Abstract
Background: Studies have shown an association between frailty and hypertension. However, it remains uncertain whether this association reflects causality. We performed a Chinese Longitudinal Health Longevity Survey (CLHLS) analysis and a bidirectional Mendelian randomization (MR) study to assess the relationship between frailty and hypertension. Corroborative evidence for other heart diseases, including atrial fibrillation (AF), coronary artery disease (CAD), and heart failure (HF), was also analyzed. Methods: We performed the cross-sectional analysis based on CLHLS 2018 and used multivariable logistic regression to analyze the association between frailty and HTN. Then, we extracted independent single nucleotide polymorphisms for each phenotype at genome-wide significance levels from the latest genome-wide association summary data of European descent, including FI (N=175,226), HTN (N=462,933), AF (N=138,994), and HF (N= 977,323). The inverse variance weighted method was primarily used, followed by sensitivity and validation analyses. Results: In the cross-sectional study, compared to non-frail individuals, frail patients revealed a significantly higher risk of HTN (OR 5.32, 95% CI 3.46-8.17 P< 0.001) and heart disease (OR 13.50, 95% CI 8.18-22.28 P = 0.017) after full adjustment. In the MR study, higher FI significantly increased the risk of HTN (OR 1.12, 95% CI 1.07-1.16 P<0.001) and CAD (OR 2.57, 95% CI 1.72-3.84 P<0.001). FI suggestively increased the risk of AF (OR 1.83 95%CI 1.11-3.01 P<0.05). No association between FI and HF was observed (OR 1.30, 95% CI 1.00-1.71 P>0.05). In the reverse analysis, genetic predisposition to HTN (β 0.662, 95% CI 1.71, 2.19 P<0.001) and CAD (β 0.067, 95% CI 01.049-1.090 P<0.001) significantly increased FI. A suggestive causality from HF (β 0.088, 95% CI 1.000-1.192 P<0.05) to FI was also observed. No causality between AF to FI was observed (β 0.014, 95% CI 0.998-1.030 P>0.05). Conclusion: Our findings add new evidence to support the bidirectional causality between frailty and HTN. A deeper exploration of such associations is imperative to optimize the management of older patients.
Published Version
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