Unlike common pneumonia, COVID-19 is a risk factor for multiple cardiovascular diseases: A two-sample Mendelian randomization study

Abstract

This study investigates the differences between COVID-19 and past common forms of pneumonia and to determine if COVID-19 acts as a contributing factor in various cardiovascular diseases (CVDs). We retrieved large-sample genome-wide association study data from the Open GWAS database related to COVID-19, bacterial pneumonia (BP), viral pneumonia (VP), stable angina (SA), unstable angina (UA), heart failure (HF), ischemic heart disease (IHD), atrial fibrillation (AF), and myocardial infarction (MI). We selected single-nucleotide polymorphisms with strong correlations as instrumental variables (P < 5E-06), and set the threshold for the F-statistic to be over 10. Five statistical methods were used for analysis including inverse variance weighted, Mendelian randomization-Egger, weighted median, simple mode, and weighted mode, with inverse variance weighted as the primary method. We assessed the reliability of our results through heterogeneity, pleiotropy, and sensitivity testing; Our analysis probed the relationship between COVID-19, BP, VP, and 6 CVDs. COVID-19 infection was found to enhance the incidence of SA, UA, HF, and MI (SA: odds ratio [OR], 1.12; 95% confidence interval [CI], 1.04-1.20; P = .002; UA: OR, 1.14; 95% CI, 1.01-1.29; P = .041; HF: OR, 1.12; 95% CI, 1.03-1.23; P = .012; MI: OR, 1.11; 95% CI, 1.02-1.25; P = .032). There was no significant effect on the incidence of AF or IHD (P > .05), and no pleiotropy or sensitivity issues were found in the results. In contrast, neither past common BP nor VP was found to contribute to the progression of these 6 CVDs (P > .05). Unlike past common BP or VP, COVID-19 was found to increase the risks of SA, UA, HF, and MI, with no evidence supporting an increased risk for AF or IHD following COVID-19 infection.

Figure 1.

Mendelian randomization flow chart. AF = atrial fibrillation, COVID-19 = coronavirus disease 2019, HF = heart failure, IHD = ischemic heart disease, IVs = instrumental variables, MI = myocardial infarction, MR = Mendelian randomization, SA = stable angina, SNP = single-nucleotide polymorphism, UA = unstable angina.

Figure 2.

Two-sample Mendelian randomization analysis results. CI = confidence interval; OR = odds ratio.

Figure 3.

Scatter plots for two-sample Mendelian randomization analysis. (A) COVID-19 and SA; (B) COVID-19 and UA; (C) COVID-19 and HF; (D) COVID-19 and MI. Scatter plot represents the estimated effect of using 5 statistical methods to analyze the causal association of COVID-19 (x-axis) on each outcome (y-axis). The slope of each line represents the OR value of this method. HF = heart failure, MI = myocardial infarction, OR = odds ratio, SA = stable angina, UA = unstable angina.

Figure 4.

Two-sample Mendelian randomization analysis forest legend. (A) COVID-19 and SA; (B) COVID-19 and UA; (C) COVID-19 and HF; (D) COVID-19 and MI. Each black point in the Forest plot represents the risk effect value estimate of a single SNP of COVID-19 on the outcome, and the black line represents the 95% CI. The 2 red dots represent the estimates of the overall effect size between COVID-19 and outcome using MR-Egger and IVW respectively, and the red line represents the 95% CI. CI = confidence interval, HF = heart failure, MI = myocardial infarction, OR = odds ratio, SA = stable angina, UA = unstable angina.