Arterial hypertension in the post-Covid period: literature review

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Abstract

During the pandemic of the new coronavirus infection, the most common comorbid pathology in patients with laboratory confirmed cases of COVID-19 was arterial hypertension (AH) due to the participation of the renin-angiotensin-aldosterone system components in the penetration of the SARS-CoV-2 virus into the human body and the similarity of the pathogenesis of these diseases. One of the manifestations of post-Covid syndrome in АН is destabilization of blood pressure, insufficiency of antihypertensive therapy effectively conducted before, uncontrolled hypertension, requiring intensified therapy, the development of resistant hypertension in some cases, high incidence of target organs damage. The frequency of new cases of hypertension 3 and 4–6 months after COVID-19 was low.

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The most common comorbid pathology in patients with laboratory-confirmed cases of COVID-19 is arterial hypertension (AH), ranging from 9 to 35 % [1; 2]. According to the international registry “ACTIVE SARS-CoV-2,” which included patients from the Eurasian region, the prevalence of AH in COVID-19 cases was 59.4 % among hospitalized patients and 48.8 % among outpatients [3].

The high prevalence of AH, which is one of the main causes of mortality worldwide (up to 10.4 million deaths per year) [4; 5], the involvement of the renin-angiotensin-aldosterone system (RAAS) components in the penetration of the SARS-CoV-2 virus into the human body, the similarity in the pathogenesis of the novel coronavirus infection (NCI) and AH characterized by the development of systemic inflammation, endothelial dysfunction, activation of both systemic and local RAAS in the central nervous system [6; 7] make further study of the features of the course of the disease in patients who have had this infection essential.

Currently, there are no long-term researches on the condition of patients who have recovered from COVID-19 [8; 9].

According to the definition, post-COVID syndrome (PCS) (Long COVID, post-COVID-19 condition) is characterized by the presence of complaints and symptoms that develop during or after COVID-19, persist for more than 12 weeks and aren’t manifestations of another pathology [10; 11]. The average prevalence of PCS is 50.9 % (95 % CI: 45.0–56.7 %) [12; 13].

In PCS, patients with AH experience the most severe conditions, as confirmed by a higher number of post-COVID symptoms (mean: 2.1; SD: 1.4) (IRR 1.16, 95% CI: 1.03–1.30; p = 0.012), compared to patients without AH (mean: 1.8; SD: 1.4). In these individuals, among numerous comorbid diseases (χ²: 56.340; p < 0.001), cardiovascular pathology, diabetes mellitus (DM), and obesity predominated (all p < 0.01) [14].

The literature data on the relationship between AH and COVID-19 are contradictory. On the one hand, the role of AH as one of the factors in the severity of NCI cannot be excluded; on the other hand, a potential role of COVID-19 in the development of AH is suggested.

One of the manifestations of PCS in patients with AH is unstable blood pressure (BP) control. According to the “ACTIVE…” registry, the most common reason for an unscheduled visit to a doctor (in 40.2 % of cases) was uncontrolled hypertension [15; 16]. According to the registry of the Eurasian Association of Therapists, during the first 3 months, 18.6 % of patients reported elevated BP despite previously effective antihypertensive therapy; 3 months after recovery from COVID-19, 20.1 % of patients experienced uncontrolled hypertension [17]. In the post-hospitalization period, 29.2 % of patients sought unscheduled medical care. 4.2 % and 4.4 % of them were hospitalized in 3 and 6 months respectively; emergency medical services were called in by 2.5 % and 2.3 % of patients [15].

In the post-COVID period, 80.6 % of patients experienced worsening of AH, and 69.4 % of them required intensification of antihypertensive therapy, resistant hypertension being diagnosed in 16.7 % of cases. A high incidence of target organ damage was identified (left ventricular hypertrophy: 71.9 %, chronic kidney disease of stages II–IIIb: 56.3 %), in 51.1 % of cases, an increased level of brain natriuretic peptide in blood plasma was detected; cognitive impairments were observed in 71.9 % of patients [18; 19].

Similar data were obtained in a comparative population-based analysis of self-measured BP over one-year period in 72,706 patients with AH and 33,440 patients before COVID-19. A higher mean monthly adjusted systolic BP was revealed (131.6 vs. 127.5 mmHg; p < 0.001); diastolic BP (80.2 vs. 79.2 mmHg; p < 0.001), and mean BP (97.4 vs. 95.3 mmHg; p < 0.001). Compared to the pre-pandemic period, during the COVID-19 infection period, the number of patients with uncontrolled hypertension increased from 15 % to 19 % [20].

