Vegetable intake and cardiovascular risk: genetic evidence from Mendelian randomization

Background: Observational studies have demonstrated inverse associations between vegetable intake and cardiovascular diseases. However, the results are prone to residual confounding. The separate effects of cooked and raw vegetable intake remain unclear. This study aims to investigate the association between cooked and raw vegetable intake with cardiovascular outcomes using Mendelian randomization (MR). Methods: We identified 15 and 28 genetic variants associated statistically and biologically with cooked and raw vegetable intake, which were used as instrumental variables to estimate the associations with coronary heart disease (CHD), stroke, heart failure (HF) and atrial fibrillation (AF). In one sample analysis using individual participant data from UK Biobank, we adopted two stage least square approach. In two sample analysis, we used summary level statistics from genome-wide association analyses. The independent effects of cooked and raw vegetable intake were examined with multivariable MR analysis. The one sample and two sample estimates were combined via meta analysis. Bonferroni correction was applied for multiple comparison. Results: In the meta analysis of 1.2 million participants on average, we found null evidence for associations between cooked and raw vegetable intake with CHD, HF, or AF. Raw vegetable intake was nominally associated with stroke (odds ratio [95% confidence interval] 0.82 [0.69, 0.98] per 1 serving increase daily, p = 0.03), but this association did not pass corrected significance level. Conclusions: Cooked and raw vegetable intake was not associated with CHD, AF or HF. Raw vegetable intake is likely to reduce risk of stroke, but warrants more research. Solely increasing vegetable intake may have limited protection, if any, on cardiovascular health. This calls for more rigorous assessment on health burden associated with low vegetable consumption.