Dynamics of Clinical Parameters in Arterial Hypertension Patients after COVID-19: Impact of Obstructive Airway Disease (OAD)

Introduction

Any viral infection can destabilize the cardiovascular system. After clearance of SARS-CoV-2, a substantial proportion of patients with arterial hypertension experience decompensation of their somatic status, manifesting as unstable blood pressure – particularly those who had severe COVID-19 [1].

Hypothesis: The primary target of COVID-19 is the bronchopulmonary system; patients who already have AH and a pre-existing obstructive airway disease (OAD) may endure a more severe disease course and a slower recovery of cardiovascular health parameters.

Objective: To compare the longitudinal dynamics of clinical parameters in AH patients, stratified by the presence or absence of OAD, during the year following COVID-19-related lung injury.

Material and Methods

A cohort observational study was conducted using data from the database registry “Prospective registry of persons who have had COVID-19-associated pneumonia,” which comprised 350 patients [2]. The study protocol received approval from the Biomedical Ethics Committee of the Tyumen Cardiology Research Center (Protocol No. 159, July 23, 2020) and was registered in the International Clinical Trials Registry (ClinicalTrials.gov, Identifier No.: NCT04501822). All participants provided written informed consent before inclusion.

A total of 38 patients with AH and OAD were selected from the database registry: 12 with asthma, 8 with chronic obstructive pulmonary disease (COPD), and 12 with pre-COPD (defined by a smoking history of ≥10 pack-years, “definite smokers,” with a smoking index >160). In the non-OAD group, 89 non-smoking AH patients were selected using stratified randomization; strata factors included AH stage and risk, gender, age, and BMI.

Exclusion criteria comprised coronary artery disease (CAD), oncological diseases diagnosed during the observation period, refusal to participate, suboptimal echocardiographic (EchoCG) imaging, hemodynamically significant valvular regurgitation, and atrial fibrillation. Data from the single‑infection hospital examination were assessed using hospital discharge summaries. Clinical, laboratory, and instrumental data for both groups were collected at 3 and 12 months post-discharge follow-up visits (first and second visits, respectively). Concomitant disease diagnoses were based on anamnesis, medical records, and clinical, instrumental, and laboratory examinations, in accordance with current clinical guidelines.

Heart failure with preserved ejection fraction (HFpEF) was diagnosed using the HFA-PEFF algorithm: a score of 0-1 indicated low probability (no further testing required); a score of 2-4 indicated probable HFpEF (horizontal bicycle ergometry was performed to confirm); and a score ≥5 indicated established HFpEF. Chest computed tomography (CT) was performed with a Toshiba Aquilion 64 system (Japan). EchoCG was performed on a GE Healthcare Vivid S70 ultrasound machine; images were saved in DICOM format and processed on an IntelliSpace Cardiovascular workstation using the TOMTEC program (Philips, USA). Echocardiography adhered to current guidelines, including assessment of longitudinal strain [3]. Myocardial diastolic function was assessed in accordance with guidelines [3-5]. Variable distributions were evaluated using the Shapiro-Wilk and Kolmogorov–Smirnov tests, with Liljefors significance correction applied. Between-group comparisons of quantitative parameters employed the Student’s t-test or the Mann–Whitney U test. Within-group changes over time were analyzed with the paired Student’s t-test or the Wilcoxon signed‑rank test; for comparisons across three time points, the Friedman test was used, and Bonferroni correction was applied to the resulting p-values. Qualitative variables were compared using the chi-square test or Fisher’s exact test, and temporal changes were assessed with the McNemar test. Statistical significance was set at two-sided p<0.05. A generalized linear model was used for multivariate analysis.

Results

Patients in the OAD group did not differ in age across the specific OAD subtype: those with COPD had an age of 55.1±5.6 years, those with pre-COPD 54.8±10.0 years, and those with asthma 54.7±5.2 years (p=0.996). The only significant difference observed during hospitalization was the more frequent use of carbapenems in the OAD group (Table 1), likely reflecting a higher risk of infection with multidrug-resistant flora in COPD patients. The increased LV volume (Table 2) is attributed to the higher infusion load administered during hospitalization.

