Relation of prior statin and anti-hypertensive use to severity of disease among patients hospitalized with COVID-19: Findings from the American Heart Association's COVID-19 Cardiovascular Disease Registry.

BACKGROUND: Statins have anti-inflammatory and immunomodulatory effects that may reduce the severity of coronavirus disease 2019 (COVID-19), in which organ dysfunction is mediated by severe inflammation. Large studies with diverse populations evaluating statin use and outcomes in COVID-19 are lacking. METHODS AND RESULTS: We used data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 US hospitals enrolled in the American Heart Association's COVID-19 Cardiovascular Disease (CVD) Registry to evaluate the associations between statin use and outcomes. Prior to admission, 42% of subjects (n = 4,449) used statins (7% on statins alone, 35% on statins plus anti-hypertensives). Death (or discharge to hospice) occurred in 2,212 subjects (21%). Outpatient use of statins, either alone or with anti-hypertensives, was associated with a reduced risk of death (adjusted odds ratio [aOR] 0.59, 95% CI 0.50-0.69), adjusting for demographic characteristics, insurance status, hospital site, and concurrent medications by logistic regression. In propensity-matched analyses, use of statins and/or anti-hypertensives was associated with a reduced risk of death among those with a history of CVD and/or hypertension (aOR 0.68, 95% CI 0.58-0.81). An observed 16% reduction in odds of death among those without CVD and/or hypertension was not statistically significant. CONCLUSIONS: Patients taking statins prior to hospitalization for COVID-19 had substantially lower odds of death, primarily among individuals with a history of CVD and/or hypertension. These observations support the continuation and aggressive initiation of statin and anti-hypertensive therapies among patients at risk for COVID-19, if these treatments are indicated based upon underlying medical conditions.

Antihypertensives and their relation to mortality by SARS-CoV-2 infection.

The role of antihypertensives, especially Renin-Angiotensin-Aldosterone System inhibitors, is still debatable in COVID-19-related severity and outcome. Therefore, we search for a more global analysis of antihypertensive medication in relation to SAS-CoV-2 severity using prescription data worldwide. The association between the percentage use of different types of antihypertensive medications and mortality rates due to a SARS-CoV-2 infection during the first 3 weeks of the pandemic was analyzed using random effects linear regression models for 30 countries worldwide. Higher percentages of prescribed angiotensin receptor blockers (ARBs) (ß, 95% confidence interval [CI]; -0.02 [-0.04 to -0.0012]; p = .042) and calcium channel blockers (CCBs) (ß, 95% CI; -0.023 [-0.05 to -0.0028]; p = .0304) were associated with a lower first 3-week SARS-CoV-2-related death rate, whereas a higher percentage of prescribed angiotensin-converting enzyme inhibitors (ACEis) (ß, 95% CI; 0.03 [0.0061-0.05]; p = .0103) was associated with a higher first 3-week death rate, even when adjusted for age and metformin use. There was no association between the amount of prescribed beta-blockers (BBs) and diuretics (Diu) and the first 3-week death rate. When analyzing the combination of drugs that is used by at least 50% of antihypertensive users, within the different countries, countries with the lowest first 3-week death rates had at least an angiotensin receptor blocker as one of the most often prescribed antihypertensive medications (ARBs/CCBs: [ß, 95% CI; -0.02 [-0.03 to -0.004]; p = .009], ARBs/BBs: [ß, 95% CI; -0.03 [-0.05 to -0.006]; p = .01]). Finally, countries prescribing high-potency ARBs had lower first 3-week ARBs. In conclusion, ARBs and CCB seem to have a protective effect against death from SARS-CoV-2 infection.

[Malignant arterial hypertension (HTAM) with severe systolic dysfunction of the reversible left ventricle]. / Hipertensión arterial maligna (HTAM) con disfunción sistólica grave del ventrículo izquierdo reversible.

Malignant arterial hypertension is still present in current clinical care despite the fact that for more than three decades we have had a wide range of antihypertensive drugs to control high blood pressure. It is essential to know how to detect it in time due to its high risk to life, with poor short-term prognosis if not treated properly. It may present with nonspecific, but potentially serious, clinical symptoms or manifest clinically as a hypertensive emergency accompanied by hypertensive encephalopathy and multi-organ failure. We present a case of a 49-year-old woman, attended in our hospital who had an initial hypertension of 223/170mmHg accompanied by multi-organ failure, who progressed satisfactorily with antihypertensive treatment.

