The association between fatigue and cardiometabolic diseases: Insights from the UK biobank study 2024 Sun et al

Highlights

• The research sheds light on the reciprocal connection between fatigue and cardiometabolic diseases, underscoring the crucial role of fatigue in the context of cardiometabolic health.
• Results indicate that fatigue may function as a dual-edged factor, both as a potential risk element and an outcome of cardiometabolic diseases, with substantial implications for clinical methodologies and public health strategies.
• This mutual relationship highlights the need for deeper investigations into the impact of fatigue on disease advancement, emphasizing the essential understanding of its fundamental mechanisms for tailored intervention development.
• By elucidating the bidirectional link between fatigue and cardiometabolic diseases, the study emphasizes the necessity of integrating fatigue assessment in both research and clinical frameworks for enhanced patient outcomes.
• Understanding the intricate interplay between fatigue and cardiometabolic diseases is pivotal for comprehensive patient care, suggesting that managing fatigue could potentially improve cardiometabolic health outcomes and quality of life.

Abstract

Background
Cardiometabolic diseases (CMD) are major global health concerns with significant morbidity and mortality. Fatigue, a common but often overlooked symptom, has been postulated as both a potential risk factor for and a consequence of these conditions. However, the relationships between fatigue and CMD remain unclear. This study aimed to investigate the relationship between fatigue and CMD using observational and genetic approaches.

Method
Observational study was conducted in the UK biobank. Genetic method was employed a bidirectional MR approach to examine the causal relationship between fatigue and CMD. Genetic variants associated with fatigue were identified through a GWAS, and summary statistics from the largest available GWAS were used to obtain variants associated with stroke, CAD, T2D, and HF. Inverse variance weighting (IVW) was conducted, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. Multivariable MR and mediation analysis were also employed.

Results
Observational analyses indicated that individuals with fatigue had a significantly increased risk of developing stroke (HR 1.44, 95 % CI 1.27–1.63), T2D (HR 1.46, 95 % CI 1.41–1.51), CAD (HR 1.45, 95 % CI 1.4–1.5), and HF (HR 1.60, 95 % CI 1.52–1.68). Mendelian randomization analyses further supported a causal relationship. Additionally, observational and genetic analyses showed T2D was found to be associated with increased levels of fatigue. Mediation analysis identified lipid metabolites as mediators in the relationship between fatigue and CMD.

Conclusion
This study highlights a bidirectional relationship between fatigue and CMD, underscoring the importance of considering fatigue in the context of cardiometabolic health.

Paywall, https://www.sciencedirect.com/science/article/abs/pii/S0165032724019037