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.

Acute pancreatitis due to different semaglutide regimens: An updated meta-analysis.

OBJECTIVES: Some concerns persist regarding the safety of semaglutide. The objective of this updated meta-analysis is to assess the risk of acute pancreatitis with the use of semaglutide, assessing the results according to the different administration regimens. METHODS: We performed an updated meta-analysis of randomised, placebo-controlled studies of semaglutide therapy that report acute pancreatitis. This meta-analysis was performed in line with PRISMA guidelines. A global and stratified analysis according to the therapeutic scheme used was performed using the fixed-effects model. RESULTS: Twenty-one eligible trials of semaglutide, including 34,721 patients, were identified and considered eligible for the analyses. Globally, semaglutide therapy was not associated with an increased risk of acute pancreatitis (OR 0.7; 95% CI 0.5-1.2, I2 0%). When we analysed the studies according to the different schemes used, the results were similar (group with oral semaglutide: OR 0.40; 95% CI 0.10-1.60, I2 0%; group with low subcutaneous doses of semaglutide: OR 0.80; 95% CI 0.40-1.90, I2 0%; group with high subcutaneous doses of semaglutide: OR 0.70; 95% CI 0.50-1.20, I2 0%; interaction p-value=0.689). CONCLUSION: This updated meta-analysis demonstrates that the use of semaglutide is not associated with an increased risk of acute pancreatitis compared to placebo. In the stratified analysis, the results were similar with the different semaglutide regimens analysed.

Statins and new-onset diabetes in primary prevention setting: an updated meta-analysis stratified by baseline diabetes risk.

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.

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.

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.

Screening program for familial hyperchylomicronemia syndrome detection: Experience of a university health system

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.

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.

Screening program for familial hyperchylomicronemia syndrome detection: Experience of a university health system.

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.

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.

Association between maternal epicardial adipose tissue, gestational diabetes mellitus, and pregnancy-related hypertensive disorders: a systematic review and meta-analysis.

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.

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.

Elevated lipoprotein (a) levels and risk of peripheral artery disease outcomes: A systematic review.

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.

Low-doses aspirin in the primary prevention of cardiovascular disease in patients with diabetes: Meta-analysis stratified by baseline cardiovascular risk.

BACKGROUND AND AIM: The aim of this meta-analysis was to analyze the risks and benefits of low-dose aspirin in patients with T2D without cardiovascular conditions according to the baseline cardiovascular risk. METHODS: We performed a meta-analysis including randomized clinical trials that evaluated the use of low-dose aspirin (75-100 mg/day) versus placebo/usual care in patients with T2D. Studies were classified as low, moderate and high risk based on the number of events in the placebo/control arms or by cardiovascular risk score when reported. The incidence of MACE, cardiovascular mortality and bleeding were evaluated. RESULTS: Ten eligible trials (34069 patients) were considered eligible for the analyses. According to the stratified analysis, low-dose aspirin use was associated with reduced risk for MACE in the moderate/high-risk group (OR: 0.88; 95% CI, 0.80-0.97; I2 = 0%) but not in the low-risk group (OR: 0.89; 95% CI, 0.77-1.01; I2 = 0%). Likewise, low-dose aspirin use was associated with more bleeding in the low-risk group, showing a non-significant trend in the moderate/high-risk group. There was no reduction in cardiovascular mortality in either group. Beyond the different findings in each stratum, the differences between the subgroups were not statistically significant. CONCLUSION: This study showed that low-dose aspirin in patients with T2D reduces MACE and increases bleeding. Based on the within-subgroups results, the baseline cardiovascular risk does not modify the effect of aspirin therapy. However, few studies were included and the comparison between subgroups showed a trend in favor to the highest risk group, these results should be confirmed in future studies.

[Role of the enterocyte in type 2 diabetes mellitus associated dyslipidemia]. / Rol del enterocito en la dislipidemia de la diabetes mellitus tipo 2.

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.

Rol del enterocito en la dislipidemia de la diabetes mellitus tipo 2 / Role of the enterocyte in type 2 diabetes mellitus associated dyslipidemia

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.

Serum hemorphin-7 levels are decreased in obesity.

OBJECTIVE: Hemorphin peptides exhibit biological activities that interfere with the endorphin system, the inflammatory response, and blood-pressure control. VV-hemorphin-7 and LVV-hemorphin-7 peptides exert a hypotensive effect, in particular, by inhibiting the renin-angiotensin system. Furthermore, levels of circulating hemorphin-7 peptides have been found to be decreased in diseases such as type 1 and type 2 diabetes. DESIGN AND METHODS: Because type 2 diabetes and obesity share common features, such as insulin resistance, microinflammation, high glomerular-filtration rate (GFR), and cardiovascular risk, we evaluated serum VV-hemorphin-7 like immunoreactivity (VVH7-i.r.) levels, using an enzyme-linked immunosorbent assay method, on a group of 54 obese subjects without diabetes or hypertension, compared with a group of 33 healthy normal-weight subjects. RESULTS: Circulating VVH7-i.r. levels were significantly decreased in the obese group compared with the control group (1.98 ± 0.19 vs. 4.86 ± 0.54 µmol/l, respectively, P < 0.01), and a significant negative correlation between VVH7-i.r. and diastolic blood pressure (DBP) was found in obese patients (r = -0.35, P = 0.011). There was no significant correlation between VVH7-i.r. level and insulin resistance, metabolic syndrome, or GFR. CONCLUSIONS: The decreased serum hemorphin-7 found in obese subjects, as in diabetes, may contribute to the development of hypertension and to the cardiovascular risk associated with these metabolic diseases.