Metabolic Changes Induced by Bariatric Surgery May be Mediated by PAI-1 and PCSK9 Crosstalk.

BACKGROUND: Adiposity favors several metabolic disorders with an exacerbated chronic pro-inflammatory status and tissue damage, with high levels of plasminogen activator inhibitor type 1 (PAI-1) and proprotein convertase subtilisin/kexin type 9 (PCSK9). OBJECTIVE: To demonstrate the influence of bariatric surgery on the crosstalk between PAI-1 and PCSK9 to regulate metabolic markers. METHODS: Observational and longitudinal study of 190 patients with obesity and obesity-related comorbidities who underwent bariatric surgery. We measured, before and after bariatric surgery, the anthropometric variables and we performed biochemical analysis by standard methods (glucose, insulin, triglycerides [TG], total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C] and TG/HDL-C ratio, PAI-1 and PCSK9 were measured by ELISA). RESULTS: PAI-1 levels decreased significantly after bariatric surgery, and were positively correlated with lipids, glucose, and TG, with significance on PCSK9 and TG/HDL-C alleviating the insulin resistance (IR) and inducing a state reversal of type 2 diabetes (T2D) with a significant decrease in body weight and BMI (p <0.0001). Multivariate regression analysis predicted a functional model in which PAI-1 acts as a regulator of PCSK9 (p <0.002), TG (p <0.05), and BMI; at the same time, PCSK9 modulates LDL-C HDL-C and PAI-1. CONCLUSIONS: After bariatric surgery, we found a positive association and crosstalk between PAI-1 and PCSK9, which modulates the delicate balance of cholesterol, favoring the decrease of circulating lipids, TG, and PAI-1, which influences the glucose levels with amelioration of IR and T2D, demonstrating the crosstalk between fibrinolysis and lipid metabolism, the two main factors involved in atherosclerosis and cardiovascular disease in human obesity.

Comparison between the Friedewald, Martin and Sampson Equations and LDL-C Quantification by Ultracentrifugation in a Mexican Population.

Low-density lipoprotein cholesterol (LDL-C), which makes up about 70% of the cholesterol in the blood, is critical in the formation of arteriosclerotic plaques, increasing the risk of heart disease. LDL-C levels are estimated using Friedewald, Martin and Sampson equations, though they have limitations with high triglycerides. Our aim is to compare the effectiveness of these equations versus the ultracentrifugation technique in individuals with and without dyslipidemia and identify precision. There were 113 participants, 59 healthy controls and 54 dyslipidemic patients. Samples were collected after fasting. LDL-C was estimated using the Friedewald, Martin and Sampson equations. The purified LDL-C, ultracentrifugated and dialysized control group without dyslipidemia vs. patients with coronary artery disease (CAD) showed differences in age, HDL-C, triglycerides and glucose non-HDL-C (p = 0.001 in all). There were correlations in CGWD between ultracentrifugation and Sampson R-squared (R2) = 0.791. In the dyslipidemia control group, ultracentrifugation and Friedewald R2 = 0.911. In patients with CAD, correlation between ultracentrifugation and Sampson R2 = 0.892; Bland-Altman confirmed agreement in controls without dyslipidemia. The Martin and Sampson equations are interchangeable with ultracentrifugation. Conclusion: The role of LDL analysis using precise techniques is necessary to obtain better control of disease outcomes after the use of precise therapies and suggests verifying its importance through clinical trials.

International practice patterns of dyslipidemia management in patients with chronic kidney disease under nephrology care: is it time to review guideline recommendations?

BACKGROUND: In contrast to guidelines related to lipid therapy in other areas, 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend conducting a lipid profile upon diagnosis of chronic kidney disease (CKD) and treating all patients older than 50 years without defining a target for lipid levels. We evaluated multinational practice patterns for lipid management in patients with advanced CKD under nephrology care. METHODS: We analyzed lipid-lowering therapy (LLT), LDL- cholesterol (LDL-C) levels, and nephrologist-specified LDL-C goal upper limits in adult patients with eGFR < 60 ml/min from nephrology clinics in Brazil, France, Germany, and the United States (2014-2019). Models were adjusted for CKD stage, country, cardiovascular risk indicators, sex, and age. RESULTS: LLT treatment differed significantly by country, from 51% in Germany to 61% in the US and France (p = 0.002) for statin monotherapy. For ezetimibe with or without statins, the prevalence was 0.3% in Brazil to 9% in France (< 0.001). Compared with patients not taking lipid-lowering therapy, LDL-C was lower among treated patients (p < 0.0001) and differed significantly by country (p < 0.0001). At the patient level, the LDL-C levels and statin prescription did not vary significantly by CKD stage (p = 0.09 LDL-C and p = 0.24 statin use). Between 7-23% of untreated patients in each country had LDL-C ≥ 160 mg/dL. Only 7-17% of nephrologists believed that LDL-C should be < 70 mg/dL. CONCLUSION: There is substantial variation in practice patterns regarding LLT across countries but not across CKD stages. Treated patients appear to benefit from LDL-C lowering, yet a significant proportion of hyperlipidemia patients under nephrologist care are not receiving treatment.

