Article Archive
Mind the Gap: How can we address the challenges in FH?
2014 FH Global Summit: 13-14 October, New York, USA Screening for FH needs new impetus. Family history and an elevated LDL-C are the two key screening criteria for suspected FH. The obvious role for screening for suspected FH lies with primary care. Insights from the…
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Heterogeneity in FH: What are the implications for management?
According to Professor Frederick Raal, South Africa, irrespective of genotype, what matters is reducing the LDL-C burden with lipid-lowering therapy. Familial hypercholesterolemia (FH) is an autosomal co-dominant disorder usually resulting from mutations in the LDL receptor (LDLR) gene characterised by elevated levels of LDL-cholesterol (LDL-C)…
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PCSK9 inhibition in diabetes and metabolic syndrome: an analysis from OSLER
New findings, reported at the 2014 American Diabetes Association 74th Scientific Sessions,1 show thattreatment with the PCSK9 monoclonal antibody evolocumab reduced plasma levels of low-density lipoprotein cholesterol (LDL-C) in hypercholesterolaemic patients with dysglycaemia or metabolic syndrome, without worsening glucose control. Lead author, Dr Robert R…
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Rationale and Design of the Familial Hypercholesterolemia Foundation CAscade SCreening for Awareness and Detection
Familial hypercholesterolemia (FH) is a hereditary condition caused by various genetic mutations that lead to significantly elevated low-density lipoprotein cholesterol levels and resulting in a 20-fold increased lifetime risk for premature cardiovascular disease. Although its prevalence in the United States is 1 in 300 to…
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Unmet clinical needs in cholesterol lowering
Recent decades has seen marked improvement in reducing rates of heart disease and stroke (cardiovascular disease), particularly in developed nations.1 High levels of low-density lipoprotein cholesterol (LDL-C), or ‘bad cholesterol’ are considered a major risk factor for cardiovascular disease. International guidelines state that reduction of…
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Alirocumab and Lp(a): Pooled analysis of Phase II trials
Alirocumab 150 mg every 2 weeks reduced Lp(a) by 30% compared with placebo, based on a pooled analysis of 3 phase II trials in patients treated with background lipid-lowering treatment.1 These findings were consistent with a pooled analysis of evolocumab phase II trials,2 suggesting a…
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Evidence for the effects of PCSK9 beyond the liver
Evidence for the effects of PCSK9 beyond the liver was discussed by Professor Bertrand Cariou, INSERM UMR1087, l’Institut du Thorax, Nantes, France. A seminal paper showed that PCSK9 exerts hypocholesterolaemic effects via action in both the liver and intestine; in the latter case, PCSK9 modulates…
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Reducing the burden of Disease and Death from Familial Hypercholesterolemia: A Call to Action
Familial hypercholesterolemia (FH) is a genetic disease characterized by substantial elevations of low-density lipoprotein cholesterol, unrelated to diet or lifestyle. Untreated FH patients have 20 times the risk of developing coronary artery disease, compared to the general population. Estimates indicate that as many as 1…
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IMPROVE-IT: will it prove anything?
Professor Anthony S. Wierzbicki, London UK Comments on the IMPROVE-IT debate Cardiovascular disease (CVD) guidelines are emphasising the use of clinical outcome data on major vascular events (American Heart Association/American College of Cardiology)1 or hard CVD events alone (UK NICE)2 . They have begun to…
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What does PCSK9 monoclonal antibody therapy offer to reduce residual CV risk?
Anthony S. Wierzbicki DM, DPhil, FRCPath Consultant, Department of Metabolic Medicine/Chemical Pathology Guy’s & St Thomas’ Hospitals St Thomas’ Hospital, London UK E-mail: [email protected] Cardiovascular disease (CVD) remains the greatest cause of world morbidity and mortality. Rates of CVD have decreased in parallel with reductions…
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ODYSSEY trials at ESC Congress Hotline
ESC Congress 2014: Lipids Hotline: ODYSSEY TRIALS Prof Alberto Zambon, University of Padua, Italy discusses the four ODYSSEY trials with the PCSK9 inhibitor alirocumab presented at ESC Congress Hotline Sunday. Addition of a new investigational agent – Alirocumab – to high doses of statins result…
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The role of PCSK9 inhibitors in FH
Monoclonal antibodies targeting PCSK9 have been shown to reduce low density lipoprotein cholesterol (LDL-C) by 30-40% in patients with familial hypercholesterolaemia (FH) who still have LDL receptors. Studies also show that the investigational drug, evolocumab was well tolerated, Dr Dirk Blom said.
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Take home messages from ACC2014
Results of studies presented in 2014, show that PCSK9 inhibitors: 1) very effectively reduce low density lipoprotein cholesterol (LDL-C); and 2) show consistently predictable safety profiles. The positive results of short-term studies are now being reported in longer terms and larger clinical studies, Dr Evan…
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Updates from the literature
Norsworthy PJ, Vandrovcova J, Thomas ER, Campbell A, Kerr SM, Biggs J, Game L, Soutar AK, Smith BH, Dominiczak AF, Porteous DJ, Morris AD, Scotland G, Aitman TJ: Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing: a population-based study. BMC.Med.Genet. 2014, 15:70. Abstract:…
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Why we need new approaches
Undoubtedly, LDL cholesterol is the priority target for intervention to reduce the risk of cardiovascular disease (CVD), as reaffirmed by the recent ACC/AHA guidelines for cholesterol management.1 Statins are at the cornerstone of lipid-modifying therapy. However, as recommended targets for LDL cholesterol have fallen as…
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Is there a need for a unified definition for FH?
2014 FH Global Summit: 13-14 October, New York, USA: FH is clearly underdiagnosed and undertreated in the majority of countries.1 Given this status quo, would the development of a unified global definition of FH offer advantages for detection, management and health policy? In the FH…
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Do the PCSK9 inhibitors have pleiotropic effects?
Experimental studies show that significant reductions in low density lipoprotein cholesterol (LDL-C) will significantly reduce inflammation which is important in Atherosclerosis (narrowing of the arteries) says Professor Erik Stroes.
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Lp(a) and FH
Certain conditions, notably familial hypercholesterolaemia (FH), are associated with increased Lp(a) levels. The mechanism of this is so far undefined and may not directly involve the LDL receptor pathway. Holmes DT, Schick BA, Humphries KH, Frohlich J. Lipoprotein(a) is an independent risk factor for cardiovascular…
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Lp(a) and CV risk
In epidemiological studies, levels of Lp(a) >125 nmol/L (~50 mg/dL), the 80th percentile for most populations, showed a consistent and independent positive association with CVD risk.1,2 Additionally, a large Mendelian randomisation study showed that a genetically determined doubling of Lp(a) was associated with a 22%…
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About Lp(a)
Lipoprotein(a) [Lp(a)] is an LDL-like plasma lipoprotein rich in cholesterol. Lp(a) differs from LDL as it contains an additional protein, apolipoprotein(a) [apo(a)], which is attached via a single disulphide bond. Apo(a) itself comprises a series of loop structures called kringles, named after a Danish pastry….
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