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

To date, several studies have reported that a history of cardiovascular disease (CVD) and traditional CVD risk factors, e.g., age, male sex, current smoking, hypertension, and diabetes, are associated with severe COVID-19. However, other than age, results have been inconsistent. Furthermore, few studies accounted for potential confounding by age and sex when they evaluated other potential risk factors. For example, some studies reported that hypertension is a risk factor of severe COVID-19, but their observations may simply reflect the fact that hypertension is more common in older adults. 3 Nonetheless, despite the lack of robust evidence, this observation, together with the fact SARS-CoV-2 uses angiotensin-converting enzyme 2 as an entry to human body, 4 has raised a concern about continued use of reninangiotensin system increase among some clinicians and researchers. 5, 6 In this context, we conducted a systematic review of studies reporting cardiovascular risk factors and their relation to severe manifestation of COVID-19 (i.e., death, acute respiratory distress syndrome [ARDS] , the need of mechanical ventilator support, and admission to an intensive care unit [ICU]), with a particular interest on studies that adjusted for key confounders such as age and sex.