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.

Birth weight and its relationship with endothelial function and pattern of endothelium-derived microparticles during childhood: New insight about early vascular damage.

AIMS: To investigate whether a specific endothelium-derived microparticles (EMPs) phenotype could be associated with birth weight and microvascular endothelial function in children. MATERIALS AND METHODS: A total of 95 children aged 6-14 years were recruited. Anthropometric measurements, blood pressure measurement, microvascular endothelial function testing, and biochemical profile analyses were performed. Standardized flow cytometry methods were used to identify and quantify the circulating CD144+, CD31+/annexin V+, and CD62E+ EMPs. KEY FINDINGS: The circulating number of CD31+/annexin V+ EMPs and CD144+ EMP levels were correlated with birth weight, systolic blood pressure, microvascular endothelial function, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) level. In the multivariable logistic regression models, we identified strong evidence of a higher risk of microvascular endothelial dysfunction among children with low birth weight (LBW) and increased levels of both CD31+/annexin V+ EMPs and LDL-C; LBW and elevated LDL-C levels were independent predictors of high circulating numbers of CD31+/annexin V+ and CD144+ > 75th percentile EMPs. SIGNIFICANCE: Our data provide evidence that children with LBW values showed greater numbers of circulating CD31+/annexin V+ and CD144+ EMPs. In addition, LBW and high levels of CD31+/annexin V+ and LDL-C were significant risk factors for the presence of microvascular endothelial dysfunction.

Risk stratification and lipid evaluation in mexican patients, evidence of lipid and cardiovascular analysis in REMECAR. The mexican registry of cardiovascular diseases (REMECAR group).

Background and aims: Dyslipidaemia is a significant risk factor for cardiovascular disease in the Mexican population. This analysis aimed to describe the baseline LDL-c levels of patients presenting to cardiovascular clinics and evaluate the proportion who achieved their risk-based LDL-c goals as recommended by 2021 ESC prevention guidelines. Methods: The REMECAR registry is an observational study of patients attending a specialized cardiovascular clinic for their first visit. The cardiovascular risk was retrospectively determined using the 2021 ESC guideline stratification and the SCORE2 and SCORE-OP. Results: A total of 5443 patients were included in the analysis. Within this population, 55.96% presented as very high, 39.98% as high and 4.06% as moderate to low risk. 63% of the participants were not on any lipid-lowering treatment at entry, while 12.4% were receiving high-intensity statin therapy. Patients presenting with established atherosclerotic cardiovascular disease had a mean LDL-c of 90.9 ± 40.7 mg/dL. Of these, 14.1% were achieving LDL-c levels of 70-55 mg/dL and 19.3% were achieving LDL-c levels <55 mg/dL. In diabetic patients at very high risk, only 25.7% achieved their LDL-c goal. Finally, in patients without another risk factor and very high-risk evaluated by SCORE2 & SCORE-OP, only 14% of patients achieved their LDL-c goals. Conclusions: An important number of patients were not receiving any lipid-lowering therapy. Furthermore, in those who were, a significant portion did not achieve LDL-c recommended thresholds. Our results underline the urgent need to improve the prescription and optimization of lipid-lowering therapy as the current management appears to be insufficient for achieving optimal recommended goals. Identifying key barriers in lipid management is fundamental to establishing better strategies and health system policies to reduce cardiovascular risk.

Selective effect of laparoscopic Roux-en-Y gastric bypass on lipid metabolism. / Efecto selectivo de bypass gástrico laparoscópico en Y de Roux sobre el metabolismo lipídico.

