Red Blood Cell Fatty Acid Biomarkers and Cardiovascular Disease Risk

红细胞脂肪酸生物标志物与心血管疾病风险

• 批准号: 8039996
• 负责人: WILLIAM S HARRIS
• 金额: $ 15.82万
• 依托单位: SANFORD RESEARCH/USD
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8039996
• 关键词: Address; Affect; Age; Aging; American Heart Association; Appearance; Arrhythmia; Arteries; Arthritis; Biochemical; Biological Markers; Blood; Blood Glucose; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cell physiology; Cessation of life; Cities; Clinical; Clinical Data; Communities; Conflict (Psychology); Congestive Heart Failure; Coronary heart disease; Cross-Sectional Studies; Data; Data Set; Dementia; Development; Diabetes Mellitus; Dietary Questionnaires; Dietary intake; Disease; Echocardiography; Eicosanoids; Epidemiology; Erythrocytes; Event; Evolution; Fatty Acids; Fish Oils; Fishes; Foundations; Framingham Heart Study; Funding; Future; Glycosylated hemoglobin A; Health; Heart; Heart Rate; Heart failure; Hemoglobin; Heritability; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Human; Hypertension; Immune; Incidence; Individual; Inflammatory; Insulin Resistance; Intake; Investigation; Kansas; Knowledge; Learning; Left; Left Ventricular Mass; Left Ventricular Remodeling; Left ventricular structure; Link; Lipids; Macular degeneration; Measures; Mediating; Membrane Structure and Function; Meta-Analysis; Minority; Myocardial; Myocardial Infarction; Oils; Omega-3 Fatty Acids; Outcome; Pattern; Peripheral; Physiological; Plasma; Platelet aggregation; Positioning Attribute; Predictive Value; Predisposition; Prevalence; Proteins; Relative (related person); Reporting; Research; Risk; Risk Factors; Risk Marker; Sample Size; Sampling; Serum; Smoking; Solid; Stroke; Tissues; Triglycerides; Ultrasonography; Variant; Vascular remodeling; Ventricular; Ventricular Remodeling; Work; arterial tonometry; base; blood pump; brachial artery; capsule; cardiovascular disorder risk; case control; cohort; cytokine; design; flexibility; glycemic control; heart disease risk; heart rate variability; high risk; improved; indexing; interest; offspring; prospective; sudden cardiac death; tonometry; treatment strategy

DESCRIPTION (provided by applicant): Omega-3 fatty acids (n-3 FAs) are believed to reduce risk for cardiovascular disease (CVD), especially sudden cardiac death, and for congestive heart failure (CHF). The epidemiology, however, remains conflicted, and the mechanisms by which dietary n-3 FAs operate remain speculative. A decrease in heart rate, an increase in heart rate variability, and improved endothelial function have all been associated with higher levels of n-3 FA biomarkers. These may be mediated by changes in membrane structure/function and/or eicosanoids or cytokine- induced inflammatory proteins. Red blood cell (RBC) n-3 FA content has recently been shown to be a valid surrogate biomarker of human myocardial n-3 FA levels. In addition to being more objective (relative to dietary questionnaire-based measures), RBC n-3 FAs may be preferable to plasma levels of FAs because they reflect tissue FA levels over several weeks and are less variable (analogous to hemoglobin A1C in the assessment of average blood glucose levels). No prior studies have evaluated the relationships between RBC n-3 FAs (or FA patterns) on cardiovascular outcomes and vascular risk markers. To address these gaps in knowledge, we propose to measure RBC FA composition in two Framingham Heart Study cohorts (the Offspring Study and the minority, Omni Study). The RBC n-3 FA content will be analyzed in conjunction with the rich dataset already collected on these subjects which includes classical and emerging risk factors, subclinical left ventricular (LV) remodeling, vascular stiffness, and endothelial function. These subjects are also under continuous surveillance for the development of CVD and CHF. We propose the following 3 aims: Aim 1. RBC n-3FAs and clinical correlates. To define the cross-sectional clinical correlates, the heritability and the stability of RBC n-3 FA content in a community-based sample. Aim 2. RBC n-3 FAs and vascular & ventricular remodeling. To examine the cross-sectional relations of RBC n-3 FAs to a) microcirculatory function and conduit artery stiffness (using tonometry), b) endothelial function (using ultrasound-based brachial artery flow-mediated dilation), and c) indexes of LV remodeling (using echocardiography). Aim 3. RBC n-3 FAs and the development of CVD risk factors & incident CVD. To investigate prospectively the relations of RBC n-3 FA content to longitudinal tracking of the evolution of CVD risk factors and of the incidence of CVD events. These data will not only inform future studies assessing the predictive value of RBC FAs for CVD, but also for other diseases (e.g., dementia, arthritis, macular degeneration, etc.) potentially modulated by these FAs. PUBLIC HEALTH RELEVANCE: There has been increasing interest in the heart-healthy effects of fish oils, especially the omega-3 fatty acids (EPA and DHA) that they contain. While we now know that giving fish oil supplements to people who are at high risk for heart attacks seems to reduce their risk for heart disease, we don't know how these natural oils work to help the heart, nor do we know the degree to which normal variations in blood levels are related to heart disease risk factors. This study will attempt to uncover heretofore unknown links between blood omega-3 levels and such things as how fast people develop high blood pressure, how flexible (i.e., healthy) the blood vessels are, how vigorously the heart pumps blood, or how inflamed the arteries are. All of these factors are important in determining risk for heart attacks and strokes, and so learning how they are affected by omega-3 fatty acids will help us devise new treatment strategies to reduce risk for these major diseases in the US.

