Email this article Predictors of the development of abnormal patterns of circadian blood pressure rhythm in patients with hypertension after a new coronavirus infection
- Authors: Syuzeva N.M.1, Masalkina O.V.1, Koziolova N.A.1, Chernyavina A.I.1
-
Affiliations:
- E.A. Vagner Perm State Medical University
- Issue: Vol 41, No 4 (2024)
- Pages: 87-100
- Section: Methods of diagnostics and technologies
- Submitted: 02.10.2024
- Accepted: 02.10.2024
- Published: 03.10.2024
- URL: https://permmedjournal.ru/PMJ/article/view/636661
- DOI: https://doi.org/10.17816/pmj41487-100
- ID: 636661
Cite item
Abstract
Objective. To determine the predictors of the development of abnormal patterns of circadian blood pressure (BP) rhythm in patients with arterial hypertension (AH) after a new coronavirus infection (NСVI).
Materials and methods. The study is a comparative clinical research of the same patients with hypertension before and after NCVI with retrospective evaluation of the data. Within 2 years from 842 patients with cardiovascular risk factors, according to the inclusion and non-inclusion criteria 70 patients with target levels of office BP, home monitoring and 24-hour blood pressure monitoring (ABPM) on the background of a continuous antihypertensive therapy were included in the study. Abnormal patterns of circadian BP were recorded after NCVI during ABPM in all of them. All patients with hypertension underwent a complete examination before and after NCVI.
Results. After NCVI in patients with AH who had achieved the target ranges of office BP before its development, at home measurement and ABPM against the background of continuous antihypertensive therapy with high adherence to treatment, in more than 50 % of patients BP readings were not in the target values, in more than 50 % of the examined patients, BP variability was higher than the permissible values, in 73 % of patients the average daily BP was above 53 mm Hg. Abnormal patterns of circadian BP rhythm in patients with hypertension after NCVI were detected in 61.5 %: "Non-dipper" in 28.6 %; "Night-dipper" – in 21.9 %, masked nocturnal hypertension – in 17.1 %.
Conclusion. The indicative significance of the development of abnormal patterns of circadian BP rhythm in patients with hypertension after NCVI was demonstrated by 3 qualitative indicators: glomerular filtration rate with cystatin C < 60 ml/min/1.73 m2, cardio-ankle vascular index (CAVI) ≥ 9, and a high frequency of AGT gene polymorphism – T/T genotype (in 54.3 % of patients).
Full Text
Introduction
Despite the reduction in the incidence of fatal and adverse cardiovascular events in patients after novel coronavirus infection, (nCoV) there has been growing concern about the potential impact of COVID-19 on the cardiovascular system and its association with hypertension (HTN). People with various symptoms characteristic of cardiovascular disease continue to seek medical care worldwide, even after the acute phase of SARS-CoV-2 infection has subsided [1]. More than 200 symptoms affecting various organ systems have been recognized as potential complications of COVID-19.
A meta-analysis of 30 observational studies found that 19 studies provided substantial evidence demonstrating an increased risk of developing hypertension after COVID-19 infection [2].
Various theories have been developed that suggest a link between COVID-19 and elevated blood pressure (BP). However, the exact relationship between SARS-CoV-2 infection and the long-term risk of HTN development and progression remains poorly understood. It has been suggested that endothelial injury and dysfunction of the renin-angiotensin-aldosterone system may be the causes of elevated BP after nCoV.
In the conducted studies of changes in BP levels after nCoV, office BP and its average daily values are mainly assessed when performing daily BP (ABPM) monitoring [3]. Data on the frequency and predictors of the development of abnormal patterns of daily BP rhythm in patients with hypertension (AH) after nCoV are practically absent.
All of the above highlights the need for a thorough study of the relationship between COVID-19 and the progression of AH. These insights are needed to develop effective approaches to BP prevention and management, especially in hypertensive patients who have survived COVID-19 infection.
The aim of the study is to determine predictors of the development of abnormal patterns of circadian rhythm of BP in patients with hypertension who have undergone nCoV.
Materials and methods
A fragment of a clinical prospective observational study, which has been conducted from 2017 to the present, is presented.
This study is a comparative clinical study of the same patients with AH before and after nCoV with a retrospective data evaluation.
The study was conducted in accordance with Good Clinical Practice standards and the principles of the Declaration of Helsinki. The study protocol was approved by the Ethics Committee. Written informed consent was obtained from all participants prior to inclusion in the study.
