Literature DB >> 36082666

Impact of Arterial Hypertension and Use of Antihypertensive Pharmacotherapy on Mortality in Patients Hospitalized due to COVID-19: The CRACoV-HHS Study.

Wiktoria Wojciechowska1, Michał Terlecki1, Marek Klocek1, Agnieszka Pac2, Agnieszka Olszanecka1, Katarzyna Stolarz-Skrzypek1, Marek Jastrzębski1, Piotr Jankowski1, Aleksandra Ostrowska1, Tomasz Drożdż1, Aleksander Prejbisz3, Piotr Dobrowolski3, Andrzej Januszewicz3, Marcin Krzanowski4, Maciej T Małecki5, Tomasz Grodzicki6, Reinhold Kreutz7, Marek Rajzer1.   

Abstract

BACKGROUND: Cardiovascular diseases including arterial hypertension are common comorbidities among patients hospitalized due to COVID-19. We assessed the influence of preexisting hypertension and its pharmacological treatment on in-hospital mortality in patients hospitalized with COVID-19.
METHODS: We studied all consecutive patients who were admitted to the University Hospital in Krakow, Poland, due to COVID-19 between March 2020 and May 2021. Data of 5191 patients (mean age 61.9±16.7 years, 45.2% female) were analyzed.
RESULTS: The median hospitalization time was 14 days, and the mortality rate was 18.4%. About a quarter of patients had an established cardiovascular disease including coronary artery disease (16.6%) or stroke (7.6%). Patients with hypertension (58.3%) were older and had more comorbidities than patients without hypertension. In multivariable logistic regression analysis, age above median (64 years), male gender, history of heart failure or chronic kidney disease, and higher C-reactive protein level, but not preexisting hypertension, were independent risk factors for in-hospital death in the whole study group. Patients with hypertension already treated (n=1723) with any first-line antihypertensive drug (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, or thiazide/thiazide-like diuretics) had a significantly lower risk of in-hospital death (odds ratio, 0.25 [95% CI, 0.2-0.3]; P<0.001) compared to nontreated hypertensives (n=1305).
CONCLUSIONS: Although the diagnosis of preexisting hypertension per se had no significant impact on in-hospital mortality among patients with COVID-19, treatment with any first-line blood pressure-lowering drug had a profound beneficial effect on survival in patients with hypertension. These data support the need for antihypertensive pharmacological treatment during the COVID-19 pandemic.

Entities:  

Keywords:  COVID-19; blood pressure; hypertension; mortality; pandemic; risk factors

Year:  2022        PMID: 36082666      PMCID: PMC9553221          DOI: 10.1161/HYPERTENSIONAHA.122.19575

Source DB:  PubMed          Journal:  Hypertension        ISSN: 0194-911X            Impact factor:   9.897


Our study for the first time confirms the importance of antihypertensive treatment for the improvement of survival in patients with hypertension hospitalized due to COVID-19. The use of each main antihypertensive drug class improves the prognosis of patients with hypertension hospitalized with COVID-19.

Clinical/Pathophysiological Implications?

Study results provide strong support for the use of antihypertensive treatment during the COVID-19 pandemic, thus there is no reason to discontinue or change the given antihypertensive drug only because of the fact of the SARS-CoV-2 infection. It would be difficult to indicate another phenomenon in recent history that has changed the lives of people around the world as significantly as the COVID-19.[1] Indeed, COVID-19, despite unprecedented restrictions in daily life, has led to a crisis in health care systems causing millions of serious health complications and over 6.3 million deaths worldwide.[2] Cardiovascular diseases, arterial hypertension, and diabetes were identified very early as common comorbidities, particularly in patients hospitalized due to COVID-19.[3,4] Further publications have provided evidence for the prognostic significance of these diseases for the COVID-19 severity and mortality.[5-7] Accordingly, the World Health Organization stated that people with preexisting noncommunicable diseases, including hypertension, appeared to be more vulnerable to developing a severe form of COVID-19.[8] Initial studies also reported arterial hypertension as an independent predictor of COVID-19 severity as indicated by the need for hospitalization, occurrence of acute respiratory distress syndrome, admission to intensive care units (ICU), and mortality.[7-9] However, recent studies have shown that hypertension may not represent an independent predictor of mortality in COVID-19, particularly after accounting for age and other comorbidities in adjusted analyses.[10-13] The role of antihypertensive treatment and more specifically, the relevance of renin-angiotensin-system blockers was also extensively discussed and investigated during the initial phase of the COVID-19 pandemic.[1,10,13-15] This was largely driven by the hypothesis that treatment with renin-angiotensin-system-blockers, that is, ACE (angiotensin-converting enzyme) inhibitors or angiotensin receptor blockers (ARB), may increase the risk for COVID-19 based on an unfavorable interaction with ACE2 representing the cell-entry receptor for the SARS-CoV2 virus.[16] However, a large number of original studies and meta-analyses discarded the initial findings suggesting poorer COVID-19 outcomes in patients using ACE inhibitors/ARB.[17] Nevertheless, the relevance of preexisting hypertension, its treatment as well as blood pressure (BP) control through treatment among patients with COVID-19 are still not clear and represent important knowledge gaps.[13,18] The aim of the current study was to assess the influence of diagnosed arterial hypertension and its treatment with first-line BP-lowering drugs on in-hospital mortality in patients with COVID-19, including the impact of other risk factors and comorbidities.