INTRODUCTION: Bariatric surgery (BS) has shown to reduce cardiovascular morbidity and mortality in obesity. The BS has improved the dyslipidemia of the insulin resistant patient, our objective was to evaluate if there was a difference in the lipid profile between the laparoscopic roux-en-Y gastric bypass (RYGB) technique vs. the sleeve gastrectomy (SG) technique at 18 months of follow-up. METHODS: An observational, open, prospective study of morbidly obese patients who underwent bariatric surgery at 18-month follow-up. Anthropometric analysis, body composition, energy expenditure at rest, glucose, insulin, HbA1c, LDL, HDL, TG and CT were performed. RESULTS: Absence baseline differences were found in the proportion of patients with hypertension, diabetes, steatosis, and sex between the RYGB vs SG groups. A reduction of TG was observed at 6 months in favor of RYGB vs SG: 108.60±34.86 vs. 124.59±44.58, P = 0.044), however, a decrease in both LDL levels was found at 12 and 18 months in favor of the RYGB vs. SG group: 96.23±24.33 vs. 107.83±28.88, P = 0.025; 90.98±20.62 vs 106.22±31.48, P = 0.003; the decrease in CT was observed only at 18 months in favor of the RYGB vs. SG group: 171.39±25.058 vs. 186.89±31.81, P = 0.005. CONCLUSIóN: RYBG has shown to be more effective in reducing LDL and CT levels compared to SG, which provides an additional benefit of RYGB in relation to the lipid profile of the patient.

Effect of Hydroxychloroquine on Lipid Levels: A Systematic Review and Metaanalysis.

BACKGROUND: It has been suggested that hydroxychloroquine may have positive effects on LDL-C, HDL-C, and triglyceride levels; however, the hypolipidemic activities of this drug are still uncertain. OBJECTIVE: The aim of this meta-analysis of randomized controlled trials was to explore the effect of hydroxychloroquine on circulating lipid concentrations. METHODS: Randomized controlled trials examining the impact of hydroxychloroquine on lipid parameters were searched in PubMed, Web of Science, Scopus, and Google Scholar databases. Meta-analysis was performed using a random-effects model and sensitivity analysis through the leave one-out method. RESULTS: Meta-analysis showed that patients receiving hydroxychloroquine therapy significantly decreased total cholesterol (WMD: 0.18 mmol/L, 95% CI: -0.28, -0.08, I2 = 6%, p = 0.0004), LDL-C (WMD: -0.21 mmol/L, 95% CI: -0.36, -0.06, I2 = 75%, p = 0.006), triglycerides (WMD: -0.09 mmol/L, 95% CI: -0.15, -0.04, I2 = 22%, p = 0.001), and non-HDL-C (WMD: -0.28 mmol/L, 95% CI: -0.45, -0.12, I2 = 0%, p = 0.0009), and increased HDL-C concentrations (WMD: 0.03 mmol/L, 95% CI: 0.00, 0.06, I2 = 0%, p = 0.03). CONCLUSION: Our results suggest that hydroxychloroquine improves lipid parameters by reducing total cholesterol, LDL-C, triglycerides, non-HDL-C, and increasing HDL-C levels.

The potential role of sesquiterpene lactones isolated from medicinal plants in the treatment of the metabolic syndrome - A review.

Metabolic syndrome comprises a cluster of metabolic disorders related to the development of cardiovascular disease and type 2 diabetes mellitus. In latter years, plant secondary metabolites have become of special interest because of their potential role in preventing and managing metabolic syndrome. Sesquiterpene lactones constitute a large and diverse group of biologically active compounds widely distributed in several medicinal plants used for the treatment of metabolic disorders. The structural diversity and the broad spectrum of biological activities of these compounds drew significant interests in the pharmacological applications. This review describes selected sesquiterpene lactones that have been experimentally validated for their biological activities related to risk factors of metabolic syndrome, together with their mechanisms of action. The potential beneficial effects of sesquiterpene lactones discussed in this review demonstrate that these substances represent remarkable compounds with a diversity of molecular structure and high biological activity, providing new insights into the possible role in metabolic syndrome management.

Changes in Physical Activity and Sedentary Patterns on Cardiometabolic Outcomes in the Transition to Adolescence: International Children's Accelerometry Database 2.0.

