The relationship of COVID-19 severity with cardiovascular disease and its traditional risk factors: A systematic review and meta-analysis

Kunihiro Matsushita; Ning Ding; Minghao Kou; Xiao Hu; Mengkun Chen; Yumin Gao; Yasuyuki Honda; David Dowdy; Yejin Mok; Junichi Ishigami; Lawrence J Appel

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.04.05.20054155 doi: medRxiv preprint 3.5. An important question is whether these associations are independent of major confounders, particularly age. Although we could not obtain a definite answer as very few studies ran multivariable models, our meta-regression analysis indicated some degree of confounding by age. One study by Zhou et al showed substantial attenuation of the association between coronary heart disease and severe COVID-19. On the other hand, Liang et al showed independent associations of hypertension and diabetes with severe COVID-19 in a relatively large sample size of 1,590 patients. These is also biologic plausibility. Hypertension and diabetes are leading risk factors for CVD and kidney diseases, and there is evidence that COVID-19 damages these organs. 34, 35 Available studies provide scant evidence related to the hypothesized adverse effect of renin-angiotensin system inhibitors on severity of COVID-19 infection. As noted above, there is biological plausibility for potential associations of COVID-19 with hypertension and diabetes, two comorbidities associated with use of renin-angiotensin system inhibitors. Only one study reported the prevalence of renin-angiotensin system inhibitors use. 13 In this study, ~30% of patients reported prevalent hypertension, but only ~5% of patients were taking renin-angiotensin system inhibitors. 13 Thus, it is reasonable that many expert organizations recommend continuing this category of medications until better evidence becomes available. 4 Our results can potentially be used to guide decision-making. While the lack of discrete age thresholds for severe COVID-19 complicates this process, data on case fatality rates from three countries (Web Table 2 ) suggest that age older than 60 or 65 years confers high risk of severe COVID-19 (relative risk > ~5 compared to <50 years). Our results also indicate male sex is an independent risk factor with a pooled relative risk of ~1.7. Although it is very likely that the pooled crude relative risk of ~3-3.5 for hypertension, diabetes, and CVD overestimate their impact beyond age and sex, all or some of them may each confer 1.5-2 times greater risk. Thus, using these factors, it is possible to estimate, at least crudely, the risk of severe COVID-19. For example, a man aged 60-65 years old, with either hypertension, diabetes, or prior CVD would . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.