Causal Paradigm Between Common Comorbidities of Cardiovascular and Metabolism-Related Diseases in Elderly: Evidence from Cross-Sectional and Mendelian Randomization Studies

Background: Comorbidity is a common problem among elderly people, significantly damaging individuals' health and healthcare systems. However, observational studies may be susceptible to residual confounding factors and bias. The present study aimed to assess the causal effect of common chronic disease comorbidity using the Mendelian randomization (MR) approach.Methods: Data for the present study were obtained from a community survey conducted between 2018 and 2020 in four counties in Ganzhou City, southern China. A cross-sectional survey was conducted using a multi-stage stratified random sampling method. A total of 1756 valid questionnaires were collected to analyze common chronic disease comorbidities. Genetic variants associated with hypertension, diabetes, stroke, and hyperlipidemia-related factors were selected as instrumental variables for univariate and multi-variate MR analyses.Results: The self-reported prevalence of chronic disease in the older adult population in Southern China was 68.1%, with hypertension (46.1%), diabetes (10.5%), and hyperlipidemia (8.5%) being the three most common conditions. The prevalence of chronic disease comorbidity was 20.7% among the 12 chronic diseases studied. Hypertension was identified as a predictor of diabetes (OR [95% CI]: 1.114 [1.049, 1.184], p < 0.001), and diabetes mellitus was equally identified as a risk factor for hypertension (OR [95% CI]: 1.118 [1.069, 1.187], p < 0.001). Furthermore, high triglyceride levels were identified as a risk factor for hypertension (OR [95% CI]: 1.262 [1.129, 1.411], p < 0.001). In contrast to intracranial hemorrhages, hypertension had a significant impact on ischemic stroke (OR [95% CI]: 1.299 [1.161, 1.454], p < 0.001).Conclusion: The causal association between multiple cardiovascular and metabolism-related diseases is mediated by hypertension, with a bidirectional cause-and-effect relationship between hypertension and diabetes. Hypertension is a risk factor for ischemic stroke, and the hyperlipidemia-related factor triglycerides (TG) influence hypertension. Therefore, prioritizing hypertension prevention and control in the elderly is critical for effective chronic disease management.