Cardiometabolic Risk Factors and COVID-19

In keeping with the theme of last week’s blog on the development of a high throughput preclinical airway model for testing anti-viral therapeutics against influenza and coronaviruses, we will be summarizing the final COVID-19 focus seminar published by the Journal of the American College of Cardiology. This seminar entitled Coronavirus and Cardiometabolic Syndrome outlines epidemiological/mechanistic findings from studying the health history of COVID-19 patient cohorts globally that substantiate a novel coronavirus disease–related cardiometabolic syndrome (CIRCS). Researchers highlight four key cardiometabolic risk factors —abnormal adiposity (obesity), dysglycemia (diabetes), dyslipidemia (high cholesterol), and hypertension (high blood pressure) that intersect and interact across COVID-19 that worsen patient outcomes. The central role that the renin-angiotensin system, where ACE2 is a key receptor, plays in CIRCS. The interconnectivity of these risk factors highlights the overall need to proactively/preventatively improve the population’s cardiometabolic health to mitigate complications arising from unanticipated viral challenges.

Abnormal Adiposity (Obesity)

Epidemiological studies reveal patients with obesity were significantly more likely to be admitted to the intensive care unit (ICU) after COVID-19 infection as well as having higher mortality rates than those without obesity. One of the primary mechanisms of abnormal adiposity leading to cardiovascular disease is the accumulation of inflammatory pericardial/epicardial fat, which shows an increased angiotensin-converting enzyme 2 (ACE2) expression. This is important because ACE2 is the main entry receptor for SARS-CoV-2, the virus responsible for COVID-19.

Dysglycemia (Diabetes)

SARS-CoV-2 infection rates and disease severity markers were found to be increased in patients with diabetes, specifically type 2 diabetes. This could be because of other comorbidities that typically manifest alongside diabetes like a higher incidence of obesity, hypertension (HTN), and CVD in diabetic patients. Research indicates that increased expression of ACE2 on pancreatic cells, glycosylation of the viral spike protein causes increased viral binding/entry and increased viral replication all contribute to a diabetic’s susceptibility to SARS-CoV-2 infection and potential for complications arising from infection.

Dyslipidemia (High Cholesterol)

Individuals who have high cholesterol in the context of COVID-19 infection have an increased risk for premature coronary heart disease and atherothrombosis. Statins, having both cholesterol-lowering and anti-inflammatory properties, are a standard treatment for high cholesterol to mitigate the risk of potential cardiovascular events. Interestingly, patients who were already taking statins for cholesterol reduction that became infected with a specific hyperinflammatory sub-phenotype of SARS-CoV-2 had improved survival rates over patients not taking statins.  In this case, the use of statins provided some protective benefit against COVID-19 but their ability to specifically treat COVID-19 infection remains unclear and warrants further investigation.

Hypertension (High Blood Pressure)

High blood pressure is tightly correlated with cardiovascular complications such as coronary heart disease, heart failure and stroke.  Among patients with COVID-19, hypertension was associated with frequent cardiovascular morbidities (24.3%), diabetes (15.2%), cardiac disease (6.2%), and higher mortality risk. ACE2 figures prominently in the renin-angiotensin system, the key blood pressure regulating cascade and is implicated in cardioprotective mechanisms. The loss of ACE2 function caused by SARS-CoV-2 binding is thought to lead to CIRCS development.

CIRCS Prevention

The epidemiological evidence presented supports a connection between the cluster of metabolic drivers and COVID-19 disease severity that forms a CIRCS framework. As a preventative measure against the development of CIRCS, the authors recommend lifestyle changes (exercise and diet) and pharmacotherapy targeting metabolic drivers for patients to improve overall cardiometabolic health to decrease the prevalence of risk factors that make individuals susceptible to disease complications. Individuals presenting with pre-existing/underlying metabolic and cardiovascular dysfunction who become infected with SARS-CoV-2 are more likely to experience blood clotting and poor immune function that have acute and long-term ramifications, underscoring the need to proactively address cardiometabolic health to improve patient outcomes both in the short- and long-term.

To read the summaries of the other JACC Focus Seminars in this series, please see the links below:

• Coronavirus and Cardiovascular Disease, Myocardial Injury, and Arrhythmia
• Coronavirus Historical Perspective, Disease Mechanisms, and Clinical Outcomes

Please join us here on the Lifeline Cell Technology blog for more publication reviews and industry insights.