Frederick J. Raal Articles
Is baseline PCSK9 a determinant of LDL cholesterol lowering with a PCSK9 inhibitor?
Is baseline PCSK9 a determinant of LDL cholesterol lowering with a PCSK9 inhibitor? This report addresses this question by investigating the association between plasma PCSK9 and the LDL cholesterol reduction attained with the PCSK9 inhibitor evolocumab. The authors evaluated pooled data from 3,016 patients (40%…
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First data on familial hypercholesterolaemia in China
Most of the information relating to familial hypercholesterolaemia (FH, inherited high cholesterol) is from Caucasian populations. In Northern Europe, about 1 in 200-250 individuals have FH; results from the US are similar (1,2). However, there are many ‘black holes’ where there is no information on…
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No effect of PCSK9 inhibitors on new-onset diabetes
Treatment with alirocumab for up to 18 months did not affect the incidence of new-onset diabetes, according to this pooled analysis of Phase III trials from the ODYSSEY programme. These findings are in line with reports with evolocumab which showed no effect on glycaemic measures…
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Is lipoprotein(a) a cause of clinical familial hypercholesterolaemia?
Familial hypercholesterolaemia (FH, inherited high cholesterol) is a common autosomal dominant condition which is characterized by raised LDL cholesterol, family history of dyslipidaemia, and early onset of coronary heart disease. Beyond mutations in the LDLR, APOB and PCSK9 genes, a new study from the University…
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Low LDL-C, PCSK9 and dementia risk?
An ongoing debate among the experts is whether the very low levels of LDL cholesterol with PCSK9 inhibitor treatment might be associated with neurocognitive events. In fact, the debate predates the PCSK9 inhibitors, with statins linked with cognitive impairment (1-4). However, when the statin data…
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TAUSSIG: Does adding evolocumab reduce cardiovascular events in homozygous FH?
84th European Atherosclerosis Society Congress, 29 May- 1 June, Innsbruck, Austria Patients with homozygous familial hypercholesterolaemia (FH, inherited high cholesterol) are at extremely high risk of premature cardiovascular events due to the burden of elevated LDL cholesterol. Indeed, cardiovascular death at an early age is…
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How do PCSK9-inhibitors reduce lipoprotein(a)?
Beyond lowering LDL cholesterol, PCSK9 inhibition also reduces lipoprotein(a). Prof Derick Raal, University of the Witwatersrand, Johannesburg, South Africa discusses the underlying mechanism. Lipoprotein (a) [Lp(a)] is an LDL-like particle consisting of apolipoprotein(a) [apo(a)] that is disulphide-linked to the apoB moiety of LDL (1). Lp(a)…
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Why PCSK9 inhibitors are needed in FH: SAFEHEART highlights poor LDL cholesterol control
Five-year follow-up data from the Spanish SAFEHEART registry of patients with familial hypercholesterolaemia (FH, inherited high cholesterol) show that attainment of LDL cholesterol is still a major issue. Only 11% attained an LDL-C level of <2.5 mmol/L (100 mg/dl). This was despite increasing maximally tolerated…
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LY3015014: Another PCSK9 monoclonal enters the arena
Hot on the heels of alirocumab, evolocumab and bococizumab, comes the next PCSK9 monoclonal antibody, LY3015014. In this aaleport, dosing every 4 weeks with LY3015014 resulted in about 50% reduction in LDL cholesterol, comparable to that observed with these other monoclonal antibodies. LY3015014 is a…
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AHA Agenda on FH: Addressing the burden of underdiagnosed and undertreated FH
Underdiagnosed and undertreated familial hypercholesterolaemia (FH, inherited high cholesterol), is an important contributor to overall coronary heart disease (CHD) death and disability. This issue is clearly highlighted by a study presented at the American Heart Association Scientific Sessions 2015 (1). The investigators used a Markov…
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Stroke risk in heterozygous FH
Are individuals with heterozygous familial hypercholesterolaemia (FH, inherited high cholesterol) at higher risk of stroke? And if so, does statin treatment ameliorate this risk? Results from this meta-analysis suggest this may be the case. Heterozygous FH is undoubtedly associated with an increased risk of premature…
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ODYSSEY 78-week data in heterozygous FH: PCSK9 FORUM Expert view
ESC Congress 2015, 1 September 2015 Familial hypercholesterolaemia (FH, inherited high cholesterol) represents one of the key priorities for PCSK9 monoclonal antibody therapy. This analysis from the ODYSSEY clinical programme with alirocumab, which has the largest group of heterozygous FH patients studied to date, establishes…
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Peripheral arterial disease affects 1 in 5 FH patients
According to a new study from Brazil, nearly 1 in 5 patients with heterozygous familial hypercholesterolaemia (FH, inherited high cholesterol) have peripheral arterial disease (PAD), as detected by ankle-brachial index (ABI). This prevalence was 6-fold higher than in controls with normal cholesterol. Importantly, more than…
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Start treatment early: Maximise benefit
FH is the most common inherited disease in the world – affecting about 30 million people worldwide – of whom only about 1% have been diagnosed. Therefore, it is critically important there is a global effort to start treatment early to prevent children ever developing…
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Genotypic and phenotypic variation in FH – relevance to cardiovascular risk
Professor Frederick Raal FRCP, FRCPC, FCP(SA), MMED, PhD Director, Carbohydrate & Lipid Metabolism Research Unit
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LDL cholesterol lowering, PCSK9 and neurocognitive effects?
The possibility of neurocognitive effects with low-density lipoprotein (LDL) cholesterol lowering has been much debated. A new study (1) raises this issue again, suggesting increased risk of memory loss during the 30 days following the start of treatment, when comparing statin users and nonusers of…
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FH in Africa and the Middle East – the great unknown
Why we need a global initiative on FH: FH Connect: Prof Derick Raal, University of the Witwatersrand, Johannesburg, South Africa Expert consensus has already highlighted the extent of underdiagnosis and undertreatment of familial hypercholesterolaemia (FH, inherited high cholesterol), which if untreated increases the lifetime risk…
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ISA 2015: Evolocumab in TAUSSIG homozygous FH cohort
News from one of the largest cohort of patients with homozygous familial hypercholesterolaemia (FH, inherited high cholesterol) in the TAUSSIG (Trial Assessing Long-Term Use of PCSK9 Inhibition in Subjects With Genetic LDL Disorders) study strengthens the data for evolocumab.1 In 100 patients with homozygous FH,…
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ACC 2015: What do the OSLER and ODYSSEY data really show? Expert analysis from Professor Derick Raal
March 15, 2015 At an eagerly anticipated hotline at ACC 2015, a pre-specified, exploratory analysis of the OSLER studies, showed that the PCSK9 monoclonal antibody evolocumab reduced low-density lipoprotein (LDL) cholesterol by 61%, and that this was associated with a 53% reduction in cardiovascular events…
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Cascade Screening for FH: Lessons from Brazil
How can we improve on the detection and treatment of FH? PCSK9 Forum Editor Professor Frederick Raal discusses insights from a recent study in Brazil. Familial hypercholesterolemia (FH) is the most common dominantly inherited condition in humans, affecting 1:200 to 1:500 people or over 30…
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