Over a period of 2 years, 842 patients with cardiovascular risk factors were examined; the present study included 70 patients with AH with target levels of office BP, with home monitoring and with daily ABPM monitoring against the background of continuous antihypertensive therapy, in whom abnormal patterns of the daily BP rhythm were recorded after nCoV during 24-hour blood pressure monitoring. All patients with AH underwent a comprehensive examination before and after the transferred nCoV. The diagnosis of the past nCoV was confirmed by the polymerase chain reaction test (PCR test) and a smear for the SARS-CoV-2 coronavirus (Vector Best JSC, Russia).
Inclusion criteria for the study: confirmed diagnosis of hypertension of any degree of increased BP, stages I–II before the development of nCoV; achievement of the target level of office BP during ABPM before the development of nCoV; continuous use of antihypertensive therapy with a high level of adherence to treatment; after nCoV – the presence of abnormal patterns of the daily rhythm of BP during nCoV.
Exclusion criteria: presence of associated clinical conditions, secondary AH, presence of acute respiratory viral infection or pneumonia with a negative PCR test for nCoV less than 3 months old; history of severe liver disease (chronic hepatitis, cirrhosis); history of severe chronic kidney disease (CKD) (stage 4–5 according to glomerular filtration rate (GFR), defined by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula, dialysis, transplantation); severe blood diseases and autoimmune blood diseases in the anamnesis; thyroid dysfunction; diabetes mellitus type 1 and 2; oncological diseases; acute inflammatory and infectious diseases, including a history of pulmonary tuberculosis; severe dementia and mental disorders that prevent the patient from signing informed consent.
All patients had their office (clinical) BP measured before and after the past nCoV (no later than 3 months), their average BP measured at home was calculated (according to the diary for the last 7 days), and daily BP monitoring (ABPM) was performed using the Card (X) plore device (Meditech, Hungary). During ABPM, the average daily ambulatory, average nighttime and average daytime systolic (MAP) and diastolic (DBP) BP, the daily index (DI) of MAP and DBP, the frequency of occurrence of various types of daily curves, the variability of MAP and DBP during the day and night were determined, average daily pulse BP (positive pressure MAP and positive pressure DBP), morning rise value (MRV) of MAP and DBP, target BP range depending on age and damage to target organs. Normal values of BP indicators are presented in Table 1 [4; 5]. Normal values of BP indicators are presented in Table 1 [4; 5].
Table 1
Normal BP indicators
Indicator | Data | Day | Night |
BP at home, mm Hg | < 135/85 |
|
|
Average daily BP, | < 130/80 |
|
|
Average daily BP, |
| < 135/85 |
|
Average daily BP, |
|
| < 120/70 |
Degree of nighttime decrease in MAP and DBP, % | 10–20 |
|
|
MAP variability, mm Hg |
| < 15 | < 15 |
DBP variability, mm Hg |
| < 14 | < 12 |
The magnitude of the morning rise in MAP, mm Hg | < 56 |
|
|
The magnitude of the morning rise in DBP, mm Hg | < 36 |
|
|
Average daily BP, | < 53 |
|
|
Note: MAP – systolic BP, DBP – diastolic BP.
According to the level of reduction in MAP and DBP at night, four types of daily curves were determined (Table 2) [5].
Table 2
Types of circadian BP rhythm curves
Nocturnal Decrease | Curves | Daily |
Normal degree of | dipper | 10–20 |
Insufficient degree of nocturnal decrease in BP | non-dipper | < 10 |
Increased degree of | over-dipper | > 20 |
Persistent increase in nocturnal BP | night peaker | < 0 |
To verify masked nocturnal hypertension, the following criteria were used: mean daytime ambulatory BP < 135 / 85 mm Hg, mean nighttime ambulatory BP ≥ 120 / 70 mm Hg, regardless of the mean daily ambulatory BP with office BP < 140 / 90 mm Hg [6].
The following methods were used to assess adherence: keeping a diary of self-monitoring of BP and medication intake, a modified Morisky-Green questionnaire (MMAS-8), and achieving target indicators during treatment. High adherence to treatment was defined as having 8 points on the Morisky-Green questionnaire, average – having 6–7 points, and poor – having less than 6 points.
