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AIMS: The availability of novel lipid-lowering therapies (LLTs) has remarkably changed the clinical management of homozygous familial hypercholesterolaemia (HoFH). The impact of these advances was evaluated in a cohort of 139 HoFH patients followed in a real-world clinical setting. METHODS AND RESULTS: The clinical characteristics of 139 HoFH patients, along with information about LLTs and low-density lipoprotein cholesterol (LDL-C) levels at baseline and after a median follow-up of 5 years, were retrospectively retrieved from the records of patients enrolled in the LIPid transport disorders Italian GEnetic Network-Familial Hypercholesterolaemia (LIPIGEN-FH) Registry. The annual rates of major atherosclerotic cardiovascular events (MACE-plus) during follow-up were compared before and after baseline. Additionally, the lifelong survival free from MACE-plus was compared with that of the historical LIPIGEN HoFH cohort. At baseline, LDL-C level was 332 ± 138â mg/dL. During follow-up, the potency of LLTs was enhanced and, at the last visit, 15.8% of patients were taking quadruple therapy. Consistently, LDL-C decreased to an average value of 124â mg/dL corresponding to a 58.3% reduction (Pt < 0.001), with the lowest value (â¼90â mg/dL) reached in patients receiving proprotein convertase subtilisin/kexin type 9 inhibitors and lomitapide and/or evinacumab as add-on therapies. The average annual MACE-plus rate in the 5-year follow-up was significantly lower than that observed during the 5 years before baseline visit (21.7 vs. 56.5 per 1000 patients/year; P = 0.0016). CONCLUSION: Our findings indicate that the combination of novel and conventional LLTs significantly improved LDL-C control with a signal of better cardiovascular prognosis in HoFH patients. Overall, these results advocate the use of intensive, multidrug LLTs to effectively manage HoFH.
Contemporary real-world data from the Italian cohort of patients affected by homozygous familial hypercholesterolaemia demonstrated that the addition of novel, low-density lipoprotein receptor (LDLR)-independent medications to conventional therapies allowed the achievement of unprecedented low-density lipoprotein cholesterol (LDL-C) values with a trend towards a reduction of cardiovascular risk.
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LDL-Colesterol , Hiperlipoproteinemia Tipo II , Sistema de Registros , Humanos , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/diagnóstico , Masculino , Femenino , Italia/epidemiología , LDL-Colesterol/sangre , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Homocigoto , Resultado del Tratamiento , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/epidemiología , Medición de Riesgo , Factores de Tiempo , Biomarcadores/sangre , Factores de Riesgo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Anticolesterolemiantes/uso terapéutico , Predisposición Genética a la Enfermedad , Inhibidores de PCSK9/uso terapéutico , Hipolipemiantes/uso terapéuticoRESUMEN
BACKGROUND: Familial hypercholesterolemia (FH) is a genetically determined monogenic disorder of predominantly autosomal dominant inheritance. A number of studies on differences in the genetic profile of patients with FH have demonstrated the importance of a more substantive evaluation of genetic features. The aim of this study was to evaluate the genetic profile of patients with clinical FH among Italian and Russian patients. METHODS: We included 144 Italian and 79 Russian FH patients; clinical diagnosis was based on the same criteria. Patients were divided in: positive to genetic test (one causative variant), inconclusive (only variants of uncertain clinical significance [VUS]), and negative (with likely benign/benign variants, heterozygous variants in LDLRAP1 gene, or without causative variants). RESULTS: The genetic test was positive in 76.4 % of the Italian patients and in 49.4 % of the Russian patients. The presence of VUS alone was detected in 7.6 % and in 19.0 % (p < 0.001), respectively. Among patients with positive genetic diagnosis, pre-treatment LDL-C levels were higher in the Russian cohort (353.5 ± 111.3 vs. 302.7 ± 52.1 mg/dL, p = 0.009), as well as the percentage of treated patients (53.8 % vs. 14.5 %, p < 0.001) and the prevalence of premature coronary heart disease (12.8 % vs. 3.6 %, p = 0.039). Among patients carrying only VUS, mean pre-treatment LDL-C levels were similar between the cohorts (299.5 ± 68.1 vs. 295.3 ± 46.8 mg/dL, p = 0.863). Among pathogenic/likely pathogenic variants and VUS, only 5 % and 4 % was shared between the two cohorts, respectively. CONCLUSION: The genetic background of patients clinically diagnosed with FH in two different countries is characterized by high variability.
