Genetics in familial hypercholesterolaemia – from genetic research to new guidelines

2019 ◽  
Vol 88 (3) ◽  
pp. 192-194
Author(s):  
Edyta Kinga Prokop ◽  
Paweł Piotr Jagodziński ◽  
Stefan Grajek
Keyword(s):  
Familial Hypercholesterolaemia ◽  
Disease Risk ◽  
Genetic Disorder ◽  
Cardiovascular Disease Risk ◽  
Genetic Research ◽  
Ldl Receptor ◽  
Early Death ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
European Society Of Cardiology

Familial Hypercholesterolaemia (FH) is genetic disorder touching up to 1 to 250 people, increasing the risk of atherosclerotic cardiovascular disease risk and early death by 3–13 times. The majority of mutations are autosomal dominant among 3 genes related to cholesterole metabolism: LDL‑receptor (LDLR), apolipoprotein B (APOB) or proprotein convertase subtilisin/kexin type 9 (PCSK9). It comprises 60% of reported cases, which still is not at satisfactory level. This article summarizes new research in the field of FH and points out new therapeutic methods — PCSK9 inhibitors as advised in new European Society of Cardiology guidelines od dyslipidaemias.

Should we Consider Lipoprotein (a) in Cardiovascular Disease Risk Assessment in Patients with Familial Hypercholesterolaemia?

2019 ◽  
Vol 24 (31) ◽  
pp. 3665-3671 ◽  
Author(s):  
Panagiotis Anagnostis ◽  
Pavlos Siolos ◽  
Dimitrios Krikidis ◽  
Dimitrios G. Goulis ◽  
John C. Stevenson
Keyword(s):  
Cardiovascular Disease ◽  
Familial Hypercholesterolaemia ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pcsk9 Inhibitors ◽  
Cvd Risk ◽  
Lipoprotein A ◽  
Increased Risk

Background: Familial hypercholesterolaemia (FH) is a genetically determined lipid disorder, affecting 1 per 200-500 individuals in the general population. It is significantly and independently associated with an increased risk of Cardiovascular Disease (CVD), although it remains still an underrecognized and undertreated disease. Lipoprotein (a) [Lp(a)] is a low-density-lipoprotein (LDL)-like molecule, containing an additional protein, apolipoprotein (a). Objective: This review aims to present and discuss available data on the role of Lp(a) in patients with FH, in terms of its potential augmentation of CVD risk. Methods: A comprehensive search of the literature was performed to identify studies evaluating the CV effects of Lp(a) in patients with FH. Results: Lp(a) has been recognised as an independent risk factor for CVD, mainly coronary artery disease (CAD). Most, but not all, studies show increased Lp(a) concentrations in adults and children with FH. There is also evidence of an independent association between Lp(a) and CVD (mainly CAD) risk in these patients. Conclusion: Some therapeutic modalities, such as niacin, oestrogens, tibolone and proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibitors may effectively reduce Lp(a) concentrations by 25-30%, although their clinical benefit of this effect remains to be established.

scholarly journals Current Treatment of Familial Hypercholesterolaemia

2014 ◽  
Vol 9 (2) ◽  
pp. 76 ◽  
Author(s):  
Cameron T Lambert ◽  
Pratik Sandesara ◽  
Ijeoma Isiadinso ◽  
Maria Carolina Gongora ◽  
Danny Eapen ◽  
...  
Keyword(s):  
Familial Hypercholesterolaemia ◽  
Lifestyle Modification ◽  
Receptor Gene ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Autosomal Dominant Disorder

Familial hypercholesterolaemia is an autosomal-dominant disorder associated with mutations in the LDL receptor gene resulting in markedly elevated plasma low-density lipoprotein cholesterol levels. FH is significantly underrecognised with as many as 1 in 300 having the heterozygous form and 1 in 1 million having the homozygous form of the disease. Early diagnosis and treatment of FH is paramount to reduce the risk of premature atherosclerotic cardiovascular disease and death. The goal of treatment is to reduce LDL-C by 50 % from baseline levels with lifestyle modification, pharmacologic lipid-lowering therapy, LDL apheresis and in rare cases, liver transplantation. Pharmacologic treatment ranges from statin medications to newer agents such as lomitapide, mipomersin and PCSK9 inhibitors. Combination therapy is frequently required to achieve goal lipoprotein level reductions and prevent complications.

