key: cord-0877553-el11o2cg
authors: Botly, Leigh C.P.; Martin-Rhee, Michelle; Kasiban, Adrienne; Swartz, Richard H.; Mulvagh, Sharon L.; Lindsay, M. Patrice; Goia, Cristina; Smith, Eric E.; Hill, Michael D.; Field, Thalia S.; Krahn, Andrew D.; Oudit, Gavin Y.; Zieroth, Shelley; Yip, Cindy Y.Y.
title: COVID-19 Pandemic: Global Impact and Potential Implications for Cardiovascular Disease in Canada
date: 2020-06-06
journal: CJC Open
DOI: 10.1016/j.cjco.2020.06.003
sha: 62122b2909a1741aad2f477628b92bb1f4f4eede
doc_id: 877553
cord_uid: el11o2cg

BACKGROUND: Literature indicates that cardiovascular disease (CVD, including stroke), older age, and availability of healthcare resources impact COVID-19 case fatality rates (CFR). The cumulative effect of COVID-19 CFR in global CVD populations and the extrapolated impact on access to healthcare services in the CVD population in Canada are not fully known. This study explored the relationships of factors that may impact COVID-19 CFR and estimated the potential indirect impact of COVID-19 on Canadian healthcare resources. METHODS: Country-level epidemiological data were analyzed to study the correlation, main effect, and interaction between COVID-19 CFR and: a) proportion of the population with CVD, b) proportion of the population ≥ 65 years, and c) availability of essential health services as defined by the World Health Organization Universal Health Coverage (UHC) index. For indirect implications on healthcare resources, estimates of the volume of postponed coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) and valve surgeries in Ontario were calculated. RESULTS: Positive correlations were found between COVID-19 CFR and a) proportion of the population with CVD (ρ=0.40, p=0.001), b) proportion of the population ≥ 65 years (ρ=0.43, p=0.0005) and c) UHC index (ρ=0.27, p=0.03). For every 1% increase in proportion of the population ≥ 65 years or proportion of the population with CVD, COVID-19 CFR was 9% and 19% higher, respectively. Approximately 1,252 procedures would be postponed monthly in Ontario due to current public health measures. CONCLUSIONS: Countries with more prevalent CVD reported higher COVID-19 CFR. Strain on healthcare resources is likely in Canada.

A growing number of publications indicate that underlying cardiovascular disease (CVD, 2 including stroke), older age (≥ 65 years), and availability of healthcare resources can impact the 3 risk of fatality from COVID-19 [1] [2] [3] [4] [5] [6] [7] . Underlying CVD confers up to a four times greater COVID- 4 19 mortality risk relative to those without CVD 4, 8 . Moreover, upwards of 20% of hospitalized 5 COVID-19 patients develop cardiac injury with a mortality rate as high as 51% 4, 9 . Variation in 6 healthcare resource availability and accessibility was linked to regional disparities in COVID-19 7 mortality rates 7 and differences in the reporting of COVID-19 test rates may influence the 8 interpretation of case fatality rates (CFR) 10 . The cumulative effect of proportion of the 9 population with CVD, proportion of the population ≥ 65 years, and availability of essential 10 health services on COVID-19 CFR in global CVD populations is not known. 11 Further to the immediate impact that an increased risk of COVID-19 mortality will have 12 on individuals with CVD, this pandemic may have long lasting implications for healthcare 13 resources supporting CVD populations. Additional strain on the health of CVD populations and 14 healthcare resources is implicit, due to a combination of factors including postponement of non- 15 urgent CVD medical appointments and procedures in order to create capacity for COVID-19 16 patients, adherence to appropriate public health measures, and rationing of personal protective 17 equipment 11, 12 . The extrapolated impact on access to healthcare services in the CVD population 18 in Canada has not been reported. This information may inform healthcare planners on the 19 anticipated changes in healthcare demand caused by disruption to the continuity of CVD care. 20 The goal of Heart and Stroke Foundation of Canada (HSFC) is to work with its partners 21 to expedite knowledge translation and facilitate changes to clinical practice with the aim of 22 improving outcomes for people with CVD. Herein, an analysis of country-level epidemiological data was conducted to explore how the factors of proportion of the population with CVD, 1 proportion of the population ≥ 65 years, availability of essential health services as defined by the 

