Systemic arterial hypertension as a risk factor for the severe form of covid-19: scoping review

Ribeiro, Ana Cristina; Uehara, Sílvia Carla da Silva André

doi:10.11606/s1518-8787.2022056004311

Brasil

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Review • Rev. Saúde Pública 56 • 2022 • https://doi.org/10.11606/s1518-8787.2022056004311 linkcopy

Systemic arterial hypertension as a risk factor for the severe form of covid-19: scoping review

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

OBJECTIVE Identify whether systemic arterial hypertension is a risk factor for the severe form of covid-19.

METHODS This is a scoping review, searches were performed on the Lilacs, PubMed, SciELO and Web of Science databases.

RESULTS Thirteen articles were selected. The studies presented systemic arterial hypertension as the most common chronic disease in subjects diagnosed with covid-19. Hypertensive subjects were older, and men were more likely to develop severe covid-19. Hypertensive subjects without antihypertensive treatment were associated with a higher risk of mortality.

CONCLUSIONS subjects with chronic diseases tend to have a different clinical profile. Blood pressure should be controlled in hypertensive subjects that should be continuously monitored during the covid-19 infection.

COVID-19, complications; Risk Factors; Hypertension; Review

DATABASE	SEARCH STRATEGIES
PubMed	((hypertension[Title] OR “arterial hypertension”[Title]) AND (((coronavirus[Title] OR “COVID-19”[Title]) OR “SARS-CORONAVIRUS”[Title]) OR “SARS-COV-2”[Title])) NOT pulmonary[Title]
Web of Science	TI=(hyperttension OR “arterial hypertension”) NOT TI=(pulmonary) AND TI=(coronavirus OR Covid-19 OR SARS-CORONAVIRUS OR SARS-COV-2)
Lilacs	(hypertension OR arterial hypertension [Title words] and coronavirus OR Covid-19 OR sars-coronavirus OR Sars-cov-2 [Title words] and not pulmonary [Title words])
SciELO	TI=(hypertension OR “arterial hypertension”) NOT TI=(pulmonary) AND TI=(coronavirus OR Covid-19 OR SARS-CORONAVIRUS OR SARS-COV-2)