Methods

In this retrospective study, all consecutive patients who were admitted between 6 March 2020 and 13 May 2021 to the University Hospital in Krakow (Poland), which was converted temporarily into an infectious disease hospital dedicated only to COVID-19 treatment, were included in this study (CRACoV-HHS Study [Cracow in COVID Pandemics - Home, Hospital and Staff]). Data available on request from the authors. Patients were admitted from the whole Malopolska Voivodship and neighboring regions. The Małopolska Voivodship is one of 16 administrative regions in Poland with its capital in Krakow. Over 3.4 million people live in an area of 15 108 square kilometers, mostly Poles of White descent. Patients were diagnosed with COVID-19 according to World Health Organization and Polish guidelines with the use of real-time polymerase chain reaction.[19-21] The treatment algorithm for COVID-19 was in accordance with the recommendations of the Polish Association of Epidemiologists and Infectiologists.[20,21] Individual patient data were obtained from the Hospital Information System. Information on diagnosis of hypertension, other cardiovascular risk factors, and comorbidities were identified based on the medical history of prehospital diagnoses. Importantly, the diagnosis of hypertension was based on prehospital data about hypertension diagnosis or treatment. Diagnosis of hypertension was based on the current European Society of Cardiology Guidelines,[22] that is, systolic BP ≥140 mm Hg or diastolic ≥90 mm Hg measured at two different ambulatory visits. BP values obtained at admission to the hospital due to COVID-19 were not considered as a criterion for hypertension diagnosis. Prehospital diagnosis of hyperlipidemia and diabetes was established according to criteria provided by the European Guidelines,[23,24] whereas obesity was defined as body mass index ≥30 kg/m2. Data on drug treatment including antihypertensive treatment were also obtained from in-hospital medical records. The primary end point of our study was in-hospital mortality from any cause. The study was approved by the Jagiellonian University Ethics Committee, decision number 1072.6120.278.2020. The retrospective nature of the analysis precluded the collection of separate informed consents. Before admission, each patient signed an agreement to be hospitalized and to have their data processed. Approval by the Local Ethics committee was granted to use anonymized data from Hospital Information System for this study.

Statistical Analysis

We used the SAS software, version 9.3 (SAS Institute, Cary, NC), for database management and statistical analysis. The results were expressed as numerical values and percentages for categorical variables and mean values and SD if normally distributed (assessed using the Kolmogorov-Smirnov test) or median and interquartile range for continuous variables. To test the differences between patients with COVID-19 with and without preexisting hypertension and between treated and untreated hypertensives in means and proportions, we applied the t test and the χ2 statistic, respectively, while in the case of nonparametric data, the Wilcoxon Rank-sum test was used. We also adjusted these differences for age by means of a general regression model. In multivariable logistic regression, we searched for possible covariates of the likelihood of in-hospital death. Then odds ratios and corresponding 95% CI were calculated for covariates influencing in-hospital death. Then, separate models were constructed for patients with and without hypertension, treated and untreated hypertensives as well as for patients with cardiovascular risk factors but without comorbidities, that is, coronary artery disease and stroke or heart failure and chronic kidney disease and selected drugs used in pharmacological treatment. We also constructed separate models for each antihypertensive drug class to assess the effect of their use in patients with hypertension (each model besides the antihypertensive drug class use versus not use, included: age, gender, diabetes, atrial fibrillation, coronary artery disease, heart failure, stroke, chronic kidney disease, chronic obstructive pulmonary disease, cancer, and increase of highly sensitive C-reactive protein). Patients with missing data were excluded from regression analyses. In all analyses, a P value of ≤0.05 was considered statistically significant.

