Studies find hypertension most prevalent comorbidity in patients hospitalized for COVID-19
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The most prevalent comorbidity in patients hospitalized for COVID-19 was hypertension, which was also a risk factor for acute kidney injury in the ED and mortality in these patients, researchers found in two separate studies.
In another study, use of ACE inhibitors and angiotensin II receptor antagonists was linked with unadjusted higher rates of in-hospital mortality in patients with COVID-19, but the difference did not remain after multivariable analysis.
Data from the three studies were presented at the American Heart Association Hypertension Scientific Sessions.
Comorbidities in COVID-19
Vikramaditya Reddy Samala Venkata, MD, internist at Dartmouth-Hitchcock Medical Center in Keene, New Hampshire, and colleagues analyzed data from more than 11,000 patients hospitalized with COVID-19. These data were obtained from 22 retrospective studies conducted in eight countries, all of which reported on the prevalence of hypertension in these patients.
“During the initial pandemic months, we were seeing a lot of COVID-19 patients, and there was a lot of uncertainty about COVID-19,” Venkata told Healio. “There was not enough information about factors affecting prognosis in this population, so we looked at the available studies done at that time and did a meta-analysis to better understand the factors affecting prognosis in COVID-19 patients.”
The most prevalent comorbidities in these patients were hypertension (42%) and diabetes (23%). Hypertension alone was linked to increased rates of mortality.
Researchers found several less prevalent comorbidities, including chronic kidney disease (6%), nonhypertensive CVD (11%), chronic obstructive pulmonary disease (4.3%) and cerebrovascular accident (5%).
“One of the major findings in our study was the prevalence of hypertension when compared to other baseline comorbidities in hospitalized COVID-19 patients,” Venkata said in an interview. “Patients with baseline hypertension had double the odds of death when compared to patients without baseline hypertension. This will alert clinicians to better stratify/triage COVID-19 patients with baseline hypertension.”
Medications and COVID-19 outcomes
In a single-center retrospective cohort study, Baher Al-Abbasi, MD, internal medicine resident at University of Miami Miller School of Medicine, and colleagues analyzed data from 172 patients (mean age, 58 years; 51% women) diagnosed with COVID-19 between March and May. Researchers assessed the effect of ACE inhibitors and angiotensin II receptor antagonists on ICU admission, in-hospital mortality, ICU length of stay and hospital length of stay.
Patients with a history of taking ACE inhibitors or angiotensin II receptor antagonists were more likely to be older compared with those with no history of taking these medications (68 years vs. 54 years; P < .0001). These patients were also more likely to have hypertension (100% vs. 33%; P < .0001), obesity (65% vs. 40%; P = .0054), chronic kidney disease (11% vs. 0.8%; P = .0011) and diabetes (40% vs. 10%; P < .0001). The groups had similar prevalence of chronic HF (P = .8037) and CAD (P = .3791).
Patients with a history of taking ACE inhibitors or angiotensin II receptor antagonists had higher unadjusted in-hospital mortality compared with those without a history of use (33% vs. 13%; P = .0039), but the difference was attenuated after multivariable logistic regression analysis.
ICU admission was more common in patients with a history of taking ACE inhibitors or angiotensin II receptor antagonists vs. those with no history (28% vs. 13%; P = .0384). Patients with and without a history of use had similar lengths of stay in the hospital (6 days vs. 4 days, respectively; P = .124) and in the ICU (12 days vs. 8 days, respectively; P = .3253).
“This study suggests that the use of [ACE inhibitors/angiotensin receptor blockers is] associated with higher mortality in patients with COVID-19,” Al-Abbasi and colleagues wrote in the abstract. “This is likely attributed to the fact that patients who use these medications are older and are more likely to have diabetes mellitus and hypertension.”
Hypertension and acute kidney injury
Paolo Manunta, MD, PhD, chair of nephrology at San Raffaele University in Milan, and colleagues monitored renal function in 392 patients (mean age, 67 years; 74.7% men) hospitalized for COVID-19 from March 2 to April 25.
Main comorbid factors found in this study included a history of hypertension (58%) and drug medications (86.1%).
Acute kidney injury was observed in 6.2% of patients in the ED. The main determinants of acute kidney injury in the ED were baseline kidney function and hypertension. Compared with patients without hypertension, those with hypertension were more likely to have acute kidney injury at the ED (89.5% vs. 56.4%; P = .004), which accounted for an increased risk of 4.98 (95% CI, 1.04-23.8; P = .044) after adjusting for independent covariates, including respiratory distress and age.
Patients had increased risk for acute kidney injury at the ED if they had severe hypotension (RR = 3.95; 95% CI, 1.41-11.04) or mild hypotension (RR = 9.13; 95% CI, 1.4-59.77). Mean arterial BP was not linked to the severity of respiratory distress. No effect was observed with the use of antihypertensive pharmacologic treatments.
