Cytomegalovirus and diseases of aging: a secondary analysis of NHANES III data

巨细胞病毒与衰老疾病：NHANES III 数据的二次分析

• 批准号: 8247692
• 负责人: Ann B Hill
• 金额: $ 6.31万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8247692
• 关键词: Age; Aging; Aging-Related Process; Anemia due to Chronic Disorder; Antibodies; Antiviral Agents; Autoimmune Diseases; Biological Markers; Biology; CD28 gene; CD8B1 gene; Cardiovascular Diseases; Chronic; Chronic Disease; Clinical Management; Clinical Research; Cognitive; Communicable Diseases; Cytomegalovirus; Cytomegalovirus Infections; Data; Data Analyses; Data Set; Disease; Disease Association; Elderly; Epidemiologic Studies; Evaluation; Failure; Fibrinogen; Future; Gender; Health; Herpesvirus 1; Immune; Immune response; Impaired cognition; Incidence; Individual; Infection; Inflammation; Inflammatory; Lead; Life; Literature; Malignant Neoplasms; Measures; Menopause; Modeling; National Health and Nutrition Examination Survey; Osteoporosis; Outcome; Participant; Pathogenesis; Pharmaceutical Preparations; Play; Population; Population Study; Premature Mortality; Prevalence; Prevention; Process; Public Health; Publishing; Quality of life; Race; Regression Analysis; Relative Risks; Reporter; Reporting; Rheumatoid Arthritis; Risk; Risk Factors; Role; Serologic tests; Seroprevalences; Serum; Severity of illness; Smoking; Socioeconomic Status; Specificity; Surveys; T cell response; T-Lymphocyte; Viral; Woman; age group; aged; base; cardiovascular disorder risk; cytokine; demographics; design; experience; falls; frailty; hazard; immunosenescence; inflammatory marker; influenza virus vaccine; interest; mortality; osteoporosis with pathological fracture; pathogen exposure; public health relevance; response; sex; vaccine development

DESCRIPTION (provided by applicant): Accumulating evidence over the last decade indicates that cytomegalovirus (CMV) is a major cause of the immunological changes that accompany aging, and that it contributes to multiple inflammatory processes and mortality in the elderly. This project will analyze data from the third National Health and Examination Survey (NHANES III, 1998-2002) to determine whether people infected with cytomegalovirus (CMV) are at greater risk for several chronic inflammatory conditions commonly associated with aging (cardiovascular disease, cognitive decline, frailty and osteoporosis), as well as for increased mortality, both all-cause and attributable to cardiovascular disease or cancer. These endpoints were chosen based on literature reports that CMV- associated biomarkers predict the incidence of the disease or premature mortality. However, because CMV seropositivity is so high in the elderly, and most studies were small, all but two of the previous studies have been limited to reporting associations with biomarkers of a large immune response to CMV, rather than comparing the risk in CMV seropositives versus seronegatives. Since there are alternative explanations for an association between the size of the immune response to CMV and poor aging, it is important to analyze data from a study large enough to obtain a valid statistical comparison between CMV-seropositive and CMV- seronegative individuals. NHANES III reports CMV serology on 5,298 participants over the age of 60, of whom 86% were seropositive. Preliminary analysis indicated that the datasets for the disease and mortality outcomes above contain sufficient cases for valid statistical analysis. We will perform Cox proportional hazard regression modeling to determine the relative risk attributable to CMV, after adjusting for all possible confounders that are overrepresented in the CMV seropositive group. Additional, more exploratory analyses will be performed to guide design of future studies. These include analysis of interactions between inflammatory markers, CMV and outcome, and to determine the age and gender groups most at risk for CMV-exacerbated disease. PUBLIC HEALTH RELEVANCE: As the population ages, there is increasing effort to increase the "health-span" - i.e. the period of life in which individuals experience good health and quality of life. Inflammation is thought to be the underlying cause of many conditions that most impact health in this age group, including cardiovascular disease, cognitive decline and frailty. CMV is an infectious disease that has been implicated in these conditions, and that may contribute to inflammation. However, there is valid concern that some of the associations with CMV may have been misinterpreted. It is important to be certain whether CMV is causally involved in these conditions. If CMV is causally involved (a) anti-viral drugs might be useful adjuncts to treatment or prevention, especially if safer anti-virals can be developed, and (b) reducing the rate of CMV infection, either by vaccine development or by reducing exposure, would be a powerful public health measure.

描述（由申请人提供）：过去十年积累的证据表明，巨细胞病毒（CMV）是伴随衰老而来的免疫变化的主要原因，并且它导致老年人的多种炎症过程和死亡。该项目将分析第三次全国健康和检查调查（NHANES III，1998-2002）的数据，以确定感染巨细胞病毒（CMV）的人是否更有可能患上几种通常与衰老相关的慢性炎症性疾病（心血管疾病、认知能力下降、虚弱和骨质疏松症），以及死亡率增加（全因死亡率和心血管疾病或癌症所致死亡率）。这些终点的选择基于文献报道，即 CMV 相关生物标志物可预测疾病的发生率或过早死亡。然而，由于老年人中 CMV 血清阳性率如此之高，而且大多数研究规模较小，因此除了两项研究外，之前的所有研究都仅限于报告与 CMV 大规模免疫反应的生物标志物的关联，而不是比较 CMV 血清阳性与血清阴性的风险。由于对 CMV 免疫反应大小与衰老不良之间的关联存在其他解释，因此分析足够大的研究数据以获得 CMV 血清阳性和 CMV 血清阴性个体之间的有效统计比较非常重要。 NHANES III 报告了 5,298 名 60 岁以上参与者的 CMV 血清学结果，其中 86% 呈血清阳性。初步分析表明，上述疾病和死亡结果的数据集包含足够的病例进行有效的统计分析。在调整 CMV 血清阳性组中比例过高的所有可能的混杂因素后，我们将进行 Cox 比例风险回归模型，以确定 CMV 的相对风险。此外，还将进行更多探索性分析以指导未来研究的设计。其中包括分析炎症标志物、CMV 和结果之间的相互作用，并确定最有可能罹患 CMV 加剧疾病的年龄和性别群体。 公共卫生相关性：随着人口老龄化，人们越来越努力地延长“健康寿命”，即个人在生命中体验良好健康和生活质量的时期。炎症被认为是许多对该年龄段健康影响最大的疾病的根本原因，包括心血管疾病、认知能力下降和虚弱。 CMV 是一种与这些病症有关的传染病，可能会导致炎症。然而，人们担心某些与 CMV 的关联可能被误解了。确定 CMV 是否与这些病症有关非常重要。如果 CMV 是因果关系，那么（a）抗病毒药物可能是治疗或预防的有用辅助手段，特别是如果可以开发出更安全的抗病毒药物，并且（b）通过开发疫苗或减少接触来降低 CMV 感染率将是一项强有力的公共卫生措施。