Results

During analyzed period a total of 5191 patients (mean age, 61.9± 16.7 years) were hospitalized due to COVID-19 and completed their hospital course (ie, from admission to discharge or death). The study sample comprised 2348 women (mean age, 62.6±17.9 years) and 2843 men (mean age 61.2±15.6 years). A preexisting diagnosis of arterial hypertension was recorded in 3028 patients (58%), rendering this diagnosis the most common cardiovascular risk factor, followed by diabetes (26.2%), hyperlipidemia (20.7%), and obesity (17.5%, Table 1). The prevalence of preexisting chronic diseases is summarized in Table 1; about a quarter of patients had an established cardiovascular disease, that is, coronary artery disease (16.6%) or stroke (7.6%).
Table 1.

Initial Characteristics of the Patients

Initial Characteristics of the Patients The median time of hospitalization was 14 days (Table 2). Admission to the ICU was needed in 12.2% of patients, and the median length of ICU stay was 11 days. The overall in-hospital mortality was 18.4% (953 of 5191 patients, Table 2). In-hospital mortality was significantly higher among patients older than 64 years (the median age in the study cohort) compared to younger patients (14.7% versus 3.6%, P<0.01).
Table 2.

Clinical Characteristics, Drug Therapy, and Outcomes During Hospitalization

Clinical Characteristics, Drug Therapy, and Outcomes During Hospitalization Overall, 33.2% of patients were treated with first-line BP-lowering drugs, including 14.7% of patients using ACE inhibitors, 5.3% ARBs, 28.9% ß-blockers, 13.5% calcium channel blockers, 6.5% thiazide or thiazide-like diuretics; 30% were treated with loop diuretics. Statins were used in 13.9%, antiplatelet drugs in 14.6%, new oral anticoagulants in 6.1%, and vitamin K antagonists in 1.0% of patients (Table 2).

Comparison of Patients With and Without Hypertension

Patients with hypertension were older and had a higher prevalence of other cardiovascular risk factors including hyperlipidemia (31.2% versus 6.2%), diabetes (37.2% versus 10.8%), and obesity (20.0% versus 13.9%) than those without hypertension after adjusting for age (P<0.0001). Patients with hypertension had also more comorbidities and were more frequently treated with cardiovascular medications, including BP-lowering drugs (Tables 1 and 2). The prevalence of in-hospital death in patients with hypertension was almost 2× higher than in patients without hypertension (22.2% versus 12.9%, P=0.02, after adjusting for age). The median length of hospitalization was longer in hypertensives than in patients without hypertension (Table 2); however, the need for admission to the ICU and the length of stay in the ICU were similar in both groups (Table 2). Compared with patients without hypertension, patients with hypertension had (at admission) higher systolic BP, mean BP, and pulse pressure, but not diastolic BP. Patients with hypertension had significantly higher respiratory rates and NT-proBNP levels than patients without hypertension (P<0.05 after adjusting for age; Table 2), whereas blood oxygen saturation, heart rate, and immune-inflammatory markers at admission were similar in both groups (Table 2).

Comparison of Patients With Hypertension Treated and Untreated With First-Line BP-Lowering Drugs

Among 3028 patients with hypertension, 1723 (57%) were treated with first-line BP-lowering medications, whereas 1305 (43%) were not. In comparison to untreated patients, those with treated hypertension were more commonly women and had higher prehospital prevalence of diagnosed hypercholesterolemia and stroke but less frequently chronic obstructive pulmonary disease (Table 1). Treated hypertensive individuals were also characterized by higher BP values and oxygen saturation at admission, while lower heart rate, respiratory rate, CRP (C-reactive protein), IL (interleukin) 6, and D-Dimer levels than untreated hypertensives (Table 2). Of note is that the number of in-hospital deaths in patients with hypertension who were treated by any drug belonging to the first-line BP-lowering drug class (ie, ACE inhibitors, ARB, β-blockers, calcium channel blockers, or thiazide/thiazide-like diuretics) was significantly lower than in untreated hypertensives (Table 2).

