Asociación entre los marcadores lipídicos en la infancia/ adolescencia y los eventos cardiovasculares en la adultez: una revisión sistemática / Association between lipid markers in childhood/ adolescence and cardiovascular events in adulthood: A systematic review

Introducción. La asociación entre los marcadores lipídicos en la infancia/adolescencia y la incidencia de eventos clínicos cardiovasculares en la adultez está poco explorada en la literatura. El objetivo de esta revisión sistemática fue analizar la evidencia disponible sobre este tema. Población y métodos. Esta revisión sistemática se realizó de acuerdo con las guías PRISMA. Se realizó una búsqueda bibliográfica para detectar los estudios que evaluaron la asociación entre los niveles lipídicos en la edad pediátrica y la incidencia de eventos cardiovasculares en la edad adulta. No hubo restricciones idiomáticas ni geográficas en la búsqueda. Resultados. En total, cinco estudios observacionales (todas cohortes prospectivas) que incluyeron 43 540 pacientes fueron identificados y considerados elegibles para este estudio. Cuatro estudios evaluaron el nivel de triglicéridos; todos reportaron una asociación significativa entre este marcador en la edad pediátrica y los eventos cardiovasculares en la adultez. Un estudio reportó la misma asociación con el nivel de colesterol total, mientras que otro evidenció el valor predictivo de la lipoproteína (a) para el mismo desenlace clínico. Un solo estudio evaluó el colesterol asociado a lipoproteínas de alta densidad (C-HDL), sin encontrar una relación con el punto final de interés. El análisis del colesterol asociado a lipoproteínas de baja densidad (C-LDL) arrojó resultados contradictorios, aunque la asociación fue significativa en los estudios con un tamaño muestral más grande y con un mayor número de eventos durante el seguimiento. Conclusión. Los datos de esta revisión sugieren que las alteraciones de los marcadores lipídicos en la infancia y la adolescencia se asocian con un mayor riesgo cardiovascular en la adultez temprana y media.

Introduction. The association between lipid markers in childhood/adolescence and the incidence of clinical cardiovascular events in adulthood has been little explored in the bibliography. The objective of this systematic review was to analyze available evidence on this topic. Population and methods. This systematic review was conducted in accordance with the PRISMA guidelines. A comprehensive bibliographic search was done to find studies assessing the association between lipid levels in childhood and the incidence of cardiovascular events in adulthood. There were no language or geographic restrictions. Results. A total of 5 observational studies (all prospective cohorts) including 43 540 patients were identified and considered eligible for this study. Four studies assessed triglyceride levels; all reported a significant association between this lipid marker in childhood and cardiovascular events in adulthood. A study reported the same association with total cholesterol level, while another showed the predictive value of lipoprotein (a) for the same clinical outcome. Only one study assessed high-density lipoprotein cholesterol (HDL-C), but it did not find an association with the endpoint of interest. The analysis of lowdensity lipoprotein cholesterol (LDL-C) showed contradictory results, although the association was significant in the studies with a larger sample size and a higher number of events during follow-up. Conclusion. According to this review, alterations in lipid markers in childhood and adolescence are associated with a higher cardiovascular risk in early and middle adulthood.

Dyslipidemia in adults with congenital heart disease: A systematic review and meta-analysis.

AIMS: Several particular characteristics of patients with congenital heart disease could affect lipid levels. The objectives of this study were: a) to analyze the prevalence of dyslipidemia in congenital heart disease patients; 2) to compare lipid levels between congenital heart disease patients and a control group. DATA SYNTHESIS: This systematic review and meta-analysis was performed according to PRISMA guidelines (PROSPERO CRD42023432041). A literature search was performed to detect studies that have reported lipid levels or the prevalence of dyslipidemia in congenital heart disease patients. We performed a qualitative analysis (studies that reported dyslipidemia prevalence) and quantitative analysis (studies that compared lipid values between congenital heart disease patients and controls). In total, 29 observational studies involving 22,914 patients with congenital heart disease and 641,086 controls were eligible for this review. The reported presence of "hyperlipidemia" or "dyslipidemia" ranged from 14.3% to 69.9%. When studies analyzed lipid variables dichotomously between congenital heart disease patients and controls, the results were conflicting. The quantitative analysis showed that patients with congenital heart disease have lower levels of total cholesterol (MD: -18.9 [95% CI: -22.2 to -15.7]; I2 = 93%), LDL-C (MD: -10.7 [95% CI: -13.1 to -8.3]; I2 = 90%) and HDL-C (MD: -6.3 [95% CI: -7.7 to -4.9]; I2 = 95%) compared to controls. CONCLUSIONS: The qualitative analysis showed some concerns, but the quantitative analysis indicates that congenital heart disease patients showed lower levels of total cholesterol, LDL-C, and HDL-C compared to controls. New research should be developed to clarify this relevant topic.