To assess cognitive functions, the Mini Mental State Examination (MMSE) score was determined. The results were interpreted as follows: 28 points – mild cognitive impairment; 25–27 points – moderate cognitive impairment; 20–24 points – mild dementia; 10–19 points – moderate dementia; < 10 points – severe dementia. The results were interpreted as follows: 28 points – mild cognitive impairment; 25–27 points – moderate cognitive impairment; 20–24 points – mild dementia; 10–19 points – moderate dementia; < 10 points – severe dementia.
To assess anxiety and depression, the number of points on the HADS (The Hospital Anxiety and Depression Scale) was determined [7]. The Scale consists of 14 statements and includes two parts: anxiety (Part I) and depression (Part II). To interpret the results, scores were determined for each part separately: 0–7 points – no symptoms of anxiety and depression; 8–10 points – subclinically expressed anxiety / depression; 11 points and above – clinically expressed anxiety / depression.
To assess kidney damage in patients with AH, serum creatinine was determined with calculation of the glomerular filtration rate (GFR) using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula, and the concentration of cystatin C in the serum was determined by enzyme immunoassay using the BioVendor reagent (Czech Republic) on an Immulite 1000 analyzer (DPC, USA) with calculation of the GFR based on cystatin C. The reference values for cystatin C were considered to be 1043.1 ± 107.5 ng/ml. The increase in albumin / protein excretion in urine was determined using test strips.
To assess the indicators of the structural and functional state of the heart, transthoracic echocardiography (EchoCG) was used on the Vivid S5 device (GE Healthcare, USA) with determination of the size of the left ventricle (LV), systolic and diastolic functions, calculation of the LV myocardial mass (LVMM), and the LVMM index (LVMI). In patients with normal body weight, LVMI was calculated as the ratio of LVMI to body surface area (BSA), the criterion for LVH was LVMI > 115 g / m2 in men and > 95 g / m2 in women. For overweight and obese patients, LVMI was estimated using the ASE formula as the ratio of LVMI to height in meters2; the LVH criterion was LVMI for men > 50 g / m2, for women > 47 g / m2.
To assess arterial damage in patients with AH, volumetric sphygmoplethysmography was performed using the VaSera VS-1000 device (Fucuda Denshi, Japan). The following parameters were assessed: determination of the cardio-ankle-vascular index (CAVI1), carotid-femoral pulse wave velocity (PWVcf), PWV in the brachial-ankle segment on the right and left (R-PWV and L-PWV), PWV of the brachial artery (B-PWV), PWV in the aorta (PWVa), PWV in the carotid artery (C-PWV), ankle-brachial index on the right and left (R-ABI and L-ABI) and augmentation index (R-AI). An increase in arterial stiffness was assessed by PWVcf > 10 m/s and / or R-PWV and L-PWV ³ 18 m/s and / or CAVI1 index > 9 and / or ABI < 0.9.
Patients underwent genotype determination using the markers AGT Thr174Met variant rs4762, GNB3 C825T variant rs5443, MTHFR C677T variant rs1801133, MTRR Ile22Met variant rs1801394, ApoE Cys130Arg variant rs429358, PPARa G/C variant rs4253778. The following genotypes were determined: for the AGT gene – C/C, C/T, T/T; for the GNB3 gene – C/C, C/T, T/T; for the MTHFR gene – C/C, C/T, T/T; for the MTRR gene – A/A, A/G, G/G; for the ApoE gene – T/T, T/C, C/C; for the PPARa gene – G/G, G/C, C/C.
Statistical data processing was performed using the Statistica 10.0 software package. When performing statistical data processing, the critical value of the level of statistical significance when testing null hypotheses was taken to be 0.05. The normality of distribution of features in groups was tested using the Shapiro – Wilk and Kolmogorov – Smirnov criteria. For quantitative characteristics corresponding to the normal distribution law, the arithmetic mean values and standard deviations (M ± SD) were calculated; for distributions not corresponding to the normal distribution law, the medians, 25th and 75th quartiles (Med) were calculated. For categorical characteristics, the absolute frequency and the frequency of occurrence of the characteristic in percent (%) were calculated. When comparing average quantitative indicators and normal distribution, the Student's criterion was used; for a distribution that does not correspond to the normal distribution law, the Mann – Whitney criterion was used; for categorical indicators, the c2 criterion with Yates's correction for continuity was used.
To determine the presence of a relationship between quantitative characteristics, Spearman's correlation analysis was used; between qualitative characteristics, A.A. Chuprov's coefficient of mutual contingency was used. In accordance with the recommendations of Rea and Parker, the significance level of the obtained relationships was determined. The critical level of statistical significance of null hypotheses when assessing the relationship was
p < 0.05. When compiling contingency tables, odds ratios (OR), relative risk (RR), and 95 % confidence interval (CI) for these indicators were determined.
