Publications by authors named "Pedro Mata"

110 Publications

Improving Familial Hypercholesterolemia Index Case Detection: Sequential Active Screening from Centralized Analytical Data.

J Clin Med 2021 Feb 13;10(4). Epub 2021 Feb 13.

Department of Cardiology, Complejo Hospitalario Universitario de Toledo, 45004 Toledo, Spain.

The majority of familial hypercholesterolemia index cases (FH-IC) remain underdiagnosed and undertreated because there are no well-defined strategies for the universal detection of FH. The aim of this study was to evaluate the diagnostic yield of an active screening for FH-IC based on centralized analytical data. From 2016 to 2019, a clinical screening of FH was performed on 469 subjects with severe hypercholesterolemia (low-density lipoprotein cholesterol ≥220 mg/dL), applying the Dutch Lipid Clinic Network (DLCN) criteria. All patients with a DLCN ≥ 6 were genetically tested, as were 10 patients with a DLCN of 3-5 points to compare the diagnostic yield between the two groups. FH was genetically confirmed in 57 of the 84 patients with DLCN ≥ 6, with a genetic diagnosis rate of 67.9% and an overall prevalence of 12.2% (95% confidence interval: 9.3% to 15.5%). Before inclusion in the study, only 36.8% ( = 21) of the patients with the FH mutation had been clinically diagnosed with FH; after genetic screening, FH detection increased 2.3-fold ( < 0.001). The sequential, active screening strategy for FH-IC increases the diagnostic yield for FH with a rational use of the available resources, which may facilitate the implementation of FH universal and family-based cascade screening strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10040749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918446PMC
February 2021

Detection of Familial Hypercholesterolemia through centralized analytical data. HF HUELVA DETECTA Program.

Endocrinol Diabetes Nutr 2021 Feb 27. Epub 2021 Feb 27.

Fundación de Hipercolesterolemia Familia, Madrid, España.

Background: Familial Hypercholesterolemia is the most frequent genetic cause of premature coronary heart disease. The delay in the diagnosis prevents the correct early treatment. There are no effective screening strategies at the national level that ensure a correct diagnosis.

Objective: To determine the capacity of a centralized laboratory for the diagnosis of Familial Hypercholesterolemia through the creation of a health program for population screening in the province of Huelva.

Method: Active search of patients with primary hypercholesterolemia through the blood tests carried out in the reference laboratories with results of low-density lipoprotein cholesterol greater than 200mg/dl and assessment in the Lipid Unit of Huelva to identify index cases, with subsequent family cascade screening.

Results: 37,440 laboratory tests with lipid profile were examined. After screening, 846 individuals were seen in the Lipid Unit, of which they were diagnosed according to criteria of the Dutch Lipid Clinic Network as possible 654 and probable/definitive 192 individuals, representing 1.74% and 0.51% of the general population examined respectively.

Conclusions: The point prevalence of Familial Hypercholesterolemia in patients submitted to laboratory lipid profile tests was 1:195, higher compared to the prevalence of Familial Hypercholesterolemia in the general population (based on 1 in 200-300). The opportunistic search strategy of the index case through a laboratory alert and centralized screening is an efficient strategy to implement a national screening for the diagnosis of Familial Hypercholesterolemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.endinu.2020.09.011DOI Listing
February 2021

Lipoprotein(a), LDL-cholesterol, and hypertension: predictors of the need for aortic valve replacement in familial hypercholesterolaemia.

Eur Heart J 2021 Jan 12. Epub 2021 Jan 12.

Fundación Hipercolesterolemia Familiar, Madrid, Spain.

Aims: Familial hypercholesterolaemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Aortic valve stenosis (AVS) is the most prevalent valvular heart disease and low-density lipoprotein cholesterol (LDL-C) and Lp(a) may be involved in its pathobiology. We investigated the frequency and predictors of severe AVS requiring aortic valve replacement (AVR) in molecularly defined patients with FH.

Methods And Results: SAFEHEART is a long-term prospective cohort study of a population with FH and non-affected relatives (NAR). We analysed the frequency and predictors of the need for AVR due to AVS in this cohort. Five thousand and twenty-two subjects were enrolled (3712 with FH; 1310 NAR). Fifty patients with FH (1.48%) and 3 NAR (0.27%) required AVR [odds ratio 5.71; 95% confidence interval (CI): 1.78-18.4; P = 0.003] after a mean follow-up of 7.48 (3.75) years. The incidence of AVR was significantly higher in patients with FH (log-rank 5.93; P = 0.015). Cox regression analysis demonstrated an association between FH and AVR (hazard ratio: 3.89; 95% CI: 1.20-12.63; P = 0.024), with older age, previous ASCVD, hypertension, increased LDL-CLp(a)-years, and elevated Lp(a) being independently predictive of an event.

Conclusion: The need for AVR due to AVS is significantly increased in FH patients, particularly in those who are older and have previous ASCVD, hypertension, increased LDL-CLp(a)-years and elevated Lp(a). Reduction in LDL-C and Lp(a) together with control of hypertension could retard the progression of AVS in FH, but this needs testing in clinical trials.ClinicalTrials.gov number NCT02693548.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehaa1066DOI Listing
January 2021

Coronary plaque burden, plaque characterization and their prognostic implications in familial hypercholesterolemia: A computed tomographic angiography study.

Atherosclerosis 2021 01 18;317:52-58. Epub 2020 Nov 18.

Fundación Hipercolesterolemia Familiar, Madrid, Spain. Electronic address:

Background And Aims: Heterozygous familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular disease. Semi-automated plaque characterization (SAPC) by coronary computed tomographic angiography (CTA) provides information regarding coronary plaque burden and plaque characterization. Our aim was to quantify and characterize the coronary plaque burden of patients with FH using SAPC analysis and to identify which factors are related to plaque burden and plaque characteristics. A second aim was to analyse the prognostic implications of these parameters.

Methods: Two hundred and fifty-nine asymptomatic individuals with molecularly determined FH were enrolled in this follow-up cohort study and underwent a coronary CTA analysed with SAPC.

