Is Lone Hypertension a Risk Factor for More Severe COVID-19 Outcomes?

Background: Based on current evidence, it is not clear whether lone hypertension increases the risk for severe illness from COVID-19, or if increased risk is mainly associated with age, obesity and diabetes. The objective of the study was to evaluate whether lone hypertension is associated with increase mortality or a more severe course of COVID-19, and if treatment and control of hypertension mitigates this risk. Methods: This is a prospective multi-center observational cohort study with 30-day outcomes of 9,531 consecutive SARS-CoV-2 PCR-positive patients ≥ 18 years old (41.9 ± 9.7 years, 49.2% male), Uzbekistan, June 1-September 30, 2020. Patients were subclassified according to JNC8 criteria into six blood pressure stages. Univariable and multiple logistic regression was conducted to examine how variables predict outcomes. Results: The 30-days all-cause mortality was 1.18% (n = 112) in the whole cohort. After adjusting for age, sex, history of myocardial infarction (MI), type-2 diabetes, and obesity, none of six JNC8 groups showed any significant difference in all-cause mortality. However, age was associated with an increased risk of 30-days all-cause mortality (OR = 1.09, 95%CI [1.07-1.12], p < 0.001), obesity (OR = 7.18, 95% CI [4.18-12.44], p < 0.001), diabetes (OR 4.18, 95% CI [2.58-6.76], p < 0.001), and history of MI (OR = 2.68, 95% CI [1.67-4.31], p < 0.001). In the sensitivity test, being ≥ 65 years old increased mortality 10.56-fold (95% CI [5.89-18.92], p < 0.001). Hospital admission was 12.4% (n = 1,183), ICU admission 1.38% (n = 132). The odds of hospitalization increased having stage-2 untreated hypertension (OR = 4.51, 95%CI [3.21-6.32], p < 0.001), stage-1 untreated hypertension (OR = 1.97, 95%CI [1.52-2.56], p < 0.001), and elevated blood pressure (OR = 1.82, 95% CI [1.42-2.34], p < 0.001). Neither stage-1 nor stage-2 treated hypertension patients were at statistically significant increased risk for hospitalization after adjusting for confounders. Presenting with stage-2 untreated hypertension increased the odds of ICU admission (OR = 3.05, 95 %CI [1.57-5.93], p = 0.001). Conclusions: Lone hypertension did not increase COVID-19 mortality or in treated patients risk of hospitalization.

Renin-angiotensin-system inhibitors and all-cause mortality in patients with COVID-19: a systematic review and meta-analysis of observational studies.

AIMS: We sought to evaluate the association of angiotensin-converting-enzyme inhibitors (ACEI) or AT1 blockers (ARB) therapy with clinical outcomes in patients with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: Electronic databases were searched to identify published studies that reported clinical outcomes in patients with COVID-19 who were or were not taking an ACEI/ARB. We studied all-cause mortality and/or severe disease outcomes. Fully adjusted effect estimates from individual studies were pooled using a random-effects model. In total, 34 (31 cohort-based and three case-control) studies met our eligibility criteria. Due to the inherent differences between cohort and case-control studies, we did not combine results of these studies but used them to identify the consistency of their results. The 31 cohort studies provided outcome data for 87 951 patients with COVID-19, of whom 22 383/83 963 (26.7%) were on ACEI/ARB therapy. In pooled analysis, we found no association between the use of ACEI/ARB and all-cause mortality/severe disease [relative risk: 0.94, 95% confidence interval (CI): 0.86-1.03, I2 = 57%, P = 0.20] or occurrence of severe disease (relative risk: 0.93, 95% CI: 0.74-1.17, I2 = 56%, P = 0.55). Analysis of three population-based case-control studies identified no significant association between ACEI/ARB (pooled odds ratio: 1.00, 95% CI: 0.81-1.23, I2 = 0, P = 0.98) and all-cause mortality/severe disease. In 13 of the 31 cohort studies as well as in three case-control studies that reported outcomes separately for ACEI and ARB, there was no differential effect for mortality/severe disease outcomes. CONCLUSION: In patients with COVID-19, we found no association between ACEI/ARB treatment and mortality/severe disease. ACEI/ARB should not be discontinued, unless clinically indicated.

Special Article - Acute myocardial injury in patients hospitalized with COVID-19 infection: A review.

The Coronavirus Disease 2019 (COVID-19) is now a global pandemic with millions affected and millions more at risk for contracting the infection. The COVID-19 virus, SARS-CoV-2, affects multiple organ systems, especially the lungs and heart. Elevation of cardiac biomarkers, particularly high-sensitivity troponin and/or creatine kinase MB, is common in patients with COVID-19 infection. In our review of clinical analyses, we found that in 26 studies including 11,685 patients, the weighted pooled prevalence of acute myocardial injury was 20% (ranged from 5% to 38% depending on the criteria used). The plausible mechanisms of myocardial injury include, 1) hyperinflammation and cytokine storm mediated through pathologic T-cells and monocytes leading to myocarditis, 2) respiratory failure and hypoxemia resulting in damage to cardiac myocytes, 3) down regulation of ACE2 expression and subsequent protective signaling pathways in cardiac myocytes, 4) hypercoagulability and development of coronary microvascular thrombosis, 5) diffuse endothelial injury and 'endotheliitis' in several organs including the heart, and, 6) inflammation and/or stress causing coronary plaque rupture or supply-demand mismatch leading to myocardial ischemia/infarction. Cardiac biomarkers can be used to aid in diagnosis as well as risk stratification. In patients with elevated hs-troponin, clinical context is important and myocarditis as well as stress induced cardiomyopathy should be considered in the differential, along with type I and type II myocardial infarction. Irrespective of etiology, patients with acute myocardial injury should be prioritized for treatment. Clinical decisions including interventions should be individualized and carefully tailored after thorough review of risks/benefits. Given the complex interplay of SARS-CoV-2 with the cardiovascular system, further investigation into potential mechanisms is needed to guide effective therapies. Randomized trials are urgently needed to investigate treatment modalities to reduce the incidence and mortality associated with COVID-19 related acute myocardial injury.