Independent Predictors of In-Hospital Death

We used multivariable logistic regression analysis to identify independent predictors of in-hospital death. In these analyses, age above a median of the cohort, male gender, and a history of heart failure or chronic kidney disease as well as increased hsCRP (high-sensitivity CRP) level were independent predictors of in-hospital death, while a preexisting diagnosis of hypertension was not (Figure 1). The use of first-line BP-lowering drugs, however, improved in-hospital survival in the whole study group (Figure S1). In sensitivity analysis, we also assessed whether differences between pandemic periods may have influenced the relationship between hypertension and its treatment with mortality outcome. Accordingly, the pandemic period in our study was divided into three separate periods (waves) reflecting the trends of admission increase: (1) from March 6 to July 31, 2020; (2) from August 1 to January 31, 2021; (3) from February 1, 2021 to May 13, 2021. Independently of admission period, hypertension diagnosis did not influence in-hospital mortality, whereas BP-lowering drug use improved prognosis (Figure S1).
Figure 1.

Independent predictors of in-hospital death in multivariable logistic regression analysis in whole study group N= 5191 (171 patients excluded due to missing data. Age: indicates patients at age equal or above median for study group; AF - atrial fibrillation, CAD - coronary artery disease, HF - heart failure, Stroke; CKD - chronic kidney disease, COPD - chronic obstructive pulmonary disease; CRP (C-reactive protein) units - indicates increase in 10 mg/L of hsCRP (high-sensitivity C-reactive protein).

Independent predictors of in-hospital death in multivariable logistic regression analysis in whole study group N= 5191 (171 patients excluded due to missing data. Age: indicates patients at age equal or above median for study group; AF - atrial fibrillation, CAD - coronary artery disease, HF - heart failure, Stroke; CKD - chronic kidney disease, COPD - chronic obstructive pulmonary disease; CRP (C-reactive protein) units - indicates increase in 10 mg/L of hsCRP (high-sensitivity C-reactive protein). In further analysis, we assessed in more detail the role of treatment status with first-line BP-lowering drugs in patients with hypertension. This analysis revealed that use of any drug belonging to the first-line BP-lowering drug classes was associated with reduced mortality (odds ratio, 0.25 [95% CI, 0.20–0.30]; P<0.001) (Figure 2). In this analysis, older age, increased hsCRP, history of coronary artery disease, heart failure, and chronic kidney disease were also independent predictors of in-hospital death (Figure 2; Figure S2A and S2B). The positive influence of antihypertensive drug treatment on survival in COVID-19 persisted after inclusion into the model the treatment with other cardiovascular drugs including statins, antiplatelet drugs, heparins, and new oral anticoagulants (Figure S3A and S3B).
Figure 2.

Independent predictors of in-hospital death in multivariable logistic regression analysis in patients with hypertension N=3028 (59 patients excluded due to missing data). The models include age, sex, diabetes, atrial fibrillation, coronary artery disease, heart failure, stroke, chronic kidney disease, chronic obstructive pulmonary disease, cancer, and highly sensitive C-reactive protein level increase (the whole models are presented in Figure S2). ACE inhibitor indicates angiotensin-converting enzyme inhibitor; AHT, treatment with any class of main antihypertensive drugs; ARB, angiotensin receptor blockers; CCB, calcium channel blockers; and Thiazides, thiazide diuretics or thiazides like diuretics.

Independent predictors of in-hospital death in multivariable logistic regression analysis in patients with hypertension N=3028 (59 patients excluded due to missing data). The models include age, sex, diabetes, atrial fibrillation, coronary artery disease, heart failure, stroke, chronic kidney disease, chronic obstructive pulmonary disease, cancer, and highly sensitive C-reactive protein level increase (the whole models are presented in Figure S2). ACE inhibitor indicates angiotensin-converting enzyme inhibitor; AHT, treatment with any class of main antihypertensive drugs; ARB, angiotensin receptor blockers; CCB, calcium channel blockers; and Thiazides, thiazide diuretics or thiazides like diuretics. Subsequent separate logistic regression analysis for the use of each first-line antihypertensive drug class confirmed the effect on in-hospital death reduction for each analyzed drug class (Table S1). The independent predictors of in-hospital death in treated and untreated patients with hypertension are summarized in Figure S4. In patients without preexisting arterial hypertension, the main factors increasing the odds of in-hospital death were slightly different from patients with hypertension and included older age, history of heart failure or chronic kidney disease, and higher hsCRP, but not a history of cardiovascular disease. In this group, use of ACE inhibitors but not use of any other BP-lowering drug class was related to lower risk of in-hospital death (Figure S5). In the subgroup of patients without preexisting established cardiovascular diseases or chronic kidney disease not treated with any cardiovascular medication, including BP-lowering drugs, multivariable logistic regression still showed that preexisting diagnosis of hypertension was a significant factor increasing the risk of in-hospital death (Figure 3).
Figure 3.