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LDL-Colesterol , Pruebas Genéticas , Hiperlipoproteinemia Tipo II , Humanos , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/epidemiología , Femenino , Masculino , Italia/epidemiología , Persona de Mediana Edad , Adulto , Federación de Rusia/epidemiología , LDL-Colesterol/sangre , Heterogeneidad Genética , Proteínas Adaptadoras Transductoras de Señales/genética , Anciano , MutaciónRESUMEN
Detection and treatment of patients with familial hypercholesterolemia (FH) starting from childhood is fundamental to reduce morbidity and mortality. The activity of National realities such as the LIPIGEN (LIpid transPort disorders Italian GEnetic Network) Paediatric Group, founded in 2018, is a milestone in this context. The aim of this exploratory survey, conducted in October 2021 among Italian lipid clinics included in the LIPIGEN Paediatric Group, was to investigate the current clinical approach in the management and treatment of paediatric patients with suspected FH. A digital questionnaire composed of 20 questions investigating nutritional treatment and nutraceutical and pharmacological therapy for children and adolescents with FH was proposed to the principal investigators of 30 LIPIGEN centres. Twenty-four centres responded to the section referring to children aged < 10 years and 30 to that referring to adolescents. Overall, 66.7% of children and 73.3% of adolescents were given lipid-lowering nutritional treatment as the first intervention level for at least 3-4 months (29.2% and 23.3%) or 6-12 months (58.3% and 53.3%). Nutraceuticals were considered in 41.7% (regarding children) and 50.0% (regarding adolescents) of the centres as a supplementary approach to diet. Lipid-lowering drug therapy initiation was mainly recommended (91.7% and 80.0%). In 83.3% of children and 96.7% of adolescents, statins were the most frequently prescribed drug. We highlighted several differences in the treatment of paediatric patients with suspected FH among Italian centres; however, the overall approach is in line with the European Atherosclerosis Society (EAS) recommendations for FH children and adolescents. We consider this survey as a starting point to reinforce collaboration between LIPIGEN centres and to elaborate in the near future a consensus document on the management of paediatric patients with suspected FH so as to improve and uniform detection, management, and treatment of these patients in our country.
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Anticolesterolemiantes , Dieta , Suplementos Dietéticos , Hiperlipoproteinemia Tipo II , Humanos , Masculino , Femenino , Niño , Adolescente , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/terapia , Anticolesterolemiantes/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age. METHODS: From the Italian LIPIGEN cohort, we selected 1188 (≥18 years) and 708 (<18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation. RESULTS: The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives. CONCLUSIONS: In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age.
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Enfermedad de la Arteria Coronaria , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Adulto , Humanos , Niño , Adolescente , Factores de Riesgo , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiología , Hiperlipoproteinemia Tipo II/genética , HeterocigotoRESUMEN
Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH.
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Hiperlipoproteinemia Tipo II , Lipoproteína(a) , Humanos , Lipoproteína(a)/genética , Redes Reguladoras de Genes , Factores de Riesgo , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/complicaciones , Genotipo , LDL-ColesterolRESUMEN
[This corrects the article DOI: 10.3389/fgene.2022.912510.].
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BACKGROUND AND AIMS: The European Atherosclerosis Society (EAS) Lipid Clinics Network promoted a survey in order to identify and understand how and when lipoprotein(a) [Lp(a)] is tested and clinically evaluated in lipid clinics throughout Europe, and the challenges that may prevent evaluation from being carried out. METHODS: This survey was divided into three areas of inquiry: background and clinical setting information of clinicians, questions for doctors who claimed not to measure Lp(a), in order to understand what were the reasons for not ordering the test, and questions for doctors who measure Lp(a), to investigate the use of this value in the management of patients. RESULTS: A total of 151 centres clinicians filled in the survey, out of 226 invited. The proportion of clinicians who declare to routinely measure Lp(a) in clinical practice was 75.5%. The most common reasons for not ordering the Lp(a) test were the lack of reimbursement or of treatment options, the non-availability of Lp(a) test, and the high cost of performing the laboratory test. The availability of therapies targeting this lipoprotein would result in a greater propensity of clinicians to start testing Lp(a). Among those who declared to routinely measure Lp(a), the Lp(a) measurement is mostly requested to further stratify patients' cardiovascular risk, and half of them recognized 50 mg/dL (approx. 110 nmol/L) as the threshold for increased cardiovascular risk due. CONCLUSIONS: These results warrant for a great deal of effort from scientific societies to address the barriers that limit the routine use of the measurement of Lp(a) concentration and to recognise the importance of Lp(a) as a risk factor.