Results: Mean follow-up time after coronary CTA was 3.9 ± 2 years. Mean age was 46.9 (10.7) years (130 women, 50.2%). Median plaque burden was 25.0% (19.0-29.0), non-calcified plaque burden 22.83% (17.94-26.88), calcified plaque-burden 1.12% (0.31-2.86) and CCS 8.9 (0-93). Five-year risk was independently related to plaque burden, non-calcified plaque burden, calcified plaque burden and coronary calcium score (B:3.75, 95%CI:2.92-4.58; p < 0.001, B:2.9, 95%CI:2.15-3.66; p < 0.001, B:0.75, 95%CI 0.4-1.1; p < 0.001 and B:82.2, 95%CI:49.28-115.16; p < 0.001 respectively). During follow-up, there were 15 (5.81%) nonfatal events and 1 (0.4%) fatal event. Plaque burden was significantly related to event-free survival during follow-up (HR:1.11; 95%CI:1.05-1.18; p < 0.001).

Conclusions: Coronary atherosclerosis and its qualitative components may be quantified by means of SAPC in patients with FH. Plaque burden, calcified plaque burden and non-calcified plaque burden were independently related to the estimated cardiovascular risk. Plaque burden was also related to prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2020.11.012DOI Listing
January 2021

Loss-of-function mutation of PCSK9 as a protective factor in the clinical expression of familial hypercholesterolemia: A case report.

Medicine (Baltimore) 2020 Aug;99(34):e21754

Fundación Hipercolesterolemia Familiar, Madrid, Spain.

Rationale: Proprotein convertase subtilisin/kexin 9 or PCSK9 is a protein whose main function is to regulate the number of low-density lipoprotein receptors (LDLR) present on the cell surface. Loss-of-function mutations in PCSK9 have been related to low LDL-cholesterol levels and a decrease in the risk of cardiovascular events.

Patient Concerns: We present the case of a 27-year-old woman, offspring of a patient with familial homozygous hypercholesterolemia, who presented with mild-moderate hypercholesterolemia.

Diagnosis: Genetic analysis was performed by next generation sequencing using a customized panel of 198 genes. Sanger sequencing was used to confirm the presence of the variants of interest. The genetic analysis showed a pathogenic heterozygous mutation in LDLR [exon 6:c.902A>G:p(Asp301Gly)], as well as a loss-of-function heterozygous variant in PCSK9 [exon1:c.137 G>T:p.(Arg46Leu)]. The genetic analysis of the index case's mother revealed compound heterozygosity for 2 different mutations in LDLR [c.902A>G:p.(Asp301Gly); c.1646G>T:p.(Gly549Val)] in exon 6 and in exon 11, respectively, and the same loss-of-function variant in PCSK9 that had been found in her daughter [(PCSK9:exon1:c.137G>T:p.(Arg46Leu)]. The maternal grandfather of the index case presented the same genetic variants as his granddaughter.

Interventions: The index case did not receive any specific treatment for hypercholesterolemia. The loss-of-function variant in PCSK9 protected her from higher LDL-cholesterol levels, provided she kept partial activity of the LDLR. In her mother, instead, a PCSK9 inhibitor was tried but failed to achieve lipid control. The reason for this may be the complete absence in LDL receptor activity. LDL apheresis was started afterwards, resulting in adequate lipid level control.

Outcomes: To the date, the index case has achieved to maintain adequate total and LDL-cholesterol levels without any other intervention. She has had no known cardiovascular complication.

Lessons: Loss-of-function mutations in PCSK9 could protect from developing more severe forms of hypercholesterolemia. The finding of these mutations (LDLR-PCSK9) in three consecutive generations could imply an adaptive mechanism against the development of hypercholesterolemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000021754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447476PMC
August 2020

Phenotypical, Clinical, and Molecular Aspects of Adults and Children With Homozygous Familial Hypercholesterolemia in Iberoamerica.

Arterioscler Thromb Vasc Biol 2020 10 6;40(10):2508-2515. Epub 2020 Aug 6.

Heart Institute (InCor) University of São Paulo Medical School Hospital São Paulo, Brazil (C.E.J., A.P.C., J.E.K., R.D.S.).

Objective: Characterize homozygous familial hypercholesterolemia (HoFH) individuals from Iberoamerica. Approach and Results: In a cross-sectional retrospective evaluation 134 individuals with a HoFH phenotype, 71 adults (age 39.3±15.8 years, 38.0% males), and 63 children (age 8.8±4.0 years, 50.8% males) were studied. Genetic characterization was available in 129 (96%). The majority (91%) were true homozygotes (true HoFH, n=79, 43.0% children, 46.8% males) or compound heterozygotes (compound heterozygous familial hypercholesterolemia, n=39, 51.3% children, 46.2% males) with putative pathogenic variants in the . True HoFH due to variants had higher total (=0.015) and LDL (low-density lipoprotein)-cholesterol (=0.008) compared with compound heterozygous familial hypercholesterolemia. Children with true HoFH (n=34) tended to be diagnosed earlier (=0.051) and had a greater frequency of xanthomas (=0.016) than those with compound heterozygous familial hypercholesterolemia (n=20). Previous major cardiovascular events were present in 25 (48%) of 52 children (missing information in 2 cases), and in 43 (67%) of 64 adults with variants. Children who are true HoFH had higher frequency of major cardiovascular events (=0.02), coronary heart (=0.013), and aortic/supra-aortic valve diseases (=0.022) than compound heterozygous familial hypercholesterolemia. In adults, no differences were observed in major cardiovascular events according to type of variant. From 118 subjects with variants, 76 (64%) had 2 likely pathogenic or pathogenic variants. In 89 subjects with 2 variants, those with at least one null allele were younger (=0.003) and had a greater frequency of major cardiovascular events (=0.038) occurring at an earlier age (=0.001).