Author, Year and Site	Objective	Type of study and sampling (n)	Main results
Chen R, 2020, China¹⁵	Investigate the association between in-hospital blood pressure control and covid-19-related outcomes, and compare the effects of different antihypertensive treatments.	Retrospective cohort study. n = 2,828, 51.0% male, and mean age 60.0 years.	Elevated cardiomyocyte damage biomarkers in grade 2 and grade 3 groups (p < 0.001). Subjects grade 3 group higher B-type natriuretic peptide and worse cardiac function (p < 0.001). Survival rate of adverse clinical outcomes significantly higher in subjects previously treated with renin-angiotensin-aldosterone system inhibitors (HR: 0.35, 95%CI: 0.13–0.97, p = 0.043) or after (HR 0.18, 95%CI: 0.04–0.86, p = 0.031) admission than treated with other antihypertensive medications.
Rodilla E, 2020, Spain³²	Analyze whether hypertension represents an independent risk factor for death as a difficult outcome in hospitalized subjects with SARS-CoV-2 in Spain.	Cross-sectional, observational, multicenter retrospective study. n = 12,226, mean age 67.5, and 42.6% female.	After adjustment for sex, age tertiles, and Charlson Comorbidity Index scores, hypertension was significantly predictive of all-cause mortality when treated with angiotensin-converting enzyme inhibitors (OR: 1.6, p = 0.002) or other than renin-angiotensin-aldosterone blockers (OR: 1.3, p = 0.001) or angiotensin II receptor blockers (OR: 1.2, p = 0.035).
Huang S. 2020, China²¹	Explore the effect of hypertension on disease progression and prognosis in subjects with coronavirus 2019 disease (covid-19).	Multicenter retrospective observational study. n = 310, 56.1% male, and mean age 62 years.	Comparison hypertensive and non-hypertensive subjects with covid-19 without other comorbidities: hypertension showed no significant correlation with length of stay (p = 0.409) or mortality (p = 0.189) of covid-19 disease, hypertensive subjects higher proportion of severe cases (p < 0.001), higher proportion of intensive care unit admission (p = 0.045). Comparison of laboratory indices between hypertensive subjects with covid-19 with and without other comorbidities, most laboratory indices were not significantly different.
Okay G, 2020, Turkey²²	Investigate the effect of hypertension on clinical severity and prognosis of Coronavirus subjects with covid-19.	Retrospective observational study. n = 260, 55.4% male and mean age 54.1 ± 15.5 years.	Subjects with severe and critical clinic higher in the hypertensive than in the non-hypertensive group (p < 0.001). Greater use of oxygen therapy in hypertensive than in non-hypertensive subjects (p = 0.001). Higher rate of admission to intensive care unit in hypertensive subjects than in the non-hypertensive group (p = 0.01). Median values of neutrophil count, aspartate aminotransferase, lactate dehydrogenase and creatinine higher in hypertensive subjects than in non-hypertensive subjects. (p = 0.001; p = 0.016; p = 0.002; p < 0.001, respectively). Median albumin values and glomerular filtration rate lower in hypertensive subjects (p = 0.002 and p < 0.001, respectively).
Ghao G, 2020, China²⁹	Investigate whether treatment of hypertension, primarily with renin-angiotensin-aldosterone system (RASA) inhibitors, can impact mortality in subjects with covid-19.	Retrospective observational study. n = 2,877, hypertensives n = 850 (83.5% taking antihypertensive medications).	Hypertensive subjects without antihypertensive treatment: higher mortality rate compared to those with antihypertensive treatments (7.9% vs. 3.2%, HR: 2.52, 95%CI: 1.23–5.17, p = 0.012). After adjustment, even higher mortality risk in subjects without antihypertensive treatment (HR: 2.17, 95%CI: 1.03– 4.57,= 0.041). The numerical difference in mortality rates between the renin-angiotensin-aldosterone system inhibitor and non-inhibitor cohorts were not significant before or after adjustment (2.2% vs. 3.6%, adjusted HR: 0.85, 95%CI: 0.28–2.58, p = 0.774).
Yao Q, 2020, China²⁴	Explore the characteristics and differences in outcomes between hypertensive and non-hypertensive subjects with covid-19.	Observational retrospective study. n = 414, median age 61 years 50.1% male, and 36.0% hypertensive participants.	Compared with normotensives, hypertensive participants had a higher risk of death (HR: 2.68, 95%CI:1.46– 4.91), after adjustment for age and sex, no difference was shown (HR:1.77, 95%CI: 0.93–3.36). Hypertensive subjects had more complications: shock (p = 0.009), acute respiratory distress syndrome (p = 0.003), acute kidney injury (p = 0.001), greater use of non-invasive mechanical ventilation (p = 0.026), and invasive mechanical ventilation IMV (p = 0.020). Lab results on admission: hypertensive subjects had higher levels of hemoglobin (p = 0.049), D-dimer (p = 0.007), blood urea nitrogen (p = 0.000) and serum creatinine (p = 0.000).