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Aterosclerosis , Enfermedades Cardiovasculares , Humanos , Lipoproteína(a) , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/prevención & control , Factores de Riesgo , Europa (Continente) , Aterosclerosis/diagnóstico , Aterosclerosis/prevención & controlRESUMEN
Pathology registers can be a useful tool to overcome obstacles in the identification and management of familial hypercholesterolemia since childhood. In 2018, the LIPIGEN pediatric group was constituted within the Italian LIPIGEN study to focus on FH subjects under 18 years. This work aimed at discussing its recent progress and early outcomes. Demographic, biochemical, and genetic baseline characteristics were collected, with an in-depth analysis of the genetic defects. The analysis was carried out on 1,602 children and adolescents (mean age at baseline 9.9 ± 4.0 years), and almost the whole cohort underwent the genetic test (93.3%). Overall, the untreated mean value of LDL-C was 220.0 ± 97.2 mg/dl, with an increasing gradient from subjects with a negative (N = 317; mean untreated LDL-C = 159.9 ± 47.7 mg/dl), inconclusive (N = 125; mean untreated LDL-C = 166.4 ± 56.5 mg/dl), or positive (N = 1,053; mean untreated LDL-C = 246.5 ± 102.1 mg/dl) genetic diagnosis of FH. In the latter group, the LDL-C values presented a great variability based on the number and the biological impact of involved causative variants. The LIPIGEN pediatric group represents one of the largest cohorts of children with FH, allowing the deepening of the characterization of their baseline and genetic features, providing the basis for further longitudinal investigations for complete details.
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BACKGROUND AND AIMS: Little is known about the role of Lp(a) in the assessment of cardiovascular risk in the paediatric population. Trying to clarify the clinical relevance of Lp(a) in risk stratification, the aim of the study is to evaluate the association between Lp(a) plasma levels in children with familial hypercholesterolaemia (FH) and positive family history for premature cardiovascular disease (pCVD) in first- and second-degree relatives. METHODS: 653 Caucasian children and adolescents (334 females and 319 males), aged 2-17 years, with diagnosis of FH from a paediatric cohort included in the LIPIGEN Network, were selected. We compared family history of pCVD, lipid and genetic profile in two groups based on Lp(a) levels below or above 30 mg/dL. To determine the independent predictors of pCVD, a multivariate logistic regression was used, with all clinical characteristics and blood measurements as predictors. RESULTS: Subjects with Lp(a) > 30 mg/dl more frequently reported positive family history of pCVD compared to subjects with Lp(a)≤30 mg/dl (69.90% vs 36.66%, p < 0.0001), while did not show differences in terms of median [interquartile range] LDL-cholesterol level (153.00 [88.00 vs 164.50 [90.25] mg/dL, p = 0.3105). In the regression analysis, Lp(a) > 30 mg/dl was an independent predictor of family history of pCVD. Comparing subjects with or without family history of pCVD, we reported significant differences for Lp(a) > 30 mg/dl (46.25% vs 17.65%, p < 0.0001), FH genetic mutation (50.48% vs 40.75%, p = 0,0157), as well as for LDL-cholesterol (p = 0.0013) and total cholesterol (p = 0.0101). CONCLUSIONS: Children/adolescents with FH and Lp(a) > 30 mg/dl where more likely to have a positive family history of pCVD. Lp(a) screening in children and adolescents with FH may enhance risk assessment and help identify those subjects, children and relatives, at increased pCVD risk.
