Familial Hypercholesterolemia Patients with COVID-19—Effective Cholesterol-Lowering Therapy is Urgent both during and after Infection

Abstract

Heterozygous familial hypercholesterolemia (HeFH) patients are the prime example of subjects who are at high risk for both acute myocardial infarction (AMI) and ischemic stroke during, and post, SARS-CoV-2 infection. HeFH per se, if left untreated, results in premature clinical atherosclerosis often presenting in the fourth or fifth decade of life. The other concern in HeFH is endothelial dysfunction which is already evident from early childhood. In untreated HeFH patients, the severe hypercholesterolemia causes endothelial dysfunction from an early age, and as a result thereof, atherosclerotic lesions develop prematurely, particularly in the coronary arteries, and result in further endothelial dysfunction and inflammation in these critical segments of the arterial tree. As the pre-existing endothelial dysfunction in HeFH patients is most likely sensitive to further direct and indirect SARS-CoV-2 virus-dependent damage, we can infer that HeFH serves as an example of a comorbidity that predicts a poorer prognosis with COVID-19 infection. Indeed, a large US national database study showed that patients diagnosed with HeFH and SARS-CoV-2 infection had significantly increased Annualized Incidence Density Rates (AIDRs) of AMI when compared to matched HeFH controls not having been diagnosed with SARS-CoV-2 infection. Effective cholesterol lowering is essential for the prevention, or at least alleviation, of the detrimental effects of SARS-CoV-2 infection among HeFH patients. Due to the pre-existing subclinical or even clinical atherosclerotic cardiovascular disease in subjects with HeFH, cholesterol-lowering treatment needs to be continued or, better still, intensified during, and for an extended period post, SARS-CoV-2 infection.

SARS-CoV-2 reinfection: Adding insult to dysfunctional endothelium in patients with atherosclerotic cardiovascular disease

“…Since the risk caused by reinfection builds on the residual risk caused by the first infection, the cardiovascular consequences of the first infection in the general population and the relatively rare autosomal dominant disorder familial hypercholesterolemia (FH) will be presented first. Previously, we have summarized the current understanding of the high vulnerability of FH patients to the first SARS-CoV-2 infection, with endothelial dysfunction supposedly playing a noticeable role in the generation of adverse clinical consequences [ [5] , [6] , [7] , [8] ]. Although we focus on the clinical pieces of evidence showing that COVID-19 infection raises the risk for cardiovascular diseases and their complications, we also recognize that patients suffering from cardiovascular diseases are more prone to SARS-CoV-2 infection, revealing that such a two-way connection between viral infections and cardiovascular disease risk may exist [ 9 ].…”