The predictive significance of candidate predictors for the development of abnormal circadian rhythm patterns was assessed using logistic regression analysis. To assess the quality of logistic regression, ROC (Receiver Operating Characteristic) analysis was used with the calculation of the quantitative indicator of the area under the curve (AUC – Area Under Curve) > 0.5 at p < 0.05, its sensitivity and specificity were assessed.
Results and discussion
The average period of inclusion of patients before nCoV was 2.8 ± 0.4 months, after nCoV – 2.1 ± 0.6 months (p = 0.117). The average age of patients was 54.2 ± 8.7 years, 31 (44.3 %) women and 39 (55.7 %) men. Adherence to antihypertensive therapy was 7.81 ± 0.05 and 7.90 ± 0.08 points according to the modified Morisky-Green questionnaire, respectively, before and after nCoV (p = 0.496). Patients before and after the development of nCoV did not differ in cardiovascular risk factors, concomitant pathology, or the use of constant antihypertensive therapy.
Table 3 shows the BP values in patients with AH before and after the development of nCoV.
Table 3
Blood pressure indicators in patients with hypertension before and after nCoV disease, n = 70
Parameter | Patients | Patients | p |
Office MAP, mm Hg | 128 ± 12 | 142 ± 16 | < 0.001 |
Office DBP, mm Hg | 76 ± 5 | 94 ± 8 | < 0.001 |
Target office BP level, abs. (%) | 69 (98.6) | 32 (45.7) | < 0.001 |
MAP for home measurement, mm Hg | 131 ± 10 | 141 ± 18 | < 0.001 |
DBP for home measurement, mm Hg | 82 ± 7 | 93 ± 11 | < 0.001 |
Target BP level for home measurement, abs. (%) | 70 (100.0) | 35 (50.0) | < 0.001 |
Average daily MAP, mm Hg | 132 ± 6 | 149 ± 18 | < 0.001 |
Average daily DBP, mm Hg | 85 ± 4 | 94 ± 12 | < 0.001 |
Target BP of the average daily BP, abs. (%) | 68 (97.1) | 18 (25.7) | < 0.001 |
Average daily MAP, mm Hg | 129 ± 7 | 152 ± 19 | < 0.001 |
Average daily DBP, mm Hg | 78 ± 3 | 98 ± 11 | < 0.001 |
Target level of average daytime BP, abs. (%) | 69 (98.6) | 22 (31.4) | < 0.001 |
Average nighttime MAP, mm Hg | 116 ± 7 | 144 ± 21 | < 0.001 |
Average nighttime DBP, mm Hg | 68 ± 5 | 89 ± 18 | < 0.001 |
Target level of average nighttime BP, abs. (%) | 65 (92.9) | 3 (4.3) | < 0.001 |
Degree of nocturnal decrease in MAP, % | 15.4[10.8; 18.6] | 7.1[–7.6; 11.4] | < 0.001 |
Degree of nocturnal decrease in DBP, % | 12.5[11.4; 17.9] | 6.3[–8.1; 12.7] | < 0.001 |
Number of patients in the dipper category, abs. (%) | 64 (91.4) | 16 (22.9) | < 0.001 |
Number of patients in the non-dipper category, abs. (%) | 2 (2.9) | 21 (28.6) | < 0.001 |
Number of patients in the over-dipper category, abs. (%) | 4 (5.7) | 0 (0) | 0.121 |
Number of patients in the night peaker category, abs. (%) | 0 (0) | 23 (32.9) | < 0.001 |
MAP variability, mm Hg | 11.4[4.8; 14.0] | 18.5[13.7; 24.8] | < 0.001 |
MAP variability > 15 mm Hg, abs. (%) | 2 (2.9) | 41 (58.6) | < 0.001 |
DBP variability, mm Hg | 9.1[5.6; 13.0] | 16.7[11.7; 19.3] | < 0.001 |
DBP variability > 14 by day, | 3 (4.3) | 37 (52.9) | < 0.001 |
The magnitude of the morning rise in MAP, mm Hg | 23.5 ± 6.8 | 58.9 ± 14.4 | < 0.001 |
The magnitude of the morning rise in MAP > 56 mm Hg, abs. (%) | 5 (7.1) | 28 (40.0) | < 0.001 |
Morning rise in DBP, mm Hg, abs. (%) | 16.7 ± 5.8 | 31.1 ± 7.4 | < 0.001 |
The magnitude of the morning rise in DBP > 36 mm Hg, abs. (%) | 2 (2.9) | 21 (30.0) | < 0.001 |
Average daily sphygmic BP, mm Hg | 43.7 ± 8.2 | 61.1 ± 18.4 | < 0.001 |
Average daily sphygmic BP > 53 mm Hg, abs. (%) | 6 (8.6) | 51 (72.9) | < 0.001 |
Presence of masked nocturnal AH, abs. (%) | 2 (2.9) | 12 (17.1) | 0.012 |
Note: nCoV – novel coronavirus infection; MAP – systolic BP, DBP – diastolic BP.
