Prevención cardiovascular en la diabetes mellitus. ¿Es adecuado hablar de riesgo moderado o intermedio? / Cardiovascular prevention in diabetes mellitus. Is it appropriate to speak of moderate or intermediate risk?

La diabetes, especialmente la tipo 2, está considerada como una situación de riesgo de enfermedad cardiovascular aterosclerosa (ECVA). Los sujetos con diabetes tipo 2 tienen una mortalidad por ECVA 3 veces superior a la de la población general, atribuida a la hiperglucemia y a la frecuente asociación de otros factores de riesgo cardiovascular, como la dislipidemia aterogénica. Numerosas sociedades científicas han establecido una clasificación de riesgo de ECVA en la diabetes basada en 3 grados (moderado, alto y muy alto). Los objetivos del control de la dislipidemia están claramente definidos y aceptados, y varían dependiendo del riesgo cardiovascular previamente establecido. En el riesgo moderado o intermedio, las guías proponen una intervención menos intensiva, manteniendo cifras de c-LDL<100mg/dL y de c-no-HDL<130mg/dL, y esperar 10 años hasta alcanzar la categoría de alto riesgo para iniciar un tratamiento más intensivo. Sin embargo, durante la década de seguimiento preconizada en las guías, el depósito de colesterol en la pared arterial va aumentando, facilitando el desarrollo de una placa de ateroma inestable e inflamatoria, y el desarrollo de ECVA. Alternativamente, se podría considerar desde el inicio que la diabetes conlleva una situación de alto riesgo y el objetivo debería ser c-LDL<70mg/dL. Además, mantener cifras de c-LDL<70mg/dL contribuye a reducir y estabilizar la placa de ateroma, evitando o disminuyendo episodios de mortalidad por ECVA durante esos años de evolución de la diabetes. ¿Deberíamos mantener los objetivos propuestos en los sujetos con diabetes y riesgo moderado durante una década hasta alcanzar la fase de alto riesgo cardiovascular o, por el contrario, adoptar desde el inicio una postura más intensiva buscando reducir el riesgo cardiovascular en la mayoría de los pacientes con diabetes? ¿Es mejor esperar o prevenir con medidas terapéuticas efectivas desde el primer momento? (AU)

Diabetes, especially type 2, is considered a risk situation for atherosclerotic cardiovascular disease (ASCVD). Subjects with diabetes type 2 have a mortality rate due to ASCVD 3 times higher than that found in the general population, attributed to hyperglycemia and the frequent association of other cardiovascular risk factors, such as atherogenic dyslipidemia. Numerous scientific societies have established a risk classification for ASCVD in diabetes based on 3 degrees (moderate, high and very high). The objectives of dyslipidemia control are clearly defined and accepted, and vary depending on the previously established cardiovascular risk. In moderate or intermediate risk, the guidelines propose a less intensive intervention, maintaining LDL-C levels<100mg/dL and NO-HDL-C levels<130mg/dL, and waiting 10 years until reaching the high-risk category to initiate more intensive treatment. However, during the decade of follow-up recommended in the guidelines, cholesterol deposition in the arterial wall increases, facilitating the development of an unstable and inflammatory atheromatous plaque, and the development of ASCVD. Alternatively, diabetes could be considered from the outset to be a high-risk situation and the goal should be LDL-C<70mg/dL. Furthermore, maintaining LDL-C levels<70mg/dL contributes to reducing and stabilizing atheromatous plaque, avoiding or reducing mortality episodes due to ASCVD during those years of diabetes evolution. Should we maintain the proposed objectives in subjects with diabetes and moderate risk for a decade until reaching the high cardiovascular risk phase or, on the contrary, should we adopt a more intensive stance from the beginning seeking to reduce cardiovascular risk in the majority of patients with diabetes? Is it better to wait or prevent with effective therapeutic measures from the first moment? (AU)

Association of carotid atheroma plaque with IL-18 levels and with polymorphisms in the IL-18 receptor gene in a Mediterranean population. / Asociación de la placa de ateroma carotídea con los niveles plasmáticos de IL-18 y con polimorfismos en el gen del receptor de la IL-18 en la población mediterránea.

