Abstract
AIMS: Cardiovascular disease is the leading cause of death worldwide. Anxiety disorders are common psychiatric conditions associated with cardiovascular outcomes. This two-sample Mendelian randomization (MR) study investigated the causal relationship between anxiety disorders and coronary heart disease (CHD), myocardial infarction (MI), heart failure (HF), and atrial fibrillation (AF). METHODS: Single nucleotide polymorphisms (SNPs) associated with anxiety disorders (16 730 cases; 101 021 controls) were obtained from the UK Biobank genome-wide association study (GWAS). Cardiovascular outcome data were derived from the FinnGen study (CHD: 21 012 cases and 197 780 controls; MI: 12 801 cases and 187 840 controls; HF: 23 397 cases and 194 811 controls; and AF: 22 068 cases and 116 926 controls). Inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode analyses examined causality. RESULTS: IVW analysis demonstrated significant causal relationships between anxiety disorders and increased risk of CHD [odds ratio (OR): 4.496; 95% confidence interval (CI): 1.777-11.378; P = 0.002], MI (OR: 5.042; 95% CI: 1.451-17.518; P = 0.011), and HF (OR: 3.255; 95% CI: 1.461-7.252; P = 0.004). No relationship was observed with AF (OR: 1.775; 95% CI: 0.612-5.146; P = 0.29). Other methods showed non-significant associations. Two-way analysis indicated no reverse causality. CONCLUSIONS: Anxiety disorders were causally associated with greater risk of CHD, MI, and HF but not AF among individuals of European descent. Further research on mediating mechanisms and in diverse populations is warranted.