RESUMO

In recent years, novel apoC3 inhibitor therapies for the treatment of hypertriglyceridemia have been developed and assessed through phase II and III clinical trials. The objective of this study was to perform an updated meta-analysis on the impact of new apoC3 inhibitor drugs on triglyceride and apoC3 levels, as well as on the incidence of pancreatitis. We conducted a meta-analysis of randomized, placebo-controlled studies assessing the effects of apoC3 inhibitors therapy (antisense oligonucleotides and small interfering RNA) on triglyceride levels, apoC3 levels, and the occurrence of acute pancreatitis. This meta-analysis was performed according to PRISMA guidelines. The random-effects model was performed. Nine randomized clinical trials (n = 717 patients) were considered eligible for this systematic review. ApoC3 inhibitor drugs were consistently associated with decreased triglyceride levels (MD -57.0%; 95% CI -61.9 to -52.1, I2 82%) and lowered apoC3 values (MD -76; 95% CI -80.1 to -71.8, I2 77%) when compared to placebo. Furthermore, the use of apoC3 inhibitor drugs demonstrated a reduction in the risk of acute pancreatitis (OR 0.11; 95% CI 0.04 to 0.27, I2 0%). The present updated meta-analysis of randomized clinical trials demonstrated that the utilization of apoC3 inhibitors in patients with hypertriglyceridemia correlated with reduced apoC3 and triglyceride levels, along with a decreased risk of acute pancreatitis compared to the placebo.

Assuntos

RESUMO

The development of advanced technologies in artificial intelligence (AI) has expanded its applications across various fields. Machine learning (ML), a subcategory of AI, enables computers to recognize patterns within extensive datasets. Furthermore, deep learning, a specialized form of ML, processes inputs through neural network architectures inspired by biological processes. The field of clinical lipidology has experienced significant growth over the past few years, and recently, it has begun to intersect with AI. Consequently, the purpose of this narrative review is to examine the applications of AI in clinical lipidology. This review evaluates various publications concerning the diagnosis of familial hypercholesterolemia, estimation of low-density lipoprotein cholesterol (LDL-C) levels, prediction of lipid goal attainment, challenges associated with statin use, and the influence of cardiometabolic and dietary factors on the discordance between apolipoprotein B and LDL-C. Given the concerns surrounding AI techniques, such as ethical dilemmas, opacity, limited reproducibility, and methodological constraints, it is prudent to establish a framework that enables the medical community to accurately interpret and utilize these emerging technological tools.

RESUMO

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.

Assuntos

RESUMO

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.

Assuntos

RESUMO

AIMS: The use of statins has been associated with an increased risk of new-onset diabetes. The characteristics of the population could influence this association. The objective of this study was to determine the risk of new-onset diabetes with the use of statins in patients in primary prevention, with an assessment of the results according to the baseline risk of developing diabetes of the included population. METHODS: We performed an updated meta-analysis including randomized trials of statin therapy in primary prevention settings that report new-onset diabetes. The rate of new cases of diabetes in the control arms was estimated for each study. The studies were classified into two groups (low rate: < 7.5 events per 1000 patients-year; high rate; ≥ 7.5 events per 1000 patients-year). The fixed-effects model was performed. RESULTS: Eight studies (70,453 patients) were included. Globally, statin therapy was associated with an increased risk of new-onset diabetes (OR 1.1; 95% CI 1.0-1.2, I2 35%). When we analyzed the studies according to the baseline diabetes risk in the control groups, the results showed that there was a greater risk only in the studies with a high baseline rate (OR 1.2; 95% CI 1.1-1.3, I2 0%; interaction p value = 0.01). CONCLUSION: Globally, the use of statins in patients in primary prevention was associated with an increased risk of new-onset diabetes. In the stratified analysis, this association was observed only in the group of studies with a high baseline rate of events.

Assuntos

RESUMO

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.

RESUMO

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.