Conclusions: There was a high frequency of cardiovascular disease even in children. Phenotype and cardiovascular complications were heterogeneous and associated with the type of molecular defect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/ATVBAHA.120.313722DOI Listing
October 2020

Incidence of cardiovascular events and changes in the estimated risk and treatment of familial hypercholesterolemia: the SAFEHEART registry.

Rev Esp Cardiol (Engl Ed) 2020 Oct 20;73(10):828-834. Epub 2020 Mar 20.

Fundación Hipercolesterolemia Familiar, Madrid, Spain.

Introduction And Objectives: The SAFEHEART study was designed to analyze the situation of familial heterozygous hypercholesterolemia (FHH) and improve knowledge of this disease in Spain. Our objective was to determine the incidence rate of cardiovascular events, the estimated risk of developing an event and its modification, the use of lipid-lowering treatment, and the achievement of low-density lipoprotein cholesterol targets in patients with FHH.

Methods: SAFEHEART is a prospective, open, multicenter, nationwide cohort study, with long-term protocol-based follow-up in a population of individuals with molecularly-characterized FHH. We analyzed patients older than 18 years with complete follow-up.

Results: We included 2648 patients with FHH. The median follow-up was 6.6 (4.8-9.7) years. The overall incidence rate of cardiovascular events was 1.3 events/100 patient-years. After the follow-up, the 10-year estimated risk of developing a cardiovascular event was reduced from 1.6% to 1.3% (P <.001). In the last follow-up, 20.6% and 22.2% of the patients in primary and secondary prevention achieved low-density lipoprotein cholesterol values <100mg/dL and <70mg/dL, respectively.

Conclusions: This study was performed in the largest population of patients with FHH in Spain. We identified the incidence rate of cardiovascular events, the estimated risk of developing a cardiovascular event and its modification, the achievement of low-density lipoprotein cholesterol targets, and the therapeutic management in this population. Although the cardiovascular risk of FHH is high, appropriate treatment reduces the likelihood of an event.

Clinical Trial Registration: http://www.clinicaltrials.gov. Identifier: NCT02693548.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rec.2019.10.028DOI Listing
October 2020

High miR-133a levels in the circulation anticipates presentation of clinical events in familial hypercholesterolaemia patients.

Cardiovasc Res 2021 Jan;117(1):109-122

Cardiovascular-Program ICCC, Research Institute Hospital Santa Creu i Sant Pau, IIB-Sant Pau, Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.

Aims: Presentation of acute events in patients with atherosclerosis remains unpredictable even after controlling for classical risk factors. MicroRNAs (miRNAs) measured in liquid biopsies could be good candidate biomarkers to improve risk prediction. Here, we hypothesized that miRNAs could predict atherosclerotic plaque progression and clinical event presentation in familial hypercholesterolaemia (FH) patients.

Methods And Results: Circulating miRNAs (plasma, exosomes, and microvesicles) were investigated by TaqMan Array and RT-qPCR assays. Patients with genetic diagnosis of FH and healthy relatives from the SAFEHEART cohort were included. A differential signature of 10 miRNA was obtained by comparing two extreme phenotypes consisting of FH patients suffering a cardiovascular event (CVE) within a 8-year follow-up period (FH-CVE, N = 42) and non-FH hypercholesterolaemic relatives from the same cohort, matched for age and treatment, without CVE during the same period (nFH-nCVE, N = 30). The validation studies included two independent groups of patients with FH background (discovery group, N = 89, validation group N = 196), developing a future CVE (FH-CVE) or not (FH-nCVE) within the same time period of follow-up. Of the 10 miRNAs initially selected, miR-133a was significantly higher in FH-CVE than in FH-nCVE patients. Receiver operating characteristic analysis confirmed miR-133a as the best microRNA for predicting CVE in FH patients (0.76 ± 0.054; P < 0.001). Furthermore, Kaplan-Meier and COX analysis showed that high plasma miR-133a levels associated to the higher risk of presenting a CVE within the next 8 years (hazard ratio 3.89, 95% confidence interval 1.88-8.07; P < 0.001). In silico analysis of curate biological interactions related miR-133a with target genes involved in regulation of the cell-membrane lipid-receptor LRP6 and inflammatory cytokines (CXCL8, IL6, and TNF). These predictions were experimentally proven in human macrophages and endothelial cells transfected with agomiR-133a.

Conclusion: Elevated levels of miR-133a in the circulation anticipate those FH patients that are going to present a clinical CVE within the next 2 years (average). Mechanistically, miR-133a is directly related with lipid- and inflammatory signalling in key cells for atherosclerosis progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cvr/cvaa039DOI Listing
January 2021

Barriers to Early Diagnosis and Treatment of Familial Hypercholesterolemia: Current Perspectives on Improving Patient Care.

Vasc Health Risk Manag 2020 9;16:11-25. Epub 2020 Jan 9.

Fundación Hipercolesterolemia Familiar, Madrid, Spain.

Familial hypercholesterolemia (FH) is a frequent disorder associated with premature atherosclerotic cardiovascular disease. Different clinical diagnosis criteria are available, and cost of genetic testing has been reduced in the last years; however, most cases are not diagnosed worldwide. Patients with FH are at high cardiovascular risk and the risk can be reduced with lifelong lifestyle and pharmacological treatment. Statins and ezetimibe are available as generic drugs in most countries reducing the cost of treatment. However, the use of high-intensity statins combined with ezetimibe and PCSK9 inhibitors, if necessary, is low for different reasons that contribute to a high number of patients not reaching LDL-C targets according to guidelines. On the other hand, cardiovascular risk varies greatly in families with FH; therefore, risk stratification strategies including cardiovascular imaging is another element to consider for improving care and management of FH. There are numerous barriers depending on the awareness, knowledge, perception of risk, management and care of patients living with FH that impact in the diagnosis and treatment of the disorder. In this contemporary review, we analyze different barriers in the diagnosis and care of patients to improve patients' care and prevention of atherosclerotic cardiovascular disease and describe recent advances and strategies to improve the gaps in the care of FH, including global collaboration and advocacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/VHRM.S192401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957097PMC
February 2020

Familial hypercholesterolaemia: evolving knowledge for designing adaptive models of care.

