Cardiovascular risk factors and mortality in hospitalized patients with COVID-19: systematic review and meta-analysis of 45 studies and 18,300 patients

Abstract

Background: A high prevalence of cardiovascular risk factors including age, male sex, hypertension, diabetes, and tobacco use, has been reported in patients with Coronavirus disease 2019 (COVID-19) who experienced adverse outcome. The aim of this study was to investigate the relationship between cardiovascular risk factors and in-hospital mortality in patients with COVID-19.

Methods: MEDLINE, Cochrane, Web of Sciences, and SCOPUS were searched for retrospective or prospective observational studies reporting data on cardiovascular risk factors and in-hospital mortality in patients with COVID-19. Univariable and multivariable age-adjusted analyses were conducted to evaluate the association between cardiovascular risk factors and the occurrence of in-hospital death.

Results: The analysis included 45 studies enrolling 18,300 patients. The pooled estimate of in-hospital mortality was 12% (95% CI 9-15%). The univariable meta-regression analysis showed a significant association between age (coefficient: 1.06; 95% CI 1.04-1.09; p < 0.001), diabetes (coefficient: 1.04; 95% CI 1.02-1.07; p < 0.001) and hypertension (coefficient: 1.01; 95% CI 1.01-1.03; p = 0.013) with in-hospital death. Male sex and smoking did not significantly affect mortality. At multivariable age-adjusted meta-regression analysis, diabetes was significantly associated with in-hospital mortality (coefficient: 1.02; 95% CI 1.01-1.05; p = 0.043); conversely, hypertension was no longer significant after adjustment for age (coefficient: 1.00; 95% CI 0.99-1.01; p = 0.820). A significant association between age and in-hospital mortality was confirmed in all multivariable models.

Conclusions: This meta-analysis suggests that older age and diabetes are associated with higher risk of in-hospital mortality in patients infected by SARS-CoV-2. Conversely, male sex, hypertension, and smoking did not independently correlate with fatal outcome.

Keywords: COVID-19; Cardiovascular risk factors; Diabetes; Hypertension; Mortality; Novel coronavirus; Outcome; SARS-CoV-2; Smoking.

Fig. 1

Flow diagram of the study selection process

Fig. 2

Individual and overall incidence for in-hospital mortality and ARDS. Solid squares indicate the weighted estimate of incidence for each single study; horizontal bars indicate 95% CI; red diamond indicates the overall estimated incidence

Fig. 3

Exploratory analyses for the effects of ARDS, IMV and ICU on in-hospital mortality. Scatter plots showing the association between the proportion of ARDS and IMV use and in-hospital mortality (a, b). Each circle size represents a study, telescoped by its weight in the analysis. The x-axis shows the prevalence of each covariate. The y-axis shows the incidence of in-hospital mortality. The regression line is calculated by the univariable meta-regression model. Subgroup analysis for studies including only ICU patients versus studies enrolling mixed population (both ward and ICU; c). Solid squares indicate the weighted estimate of incidence for each single study; horizontal bars indicate 95% CI; red diamond indicates the overall estimated incidence. ARDS acute respiratory distress syndrome, ICU intensive care unit, IMV invasive mechanical ventilation

Fig. 4

Meta-Regression analysis of the effects of cardiovascular risk factors on in-hospital mortality. Scatter plots showing the association between cardiovascular risk factors and in-hospital mortality. Each circle size represents a study, telescoped by its weight in the analysis. The x-axis shows the prevalence of each covariate. The y-axis shows the incidence of in-hospital mortality. The regression line is calculated by the univariable meta-regression model

Fig. 5

Funnel plot for in-hospital mortality. The analysis showed no asymmetry suggestive for a significant risk of publication bias