Association between lipid markers in childhood/adolescence and cardiovascular events in adulthood: A systematic review. / Asociación entre los marcadores lipídicos en la infancia/adolescencia y los eventos cardiovasculares en la adultez: una revisión sistemática.

Introduction. The association between lipid markers in childhood/adolescence and the incidence of clinical cardiovascular events in adulthood has been little explored in the bibliography. The objective of this systematic review was to analyze available evidence on this topic. Population and methods. This systematic review was conducted in accordance with the PRISMA guidelines. A comprehensive bibliographic search was done to find studies assessing the association between lipid levels in childhood and the incidence of cardiovascular events in adulthood. There were no language or geographic restrictions. Results. A total of 5 observational studies (all prospective cohorts) including 43 540 patients were identified and considered eligible for this study. Four studies assessed triglyceride levels; all reported a significant association between this lipid marker in childhood and cardiovascular events in adulthood. A study reported the same association with total cholesterol level, while another showed the predictive value of lipoprotein (a) for the same clinical outcome. Only one study assessed high-density lipoprotein cholesterol (HDL-C), but it did not find an association with the endpoint of interest. The analysis of lowdensity lipoprotein cholesterol (LDL-C) showed contradictory results, although the association was significant in the studies with a larger sample size and a higher number of events during follow-up. Conclusion. According to this review, alterations in lipid markers in childhood and adolescence are associated with a higher cardiovascular risk in early and middle adulthood.

Introducción. La asociación entre los marcadores lipídicos en la infancia/adolescencia y la incidencia de eventos clínicos cardiovasculares en la adultez está poco explorada en la literatura. El objetivo de esta revisión sistemática fue analizar la evidencia disponible sobre este tema. Población y métodos. Esta revisión sistemática se realizó de acuerdo con las guías PRISMA. Se realizó una búsqueda bibliográfica para detectar los estudios que evaluaron la asociación entre los niveles lipídicos en la edad pediátrica y la incidencia de eventos cardiovasculares en la edad adulta. No hubo restricciones idiomáticas ni geográficas en la búsqueda. Resultados. En total, cinco estudios observacionales (todas cohortes prospectivas) que incluyeron 43 540 pacientes fueron identificados y considerados elegibles para este estudio. Cuatro estudios evaluaron el nivel de triglicéridos; todos reportaron una asociación significativa entre este marcador en la edad pediátrica y los eventos cardiovasculares en la adultez. Un estudio reportó la misma asociación con el nivel de colesterol total, mientras que otro evidenció el valor predictivo de la lipoproteína (a) para el mismo desenlace clínico. Un solo estudio evaluó el colesterol asociado a lipoproteínas de alta densidad (C-HDL), sin encontrar una relación con el punto final de interés. El análisis del colesterol asociado a lipoproteínas de baja densidad (C-LDL) arrojó resultados contradictorios, aunque la asociación fue significativa en los estudios con un tamaño muestral más grande y con un mayor número de eventos durante el seguimiento. Conclusión. Los datos de esta revisión sugieren que las alteraciones de los marcadores lipídicos en la infancia y la adolescencia se asocian con un mayor riesgo cardiovascular en la adultez temprana y media.

Stratification in Heterozygous Familial Hypercholesterolemia: Imaging, Biomarkers, and Genetic Testing.

PURPOSE OF REVIEW: Heterozygous familial hypercholesterolemia (HeFH) is the most common monogenic autosomal dominant disorder. However, the condition is often underdiagnosed and undertreated. The objective of this review is to provide an update on the risk stratification in patients with HeFH, incorporating new cardiovascular imaging techniques, various biomarkers, and genetic studies. RECENT FINDINGS: The diagnosis of HeFH places patients in a high cardiovascular risk category due to the increased incidence of premature atherosclerotic cardiovascular disease. However, the level of risk varies significantly among different individuals with HeFH. Achieving an optimal stratification of cardiovascular risk is crucial for establishing appropriate and accurate treatment and management strategies. Different new tools such as risk scores have emerged in recent years, aiding physicians in assessing the risk stratification for HeFH using imaging, biomarkers, and genetics. This review emphasizes that not all patients with HeFH face the same cardiovascular risk. By utilizing different assessment tools, we can identify those who require more intensive monitoring, follow-up, and treatment.

Elevated Lipoprotein(a) Levels and Atrial Fibrillation: A Systematic Review.

