Association of asthma with the risk of cardiovascular disease: A Mendelian randomization study

Background: Association of asthma with the risk of cardiovascular disease has not been fully elucidated. So, this study tried to explore the genetic effect of asthma on five cardiovascular diseases and 90 peripheral cardiovascular proteins to answer the above topic. Methods: Instrumental variables predicting asthma was extracted from its genome-wide association study data. Two-sample and multivariate MR approaches were used to assess the genetic association of exposure factor (i.e., asthma) with outcome factors (i.e., hypertension, atrial fibrillation, angina pectoris, myocardial infarction, heart failure, and 90 peripheral cardiovascular proteins). Results: First, asthma nominally increased the risk of hypertension and atrial fibrillation (OR = 1.009, 95%CI = 1.003-1.016, P = 0.004; OR = 1.074, 95%CI = 1.024-1.127, P = 0.003). Second, of the 90 cardiovascular proteins, asthma was associated with the increased levels of tumor necrosis factor ligand superfamily member 14 and C-C motif chemokine 4 ((3 = 0.145, 95%CI = 0.077-0.212, P = 2.936e-05; (3 = 0.128, 95%CI = 0.063-0.193, P = 1.036e-04). Third, C-C motif chemokine 4 increased the risk of hypertension (P = 0.043); and after adjusting for this protein, asthma still increased the risk of hypertension, but the strength of its P-value changed from 0.004 to 0.011. Conclusion: Asthma was a risk factor for hypertension and atrial fibrillation at the genetic level, and C-C motif chemokine 4 might play a mediating role in the mechanism by which asthma promoted hypertension. Thus, effective control of asthma may help reduce the risk of some cardiovascular diseases in older adults.