Table 4 presents the parameters in patients with hypertension, reflecting the filtration function of the kidneys, before and after the development of nCoV.
Table 4
Parameters reflecting filtration function of kidneys in patients with hypertension before and after nCoV disease, n = 70
Parameter | Patients | Patients | p |
Serum creatinine, µmol/l | 87.8[67.7; 105.8] | 94.2[78.6; 137.6] | 0.126 |
Urea, mmol/l | 6.7[5.4; 7.2] | 7.2[5.3; 8.6] | 0.348 |
CKD-EPI, mL/min/1.73 m2 (CKD-EPI) | 74.5 ± 12.7 | 69.3 ± 14.4 | 0.013 |
CKD-EPI < 60 mL/min/1.73 m2, abs. (%) | 12 (17.1) | 28 (40.0) | 0.006 |
Cystatin С, ng/mL | 886 ± 108 | 1256 ± 203 | < 0.001 |
GFR cys (CKD-EPI), mL/min/1.73 m2 | 88.5 ± 9.1 | 57.0 ± 8.6 | < 0.001 |
GFR cys (CKD-EPI) < 60 mL/min/1.73 m2, abs. (%) | 15 (21.4) | 37 (52.9) | < 0.001 |
Increased albumin escretion / protein with urine, abs. (%) | 18 (25.7) | 54 (77.1) | < 0.001 |
Note: nCoV – novel coronavirus infection, GFR – glomerular filtration rate.
Correlation analysis showed that with abnormal patterns of the daily rhythm of blood pressure among the parameters reflecting the filtration function of the kidneys, in patients with hypertension after nCoV only GFRcys (K = 0.202; p = 0.017) with an inverse average degree of correlation severity and the presence of an increase in the excretion of albumin / protein in the urine (K = 0.407; p < 0.001) with a direct average degree of correlation severity were interconnected.
Patients did not differ statistically significantly before and after the past nCoV in all echocardiographic parameters reflecting structural and functional changes in the heart. Before and after nCoV, 34 (48.6 %) and 35 (50.0 %) patients, respectively, had Left Ventricular Hypertrophy (LVH) (p = 0.866), 56 (80.0 %) and 64 (91.4 %), respectively, had LVDD (p = 0.091), and 8 (11.4 %) and 17 (24.3 %), respectively, had an increase in left atrial volume index (LAVI) (p = 0.078).
Table 5 presents data in patients with AH, reflecting the remodeling of the arterial wall, before and after the disease nCoV.