Objective: The role of lipoprotein(a) (Lp[a]) as a possibly causal risk factor for atherosclerotic cardiovascular disease has been well established. However, the clinical evidence regarding the association between Lp(a) levels and atrial fibrillation (AF) remains limited and inconsistent. This study aimed to analyze the association between elevated Lp(a) levels or single-nucleotide polymorphisms (SNPs) related to high levels of Lp(a) and AF. Methods: This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A literature search was performed to identify studies that evaluated the association between Lp(a) levels or SNPs related to high levels of Lp(a) and AF. Observational studies with a cross-sectional, case-control, or cohort design were included in this systematic review, without limitations according to language, country, or publication type. Results: Eleven observational studies including 1,246,817 patients were eligible for this systematic review. Two cross-sectional studies, 5 prospective/retrospective cohort studies, and 4 Mendelian randomization studies were analyzed. Two cross-sectional studies that compared Lp(a) levels between patients with and without AF showed conflicting results. Cohort studies that evaluated the incidence of AF according to Lp(a) levels showed different results: no association (3 studies), a positive association (1 study), and an inverse relationship (1 study). Finally, Mendelian randomization studies also showed heterogeneous results (positive association: 2 studies; inverse association: 1 study; no association: 1 study). Conclusion: Although there could be an association between Lp(a) levels and AF, the results of the studies published to date are contradictory and not yet definitive. Therefore, further research should clarify this issue.

Ethnic/Racial and Geographic Disparities on Major Cardiovascular Events in Glucagon Like Peptide-1 receptor Agonists Trials: A Meta-Analysis.

Higher rates of type 2 diabetes mellitus (T2D) are found among racial and ethnic minorities in the United States. These groups also experience a higher rate of cardiovascular and renal complications. Despite the previously mentioned high risk, these minority groups are usually underrepresented in clinical trials. The purpose of this study was to report the effect of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on major cardiovascular events (MACE) in subgroup analysis along different ethnic/racial and geographical groups in patients with T2D included in cardiovascular outcomes trials (CVOTs). A meta-analysis of randomized studies that evaluated the use of GLP-1 RAs in patients with T2D and reporting MACE across ethnic/race and geographical regions groups was performed after searching the PubMed/MEDLINE, Embase, Scielo, Google Scholar, and Cochrane Controlled Trials databases. This meta-analysis was performed according to PRISMA guidelines. Measures of the effect size were expressed as odds ratios (ORs). Fixed or random effects models were used. Seven trials, including 58,294 patients, were identified and considered eligible for the analyses. GLP-1 RAs were associated with a reduction in MACE incidence in Europe (OR 0.77, 95% CI: 0.65-0.91) and Asia/Pacific (OR 0.70, 95% CI: 0.55-0.90) regions with no significant reduction observed in North America (OR 0.95, 95% CI: 0.86-1.05) and Latin America (OR 0.87, 95%CI: 0.63-1.21) MACE reduction was observed in all ethnic/race groups evaluated with exception to black patients. In this meta-analysis, we observed ethnic/racial and geographic disparities in MACE reduction with GLP-1 RAs in CVOTs. Consequently, we believe it is essential to systematically include and assess ethnic/racial minorities in clinical studies.

Lipoprotein(a) and heart failure: a systematic review.

The role of lipoprotein(a) [Lp(a)] as a possible causal risk factor for atherosclerotic artery disease and aortic valve stenosis has been well established. However, the information on the association between Lp(a) levels and heart failure (HF) is limited and controversial. The main objective of the present study was to assess the association between Lp(a) levels and HF. This systematic review was performed according to PRISMA guidelines. A literature search was performed to detect studies that evaluated the association between Lp(a) levels and HF. Eight studies, including 73,410 patients, were eligible for this research. Seven prospective or retrospective cohorts and one cross-sectional study were analyzed. Five studies analyzed populations without HF; another three included patients with HF or left ventricular dysfunction. The endpoints evaluated varied according to the study analyzed, including incident HF, HF hospitalizations, and decreased left ventricular ejection fraction. Lp(a) levels were also analyzed in different ways, including analysis of Lp(a) as a continuous or categorical variable (distinct cut-off points or percentiles). Globally, the studies included in this review found predominantly positive results. Data on some relevant subgroups, such as HF of ischemic or non-ischemic etiology or HF with or without left ventricular dysfunction, was poorly reported. This systematic review suggests that there would be a positive relationship between Lp(a) levels and HF. Given the complexity and heterogeneity of HF, new studies should be developed to clarify this topic.

Plasma Lipoprotein(a) Levels in Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis.