Nat Rev Cardiol 2020 06 23;17(6):360-377. Epub 2020 Jan 23.

Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London, UK.

Optimal care for familial hypercholesterolaemia (FH) requires patient-centred management, multidisciplinary teamwork, involvement of primary care practitioners, patient networks, support groups and high-quality clinical registries, implemented through models of care adapted to FH. Models of care - evidence-based and context-specific frameworks that aim to deliver the highest quality of care for patients and their families - allow the application of precision and multidisciplinary medicine to FH care and can serve as paradigms for the prevention of premature atherosclerotic cardiovascular disease in all at-risk patients and families worldwide. The exponential growth in the number of publications on diverse aspects of FH has provided new knowledge for developing essential elements of existing models of care. These elements include clinical diagnostic criteria and genetic testing; risk restratification strategies; LDL-cholesterol treatment targets; management protocols for children; care of women in pregnancy; use of pharmacotherapies, including ezetimibe and PCSK9 inhibitors; use of lipoprotein apheresis for severe FH; and addressing barriers to care. However, substantial gaps remain that need to be addressed by a broad research agenda, implementation strategies and global collaboration and advocacy, aimed at improving the uptake, cost-effectiveness and routine implementation of evidence-based standards. In this Review, we summarize the dramatic increase in knowledge that informs adaptive models of care, with an emphasis on articles published since 2014.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41569-019-0325-8DOI Listing
June 2020

Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia: A Global Call to Action.

JAMA Cardiol 2020 02;5(2):217-229

Familial Hypercholesterolemia Foundation, Pasadena, California.

Importance: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. Familial hypercholesterolemia affects 1 in 200 to 250 people around the world of every race and ethnicity. The lack of general awareness of FH among the public and medical community has resulted in only 10% of the FH population being diagnosed and adequately treated. The World Health Organization recognized FH as a public health priority in 1998 during a consultation meeting in Geneva, Switzerland. The World Health Organization report highlighted 11 recommendations to address FH worldwide, from diagnosis and treatment to family screening and education. Research since the 1998 report has increased understanding and awareness of FH, particularly in specialty areas, such as cardiology and lipidology. However, in the past 20 years, there has been little progress in implementing the 11 recommendations to prevent premature atherosclerotic cardiovascular disease in an entire generation of families with FH.

Observations: In 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation convened the international FH community to update the 11 recommendations. Two meetings were held: one at the 2018 FH Foundation Global Summit and the other during the 2018 World Congress of Cardiology and Cardiovascular Health. Each meeting served as a platform for the FH community to examine the original recommendations, assess the gaps, and provide commentary on the revised recommendations. The Global Call to Action on Familial Hypercholesterolemia thus represents individuals with FH, advocacy leaders, scientific experts, policy makers, and the original authors of the 1998 World Health Organization report. Attendees from 40 countries brought perspectives on FH from low-, middle-, and high-income regions. Tables listing country-specific government support for FH care, existing country-specific and international FH scientific statements and guidelines, country-specific and international FH registries, and known FH advocacy organizations around the world were created.

Conclusions And Relevance: By adopting the 9 updated public policy recommendations created for this document, covering awareness; advocacy; screening, testing, and diagnosis; treatment; family-based care; registries; research; and cost and value, individual countries have the opportunity to prevent atherosclerotic heart disease in their citizens carrying a gene associated with FH and, likely, all those with severe hypercholesterolemia as well.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamacardio.2019.5173DOI Listing
February 2020

Long-term effect of 2 intensive statin regimens on treatment and incidence of cardiovascular events in familial hypercholesterolemia: The SAFEHEART study.

J Clin Lipidol 2019 Nov - Dec;13(6):989-996. Epub 2019 Oct 11.

Fundación Hipercolesterolemia Familiar, Madrid, Spain. Electronic address:

Background: Maximal doses of potent statins are the basement of treatment of familial hypercholesterolemia (FH). Little is known about the use of different statin regimens in FH.

Objectives: The objectives of the study were to describe the treatment changes and low-density lipoprotein cholesterol (LDL-C) goal achievement with atorvastatin (ATV) and rosuvastatin (RV) in the SAFEHEART cohort, as well as to analyze the incidence of atherosclerotic cardiovascular events (ACVEs) and changes in the cardiovascular risk.

Methods: SAFEHEART is a prospective follow-up nationwide cohort study in a molecularly defined FH population. The patients were contacted on a yearly basis to obtain relevant changes in life habits, medication, and ACVEs.

Results: A total of 1939 patients were analyzed. Median follow-up was 6.6 years (5-10). The estimated 10-year risk according the SAFEHEART risk equation was 1.61 (0.67-3.39) and 1.22 (0.54-2.93) at enrollment for ATV and RV, respectively (P < .001). There were no significant differences at the follow-up: 1.29 (0.54-2.82) and 1.22 (0.54-2.76) in the ATV and RV groups, respectively (P = .51). Sixteen percent of patients in primary prevention with ATV and 18% with RV achieved an LDL-C <100 mg/dL and 4% in secondary prevention with ATV and 5% with RV achieved an LDL-C <70 mg/dL. The use of ezetimibe was marginally greater in the RV group. One hundred sixty ACVEs occurred during follow-up, being its incidence rate 1.1 events/100 patient-years in the ATV group and 1.2 in the RV group (P = .58).

Conclusion: ATV and RV are 2 high-potency statins widely used in FH. Although the reduction in LDL-C levels was greater with RV than with ATV, the superiority of RV for reducing ACVEs was not demonstrated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacl.2019.10.005DOI Listing
July 2020

Association of dietary components with dyslipidemia and low-grade inflammation biomarkers in adults with heterozygous familial hypercholesterolemia from different countries.

Eur J Clin Nutr 2019 12 6;73(12):1622-1625. Epub 2019 Nov 6.

Heart Institute (InCor) University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil.