Table 5
Parameters reflecting arterial wall remodeling in patients with hypertension before and after nCoV, n = 70
Parameter | Patients before nCoV | Patients after nCoV | p |
R-ABI | 1.06 ± 0.05 | 1.03 ± 0.08 | 0.078 |
R-ABI < 0.9, abs. (%) | 1 (1.4) | 3 (4.3) | 0.612 |
L-ABI | 1.08 ± 0.08 | 1.04 ± 0.05 | 0.078 |
L-ABI < 0.9, abs. (%) | 1 (1.4) | 3 (4.3) | 0.612 |
R-PWV, m/s | 14.2 [12.4; 16.9] | 16.1 [13.7; 20.5] | 0.148 |
R-PWV > 18 m/s, abs. (%) | 5 (7.1) | 24 (34.3) | < 0.001 |
L-PWV, m/s | 13.2 [11.6; 15.1] | 16.8 [13.2; 21.1] | 0.095 |
L-PWV > 18 m/s, abs. (%) | 6 (8.6) | 28 (40.0) | < 0.001 |
B-PWV, m/s | 6.7 [5.9; 7.0] | 7.5 [6.4; 8.0] | 0.284 |
C-PWV, m/s | 5.1 [4.6; 6.8] | 6.0 [4.8; 7.3] | 0.261 |
PWVao, m/s | 7.6 [7.1; 8.5] | 8.2 [6.5; 8.9] | 0.138 |
PWVcf, m/s | 9.8 [7.2; 10.5] | 11.0 [7.1; 11.6] | 0.012 |
PWVcf > 10 m/s, abs. (%) | 12 (17.1) | 40 (57.1) | < 0.001 |
R-AI | 1.05 [1.00; 1.12] | 1.07 [0.99; 1.18] | 0.461 |
CAVI | 8.02 [7.43; 8.56] | 9.37 [8.12; 11.03] | < 0.001 |
CAVI > 9 | 14 (20.0) | 45 (64.3) | < 0.001 |
Note: R-ABI and L-ABI are the ankle-brachial index on the right and left, R-PWV and L-PWV are the pulse wave velocity (PWV) in the brachial-ankle segment on the right and left, B-PWV is the PWV of the brachial artery, C-PWV is the PWV in the carotid artery, PWVa is the PWV in the aorta, PWVcf is the PWV in the carotid-femoral segment, R-AI is the augmentation index, CAVI1 is the cardio-ankle vascular index.
In patients with hypertension after undergoing nCoV, the parameters reflecting an increase in arterial stiffness were statistically significantly higher, such as R-PWV > 18 m/s, L-PWV > 18 m/s, PWVcf, m/s, PWVcf > 10 m/s, CAVI, CAVI > 9. However, according to the correlation analysis, only PWVcf > 10 m/s (K = 0.244; p = 0.007) and CAVI index > 9 (K = 0.314; p < 0.001) were associated with abnormal patterns of circadian rhythm of BP in patients with hypertension after nCoV, with a direct moderate degree of correlation.
Table 6 presents additional laboratory parameters in patients with hypertension that differ before and after the development of nCoV.
Table 6
Additional laboratory parameters in patients with hypertension that differ before and after nCoV disease, n = 70
Parameter | Patients before nCoV | Patients after nCoV | p |
Lymphocytes, % | 28.5 ± 4.8 | 21.9 ± 7.6 | < 0.001 |
Lymphocytes < 19 %, abs. (%) | 4 (5.7) | 22 (31.4) | < 0.001 |
ESR, mm/h | 18.6 ± 5.7 | 29.6 ± 7.9 | < 0.001 |
ESR mm/h above normal in males and | 8 (11.4) | 34 (48.6) | < 0.001 |
CRP, mg/l | 4.1 ± 0.9 | 12.7 ± 1.5 | < 0.001 |
CRP > 5 mg/l, abs. (%) | 5 (7.1) | 59 (84.3) | < 0.001 |
Plasma glucose in the fasted state, mmol/l | 5.1 [4.2; 5.8] | 5.7 [4.6; 6.7] | 0.005 |
Plasma glucose in the fasted state | 8 (11.4) | 17 (24.3) | 0.078 |
Nt-proBNP, pg/ml | 36.9 [24.8; 85.4] | 89.7 [38.6; 128.3] | < 0.001 |
Nt-proBNP > 125 pg/ml, abs. (%) | 1 (1.4) | 12 (17.1) | 0.004 |
Note: ESR – erythrocyte sedimentation rate, CRP – C-reactive protein, Nt-proBNP – N-terminal brain natriuretic propitide.
Among the additional laboratory parameters that differed in patients before and after nCoV, when conducting a correlation analysis, the presence of a direct strong degree of dependence on the relationship with abnormal patterns of the daily rhythm of BP in patients with AH after nCoV was demonstrated only by the concentration of C-reactive protein in the blood (K = 0.463; p < 0.001).
Table 7 presents parameters reflecting the state of cognitive functions, anxiety and depression in patients with hypertension before and after nCoV.