INTRODUCTION: The polycystic ovary syndrome (PCOS) may represent an important model of lipid alterations. Lipoprotein(a) [Lp(a)] has emerged as a new marker of cardiovascular risk. AIM: The main objective of this meta-analysis was to analyze the available evidence on Lp(a) levels in patients with PCOS compared to a control group. METHODS: This meta-analysis was performed according to PRISMA guidelines. A literature search was performed to detect studies that have quantified Lp(a) levels in women with PCOS compared to a control group. The primary outcome was Lp(a) levels expressed in mg/dL. Random effects models were used. RESULTS: Twenty-three observational studies including 2,337 patients were identified and considered eligible for this meta-analysis. In the overall analysis, the quantitative analysis showed that patients with PCOS have a higher Lp(a) levels (SMD: 1.1 [95% CI: 0.7 to 1.4]; I2=93%) compared to the control group. The results were similar in the analysis of the subgroups of patients according to body mass index (normal weight group: SMD: 1.2 [95% CI: 0.5 to 1.9], I2=95%; overweight group: SMD: 1.2 [95% CI: 0.5 to 1.8], I2=89%). Sensitivity analysis showed that the results were robust. CONCLUSIONS: This meta-analysis shows that women with PCOS had higher levels of Lp(a) compared to healthy women used as a control group. These findings were observed in both overweight and non-overweight women.

Hipertrigliceridemia grave en Argentina: prevalencia y características clínicas / Severe Hypertriglyceridemia in Argentina: Prevalence and Clinical Characteristics

RESUMEN Introducción : La hipertrigliceridemia grave (HTGG) es un desorden metabólico con múltiples causas e implicancias tera péuticas. Se desconocen hasta la fecha las características clínicas, la prevalencia y sus posibles causas en nuestra población. Objetivo : estimar la prevalencia, describir las características clínicas y causas subyacentes de la HTGG en un hospital de tercer nivel del municipio de General Pueyrredón. Materia y métodos : Estudio descriptivo y observacional realizado con pacientes ambulatorios e internados de un hospital provincial. Se incluyeron pacientes adultos con triglicéridos (TG) mayores que 885 mg/dL (10 mmol/L) evaluados desde enero de 2018 a diciembre de 2021. Se extrajeron sus historias clínicas y, luego, se los contactó para obtener medidas antro pométricas, variables sociodemográficas, antecedentes personales y familiares, causas secundarias de hipertrigliceridemia y el tratamiento recibido. Resultados : Se analizaron 16 029 muestras; 46 presentaron HTGG, lo que representa una prevalencia total del 0,28% (IC 95% 0,20-0,40%) (IC 95% 0,20-0,40%); se incluyeron 19 participantes en el análisis. La edad media fue de 48,47 años (DE ±16); el 84,2% de ellos eran hombres. La mediana de triglicéridos fue 1821 mg/dL (rango intercuartílico 917-7000 mg/dL); 17 participantes (84,97%) presentaban hipercolesterolemia (colesterol total mayor que 200 mg/dL). Casi el 50% refirió consumo de alcohol, el 55% presentaba obesidad y el 68% diabetes tipo II. Solo 9 participantes se encontraban en tratamiento, 4 con fibratos y 5 con estatinas. Conclusión : se encontró una prevalencia del 0,28%, más alta que la esperada y reportada en series previas. Por otro lado, se destaca la subutilización de medicación para el tratamiento de esta dislipidemia grave.

ABSTRACT Background : Severe hypertriglyceridemia (SHTG) is a metabolic disorder with multiple origins and management implications. Prevalence, clinical characteristics, and its possible causes are unknown in Argentina. Objective : The aim of this study was to estimate the prevalence and describe the clinical characteristics and underlying SHTG causes in a third level hospital in the municipality of General Pueyrredón. Methods : An observational, descriptive study was performed using an electronic database from a provincial Hospital. It included adult patients with triglyceride (TG) levels above 885 mg/dL (10 mmol/L) evaluated from January 2018 to December 2021. Medical records were collected, and patients were then contacted to obtain anthropometric measurements, sociodemographic variables, personal and family history, secondary causes of hypertriglyceridemia, and treatment received. Results : Among 16 029 patients analyzed, 46 presented SHTG, representing a total prevalence of 0.28% (95% CI 0.20-0.40%). Finally, 19 participants with mean age 48.47±16 years and 84.2% men were included in the analysis. Median TG level was 1821 mg/dL (interquartile range 917-7000 mg/dL), and 17 participants (84.97%) had hypercholesterolemia (total cholesterol >200 mg/dL). Almost 50% reported alcohol consumption, 55% were obese and 68% had type II diabetes. Nine participants were under pharmacological treatment, 4 with fibrates and 5 with statins. Conclusion : A prevalence of 0.28% SHTG was found, higher than that reported in other series. Another finding was the underuse of medication for this severe dyslipidemia.

