Frederik Raal

Bio: Frederik Raal is an academic researcher from University of the Witwatersrand. The author has contributed to research in topics: Familial hypercholesterolemia & PCSK9. The author has an hindex of 1, co-authored 1 publications receiving 1 citations.

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

Abstract: 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.

Prevention of Cardiovascular Burden in COVID-19 Patients Suffering from Familial Hypercholesterolemia: A Global Challenge.

Abstract: A recent meta-analysis of over 20,000 individuals showed that hospitalized COVID-19 patients with acute myocardial injury had more than fourfold higher mortality than those without such injury. Since the COVID-19 pandemic exacerbates already existing health inequalities, there is an urgent need to create measures to protect the most vulnerable patient groups, including those with a pre-existing increased risk of atherosclerotic cardiovascular disease (ASCVD). A typical example is familial hypercholesterolemia (FH), a common genetic disease affecting over 30 million individuals worldwide. If left untreated or undertreated, FH patients suffer from complications of premature ASCVD, such as acute coronary syndromes, resulting in acute myocardial injury/infarction. A recent population-based analysis provided strong evidence suggesting that COVID-19 poses an even higher risk for myocardial injury in FH patients. From the long-term preventive point of view, it is important to note that, in addition to the acutely elevated risk of myocardial injury, an elevated risk of ASCVD and its complications will persist after COVID-19. The decline in outpatient preventive care during the pandemic is likely to influence ASCVD risk and outcomes, particularly in high-risk patients, such as those with FH. This commentary aims to raise global awareness of the challenges that clinicians treating FH patients continue to face during the COVID-19 pandemic, with two low- to middle-income countries, South Africa and Brazil, serving as examples.

Long-Term Cardiovascular and Cerebrovascular Challenges Posed by COVID-19 in Patients With Familial Hypercholesterolemia

Abstract: Follow-up studies have revealed that during the severe acute respiratory syndrome (SARS) caused by coronavirus SARS-CoV epidemic between 2002 and 2003, a significant proportion of those infected had a deterioration in the general health and exercise capacity, especially during the 24 months postinfection (Ngai et al., 2010; Zhang et al., 2020a). Although the emphasis of the follow-up by Ngai and coworkers (2010) was on monitoring alterations in the lung function, a significant impairment in quality of life, as assessed by the SF-36 quality-of-life measures, was reported (Ngai et al., 2010). The long-term effects of SARS-CoV infection have been found to also affect lipid and glucose metabolism in recovered SARS patients (Wu et al., 2017). Thus, the impaired metabolic pathologies were observed 12 years after the infection, and they were considered to be long-term effects of the initial lung damages, and to be potentially also related to the one-month-long high-dose prednisolone treatment given during the acute phase of the disease. Long-term symptoms, usually lasting for about 24 months, have also been reported in survivors of the epidemic influenza A (H7N9) (Chen et al., 2017) and Dengue (Garcia et al., 2011). As could have been envisaged, numerous COVID-19 patients also suffer from long-term impairment of health after an acute SARS-CoV-2 infection, particularly if the symptoms of the disease have been severe and the patients had to be hospitalized (Nalbandian et al., 2021). In an earlier commentary, we have discussed the acute phase of COVID-19 in patients with familial hypercholesterolemia (FH) (Vuorio et al., 2021a). We now wish to highlight concerns related to the long-term effects of SARS-CoV-2 infections and the increases in the risk for complications and potentially a poor outcome in this group of patients.

Familial hypercholesterolemia: The nexus of endothelial dysfunction and lipoprotein metabolism in COVID-19

Abstract: Purpose of review Patients with heterozygous familial hypercholesterolemia (HeFH) are at increased risk for COVID-19 cardiovascular complications in the acute phase of the infection. Elevated levels of LDL-C and often lipoprotein(a) are present from birth and lead to endothelial dysfunction, which is aggravated by a direct viral attack of the endothelial cells and their exposure to the toxic levels of circulating proinflammatory and prothrombotic mediators during the hyperinflammatory reaction typical of COVID-19. Recent findings Evidence to date shows the benefit of lipid-lowering therapy in patients with COVID-19. In HeFH patients who are at much higher cardiovascular risk, the focus should, therefore, be on the effective lowering of LDL-C levels, the root cause of the greater cardiovascular vulnerability to COVID-19 infection in these patients. The ongoing use of statins and other lipid-lowering therapies should be encouraged during the ongoing COVID pandemic to mitigate the risk of cardiovascular complications from COVID-19, particularly in HeFH patients. Summary Epidemiologic registry data show that the incidence of myocardial infarction is increased in SARS-CoV-2-infected HeFH patients. There is a need to study whether the risk for acute cardiovascular events is increased in the long-term and if there are changes in lipid metabolism after SARS-CoV infection(s) in patients with HeFH.

Coronary microcirculatory dysfunction in hypercholesterolemic patients with COVID-19: potential benefit from cholesterol-lowering treatment

Abstract: Abstract Patients with hypercholesterolemia often have coronary microvascular dysfunction (CMD). Viral infections, such as the SARS-CoV-2 infection, may also result in CMD. Three non-randomized studies have shown significant beneficial effects of statins on CMD in non-infected patients. Similarly, in SARS-CoV-2 - infected patients one beneficial mechanism of action of statins may be the amelioration of endothelial dysfunction, which is a major driver of CMD. Apart from statins, lipoprotein apheresis and PCSK9 inhibitors can also improve or even reverse CMD. The potential reversal of CMD by using effective cholesterol-lowering medications during and after COVID-19 infection, especially in hypercholesterolemic COVID-19 patients, is important. KEY MESSAGES Coronary microvascular dysfunction (CMD) is common in patients hospitalized with SARS-CoV-2 infection Three nonrandomized studies in non-infected patients are showing the beneficial effects of statin treatment on CMD Effective cholesterol-lowering medication during and after SARS-CoV-2 infection, especially in hypercholesterolemic COVID-19 patients, is of great significance