The Association Between Psoriasis and Risk of Cardiovascular Disease: A Mendelian Randomization Analysis

Abstract

Background: A large number of observational studies showed that patients with psoriasis have a higher risk of cardiovascular disease (CVD), but most studies did not fully adjust for confounding factors, so it is not clear whether the risk of CVD is directly attributed to psoriasis. We used Mendelian randomization (MR) to evaluate the potential causal relationship between psoriasis and CVD.

Methods: We used genetic instruments from the genome-wide association study (GWAS) of European descent for psoriasis to investigate its relationship with CVD. Inverse variance-weighted (IVW) MR analyses were used for the primary analysis. In addition, a variety of other methods were used to replicate the analysis.

Results: The fixed-effects IVW method indicated that genetic susceptibility to psoriasis was associated with a higher risk of heart failure (HF) [odds ratio (OR) = 1.04; 95% CI, 1.01-1.06, P = 2.72E-03], atrial fibrillation (AF) (OR = 1.04; 95% CI, 1.02-1.07, P = 3.27E-04), myocardial infarction (MI) (OR = 1.07; 95% CI, 1.01-1.12, P = 0.01), valvular heart disease (VHD) (OR = 1.001; 95% CI, 1.000-1.002, P = 1.85E-03), and large artery stroke (LAS) (OR = 1.11; 95% CI, 1.05-1.18, P = 5.37E-04) but not with the other two subtypes of ischemic stroke (IS) [cardioembolic stroke (CES) (OR = 1.03; 95% CI, 0.98-1.07, P = 0.27) and small vessel stroke (SVS) (OR = 1.00; 95% CI, 0.95-1.07), P = 0.88)]. Sensitivity analysis found weak evidence of horizontal diversity and heterogeneity to ensure the stability of the results.

Conclusion: Our study provided evidence for a potential causal link between psoriasis and CVD. These findings partly suggest that early monitoring of cardiovascular risk in patients with psoriasis is intentional.

Keywords: Mendelian randomization (MR); cardiovascular disease; genome-wide association study (GWAS); psoriasis; the causal link.

Figure 1

Mendelian randomization estimates of psoriasis on the risk for cardiovascular disease (CVD). SNPs, single-nucleotide polymorphisms; OR, odds ratio; CI, confidence interval; IVW, inverse variance-weighted; IVW (fixed), fixed-effects inverse variance-weighted; MR-RAPS, MR-robust adjusted profile score; MR-PRESSO, MR-pleiotropy residual sum and outlier. *No outlier was detected.