Relationship between lipoprotein(a) levels, cardiovascular outcomes and death in patients with chronic kidney disease: a systematic review of prospective studies.

INTRODUCTION AND AIM: In the general population, high levels of lipoprotein(a) (Lp(a)) are an independent risk factor for atherosclerotic cardiovascular diseases. However, the information available in patients with chronic kidney disease (CKD) is less robust. The main objective of this updated systematic review of prospective studies was to analyze the association between elevated Lp(a) levels and cardiovascular outcomes or death in patients with CKD. METHODS: The PRISMA guidelines were used to carry out this systematic review. Randomized clinical trials or prospective observational studies that evaluated the association between Lp(a) levels and cardiovascular outcomes or death in CKD patients were searched in the current literature. RESULTS: Fifteen studies including 12,260 individuals were identified and considered eligible for this systematic review. In total, 14 prospective cohorts and one post-hoc analysis of a randomized clinical trial were analyzed. Eight studies evaluated hemodialysis patients, one study analyzed patients on peritoneal dialysis, while six studies evaluated subjects with different stages of CKD. Median follow-up duration ranged from 1 to 8.6 years. Our findings showed that elevated Lp(a) values were associated with a higher risk of cardiovascular events or death in most studies, despite adjusting for traditional risk factors. CONCLUSION: The findings of this systematic review show that there is a positive association between Lp(a) levels and fatal and non-fatal cardiovascular events in patients with CKD.

High lipoprotein(a) levels and mitral valve disease: A systematic review.

AIMS: The role of lipoprotein(a) [Lp(a)] as a possibly causal risk factor for atherosclerotic artery disease and aortic valve stenosis has been well established. However, the information available on the association between Lp(a) levels and mitral valve disease is limited and controversial. The main objective of the present study was to assess the association between Lp(a) levels and mitral valve disease. DATA SYNTHESIS: This systematic review was performed according to PRISMA guidelines (PROSPERO CRD42022379044). A literature search was performed to detect studies that evaluated the association between Lp(a) levels or single-nucleotide polymorphisms (SNPs) related to high levels of Lp(a) and mitral valve disease, including mitral valve calcification and valve dysfunction. Eight studies including 1,011,520 individuals were considered eligible for this research. The studies that evaluated the association between Lp(a) levels and prevalent mitral valve calcification found predominantly positive results. Similar findings were reported in two studies that evaluated the SNPs related to high levels of Lp(a). Only two studies evaluated the association of Lp(a) and mitral valve dysfunction, showing contradictory results. CONCLUSIONS: This research showed disparate results regarding the association between Lp(a) levels and mitral valve disease. The association between Lp(a) levels and mitral valve calcification seems more robust and is in line with the findings already demonstrated in aortic valve disease. New studies should be developed to clarify this topic.

Relationship Between Lipoprotein(a) Levels and Cardiovascular Outcomes in Postmenopausal Women: A Systematic Review.

Elevated lipoprotein(a) [Lp(a)] levels are independently associated with atherosclerotic cardiovascular disease, although this association is less explored in postmenopausal women. The main objective of this systematic review was to analyze the association between elevated Lp(a) levels and cardiovascular outcomes in posmenopausal women. Studies that evaluated this association were searched in the current literature. Ten studies including 157.690 women were considered eligible for this study. In total, 4 prospective cohorts, 3 cross-sectional studies, 2 nested case-control studies, and one post-hoc analysis from a randomized clinical trial were analyzed. The included studies showed different results regarding the association between Lp(a) levels and cardiovascular outcomes: a positive association (4 studies), no association (2 studies), or different results depending on the subgroups or outcomes evaluated (4 studies). The results were robust when evaluating coronary events. The reduction in coronary events attributed to a hormone replacement therapy-associated decrease in Lp(a) levels was controversial.

Reduction of cardiovascular events with the use of lipid-lowering medication in patients with familial hypercholesterolemia or severe primary hypercholesterolemia: A systematic review.

BACKGROUND: Lipid-lowering medication is effective in reducing the risk of cardiovascular disease in several clinical scenarios. However, the evidence in patients with familial hypercholesterolemia (FH) and severe primary hypercholesterolemia is less robust. OBJECTIVES: The main objective of the present systematic review was to analyze the association between lipid-lowering medication and cardiovascular risk reduction in patients with FH or severe primary hypercholesterolemia. METHODS: This systematic review was performed according to PRISMA guidelines. A literature search was performed to detect studies that evaluated the association between lipid-lowering medication and cardiovascular events in FH patients. The diagnosis of FH varied in the studies analyzed. Genetic and clinical criteria or a combination of both were used. Likewise, we considered patients with severe primary hypercholesterolemia. RESULTS: Fourteen studies including 21059 patients were considered eligible for this research. This systematic review showed that the vast majority of the studies with statins reported a significant cardiovascular risk reduction. Statin use was associated with a lower risk of major adverse cardiovascular events (3 studies), coronary heart disease (2 studies), cardiovascular death (4 studies), all-cause mortality (4 studies) and combined endpoint of coronary heart disease and mortality (1 study). When analyzing the association between non-statin lipid-lowering medications and the incidence of cardiovascular events, the results were conflicting. CONCLUSION: Despite the low level of evidence, this systematic review showed that statins reduce cardiovascular events in patients with HeFH. Evidence for other lipid-lowering drugs is not conclusive.

