key: cord-0862513-3oorfqip
authors: Salazar, Martin R.
title: Is hypertension without any other comorbidities an independent predictor for COVID‐19 severity and mortality?
date: 2020-12-23
journal: J Clin Hypertens (Greenwich)
DOI: 10.1111/jch.14144
sha: 13978dcc65da11818d597325baabf34f534ce948
doc_id: 862513
cord_uid: 3oorfqip

nan

by the increased age and higher prevalence of cardiovascular disease, both well-known risk factors for mortality in critical patients. Therefore, in order to identify independent predictors of COVID-19 mortality or severity, models should be properly adjusted to exclude potential confounding effects. 7 The study by Sun and colleagues 8 They performed a retrospective analysis of 3400 adults with confirmed COVID-19 hospitalized at two hospitals in Wuhan, China.

Patients with type 1 diabetes mellitus were excluded. The authors used a multivariate logistic analysis in order to estimate the effect of hypertension, type 2 diabetes mellitus and their combination on the risk of developing death (it was the primary outcome), respiratory failure, and severe COVID- 19 were also independent risk factors for adverse outcomes. To exclude possible confounding effects of these comorbid conditions, the authors performed a sensitivity analysis among 2304 patients who did not have any other identified comorbidities beyond hypertension or diabetes. This analysis confirmed that diabetes, but not hypertension, increased the risk of death.

The lack of relationship between hypertension and severe/ lethal COVID-19 found by Sun and colleagues 8 was contradictory with some previously published studies. Guan et al found in 1099 patients with confirmed COVID-19 that hypertension was a more prevalent condition in those who had a primary composite end point (admission to critical care unit, use of mechanical ventilation or death), 35.8% versus 13.7%. 5 Ruan and colleagues also described in 150 patients with confirmed COVID-19 that cardiovascular disease and hypertension were more frequent in patients who died compared with those who were discharged (19% versus 0%, P < .001, and 43% versus 28%, P = .07, respectively). 9 were predictors for poor outcome to a similar degree. 11 However, the adjustment was only performed for age and smoking. Thus, the | 233 COMMENTARY effect of arterial hypertension on the severity or mortality could be explained by potential confounders. Rodilla and colleagues, in a retrospective analysis of 12 226 patients who required hospital admission in Spain, found that hypertension, diabetes, coronary heart disease, heart failure, atrial fibrillation, stroke, and chronic kidney disease were significantly more frequent in non-survivals. 12 Using multivariable analysis adjusted for age and sex, the authors stated that pre-existing hypertension (but not diabetes) had an independent prognostic value for mortality in patients with COVID-19 who required hospitalization.

On the other hand, data of some studies using multivariate logistic regression models to identify independent clinical predictors for mortality or severity support the results of Sun and colleagues The studies by Chen and colleagues 13 However, diabetes mellitus (OR 2.78) but not hypertension had a significant impact on the mortality rate. 15 While the roll of hypertension without any other comorbidities in predicting death among COVID-19 patients seems debatable, diabetes appears as a well-established risk factor. The results found by Sun and colleagues 8 was consistent with many previously published studies. Since the initial COVID-19 outbreak in China several retrospective studies, 11, 16, 17 cohort studies, 18 and metanalysis 19 support the association between diabetes and COVID-19 mortality or severity. Although initial reports were mainly on people with type 2 diabetes, recent surveys have shown that individuals with type 1 diabetes are also at risk of severe COVID-19. 18 However, individuals with diabetes often had comorbidities such as hypertension, obesity, and cardiovascular disease. In a retrospective analysis of patients with COVID-19, those with diabetes had a greater prevalence of hypertension (56.9% vs 28.8%), cardiovascular disease (20.9% vs 11.1%), and cerebrovascular disease (7.8% vs 1.3%) than those without diabetes. 18 Moreover, specifically in patients with diabetes, non-survivors had a greater prevalence of comorbidities than survivors. Consistent with the study by Sun and colleagues, 8 in a Cox regression analysis performed on patients with diabetes hypertension was and independent risk factor for in-hospital death (HR 3.10, 95% CI 1.14-8.44). 18 Remarkably, in most studies, cardiovascular disease was strongly associated with poor COVID-19 outcome in univariate and multivariate analysis. The prevalence of diabetes, hypertension, and cardiovascular disease increases with age and frequently coexists in the same patient. Thus, age, vascular aging, and cardiovascular disease could be a linchpin between diabetes, hypertension, and COVID-19 poor outcomes.

