It is unknown whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have a positive, neutral, or negative effect on clinical outcomes in patients with ...coronavirus disease 2019 (COVID-19).
To determine whether discontinuation compared with continuation of ACEIs or ARBs changed the number of days alive and out of the hospital through 30 days.
A randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization (enrolled: April 9-June 26, 2020; final follow-up: July 26, 2020).
Discontinuation (n = 334) or continuation (n = 325) of ACEIs or ARBs.
The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression.
Among 659 patients, the median age was 55.1 years (interquartile range IQR, 46.1-65.0 years), 14.7% were aged 70 years or older, 40.4% were women, and 100% completed the trial. The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of less than 94% of room air at baseline. In terms of clinical severity, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate. There was no significant difference in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days SD, 8 days) vs patients in the continuation group (mean, 22.9 days SD, 7.1 days) and the mean ratio was 0.95 (95% CI, 0.90-1.01). There also was no statistically significant difference in death (2.7% for the discontinuation group vs 2.8% for the continuation group; odds ratio OR, 0.97 95% CI, 0.38-2.52), cardiovascular death (0.6% vs 0.3%, respectively; OR, 1.95 95% CI, 0.19-42.12), or COVID-19 progression (38.3% vs 32.3%; OR, 1.30 95% CI, 0.95-1.80). The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs 7.7% in the continuation group), shock requiring vasopressors (8.4% vs 7.1%, respectively), acute myocardial infarction (7.5% vs 4.6%), new or worsening heart failure (4.2% vs 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs 2.8%).
Among patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment.
ClinicalTrials.gov Identifier: NCT04364893.
In the current study, two euglossine species, Exaerete smaragdina and Eulaema nigrita, a cleptoparasite bee and its host, respectively, were used as models to: (i) access the genetic diversity and ...population structure of both species, sampled along a wide latitudinal range of Atlantic Forest, where the distribution of El. nigrita and Ex. smaragdina co-occurs; (ii) investigate the evolutionary history of these species through the Atlantic Forest, and in a wider scenario, to examine the evolutionary history of these species across others forest domains. Analyses involved males of El. nigrita and Ex. smaragdina sampled through Brazilian territory, including 19 sites in the Atlantic Forest. Bayesian Skyline Plot (BSP) was used to infer possible climate oscillations on population of both species over time. The BSP revealed stability in effective population size for both species in most of the Plio-Pleistocene period. However, BSP results aligned to the starlike configuration in the haplotype network, neutrality test, and population diversity patterns indicated population expansion of the two species during the late Pleistocene. Our findings suggest areas of potential refugia to the climatic oscillations of the Pleistocene in the Atlantic Forest in the Brazilian states of Espírito Santo for El. nigrita and Pernambuco for Ex. smaragdina.
Objectives We attempted to determine the prognostic value of coronary computed tomographic angiography (CTA) in patients with inconclusive functional stress tests. Background Patients with suspected ...coronary artery disease (CAD) and inconclusive noninvasive cardiac stress tests represent a frequent management challenge. Methods We examined 529 consecutive patients with suspected CAD and prior inconclusive functional stress tests. All patients underwent a coronary CTA scan using a 64-slice multidetector row scanner. CAD severity by coronary CTA was categorized as: 1) no evidence of CAD; 2) nonobstructive coronary plaques (<30%); 3) mild stenosis (30% to 49%); 4) moderate stenosis (50% to 69%); and 5) severe stenosis (≥70%). Patients were also categorized according to a modified Duke prognostic CAD index. Survival analyses were performed using Cox proportional hazards models adjusted for baseline risk factors and coronary artery calcium score. The primary outcome of the study was the combined endpoint of all-cause mortality and nonfatal myocardial infarction. Results Among patients with inconclusive stress tests, the large majority (69%) did not demonstrate significant CAD by coronary CTA. During a mean follow-up of 30.1 ± 11.1 months, there were 20 (3.8%) deaths and 17 (3.2%) nonfatal myocardial infarctions. Multivariable Cox regression analysis revealed that the presence of increasing degrees of obstructive CAD by CTA was an independent predictor of adverse events (hazard ratio HR: 1.66 95% confidence interval (CI): 1.23 to 2.23, p = 0.001). Indeed, the presence of ≥50% coronary stenosis was associated with an increased risk of events (HR: 3.15 95% CI: 1.26 to 7.89, p = 0.01). Likewise, the Duke prognostic CAD index was also found to be an independent predictor of events (HR: 1.54 95% CI: 1.20 to 1.97, p = 0.001). Conclusions Among patients with inconclusive functional stress tests, the noninvasive assessment of CAD severity by coronary CTA has been shown to provide incremental prognostic information beyond the evaluation of traditional risk factors and coronary artery calcium score.