Effect of Yerba Mate (Ilex paraguariensis) on Lipid Levels: A Systematic Review and Meta-Analysis.

Several studies have evaluated the lipid-lowering properties of yerba mate, although the results were conflicting. The objective of this systematic review was to assess the effect of yerba mate consumption on lipid levels. A literature search was performed to detect observational and experimental studies that evaluated the association between yerba mate consumption and lipid levels. A quantitative analysis was performed with the subgroup of experimental studies. A meta-regression was performed considering the difference in baseline lipid values between the intervention and control groups as a covariate. Thirteen studies were considered eligible for this systematic review and seven studies (378 patients) were selected for quantitative analysis. In the qualitative analysis, the results were conflicting, both in the observational and in the experimental studies. In quantitative analysis, we found no differences in total cholesterol [mean difference 6.4 (CI 95% -2.2 to 15.0)], LDL-C [mean difference 5.5 (CI 95% - 1.5 to 12.6)], HDL-C [mean difference 0.4 (CI 95% -2.8 to 3.7)] and triglycerides [mean difference 5.7 (CI 95% 0.0 to 11.4)] levels when comparing the yerba mate and control groups. According to meta-regression, differences between baseline levels could influence the findings on total cholesterol and LDL-C but not on HDL-C or triglycerides. In conclusion, this research showed that yerba mate consumption was not associated with a significant change in lipid levels. Since the results are based on small inconclusive studies, more research is needed to confirm these findings.

New Therapies for Primary Hyperlipidemia.

Primary hyperlipidemias include a heterogeneous set of monogenic and polygenic conditions characterized by a strong family aggregation, severe forms of hypercholesterolemia and/or hypertriglyceridemia, appearance early on life, and a high risk of cardiovascular events and/or recurrent pancreatitis. In real life, a small proportion of the primary hyperlipidemia cases is recognized and treated properly. Our goal is to present an update of current and upcoming therapies for patients with primary hyperlipidemia. Recently, new lipid-lowering medications have obtained authorization from the U.S. Food and Drug Administration and the European Medicines Agency. These drugs target metabolic pathways, including (adenosine 5'-triphosphates)-citrate lyase (bempedoic acid), proprotein convertase subtilisin/kexin 9 (inclisiran), apolipoprotein CIII (volanesorsen), and angiopoietin-like 3 (volanesorsen), that have additive effects with the actions of the currently available therapies (i.e., statins, ezetimibe or fibrates). We discuss the potential clinical indications for the novel medications. To conclude, the addition of these new medications to the therapeutic options for primary hyperlipidemia patients may increase the likelihood of achieving the treatment targets. Also, it could be a safer alternative for patients with side effects for the currently available drugs.

Effect of Colchicine vs Usual Care Alone on Intubation and 28-Day Mortality in Patients Hospitalized With COVID-19: A Randomized Clinical Trial.