The association of components of a low saturated fat (SFA) and of a Mediterranean diet was tested with atherosclerosis biomarkers in 190 familial hypercholesterolemia adults (FH) from Brazil (BR) and Spain (SP). Median blood LDL-C, Apolipoprotein B (apoB), and C reactive protein (hs-CRP) concentrations were higher in BR than in SP: 179.0 vs.161 mg/dL; 141 vs. 103 mg/dL; and 1.6 vs. 0.8 mg/L respectively (all p < 0.001). In BR there was lower median total fat (22.3 vs. 38.3%) and SFA (8.1 vs. 12.5%) but higher cholesterol (283.3 mg vs.188.9 mg) and carbohydrate (57.1 vs. 42.5%) consumption (all p < 0.001). Inverse associations were encountered between fibers, mono, and polyunsaturated fats and their ratios to SFA with LDL-C and ApoB (all p < 0.001). There was a direct association respectively of cholesterol with lipid biomarkers and of carbohydrates and trans-fatty acids with hs-CRP while other fats showed inverse relations with the latter (p < 0.001).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41430-019-0529-3DOI Listing
December 2019

Lomitapide: a review of its clinical use, efficacy, and tolerability.

Core Evid 2019 1;14:19-30. Epub 2019 Jul 1.

Familial Hypercholesterolemia Foundation, Madrid, Spain.

Lomitapide is an inhibitor of MTP, an enzyme located in the endoplasmic reticulum of hepatocytes and enterocytes. This enzyme is responsible for the synthesis of very low-density lipoproteins in the liver and chylomicrons in the intestine. Lomitapide has been approved by the US Food and Drug Administration, European Medicines Agency, and other regulatory agencies for the treatment of hypercholesterolemia in adult patients with homozygous familial hypercholesterolemia. Clinical trials have shown that lomitapide reduces low-density-lipoprotein cholesterol levels by around 40% in homozygous familial hypercholesterolemia patients on treatment with statins with or without low-density-lipoprotein apheresis, with an acceptable safety and tolerance profile. The most common adverse events are gastrointestinal symptoms that decrease in frequency with long-term treatment, and the increase in liver fat remains stable. This review analyzes the clinical use, efficacy, and tolerability of lomitapide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CE.S174169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615460PMC
July 2019

Potential utility of the SAFEHEART risk equation for rationalising the use of PCSK9 monoclonal antibodies in adults with heterozygous familial hypercholesterolemia.

Atherosclerosis 2019 07 4;286:40-45. Epub 2019 May 4.

Fundación Hipercolesterolemia Familiar, Madrid, Spain. Electronic address:

Background And Aims: Patients with familial hypercholesterolaemia (FH) may require proprotein convertase subtilisin/kexin-type 9 (PCSK9) mAb as add-on therapy to achieve LDL-cholesterol (LDL-C) goals. However, the current cost of these therapies means that choosing suitable patients is based on consensus or clinical judgement rather than a quantitative risk assessment. We used the SAFEHEART Risk Equation (RE) to estimate the number needed to treat (NNT) at different risk thresholds and baseline LDL-C to identify those FH patients more likely to derive the greatest benefit from PCSK9 mAb.

Methods: Five-year event rates were calculated using the SAFEHEART-RE for every patient, overall and across LDL-C strata. A 60% reduction of LDL-C after theoretical treatment with PCSK9 mAb was assumed. Individual absolute risk simulating the effects of PCSK9 inhibition was calculated using the SAFEHEART-RE and, in a similar way, by using the Cholesterol Treatment Trialists' (CTT) Collaboration criteria. Absolute risk reduction and NNTs were calculated.

Results: Of the total SAFEHEART population, 2,153 were FH cases aged 18 years or older, on maximum tolerated lipid lowering treatment. NNTs were dependent of both baseline predicted risk and baseline LDL-C level ranging from 44 to 17 for those with 5-year risk of ≥1 to ≥5. The smallest NNT (12) was observed among those with 5-year risk of ≥5% and LDL-C ≥160 mg/dl. Using the CTT criteria produced similar results.

Conclusions: The SAFEHEART-RE may provide a useful quantitative tool for rationalising the selection of FH patients who might derive greater absolute benefits from PCSK9 mAb.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2019.05.003DOI Listing
July 2019

Liquid Biopsy of Extracellular Microvesicles Predicts Future Major Ischemic Events in Genetically Characterized Familial Hypercholesterolemia Patients.

Arterioscler Thromb Vasc Biol 2019 06;39(6):1172-1181

From the Cardiovascular-Program ICCC, Research Institute Hospital Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain (R.S., T.P., J.C., L.B.).

Objective- Circulating microvesicles (cMVs) exert regulatory roles in atherothrombosis. Patients with familial hypercholesterolemia (FH) that are at high risk for premature cardiovascular events (CVEs) have previously shown high levels of cMVs related to disease severity. However, much remains unknown about their value as markers of CVE. We sought to investigate the prognostic cMV signature for future major CVE presentation in patients with FH. Approach and Results- Liquid biopsies from genetically characterized patients with FH from the SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study)-cohort without clinical manifestation of disease at entry that were going to suffer a CVE within a mean period of 3.3±2.6 years postsampling (CVE, N=92) and from age/cardiovascular risk factor/treatment-matched patients with FH that did not suffer an event within the same time-period (non-CVE, N=48) were investigated. cMVs were phenotyped by flow cytometry to identify activated parental cells. Patients with CVE had higher number of overall procoagulant annexin V-cMVs than non-CVE ( P<0.05). Pan-leukocyte-derived and neutrophil-derived cMVs, as well as activated platelet-derived cMVs, were significantly higher in patients with CVE. Baseline number of cMVs derived from lymphocytes, neutrophils, and activated platelets were positively associated with mortality at follow-up ( P<0.05). Patient-risk calculated by classical cardiovascular risk-factor scores did not correlate with cMVs. Inclusion of the cMV signature into the SAFEHEART risk model for patients with FH for the prediction of ischemic events increased the area under the curve from 0.603±0.050 to 0.768±0.042 ( P<0.005). Conclusions- Patients with FH who are going to suffer a CVE within a mean period of 3.3 years, despite being treated according to guidelines, have ongoing innate immune cell and platelet activation. The proposed cMV signature is a prognostic marker for accelerated atherosclerosis and clinical event presentation in patients with FH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/ATVBAHA.119.312420DOI Listing
June 2019

VEGFR2 and OPG genes modify the risk of subclinical coronary atherosclerosis in patients with familial hypercholesterolemia.

