Attainment of LDL-Cholesterol Treatment Goals in Patients With Familial Hypercholesterolemia

Isla, Leopoldo Pérez de; Alonso, Rodrigo; Watts, Gerald F.; Mata, Nelva; Cerezo, Adriana Saltijeral; Muñiz, Ovidio; Fuentes, Francisco; Díaz‐Díaz, José Luis; Andrés, Raimundo de; Zambón, Daniel; Rubio-Marín, Patricia; Barba-Romero, Miguel Ángel; Sáenz, Pedro Luis Ruiz; Muñoz-Torrero, Juan Francisco Sánchez; Martínez-Faedo, Ceferino; Miramontes-González, José Pablo; Badimón, Lina; Mata, Pedro; Investigators, Safeheart; Aguado, Rocío; Almagro, Fátima; Arrieta, Francisco; Barba, Miguel Ángel Elvira; Brea, Ángel; Cepeda, José María; Dí­az, Gonzalo; Palencia, José Luis Díaz; Galiana, Jesús; Garrido, Juan Antonio; Irigoyen, Luis; Manjón, Laura; Martín, A. León; Piedecausa, Mar; Mauri, Marta; Miramontes, Pablo; Pereyra, Fernando Xavier; Pérez, Leire; Pintó, Xavier; Pujante, Pedro; Ruíz, Enrique; Sánchez, Juan F. Plaza; Vidal, Jose I.; Argüeso, Rosa

doi:10.1016/j.jacc.2016.01.008

Cited by 221 publications

(77 citation statements)

References 24 publications

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“…5 The SAFEHEART program in Spain showed that genetic screening identified patients at a younger age (median age, 49.5 years) and improved treatment initiation and adherence. 6 …”

Section: How Cascade Screening For Fh Workmentioning

confidence: 99%

Cascade Screening for Familial Hypercholesterolemia and the Use of Genetic Testing

Knowles

Rader

Khoury

2017

JAMA

147

134

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Familial hypercholesterolemia(FH) is a dominantly inherited genetic disorder affecting approximately 1 in 250 individuals. It is characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease (ASCVD). 1 Persons with FH have a 2.5to 10-fold in-creased risk of ASCVD com pared with controls, but when FH is diagnosed and treated early in life, the risk is greatly reduced (≈ 80%). 1 However, most people with FH have never been diagnosed or treated. Active case finding of FH plus family-based cascade screening can help identify individuals with FH and ensure treatment before ASCVD onset.

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“…5 The SAFEHEART program in Spain showed that genetic screening identified patients at a younger age (median age, 49.5 years) and improved treatment initiation and adherence. 6 …”

Section: How Cascade Screening For Fh Workmentioning

confidence: 99%

Cascade Screening for Familial Hypercholesterolemia and the Use of Genetic Testing

Knowles

Rader

Khoury

2017

JAMA

147

134

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“…For example, registries have been used to identify diagnosis and treatment gaps and refine risk prediction in patients with FH. 53,80,[94][95][96][97][98] However, as many have been established only within the last decade, significant potential exists for important translational research questions to be answered at a national and international level.…”

Section: Lysosomal Acid Lipase Deficiencymentioning

confidence: 99%

Widening the spectrum of genetic testing in familial hypercholesterolaemia: Will it translate into better patient and population outcomes?

2019

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Familial hypercholesterolaemia (FH) is caused by pathogenic variants in LDLR, APOB or PCSK9. Impaired low‐density lipoprotein (LDL) receptor function leads to decreased LDL catabolism and premature atherosclerotic cardiovascular disease (ASCVD). Thousands of LDLR variants are known, but assignation of pathogenicity requires accurate phenotyping, family studies and assessment of LDL receptor function. Precise, genetic diagnosis of FH using targeted next generation sequencing allows for optimal treatment, distinguishing FH from pathogenically distinct disorders requiring different treatment. Polygenic hypercholesterolaemia resulting from an accumulation of LDL cholesterol‐raising single nucleotide polymorphisms (SNPs) could also be suspected by this approach. Similarly, ASCVD risk could be estimated by broader sequencing of cholesterol and non‐cholesterol‐related genes. Both of these areas require further research. The clinical management of FH, focusing on the primary or secondary prevention of ASCVD, has been boosted by PCSK9 inhibitor therapy. The efficacy of PCSK9 inhibitors in homozygous FH may be partly predicted by the LDLR variants. While expanded genetic testing in FH is clinically useful in providing an accurate diagnosis and enabling cost‐effective testing of relatives, further research is needed to establish its value in improving clinical outcomes.

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“…29 Drugs that lower LDL cholesterol concentrations by enhancing clearance through the LDL receptor depend on the generation of functional LDL receptors by hepatocytes; therefore, patients with heterozygous FH, who possess 1 normal LDLR, typically respond reasonably well to statin therapy; however, many patients remain suboptimally treated with standard therapy. A registry-based study incorporating 2170 patients with heterozygous FH found that only 11.2% of patients achieved an LDL cholesterol target of 2.6 mmol/ L. 33 Radical therapy with lipoprotein apheresis (LA) is indicated in a proportion of heterozygous patients with progressive atherosclerotic cardiovascular disease (ASCVD). 34 LA is a lifelong treatment, requiring the patient to attend for extracorporeal removal of lipoproteins, which takes several hours, every 1 to 4 weeks.…”

Section: Familial Hypercholesterolaemiamentioning

confidence: 99%

PCSK9 in context: A contemporary review of an important biological target for the prevention and treatment of atherosclerotic cardiovascular disease

Page

Watts

2017

Diabetes Obesity Metabolism

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The identification of the critical role of proprotein convertase subtilisin/kexin type 9 (PCSK9) has rapidly led to the development of PCSK9 inhibition with monoclonal antibodies (mAbs). PCSK9 mAbs are already in limited clinical use and are the subject of major cardiovascular outcomes trials, which, if universally positive, could see much wider clinical application of these agents. Patients with familial hypercholesterolaemia are the most obvious candidates for these drugs, but other patients with elevated cardiovascular risk, statin intolerance or hyperlipoproteinaemia(a) may also benefit. PCSK9 mAbs, administered once or twice monthly, reduce LDL cholesterol levels by 50% to 70%, and appear to be safe and acceptable to patients over at least 2 years of treatment; however, treatment-emergent adverse effects are not always identified in clinical trials, as well-evidenced by statin myopathy. Inclisiran is a promising RNA-based therapy that promotes the degradation of PCSK9 mRNA transcripts and has similar efficacy to mAbs, but with a much longer duration of action. The cost-effectiveness and long-term safety of therapies targeted at inhibiting PCSK9 remain to be demonstrated if they are to be used widely in coronary prevention.

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Attainment of LDL-Cholesterol Treatment Goals in Patients With Familial Hypercholesterolemia

Cited by 221 publications

References 24 publications

Cascade Screening for Familial Hypercholesterolemia and the Use of Genetic Testing

Cascade Screening for Familial Hypercholesterolemia and the Use of Genetic Testing

Widening the spectrum of genetic testing in familial hypercholesterolaemia: Will it translate into better patient and population outcomes?

PCSK9 in context: A contemporary review of an important biological target for the prevention and treatment of atherosclerotic cardiovascular disease

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