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Frailty index and risk of cardiovascular diseases: a mendelian randomization study
1Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Insights
This study used Mendelian randomization to investigate the causal link between frailty index (FI) and cardiovascular diseases (CVDs). Genetic evidence supports a causal relationship between higher FI and increased risk of coronary artery disease, myocardial infarction, and heart failure.
Area of Science:
- Genetics and Cardiovascular Epidemiology
- Gerontology and Public Health
Background:
- Epidemiological studies suggest a link between frailty and cardiovascular diseases (CVDs).
- The causal relationship between frailty index (FI) and specific cardiovascular outcomes remains unclear.
Purpose of the Study:
- To investigate the potential causal association between the frailty index (FI) and major cardiovascular outcomes.
- Utilizing Mendelian randomization to assess causality between frailty and coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF).
Main Methods:
- Employed Mendelian randomization analysis using genome-wide association study (GWAS) summary statistics.
- Identified single nucleotide polymorphisms (SNPs) associated with FI from a large GWAS meta-analysis.
- Examined SNP associations with CAD, MI, AF, and HF in independent GWAS datasets and FinnGen for replication.
Main Results:
- Genetically predicted higher FI was causally associated with increased odds of CAD (OR=1.46), MI (OR=1.62), and HF (OR=1.46).
- No significant causal association was found between FI and the risk of AF (OR=1.43).
- Complementary analyses supported the main findings, reinforcing the causal link for CAD, MI, and HF.
Conclusions:
- Provided genetic evidence supporting a causal role of the frailty index in the risk of CAD, MI, and HF.
- Further research is needed to elucidate the potential causal relationship between FI and AF risk.
Background:
Previous epidemiological evidence has suggested that frailty status might be associated with cardiovascular diseases (CVDs). However, the exact causality remains unestablished. In this study, we employed Mendelian randomization and sought to investigate the potential causality in association of frailty index (FI) with cardiovascular outcomes [coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF)].
Methods:
Independent single nucleotide polymorphisms (SNPs) at genome-wide significance for FI were obtained from a recent genome-wide association study (GWAS) meta-analysis of European descent (n=175,226). The association of these SNPs with CVDs was examined in summary statistics from corresponding GWASs of European descent (CAD: 184,305 cases and 60,801 controls; MI: 184,305 cases and 43,676 controls; AF: 1,030,836 cases and 60,620 controls; and HF: 977,323 cases and 47,309 controls). Replication analyses were performed using GWAS datasets from FinnGen.
Results:
In the meta-analysis of inverse-variance weighted estimates from different data sources, genetically determined higher FI conferred an odds ratio (OR) of 1.46 [95% confidence interval (CI): 1.13 to 1.87; P=0.003] for CAD, 1.62 (95% CI: 1.21 to 2.17, P=0.001) for MI, and 1.46 (95% CI: 1.24 to 1.72; P=4.89×10-6) for HF. However, FI failed to be potentially influential on AF risk (OR, 1.43; 95% CI: 0.93 to 1.66; P=0.107). Several complementary analyses also received broadly concordant results.
Conclusions:
We have provided genetic evidence of a causal association between FI and the risk of CAD, MI, and HF. Further studies are warranted to clarify whether FI is causally related to AF risk.
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