Table 1. Clinical characteristics of hypertensive patients hospitalized for COVID-19-related lung injury, stratified by obstructive airway disease (OAD)

AH, arterial hypertension; CAD, coronary artery disease; HFA PEFF, algorithm for diagnosing heart failure with preserved ejection fraction; HFpEF, heart failure with preserved ejection fraction; CKD, chronic kidney disease; GFR, glomerular filtration rate. Significant differences (p<0.05) are highlighted in bold.

After discharge (Table 2) at the second visit in the non-OAD group, a significant increase in BMI and in the frequency of stage 3 AH was observed, driven by a rise in the number of patients with chronic kidney disease (CKD) stages 2 and 3A according to the glomerular filtration rate (GFR). Newly diagnosed CAD also appeared: it was first identified in five non-OAD patients and in one OAD patient.

In the absence of baseline differences in HFpEF, the OAD group showed a dynamic decrease in the number of patients with probable HFpEF (candidates for diastolic stress testing). At the first visit, normalization of chest-CT data in the OAD group was detected less frequently, but at the second visit, the frequency of residual lung changes was low and did not differ between the groups. The mean levels of laboratory parameters during outpatient observation were within normal limits, except for elevated total cholesterol and low‑density lipoproteins in both groups, with no inter‑group differences (Table 2).

According to echocardiography, left‑ventricular ejection fraction (LVEF) remained within the normal range for all patients throughout the study (Table 3). At the first visit, LVEF was lower in the non‑OAD group than in the OAD group, but this difference disappeared by the second visit. A more sensitive marker of systolic function, global longitudinal strain (LV GLS), showed a trend toward decline in the non‑OAD group at the second visit (Table 4). The proportion of patients with reduced LV GLS increased, although not significantly; at the second visit, 35 % of the non‑OAD group and 25% of the OAD group exhibited reduced LV GLS, yet the difference between groups was not statistically significant.

Table 3. Comparative dynamics of echocardiographic parameters in patients with AH 3 and 12 months after COVID-19-related lung injury, with OAD (n=38) versus without OAD (n=89)

Table 4. Comparative dynamics of left‑heart echocardiographic parameters in hypertensive patients 3 and 12 months after COVID-19-related lung injury, stratified by OAD status (OAD cohort n=38; non-OAD cohort n=89)

LV isovolumic relaxation time (IVRT) and the proportion of IVRT>100 ms increased in the non-OAD cohort, indicating an elevated level of initial manifestations of left‑ventricular diastolic dysfunction. The ratio of early to late diastolic filling velocities (E/A)<0.7 showed an upward trend only in the non-OAD cohort. Consequently, although LV relaxation disturbances were evident at the first visit in both groups, progression was observed only in the non-OAD cohort. As a result, intergroup differences emerged in the E/e′ ratio – the age‑independent measure of early LV diastolic filling velocity relative to early diastolic mitral annulus velocity. The E/e′ value was higher in the non-OAD cohort, and the proportion of patients with E/e′≥9 – an indicator of impaired LV relaxation – was greater in the non‑OAD cohort than in the OAD cohort.

During hospitalization, the only parameter that significantly differentiated the groups was right atrial volume, which was larger in the OAD cohort (Table 2). This likely reflects the increased load on the right atrium due to concomitant OAD. Assessment of right-heart chamber dimensions (Tables 2 and 5) showed that, although within normal limits throughout the study, these dimensions decreased in both groups by the first visit. However, by the second visit, the non-OAD cohort exhibited a significant increase in right‑ventricular (RV) volume and basal width, accompanied by a significant decline in RV systolic function as measured by tricuspid annular plane systolic excursion (TAPSE) and early diastolic velocity. The number of patients with reduced RV GLS at the second visit decreased not significantly and did not differ between groups.