Magnitude and associated factors of poor medication adherence among diabetic and hypertensive patients visiting public health facilities in Ethiopia during the COVID-19 pandemic.

OBJECTIVE: This study aims to assess the magnitude and associated factors of poor medication adherence among diabetic and hypertensive patients visiting public health facilities in Addis Ababa, Ethiopia during the COVID-19 pandemic. METHODS: A multi-site cross-sectional design was conducted from 1st through 30th of August 2020 at public health facilities of the study area. Adult outpatients with T2DM and hypertension visiting hospitals and health centers were included in the study. A proportion to size allocation method was used to determine the required sample size per facility. Data was collected using the 8-item Morisky medication adherence scale. Descriptive statistics and binary logistic regression were used to analyze data. A 95% confidence interval and p≤0.05 statistical significance was considered to determine factors associated with poor medication adherence. RESULTS: A total of 409 patients were included in the present study. About 57% of the patients reported that the COVID-19 pandemic has posed negative impacts on either of their follow-up visits, availability of medications, or affordability of prices. And, 21% have reported that they have been affected in all aspects. The overall magnitude of poor medication adherence was 72%. Patients with extreme poverty were more likely to have good medication adherence (AOR: 0.59; 95%C.I: 0.36-0.97), whereas attendance to a health center (AOR: 1.71; 95%C.I: 1.02-2.85), presence of comorbidity (AOR: 2.05; 95%C.I: 1.13-3.71), and current substance use history (AOR: 11.57; 95%C.I: 1.52-88.05) predicted high odds of poor adherence. CONCLUSION: Over a three-fourth of the patients, in the study setting, have poor adherence to their anti-diabetic and antihypertensive medications. Health facility type, income level, comorbidity, and current substance use history showed a statistically significant association with poor adherence to medication. Stakeholders should set alternative strategies as perceived impacts of the COVID-19 pandemic on medication adherence are high in the study area.

The role of anti-hypertensive treatment, comorbidities and early introduction of LMWH in the setting of COVID-19: A retrospective, observational study in Northern Italy.

BACKGROUND: There is a great deal of debate about the role of cardiovascular comorbidities and the chronic use of antihypertensive agents (such as ACE-I and ARBs) on mortality on COVID-19 patients. Of note, ACE2 is responsible for the host cell entry of the virus. METHODS: We extracted data on 575 consecutive patients with laboratory-confirmed SARS-CoV-2 infection admitted to the Emergency Department (ED) of Humanitas Center, between February 21 and April 14, 2020. The aim of the study was to evaluate the role of chronic treatment with ACE-I or ARBs and other clinical predictors on in-hospital mortality in a cohort of COVID-19 patients. RESULTS: Multivariate analysis showed that a chronic intake of ACE-I was associated with a trend in reduction of mortality (OR: 0.53; 95% CI: 0.27-1.03; p = 0.06), differently from a chronic intake of ARB (OR: 1.1; 95% CI: 0.5-2.8; p=0.8). Increased age (ORs ranging from 3.4 to 25.2 and to 39.5 for 60-70, 70-80 and >80 years vs <60) and cardiovascular comorbidities (OR: 1.90; 95% CI: 1.1-3.3; p = 0.02) were confirmed as important risk factors for COVID-19 mortality. Timely treatment with low-molecular-weight heparin (LMWH) in ED was found to be protective (OR: 0.36; 95% CI: 0.21-0.62; p < 0.0001). CONCLUSIONS: This study can contribute to understand the reasons behind the high mortality rate of patients in Lombardy, a region which accounts for >50% of total Italian deaths. Based on our findings, we support that daily intake of antihypertensive medications in the setting of COVID-19 should not be discontinued and that a timely LMWH administration in ED has shown to decrease in-hospital mortality.

Prognostic Significance of COVID-19 Receptor ACE2 and Recommendation for Antihypertensive Drug in Renal Cell Carcinoma.