Background:
Cardiovascular comorbidities such as hypertension and inflammatory response dysregulation are associated with worse COVID-19 prognoses. Different cytokines have been proposed to play ...vital pathophysiological roles in COVID-19 progression, but appropriate prognostic biomarkers remain lacking. We hypothesized that the combination of immunological and clinical variables at admission could predict the clinical progression of COVID-19 in hypertensive patients.
Methods:
The levels of biomarkers, including C-reactive protein, lymphocytes, monocytes, and a panel of 29 cytokines, were measured in blood samples from 167 hypertensive patients included in the BRACE-CORONA trial. The primary outcome was the highest score during hospitalization on the modified WHO Ordinal Scale for Clinical Improvement. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and biomarkers associated significantly with the primary outcome.
Results:
During hospitalization, 13 (7.8%) patients showed progression to more severe forms of COVID-19, including three deaths. Obesity, diabetes, oxygen saturation, lung involvement on computed tomography examination, the C-reactive protein level, levels of 15 cytokines, and lymphopenia on admission were associated with progression to severe COVID-19. Elevated levels of interleukin-10 and interleukin-12 (p70) combined with two or three of the abovementioned clinical comorbidities were associated strongly with progression to severe COVID-19. The risk of progression to severe disease reached 97.5% in the presence of the five variables included in our model.
Conclusions:
This study demonstrated that interleukin-10 and interleukin-12 (p70) levels, in combination with clinical variables, at hospital admission are key biomarkers associated with an increased risk of disease progression in hypertensive patients with COVID-19.
The G894T polymorphism in endothelial nitric oxide synthase enzyme gene plays an important role in heart failure (HF) and its frequency varies among populations. We investigated this association in ...highly admixed samples in terms of ancestry. The cohort included 210 HF patients and 106 healthy individuals. Self-reported race and NYHA class were analyzed for HF patients. G894T polymorphism was analyzed by polymerase chain reaction (PCR) and by restriction fragment length polymorphism technique. Ancestry was estimated using a PCR reaction containing 46 autosomal ancestry informative markers and an analysis by capillary electrophoresis. The GG homozygous genotype had a higher frequency in HF patients (63.8%) than in healthy individuals (48.1%), showing an increased chance (odds ratio 1.90, 95% confidence interval 1.18–3.05). The ancestry profiles in patients and controls were similar, with a major European contribution (57.1% and 63.2%), followed by African (30.2% and 24.0%) and Native American (12.7% and 12.8%), without a significant difference between both samples (p = 0.28). The GG genotype is associated to HF prognosis, and this association remains present in highly admixed sample groups.
•Heart failure can be influenced by genetic polymorphisms.•Nitric oxide synthase enzyme plays an important role in the disease.•The G894T polymorphism varies the frequency among populations ancestries.•Individuals with GG genotype have more chance of developing heart failure.
Myocardial injury (MI), defined by troponin elevation, has been associated with increased mortality and adverse outcomes in patients with coronavirus disease 2019 (COVID-19), but the role of this ...biomarker as a risk predictor remains unclear. Data from adult patients hospitalized with COVID-19 were recorded prospectively. A multiple logistic regression model was used to quantify associations of all variables with in-hospital mortality, including the calculation of odds ratios (ORs) and confidence intervals (CI). Troponin measurement was performed in 1476 of 4628 included patients, and MI was detected in 353 patients, with a prevalence of 23.9%; 95% CI, 21.8–26.1%. The total in-hospital mortality rate was 10.9% 95% CI, 9.8–12.0%. The mortality was much higher among patients with MI than among those without MI, with a prevalence of 22.7% 95% CI, 18.5–27.3% vs. 5.5% 95% CI, 4.3–7.0% and increased with each troponin level. After adjustment for age and comorbidities, the model revealed that the mortality risk was greater for patients with MI OR = 2.99; 95% CI, 2.06–4.36%, and for those who did not undergo troponin measurement OR = 2.2; 95% CI, 1.62–2.97%, compared to those without MI. Our data support the role of troponin as an important risk predictor for these patients, capable of discriminating between those with a low or increased mortality rate. In addition, our findings suggest that this biomarker has a remarkable negative predictive value in COVID-19.
