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Background <p>Evidence suggests that antigout medications may influence the risk of cardiovascular diseases (CVDs), but findings remain inconsistent and may be biased by confounding and reverse causation due to the observational design of most studies.</p> Methods <p>We used a drug‑target Mendelian randomization (MR) approach to investigate the causal effects of genetically proxied inhibition of drug targets for colchicine, non‑steroidal anti‑inflammatory drugs (NSAIDs), and allopurinol on eight CVD outcomes, including angina pectoris, myocardial infarction, coronary artery disease, heart failure, arrhythmia, pericarditis, atrial fibrillation, and ischemic stroke. C‑reactive protein (CRP) was included as a positive control. The inverse variance weighted (IVW) method was used for primary causal estimation, and Bayesian colocalization was performed to strengthen instrument validity.</p> Results <p>Genetically proxied TUBB6 inhibition (colchicine target) was associated with lower risks of myocardial infarction (OR = 0.951, 95% CI: 0.913–0.990, P = 0.013), coronary artery disease (OR = 0.979, 95% CI: 0.944–0.996, P = 0.025), and heart failure with coexisting obesity (OR = 0.954, 95% CI: 0.917–0.992, P = 0.017). In contrast, genetically proxied PTGS2 inhibition (NSAID target) was associated with increased risks of stable angina (OR = 1.066, 95% CI: 1.010–1.123, P = 0.021), myocardial infarction (OR = 1.079, 95% CI: 1.013–1.148, P = 0.018), and coronary artery disease (OR = 1.045, 95% CI: 1.004–1.088, P = 0.030). Additionally, genetic proxies for allopurinol use showed an association with higher risk of stable angina (OR = 21.371, 95% CI: 2.206–207.026, P = 0.008). Colocalization generally supported shared causal variants.</p> Conclusions <p>Our findings suggest that colchicine‑related TUBB6 inhibition may confer cardiovascular protection, whereas NSAID‑related PTGS2 inhibition and allopurinol use may increase CVD risk. These gene‑targeted MR results highlight TUBB6 and PTGS2 as potential biological targets for cardiovascular prevention and risk evaluation.</p>

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The impact of anti-gout medications on eight cardiovascular diseases: a Mendelian randomized study

  • 期刊论文

  • 发表日期：

    2026年1月19日

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  • Pingping Peng,
  • Jingting Wang,
  • Miaozhen Huang,
  • Congting Hu,
  • Suyan Liu,
  • Jia Liu,
  • Jiaqin Cai,
  • Xiaoxia Wei,
  • Hong Sun

摘要

Background

Evidence suggests that antigout medications may influence the risk of cardiovascular diseases (CVDs), but findings remain inconsistent and may be biased by confounding and reverse causation due to the observational design of most studies.

Methods

We used a drug‑target Mendelian randomization (MR) approach to investigate the causal effects of genetically proxied inhibition of drug targets for colchicine, non‑steroidal anti‑inflammatory drugs (NSAIDs), and allopurinol on eight CVD outcomes, including angina pectoris, myocardial infarction, coronary artery disease, heart failure, arrhythmia, pericarditis, atrial fibrillation, and ischemic stroke. C‑reactive protein (CRP) was included as a positive control. The inverse variance weighted (IVW) method was used for primary causal estimation, and Bayesian colocalization was performed to strengthen instrument validity.

Results

Genetically proxied TUBB6 inhibition (colchicine target) was associated with lower risks of myocardial infarction (OR = 0.951, 95% CI: 0.913–0.990, P = 0.013), coronary artery disease (OR = 0.979, 95% CI: 0.944–0.996, P = 0.025), and heart failure with coexisting obesity (OR = 0.954, 95% CI: 0.917–0.992, P = 0.017). In contrast, genetically proxied PTGS2 inhibition (NSAID target) was associated with increased risks of stable angina (OR = 1.066, 95% CI: 1.010–1.123, P = 0.021), myocardial infarction (OR = 1.079, 95% CI: 1.013–1.148, P = 0.018), and coronary artery disease (OR = 1.045, 95% CI: 1.004–1.088, P = 0.030). Additionally, genetic proxies for allopurinol use showed an association with higher risk of stable angina (OR = 21.371, 95% CI: 2.206–207.026, P = 0.008). Colocalization generally supported shared causal variants.

Conclusions

Our findings suggest that colchicine‑related TUBB6 inhibition may confer cardiovascular protection, whereas NSAID‑related PTGS2 inhibition and allopurinol use may increase CVD risk. These gene‑targeted MR results highlight TUBB6 and PTGS2 as potential biological targets for cardiovascular prevention and risk evaluation.