OBJECTIVE: To examine the associations of changes in physical activity and sedentary patterns with changes in cardiometabolic outcomes from childhood to adolescence. STUDY DESIGN: Youth from the International Children's Accelerometry Database (n = 1088; 55% girls), aged 8-13 years and followed for ∼4 years, were used in this analysis. Hip-mounted accelerometers were used and all physical activity intensities were expressed as the % of total wear-time. Sedentary time was separated into time spent in bouts <10 minutes and ≥10 minutes. A composite z score for cardiometabolic risk (CMR score) was computed by summing the standardized values for systolic and diastolic blood pressure, triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and the inverse high-density lipoprotein cholesterol. Multivariate analyses were performed using adjusted linear regression models. RESULTS: Increase in sedentary time was unfavorably associated with changes in CMR score (ß = 0.021; CI 0.004-0.037), TG (ß = 0.003; CI 0.001-0.005), and diastolic blood pressure (ß = 0.068; CI 0.009-0.128). Decrease in moderate-to-vigorous physical activity was unfavorably associated with changes in LDL-c (ß = -0.009; CI -0.017 to -0.001) and TG (ß = -0.007; CI -0.013 to -0.001). Increase in ≥10 minutes sedentary time was unfavorably associated with changes in CMR score (ß = 0.017; CI 0.004-0.030), LDL-c (ß = 0.003; CI 0.000-0.005), and TG (ß = 0.003; CI 0.000-0.004). Decrease in light-intensity physical activity was unfavorably associated with changes in CMR score (ß = -0.020; CI = -0.040 to 0.000). CONCLUSIONS: More physical activity and less prolonged sedentary time are beneficial for cardiometabolic health in youth transitioning to adolescence.

A Narrative Review and Expert Panel Recommendations on Dyslipidaemia Management After Acute Coronary Syndrome in Countries Outside Western Europe and North America.

Patients who have experienced an acute coronary syndrome (ACS) are at very high risk of recurrent atherosclerotic cardiovascular disease (CVD) events. Dyslipidaemia, a major risk factor for CVD, is poorly controlled post ACS in countries outside Western Europe and North America, despite the availability of effective lipid-modifying therapies (LMTs) and guidelines governing their use. Recent guideline updates recommend that low-density lipoprotein cholesterol (LDL-C), the primary target for dyslipidaemia therapy, be reduced by ≥ 50% and to < 1.4 mmol/L (55 mg/dL) in patients at very high risk of CVD, including those with ACS. The high prevalence of CVD risk factors in some regions outside Western Europe and North America confers a higher risk of CVD on patients in these countries. ACS onset is often earlier in these patients, and they may be more challenging to treat. Other barriers to effective dyslipidaemia control include low awareness of the value of intensive lipid lowering in patients with ACS, physician non-adherence to guideline recommendations, and lack of efficacy of currently used LMTs. Lack of appropriate pathways to guide follow-up of patients with ACS post discharge and poor access to intensive medications are important factors limiting dyslipidaemia therapy in many countries. Opportunities exist to improve attainment of LDL-C targets by the use of country-specific treatment algorithms to promote adherence to guideline recommendations, medical education and greater prioritisation by healthcare systems of dyslipidaemia management in very high risk patients.

Impact of the 2019 European Guidelines on Diabetes in Clinical Practice: Real and Simulated Analyses of Lipid Goals.

BACKGROUND: Recent European guidelines on diabetes, prediabetes, and cardiovascular disease developed for the European Society of Cardiology (ESC) in collaboration with the European Association for the Study of Diabetes (EASD) significantly changed some concepts on risk stratification, lipid goals, and recommendations for the use of lipid-lowering drugs. The objectives of this work were to describe the lipid-lowering treatment prescribed for patients with diabetes and to determine the percentage of patients that achieved the lipid goals recommended by the 2019 ESC/EASD Guidelines on Diabetes in real and simulated scenarios. METHODS: A multicenter, cross-sectional study was performed. Subjects >18 years with type 2 diabetes were included. The recommendations of the 2019 ESC/EASD Guidelines were followed. The real and simulated (ideal setting using adequate doses of statins ± ezetimibe) scenarios were analyzed. RESULTS: Overall, 528 patients were included. In total, 62.5% of patients received statins (17.1% high intensity). Most patients were stratified as "very high risk" (54.2%) or "high risk" (43.4%). Only 13.3% achieved the double lipid goal (LDL-C and non-HDL-C goals according to the risk categories). In the simulation analysis, the proportion of subjects that did not reach the therapeutic objective decreased in all risk strata, although a considerable proportion of subjects persisted outside the target. CONCLUSION: The difficulty of achieving lipid goals in diabetic patients was considerable when applying the new guidelines. The situation would improve if we optimized treatment, but the prescription of new lipid-lowering drugs could be limited by their high cost.