Xiong TY, 2020, China²⁵	Characterize the prevalence and clinical implications of comorbidities in subjects with covid-19.	Retrospective multicenter study. n = 472 53.0% male, median age 43 years, hypertensive subjects n = 71.	Comparison hypertensive and non-hypertensive subjects: the hypertensive ones more prone to treatments with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB), β-blockers, calcium channel blocker (CCB) (p < 0, 001) and statins (p = 0.006), greater chance of experiencing the composite outcome (p < 0.001) and individual outcome, including intensive care unit admission (p < 0.001), mechanical ventilation (p < 0.001) and death (p = 0.012). Occurrence of adverse events did not differ between subjects treated with and without antihypertensive drugs.
Li J, 2020, China³⁰	Investigate the association between angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), and disease severity and mortality in subjects with hypertension hospitalized for covid-19 infection.	Retrospective study. n = 1,178, hypertensive subjects n = 362 (52.2% male, 71.5% older than 60 years, and 31.8% were on ACEI / ARBs).	Analysis in the hypertensive group: similar laboratory profile results, except higher alkaline phosphatase in those not taking angiotensin-converting enzyme inhibitors (ACEI) / angiotensin receptor blockers (ARB) (p < 0.001), frequency of disease severity, acute respiratory distress syndrome and mortality did not differ in relation to ACEI / ARB therapy. With regard to IECA/ARB use, there was no difference between those with severe versus non-severe disease in the use of IECA (p = 0.80), ARBs (p = 0.40), or the composite of IECA / ARBs (p = 0.65). Similarly, there were no differences between non-survivors and survivors in the use of IECA (p = 0.85), ARBs (p = 0.42), or the composite of IECA / ARBs (p = 0.34).
Zhou X, 2020, China²⁷	Explore the clinical features of covid-19 complicated by hypertension.	Single center retrospective study. n = 110, mean age 57.7 years, 54.5% male, hypertensive subjects n = 36 (52.8% male).	Compared to non-hypertensive subjects, those hypertensive had higher occurrence of dyspnea (p < 0.001), diabetes (p < 0.001) and cardiovascular disease (p = 0.022), lower lymphocyte count on admission (p < 0.01), higher crude mortality rate (p < 0.01). Taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was not significantly associated with prognosis (p = 0.162).
Chengyi HU, 2020, China²⁶	Determine the impact of hypertension on outcomes in subjects with covid-19.	Observational retrospective cohort study. n = 442, hypertensive subjects n = 61.	Compared to normotensive subjects, those hypertensive were more likely to develop bacterial infections (p = 0.002), higher neutrophil counts (p = 0.007), neutrophil to lymphocyte ratio (p = 0.045) and lactate dehydrogenase (p = 0.035). A higher proportion of subjects had bilateral irregular opacities on chest CT scan (p = 0.012) in the hypertension group than in the normotensive group. Hypertensive subjects were more likely to receive antibiotics (p = 0.035) and corticosteroid therapy (p = 0.035).
Pan W, 2020, China³¹	Clarify the impact of hypertension on covid-19, and investigate whether prior use of renin-angiotensin-aldosterone system (RAAS) inhibitors affects the prognosis of covid-19.	Single center retrospective study. n = 996, hypertensive subjects n = 282.	Hypertension unpaired cohort (HR 1.80, 95%CI: 1.20–2.70); paired cohort (HR 2.24, 95%CI: 1.36–3.70) independently associated with all causes of mortality in subjects with covid-19. There were no significant differences in baseline clinical characteristics between subjects with hypertension who used and did not use renin-angiotensin-aldosterone system (RASA) inhibitors. All-cause mortality rate was significantly lower in the SRAA inhibitor treatment group than in the no-SRAA inhibitor treatment group (p = 0.037).
Trump S, 2020, Germany²³	Evaluate the effect of coexisting cardiovascular disease, in particular hypertension and antihypertensive treatment, on covid-19 pathology and viral clearance.	Prospective observational cohort study. n = 144, 67.4% male. Hypertensive subjects with or without cardiovascular disease n = 90, and subjects without hypertension and without cardiovascular disease n = 54.	Higher risk of developing critical covid-19 for hypertensive subjects with/without coexisting cardiovascular disease compared to non-hypertensive subjects (adjusted odds ratio (adjOR) = 4.28, 95%CI: confidence interval: 1.60–11.46, p = 0.028). Patients treated with angiotensin receptor blockers (ARB) increased risk of critical covid-19 compared with non-hypertensive subjects (adjOR = 4.14, 95%CI: 1.01–17.04, p = 0.044). Risk of critical disease lower than for hypertensive subjects without treatment with angiotensin-converting enzyme inhibitors (ACEIs) or ARBs (adjOR = 8.17, 95%CI: 1.65–40.52, p = 0.009). No difference in ACE2 expression and initial viral concentration between subject groups.
Yang Q, 2020, China²⁸	Explore the impact of hypertension on outcomes in subjects with covid-19.	Retrospective cohort study. n = 226, hypertensive subjects n = 84.	Subjects divided into survivor and non-survivor groups. Ratio of hypertensive subjects among non-survivors was higher than among survivors (26.70% vs. 74.00%; p < 0.001). Hypertensive subjects had higher risk of death (HR: 2.679, 95%CI: 1.237–5.805; p = 0.012), elevated D-dimer levels (HR: 1.025, 95%CI: 1.011–1.039; p < 0.001) and higher neutrophil to lymphocyte ratio (HR: 1.107, 95%CI: 1.053–1.164; p < 0.001).

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