key: cord-0715662-9dpq8mt8 authors: He, Chunyan; Liu, Chuan; Yang, Jie; Tan, Hu; Ding, Xiaohan; Gao, Xubin; Yang, Yuanqi; Shen, Yang; Xiang, Hedong; Ke, Jingbin; Yuan, Fangzhengyuan; Chen, Renzheng; Cheng, Ran; Lv, Hailin; Li, Ping; Zhang, Limin; Huang, Lan title: Prognostic significance of day‐by‐day in‐hospital blood pressure variability in COVID‐19 patients with hypertension date: 2022-02-07 journal: J Clin Hypertens (Greenwich) DOI: 10.1111/jch.14437 sha: 680ad8ab986128ec41a00c203cfacd0aa60e9cbd doc_id: 715662 cord_uid: 9dpq8mt8 Hypertension is the most common comorbidity in patients with coronavirus disease 2019 (COVID‐19) and increases in‐hospital mortality. Day‐by‐day blood pressure (BP) variability (BPV) is associated with clinical outcomes in hypertensive patients. However, little information is available on the association of BPV with the outcomes of COVID‐19 patients with hypertension. This study aimed to demonstrate whether day‐by‐day in‐hospital BPV had prognostic significance in these patients. The authors included 702 COVID‐19 patients with hypertension from Huoshenshan Hospital (Wuhan, China), who underwent valid in‐hospital BP measurements on at least seven consecutive days. Day‐by‐day BPV was assessed by standard deviation (SD), coefficient of variation (CV), and variation independent of mean (VIM). Overall, patients with severe COVID‐19 and non‐survivors had higher BPV than moderate cases and survivors, respectively. Additionally, higher BPV was correlated with greater age and higher levels of C‐reactive protein, procalcitonin, high‐sensitive cardiac troponin I, and B‐type natriuretic peptide. In multivariable Cox regression, SD of systolic BP (SBP) was predictive of mortality [hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.05–1.30] as well as acute respiratory distress syndrome (ARDS) (HR 1.09, 95% CI 1.01–1.16). Similar trends were observed for CV and VIM of SBP, but not indices of diastolic BP variability. The authors demonstrated that day‐by‐day in‐hospital SBP variability can independently predict mortality and ARDS in COVID‐19 patients with hypertension. And high BPV might be correlated with severe inflammation and myocardial injury. Further studies are needed to clarify whether early reduction of BPV will improve the prognosis of these patients. Coronavirus disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly developed into a global pandemic since December 2019. With high transmission and lack of specific treatment, more than 200 million COVID-19 cases have been confirmed worldwide, and four million patients had progressed to death as of September 2021, which poses a great threat to global health. SARS-CoV-2 mainly attacks the respiratory system, with some patients progressing to acute respiratory distress syndrome (ARDS). 1 As reported, patients with comorbidities are more likely to develop severe pneumonia and adverse clinical outcomes. 2, 3 Hypertension has been reported to be the most common comorbidity in COVID-19 patients and it is associated with pronounced increase in disease severity and the risk of mortality. 4, 5 Hence, it should be treated to prevent adverse outcomes. Blood pressure (BP) monitoring in clinical settings or out of office has generally been used for clinical management of hypertension. Recently, blood pressure variability (BPV), which represents the fluctuation of BP in a period of time, has been identified as an accurate assessment of BP that helps to avoid oscillations of mean BP. 6 Increasing evidence suggests that BPV is associated with higher risk of incident cardiovascular diseases and all-cause mortality, which is independent of mean BP. [7] [8] [9] Day-by-day BP measurement is commonly used to assess mid-term BPV, which provides incremental value of risk assessment over BP level. 6 However, it remains to be determined whether BPV correlates with adverse outcomes in COVID-19 patients with hypertension. Therefore, in this study, we investigated 702 COVID-19 patients with hypertension who were consecutively admitted to Huoshenshan Hospital in Wuhan, China. The aim of the study was to investigate the relationships between BPV and background factors, and further demonstrate whether day-by-day in-hospital BPV had prognostic significance in these patients. This was a retrospective cohort study of consecutive patients at Day-by-day BP measurements were collected from the electronic nursing records. Trained nurses measured the BP of patients daily between 6:00 a.m. and 9:00 a.m. (before breakfast and intake of anti-hypertensive drugs) using an automatic cuff sphygmomanometer (Omron HEM-7122, Omron Healthcare, Kyoto, Japan). 13 Hg were discarded to retain physiologically meaningful measurements in the analysis and to ensure the reliability of BPV indexes. 15 Dayby-day BPV was evaluated using three indices including the standard deviation (SD) of BP, coefficient of variation (CV) of BP, and variation independent of mean (VIM). 