Data sources for analysis: 13 COVID-19 CFR. Data on COVID-19 CFR by country were obtained from global 14 epidemiological data from January 21 to April 30, 2020 extracted from WHO Situation Reports 13 15 and from the Johns Hopkins University (JHU) Center for Systems Science and Engineering 14 . 16 Only countries with at least 60 days since first confirmed cases of COVID-19 were included in 17 this study. The CFR as defined by the WHO is the proportion of reported cases of a specific 18 disease or condition which are fatal within a specified time. Proportion of population ≥ 65 years. Data on country-specific population age distribution 10 were obtained from the World Bank 18 and United Nations 19 for the year 2017 to ensure time 11 period consistency with the global CVD and health services data. 12 Affordability and access to health services. The WHO Universal Health Coverage (UHC) 13 service coverage index 20 was used as a measure of availability of essential health services in each 14 country 21 . The UHC service coverage index is comprised of sixteen tracer indicators, which 15 cover four essential health services categories of reproductive, maternal, newborn, and child 16 health; infectious diseases; non-communicable diseases; and services capacity and access. 17 Across countries, the median value associated with this index was 65 out of 100, with a range of Statistical analyses: 6 The relationships among key variables were assessed using Spearman rank correlations. 7 These were calculated between COVID-19 CFR and a) proportion of the population with CVD, 8 b) proportion of the population ≥ 65 years, c) UHC index, and d) test rate. The Spearman rank 9 correlation was chosen as it is non-parametric. 10 To further explore possible collinearity, a linear regression model was fitted with 11 COVID-19 CFR as the outcome variable, and proportion of the population with CVD, proportion 12 of the population ≥ 65 years and UHC index as independent variables. All three independent 13 variables were continuous. variables were continuous. A stepwise selection method was used to determine best fit. UHC 8 index was not included as an independent variable in these two models as the UHC index for 15 9 of the 18 countries was skewed to the upper range (i.e. UHC index ≥70; Table 1 ). 10 At the time of this study, the expected duration of imposed public health measures was 11 unknown. Data on percentage decrease in CVD procedures were available from the CorHealth Figure 1 and Table 2 ]. Of note, proportion of the population with CVD and proportion 4 of the population ≥ 65 years were highly correlated (ρ=0.93, p=0.0001). 5 The linear regression revealed a variance inflation factor (VIF) of 7.5 and 7.9 for Table S4 ). This indicated high collinearity between these variables and 8 identified the need to separate out these predictors to determine their unique relationships to 9 COVID-19 CFR. 10 A total of four negative binomial regression models (1a, 1b, 2a and 2b) were performed. (Table 3) . 16 The interaction between UHC index and proportion of the population with CVD was marginally 17 significant (interaction β=0.80, 95% CI= 0.01 to 1.59, p=0.05; Table 3 ). In Model 1b, the 18 interaction between proportion of the population ≥ 65 years and UHC index on COVID-19 CFR 19 was not significant (interaction β=0.32, 95% CI= -0.11 to 0.76, p=0.15; Table 3 ). 20 Model 2 added test rate as an independent variable and included only countries that 21 reported the number of individuals tested per 100,000. There were 18 countries included in this 22 analysis. Two separate models (Model 2a and 2b) (Table 4) . 16 

To date, the majority of publications on COVID-19 have been limited to cohorts from 18 China, Italy and the United States. Incorporating data from 63 countries, the findings from this 19 study suggest that the cumulative impact and interaction of proportion of the population with 20 CVD, proportion of the population ≥ 65 years, and availability of healthcare services on COVID- 21 19 CFR is complex. Regression modelling showed a nuanced pattern of relationships between 22 these variables. Surprisingly, the proportion of the population with CVD was only related to higher COVID-19 CFR in countries with a higher UHC index, such as Canada. While further 1 studies are necessary to fully understand this unexpected finding, one possible explanation is that 2 more available essential healthcare services in these countries may lead to more individuals 3 surviving and living with CVD relative to countries with less healthcare availability. Indeed, 4 three quarters of global CVD deaths take place in low-and middle-income countries 23 When evaluating the relationship for countries such as Canada that report COVID-19 test 12 rate as the number of people tested per 100,000, COVID-19 test rate alone negatively affected 13 COVID-19 CFR. That is, countries conducting more COVID-19 tests had lower COVID-19 14 CFR. For every 1% increase in COVID-19 test rate, one would expect COVID-19 CFR to be 4% 15 lower. This may be driven by both causative and correlative factors. Countries that have higher 16 test rates for COVID-19 are likely capturing a greater number of milder and asymptomatic cases, 17 increasing the size of the denominator used to calculate the CFR and thereby reducing the CFR. 18 These countries may have more available healthcare resources to treat people infected with 19 SARS-CoV-2. However, when evaluating the interactions between test rate and proportion of the 20 population with CVD or proportion of the population ≥ 65 years, no interactions were found. 21 This means, independent of test rate, higher COVID-19 CFR were observed in countries whose It is important to note that the results of all correlation analyses and regression modelling 4 are based on country-level data and the relationships reported between variables should not be 5 generalized to the individual patient level. There were several limitations to this study. First, 6 male sex has been reported to be a risk factor for COVID-19 mortality 27 . However, country-7 specific sex-disaggregated data for COVID-19 CFR were unavailable at the time of this study 8 and including sex as an independent variable in the analyses was not possible. Second, there was 9 significant variation in how countries report test rate, which limited our ability to evaluate the Sample size of 63. 

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