Independent predictors of in-hospital death in multivariable logistic regression analysis in patients without history of the following disease: heart failure, coronary artery disease, chronic kidney disease, stroke, atrial fibrillation, and without antihypertensive treatment (nontreated with β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers or thiazide diuretics; 112 patients excluded due to missing data). N= 2281 including 1061 women, 704 patients with arterial hypertension, 338 with diabetes; 66 with chronic obstructive pulmonary disease (COPD), and 238 with history of cancer. hsCRP indicates high-sensitivity C-reactive protein.

Independent predictors of in-hospital death in multivariable logistic regression analysis in patients without history of the following disease: heart failure, coronary artery disease, chronic kidney disease, stroke, atrial fibrillation, and without antihypertensive treatment (nontreated with β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers or thiazide diuretics; 112 patients excluded due to missing data). N= 2281 including 1061 women, 704 patients with arterial hypertension, 338 with diabetes; 66 with chronic obstructive pulmonary disease (COPD), and 238 with history of cancer. hsCRP indicates high-sensitivity C-reactive protein.

Discussion

Hypertension was the most common clinical condition in the group of patients hospitalized due to COVID-19 in this study. This prevalence of about 60% was similar to the prevalence observed among subjects in the general population over 50 years of age in epidemiological studies from Poland.[25] Overall, patients with hypertension in our cohort were older and had more coexisting comorbidities with a potential impact on clinical outcome than patients without hypertension. Therefore, in-hospital mortality in patients with preexisting hypertension was higher in crude analysis than in patients without hypertension. However, the preexisting diagnosis of hypertension per se was not an independent predictor of in-hospital death. In contrast, significant predictors of death, besides older age and male sex were higher hsCRP levels, heart failure, and chronic kidney disease. The 2 latter conditions are widely recognized as a consequence of long-lasting hypertension.[22,24] Preexisting hypertension was an independent predictor of in-hospital death during COVID-19 only in patients free of cardiovascular diseases. This can be explained also as these patients had not been used to get medical treatment. Of interest, the treatment with first-line BP-lowering drugs had a significant impact on mortality in patients with hypertension, that is, the use of any class of first-line antihypertensive medications as recommended in guidelines[22,24] increased the probability of surviving COVID-19 hospitalization. Prior studies have also shown that there is a high prevalence of hypertension ranging from 27% to 59%[3,6,10,11] in patients hospitalized due to COVID-19. The prevalence was even higher, up to 70%, in those who died due to COVID-19.[10,11] Consequently, the question arises whether preexisting hypertension is a factor influencing in-hospital prognosis in patients hospitalized due to COVID-19, as it is a significant long-term prognostic factor in the general population.[27] Available data on the role of hypertension in COVID-19 prognosis are, however, equivocal.[5,6,10,12,17,28,29] In an early study from Wuhan, China, coexisting hypertension, observed in 28% of patients, was independently associated with all-cause mortality (hazard ratio, 1.8 [95% CI, 1.2–2.7]) in patients treated due to COVID-19.[5] Moreover, in the analyses of 13 early studies, which included a total of 3822 patients, there was a significant association of hypertension with mortality due to COVID-19.[28] However, in the study of Sun et al,[12] hypertension was a predictor of death but only in combination with diabetes (odds ratio, 3.02 [95% CI, 1.48–6.15]). Other recently published data did not confirm the previous observation about the negative influence of hypertension on prognosis in patients with COVID-19.[6] In a meta-analysis of 18 studies (14 558 individuals), the estimated pooled relative risk of mortality among patients with COVID-19 was significantly increased for comorbidities, including cardiovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, and cancer, but not for hypertension or diabetes.[6] In a study by the Italian Society of Hypertension of 1591 patients hospitalized due to COVID-19 in multivariable analyses, only older age, diabetes, chronic obstructive pulmonary disease, and chronic kidney disease but not hypertension predicted increased mortality.[10] In a different group of Italian patients hospitalized with COVID-19 and admitted to intensive care units, hypertension was also not an independent predictor of in-hospital mortality.[29] Similarly, in our results, we did not identify preexisting hypertension as an independent predictor of in-hospital death when analyzed along with other comorbidities and other risk factors. Among those comorbidities, only a history of heart failure or chronic kidney disease—well-known consequences of hypertension—were associated with in-hospital death. In a Massachusetts community-based observational study, hypertension was an independent predictor of severe COVID-19 defined as need for hospitalization or death, only in patients younger than 65 years.