Beyond the controversies regarding which are independent predictors for risk, in the clinical practice hypertension, diabetes, and chronic cardiac and renal disease identify a subset of subjects at risk of developing severe COVID-19. However, for some clinical decisions, a fine-tuning of our knowledge could be necessary.

Understanding the clinical characteristics that anticipate the worse outcome of COVID-19 is necessary for an appropriate use of the resources. For instance, when effective vaccines become available, priorities for vaccination should be defined. In this context, to identify independent risk factors appears as a critical issue, especially if a supposed risk factor is highly prevalent. Hypertension is the most prevalent risk factor: roughly one-third of the population in developed and developing countries is expected to be affected by this condition; the global prevalence of hypertension was estimated to be 1.13 billion in 2015. 20 Also, in many regions, >60% of the population above 60 years old is hypertensive. 21 While individuals with diabetes and/or established cardiovascular disease undoubtedly emerge as priorities for vaccination, the risk of individuals with hypertension without established cardiovascular disease or end-organ damage seems less well defined.

In this matter, the study of Sun and colleagues 8 does not support a significant effect of hypertension on COVID-19 mortality.

However, their conclusion should not be generalized for many reasons. First, it was a retrospective analysis performed in two hospitals of a single region of China. The prevalence of hypertension varies widely between ethnic groups and regions. Moreover, regional differences in the level of hypertension knowledge, treatment and control could modify the prevalence of established cardiovascular disease and, in consequence, the risk for severe or fatal COVID-19.

Second, the study had a surprisingly low rate of fatal events, and comparisons with other studies could be non-appropriate. For example, the study by Rodilla and colleagues 12 had 10 times higher mortality than the study by Sun and colleagues 8 Also, the scarce number of fatal events made the multivariable analysis less confident. Finally, since it was a retrospective analysis, several sources of bias related with levels of blood pressure, treatments and end-organ damage cannot be discharged. The possibility of this bias was suggested by the unexpected lower risk of diabetes plus hypertension compared to diabetes alone. Beyond these limitations, the study by Sun and colleagues 8 highlights the importance of encouraging the development of regional well designed, multivariable adjusted studies in order to identify accurate predictors for severe or fatal COVID-234 | COMMENTARY In conclusion and regarding the initial question, "Is hypertension an independent predictor of COVID-19 severity and mortality?" I believe that we cannot count on a single answer for the wide spectrum of patients with hypertension. Thus, it is probable that the answer will vary according to the severity of hypertension and the presence of other risk factors, such as end-organ damage or established cardiovascular disease. Also, the published analysis was based on self-reported or casual and office blood pressure recordings; the presence of white coat and masked hypertension could modify the relationship between hypertension and COVID-19 poor outcomes.

Finally, hypertension prevalence increases with age as well, and so do other risk factors, such as diabetes mellitus, chronic kidney disease, and cardiovascular disease. How to correct the effect caused by age, established end-organ damage, level of blood pressure and treatments, is an unresolved issue; possibly due to the high collinearity of these conditions and the inherent limitations of multivariate regression analysis.

We acknowledge Luz Salazar Landea for the final English corrections.

https://orcid.org/0000-0002-7103-5505

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Clinical characteristics of 138 Hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan

Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Clinical characteristics of coronavirus disease 2019 in China

Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention

Arterial hypertension and the risk of severity and mortality of COVID-19

Independent and Combined Effects of Hypertension and Diabetes on Clinical Outcomes in Patients with COVID-19: a retrospective cohort study of Huoshen Mountain Hospital and Guanggu Fangcang Shelter Hospital

Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

Prevalence of comorbidities and its effects in coronavirus disease 2019 patients: a systematic review and meta-analysis

Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis

Association of hypertension with all-cause mortality among hospitalized patients with COVID-19

Analysis of myocardial injury in patients with COVID-19 and association between concomitant cardiovascular diseases and severity of COVID-19

Age and multimorbidity predict death among COVID-19 patients: results of the SARS-RAS Study of the Italian Society of Hypertension

Coronavirus disease (COVID-19): a systematic review and meta-analysis to evaluate the impact of various comorbidities on serious events

Association of diabetes mellitus with disease severity and prognosis in COVID-19: a retrospective cohort study

Factors associated with hospital admission and critical illness among 5279 people with corona virus disease 2019 in New York City: prospective cohort study

Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole population study

Diabetic patients with COVID-19 infection are at higher risk of ICU admission and poor short-term outcome

Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants

Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries

How to cite this article: Salazar MR. Is hypertension without any other comorbidities an independent predictor for COVID-19 severity and mortality