Table 5. Comparative dynamics of right-heart echocardiographic parameters in hypertensive patients 3 and 12 months after COVID-19-related lung injury, stratified by OAD status (OAD cohort n=38; non-OAD cohort n=89)

During the outpatient phase of the study, all participants were monitored under close supervision of a cardiologist, which led to expanded medication regimens (Table 6). The spectrum of antihypertensive agents used broadened in both groups, with greater utilization of angiotensin II receptor blockers, statins, and diuretics (Table 7). Consequently, adherence to antihypertensive therapy among study participants varied from 64.3 % to 100 % (Figure 1). Adherence was highest for β‑blockers and angiotensin II receptor antagonists and lowest for statins in both groups. Multivariate analysis revealed no significant associations between the prescribed medications and the presence of OAD with the structural and functional parameters of the right heart (Table 8).

Table 6. Comparative characteristics of prescribed therapy at inclusion (3 months post-COVID-19 lung injury) and at 9 months post-inclusion (12 months post-COVID-19 lung injury) according to OAD status

Table 7. Comparative characteristics of medication taken

Table 8. Multivariate analysis of medication effects on right heart parameters

Figure 1. Adherence to Antihypertensive Therapy. Adherence of hypertensive patients at the second visit to treatment prescribed at the first visit. ACE, adenosine‑converting enzyme.

At the first visit, only four of the eight patients with COPD received bronchodilator therapy. Among these, one patient was placed on monotherapy with the long-acting anticholinergic tiotropium bromide; another received combined tiotropium bromide therapy with situational administration of short-acting β₂‑agonists (SABA) (ipratropium bromide + fenoterol); a third was treated with a combination of inhaled glucocorticosteroids (IGC) and long-acting β₂‑agonists (LABA) (budesonide/formoterol); and the fourth used SABA on demand (ipratropium bromide + fenoterol). All patients with COPD and pre-COPD were advised to cease smoking, and all COPD patients received training on the correct inhaler technique. The eight patients were prescribed short-acting bronchodilators for as-needed use; two patients with severe COPD were recommended a fixed combination of LABA and long-acting anticholinergic (LAMA) to achieve greater bronchodilation, while six patients received LAMA monotherapy.

All eighteen asthmatic patients received baseline therapy at the first visit: three were on inhaled glucocorticosteroids (IGC) monotherapy (two with budesonide, one with beclomethasone), and three combined IGC monotherapy with a short acting combination of ipratropium bromide + fenoterol as needed. Nine asthmatic patients were prescribed a fixed combination of IGC/LABA (budesonide/formoterol) both as basic therapy and for symptom relief. Three asthmatic patients did not receive anti-inflammatory therapy but used short-acting IGC/SABA on an as-needed basis, followed by monitoring of therapeutic effectiveness.

A multivariate analysis demonstrated no significant influence of the medications taken or OAD on the structural and functional parameters.

Discussion

The small size of the OAD group is a consequence of the study’s reliance on data from the database registry “Prospective registry of persons who have had COVID-19-associated pneumonia” [2] and is limited by the total sample size of 350 patients at baseline. According to the 2025 consensus statement of the European Society of Cardiology and the European Association of Cardiovascular Imaging, clinical cardiologists and researchers are encouraged to use registry data, as registries provide large, unselected, consecutive cohorts for collecting real‑world prospective data in a standardized manner, whereas randomized clinical trial samples are limited. Registries are therefore key research tools for assessing the real‑world consequences of the phenomenon under study.

Patients with COPD, pre‑COPD, and bronchial asthma were combined into the OAD group based on the commonality of echocardiographic manifestations – the ability of OAD to cause right‑ventricular overload.

It has been previously shown that in patients with AH, RV diastolic dysfunction accompanies LV diastolic dysfunction regardless of the presence or absence of pulmonary arterial hypertension [6]. Moreover, diastolic dysfunction of the LV and RV develops asynchronously in 36% of AH patients, and disturbances in RV diastolic function are accompanied by RV enlargement [7]. This was observed in our cohort: in the non-OAD group, a decrease in early diastolic tricuspid annular velocity was accompanied by an increase in basal RV dimension.