PURPOSE: Owing to its worldwide spread, the coronavirus disease (COVID-19) epidemic was declared a pandemic by the World Health Organization on March 11, 2020. Angiotensin-converting enzyme 2 (ACE2) is the outer surface protein of the cell membrane that is abundantly distributed in the heart, lungs, and kidneys and plays an important role in molecular docking of the severe acute respiratory syndrome coronavirus 2. In this study, we aimed to analyze the difference in the survival rate according to ACE2 expressions in pan-cancer. MATERIALS AND METHODS: We downloaded clinical and genomic data from The Cancer Genome Atlas. We used Kaplan-Meier with a log-rank test, and the Cox proportional hazards regression to analyze prognostic significance. RESULTS: In the Kaplan-Meier curve, clear cell renal cell carcinoma (ccRCC), uveal melanoma, and prostate adenocarcinoma showed statistical significance. In the Cox regression, thyroid carcinoma and glioblastoma multiforme and ccRCC showed significant results. Only ccRCC had statistical significance, and high ACE2 expression is related to good prognosis. It is known that the ACE inhibitor, a primary antihypertensive agent, increases ACE2 expression. CONCLUSION: Based on these results, we believe that the ACE inhibitor will be important to increase the lifespan of ccRCC patients. This study is the first research to offer a recommendation on the use of anti-hypertensive drugs to ccRCC patients.

Considerations on the use of antihypertensive blockers of the renin-angiotensin system in adults and children in the face of the COVID-19 pandemic.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with hypertension and other cardiovascular comorbidities develop more severe coronavirus disease (COVID)-19 and are at high risk of death, a controversy arose about the use of antihypertensives as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs). Such drugs might increase the expression of the fundamental receptor of this new infectious agent: the angiotensin-converting enzyme 2 (ACE2). Preclinical observations indicate that the increase of ACE2 expression or the activity by ACEis and ARBs leads to a greater transformation of angiotensin (Ang)-II to Ang-(1-7), which is associated with positive effects on cardiovascular and pulmonary pathophysiology. This association has been demonstrated in observational studies in patients with cardiovascular pathology and pneumonia. It has not been possible to confirm whether users of ACEis or ARBs are more infected by the new coronavirus, due to methodological issues in studies with patients infected with SARS-CoV-2. However, the use of such antihypertensive treatments in both children and adults might reduce the virulence of infection. Therefore, changes in the antihypertensive therapy of patients at risk of contracting COVID-19 are not recommended.

Los pacientes con hipertensión y otra comorbilidad cardiovascular infectados con SARS-CoV-2 desarrollan cuadros más graves de COVID-19 y con mayor frecuencia fallecen. Este hecho ha originado una controversia acerca del uso de antihipertensivos inhibidores de la enzima convertidora de la angiotensina (IECA) y de antagonistas de los receptores de la angiotensina II (ARA-II), pues tales medicamentos pueden incrementar la expresión del receptor funcional de este nuevo agente infeccioso: la enzima convertidora de la angiotensina 2 (ECA2). Las observaciones preclínicas indican que el aumento de la expresión o de la actividad de la ECA2 por uso de IECA o ARA-II conduce a una mayor transformación de angiotensina 2 a a angiotensina 1-7, la cual se asocia con efectos positivos sobre la fisiopatología pulmonar y cardiovascular. En estudios observacionales de pacientes con patología cardiovascular y neumonía se ha confirmado esta asociación. La falta de evidencia contundente debida a aspectos metodológicos en estudios con pacientes infectados con SARS-CoV-2 no permite confirmar si los usuarios de IECA o ARA-II se contagian más con el nuevo coronavirus. Sin embargo, continuar con tales medicamentos antihipertensivos, tanto en adultos como en niños, podría reducir la virulencia de la infección. Por ello, no se recomienda cambiar la terapia antihipertensiva en los pacientes susceptibles a la COVID-19.

SARS-COV-2 infection during pregnancy, a risk factor for eclampsia or neurological manifestations of COVID-19? Case report.