Importance: Hospitalized patients with COVID-19 pneumonia have high rates of morbidity and mortality. Objective: To assess the efficacy of colchicine in hospitalized patients with COVID-19 pneumonia. Design, Setting, and Participants: The Estudios Clínicos Latino América (ECLA) Population Health Research Institute (PHRI) COLCOVID trial was a multicenter, open-label, randomized clinical trial performed from April 17, 2020, to March 28, 2021, in adults with confirmed or suspected SARS-CoV-2 infection followed for up to 28 days. Participants received colchicine vs usual care if they were hospitalized with COVID-19 symptoms and had severe acute respiratory syndrome or oxygen desaturation. The main exclusion criteria were clear indications or contraindications for colchicine, chronic kidney disease, and negative results on a reverse transcription-polymerase chain reaction test for SARS-CoV-2 before randomization. Data were analyzed from June 20 to July 25, 2021. Interventions: Patients were assigned in a 1:1 ratio to usual care or usual care plus colchicine. Colchicine was administered orally in a loading dose of 1.5 mg immediately after randomization, followed by 0.5 mg orally within 2 hours of the initial dose and 0.5 mg orally twice a day for 14 days or discharge, whichever occurred first. Main Outcomes and Measures: The first coprimary outcome was the composite of a new requirement for mechanical ventilation or death evaluated at 28 days. The second coprimary outcome was death at 28 days. Results: A total of 1279 hospitalized patients (mean [SD] age, 61.8 [14.6] years; 449 [35.1%] women and 830 [64.9%] men) were randomized, including 639 patients in the usual care group and 640 patients in the colchicine group. Corticosteroids were used in 1171 patients (91.5%). The coprimary outcome of mechanical ventilation or 28-day death occurred in 160 patients (25.0%) in the colchicine group and 184 patients (28.8%) in the usual care group (hazard ratio [HR], 0.83; 95% CI, 0.67-1.02; P = .08). The second coprimary outcome, 28-day death, occurred in 131 patients (20.5%) in the colchicine group and 142 patients (22.2%) in the usual care group (HR, 0.88; 95% CI, 0.70-1.12). Diarrhea was the most frequent adverse effect of colchicine, reported in 68 patients (11.3%). Conclusions and Relevance: This randomized clinical trial found that compared with usual care, colchicine did not significantly reduce mechanical ventilation or 28-day mortality in patients hospitalized with COVID-19 pneumonia. Trial Registration: ClinicalTrials.gov Identifier: NCT04328480.

Challenges in familial chylomicronemia syndrome diagnosis and management across Latin American countries: An expert panel discussion.

Familial chylomicronemia syndrome (FCS) is a rare genetic disorder characterized by extremely high triglyceride levels due to impaired clearance of chylomicrons from plasma. This paper is the result of a panel discussion with Latin American specialists who raised the main issues on diagnosis and management of FCS in their countries. Overall FCS is diagnosed late on the course of the disease, is characterized by heterogeneity on the occurrence of pancreatitis, and remains a long time in care of different specialists until reaching a lipidologist. Pancreatitis and secondary diabetes are frequently seen, often due to late diagnosis and inadequate care. Molecular diagnosis is unusual; however, loss of function variants on the lipoprotein lipase gene are apparently the most frequent etiology. A founder effect of the glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 gene has been described in the northeast of Brazil. Low awareness of the disease amongst health professionals contributes to inadequate care and an inadequate patient journey.

Estudio prospectivo sobre uso y persistencia de tratamiento hipolipidemiante en pacientes con hipercolesterolemia severa / Use and persistence of lipid-lowering therapy in patients with severe hypercholesterolemia: A prospective study

Introducción: Las estatinas son la primera línea de tratamiento en pacientes con hipercolesterolemia severa (HS). A pesar de la evidencia disponible sobre su eficacia y seguridad para prevenir eventos cardiovasculares, el correcto tratamiento sigue siendo un desafío. Materiales y métodos: Estudio observacional prospectivo diseñado para determinar mediante entrevista telefónica la presencia de factores de riesgo, seguimiento clínico anual, persistencia/uso de estatinas y aparición de nuevos eventos cardiovasculares (ECV) después de 5 años, en pacientes con HS incluidos en un programa de Detección de Hipercolesterolemia Familiar. Resultados: Se evaluó a 115 participantes, la edad media fue de 56 ± 10, siendo el 74% mujeres. El 63,4% de las mujeres y el 43% de los hombres refirió estar en seguimiento y control clínico en el último año. El 38,8% de las mujeres recibió estatinas vs. el 26,7% de los hombres y solo 22 participantes (31,8%) fueron persistentes con el tratamiento desde 2015. El 15,5% de los participantes presentó un ECV no fatal y el 3,4% fatal. En el análisis multivariado no se detectaron predictores para presentar un ECV. Conclusiones: En nuestra población con HS encontramos un alto riesgo de presentar un ECV y una dramática baja tasa de uso y persistencia al tratamiento con estatinas.(AU)

Introduction: Statins are the first line of treatment in patients with severe hypercholesterolemia (SH). However, despite the knowledge regarding its effectiveness and security for preventing cardiovascular diseases, treatment is a major challenge. Material and methods: A prospective observational study was conducted by telephone survey to determine cardiovascular risk factors, annual monitoring, statins use and persistence and new-onset cardiovascular events (CVE) after 5 years in patients with SH including in a program for detection of familial hypercholesterolemia. Results: 115 participants were analysed, the median age was 56 ±10 being 74% females. 63.4% of women and 43% of men had been correctly controlled in the last year. Patients on lipid lowering drugs stratified by sex was 38.8% in women and 26.7% in men, however, only 22 participants (31.8%) were persistence with statins since 2015.Overall, 48% of the patients presented a CVE and 3.4% died. Multivariate analysis did not reveal predictors for CVE. Conclusions: In our population with SH we found a high risk to present a CVE and a dramatic low use and persistence with the treatment.(AU)

Use and persistence of lipid-lowering therapy in patients with severe hypercholesterolemia: A prospective study. / Estudio prospectivo sobre uso y persistencia de tratamiento hipolipidemiante en pacientes con hipercolesterolemia severa.