Table 7
Parameters Reflecting the state of cognitive functions, the presence and severity of anxiety and depression in patients with hypertension before and after nCoV disease, n = 70
Parameter | Patients before nCoV | Patients after nCoV | p |
MMSE, scores | 29.1 [28.6; 30.0] | 26.7 [25.4; 28.4] | 0.004 |
MMSE 29–30 scores, abs. (%) | 67 (95.7) | 55 (78.6) | 0.006 |
MMSE 28 scores, abs. (%) | 2 (2.9) | 8 (11.4) | 0.101 |
MMSE 25–27 scores, abs. (%) | 1 (1.4) | 4 (5.7) | 0.363 |
MMSE 20–24 scores, abs. (%) | 0 (0) | 2 (2.9) | 0.477 |
MMSE 10–19 scores, abs. (%) | 0 (0) | 1 (1.4) | 0.998 |
Cognitive deterioration+ dementia, abs. (%) | 3 (4.3) | 15 (21.4) | 0.006 |
HADS anxiety, scores | 6.8 [2.4; 10.8] | 9.7 [6.1; 12.7] | < 0.001 |
HADS anxiety 0–7 scores, abs. (%) | 51 (72.9) | 34 (48.6) | 0.006 |
HADS anxiety 8–10 scores, abs. (%) | 14 (20.0) | 18 (25.7) | 0.546 |
HADS anxiety 11 scores and above, abs. (%) | 5 (7.1) | 18 (25.7) | 0.007 |
Anxiety, abs. (%) | 19 (27.1) | 36 (51.4) | 0.006 |
HADS depression, scores | 5.7 [2.8; 9.2] | 7.0 [4.1; 10.9] | < 0.001 |
HADS depression 0–7 scores, abs. (%) | 62 (88.6) | 48 (68.6) | 0.008 |
HADS depression 8–10 scores, abs. (%) | 7 (10.0) | 17 (24.3) | 0.044 |
HADS depression 11 scores and above, аbs. (%) | 1 (1.4) | 5 (7.1) | 0.211 |
Depression, abs. (%) | 8 (11.4) | 22 (31.4) | 0.008 |
Impairment of cognitive functions and the presence of depression in patients with hypertension after nCoV were not associated with the development of abnormal patterns of circadian rhythm of BP. The presence of anxiety showed a direct weak but statistically significant relationship with abnormal patterns of circadian rhythm of BP in patients with hypertension after past nCoV (K = 0.188; p = 0.040).
Table 8 presents the frequency of occurrence of gene polymorphisms in the examined patients with hypertension and abnormal patterns of daily BP profile.
Table 8
Frequency of occurrence of gene polymorphisms in examined patients, n = 70
Gene Polymorphism | Genotype | All Patients with AH, n = 70 |
AGT, abs. (%) | С/С | 8 (11.4) |
С/Т | 7 (10.0) | |
Т/Т | 38 (54.3) | |
GNB3, abs. (%) | С/С | 12 (17.1) |
С/Т | 8 (11.4) | |
Т/Т | 7 (10.0) | |
MTHFR, abs. (%) | С/С | 37 (52.9) |
С/Т | 7 (10.0) | |
Т/Т | 35 (50.0) | |
MTRR, abs. (%) | А/А | 6 (8.6) |
А/G | 5 (7.1) | |
G/G | 11 (15.7) | |
АроЕ, abs. (%) | Т/Т | 12 (17.1) |
Т/С | 4 (5.7) | |
С/С | 3 (4.3) | |
PPARα, abs. (%) | G/G | 9 (12.9) |
G/C | 3 (4.3) | |
C/C | 3 (4.3) |
When conducting a correlation analysis, direct medium-strength relationships were obtained between the abnormal patterns of circadian rhythm of BP in patients with AH after nCoV and the frequency of the AGT gene polymorphism – genotype T/T (K = 0.211; p = 0.018), and the frequency of the MTHFR gene polymorphism – genotype C/C (K = 0.202; p = 0.027).
When conducting a logistic regression analysis, only three qualitative indicators out of 8 candidate predictors, showed prognostic significance for the development of abnormal patterns of circadian rhythm of BP in patients with AH after suffering from nCoV: GFRcys < 60 ml/min/1.73 m2, CAVI > 9 and a high frequency of AGT gene polymorphism – genotype T/T (Fig. 1–3).