[14] This finding is consistent with our results showing that hypertension predicts in-hospital death only among patients free of established cardiovascular diseases. This group in our study was also younger than patients with any cardiovascular disease (median of age 56 versus 70 years). The importance of antihypertensive treatment for COVID-19 morbidity and mortality was a subject of interest from the very beginning of the pandemic, mainly due to the mechanisms of virus incorporation into cells in the respiratory tract via angiotensin-converting enzyme 2 and a postulated interaction of ACE inhibitors and ARB treatment with this mechanism.[30-32] However, the majority of data obtained in observational studies and randomized trials have shown and reassured that treatment with ACE inhibitors or ARB has a neutral impact on the outcomes of patients with COVID-19.[33-37] In one of the largest population-based case-controlled analyses in the United Kingdom, there was no evidence that the use of antihypertensive medication is associated with increased risk of COVID-19 diagnosis or mortality.[38] It is of interest that some studies indicated that treatment with ACE inhibitors or ARB may even protect against infection and reduce mortality in COVID-19.[12,15,18] In the study by the Italian Society of Hypertension, there was no interference of antihypertensive therapy with COVID-19 mortality.[10] In the study of Ran et al,[39] ARBs did not increase the risk of adverse events in patients with hypertension; moreover, poor BP control was independently associated with higher risks of adverse outcomes of COVID-19, including heart failure, which in our study was a main determinant of in-hospital mortality. With respect to medical treatment, Bauer et al. found that therapy with any first-line antihypertensive drug does not worsen COVID-19 severity.[14] Another large observational study suggests a lower risk of worse COVID-19 outcome (hospitalization and death or intubation) in patients with hypertension treated over a long period with ACE inhibitors or ARBs compared to those treated with calcium channel blockers.[40] However, some limitations of the evidence on the role of antihypertensive treatment in patients with COVID-19 presented to date should also be taken into consideration. A high proportion of studies was based on small sample sizes, and many studies failed to include adequate adjustments for confounding variables. In our study, the use of any first-line BP-lowering drug had a profound beneficial effect on survival in patients with COVID-19 with hypertension, after adjustment for covariates. Consequently, the treatment status in patients with preexisting hypertension had a major influence on mortality during hospitalization due to COVID-19, irrespective of the drug class used. There is also a possibility that treated patients with antihypertensive medications were admitted earlier than untreated attributable to a potentially higher socioeconomic status or education level resulting in higher health awareness and earlier reach out for medical care. This may also partially explain the between-group differences in clinical condition on admission. However, it appears still important to emphasize that the positive effect of antihypertensive treatment on the prognosis in multivariable logistic regression was independent of inflammation severity at admission as assessed by hsCRP level. Based on the available data in our study, we cannot precisely identify the decisive factors for whether attending physicians treat their patients with a recommended first-line BP-lowering pharmacotherapy. It appears conceivable that the untreated patients may represent patients with a lower risk or a more recent diagnosis of hypertension, with the treating physicians initiating treatment with lifestyle changes but not with pharmacotherapy. However, the patient characteristics (as evident from Table 1) showed only subtle differences between the treated and untreated groups of patients with hypertension. Interestingly, all BP values measured at admission to the hospital were significantly higher in the patients under antihypertensive pharmacotherapy, which would confirm more advanced hypertension in this group. In a recent study by Sheppard et al,[15] better BP control in the period before admission to hospital was shown to be associated with a worse COVID-19 outcome. The authors explained this phenomenon by a potentially more advanced target organ damage in patients with better BP control because their corresponding patients were older, had more comorbidities, and had been diagnosed with hypertension for a longer period of time.[15] The positive influence of antihypertensive treatment on prognosis in patients with hypertension hospitalized due to COVID-19 might be explained by 2 well-known facts. First, the results of numerous RCT studies from the prepandemic era show that each antihypertensive treatment improves prognosis irrespective of the drug class used.[22,24] A second explanation is the positive effect of different antihypertensive drugs on the endothelium as it is a well-known fact that the endothelium is widely involved in COVID-19 pathogenesis and its complications.[41,42]

