Factors; Role; Smoking; Strategic Planning; Stroke; Subgroup; Survival Rate; Techniques; Time; Training; Treatment Cost; United States National Institutes of Health; Variant; Ventricular; Woman; Women' s Health; Writing; cardiovascular disorder epidemiology; career; career development; clinical practice; cohort; cost effective; fatty acid metabolism; follow-up; genetic epidemiology; genetic variant; high risk; lifestyle factors; men; mortality; nutritional epidemiology; patient population; prevent; prospective; public health relevance; skills; sudden cardiac death

DESCRIPTION (provided by applicant): Sudden cardiac death (SCD) accounts for ~50% of all CHD deaths and, for the majority of victims, SCD is the first manifestation of heart disease. There is an accumulating body of evidence that fatty acids, particularly n-3 fatty acids, hold great promise as predictors of and preventive interventions against SCD, although studies have been inconsistent. These conflicting results may be due to differences in population characteristics (with and without CHD; men v. women) or methods of fatty acid assessment (dietary intake v. biomarker levels). Thus, more research is needed to understand the differences in risk among these various subgroups and to evaluate different methods of fatty acid measurements. Additionally, genetic and environmental influences on fatty acid metabolism are not well understood. Dr. Stephanie Chiuve's goals for this grant are to develop expertise in genetic epidemiology, advanced biostatistics, and dietary data collection, and then use this knowledge to study the role of fatty acids on SCD. Her career goal is to become an independent investigator in the field of "Nutritional Epidemiology of Cardiac Arrhythmic Disorders". Her primary mentor will be Dr. Christine Albert, a practicing clinical cardiac electrophysiologist and a leading epidemiologist in the field of cardiac arrhythmias and sudden cardiac death. In addition, several co-mentors with complimentary areas of expertise in biostatistics, genetic and cardiovascular epidemiology and fatty acid biology, who have strong records of successful mentorship, will supplement her training. During the K99 phase of this career development award, Dr. Chiuve will devote her time to scientific training in genetic epidemiology, biostatistics and fatty acid biology, through coursework, and mentored training through the analysis of dietary fatty acids and risk of SCD. She will also focus on her nonscientific career development by obtaining training in skills that will enhance the transition to independent investigator, including grant writing, scientific communication, mentoring and development and administration of a dietary questionnaire, and this training will continue throughout the award. During the R00 phase of the award, Dr. Chiuve use the skills gained in the K99 phase to study red blood cell (RBC) fatty acids and risk of SCD. She will also examine the influence of genetic variation in RBC fatty acids. She will investigate these aims within 6 large, NIH-funded prospective cohort studies that include both men and women and individuals with and without established CHD. Strengths of this proposal include the use of dietary and RBC fatty acid measures as means to predict individuals at high risk of SCD and the identification of subgroups that may benefit from a low-cost treatment such as modifying dietary fatty acid intake. These aims correspond to one goal in the NHLBI's strategic plan to "develop means to predict and prevent sudden cardiac death". PUBLIC HEALTH RELEVANCE: There are up to 400,000 sudden cardiac deaths (SCD) in the US annually, accounting for up to 20% of total mortality, and these deaths come with no forewarning. We aim to assess whether fatty acids, measured in the diet and in blood, can effectively predict risk of SCD and provide clinicians with the means to inform their patients of their heightened risk for SCD and suggest behavior or diet modification. This proposal is relevant to the NHLBI's strategic plan which aims "to develop non-invasive techniques, such as biological markers, to clinically identify patients at high risk of SCD".

描述（由申请人提供）：心源性猝死 (SCD) 约占所有 CHD 死亡的 50%，对于大多数受害者来说，SCD 是心脏病的首发表现。越来越多的证据表明，脂肪酸，特别是 n-3 脂肪酸，作为 SCD 的预测因子和预防性干预措施具有广阔的前景，尽管研究结果不一致。这些相互矛盾的结果可能是由于人群特征（有或没有先心病；男性与女性）或脂肪酸评估方法（膳食摄入量与生物标志物水平）的差异造成的。因此，需要更多的研究来了解这些不同亚组之间的风险差异，并评估不同的脂肪酸测量方法。此外，遗传和环境对脂肪酸代谢的影响尚不清楚。 Stephanie Chiuve 博士获得这笔资助的目标是发展遗传流行病学、高级生物统计学和饮食数据收集方面的专业知识，然后利用这些知识来研究脂肪酸对 SCD 的作用。她的职业目标是成为“心律失常疾病营养流行病学”领域的独立研究者。她的主要导师是 Christine Albert 博士，她是一位执业临床心脏电生理学家，也是心律失常和心源性猝死领域的领先流行病学家。此外，几位在生物统计学、遗传和心血管流行病学以及脂肪酸生物学领域拥有丰富专业知识的共同导师也将补充她的培训，他们拥有丰富的成功指导记录。在该职业发展奖的 K99 阶段，Chiuve 博士将通过课程作业投入遗传流行病学、生物统计学和脂肪酸生物学方面的科学培训，并通过分析膳食脂肪酸和 SCD 风险进行指导培训。她还将通过接受技能培训来专注于她的非科学职业发展，这些技能将促进向独立研究者的过渡，包括资助写作、科学沟通、指导以及饮食调查问卷的开发和管理，并且这种培训将在整个奖项期间持续进行。在该奖项的 R00 阶段，Chiuve 博士利用 K99 阶段获得的技能来研究红细胞 (RBC) 脂肪酸和 SCD 风险。她还将研究遗传变异对红细胞脂肪酸的影响。她将在 NIH 资助的 6 项大型前瞻性队列研究中研究这些目标，其中包括男性和女性以及患有或未患有先心病的个体。该提案的优点包括使用饮食和红细胞脂肪酸测量作为预测 SCD 高风险个体的手段，以及识别可能受益于低成本治疗（例如改变饮食脂肪酸摄入量）的亚组。这些目标与 NHLBI 战略计划中的一个目标相对应，即“开发预测和预防心源性猝死的方法”。 公共卫生相关性：美国每年有多达 400,000 例心源性猝死 (SCD)，占总死亡率的 20%，而且这些死亡是在没有任何预警的情况下发生的。我们的目的是评估饮食和血液中测量的脂肪酸是否可以有效预测 SCD 风险，并为临床医生提供告知患者 SCD 风险较高的方法，并建议行为或饮食调整。该提案与 NHLBI 的战略计划相关，该计划旨在“开发生物标记等非侵入性技术，以临床识别 SCD 高风险患者”。

项目成果

Dietary fat quality and risk of sudden cardiac death in women.

膳食脂肪质量和女性心源性猝死的风险。

• DOI: 10.3945/ajcn.112.040287
• 发表时间: 2012-09-01
• 期刊: The American journal of clinical nutrition
• 作者: Stephanie E. Chiuve;E. Rimm;R. S;hu;hu;A. Bernstein;K. Rexrode;J. Manson;W. Willett;C. Albert
• 通讯作者: C. Albert

Adherence to a low-risk, healthy lifestyle and risk of sudden cardiac death among women.

女性坚持低风险、健康的生活方式和心源性猝死的风险。

• 发表时间: 2011-07-06
• 作者: Chiuve, Stephanie E;Fung, Teresa T;Rexrode, Kathryn M;Spiegelman, Donna;Manson, JoAnn E;Stampfer, Meir J;Albert, Christine M
• 通讯作者: Albert, Christine M