Subclinical LV systolic dysfunction is characteristic of AH patients with LV hypertrophy, a finding that aligns with our results: the frequency of reduced LV global longitudinal strain at the end of the study was relatively high – 35% in the non-OAD group and 25% in the OAD group (for comparison, the prevalence of LV hypertrophy was 38% in the non-OAD group and 34 % in the OAD group). LV damage with systolic and diastolic dysfunction after pulmonary injury associated with COVID-19 has also been shown to be associated with levels of immune‑inflammation markers [8]. No data were found regarding the incidence of subclinical RV systolic dysfunction in AH patients one year after COVID-19. In our study, its frequency was 22% in the non-OAD group and 29% in the OAD group.

Thus, the hospitalization course for patients with AH was essentially the same regardless of their OAD status. During outpatient follow-up, OAD patients had a lower incidence of HFpEF, whereas non-OAD patients exhibited more than a twofold increase in the frequency of stage 3 hypertension, primarily attributable to CKD stages 2 and 3A as defined by GFR. One year after discharge, non-OAD patients had a higher incidence of LV relaxation abnormalities and displayed worsening right‑heart parameters – both structural (increased right-atrial volume and basal right‑ventricular dimension) and functional (decreased TAPSE and early diastolic tricuspid annular velocity). A trend toward reduced tricuspid annular systolic velocity further suggests impaired RV systolic function in non-OAD patients. These findings imply a comparatively favorable recovery trajectory from COVID-19 in the OAD group.

Our results align with those reported by other investigators. A retrospective observational study of COVID-19 outpatients, with and without asthma, found better outcomes in asthmatic patients, including lower rates of hospitalization, intensive care unit admission, and shorter hospital stays [9]. A single-center study confirmed a relatively benign course of COVID-19 in asthmatic individuals, noting that asthma does not predispose to severe disease and that its treatment may positively influence the disease course. However, the coexistence of asthma with AH, obesity, and diabetes is recognized as worsening the prognosis of COVID-19 [10].

Consequently, the initial hypothesis was not supported; OAD patients proved more resistant to the factors that drive pathological (structural and functional) cardiac remodeling in AH patients during the late phase of pulmonary injury in COVID-19.

The adaptation of the myocardium in OAD patients to the factors responsible for pathological remodeling during the late recovery phase of COVID-19 can be explained by myocardial preconditioning – a metabolic adaptation to ischemia that arises after repeated episodes of reduced oxygen delivery to the myocardium and confers increased resistance to subsequent prolonged hypoxia. Accordingly, OAD may act as a chronic hypoxic stressor.

Another plausible explanation involves the protective effect of basic therapy in OAD patients. Of the 38 OAD patients, 22 did not receive basic therapy during hospitalization or at the first follow‑up visit. Nevertheless, drawing conclusions about the role of basic therapy in preventing RV remodeling would require a larger OAD cohort.

In contrast, non-OAD patients were prescribed β‑blockers and adenosine‑converting enzyme inhibitors significantly more frequently at both visits, a factor that could have improved structural and functional myocardial parameters in this group. However, such improvement was not observed; echocardiography parameters in the non-OAD group worsened. The results could have been influenced by the administration of β‑blockers in patients without OAD at the second visit; however, any observed relationship was inverse (Table 8). Therefore, the negative trends in echocardiographic parameters among non-OAD patients provide grounds to exclude the impact of differential drug therapy on the study outcomes.

Limitations

1.  A small cohort of patients with OAD.
2.  Absence of pre-COVID-19 data.
3.  Lack of spirometry data with bronchodilator in pre-COPD patients.

Conclusion

In patients with AH, the hospital period of lung injury during acute COVID-19 does not differ between those with and without OAD. One year after discharge, OAD patients show a significantly lower likelihood of HFpEF compared with assessments at three months post-COVID-19. In non-OAD patients, one year after COVID-19, BMI, and the prevalence of stage 3 AH increase, LV relaxation abnormalities are more frequently detected, and structural and functional parameters of the right heart are worse compared with OAD patients.

Conflict of Interest

The authors declare no conflict of interest.

Ethical Approval

All procedures involving human participants complied with the ethical standards of the institutional and/or national research committee, the 1964 Declaration of Helsinki, and its subsequent amendments. Written informed consent was obtained from all individual participants included in the study.

AI Disclosure Statement

During the preparation of this work, the authors did not use any generative AI or AI-assisted tools for the generation of content, data analysis, or the production of figures.