Mortality from coronavirus disease 2019 (COVID-19) is strongly associated with cardiovascular disease, diabetes, and hypertension. These disorders share underlying pathophysiology related to the renin-angiotensin system (RAS) that may be clinically insightful. In particular, activity of the angiotensin-converting enzyme 2 (ACE2) is dysregulated in cardiovascular disease, and this enzyme is used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to initiate the infection. Cardiovascular disease and pharmacologic RAS inhibition both increase ACE2 levels, which may increase the virulence of SARS-CoV-2 within the lung and heart. Conversely, mechanistic evidence from related coronaviruses suggests that SARS-CoV-2 infection may downregulate ACE2, leading to toxic overaccumulation of angiotensin II that induces acute respiratory distress syndrome and fulminant myocarditis. RAS inhibition could mitigate this effect. With conflicting mechanistic evidence, we propose key clinical research priorities necessary to clarify the role of RAS inhibition in COVID-19 mortality that could be rapidly addressed by the international research community.

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Thrombotic complications are frequent in COVID-19 and contribute significantly to mortality and morbidity. We review several mechanisms of hypercoagulability in sepsis that may be upregulated in COVID-19. These include immune-mediated thrombotic mechanisms, complement activation, macrophage activation syndrome, antiphospholipid antibody syndrome, hyperferritinemia, and renin-angiotensin system dysregulation. We highlight biomarkers within each pathway with potential prognostic value in COVID-19. Lastly, recent observational studies have evaluated a role for the expanded use of therapeutic anticoagulation in COVID-19. We review strengths and weaknesses of these studies, and we also discuss the hypothetical benefit and anticipated challenges of fibrinolytic therapy in COVID-19. 2 | OVERVIEW OF COVID-19 ASSOCIATED HYPERCOAGULOPATHY Coronavirus disease 2019 induces a prothrombotic state, and a high frequency of reported major thrombotic events raises concern for unique

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Hypertension is a major risk factor for cardiovascular and renal diseases in the United States and worldwide. Obesity accounts for much of the risk for primary hypertension through several mechanisms, including neurohormonal activation, inflammation, and kidney dysfunction. As the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed. Lifestyle modification, including diet, reduced sedentariness, and increased physical activity, is usually recommended for patients with obesity; however, the long-term success of these strategies for reducing adiposity, maintaining weight loss, and reducing blood pressure has been limited. Effective pharmacotherapeutic and procedural strategies, including metabolic surgeries, are additional options to treat obesity and prevent or attenuate obesity hypertension, target organ damage, and subsequent disease. Medications can be useful for short- and long-term obesity treatment; however, prescription of these drugs is limited. Metabolic surgery is effective for producing sustained weight loss and for treating hypertension and metabolic disorders in many patients with severe obesity. Unanswered questions remain related to the mechanisms of obesity-related diseases, long-term efficacy of different treatment and prevention strategies, and timing of these interventions to prevent obesity and hypertension-mediated target organ damage. Further investigation, including randomized controlled trials, is essential to addressing these questions, and emphasis should be placed on the prevention of obesity to reduce the burden of hypertensive cardiovascular and kidney diseases and subsequent mortality.

Purpose of Review Several interrelated mechanisms play a role in the development of hypertension in obesity, often contributing to end organ damage including cardiovascular disease and chronic kidney disease. Recent Findings The treatment of hypertension in obesity is complicated by a high prevalence of resistant hypertension, as well as unpredictable hemodynamic effects of many medications. Weight loss stabilizes neurohormonal activity and causes clinically significant reductions in blood pressure. While lifestyle interventions can improve blood pressure, they fail to consistently yield sustained weight loss and have not demonstrated long-term benefits. Weight loss surgery provides more permanent weight reduction, corresponding with dramatic declines in blood pressure and attenuation of long-term cardiovascular risk. Summary Hypertension is closely linked to the prevalence, pathophysiology, and morbidity of obesity. There are multiple barriers to managing hypertension in obesity. Surgical weight loss offers the most promise in reducing blood pressure and decreasing end organ damage in this patient population.

Background and Aims Outcomes with anticoagulation (AC) are understudied in advanced liver disease. We investigated effects of AC with warfarin and direct oral anticoagulants (DOACs) on all‐cause mortality and hepatic decompensation as well as ischemic stroke, major adverse cardiovascular events, splanchnic vein thrombosis, and bleeding in a cohort with cirrhosis and atrial fibrillation (AF). Approach and Results This was a retrospective, longitudinal study using national data of U.S. veterans with cirrhosis at 128 medical centers, including patients with cirrhosis with incident AF, from January 1, 2012 to December 31, 2017 followed through December 31, 2018. To assess the effects of AC on outcomes, we applied propensity score (PS) matching and marginal structural models (MSMs) to account for confounding by indication and time‐dependent confounding. The final cohort included 2,694 veterans with cirrhosis with AF (n = 1,694 and n = 704 in the warfarin and DOAC cohorts after PS matching, respectively) with a median of 4.6 years of follow‐up. All‐cause mortality was lower with warfarin versus no AC (PS matched: hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.55‐0.76; MSM models: HR, 0.54; 95% CI, 0.40‐0.73) and DOACs versus no AC (PS matched: HR, 0.68; 95% CI, 0.50‐0.93; MSM models: HR, 0.50; 95% CI, 0.31‐0.81). In MSM models, warfarin (HR, 0.29; 95% CI, 0.09‐0.90) and DOACs (HR, 0.23; 95% CI, 0.07‐0.79) were associated with reduced ischemic stroke. In secondary analyses, bleeding was lower with DOACs compared to warfarin (HR, 0.49; 95% CI, 0.26‐0.94). Conclusions Warfarin and DOACs were associated with reduced all‐cause mortality. Warfarin was associated with more bleeding compared to no AC. DOACs had a lower incidence of bleeding compared to warfarin in exploratory analyses. Future studies should prospectively investigate these observed associations.