In patients with mild and moderate COVID-19, hypertension remained uncontrolled despite receiving combination antihypertensive therapy. According to 24-hour BP monitoring in these patients, the day-to-night systolic BP ratio was significantly lower compared to those who had not contracted the disease (p1–2 = 0.0004; p1–3 = 0.015); a higher frequency of the Non-dippers pattern was identified in the period up to 12 weeks after COVID-19 (17.6 %) compared to the period over 12 weeks (4.4 %) (χ² = 4.18; p = 0.042). According to A. Yu. Ryabova et al. [16], BP destabilization should be considered a manifestation of PCS. The BP phenotype in stage 2 AH 12 weeks after COVID-19 was more favorable, as evidenced by a significant decrease in the number of patients with the Non-dippers pattern.

In a prospective 6-month follow-up of patients who had COVID-19 with lung involvement, periodic elevations in blood pressure were observed, with the maximum increase occurring in the first month after the illness, followed by a decrease by the third month and a subsequent rise to the previous level by the sixth month of observation (p < 0.05), which indicates a progressive course of hypertension and the need for longer-term BP monitoring. By that time, the prevalence of AH reached 12 %. Arterial hypertension increases the load on the left heart chambers, contributing to the development of diastolic dysfunction in the post-COVID period [21].

An examination of 437 patients with AH and a history of COVID-19 revealed a statistically significant more unstable course of the disease (p = 0.031) in those treated in a hospital for the infection. Within one month, despite antihypertensive therapy, BP levels did not reach target values [22]. Statistically significant differences were also identified in most indicators of 24-hour BP monitoring compared to the patients who had not contracted the novel coronavirus infection. The data on the influence of time elapsed after infection on the course of AH are rather contradictory [17; 21].

Among individuals examined 6 months after being diagnosed with COVID-19 who had an unstable course of hypertension, women (66.7 %; p < 0.005) of older age (by 15.02 years), active smokers (73.3 %), and those with an average body mass index 7.3 kg/m² higher (95 % CI: 5.01–9.61 kg/m²; p > 0.0001) were more common [23].

A study in which 3,066 Indian physicians participated, showed that up to 20 % of patients who had recovered from COVID-19 had uncontrolled AH. Almost 52 % of healthcare professionals managing BP in patients with AH after COVID-19 switched from monotherapy to dual therapy, 20 % increased the dose of dual therapy, and 13 % used triple therapy [24].

According to the Eurasian Association of Therapists’ registry data, after 6 months of observation, the number of patients with uncontrolled hypertension decreased from 20.1 % to 4 % [17].

As a result of the examination of 200 patients who had recovered from NCI, it was found out that one of the seven individuals is at risk of developing either new-onset of AH or a worsening of the existing condition. Considering the prolonged asymptomatic course of AH, it is recommended to monitor all patients who have had COVID-19 within 6–12 months after the infection [25].

According to M. Akpek [26], among 211 patients who had COVID-19 (age 46.5 ± ± 12.7 years), in some cases the onset of AH occurred at 31.6 ± 5.0 days (p < 0.001). The authors suggest that NCI may potentiate the onset of AH. According to the registry of the Eurasian Association of Therapists, which includes more than 7,500 patients who had COVID-19, 2.6 % of cases had newly diagnosed AH [17]. New cases of AH in the 3- and 4–6-month periods after COVID-19 accounted for 2.3 % and 2.8 %, respectively [27]. After 3 months, AH was detected in 23 % of patients with mild pneumonia and in 63 % of those with moderate one [28].

Thus, the most common comorbid pathology in patients with laboratory-confirmed cases of COVID-19 is AH. To date, it has not been proven that it is an independent factor of a severe course of COVID-19. Arterial hypertension in the post-COVID period is characterized by a high frequency of an unstable course despite the administration of combined antihypertensive therapy, as well as target organ damage and greater severity in the presence of comorbid conditions, and less frequently by the development of new cases of AH.

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About the authors

E. V. Zolotukhina

Novosibirsk State Medical University

Email: LAP232@yandex.ru
ORCID iD: 0009-0007-1364-711X

Postgraduate Student of the Department of Hospital Therapy and Medical Rehabilitation

Russian Federation, Novosibirsk

L. A. Panacheva

Novosibirsk State Medical University

Author for correspondence.
Email: LAP232@yandex.ru
ORCID iD: 0000-0002-8230-8142

Postgraduate Student of the Department of Hospital Therapy and Medical Rehabilitation

Russian Federation, Novosibirsk

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