Performance of LDL-C calculated with Martin's formula compared to the Friedewald equation in familial combined hyperlipidemia.

BACKGROUND AND AIMS: A novel method to estimate low density lipoprotein cholesterol (LDL-C) has been proposed by Martin et al. This may permit a more accurate estimation of cardiovascular risk, however, external validation is needed. Here, the performance of LDL-C using this new method (LDL-N) is compared with LDL-C estimated with Friedewald equation (LDL-F) in familial combined hyperlipidemia (FCHL), a common primary dyslipidemia in which apolipoprotein B containing particle composition is abnormal and interferes with LDL-C estimation. METHODS: A total of 410 FCHL subjects were included. LDL-C was estimated with both the Friedewald equation (LDL-F) and the novel formula (LDL-N). Apolipoprotein B levels and non- HDL-C were recorded. The correlation and concordance between LDL-F and LDL-N and both Apolipoprotein B and non-HDL-C levels were calculated. Analysis stratifying for triglyceride tertiles and FCHL lipid phenotypes was also carried out. RESULTS: The correlations between LDL-N and Apo B and non-HDL-C were ρ = 0.777 (95%CI 0.718-0.825) and ρ = 0.735 (95%CI 0.648-0.816), respectively. The corresponding correlations for LDL-F were ρ = 0.551(95%CI 0.454-0.637) and ρ = 0.394 (95%CI 0.253-0.537), respectively. In mixed dyslipidemia or isolated hypertriglyceridemia, these correlations were significantly better using LDL-N. With respect to concordance, LDL-N performed significantly better than LDL-F when considering apoB <90 mg/dL (κLDL-N = 0.495 vs. κLDL-F = 0.165) and non-HDL-C <130 (κLDL-N = 0.724 vs. κLDL-F = 0.253). CONCLUSIONS: In FCHL, LDL-C estimation using Martin's formula showed greater correlation and concordance with non-HDL-C and Apo B compared with the Friedewald equation.

El legado científico y el papel actual de la atorvastatina en el manejo del riesgo de enfermedad cardiovascular aterosclerótica / The scientific legacy and the current role of atorvastatin in the management of risk of atherosclerotic cardiovascular disease

Resumen Durante mucho tiempo, los esfuerzos para disminuir el riesgo cardiovascular en los adultos se centraron en el intento de reducir tanto como fuese posible las concentraciones plasmáticas de colesterol 6, LDL (c-LDL). Hasta muy recientemente se concluyó que en los estudios clínicos de medicamentos con acción en los lípidos circulantes no existía evidencia directa que permitiera determinar cuál es la mejor meta de c-LDL para la disminución del riesgo cardiovascular y tampoco se concedió importancia suficiente a los eventos adversos de las diferentes combinaciones farmacológicas recomendadas para el logro de las concentraciones de c-LDL más bajas posibles. El análisis exhaustivo realizado para la actualización del Programa para el Control del Colesterol en el Adulto de Estados Unidos (NCEP-ATP-III), que comprendió una gran cantidad de estudios controlados con distribución al azar, permitió en 2013 la postulación de un nuevo paradigma de tratamiento que abandona el concepto de metas determinadas de c-LDL y que insiste en la importancia de las modificaciones favorables en el estilo de vida, además de que recomienda la administración preferencial de estatinas, en tipos y dosis fijas, debido a que un importante volumen de evidencia ha demostrado que estos agentes atenúan la progresión de la aterosclerosis coronaria y promueven la regresión de ésta, con lo que disminuyen significativamente la morbilidad y mortalidad cardiovasculares en la prevención primaria y en la secundaria. En este nuevo paradigma terapéutico fue posible también la identificación de los grupos de pacientes que pueden beneficiarse con la administración de estatinas. En consensos y guías más recientes, algunas asociaciones sostienen la necesidad de lograr ciertas metas de cLDL de acuerdo con el riesgo, pero mantienen a las estatinas como el pilar del tratamiento, solas o en combinación con ezetimiba o con antagonistas de la convertasa de proproteínas subtilisina/kexina de tipo 9 (PCSK9: proprotein convertase subtilisin/kexin type 9). En este artículo se revisa la evidencia clínica relativa a la administración de atorvastatina, que en gran medida permitió el desarrollo del nuevo paradigma de manejo del riesgo cardiovascular.