描述（由申请人提供）：据信omega-3脂肪酸（N-3 FAS）降低心血管疾病（CVD），尤其是心脏猝死和充血性心力衰竭（CHF）的风险。然而，流行病学仍然存在冲突，饮食N-3 FAS的机制仍然投机。心率降低，心率变异性的提高和改善的内皮功能都与较高水平的N-3 FA生物标志物有关。这些可能是由膜结构/功能和/或类eicosanoids或细胞因子诱导的炎性蛋白的变化所介导的。红细胞（RBC）N-3 FA含量最近已被证明是人类心肌N-3 FA水平的有效替代生物标志物。除了更客观（相对于基于饮食问卷的措施）之外，RBC N-3 FA可能比血浆FAS的水平更可取，因为它们反映了几周内的组织FA水平，并且在评估平均血糖水平的评估时与血红蛋白A1C相似（类似于血红蛋白A1C）。没有先前的研究评估RBC N-3 FAS（或FA模式）在心血管结局和血管风险标记上的关系。为了解决这些知识的差距，我们建议在两个Framingham心脏研究队列中测量RBC FA组成（后代研究和少数族裔，OMNI研究）。 RBC N-3 FA含量将与已经在这些受试者上收集的丰富数据集进行分析，这些受试者包括经典和新兴的危险因素，亚临床左心室（LV）重塑，血管僵硬和内皮功能。这些受试者在CVD和CHF的发展方面也处于连续监视之下。我们提出以下3个目标：目标1。RBCN-3FA和临床相关。为了定义横截面临床相关性，在基于社区的样本中，RBC N-3 FA含量的遗传力和稳定性。 AIM2。RBCN-3 FAS和血管和心室重塑。为了检查RBC N-3 FAS与A）微循环功能和导管动脉刚度的横截面关系（使用Tonometry），b）内皮功能（使用基于超声的臂动脉流介导的扩张），以及C）LV重塑的索引（使用Echarcartiography）。 AIM3。RBCN-3 FAS和CVD风险因素和事件CVD的发展。前瞻性地研究RBC N-3 FA含量与CVD危险因素进化和CVD事件发生率的纵向跟踪的关系。这些数据不仅会为评估CVD的RBC FAS的预测价值的未来研究提供信息，还将为其他疾病（例如痴呆症，关节炎，黄斑变性等）提供了可能由这些FAS调节的其他疾病（例如痴呆症，关节炎，黄斑变性等）。公共卫生相关性：对鱼油的心脏健康影响，尤其是它们所包含的omega-3脂肪酸（EPA和DHA）的兴趣越来越大。虽然我们现在知道，向患有心脏病发作高风险的人提供鱼油补充剂似乎会降低其心脏病的风险，但我们不知道这些天然油如何帮助心脏，也不知道血液水平正常变异与心脏病危险因素有关的程度。这项研究将试图发现血液omega-3水平之间的未知联系以及人们发展高血压的速度，血管的柔韧性（即健康）的速度，血管的柔韧性，心脏的剧烈泵血或动脉的发炎程度。所有这些因素对于确定心脏病发作和中风的风险都很重要，因此学习如何受到omega-3脂肪酸的影响将有助于我们制定新的治疗策略，以减少美国这些主要疾病的风险。

项目成果

Aspirin and omega-3 fatty acid status interact in the prevention of cardiovascular diseases in Framingham Heart Study.

• DOI: 10.1016/j.plefa.2021.102283
• 发表时间: 2021-06
• 期刊: Prostaglandins, leukotrienes, and essential fatty acids
• 作者: Block RC;Shearer GC;Holub A;Tu XM;Mousa S;Brenna JT;Harris WS;Tintle N
• 通讯作者: Tintle N

Erythrocyte long-chain omega-3 fatty acid levels are inversely associated with mortality and with incident cardiovascular disease: The Framingham Heart Study.

• DOI: 10.1016/j.jacl.2018.02.010
• 发表时间: 2018-05
• 期刊: Journal of clinical lipidology
• 影响因子: 4.4
• 作者: Harris WS;Tintle NL;Etherton MR;Vasan RS
• 通讯作者: Vasan RS

Structural equation modeling for analyzing erythrocyte fatty acids in Framingham.

• DOI: 10.1155/2014/160520
• 发表时间: 2014
• 期刊: Computational and mathematical methods in medicine
• 作者: Pottala JV;Djira GD;Espeland MA;Ye J;Larson MG;Harris WS
• 通讯作者: Harris WS

Clinical correlates and heritability of erythrocyte eicosapentaenoic and docosahexaenoic acid content in the Framingham Heart Study.

• DOI: 10.1016/j.atherosclerosis.2012.05.030
• 发表时间: 2012-12
• 期刊: ATHEROSCLEROSIS
• 影响因子: 5.3
• 作者: Harris, William S.;Pottala, James V.;Lacey, Sean M.;Vasan, Ramachandran S.;Larson, Martin G.;Robins, Sander J.
• 通讯作者: Robins, Sander J.