Atherosclerosis 2019 06 31;285:17-22. Epub 2019 Mar 31.

Fundación Hipercolesterolemia Familiar, Madrid, Spain. Electronic address:

Background And Aims: Heterozygous familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C). The magnitude of atherosclerotic cardiovascular disease (ASCVD) risk in FH patients is highly variable, and this can result from genetic factors. The aim of our study was to characterize whether polymorphisms in VEGFR2 and OPG genes could influence the expression of ASCVD in FH patients.

Methods: We studied 318 FH patients from the SAFEHEART registry, without clinical diagnosis of ASCVD. A coronary tomographic angiography (CTA) was performed to determine and evaluate the presence of coronary stenosis and coronary artery calcium, as measured by coronary calcium score (CCS). Genotyping of OPG rs2073618 and VEGFR2 rs2071559 polymorphisms was performed using TaqMan 5'-exonuclease allelic discrimination assays.

Results: Homozygous GG genotype and G allele of VEGFR2 rs2071559 polymorphism were associated with decreased risk of developing coronary artery stenosis. In the analysis of OPG rs2073618 and VEGFR2 rs2071559 polymorphisms, according to the presence of coronary artery calcium, we found significant differences in both polymorphisms. Homozygous GG genotype and G allele of VEGFR2 rs2071559 polymorphism were associated with decreased risk of accumulation of coronary artery calcium measured by CCS in CTA. Moreover, being a carrier of the GG genotype and G allele of the OPG rs2073618 polymorphism increased the risk of the presence of coronary artery calcium measured by CCS in CTA.

Conclusions: Polymorphisms in VEGFR2 and OPG genes modify the risk of ASCVD in FH patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2019.03.019DOI Listing
June 2019

Liquid Biopsy of Extracellular Microvesicles Maps Coronary Calcification and Atherosclerotic Plaque in Asymptomatic Patients With Familial Hypercholesterolemia.

Arterioscler Thromb Vasc Biol 2019 05;39(5):945-955

From the Cardiovascular Science Institute - ICCC; IIB-Sant Pau, Hospital de Sant Pau, Barcelona, Spain (G.C.-B., T.P., J.C., L.B.).

Objective- Heterozygous familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular disease. Circulating microvesicles (cMV) are released when cells are activated. We investigated whether cMV could provide information on coronary calcification and atherosclerosis in FH patients. Approach and Results- Eighty-two patients (mean of 44±9 years old) with molecular diagnosis of heterozygous FH and asymptomatic cardiovascular disease were investigated. Atherosclerotic plaque characterization was performed by computed tomography angiography, and Agatston coronary calcium score and plaque composition sum were calculated. cMV were quantified by flow cytometry using AV (annexin V) and cell surface-specific antibodies. Of the 82 FH patients, 48 presented atherosclerotic plaque. Patients with atherosclerosis were men and older in a higher percentage than patients without atherosclerotic plaque. FH patients with atherosclerotic plaque showed higher levels of total AV cMV, cMV AV from platelet origin, from granulocytes and neutrophils, and cMV AV from endothelial cells than FH-patients without atherosclerotic plaque. Plaque composition sum correlated with platelet- and endothelial-derived cMV, and Agatston coronary calcium score correlated with granulocyte-, platelet-, and endothelial-derived cMV. Receiver operating characteristic curve analyses indicated that the cluster of platelet-, granulocyte-, neutrophil, and endothelial-derived cMV considered together, added significant predictive value to the specific SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) risk equation for plaque presence (area under the curve=0.866, 95% CI, 0.775-0.958; P<0.0001, P=0.030 for the increment of the area under the curve). Conclusions- Endothelial-, granulocyte-, neutrophil- and platelet-derived cMV discriminate and map coronary atherosclerotic plaque and calcification in asymptomatic patients with FH. Liquid biopsy of cMV may be a surrogate biomarker of coronary atherosclerotic plaque burden in FH patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/ATVBAHA.118.312414DOI Listing
May 2019

Value of Measuring Lipoprotein(a) During Cascade Testing for Familial Hypercholesterolemia.

J Am Coll Cardiol 2019 03;73(9):1029-1039

Fundación Hipercolesterolemia Familiar, Madrid, Spain. Electronic address:

Background: Familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Cascade testing is recommended for FH, but there are no similar recommendations for elevated Lp(a).

Objectives: This study investigated whether testing for Lp(a) was effective in detecting and risk stratifying individuals participating in an FH cascade screening program.

Methods: Family members (N = 2,927) from 755 index cases enrolled in SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) were tested for genetic FH and elevated Lp(a) via an established screening program. Elevated Lp(a) was defined as levels ≥50 mg/dl. The authors compared the prevalence and yield of new cases of high Lp(a) in relatives of FH probands both with and without high Lp(a), and prospectively investigated the association between elevated Lp(a) and ASCVD events among family members.

Results: Systematic screening from index cases with both FH and elevated Lp(a) identified 1 new case of elevated Lp(a) for every 2.4 screened. Opportunistic screening from index cases with FH, but without elevated Lp(a), identified 1 individual for 5.8 screened. Over 5 years' follow-up, FH (hazard ratio [HR]: 2.47; p = 0.036) and elevated Lp(a) (HR: 3.17; p = 0.024) alone were associated with a significantly increased risk of experiencing an ASCVD event or death compared with individuals with neither disorder; the greatest risk was observed in relatives with both FH and elevated Lp(a) (HR: 4.40; p < 0.001), independent of conventional risk factors.

