Familial hypercholesterolaemia and COVID-19: A two-hit scenario for endothelial dysfunction amenable to treatment

Vuorio, Alpo; Raal, Frederick; Kaste, Markku; Kovanen, Petri T.

Patients with familial hypercholesterolemia (FH) are likely at increased risk for COVID-19 complications in the acute phase of the infection, and for a long time thereafter. As elevated levels of LDL-C are present from birth and since the degree of systemic endothelial dysfunction correlates with serum LDL-C levels, both heterozygous FH (HeFH) and, in particular, homozygous FH (HoFH) patients have dysfunctional endothelial cells which are oversensitive to further damage by the direct viral attack and the hyper-inflammatory reaction typical of severe COVID-19. Evidence to date shows the benefit of statin use in patients with COVID-19. In FH patients, the focus should therefore be on the effective lowering of LDL-C levels, the root cause of the expected excess vulnerability to COVID-19 infection in these patients. Moreover, the ongoing use of statins and other lipid-lowering therapies should be encouraged during the COVID pandemic to mitigate the risk of cardiovascular complications from COVID-19. For the reduction of the excess risk in FH patients with COVID-19, we advocate stringent adherence to the guideline determined LDL-C levels for FH patients, or maybe even to lower levels. Unfortunately, epidemiologic data are lacking on the severity of COVID-19 infections as well as the number of acute cardiac events that have occurred in FH subjects during the COVID-19 pandemic. Such data need to be urgently gathered to learn how much the risk for, and the severity of, COVID-19 in FH are increased.