RESUMO

ABSTRACT Objective: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder caused by mutations related to chylomicron metabolism. The objective of this study is to show the development and results of a screening program for FCS in Argentina. Materials and methods: A cross-sectional study was performed. All patients > 18 years with a triglyceride level ≥ 1,000 mg/dL in the period from January 1, 2017 to December 31, 2021 were included. The program was developed in three stages: (1) Review of electronic records and identification of suspected laboratory cases (triglyceride level ≥ 1,000 mg/dL); (2) Identification of suspected clinical cases (all suspected laboratory cases that had no relevant secondary factors) and application of the FCS score to define probable cases (score ≥ 10); (3) Perform genetic tests in probable cases. Results: Globally, 348 suspected laboratory cases (mean age of 49.9 years, 77.3% men) were included. The median triglycerides level was 1,309 mg/dL (interquartile range 1,175-1,607 mg/dL). In total, 231 patients were categorized as suspected clinical cases. After applying the FCS score, 3% of them were classified as "very likely FCS" (probable cases). Four variants of uncertain significance have been identified. No previously reported pathogenic variants were detected. Conclusion: This study shows a screening program for the detection of FCS. Although no patient was diagnosed with FCS, we believe that more programs of these characteristics should be developed in our region, given the importance of early detection of this metabolic disorder.

RESUMO

Objective: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder caused by mutations related to chylomicron metabolism. The objective of this study is to show the development and results of a screening program for FCS in Argentina. Materials and methods: A cross-sectional study was performed. All patients > 18 years with a triglyceride level ≥ 1,000 mg/dL in the period from January 1, 2017 to December 31, 2021 were included. The program was developed in three stages: (1) Review of electronic records and identification of suspected laboratory cases (triglyceride level ≥ 1,000 mg/dL); (2) Identification of suspected clinical cases (all suspected laboratory cases that had no relevant secondary factors) and application of the FCS score to define probable cases (score ≥ 10); (3) Perform genetic tests in probable cases. Results: Globally, 348 suspected laboratory cases (mean age of 49.9 years, 77.3% men) were included. The median triglycerides level was 1,309 mg/dL (interquartile range 1,175-1,607 mg/dL). In total, 231 patients were categorized as suspected clinical cases. After applying the FCS score, 3% of them were classified as "very likely FCS" (probable cases). Four variants of uncertain significance have been identified. No previously reported pathogenic variants were detected. Conclusion: This study shows a screening program for the detection of FCS. Although no patient was diagnosed with FCS, we believe that more programs of these characteristics should be developed in our region, given the importance of early detection of this metabolic disorder.

Assuntos

RESUMO

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.

Assuntos

RESUMO

Several small studies have evaluated the association between epicardial adipose tissue (EAT) and pregnancy-related cardiovascular risk factors such as gestational diabetes mellitus (GDM) or hypertensive disorders. The objective of this study was to quantitatively compare EAT thickening between patients with GDM or pregnancy-related hypertensive disorders and healthy controls. This systematic review and meta-analysis were performed according to PRISMA guidelines. A literature search was performed to detect studies that have quantified EAT in women with GDM and pregnancy-related hypertensive disorders compared to a control group. The primary outcome was EAT thickening estimated by ultrasound expressed in millimeters. Random or fixed effects models were used. Nine observational studies including 3146 patients were identified and considered eligible for this systematic review. The quantitative analysis showed that patients with GDM have a higher EAT thickness (mean difference: 1.1 mm [95% confidence interval: 1.0-1.2]; I2 = 24%) compared to the control group. Moreover, patients with pregnancy-related hypertensive disorders showed higher EAT thickness (mean difference: 1.0 mm [95% confidence interval: 0.6-1.4]; I2 = 83%) compared to the control group. In conclusion, this study demonstrated that EAT thickening is increased in patients with GDM and pregnancy-related hypertensive disorders compared with healthy controls. Whether or not this association is causal should be evaluated in prospective studies.

Assuntos

RESUMO

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.