Abstract For a long time, efforts to reduce cardiovascular risk in adults focused on the attempt to reduce plasmatic LDL cholesterol (LDLc) levels as much as possible. Until very recently, it was concluded that in clinical studies of drugs with action on circulating lipids, there was no direct evidence to determine the best LDLc target for cardiovascular risk reduction, and that adverse events, or the almost absent demonstration of impact on hard outcomes of the different pharmacological combinations recommended for the achievement of the lowest possible LDLc concentrations, were not considered. The comprehensive analysis for the update of NCEP-ATP-III (National Cholesterol Education Program, Adult Treatment Panel III), which included a large number of controlled and randomized trials, allowed in 2013 the postulation of a new treatment paradigm, which leaves the concept of specific goals of LDLc and postulates the importance of favorable lifestyle modifications and which commends the pre-ferential use of statins, fixed doses and type, because a large volume of evidence has shown that these agents attenuate the progression of coronary atherosclerosis and promote the regression of this, which significantly decrease cardiovascular morbidity and mortality in both primary and secondary prevention. In this new therapeutic paradigm, it was also possible to identify the groups of patients that can benefit from the use of statins. In more recent consensuses and guidelines, some associations support the need to achieve risk-adjusted LDLc, but keep statins as the mainstay of treatment, alone or in combination with ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCKS-9) antagonists. This article reviews the clinical evidence regarding the use of atorvastatin, which allowed the development of the new cardiovascular risk management paradigm.

Is there an Association Between Periodontitis and Atherosclerosis in Adults? A Systematic Review.

BACKGROUND: Atherosclerosis is a multifactorial inflammatory disease of the cardiovascular system. It has been suggested that periodontitis, an infectious disease of oral cavity caused by gramnegative anaerobic bacteria, could be linked to atherosclerosis. OBJECTIVE: The objective of this systematic review was to assess the evidence between the association of periodontitis and atherosclerosis in adults. METHODS: A systematic literature search was conducted in 7 databases up to January 2017, according to the Preferential Reports for Systematic Review and Meta-analysis (PRISMA) guidelines. Studies in humans with atherosclerosis were considered eligible when considering a group exposed to periodontitis and a control group (absence of periodontitis), in which the primary outcome was the association between the 2 diseases (atherosclerosis and periodontitis). The synthesis of the qualitative studies included was evaluated using previously validated checklist for assessing the risk of bias. RESULTS: Among the 2138 studies found, 4 observational studies met the eligibility criteria and were included in the qualitative synthesis. All articles were considered adequate, presenting consistent and valid information. The results of the selected studies show the expected effects, being considered as low risk of bias. CONCLUSION: The available evidence indicates an association between the 2 diseases, with elevated levels of inflammatory markers, mainly C-reactive protein and interleukin 6.

Obesity anthropometric indicators associated with cardiometabolic risk in Portuguese children and adolescents.

The purpose of this study was to determine the association between cardiometabolic risk with body mass index and skinfold independently or in combination in youth. This cross-sectional study comprised a convenience sample of 450 children and adolescents (255 girls), aged 10 to 18 years old. Indicators of body composition were measured, and hemodynamic assessment completed. The association between body mass index and/or sum of skinfolds and cardiometabolic risk (z score of the sum of triglycerides/high density lipoprotein cholesterol, waist circumference, and mean blood pressure), was calculated using Generalized Linear Models Regression. The results showed that youngsters classified as overweight or obese with the highest skinfold measurements had the strongest association with cardiometabolic risk (< beta >: 2.60; IC 95%: 2.25-3.0) when compared with those exhibiting normal skinfold thickness (< beta >: 1.78; IC 95%: 1.30-2.20). Body mass index was most strongly associated with cardiometabolic risk (< beta >: 1.78; IC 95%: 1.3-2.2), in comparison to skinfold thickness, which was associated to a lesser extent (< beta >: 0.41; IC 95%: 0.34-0.49). Results of this cross-sectional study indicate that body mass index is more strongly associated with cardiometabolic risk than skinfold thickness. However when these two measures of overweight/obesity are combined, prediction of cardiometabolic risk is further improved. It is therefore important that public health professionals consider both body mass index and sum of skinfolds to better predict cardiometabolic risk in overweight and obese youth. Implications for future research include the use of longitudinal designs and inclusion of children from other racial/ethnic groups.

