Background: Whether cardiovascular disease (CVD) and its traditional risk factors predict severe coronavirus disease 2019 (COVID-19) is uncertain, in part, because of potential confounding by age and sex. Methods: We performed a systematic review of studies that explored pre-existing CVD and its traditional risk factors as risk factors of severe COVID-19 (defined as death, acute respiratory distress syndrome, mechanical ventilation, or intensive care unit admission). We searched PubMed and Embase for papers in English with original data (≥10 cases of severe COVID-19). Using random-effects models, we pooled relative risk (RR) estimates and conducted meta-regression analyses. Results: Of the 661 publications identified in our search, 25 papers met our inclusion criteria, with 76,638 COVID-19 patients including 11,766 severe cases. Older age was consistently associated with severe COVID-19 in all eight eligible studies, with RR >~5 in >60–65 versus <50 years. Three studies showed no change in the RR of age after adjusting for covariate(s). In univariate analyses, factors robustly associated with severe COVID-19 were male sex (10 studies; pooled RR = 1.73, [95% CI 1.50–2.01]), hypertension (8 studies; 2.87 [2.09–3.93]), diabetes (9 studies; 3.20 [2.26–4.53]), and CVD (10 studies; 4.97 [3.76–6.58]). RR for male sex was likely to be independent of age. For the other three factors, meta-regression analyses suggested confounding by age. Only four studies reported multivariable analysis, but most of them showed adjusted RR ~2 for hypertension, diabetes, and CVD. No study explored renin-angiotensin system inhibitors as a risk factor for severe COVID-19. Conclusions: Despite the potential for confounding, these results suggest that hypertension, diabetes, and CVD are independently associated with severe COVID-19 and, together with age and male sex, can be informative for predicting the risk of severe COVID-19.

Background: Whether cardiovascular disease (CVD) and its traditional risk factors predict severe coronavirus disease 2019 is uncertain, in part, because of potential confounding by age and sex.Methods: We performed a systematic review of studies that explored pre-existing CVD and its traditional risk factors as risk factors of severe COVID-19 (defined as death, acute respiratory distress syndrome, mechanical ventilation, or intensive care unit admission). We searched PubMed and Embase for papers in English with original data (≥10 cases of severe COVID-19).Using random-effects models, we pooled relative risk (RR) estimates and conducted metaregression analyses.Results: Of the 373 publications identified in our search, 15 papers met our inclusion criteria, with 51,845 COVID-19 patients including 9,066 severe cases. Older age was consistently associated with severe COVID-19 in all eight eligible studies, with RR >~5 in >60-65 vs. <50 years. Two studies showed no change in the RR of age after adjusting for covariate(s). In univariate analyses, factors significantly associated with severe COVID-19 were male sex (14 studies; pooled RR=1.70, [95%CI 1.52-1.89]), hypertension (10 studies; 2.74 [2.12-3.54]), diabetes (11 studies; 2.81 [2.01-3.93]), and CVD (9 studies; 3.58 [2.06-6.21]). RR for male sex was likely to be independent of age. Meta-regression analyses were suggestive of confounding by age for the other three factors. Only two studies reported multivariable analysis, with one showing non-significant association for CVD and the other demonstrating adjusted RR ~2 for hypertension and diabetes. No study explored renin-angiotensin system inhibitors as a risk factor for severe COVID-19.Conclusions: In addition to older age and male sex, hypertension, diabetes, and CVD were associated in univariate analyses with severe COVID-19. Although there is still uncertainty

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