{"title":"Observational and genetic associations between cardiorespiratory fitness and age-related diseases: longitudinal analyses in the UK Biobank study.","authors":"Huimin Lu, Haotian Wang, Cancan Li, Xiaoni Meng, Deqiang Zheng, Lijuan Wu, Youxin Wang","doi":"10.1007/s13167-024-00382-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Observational studies have indicated that increased cardiorespiratory fitness is associated with a decreased risk of cardiovascular disease (CVD), Alzheimer's disease (AD), and Parkinson's disease (PD). However, the causal mechanisms remain unclear. The objective of this study was to assess the role of fitness in the early detection and reduction of disease risk within the framework of predictive, preventive, and personalized medicine (PPPM/3PM).</p><p><strong>Methods: </strong>The associations of fitness with CVD, AD, and PD were explored in a large cohort of up to 502,486 individuals between the ages of 40 and 69 years from the UK Biobank. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CVD, AD, and PD among participants who completed a submaximal fitness test. Causality relationships were assessed via two-sample Mendelian randomization (MR).</p><p><strong>Results: </strong>After a median of 11 years of follow-up, each 3.5 ml of O<sub>2</sub>⋅min<sup>-1</sup>⋅kg<sup>-1</sup> increase in total body mass (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviations (SDs)) was associated with decreased risks of CVD (20.0%, 95% CI 17.6-22.3%), AD (31.9%, 95% CI 26.7-33.6%), and PD (21.2%, 95% CI 11.2-31.8%). After adjusting for obesity, the observational associations were attenuated. According to the MR analyses, fitness was associated with PD (OR <sub><i>IVW</i></sub> 0.937, 95% CI 0.897-0.978) and small vessel stroke (OR <sub><i>IVW</i></sub> 0.964, 95% CI 0.933-0.995).</p><p><strong>Conclusion: </strong>Our results indicate that fitness has an effect on age-related diseases. Protective associations of higher fitness levels with the risk of CVD, AD, and PD were validated in this cohort study. These findings might be valuable for predicting, preventing, and reducing disease morbidity and mortality through primary prevention and healthcare in the context of PPPM.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-024-00382-4.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"15 4","pages":"629-641"},"PeriodicalIF":5.9000,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612119/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The EPMA journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s13167-024-00382-4","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Observational studies have indicated that increased cardiorespiratory fitness is associated with a decreased risk of cardiovascular disease (CVD), Alzheimer's disease (AD), and Parkinson's disease (PD). However, the causal mechanisms remain unclear. The objective of this study was to assess the role of fitness in the early detection and reduction of disease risk within the framework of predictive, preventive, and personalized medicine (PPPM/3PM).
Methods: The associations of fitness with CVD, AD, and PD were explored in a large cohort of up to 502,486 individuals between the ages of 40 and 69 years from the UK Biobank. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CVD, AD, and PD among participants who completed a submaximal fitness test. Causality relationships were assessed via two-sample Mendelian randomization (MR).
Results: After a median of 11 years of follow-up, each 3.5 ml of O2⋅min-1⋅kg-1 increase in total body mass (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviations (SDs)) was associated with decreased risks of CVD (20.0%, 95% CI 17.6-22.3%), AD (31.9%, 95% CI 26.7-33.6%), and PD (21.2%, 95% CI 11.2-31.8%). After adjusting for obesity, the observational associations were attenuated. According to the MR analyses, fitness was associated with PD (OR IVW 0.937, 95% CI 0.897-0.978) and small vessel stroke (OR IVW 0.964, 95% CI 0.933-0.995).
Conclusion: Our results indicate that fitness has an effect on age-related diseases. Protective associations of higher fitness levels with the risk of CVD, AD, and PD were validated in this cohort study. These findings might be valuable for predicting, preventing, and reducing disease morbidity and mortality through primary prevention and healthcare in the context of PPPM.
Supplementary information: The online version contains supplementary material available at 10.1007/s13167-024-00382-4.
背景：观察性研究表明，心肺健康的增加与心血管疾病（CVD）、阿尔茨海默病（AD）和帕金森病（PD）的风险降低有关。然而，其因果机制尚不清楚。本研究的目的是评估健康在预测、预防和个性化医疗（PPPM/3PM）框架下早期发现和降低疾病风险中的作用。方法：对来自英国生物银行的年龄在40至69岁之间的502,486人进行了大规模队列研究，探讨了健康与CVD、AD和PD的关系。Cox比例风险模型用于估计完成亚极大适合度测试的参与者患CVD、AD和PD风险的风险比（hr）和95%置信区间（ci）。通过双样本孟德尔随机化（MR）评估因果关系。结果：中位随访11年后，总体重每增加3.5 ml O2⋅min-1⋅kg-1（相当于1个代谢当量任务（MET），约0.5个标准差（sd））与CVD （20.0%, 95% CI 17.6-22.3%）、AD （31.9%, 95% CI 26.7-33.6%）和PD （21.2%, 95% CI 11.2-31.8%）的风险降低相关。在调整肥胖因素后，观察性关联减弱。根据MR分析，适应度与PD （OR IVW 0.937, 95% CI 0.897-0.978）和小血管卒中（OR IVW 0.964, 95% CI 0.933-0.995）相关。结论：我们的研究结果表明，健身对年龄相关疾病有影响。在这项队列研究中证实了较高的健康水平与心血管疾病、AD和PD风险的保护性关联。这些发现可能对在PPPM背景下通过初级预防和保健来预测、预防和降低疾病发病率和死亡率有价值。补充信息：在线版本包含补充资料，可在10.1007/s13167-024-00382-4获得。
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