BACKGROUND: There are no published cases of tonic-clonic seizures and posterior bilateral blindness during pregnancy and Severe Acute Respiratory Syndrome (SARS) Coronavirus (COV) 2 (SARS-COV-2) infection. We do not just face new and unknown manifestations, but also how different patient groups are affected by SARS-COV-2 infection, such as pregnant women. Coronavirus Disease 2019 (COVID-19), preeclampsia, eclampsia and posterior reversible leukoencephalopathy share endothelium damage and similar pathophysiology. CASE PRESENTATION: A 35-year-old pregnant woman was admitted for tonic-clonic seizures and SARS-COV-2 infection. She had a normal pregnancy control and no other symptoms before tonic-clonic seizures development. After a Caesarean section (C-section) she developed high blood pressure, and we initiated antihypertensive treatment with labetalol, amlodipine and captopril. Few hours later she developed symptoms of cortical blindness that resolved in 72 h with normal brain computed tomography (CT) angiography. CONCLUSION: The authors conclude that SARS COV-2 infection could promote brain endothelial damage and facilitate neurological complications during pregnancy.

Hypertension is a risk factor for adverse outcomes in patients with coronavirus disease 2019: a cohort study.

BACKGROUND: Comorbidities are commonly seen in patients with coronavirus disease 2019 (COVID-19), but the clinical implication is not yet well-delineated. We aim to characterize the prevalence and clinical implications of comorbidities in patients with COVID-19. METHODS: This is a retrospective multi-centre study involving patients admitted between January 16th and March 10th 2020. The composite endpoint was defined as the presence of at least one of the following, intensive care unit (ICU) admission, or the need for mechanical ventilation, or death. RESULTS: A total of 472 consecutive cases admitted to 51 certified COVID-19 tertiary care hospitals were enrolled (median age was 43 [32-53.5] years and 53.0% were male). There were 101 (21.4%) patients presented with comorbidities, including hypertension (15.0%), diabetes mellitus (7.8%), coronary artery disease (2.6%), chronic obstructive pulmonary disease (1.3%) and cerebrovascular disease (1.9%). The composite endpoint occurred in 65 (13.8%) patients. Multivariate stepwise logistic regression analysis indicated that older age (odds ratio [OR] 1.39, 95% confidence interval (CI) 1.05-1.85, per 10-year increment), antecedent hypertension (OR 2.82, 95% CI 1.09-7.29), neutrophil counts (OR 1.33, 95% CI 1.14-1.56) and lactate dehydrogenase level (OR 1.01, 95% CI 1.00-1.01) were independently associated with the presence of composite endpoint. Hypertensive patients, compared with controls, had a greater chance of experiencing the composite endpoint (p < .001) and each individual endpoint, i.e. ICU admission (p < .001), mechanical ventilation (p < .001) and death (p = .012). In the stepwise regression analysis of anti-hypertensive medications, none of the therapy predicted the composite endpoint. CONCLUSIONS: Hypertension is a common comorbidity in patients with COVID-19 and associated with adverse outcomes. KEY MESSAGES Hypertension was identified as the comorbidity associated with the prognosis of COVID-19 in this retrospective cohort. Patients with hypertension could experience an increased risk of the composite endpoint. Anti-hypertensive therapy did not affect patient outcomes.

Reorganizing the treatment of cardiovascular disease in response to coronavirus disease 2019; time for the polypill?

PURPOSE OF REVIEW: The coronavirus disease 2019 (COVID-19) pandemic has forced a redesign of healthcare services. Resource reallocation will have consequences on the routine management of chronic diseases, including cardiovascular disease (CVD). We consider how to mitigate potential adverse effects. RECENT FINDINGS: Combination therapy is well established in hypertension. Many guidelines recommend dual antihypertensive therapy as the initial treatment step as this results in faster blood pressure control, albeit with limited evidence of improved outcomes. Control of CVD risk factors through multiclass combination therapy (the polypill) was proposed many years ago. This approach has not been adopted by Western healthcare systems despite improving surrogate outcomes. Recently, the PolyIran trials have demonstrated improved CVD outcomes without increased adverse events, in both primary and secondary prevention. SUMMARY: The COVID-19 pandemic allows models of chronic healthcare to be rethought. Current practices are resource-intensive and there is a need to simplify titration and monitoring protocols in CVD. Moving toward the use of polypill combinations allied with telehealth consultations may be one solution.

Renin-Angiotensin-Aldosterone System Blockers and the Risk of Covid-19.

BACKGROUND: A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied. METHODS: We carried out a population-based case-control study in the Lombardy region of Italy. A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence. Information about the use of selected drugs and patients' clinical profiles was obtained from regional databases of health care use. Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression. RESULTS: Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women. The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile. Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex. CONCLUSIONS: In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.

Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19.

BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.