Limitations

The lack of detailed data about the preadmission period of the included patients should be considered as a first limitation of our study. Such data might have shed more light on our finding indicating a relevant beneficial prognostic effect of pharmacological treatment status in patient with preexisting hypertension and acute COVID-19 disease. We analyzed drug classes and not individual medications and could not take into account dosage of different drugs, treatment duration before admission, or adherence to therapy. A second limitation is that this is a retrospective observational study, and despite controlling for various comorbidities, some other unknown confounders might therefore play a role in affecting our results. However, we presented the data of a large cohort from a single center with a uniform hospital information system and a standardized COVID-19 management with reliable data from medical records directly available to us. Additionally, our results of reduced mortality in consecutive COVID-19 pandemic waves confirmed that COVID-19 treatment strategy improved during pandemic waves.

Conclusions

Preexisting hypertension in patients hospitalized due to COVID-19 is not overall an independent predictor of in-hospital death. However, the use of any antihypertensive drug, regardless of the class to which it belongs, resulted in a profound reduction of in-hospital mortality in patients with hypertension.

Perspectives

The future of the COVID-19 pandemic remains unpredictable, but cardiovascular risk factors and diseases including hypertension should be treated continuously to obtain a better long-term prognosis in patients with these conditions as well as for reducing COVID-19 mortality. The following indication should be considered for patients with hypertension: continuation of antihypertensive treatment during hospitalization due to COVID-19, and all antihypertensive drug classes might be recommended equally in this indication.

Article Information

Sources of Funding

This publication was supported by Polish National Center for Research and Development; CRACoV-HHS project (Cracow in COVID Pandemics - Home, Hospital and Staff; Model of multi-specialist hospital and nonhospital care for patients with SARS-CoV-2 infection) through the initiative “Support for specialist hospitals in fighting the spread of SARS-CoV-2 infection and in treating COVID-19” (contract number SZPITALE-JEDNOIMIENNE/18/2020). The described research was implemented by consortium of the University Hospital in Krakow and the Jagiellonian University Medical College, Krakow, Poland.

Disclosures

None.
  38 in total

Review 1.  2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD.

Authors:  Francesco Cosentino; Peter J Grant; Victor Aboyans; Clifford J Bailey; Antonio Ceriello; Victoria Delgado; Massimo Federici; Gerasimos Filippatos; Diederick E Grobbee; Tina Birgitte Hansen; Heikki V Huikuri; Isabelle Johansson; Peter Jüni; Maddalena Lettino; Nikolaus Marx; Linda G Mellbin; Carl J Östgren; Bianca Rocca; Marco Roffi; Naveed Sattar; Petar M Seferović; Miguel Sousa-Uva; Paul Valensi; David C Wheeler
Journal:  Eur Heart J       Date:  2020-01-07       Impact factor: 29.983

2.  Management of SARS-CoV-2 infection: recommendations of the Polish Association of Epidemiologists and Infectiologists. Annex no. 1 as of June 8, 2020.

Authors:  Robert Flisiak; Andrzej Horban; Jerzy Jaroszewicz; Dorota Kozielewicz; Małgorzata Pawłowska; Miłosz Parczewski; Anna Piekarska; Krzysztof Simon; Krzysztof Tomasiewicz; Dorota Zarębska-Michaluk
Journal:  Pol Arch Intern Med       Date:  2020-06-08

3.  2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk.

Authors:  François Mach; Colin Baigent; Alberico L Catapano; Konstantinos C Koskinas; Manuela Casula; Lina Badimon; M John Chapman; Guy G De Backer; Victoria Delgado; Brian A Ference; Ian M Graham; Alison Halliday; Ulf Landmesser; Borislava Mihaylova; Terje R Pedersen; Gabriele Riccardi; Dimitrios J Richter; Marc S Sabatine; Marja-Riitta Taskinen; Lale Tokgozoglu; Olov Wiklund
Journal:  Eur Heart J       Date:  2020-01-01       Impact factor: 29.983

4.  Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy.