Conclusions: Testing for elevated Lp(a) during cascade screening for FH is effective in identifying relatives with high Lp(a) and heightened risk of ASCVD, particularly when the proband has both FH and elevated Lp(a).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2018.12.037DOI Listing
March 2019

Adults with familial hypercholesterolaemia have healthier dietary and lifestyle habits compared with their non-affected relatives: the SAFEHEART study.

Public Health Nutr 2019 06 8;22(8):1433-1443. Epub 2019 Feb 8.

1Fundación Hipercolesterolemia Familiar,C/General Álvarez de Castro 14,28010Madrid,Spain.

Objective: Healthy lifestyle habits are the cornerstone in the management of familial hypercholesterolaemia (FH). Nevertheless, dietary studies on FH-affected populations are scarce. The present study analyses dietary habits, adherence to a Mediterranean diet pattern and physical activity in an adult population with FH and compares them with their non-affected relatives.

Design: Cross-sectional study.

Setting: Data came from SAFEHEART, a nationwide study in Spain.ParticipantsIndividuals (n 3714) aged ≥18 years with a genetic diagnosis of FH (n2736) and their non-affected relatives (n 978). Food consumption was evaluated using a validated FFQ.

Results: Total energy intake was lower in FH patients v. non-affected relatives (P<0·005). Percentage of energy from fats was also lower in the FH population (35 % in men, 36 % in women) v. those non-affected (38 % in both sexes, P<0·005), due to the lower consumption of saturated fats (12·1 % in FH patients, 13·2 % in non-affected, P<0·005). Consumption of sugars was lower in FH patients v. non-affected relatives (P<0·05). Consumption of vegetables, fish and skimmed milk was higher in the FH population (P<0·005). Patients with FH showed greater adherence to a Mediterranean diet pattern v. non-affected relatives (P<0·005). Active smoking was lower and moderate physical activity was higher in people with FH, especially women (P<0·005).

Conclusions: Adult patients with FH report healthier lifestyles than their non-affected family members. They eat a healthier diet, perform more physical activity and smoke less. However, this patient group's consumption of saturated fats and sugars still exceeds guidelines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1368980018003853DOI Listing
June 2019

Atherosclerotic cardiovascular disease risk assessment in familial hypercholesterolemia: does one size fit all?

Curr Opin Lipidol 2018 12;29(6):445-452

Fundación Hipercolesterolemia Familiar, Madrid, Spain.

Purpose Of Review: Familial hypercholesterolemia is a frequent genetic disease associated with lifelong elevation of LDL-cholesterol and premature atherosclerotic cardiovascular disease (ASCVD). Statins are the cornerstone of treatment. However, with the introduction of novel LDL-cholesterol-lowering therapies, it is necessary to identify familial hypercholesterolemia patients presenting a significantly high residual ASCVD risk. The aim of this review is to provide an update on the recent literature concerning cardiovascular risk stratification including the role of coronary imaging.

Recent Findings: Several factors have shown to be independent predictors of ASCVD in familial hypercholesterolemia. These include clinical scores with cardiovascular risk factors, coronary imaging and novel protein biomarkers. However, the recent introduction of the SAFEHEART risk-equation (SAFEHEART-RE) could allow a more accurate ASCVD risk prediction in familial hypercholesterolemia.

Summary: This article highlights the SAFEHEART-RE as a model to predict incident ASCVD in familial hypercholesterolemia. This equation is a simple and widely applicable tool for use in every clinical setting. Furthermore, coronary atherosclerosis assessed by coronary computed-tomographic angiography (coronary-CTA) is independently associated to the cardiovascular risk estimated according to the SAFEHEART-RE. This equation, as well as coronary-CTA and new biomarkers, could increase individual ASCVD risk stratification and could improve the efficiency and the use of new lipid-lowering therapies in familial hypercholesterolemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MOL.0000000000000553DOI Listing
December 2018

ClinVar database of global familial hypercholesterolemia-associated DNA variants.

Hum Mutat 2018 11;39(11):1631-1640

FH Foundation, Pasadena, California.

Accurate and consistent variant classification is imperative for incorporation of rapidly developing sequencing technologies into genomic medicine for improved patient care. An essential requirement for achieving standardized and reliable variant interpretation is data sharing, facilitated by a centralized open-source database. Familial hypercholesterolemia (FH) is an exemplar of the utility of such a resource: it has a high incidence, a favorable prognosis with early intervention and treatment, and cascade screening can be offered to families if a causative variant is identified. ClinVar, an NCBI-funded resource, has become the primary repository for clinically relevant variants in Mendelian disease, including FH. Here, we present the concerted efforts made by the Clinical Genome Resource, through the FH Variant Curation Expert Panel and global FH community, to increase submission of FH-associated variants into ClinVar. Variant-level data was categorized by submitter, variant characteristics, classification method, and available supporting data. To further reform interpretation of FH-associated variants, areas for improvement in variant submissions were identified; these include a need for more detailed submissions and submission of supporting variant-level data, both retrospectively and prospectively. Collaborating to provide thorough, reliable evidence-based variant interpretation will ultimately improve the care of FH patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206854PMC
November 2018

Familial Hypercholesterolaemia Diagnosis and Management.

Eur Cardiol 2018 Aug;13(1):14-20

Spanish Familial Hypercholesterolemia Foundation Madrid, Spain.

Familial hypercholesterolaemia is the most common monogenic disorder associated with premature coronary artery disease. Mutations are most frequently found in the LDL receptor gene. Clinical criteria can be used to make the diagnosis; however, genetic testing will confirm the disorder and is very useful for cascade screening. Early identification and adequate treatment can improve prognosis, reducing negative clinical cardiovascular outcomes. Patients with familial hypercholesterolaemia are considered at high cardiovascular risk and the treatment target is LDL cholesterol <2.6 mmol/l or at least a 50 % reduction in LDL cholesterol. Patients require intensive treatment with statins and ezetimibe and/or colesevelam. Recently, proprotein convertase subtilisin/kexin type 9 inhibitors have been approved for the management of familial hypercholesterolaemia on top of statins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15420/ecr.2018:10:2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159470PMC
August 2018

Dental hypomineralization treatment: A systematic review.