New Horizons in the Pathogenesis, Pathophysiology and Treatment of Familial Hypercholesterolaemia

2019 ◽  
Vol 24 (31) ◽  
pp. 3599-3604 ◽  
Author(s):  
Margus Viigimaa ◽  
Silver Heinsar ◽  
Dragan Lovic ◽  
Alexandra Katsimardou ◽  
Alexia Piperidou ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Familial Hypercholesterolaemia ◽  
Genetic Disorder ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Public Health Problem ◽  
Atherosclerotic Cardiovascular Disease ◽  
Significant Public Health Problem ◽  
Significant Public Health

Background: Familial Hypercholesterolaemia (FH) is an autosomal-dominant genetic disease and represents the most common genetic disorder: heterozygous 1/250 births, homozygous 1/300, 000 births. FH is characterized by high to very high low-density lipoprotein cholesterol (LDL-C), which is the main cause of increased incidence of premature atherosclerotic Cardiovascular Disease (CVD) or aortic stenosis. Objective: The aim of the review was to investigate the pathogenesis and the pathophysiology of FH. Results: The most common (60-80%) FH cause is mutations of the LDL Receptor (LDLR) protein (6 classes with a different number of receptors and functionality). Moreover, mutations in apolipoprotein B (APOB) (<5%) and gain-of-function mutations of proprotein convertase subtilisin/kexin type 9 genes (PCSK9) (<1%) contribute to its pathogenesis. An Autosomal Recessive Hypercholesterolaemia (ARH) is another cause, very rare (1/2.500 births), mainly in Sardinia. The remaining patients with a clinical diagnosis of monogenic hypercholesterolaemia do not present any known genetic cause. Since FH is a significant public health problem, early diagnosis and treatment are of utmost importance. Recent studies demonstrated the influence of the LDLR mutation type in the FH phenotype, associating a more severe clinical phenotype and worse advanced CVD in patients with null mutation than those with receptor-defective mutations. This analysis completes the adequate clinical diagnosis. Conclusion: Both homozygous and heterozygous FH are related to mutations of LDLR (mainly), APOB, PCSK9, while other rare forms exist. All aberrations lead to the impaired removal of LDL-C from the blood leading to its accumulation and subsequent CVD earlier than in the general population.

scholarly journals Rationales and uncertainties for aspirin use in COVID-19: a narrative review

2021 ◽  
Vol 9 (2) ◽  
pp. e000741
Author(s):  
Hazem A Sayed Ahmed ◽  
Eric Merrell ◽  
Mansoura Ismail ◽  
Anwar I Joudeh ◽  
Jeffrey B Riley ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Low Dose ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Narrative Review ◽  
Cochrane Library ◽  
Atherosclerotic Cardiovascular Disease ◽  
Dose Aspirin ◽  
Hospitalised Patients ◽  
Low Dose Aspirin

ObjectivesTo review the pathophysiology of COVID-19 disease, potential aspirin targets on this pathogenesis and the potential role of aspirin in patients with COVID-19.DesignNarrative review.SettingThe online databases PubMed, OVID Medline and Cochrane Library were searched using relevant headlines from 1 January 2016 to 1 January 2021. International guidelines from relevant societies, journals and forums were also assessed for relevance.ParticipantsNot applicable.ResultsA review of the selected literature revealed that clinical deterioration in COVID-19 is attributed to the interplay between endothelial dysfunction, coagulopathy and dysregulated inflammation. Aspirin has anti-inflammatory effects, antiplatelet aggregation, anticoagulant properties as well as pleiotropic effects on endothelial function. During the COVID-19 pandemic, low-dose aspirin is used effectively in secondary prevention of atherosclerotic cardiovascular disease, prevention of venous thromboembolism after total hip or knee replacement, prevention of pre-eclampsia and postdischarge treatment for multisystem inflammatory syndrome in children. Prehospital low-dose aspirin therapy may reduce the risk of intensive care unit admission and mechanical ventilation in hospitalised patients with COVID-19, whereas aspirin association with mortality is still debatable.ConclusionThe authors recommend a low-dose aspirin regimen for primary prevention of arterial thromboembolism in patients aged 40–70 years who are at high atherosclerotic cardiovascular disease risk, or an intermediate risk with a risk-enhancer and have a low risk of bleeding. Aspirin’s protective roles in COVID-19 associated with acute lung injury, vascular thrombosis without previous cardiovascular disease and mortality need further randomised controlled trials to establish causal conclusions.

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