Article Archive

Lipoprotein apheresis lowers plasma PCSK9

Lipoprotein apheresis is clearly important in the management of severe familial hyperchoelsterolaemia (FH). However, its use is not without practical and cost limitations. Evidence that lipoprotein apheresis has an additional benefit in lowering plasma PCSK9 levels, beyond effects on low-density lipoprotein cholesterol (LDL-C), suggests that…

PCSK9: From discovery to therapeutic applications

PUBMED abstract: http://www.ncbi.nlm.nih.gov/pubmed/24373748

How low should LDL cholesterol be lowered – and for how long?

Missing FH: How can we improve FH referral and diagnosis?

Heterozygous familial hypercholesterolemia (FH) is neither a rare disease nor a sentence to a life full of complications and early death. Recent evidence shows that even when founder effects are taken into account, heterozygous FH affects around 1/200-300 people instead of the historical estimate of…

Will the PCSK9 monoclonal antibodies replace other lipid lowering treatments currently used with statins?

Where will the new PCSK9 inhibitors fit into the treatment of people whose raised low density lipoprotein cholesterol (LDL-C) puts them at high risk of cardiovascular disease? Leading researcher, Professor Frederick Raal discusses this important question.

In your opinion, what are the optimum patient populations for PCSK9 monoclonal antibody therapy?

PCSK9 monoclonal antibodies offer very important new treatments to lowed low density lipoprotein cholesterol (LDL-C) in patients who cannot tolerate statins or whose LDL-C is inadequately reduced as well as those people with high LDL-C caused by Familial Hypercholesterolemia.

RUTHERFORD-2 slide deck now available

Alirocumab

A 24-Week Study of Alirocumab as Monotherapy versus Ezetimibe: The First Phase 3 Data of a Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor One Year Open-Label Treatment with Alirocumab 150 mg Every Two Weeks in Heterozygous Familial Hypercholesterolemic Patients Effects of Alirocumab, a Fully Human Monoclonal…

Will PCSK9 monoclonal antibody therapy replace other classes of drug currently used in combination therapy both in FH and non-FH indications?

Frederick J. Raal FRCP, FRCPC, FCP(SA), Cert Endo, MMED, PhD Professor and Head, Division of Endocrinology & Metabolism Director, Carbohydrate and Lipid Metabolism Research Unit University of the Witwatersrand, South Africa Elevated LDL-cholesterol(LDL-C) is considered to be the pivotal causative factor for atherosclerosis and LDL-C…

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…

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…

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…

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…

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.

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:…

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…

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.

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…

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%…

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….