SARS-CoV-2 is the virus responsible for the ongoing COVID-19 outbreak. The virus uses ACE2 receptor for viral entry. ACE2 is part of the counter-regulatory renin-angiotensin-aldosterone system and is also expressed in the lower respiratory tract along the alveolar epithelium. There is, however, significant controversy regarding the role of ACE2 expression in COVID-19 pathogenesis. Some have argued that decreasing ACE2 expression would result in decreased susceptibility to the virus by decreasing available binding sites for SARS-CoV-2 and restricting viral entry into the cells. Others have argued that, like the pathogenesis of other viral pneumonias, including those stemming from previous severe acute respiratory syndrome (SARS) viruses, once SARS-CoV-2 binds to ACE2, it downregulates ACE2 expression. Lack of the favourable effects of ACE2 might exaggerate lung injury by a variety of mechanisms. In order to help address this controversy, we conducted a literature search and review of relevant preclinical and clinical publications pertaining to SARS-CoV-2, COVID-19, ACE2, viral pneumonia, SARS, acute respiratory distress syndrome and lung injury. Our review suggests, although controversial, that patients at increased susceptibility to COVID-19 complications may have reduced baseline ACE2, and by modulating ACE2 expression one can possibly improve COVID-19 outcomes. Herein, we elucidate why and how this potential mechanism might work.
The heart and the kidneys are closely interconnected, and disease in one organ system can lead to disease in the other. This interdependence is illustrated in heart failure with reduced ejection fraction (HFrEF), where worsening heart failure can lead to renal dysfunction and vice versa. Further complicating this situation is the fact that drugs that serve as guideline directed medical therapy (GDMT) for HFrEF can affect renal function. Sodium glucose co-transporter 2 (SGLT2) inhibitors are a new class of medication with an evolving role in heart failure (HF) and chronic kidney disease (CKD). Initially found to have benefits in diabetics, new research established potential cardiovascular and renal benefits in patients with HF independent of their diabetic status and in populations with CKD. This has been established by landmark trials such as EMPEROR-Reduced, EMPA-TROPISM, CREDENCE, DAPA-CKD, DAPA-HF, and DEFINE-HF. Multiple mechanisms responsible for these benefits have been suggested by clinical and non-clinical studies, and involve cardiac and renal energetic efficiency, cardiac remodeling, preservation of renal function, immunomodulation, changes in hematocrit, and control of risk factors. As such, SGLT2 inhibitors have tremendous potential to improve outcomes in populations with HF and CKD. The purpose of this review is to discuss the current evidence and underlying mechanisms for the cardio-renal benefits of SGLT2 inhibitors in patients with HFrEF.
BackgroundAtrial fibrillation (AF) is a common cause for hospitalization, but there are limited data regarding acute kidney injury requiring dialysis (AKI‐D) in AF hospitalizations. We aimed to assess temporal trends and outcomes in AF hospitalizations complicated by AKI‐D utilizing a nationally representative database.Methods and ResultsUtilizing the Nationwide Inpatient Sample, AF hospitalizations and AKI‐D were identified using diagnostic and procedure codes. Trends were analyzed overall and within subgroups and utilized multivariable logistic regression to generate adjusted odds ratios (aOR) for predictors and outcomes including mortality and adverse discharge. Between 2003 and 2012, 3751 (0.11%) of 3 497 677 AF hospitalizations were complicated by AKI‐D. The trend increased from 0.3/1000 hospitalizations in 2003 to 1.5/1000 hospitalizations in 2012, with higher increases in males and black patients. Temporal changes in demographics and comorbidities explained a substantial proportion but not the entire trend. Significant comorbidities associated with AKI‐D included mechanical ventilation (aOR 13.12; 95% CI 9.88‐17.43); sepsis (aOR 8.20; 95% CI 6.00‐11.20); and liver failure (aOR 3.72; 95% CI 2.92‐4.75). AKI‐D was associated with higher risk of in‐hospital mortality (aOR 3.54; 95% CI 2.81‐4.47) and adverse discharge (aOR 4.01; 95% CI 3.12‐5.17). Although percentage mortality within AKI‐D decreased over the decade, attributable risk percentage mortality remained stable.Conclusions
AF hospitalizations complicated by AKI‐D have quintupled over the last decade with differential increase by demographic groups. AKI‐D is associated with significant morbidity and mortality. Without effective AKI‐D therapies, focus should be on early risk stratification and prevention to avoid this devastating complication.
Cardiovascular disease is a leading cause of mortality in the elderly. Hypertension is an important modifiable risk factor that contributes to cardiovascular morbidity and mortality. The prevalence of hypertension is known to increase with age, and hypertension has been associated with an increase in risk for cardiovascular disease in the elderly. There is a wealth of evidence that supports aggressive control of blood pressure to lower cardiovascular risk in the general population. However, there are limited data to guide management of hypertension in the elderly and frail patient subgroups. These subgroups are inadequately treated due to lack of clarity regarding blood pressure thresholds, treatment targets, comorbidities, frailty, drug interactions from polypharmacy, and high cost of care. Areas covered: We review the current evidence behind the definition, goals, and treatments for hypertension in the elderly and frail and outline a strategy that can be used to guide antihypertensive pharmacotherapy in this population. Expert commentary: Lower blood pressure to < 130/80 mm Hg in elderly patients if tolerated and promote use of combination therapy if the blood pressure is > 20/10 mm Hg over the goal blood pressure. Antihypertensive treatment regimens must be tailored to each individual based on their comorbidities, risk for adverse effects, and potential drug interactions ( Figure 1 ).
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