Authors:  Giacomo Grasselli; Massimiliano Greco; Alberto Zanella; Giovanni Albano; Massimo Antonelli; Giacomo Bellani; Ezio Bonanomi; Luca Cabrini; Eleonora Carlesso; Gianpaolo Castelli; Sergio Cattaneo; Danilo Cereda; Sergio Colombo; Antonio Coluccello; Giuseppe Crescini; Andrea Forastieri Molinari; Giuseppe Foti; Roberto Fumagalli; Giorgio Antonio Iotti; Thomas Langer; Nicola Latronico; Ferdinando Luca Lorini; Francesco Mojoli; Giuseppe Natalini; Carla Maria Pessina; Vito Marco Ranieri; Roberto Rech; Luigia Scudeller; Antonio Rosano; Enrico Storti; B Taylor Thompson; Marcello Tirani; Pier Giorgio Villani; Antonio Pesenti; Maurizio Cecconi
Journal:  JAMA Intern Med       Date:  2020-10-01       Impact factor: 21.873

5.  Antihypertensive medications and COVID-19 diagnosis and mortality: Population-based case-control analysis in the United Kingdom.

Authors:  Emma Rezel-Potts; Abdel Douiri; Phil J Chowienczyk; Martin C Gulliford
Journal:  Br J Clin Pharmacol       Date:  2021-05-10       Impact factor: 3.716

6.  A pneumonia outbreak associated with a new coronavirus of probable bat origin.

Authors:  Peng Zhou; Xing-Lou Yang; Xian-Guang Wang; Ben Hu; Lei Zhang; Wei Zhang; Hao-Rui Si; Yan Zhu; Bei Li; Chao-Lin Huang; Hui-Dong Chen; Jing Chen; Yun Luo; Hua Guo; Ren-Di Jiang; Mei-Qin Liu; Ying Chen; Xu-Rui Shen; Xi Wang; Xiao-Shuang Zheng; Kai Zhao; Quan-Jiao Chen; Fei Deng; Lin-Lin Liu; Bing Yan; Fa-Xian Zhan; Yan-Yi Wang; Geng-Fu Xiao; Zheng-Li Shi
Journal:  Nature       Date:  2020-02-03       Impact factor: 69.504

Review 7.  Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19.

Authors:  Isabelle Bernard; Daniel Limonta; Lara K Mahal; Tom C Hobman
Journal:  Viruses       Date:  2020-12-26       Impact factor: 5.048

8.  Antihypertensive Drugs and COVID-19 Risk: A Cohort Study of 2 Million Hypertensive Patients.

Authors:  Laura Semenzato; Jérémie Botton; Jérôme Drouin; Bérangère Baricault; Clémentine Vabre; François Cuenot; Laetitia Penso; Philippe Herlemont; Emilie Sbidian; Alain Weill; Rosemary Dray-Spira; Mahmoud Zureik
Journal:  Hypertension       Date:  2021-01-11       Impact factor: 10.190

Review 9.  Hypertension and related diseases in the era of COVID-19: a report from the Japanese Society of Hypertension Task Force on COVID-19.

Authors:  Shigeru Shibata; Hisatomi Arima; Kei Asayama; Satoshi Hoshide; Atsuhiro Ichihara; Toshihiko Ishimitsu; Kazuomi Kario; Takuya Kishi; Masaki Mogi; Akira Nishiyama; Mitsuru Ohishi; Takayoshi Ohkubo; Kouichi Tamura; Masami Tanaka; Eiichiro Yamamoto; Koichi Yamamoto; Hiroshi Itoh
Journal:  Hypertens Res       Date:  2020-07-31       Impact factor: 5.528

10.  Microvascular dysfunction in COVID-19: the MYSTIC study.

Authors:  Alexandros Rovas; Irina Osiaevi; Konrad Buscher; Jan Sackarnd; Phil-Robin Tepasse; Manfred Fobker; Joachim Kühn; Stephan Braune; Ulrich Göbel; Gerold Thölking; Andreas Gröschel; Hermann Pavenstädt; Hans Vink; Philipp Kümpers
Journal:  Angiogenesis       Date:  2020-10-14       Impact factor: 10.658

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