Background:
Atherothrombosis is becoming the leading cause of chronic morbidity in developing countries. This epidemiological transition will represent an unbearable socioeconomic burden in the near ...future. We investigated factors associated with 4‐year all‐cause mortality in a Latin American population at high risk.
Hypothesis:
Largely modifiable risk factors as well as polyvascular disease are the main predictors of 4‐year all‐cause and cardiovascular mortality in this Latin American cohort.
Methods:
We analyzed 1816 Latin American stable outpatients (62.3% men, mean age 67 years) with symptomatic atherothrombosis (87.1%) or with multiple risk factors only (12.9%), in the Reduction of Atherothrombosis for Continued Health registry.
Results:
Of patients with symptomatic atherothrombosis, 57.3% had coronary artery disease, 32% cerebrovascular disease, and 11.7% peripheral artery disease at baseline (9.1% polyvascular). The main risk factors were hypertension (76%), hypercholesterolemia (60%), and smoking (52.3%) in patients with established atherothrombosis; and hypertension (89.7%), diabetes (80.8%), and hypercholesterolemia (73.9%) in those with risk factors only. Four‐year all‐cause mortality steeply increased with none (6.8%), 1 (9.2%), 2 (15.5%), and 3 (29.2%) symptomatic arterial disease locations. In patients with only 1 location, cardiovascular mortality was significantly higher with peripheral artery disease (11.3%) than with cerebrovascular disease (6%) or coronary artery disease (5.1%). Significant baseline predictors of 4‐year all‐cause mortality were congestive heart failure (hazard ratio HR: 3.81), body mass index <20 (HR: 2.32), hypertension (HR: 1.84), polyvascular disease (HR: 1.69), and age ≥65 years (HR: 1.47), whereas statin use (HR: 0.49) and body mass index ≥30 (HR: 0.58) were associated with a reduced risk.
Conclusions:
Hypertension was the main modifiable risk factor for atherothrombosis and all‐cause mortality in this Latin American cohort. Nearly one‐third of the population with 3 symptomatic vascular‐disease locations died at 4‐year follow‐up.
The REACH registry is sponsored by sanofi, Bristol‐Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The REACH registry is endorsed by the World Heart Federation. The REACH registry enforces a no‐ghostwriting policy. This manuscript was written and edited by the authors, who take full responsibility for its content. Dr. Cantú‐Brito and Dr. Chiquete wrote the first draft of this manuscript.
Dr. Cantú‐Brito has received research grants from sanofi, Ferrer Grupo and Bayer, as well as speaker honoraria from sanofi. Dr. Chiquete has received research grants from sanofi and Ferrer Grupo, as well as speaker honoraria from Novartis. Dr. Ruiz‐Sandoval has received research grants from sanofi, Boehringer Ingelheim, and Ferrer Grupo. Dr. Gaxiola has received research grants from sanofi and Eli Lilly, as well as consultancy and speaker honoraria from Sanofi, Eli Lilly, Pfizer, AstraZeneca, and Abbott. Dr. Albuquerque has received research grants from sanofi, AstraZeneca, Servier, Roche, and BMS/Pfizer, as well as consultancy and speaker honoraria from sanofi and AstraZeneca. Dr. Corbalán has no relevant disclosures. Mrs. Ramos is an employee at sanofi, in the Clinical Research Department. Dr. Deepak L. Bhatt discloses the following relationships ‐ Advisory Board: Medscape Cardiology; Board of Directors: Boston VA Research Institute, Society of Chest Pain Centers; Chair: American Heart Association Get With The Guidelines Science Subcommittee; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); Research Grants: Amarin, AstraZeneca, Bristol‐Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research: PLx Pharma, Takeda. Dr. Steg has received research grants from Servier; consultancy fees/honoraria from Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol‐Myers Squibb, Daiichi Sankyo/Eli Lilly alliance, Eisai, GlaxoSmithKline, Medtronic, Merck Sharpe and Dohme, Pfizer, Roche, sanofi, Servier, and The Medicines Company; and has equity ownership in Aterovax.
The authors have no other funding, financial relationships, or conflicts of interest to disclose.
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