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

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

doi:10.1016/j.atherosclerosis.2021.01.021

Cited by 31 publications

(47 citation statements)

References 109 publications

(65 reference statements)

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“…Considering the prevalence of FH, it is estimated that among the >140 million COVID-19 patients so far reported worldwide, approximately 420 000 and 470 patients with HeFH and HoFH, respectively, have been infected. In patients with FH, the severe hypercholesterolemia, if left untreated, causes lifelong endothelial dysfunction and thereby likely renders the vascular endothelium, including both the epicardial and intramyocardial coronary arterial endothelium, particularly vulnerable to the infectious and immunoinflammatory attacks and ensuing thrombus formation inherent in COVID-19 [ 13 ]. This prediction is supported by recent results derived from a large US national database which show that COVID-19 increases the risk of myocardial infarction in FH patients with or without diagnosed ASCVD [ 14 ].…”

Section: Fh-patients With Covid-19 Are At Increased Riskmentioning

confidence: 99%

Familial hypercholesterolemia and COVID-19: A menacing but treatable vasculopathic condition

Vuorio¹,

Strandberg

Raal

et al. 2021

Atherosclerosis Plus

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SARS-CoV-2 infection continues to cause increased morbidity and mortality, and due to the slow pace of vaccination COVID-19 will probably remain a global burden to health systems for a long time. Unfortunately, the necessary prevention and treatment strategies of COVID-19 have led to restriction measures that are hampering the routine care of common chronic metabolic conditions like hypercholesterolemia. It is of particular concern that during the acute phase of COVID-19, the control of pre-existing metabolic diseases tends to get worse which again increases the risk for complications and a poor outcome in these patients. A significant contributor to these complications is endothelial dysfunction which is associated with COVID-19. This Commentary will discuss the impact of COVID-19 on endothelial function particularly in patients with familial hypercholesterolemia (FH), a metabolic inherited disease known to in itself adversely affect endothelial function. There should be no hesitation to continue with statin therapy in severe hypercholesterolemic patients with COVID-19. We argue that in FH patients with COVID-19 the clinicians need even consider intensifying statin therapy as well as the addition of other lipid-lowering agents, such as proprotein convertase subtilisin/kexin type 9(PCSK9) inhibitors. In contrast to statins, the PCSK9 inhibitors lower lipoprotein(a) [Lp(a)] level, and, accordingly, these latter drugs need to be considered particularly in FH patients with an elevated level of Lp(a). This call applies to the in-hospital stay and also beyond. When considering that the vasculopathic effects of COVID-19 may persist, a long-term follow-up of individualized therapies in FH patients is warranted.

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Section: Fh-patients With Covid-19 Are At Increased Riskmentioning

confidence: 99%

Familial hypercholesterolemia and COVID-19: A menacing but treatable vasculopathic condition

Vuorio¹,

Strandberg

Raal

et al. 2021

Atherosclerosis Plus

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“…Moreover, many FH patients are exposed to elevated lipoprotein(a) [Lp(a)] which causes further endothelial dysfunction [ 4 , 5 ]. Endothelial dysfunction pre-exposes FH patients to the surplus endothelial damage caused by the SARS-CoV-2 viral attack [6] .…”

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confidence: 99%

“…To mitigate the risk of AMI in FH patients with COVID-19, continuing ongoing efficient statin medication, whether at home or in hospital, is of utmost [ 6 , 11 ]. Indeed, strict adherence to the current evidence-based guidelines regarding serum LDL-C target levels should be aimed for.…”

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confidence: 99%

“…Indeed, strict adherence to the current evidence-based guidelines regarding serum LDL-C target levels should be aimed for. Furthermore, in very high-risk FH patients with severe COVID-19, a triple regimen including a statin, ezetimibe, and a PCSK9 inhibitor should be strongly considered - at least temporarily [ 6 , 10 ]. PCSK9 inhibitors offer the possibility to continue lipid-lowering medication in ventilated ICU-treated FH patients with COVID-19 who are unable to take oral medication.…”

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confidence: 99%

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Patients with familial hypercholesterolemia and COVID-19: Efficient and ongoing cholesterol lowering is paramount for the prevention of acute myocardial infarction

Kovanen

Raal

Vuorio

2021

American Journal of Preventive Cardiology

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“…The most recent challenge related to FH is the COVID-19 pandemic (Vuorio et al, 2021a ). It can be estimated that with a HeFH prevalence of 1 in 250, ~440,000 HeFH patients may have had SARS-Cov-2 infection by February 2021.…”

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confidence: 99%

Editorial: Genetics of Familial Hypercholesterolemia: New Insight

2021

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Editorial on the Research Topic Genetics of Familial Hypercholesterolemia: New InsightThe Research Topic "Genetics Familial Hypercholesterolemia: New Insight" attracted over 100 authors from 16 countries to submit manuscripts on topical genetic research in familial hypercholesterolemia (FH). Encouragingly, over fifty percent of the manuscripts were from lowand middle-income countries researchers from very different backgrounds. This achieved our goal of bringing together researchers from worldwide. It also reaffirmed conclusions from Vrablik et al. review article: "The coordinated international efforts should increase the chances of achieving the principal goal-to identify, diagnose and provide treatment for all FH patients early enough." The strength of this review topic was the submission of manuscripts from researchers at different stages of their research portfolio. For example, Dušková et al. analyzed in detail pathogenic variants in the low-density lipoprotein gene and their effects on protein localization, function and expression of genes associate endoplasmic reticulum representing advanced molecular biology approaches. At the same time Vasilyev et al. were working with basic molecular biology questions and they concluded that "major achievements in the genetic investigation of the molecular features of FH in Russia are yet to come."Unfortunately, FH still remains vastly underdiagnosed disease. As an example, is the study by Ramaswami et al. (2019) that was carried out in UK pediatric population. This study demonstrated that <550 children with a confirmed diagnosis of heterozygous FH (HeFH) were being managed in the health care system. This was despite an estimated prevalence of 50,000 children under the age of 18 years with HeFH in the UK based on a population prevalence of 1 in 250. Once diagnosed, it is essential to enable long-term follow-up of these patients and collating longitudinal data on the management and safety of disease modifying therapies such as statins and newer emerging treatments. This would be possible with both national and international HeFH registries. These registries could also potentially help genotype-phenotype correlations related to different HeFH pathogenic mutations in the LDLR, APOB, or PCSK9 genes. This could also apply to genes associated to HeFH diagnosis, and which are differentially expressed compared to non-FH controls Udhaya Kumar et al..

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

Cited by 31 publications

References 109 publications

Familial hypercholesterolemia and COVID-19: A menacing but treatable vasculopathic condition

Familial hypercholesterolemia and COVID-19: A menacing but treatable vasculopathic condition

Patients with familial hypercholesterolemia and COVID-19: Efficient and ongoing cholesterol lowering is paramount for the prevention of acute myocardial infarction

Editorial: Genetics of Familial Hypercholesterolemia: New Insight

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