16 CV was calculated using the formula: CV = SD/mean×100. VIM was calculated as follows: For this study, all patients were hospitalized and had definite outcomes. The criteria for discharge were absence of fever for more than 3 days, obvious remission of respiratory symptoms, obvious resolution of inflammation on pulmonary imaging, and two consecutive respiratory tract swab samples negative for nuclei acid and obtained at least 24 h apart. 11 The primary endpoint was in-hospital mortality. The secondary endpoint was ARDS, which was diagnosed based on the Berlin definition. 18 Onset date was defined as the day when COVID-19 symptoms were first noticed. The final follow-up date was April 11, 2020. Continuous variables with normal distribution were presented as mean ± SD, and those with non-normal distribution were presented as median (interquartile range, IQR A total of 2864 hospitalized adult patients were diagnosed with COVID-19 in the study center from February 4, 2020 to April 11, 2020. Among these patients, 867 had preexisting hypertension. After excluding 165 patients without blood pressure measurement on seven consecutive days, 702 patients were included in the final analysis ( Among the study patients, 418 (59.5%) were diagnosed with moderate COVID-19, whereas 284 (40.5%) were severe or critical cases (Table 1) . Correlation coefficients between BPV and background factors were illustrated in Table 2 . BPV was correlated with various background factors. For instance, SD SBP showed significant positive relationships with age, D-dimer, LDH, hs-TnI, BNP, hs-CRP, and PCT. In addition, SD DBP showed significant positive relationships with hs-TnI and BNP. Furthermore, Kaplan-Meier survival analysis was used to compare the mortality between groups stratified by BPV median. As shown in Figure 2A , two (0.9%) died among patients with lower SD SBP (SD SBP < 11.6 mm Hg), while 20 (5.7%) died among patients with higher SD SBP (SD SBP ≥11.6 mm Hg), that is, patients with higher SD SBP had significantly higher rate of mortality than those with lower SD SBP. Besides, higher SD DBP was also correlated with higher mortality ( Figure 2B ). Of all patients, 64 (9.1%) developed ARDS. Table 3 Abbreviations: BPV, blood pressure variability; SBP, systolic blood pressure; DBP, diastolic blood pressure; ALT, alanine aminotransferase; AST, aspartate aminotransferase; hs-TnI, high-sensitive cardiac troponin I; BNP, B-type natriuretic peptide; hs-CRP, high-sensitive C-reactive protein; PCT, procalcitonin; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker.. *p < 0.05. Patients with higher SD SBP (≥11.6 mm Hg) exhibited significantly higher incidence of mortality (A). In addition, patients with higher SD DBP (≥7.77 mm Hg) exhibited significantly higher incidence of mortality (B). BPV, blood pressure variability; SD, standard deviation; SBP, systolic blood pressure; DBP, diastolic blood pressure 27 Similarly, the results in this study have demonstrated the relationship between age and BPV. In addition, inflammation markers have been reported to be associated with BPV in hypertensive patients, the same as this study identified. 33 Indeed, SARS-CoV-2 infection has been considered a cytokine storm syndrome, and COVID-19 patients with ARDS showed 10-to 60-fold higher levels of interleukin-1β and interleukin-6 than patients with moderate cases. [34] [35] [36] Excessive inflammatory responses may therefore partly explain the association between high BPV and adverse outcomes in COVID-19 patients with hypertension. We also found the correlations of BNP and hs-TnI with BPV, perhaps implying the detrimental role of cardiac dysfunction and myocardial injury on BP stability. Previous study has reported the relationship between visit-to-visit SBP variability and the rate of myocardial infarction. 37 Additionally, Diaz and coworkers 38, 39 suggested that high BPV was associated with endothelial dysfunction, which could account for the link between BPV and vascular injury dis- This study has several limitations. First, due to its retrospective design, some cases patients incomplete medical records, and laboratory tests were not performed in all patients, which may have caused bias in our analyses. Second, history of antihypertensive medication prior to admission could not be ascertained, and this prevented us from excluding the confounding effect of this on the outcomes of the patients. Third, this study included only Chinese hypertensive patients with COVID-19, and further studies are needed to clarify these results in other populations with COVID-19. To the best of our knowledge, this study for the first time demonstrates that higher day-by-day in-hospital SBP variability can independently predict mortality and ARDS in COVID-19 patients with hypertension. In addition, high BPV may be correlated with severe inflammation and myocardial injury. Early reduction of BPV may improve the prognosis of these patients. The underlying mechanisms that link higher BPV and adverse outcomes need to be clarified in further studies. Acute respiratory failure in COVID-19: is it "typical" ARDS? 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