Fig. 1. ROC-curve for GFRcys < 60 ml/min/1.73 m2 as a predictor of the development of abnormal patterns of circadian rhythm of BP in patients with hypertension after nCoV (AUG = 0.873 ± 0.073, p = 0.005; sensitivity – 81 %, specificity – 76 %); False Positive Fraction – false positive result, True Positive Fraction – false negative result
Fig. 2. ROC-curve for index CAVI as a predictor of development of abnormal patterns of BP circadian rhythm in patients with hypertension after nCoV (AUG = 0,794 ± 0,071, p = 0,002; sensitivity – 78 %, specificity – 84 %); False Positive Fraction – false positive result, TruePositive Fraction – false negative result
Fig. 3. ROC-curve for gene polymorphism AGT – Т/T genotype as a predictor of development of abnormal patterns of BP circadian rhythm in patients with AH after nCoV (AUG = 0,906 ± 0,043, p < 0,001; sensitivity – 88 %, specificity – 80 %); False Positive Fraction – false positive result, True Positive Fraction – false negative result
There is an opinion that the increase in BP in patients with AH after past nCoV is not so much associated with the infection as with a combination of cardiovascular risk factors, especially in elderly patients, and COVID-19 only acts as their trigger [8]. But our study included young and middle-aged patients who were committed not only to antihypertensive therapy, but also to a healthy lifestyle.
Many researchers have proven that previous nCoV is associated with the development of diabetes mellitus and impaired renal function [9; 10].
We suggest that, on the one hand, deterioration of renal function after nCoV may be a predictor of increased BP and the development of abnormal patterns of circadian rhythm of BP, especially masked nocturnal hypertension, on the other hand, activation of the renin-angiotensin-aldosterone system, proven in nCoV, may be the cause of AH, which, in turn, negatively affects the function of the glomeruli of the kidneys.
One meta-analysis found that higher prevalence of depression, anxiety, insomnia, psychological stress and post-traumatic stress disorder among populations affected by the pandemic could be the cause of increased BP [11]. In our study, we did not obtain this relationship, which is probably due to careful monitoring of patients in the study and correction of risk factors. In the study by M. Akpek, no dependence was found between the increase in BP after nCoV and stress indicators [12].
A Russian study of hospitalized patients with COVID-19 found significantly higher CAVI index values [13]. An association was found between elevated CAVI and COVID-19 index regardless of age, hypertension, plasma glucose levels, GFR, and diabetes mellitus. Our data support the hypothesis that SARS-CoV-2 affects endothelial cells infected with this virus, increasing the production of proinflammatory cytokines and prothrombotic factors, which may induce early vascular aging and increased arterial stiffness, which in turn contributes to increased BP [14].
We found only 12 studies that studied AGT gene polymorphism in conjunction with the severity of COVID-19. We tried to prove that pathological AGT gene polymorphism – T/T genotype is associated not only with the development of nCoV, but also with the occurrence of abnormal patterns of BP profile in the post-COVID period.
Conclusions
After the previous nCoV in patients with AH, who had achieved the target ranges of office BP before its development, with home measurement and ABPM against the background of constant antihypertensive therapy with high adherence to treatment, it was revealed that in more than 50 % of patients, BP indicators were not within target values, in more than 50 % of those examined, BP variability was higher than acceptable values, in 73 % of patients, the average daily PBP was higher than 53 mm Hg. Abnormal patterns of circadian rhythm of BP were detected in 61.5 % of patients with AH after nCoV: non-dipper – in 28.6 %; night-dipper – in 21.9 %, masked nocturnal hypertension – in 17.1 %. Three qualitative indicators showed predictive significance of the development of abnormal patterns of circadian rhythm of BP in patients with AH after nCoV: GFRcys < 60 ml/min/1.73 m2, CAVI > 9 and high frequency of AGT gene polymorphism – T/T genotype (in 54.3 % of patients).
About the authors
N. M. Syuzeva
E.A. Vagner Perm State Medical University
Email: nakoziolova@mail.ru
ORCID iD: 0000-0001-8754-2950
Assistant of the Department of Propaedeutics of Internal Diseases № 2
Russian Federation, PermO. V. Masalkina
E.A. Vagner Perm State Medical University
Email: nakoziolova@mail.ru
ORCID iD: 0009-0006-3364-0591
PhD (Medicine), Associate Professor of the Department of Propaedeutics of Internal Diseases № 2
Russian Federation, PermN. A. Koziolova
E.A. Vagner Perm State Medical University
Author for correspondence.
Email: nakoziolova@mail.ru
ORCID iD: 0000-0001-7003-5186
DSc (Medicine), Professor, Head of the Department of Propaedeutics of Internal Diseases № 2
Russian Federation, PermA. I. Chernyavina
E.A. Vagner Perm State Medical University
Email: nakoziolova@mail.ru
ORCID iD: 0000-0002-0051-6694
DSc (Medicine), Associate Professor of the Department of Propaedeutics of Internal Diseases № 2
Russian Federation, PermReferences
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