Acute kidney injury occurred in 34.7% of patients during hospitalization with a mean time to development of 7 days. Patients who developed acute kidney injury during hospitalization were more likely to be aged at least 65 years (42.5% vs. 24.3%; P < .0001) and to have hypertension (43.4% vs. 20.6%; P < .0001) compared with those without acute kidney injury.
Researchers performed a survival analysis, which found that main determinants of acute kidney injury during hospitalization were hypertension, being older than 65 years and severity of respiratory distress. In a univariate Cox regression model, several factors were independently associated with an increase in overall in-hospital mortality, including chronic obstructive pulmonary disease, being older than 65 years, mean arterial BP less than 86 mm Hg at ED admission, chronic kidney disease stage 3 to 5 and illness severity.
“The clinical impact is related to the use of any antihypertensive therapy, as they should be carefully evaluated by all doctors in COVID patients and eventually stopped if the blood pressure recording is lower than 120 mm Hg [systolic]/70 mm Hg [diastolic],” Manunta told Healio.
“While we continue to learn more about the complex impact of COVID-19 every day, we know that people with cardiovascular disease and/or hypertension are at much higher risk for serious complications, including death from COVID-19,” Mariell Jessup, MD, FAHA, chief science and medical officer of the AHA, said in a press release. “We continue to monitor and review the latest research, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE inhibitor or angiotensin receptor blocker treatment regimens. The latest research findings do suggest, however, that these medications should be discontinued in patients who develop hypotension in order to avoid severe kidney damage.”
For the latest news on COVID-19 including case counts, information about the global public health response and emerging research, please visit the COVID-19 Resource Center on Healio.
References:
- Al-Abbasi B, et al. Presentation P144.
- Manunta P, et al. Presentation P145. Both presented at: American Heart Association Hypertension Scientific Sessions; Sept. 10-13, 2020 (virtual meeting).
Perspective
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Rajesh Mohandas, MD
Patients with hypertension appear to be at increased risk for SARS-CoV-2 infection and complications of COVID-19. However, whether this increased risk is due to hypertension or because patients with hypertension tend to be older and have significant comorbidities, including kidney disease is unclear. Further, the use of ACE inhibitors/angiotensin II receptor antagonists has been reported to increase expression of angiotensin-converting enzyme 2 (ACE2), the receptor required for entry of SARS-CoV2 into cells. The clinical consequences of these observations are unknown. Three studies published at the AHA Hypertension conference attempt to shed some light on these topics.
Venkata and colleagues pooled data from 22 observational studies of over 11,000 patients, and 42% of patients hospitalized with COVID-19 had hypertension. Presence of hypertension was the commonest comorbidity and was associated with higher risk for mortality.
Manunta and colleagues from Italy studied 392 patients with COVID-19. They found that acute kidney injury was present in 6.2% of patients on admission and 35% developed acute kidney injury in the hospital. Patients with hypertension were more likely to develop acute kidney injury. Interestingly, elevated BP did not correlate with risk for acute kidney injury. On the other hand, low BP increased risk for acute kidney injury.
Al-Abbasi and colleagues studied 172 patients with COVID-19. Patients who were on ACE inhibitor/AII receptor antagonist therapy were more likely to require admission to the ICU (28% vs. 13%) and more likely to die (33% vs. 13%). However, after controlling for age, obesity, hypertension, diabetes mellitus and chronic kidney disease, the use of ACE inhibitors/AII receptor antagonists was no longer associated with excess mortality.
While ACE inhibitors/AII receptor antagonists might increase ACE2 and internalization of SARS-CoV-2, an increased ACE2 can counter the vasodeleterious effects of excess angiotensin II. Further, decreased ACE2 can cause gut dysbiosis and worsen inflammation, so the final effect of ACE inhibitors/AII receptor antagonists on COVID-19 is unclear. It is reassuring to see that the use of ACE inhibitors/AII receptor antagonists is not independently associated with excess mortality. While these studies are informative, they are small and retrospective, so the evidence is too preliminary to influence clinical practice.
Randomized controlled trials are needed to answer the question whether the use of ACE inhibitors/AII receptor antagonists can worsen COVID-19. The preliminary results of the BRACE CORONA study from Brazil, which randomly assigned 659 patients to either stop or continue ACE inhibitors/AII receptor antagonists, found no differences in mortality or severity of infection on holding ACE inhibitors/AII receptor antagonists. There are several ongoing trials in the U.S. and elsewhere, the results of which should help definitively answer this question.
The majority of evidence thus far suggests that the use of ACE inhibitors/AII receptor antagonists does not adversely affect clinical outcomes in SARS-CoV-2 infection, so it is important that we continue these medications in patients with hypertension and HF.
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