COVID-19: Hypertension Tied to Twofold Increase in Mortality

Erik Greb

June 15, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Hypertension is associated with significantly increased mortality in patients with COVID-19, new research shows.

Investigators examined the medical records of patients with COVID-19 and found a twofold increase in the relative risk of mortality among patients with hypertension, compared with normotensive patients.

Among patients with COVID-19 and hypertension, untreated hypertension was associated with an approximately twofold increase in mortality, compared with treated hypertension.

Importantly, investigators did not find a significant difference in mortality between patients who took renin-angiotensin-aldosterone system (RAAS) inhibitors and those who took another class of antihypertensive medication — a finding that surprised the investigators.

"Soon after we started to treat COVID-19 patients in early February in Wuhan, we noticed that nearly half of the patients who died had high blood pressure, which was a much higher percentage compared to those with only mild COVID-19 symptoms. At the same time some researchers were raising concerns that RAAS inhibitors might be facilitating the entry of the coronavirus into cells and making people more susceptible to the disease," study investigator Professor Ling Tao, department of cardiology, Xijing Hospital in Xi'an, China said in a statement.

"We were quite surprised that these results did not support our initial hypothesis. In fact, the results were in the opposite direction with a trend in favour of ACE inhibitors and ARBS," Tao added.

The study was published online June 4 in European Heart Journal.

Retrospective Data

Previous epidemiologic research suggests hypertension is associated with increased mortality among patients with COVID-19. However, these studies did not adjust for potential confounders such as age, "which is emerging as the strongest predictor of COVID-19 related death," the investigators note.

Angiotensin-converting enzyme 2 (ACE2) is needed for SARS-CoV-2 to enter the body. Reports suggest that ACE inhibitors and angiotensin receptor blockers, the two RAAS inhibitors used as antihypertensive treatments, increase the expression of ACE2.

The researchers conducted the retrospective observational study to analyze whether the treatment of hypertension influences mortality among patients with COVID-19. The study population included all patients with confirmed COVID-19 who were admitted to Huo Shen Shan Hospital in Wuhan, China, from February 5 to March 15.

They collected patients' demographic and clinical data from electronic medical records. Diagnoses of hypertension were made before infection with SARS-CoV-2. The study's primary endpoint was all-cause mortality during hospitalization.

A total of 2877 consecutive patients were included in the analysis. The population's mean age was approximately 60 years, and about 51% of patients were male.

Overall, 29.5% of patients had a history of hypertension. Patients with hypertension were older and more likely to have a history of diabetes, angina, stroke, renal failure, or previous revascularization, compared with patients without hypertension.

In addition, 83.5% of patients with hypertension were taking antihypertensive medications. Of this group, 25.7% were treated with RAAS inhibitors, and 74.2% were treated with non-RAAS inhibitors such as beta blockers or diuretics.

The mortality rate was 4.0% among patients with hypertension and 1.1% among normotensive patients. The unadjusted hazard ratio (HR) of mortality was 3.75 among patients with hypertension, compared with normotensive patients. After adjustment for potential confounders, the HR was 2.12.

Among patients with hypertension, the unadjusted mortality rate was significantly higher for those without antihypertensive treatment (7.9% vs 3.2%; HR, 2.52). Adjustment for potential confounders did not change the character of this observed relationship (HR, 2.17).

The difference in mortality between patients treated with RAAS inhibitors and those treated with non-RAAS inhibitors was not significant before or after data adjustment. Contrary to the investigators' hypothesis, RAAS inhibitors were associated with a lower mortality rate than non-RAAS inhibitors (2.2% vs 3.6%; adjusted HR, 0.85). The small sample sizes of the two groups suggest that the finding could result from chance, the investigators note.

"These data support the European Society of Cardiology's recommendation stating that patients should not discontinue or change their antihypertensive treatment unless instructed by a physician," they write.

Interpret With Caution

Commenting on the findings for Medscape Medical News, Philip B. Gorelick, MD, adjunct professor of neurology at Northwestern University in Chicago, said, "Hypertension may set the stage for more diffuse systemic vascular occlusive disease and thus may potentiate the negative effects of COVID-19–associated complications, such as hypercoagulability...and local and generalized inflammation.

"In addition, hypertension may alter vascular function...to further reduce vascular reserve under the onslaught of COVID-19 associated complications," said Gorelick, who was not involved in the study.

The findings related to RAAS inhibitors and non-RAAS inhibitors should be interpreted cautiously because of the observational nature of the study, the small sample size, and the lack of long-term follow-up, he noted.

"The main study findings suggest no harm with the use of RAAS inhibitors, despite theoretical concerns that the ACE2 receptor may be upregulated, allowing SARS-CoV-2 to enter host cells and replicate," Gorelick continued.

"Whereas there is contrary theoretical evidence that RAAS inhibitors may have protective effects in relation to COVID-19, a key message is to follow the guidance of major cardiovascular societies and associations that patients suspected of having COVID-19 or those who are confirmed cases should continue necessary antihypertensive therapies, including RAAS inhibitors such as ACE inhibitors and ARBs."

The investigators did not report any funding for their study and have disclosed no relevant financial relationships. Gorelick was not involved in the study of interest and serves on a data monitoring committee for Novartis for LCZ 696 as a potential treatment for cognitive function in heart failure.

Eur Heart J. Published online June 4, 2020. Full text

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