INTRODUCTION: Statins are the first line of treatment in patients with severe hypercholesterolemia (SH). However, despite the knowledge regarding its effectiveness and security for preventing cardiovascular diseases, treatment is a major challenge. MATERIAL AND METHODS: A prospective observational study was conducted by telephone survey to determine cardiovascular risk factors, annual monitoring, statins use and persistence and new-onset cardiovascular events (CVE) after 5 years in patients with SH including in a program for detection of familial hypercholesterolemia. RESULTS: 115 participants were analysed, the median age was 56 ±10 being 74% females. 63.4% of women and 43% of men had been correctly controlled in the last year. Patients on lipid lowering drugs stratified by sex was 38.8% in women and 26.7% in men, however, only 22 participants (31.8%) were persistence with statins since 2015.Overall, 48% of the patients presented a CVE and 3.4% died. Multivariate analysis did not reveal predictors for CVE. CONCLUSIONS: In our population with SH we found a high risk to present a CVE and a dramatic low use and persistence with the treatment.

Phenotype of definite familial hypercholesterolemia with negative genetic study in Argentina.

Objective: Familial hypercholesterolemia (FH) is a monogenic disease, associated with variants in the LDLR, APOB and PCSK9 genes. The initial diagnosis is based on clinical criteria like the DLCN criteria. A score > 8 points qualifies the patient as "definite" for FH diagnosis. The detection of the presence of a variant in these genes allows carrying out familial cascade screening and better characterizes the patient in terms of prognosis and treatment. Methods: In the context of the FH detection program in Argentina (Da Vinci Study) 246 hypercholesterolemic patients were evaluated, 21 with DLCN score > 8 (definite diagnosis).These patients were studied with next generation sequencing to detect genetic variants, with an extended panel of 23 genes; also they were adding the large rearrangements analysis and a polygenic score of 10 SNP (single nucleotide polymorphism) related to the increase in LDL-c. Results: Of the 21 patients, 10 had variants in LDLR, 1 in APOB with APOE, 1 in LIPC plus elevated polygenic score, and 2 patients showed one deletion and one duplication in LDLR, the later with a variation in LIPA. It is highlighted that 6 of the 21 patients with a score > 8 did not show any genetic alteration. Conclusions: We can conclude that 28% of the patients with definite clinical diagnosis of FH did not show genetic alteration. The possible explanations for this result would be the presence of mutations in new genes, confusing effects of the environment over the genes, the gene-gene interactions, and finally the impossibility of detecting variants with the current available methods.

Objetivo: La hipercolesterolemia familiar (HF) es una enfermedad monogénica asociada a variantes en los genes RLDL, APOB y PCSK9. El diagnóstico inicial se basa en criterios clínicos, como el de la red de clínica de lípidos holandesa (DLCN). Un puntaje > 8 puntos califica al paciente como "definitivo" para diagnóstico de HF. La identificación de una variante en estos genes permite realizar el cribado en cascada familiar y caracterizar mejor al paciente en cuanto al pronóstico y el tratamiento. Métodos: En el marco del Programa de Detección de HF en Argentina (Estudio Da Vinci) se evaluó a 246 pacientes hipercolesterolémicos, 21 con puntaje DLCN > 8 (diagnóstico definitivo). Se estudió a estos pacientes con secuenciación de próxima generación para reconocer variantes genéticas, con un panel ampliado de 23 genes, sumado al análisis de grandes rearreglos y por último se aplicó un score poligénico de 10 SNP (polimorfismo de nucleótido único) relacionados con aumento del c-LDL. Resultados: De los 21 pacientes, 10 presentaron variantes en RLDL, uno en APOB junto a APOE, uno en LIPC más puntaje poligénico elevado, dos pacientes con una deleción y una duplicación en RLDL y este último caso con una variante en LIPA. Es destacable que 6 de los 21 pacientes con puntaje DLCN > 8 no mostraron ninguna alteración genética. Conclusiones: El 28% de los pacientes con diagnóstico clínico definitivo de HF no evidenció alteración genética. Las posibles explicaciones de este resultado serían la presencia de mutaciones en nuevos genes, los efectos confundidores del ambiente sobre los genes o la interacción gen-gen y por último la imposibilidad de detectar variantes con la metodología actual disponible.