Chronic metabolic health disorders like familial hypercholesterolemia (FH) have been associated with a risk of poorer disease trajectories and clinical outcomes in people who contract COVID-19. A commentary discussing the unique health concerns of these patients was published in Atherosclerosis Plus.

During the acute phase of a COVID-19 infection, control of pre-existing metabolic diseases is likely to deteriorate due to the endothelial dysfunction caused by the virus.

Patients with heterozygous FH (HeFH) exhibit 2-fold higher low-density lipoprotein cholesterol (LDL-C) levels from birth, predisposing them to develop premature atherosclerotic cardiovascular disease (ASCVD). ASCVD itself has been associated with increased risk for COVID-19-associated mortality and what healthcare professionals call “metabolic long COVID-19”.


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An estimated ~420,000 patients with HeFH and 470 with homozygous FH (HoFH) have been infected with COVID-19, and studies have associated FH with increased risk for myocardial infarction during infection.

COVID-19 has been found to cause a reprogramming of amino acid, glucose, and lipid metabolic pathways, and the severity of disease has been associated with activation of the sterol regulatory element-binding protein 2 (SREBP-2). Patients with HoFH were previously linked with an overexpression of SREBP-2, which is likely a contributing factor for poorer COVID-19 outcomes.

In addition to chronically elevated LDL-C levels, patients with FH often have elevated lipoprotein(a) [Lp(a)] associated with endothelial dysfunction from childhood. Elevated Lp(a) likely enhances the proinflammatory and prothrombotic effects of COVID-19, such as cytokine storm and thrombus formation.

After infection with COVID-19, Lp(a) levels may not return to preinfection levels for several months, which could lead to the destabilization of existing atherosclerotic plaques. Physicians, according to the researchers, should be aware that this patient population may be at elevated risks for acute cardiovascular events for months after discharge from the hospital.

The commentary authors recommend doctors treating patients who have both FH and COVID-19 continue treating them for hypercholesterolemia and consider that many patients will require an intensification of their therapy during illness, even persisting after hospital release. Long-term follow-up is recommended.

Although there have been reports of myocarditis and pericarditis in reaction to the mRNA-based COVID-19 vaccines, according to the authors, there had been no documented cases among patients with FH when the authors’ commentary was published. The authors contend the risks due to COVID-19 infection “clearly outweigh the risk of rare adverse events related to the vaccination” and recommended all patients with FH be fully vaccinated for COVID-19.

Additionally, the authors wrote, “there should be no hesitation to continue with statin therapy in severe hypercholesterolemic patients with COVID-19, whether they are FH patients or not.” They added clinicians should “even consider intensifying statin therapy as well as the addition of other lipid-lower agents, such as ezetimibe and proprotein convertase subtilisin/Kexin 9 (PCSK9) inhibitors.”

Disclosure: Multiple authors declared affiliations with pharmaceutical companies.. Please see the original reference for a full list of authors’ disclosures.

Reference

Vuorio A, Strandberg TE, Raal F, Santos RD, Kovanen PT. Familial hypercholesterolemia and COVID-19: a menacing but treatable vasculopathic condition. Atheroscler Plus. 2021;43:3-6. doi:10.1016/j.athplu.2021.08.001