Cardiovascular risk factors and evolution of patients attended with COVID-19 in a National Reference Hospital from Lima , Peru

Objectives. Coronavirus disease 2019 (COVID-19) fatal outcomes have been associated with multiple cardiovascular risk factors. In new epidemic areas, such as Latin America, there is a lack of studies about this. Here, we evaluated those factors in a retrospective cohort of patients in a national reference hospital of Lima, Peru. Design. A retrospective cohort observational study was done. For this study, information was obtained from clinical records of the hospital for the cases that were laboratory-diagnosed and related, during March 6 and April 30, 2020. rRT-PCR was used for the detection of the RNA of SARS-CoV-2 following the protocol Charité, Berlin, Germany, from nasopharyngeal swabs at the National Institute of Health. Calculation of the odds ratio (OR) with the respective 95% confidence interval (95% CI) was done, also logistic regression for adjusted OR (multivariate) was done. Values of p < 0.05 were considered significant for all analyses. Results. One hundred six hospitalized patients were evaluated. The mean age of patients was 61.58 years (SD 16.81). Cardiovascular risk factors among them were hypertension (46.2%), diabetes (28.3%), and obesity (28.3%), among others. Fifty-six patients died (52.8%). Mortality associated factors at the multivariate analysis were arterial hypertension (OR=1.343, 95% 1.089-1.667), myocardial injury (OR=1.303, 95% 1.031-1.642), and mechanical ventilation (OR 1.262, 95% 1.034-1.665), as associated factors. Conclusion. As observed in other regions of the world, cardiovascular risk factors represent a significant and independent threat to be considered in patients with COVID-19. Further studies and interventions in Peru and Latin America are expected.


Introduction
Coronaviruses are single-stranded positive-sense RNA viruses, with the capacity for rapid mutation and recombination. They are known to cause respiratory or intestinal infections in humans and animals. Moreover, acute respiratory infections including influenza, respiratory syncytial and bacterial pneumonia are triggers for cardiovascular diseases and, on the other hand, the underlying cardiovascular disorders are usually associated with comorbidities, which may increase tie incidence and severity of infectious diseases. [1][2][3] Cardiovascular complications associated with the coronavirus infection were described since infections with SARS-COV and recently with SARS-COV-2. The later generate the clinical pattern defined as COVID-19, described in the first time in December 2019 in Wuhan-China.
After that, there were mentioned direct effects of the virus and the consequences associated with the host immune response. 1,[4][5][6][7][8] Cardiovascular compromise in patients with COVID-19 has not been well studied because data is scarce. However, there were described cases of myocardial injury, myocarditis, thromboembolic disease, arrhythmias, among others. But there is no information about the longterm consequences of this disease 2,9 Edgardo Rebagliati Martins national hospital is the largest hospital of the Peruvian social security with 2,000 hospital beds and is considered as a national reference center for patients with COVID-19 and concentrate a higher quantity of severe cases associated with this clinical condition. 19 The objectives of the present study are to describe the prevalence of cardiovascular risk factors in the selected population, to evaluate the clinical findings, laboratory and electrocardiographic data, and describe the evolution of patients, taking into count the presence of some cardiovascular risk factors. The project was authorized for the emergency department and the Ethics and investigation committee for COVID-19 in EsSalud (study approval number: 83328). The principle of confidentiality was guaranteed. Informed consent was not obtained because the source document was secondary (an electronic clinical record), and there was not any intervention for the patient.

Results
One hundred six hospitalized patients were evaluated. They arrived in the emergency room with more than seven days of symptoms: 7.35 (SD 3.53).
Thirty-two cases (30.18%) had symptoms between 3 and 7 days and 54.71% with more than seven days.
The most frequent signs and symptoms during emergency arrival ( Figure 1) were dyspnea (82.07%), tachycardia (35.8%), and higher levels of blood pressure (17.9%), defined as levels over 140 mmHg of systolic or levels over 90 mmHg of diastolic pressure.
Troponin T values higher than 99 th percentile of superior reference limit, suggestive of myocardial injury was found in 40 of 79 patients tested (50.6%). The median value was 0.033 (IQR 0.047). Fifty-six patients died, which corresponds to a mortality rate of 52.8% (Figure 1). Mortality associated factors ( Table 2) were age more than 65 years, myocardial injury, mechanical ventilation, and arterial hypertension were associated with statistical differences in bivariate analysis. In the multivariate analysis, we found arterial hypertension, myocardial injury, and mechanical ventilation as associated factors (Table 2).

Discussion
The present report describes cardiovascular risk factors and some clinical, laboratory, and electrocardiography findings in a group of patients hospitalized for moderate to severe COVID-19 attended in a national reference hospital of social security. patients with chronic cardiovascular disease are more likely to be infected due to their weakened heart function and low immunity, developing severe disease patterns. [20][21][22] Recent studies indicate multi-organ tropism of SARS-CoV-2, including heart, vascular system, and the circulation, which is speculated to influence the course of the disease as well as aggravate preexisting conditions. The increased-myocardial expression of ACE2 in patients with cardiovascular disease and COVID-19 has been suggested as a possible mechanism of myocardial cell invasion and injury levels to worse outcomes. 21 Myocardial injury is manifested as an elevation of troponin levels above the 99 th percentile of superior normality level and is associated with an increase in mortality. It could be presented with electrocardiographic and echocardiographic changes. In some cases, could evolution to a fulminant myocarditis 1,2,6,15 We found a prevalence of myocardial injury of 50.6%, superior to report in the hospitalized population (7-17%), and ICU population (22-31%) 1,12,15 . Moreover, in a recent metanalysis of 26 clinical studies with 11,685 patients, the prevalence was 20%. 17 However in subpopulations of severe or critical COVID-19 cases, similar to the cases described in this report, the prevalence could be much higher: from 65.2% and 80%. 21 In a retrospective study of 191 patients, older age was recognized as a risk factor of mortality and has been reported as a significant predictor of mortality in SARS and MERS, probably because of age-dependent defects in T-cell and B-cell function and the excess production of type 2 cytokines that could amplify viral replication and prologs proinflammatory responses. 23 Other factors like the presence of comorbidities in older patients (particularly hypertension) are believed to be risk factors for severe disease and death for SARS-Cov-2 infection.
Moreover, in deceased patients, higher levels of cardiac troponins were associated with poorer outcomes and mortality, as was described in several reports. 16,24 In a recent study in Bolivia, the mortality rate was 5.6%, but age and hypertension (OR=3.284, 95%CI 1.276-6.291) were the main associated factors with the fatal outcomes, very similar to our current findings for this factor (Table 2). 26 Previously a preliminary description of patients with severe COVID-19 was reported in our hospital. This study described 17 patients, 5 of them died. Authors identified advanced age (6), arterial hypertension (4), and obesity (3), as the main observed risk factors in these patients. 27 This study is an exploratory case-series without randomization, that obtain data from electronic clinical reports. We did not register body mass index, and there was not a formal criterion to get troponin dosage or ECG recording in every patient hospitalized for COVID-19. Although there is an essential number of patients in this region, and describe the cardiovascular findings associated with this disease.

Conclusions
There is a high prevalence of cardiovascular risk factors in our patients with severe COVID-19 disease. Dyspnea, tachycardia, and a higher level of blood pressure at admission were the most frequent clinical manifestations. We found myocardial injury in almost half of the total population and ECG changes in more than a fourth of our population. On the other hand, arterial hypertension, the use of mechanical ventilation, and myocardial injury were associated with higher mortality in our patients.