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Enfermedades Cardiovasculares , Hiperlipoproteinemia Tipo II , Adolescente , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Niño , LDL-Colesterol , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiología , Hiperlipoproteinemia Tipo II/genética , Lipoproteína(a)/genética , Masculino , Factores de RiesgoRESUMEN
Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH-mutation negative had lower mean levels of pretreatment LDL-C than patients who were FH-mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P<0.0001). The mean value (±SD) of the polygenic LDL-C risk score was 1.00 (±0.18) in patients who were FH-mutation negative and 0.94 (±0.20) in patients who were FH-mutation positive (P<0.0001). In the receiver operating characteristic analysis, the area under the curve for recognizing subjects characterized by polygenic hypercholesterolemia was 0.59 (95% CI, 0.56-0.62), with sensitivity and specificity being 78% and 36%, respectively, at 0.905 as a cutoff value. Higher mean polygenic LDL-C risk score levels were observed among patients who were FH-mutation negative having pretreatment LDL-C levels in the range of 150 to 350 mg/dL (150-249 mg/dL: 1.01 versus 0.91, P<0.0001; 250-349 mg/dL: 1.02 versus 0.95, P=0.0001). A positive correlation between polygenic LDL-C risk score and pretreatment LDL-C levels was observed among patients with FH independently of the presence of causative mutations. Conclusions This analysis confirms the role of polymorphisms in modulating LDL-C levels, even in patients with genetically confirmed FH. More data are needed to support the use of the polygenic score in routine clinical practice.
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LDL-Colesterol , Redes Reguladoras de Genes , Hiperlipoproteinemia Tipo II , Adulto , LDL-Colesterol/sangre , Femenino , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Masculino , Persona de Mediana Edad , Herencia Multifactorial , MutaciónRESUMEN
AIMS: As the potential impact of statins on cognitive decline and dementia is still debated, we conducted a meta-analysis of observational studies to examine the effect of statin use on the risk of Alzheimer's disease (AD) and dementia. METHODS AND RESULTS: PubMed, Cochrane, and EMBASE were searched since inception to January 2021. Inclusion criteria were: (i) cohort or case-control studies; (ii) statin users compared to non-users; and (iii) AD and/or dementia risk as outcome. Estimates from original studies were pooled using restricted maximum-likelihood random-effect model. Measure of effects were reported as odds ratio (OR) and 95% confidence intervals (CIs). In the pooled analyses, statins were associated with a decreased risk of dementia [36 studies, OR 0.80 (CI 0.75-0.86)] and of AD [21 studies, OR 0.68 (CI 0.56-0.81)]. In the stratified analysis by sex, no difference was observed in the risk reduction of dementia between men [OR 0.86 (CI 0.81-0.92)] and women [OR 0.86 (CI 0.81-0.92)]. Similar risks were observed for lipophilic and hydrophilic statins for both dementia and AD, while high-potency statins showed a 20% reduction of dementia risk compared with a 16% risk reduction associated with low-potency statins, suggesting a greater efficacy of the former, although a borderline statistical significance (P = 0.05) for the heterogeneity between estimates. CONCLUSION: These results confirm the absence of a neurocognitive risk associated with statin treatment and suggest a potential favourable role of statins. Randomized clinical trials with an ad hoc design are needed to explore this potential neuroprotective effect.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Demencia , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/prevención & control , Demencia/diagnóstico , Demencia/epidemiología , Demencia/etiología , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Masculino , Oportunidad RelativaRESUMEN
BACKGROUND: The lack of functional evidence for most variants detected during the molecular screening of patients with clinical familial hypercholesterolemia (FH) makes the definitive diagnosis difficult. METHODS: A total of 552 variants in LDLR, APOB, PCSK9 and LDLRAP1 genes found in 449 mutation-positive FH (FH/M+) patients were considered. Pathogenicity update was performed following the American College of Medical Genetics and Genomics (ACMG) guidelines with additional specifications on copy number variants, functional studies, in silico prediction and co-segregation criteria for LDLR, APOB and PCSK9 genes. Pathogenicity of LDLRAP1 variants was updated by using ACMG criteria with no change to original scoring. RESULTS: After reclassification, the proportion of FH/M+ carriers of pathogenic (P) or likely pathogenic (LP) variants, and FH/M+ carriers of likely benign (LB) or benign (B) variants, was higher than that defined by standard criteria (81.5% vs. 79.7% and 7.1% vs. 2.7%). The refinement of pathogenicity classification also reduced the percentage of FH with variants of uncertain significance (VUS) (17.7% vs. 11.4%). After adjustment, the FH diagnosis by refined criteria best predicted LDL-C levels (Padj <0.001). Notably, FH with VUS variants had higher LDL-C than those with LB (all Padj ≤ 0.033), but similar to those with LP variants. CONCLUSION: Accurate variant interpretation best predicts the increase of LDL-C levels and shows its clinical utility in the molecular diagnosis of FH.
