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; 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）：在过去的十年中积累证据表明巨细胞病毒（CMV）是伴随衰老的免疫学变化的主要原因，并且它有助于老年人的多种炎症过程和死亡率。该项目将分析第三次全国健康和检查调查（NHANES III，1998- 2002年）的数据，以确定感染巨细胞病毒（CMV）的人是否面临着几种慢性炎症状况的风险更大，通常与衰老相关（心血管疾病，心脏疾病，认知能力下降，脆弱和稳定疾病），以及均与抗疾病相关的疾病，以及均与疾病相关的疾病，以及均与疾病相关的疾病，以及均与抗疾病的抗病性和抗菌被抗病。这些终点是根据文献报道选择的，即CMV相关的生物标志物预测疾病或过早死亡的发生率。但是，由于老年人的CMV血清阳性效率很高，而且大多数研究都很小，因此除了先前的两项研究以外，所有研究都仅限于报告与对CMV有较大免疫反应的生物标志物的关联，而不是比较CMV血清毒素的风险。由于有其他解释是对CMV的免疫反应和衰老不良之间的关联，因此分析来自足够大的研究数据以获得CMV - 呼吸阳性和CMV- Seronegative个体之间的有效统计比较非常重要。 NHANES III报告了60岁以上5,298名参与者的CMV血清学，其中86％的血清具有血清阳性。初步分析表明，上述疾病和死亡率的数据集包含足够的病例进行有效的统计分析。在调整了CMV血清阳性组中所有可能的混杂因素之后，我们将执行COX比例危害回归模型，以确定CMV归因的相对风险。还将进行更多的探索性分析，以指导未来研究的设计。其中包括分析炎症标记，CMV和结果之间的相互作用，并确定最有可能患有CMV的疾病风险的年龄和性别群体。 公共卫生相关性：随着人口年龄的增长，增加“健康跨度”的努力 - 即个人经历良好健康和生活质量的生活时期。炎症被认为是许多疾病的根本原因，这些疾病在该年龄段中最大程度地影响健康，包括心血管疾病，认知能力下降和脆弱。 CMV是一种与这些疾病有关的传染病，可能导致炎症。但是，有效的担忧是，与CMV的某些关联可能已经误解了。重要的是要确定CMV是否因因果关系参与这些条件。如果CMV因果关系涉及（a）抗病毒药物可能是治疗或预防的有用辅助手段，尤其是如果可以开发出更安全的抗病毒药物，并且（b）通过疫苗发育或通过降低暴露率降低CMV感染的速度，将是一项有力的公共健康措施。