Assuntos

RESUMO

BACKGROUND: Despite strong association of elevated lipoprotein (a) (Lp(a)) levels with incident coronary and cerebrovascular disease, data for incident peripheral artery disease (PAD) are less robust. The main objective of the present systematic review was to analyze the association between elevated Lp(a) levels and PAD outcomes. METHODS: This systematic review was performed according to PRISMA guidelines. A literature search was performed to detect randomized clinical trials or observational studies with a cohort design that evaluated the association between Lp(a) levels and PAD outcomes. RESULTS: Fifteen studies including 493,650 subjects were identified and considered eligible for this systematic review. This systematic review showed that the vast majority of the studies reported a significant association between elevated Lp(a) levels and the risk of PAD outcomes. The elevated Lp(a) levels were associated with a higher risk of incident claudication (RR: 1.20), PAD progression (HR: 1.41), restenosis (HR: 6.10), death and hospitalization related to PAD (HR: 1.37), limb amputation (HR: 22.75), and lower limb revascularization (HR: 1.29 and 2.90). In addition, the presence of elevated Lp(a) values were associated with a higher risk of combined PAD outcomes, with HRs in a range between 1.14 and 2.80, despite adjusting for traditional risk factors. Heterogeneity of results can be explained by different patient populations studied and varying Lp(a) cut-off points of Lp(a) analyzed. CONCLUSION: This systematic review suggests that evidence is available to support an independent positive association between Lp(a) levels and the risk of future PAD outcomes. PROSPERO Registration No.: 289253.

Assuntos

RESUMO

In type 2 diabetes mellitus there is an overproduction of chylomicron in the postprandial state that is associated with increased cardiovascular risk. Current evidence points out a leading role of enterocyte in dyslipidemia of type 2 diabetes mellitus, since it increases the production of apolipoprotein B-48 in response to a raise in plasma free fatty acids and glucose. The chylomicron metabolism is regulated by many factors apart from ingested fat, including hormonal and metabolic elements. More recently, studies about the role of gut hormones, have demonstrated that glucagon-like peptide-1 decreases the production of apolipoprotein B-48 and glucagon-like peptide-2 enhances it. Insulin acutely inhibits intestinal chylomicron production in healthy humans, whereas this acute inhibitory effect on apolipoprotein B-48 production is blunted in type 2 diabetes mellitus. Understanding these emerging regulators of intestinal chylomicron secretion may offer new mechanisms of control for its metabolism and provide novel therapeutic strategies focalized in type 2 diabetes mellitus postprandial hyperlipidemia with the reduction of cardiovascular disease risk.

Assuntos

RESUMO

En la diabetes mellitus tipo 2 el aumento en la producción de quilomicrón en el estado post-prandial se asocia a mayor riesgo cardiovascular. La evidencia actual posiciona al enterocito como actor principal en la dislipemia de la diabetes mellitus tipo 2 debido a que aumenta la producción de apolipoproteína B-48 en respuesta a una elevación de ácidos grasos libres y glucosa. El metabolismo del quilomicrón se encuentra regulado por múltiples factores independientes además de la ingesta de grasa alimentaria. Entre estos factores se destacan las hormonas intestinales, como el péptido similar al glucagón tipo 1 que disminuye la producción de apolipoproteína B-48 y el péptido similar al glucagón tipo 2 que la aumenta. Por otro lado, la insulina inhibe de forma aguda la producción de quilomicrón en el sujeto sano mientras que en la diabetes mellitus tipo 2, este efecto está ausente. La comprensión de los factores reguladores emergentes de la secreción de quilomicrón permite vislumbrar nuevos mecanismos de control en su metabolismo y aportar estrategias terapéuticas focalizadas en la hiperlipidemia posprandial en la diabetes mellitus tipo 2 con la reducción del riesgo cardiovascular.

In type 2 diabetes mellitus there is an overproduction of chylomicron in the postprandial state that is associated with increased cardiovascular risk. Current evidence points out a leading role of enterocyte in dyslipidemia of type 2 diabetes mellitus, since it increases the production of apolipoprotein B-48 in response to a raise in plasma free fatty acids and glucose. The chylomicron metabolism is regulated by many factors apart from ingested fat, including hormonal and metabolic elements. More recently, studies about the role of gut hormones, have demonstrated that glucagon-like peptide-1 decreases the production of apolipoprotein B-48 and glucagon-like peptide-2 enhances it. Insulin acutely inhibits intestinal chylomicron production in healthy humans, whereas this acute inhibitory effect on apolipoprotein B-48 production is blunted in type 2 diabetes mellitus. Understanding these emerging regulators of intestinal chylomicron secretion may offer new mechanisms of control for its metabolism and provide novel therapeutic strategies focalized in type 2 diabetes mellitus postprandial hyperlipidemia with the reduction of cardiovascular disease risk.

Assuntos