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Proteínas Adaptadoras Transductoras de Señales/genética , Apolipoproteínas B/genética , Predisposición Genética a la Enfermedad/genética , Hiperlipoproteinemia Tipo II/genética , Mutación , Proproteína Convertasa 9/genética , Receptores de LDL/genética , Adulto , Niño , LDL-Colesterol/metabolismo , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad/clasificación , Heterocigoto , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
The recent publication of the REDUCE-IT study has reopened the debate about the efficacy of omega-3 fatty acids in reducing the risk of cardiovascular (CV) events. This meta-analysis aims at investigating the effect of omega-3 long-chain polyunsaturated fatty acids (n-3 PUFA) administration on CV outcomes in published randomized clinical trials (RCTs), with a focus on the role of dose, type of n-3 PUFA, and different CV risk at baseline. This meta-analysis was conducted according to the PRISMA reporting guidelines. PubMed, Cochrane and EMBASE were searched since inception to March 2020. Inclusion criteria were: (1) RCTs; (2) including subjects with previous CV events; (3) administration of n-3 PUFA ≥ 1 g/day dosage for ≥1 year; (4) effects on all-cause mortality, cardiac death, major adverse cardiovascular events (MACE), fatal/nonfatal myocardial infarction (MI), or fatal/nonfatal stroke reported. Odds ratios (ORs) with 95 % confident intervals (95 %CI) were estimated. 16 RCTs were included in the meta-analysis accounting for 81,073 participants. Supplementation of n-3 PUFA was associated with a significant risk reduction of cardiac mortality (OR 0.91 [95 % CI, 0.85-0.98]), MACE (OR 0.90 [95 % CI, 0.82-0.99]), and MI (OR 0.83 [95 % CI, 0.71-0.98]). In subgroup analyses, the risk reduction of cardiac mortality and MI was confirmed only in RCTs that enrolled patients in secondary prevention (-21 % and -31 %, respectively). Moreover, only the administration of more than 1 g per day of n-3 PUFA was effective in reducing the risk of cardiac death (-35 %), MACE (-24 %), and MI (-33 %). Finally, EPA + DHA supplementation was only associated with a significant risk reduction of cardiac death compared with EPA administered alone (-8 %). Conversely, the efficacy of EPA administered alone seemed to be greater in terms of risk reduction of MACE (-25 %) or MI (-30 %) than the combined EPA + DHA supplementation. The pharmacological approach with n-3 PUFA significantly improves cardiovascular outcomes, with higher benefit achieved by patients in secondary CV prevention, using more than 1 g/day, and taking EPA administered alone.
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Enfermedades Cardiovasculares/prevención & control , Suplementos Dietéticos , Ácidos Grasos Omega-3/uso terapéutico , Animales , Enfermedades Cardiovasculares/epidemiología , Composición de Medicamentos , Ácidos Grasos Omega-3/administración & dosificación , Humanos , Prevención Primaria , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Prevención SecundariaRESUMEN
Familial hypercholesterolemia (FH) is a common genetic disorder of lipid metabolism, still underdiagnosed and undertreated in the general population. Pathology registers could play a crucial role in the creation of a comprehensive and integrated global approach to cover all aspects of this disease. Systematic data collection of patients affected by FH has increased dramatically worldwide in the past few years. Moreover, results from registers already established for the longest time showed their potentialities in the implementation of the knowledge of FH, comparing country-specific approaches and providing real-world data about identification, management and treatment of FH individuals in the clinical practice. The potential fields of research through registers are related to the deepening of the genetic basis of disease, the study of genotype-phenotype correlation, the local adaption and implementation of diagnostic algorithms, the comparison of pharmacological approaches and treatment gaps in real-life clinical practice, the evaluation of specific subpopulations, and the identification of factors modifying cardiovascular disease risk. Registers could become also a valid resource for other rare dyslipidaemias, contributing towards the evidence-based enhancement in the worldwide care of uncommon diseases.