Inhibición de PCSK9: una nueva alternativa para reducir el colesterol y prevenir la enfermedad cardiovascular aterosclerosa / Inhibition of PCSK9: a new alternative for cholesterol reduction and prevention of atherosclerotic cardiovascular disease

Resumen La enfermedad cardiovascular aterosclerosa ocupa el primer lugar mundial en morbilidad y mortalidad. El principal factor de riesgo de enfermedad es el colesterol unido a lipoproteínas de baja densidad (C-LDL). El tratamiento farmacológico de elección para reducir el C-LDL son las estatinas; sin embargo, han sido insuficientes para eliminar el riesgo cardiovascular, especialmente en pacientes con formas primarias de hipercolesterolemia relacionadas con mutaciones genéticas, o intolerantes a estatinas. Es de gran importancia el desarrollo de nuevos fármacos para abatir el riesgo que persiste a pesar de la administración de estatinas. La proconvertasa subtilisina-kexina 9 (PCSK9) es un regulador primordial de la cantidad de receptores de LDL, ya que su función es dirigir dichos receptores a su destrucción lisosomal. El advenimiento de anticuerpos monoclonales para bloquear la PCSK9 ha permitido mejorar la cantidad y eficiencia de los receptores de LDL, de esto resulta la disminución notable del colesterol circulante. Hasta el momento, la eficacia e inocuidad de estos anticuerpos resultan aceptables, y los datos preliminares en cuanto a su efecto en la reducción de la morbilidad y mortalidad cardiovasculares son alentadores.

Abstract Atherosclerotic cardiovascular disease represents the leading cause of morbidity and mortality in most countries. The main risk factor for developing this disease is low density lipoprotein cholesterol (LDL-C). The pharmacological treatment of choice for reducing LDL-C is statins; however, in spite of the widespread use of statins, these drugs have been insufficient to eliminate cardiovascular risk. This residual risk is most relevant in patients with primary forms of hypercholes-terolemia associated with genetic mutations, or in those who are intolerant to statins. The development of new drugs to reduce residual cardiovascular risk is of vital importance. Proprotein convertase subtilisin-kexin 9 (PCSK9) is an important regulator of the amount of LDL receptors since its function is to direct these receptors to their lysosomal destruction. The development of monoclonal antibodies to block extracellular PCSK9 has allowed us to improve the quantity and efficiency of LDL receptors, resulting in a significant decrease in plasma cholesterol. Efficacy and safety of these antibodies is currently considered acceptable and preliminary data are encouraging but still insufficient to assess the favorable impact of these antibodies in reducing cardiovascular morbidity and mortality.

ST-elevation myocardial infarction risk in the very elderly.

BACKGROUND: Despite the high incidence and mortality of ST-segment elevation myocardial infarction (STEMI) among the very elderly, risk markers for this condition remain poorly defined. This study was designed to identify independent markers of STEMI among individuals carefully selected for being healthy or manifesting STEMI in < 24 h. METHODS: We enrolled participants aged 80 years or older of whom 50 were STEMI patients and 207 had never manifested cardiovascular diseases. Blood tests, medical and psychological evaluations were obtained at study admission. Odds Ratio (OR) and attributed risk (AR) were obtained by multivariate regression models using STEMI as dependent variable. RESULTS: Low glomerular filtration rate (GFR) [OR:4.41 (1.78-10.95); p = 0.001], reduced levels of HDL-C [OR:10.70 (3.88-29.46); p = 0.001], male gender [OR:12.08 (5.82-25.08); p = 0.001], moderate to severe depressive symptoms [OR:10.00 (2.82-35.50); p = 0.001], prior smoking [OR:2.00 (1.05-3.80); p = 0.034] and current smoking [OR:6.58 (1.99-21.70); p = 0.002] were significantly associated with STEMI. No association was found between STEMI and age, diabetes, hypertension, mild depressive symptoms, triglyceride or LDL-C. CONCLUSIONS: This is the first case-control study carried out with very elderlies to assess STEMI risk. Our findings indicate that reduced HDL-C, GFR, male gender, smoking habits and moderate to severe depressive symptoms are markers of STEMI in this age group. GENERAL SIGNIFICANCE: In Individuals aged 80 or more years, a greater attention must be paid to low HDL-C and GFR at the expense of conventional STEMI risk factors for younger adults such as diabetes mellitus, hypertension and high LDL-C or triglyceride.