J Esthet Restor Dent 2019 01 4;31(1):26-39. Epub 2018 Oct 4.

Faculty of Dentistry, University of Oporto, Oporto, Portugal.

Introduction: Defects in the maturation stage of amelogenesis result in a normal volume of enamel but insufficient mineralization, called hypomineralization. Molar-incisor hypomineralization (MIH), amelogenesis imperfecta and dental fluorosis (DF) are examples of such defects.

Objective: To evaluate the effectiveness of the treatments applied to the different forms of dental hypomineralization.

Materials And Methods: PubMed, Scopus, Cochrane Library, Web of Science, and Embase were screened. The research was limited to studies published in English, Spanish, and Portuguese, until May 30, 2018. The research question was formulated following the Population, Intervention, Comparison, Outcome strategy. The quality of the methodology of each article was evaluated employing the Cochrane Handbook for Systematic Reviews.

Results: From the initial research, 7895 references were obtained, of which 33 were included in the systematic review. The following treatments were reported: desensitizing and remineralizing products, resin infiltration, restorations, fissure sealants, tooth bleaching, enamel microabrasion and calcium, and vitamins supplements.

Conclusions: Although the results are suggestive, there is a clear need for a greater uniformity of the methodologies, thus allowing for the development of clinical guidelines. Nevertheless, it was possible to identify several effective treatments for teeth with MIH (arginine pastes or fluoride varnishes) and DF (tooth bleaching and/or enamel microabrasion).

Clinical Significance: Because MIH, amelogenesis imperfecta, and DF are commonly seen in dental daily practice, it is extremely important to analyze the literature regarding its treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jerd.12420DOI Listing
January 2019

Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC).

Atherosclerosis 2018 10;277:234-255

Imperial Centre for Cardiovascular Disease Prevention (ICCP), Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, United Kingdom.

Background And Aims: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries.

Methods: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management.

Results: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited.

Conclusions: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2018.08.051DOI Listing
October 2018

Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel.

J Am Coll Cardiol 2018 08;72(6):662-680

The Familial Hypercholesterolemia Foundation, Pasadena, California; Departments of Genetics, Medicine, and Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Although awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Despite FH being a genetic disorder, genetic testing is rarely used. The Familial Hypercholesterolemia Foundation convened an international expert panel to assess the utility of FH genetic testing. The rationale includes the following: 1) facilitation of definitive diagnosis; 2) pathogenic variants indicate higher cardiovascular risk, which indicates the potential need for more aggressive lipid lowering; 3) increase in initiation of and adherence to therapy; and 4) cascade testing of at-risk relatives. The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives. Testing should include the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes include greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk stratification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2018.05.044DOI Listing
August 2018

Coronary computed tomographic angiography findings and their therapeutic implications in asymptomatic patients with familial hypercholesterolemia. Lessons from the SAFEHEART study.

J Clin Lipidol 2018 Jul - Aug;12(4):948-957. Epub 2018 Apr 17.

Fundación Hipercolesterolemia Familiar, Madrid, Spain. Electronic address:

Background: Familial hypercholesterolemia (FH) confers an increased risk of premature atherosclerotic disease. Coronary computed tomographic angiography (CTA) can assess preclinical coronary atherosclerosis.

Objectives: To describe coronary CTA findings in asymptomatic molecularly defined FH individuals, to identify those factors related to its presence and extension, and to assess the impact of these results in patients' care and estimated risk.

Methods: Four hundred and forty individuals with FH, without clinical cardiovascular disease, were consecutively enrolled and underwent a coronary CTA that was used to analyze coronary atherosclerosis based on coronary calcium score (CCS), sum of stenosis severity, and plaque composition sum (PCS). For FH patients, cardiovascular risk was estimated using the specific SAFEHEART risk equation. Follow-up was performed using a standardized protocol.

Results: Mean age was 46.4 years (231 women, 52%). Coronary calcium was present in 55%, mean CCS was 130.9, 46% had a plaque with lumen involvement, and mean PCS was 1.1. During follow-up, there were 17 (4%) nonfatal events and 2 (1%) fatal events. CCS was independently associated to the estimated risk and low-density lipoprotein-cholesterol life-years, sum of stenosis severity to the estimated risk, and PCS to the estimated risk and low-density lipoprotein-cholesterol life-years. CTA findings induced a positive change in patients' care and in their estimated risk.

Conclusion: Coronary artery atherosclerosis is highly prevalent in asymptomatic patients with FH and it is independently associated to cardiovascular risk. More advanced disease on CTA was associated with subsequent intensification of therapy and reduction of estimated risk. Further longitudinal studies are required to know if these findings might improve the risk stratification in patients with FH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacl.2018.04.003DOI Listing
October 2019

Multivariate analysis for coronary heart disease in heterozygote familial hypercholesterolemia patients.

Per Med 2018 03 31;15(2):87-92. Epub 2018 Jan 31.

Fundacion Hipercolesterolemia Familial, Madrid, Spain.

Aim: rs599839 polymorphism has been related with low levels of cholesterol and reduced coronary heart disease (CHD).

Methods: We investigated the frequency of this polymorphism in patients with heterozygous familial hypercholesterolemia (HeFH) in the Spanish familial hypercholesterolemia cohort, 230 with and 202 without CHD. Results & discussion: A lower G-allele prevalence was observed in HeFH patients with CHD with respect to controls, 35 versus 45%, respectively (p = 0.029), suggesting a protective effect. However, it was found that there was no association between rs599839 alleles and CHD in the multivariate analysis.

Conclusion: The frequency of the protective G-allele of the rs599839 polymorphism was lower in HeFH patients with CHD compared with those HeFH patients without CHD. However, its role in HeFH may be masked by very high levels of cholesterol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/pme-2017-0075DOI Listing
March 2018