BACKGROUND: Atherosclerosis is an inflammatory disease. Interleukin 18 (IL-18) is an inflammatory molecule that has been linked to the development of atherosclerosis and cardiovascular disease. OBJECTIVE: To evaluate the possible relationship between plasma levels of IL-18 and the presence of atherosclerosis evaluated at the carotid level, as well as to analyze the possible modulation by different polymorphisms in a Mediterranean population. MATERIAL AND METHODS: Seven hundred and forty-six individuals from the metropolitan area of Valencia were included, recruited over a period of 2 years. Hydrocarbon and lipid metabolism parameters were determined using standard methodology and IL-18 using ELISA. In addition, carotid ultrasound was performed and the genotype of four SNPs related to the IL-18 signaling pathway was analyzed. RESULTS: Patients with higher plasma levels of IL-18 had other associated cardiovascular risk factors. Elevated IL-18 levels were significantly associated with higher carotid IMT and the presence of atheromatous plaques. The genotype with the A allele of the SNP rs2287037 was associated with a higher prevalence of carotid atheromatous plaque. On the contrary, the genotype with the C allele of the SNP rs2293224 was associated with a lower prevalence of atheromatous plaque. CONCLUSIONS: High levels of IL-18 were significantly associated with a higher carotid IMT and the presence of atheromatous plaques, which appear to be influenced by genetic factors, as evidenced by associations between SNPs in the IL-18 receptor gene and the presence of atheroma plaque.

Cardiovascular prevention in diabetes mellitus. Is it appropriate to speak of moderate or intermediate risk? / Prevención cardiovascular en la diabetes mellitus. ¿Es adecuado hablar de riesgo moderado o intermedio?

Diabetes, especially type 2, is considered a risk situation for atherosclerotic cardiovascular disease (ASCVD). Subjects with diabetes type 2 have a mortality rate due to ASCVD 3 times higher than that found in the general population, attributed to hyperglycemia and the frequent association of other cardiovascular risk factors, such as atherogenic dyslipidemia. Numerous scientific societies have established a risk classification for ASCVD in diabetes based on 3 degrees (moderate, high and very high). The objectives of dyslipidemia control are clearly defined and accepted, and vary depending on the previously established cardiovascular risk. In moderate or intermediate risk, the guidelines propose a less intensive intervention, maintaining LDL-C levels<100mg/dL and NO-HDL-C levels<130mg/dL, and waiting 10 years until reaching the high-risk category to initiate more intensive treatment. However, during the decade of follow-up recommended in the guidelines, cholesterol deposition in the arterial wall increases, facilitating the development of an unstable and inflammatory atheromatous plaque, and the development of ASCVD. Alternatively, diabetes could be considered from the outset to be a high-risk situation and the goal should be LDL-C<70mg/dL. Furthermore, maintaining LDL-C levels<70mg/dL contributes to reducing and stabilizing atheromatous plaque, avoiding or reducing mortality episodes due to ASCVD during those years of diabetes evolution. Should we maintain the proposed objectives in subjects with diabetes and moderate risk for a decade until reaching the high cardiovascular risk phase or, on the contrary, should we adopt a more intensive stance from the beginning seeking to reduce cardiovascular risk in the majority of patients with diabetes? Is it better to wait or prevent with effective therapeutic measures from the first moment?

Atherogenic dyslipidaemia in type 2 diabetes mellitus: The PREDISAT study.

Extremely variable prevalence rates of atherogenic dyslipidaemia (AD) in type 2 diabetes (T2DM) subjects have been reported. The primary aim was to assess AD prevalence in Spanish T2DM subjects. Secondary objectives were to evaluate the differential clinical characteristics between T2DM subjects with and without AD, to describe lipid profile evolution and use of lipid-lowering treatment in clinical practice by the Spanish Lipid Units. Data was obtained from the National Registry of Dyslipidaemias of the Spanish Atherosclerosis Society, from a multicentric sub-study focused on AD prevalence in T2DM subjects (PREDISAT study). The inclusion criteria were subjects diagnosed of T2DM with age ≥18 years old. A total of 385 T2DM subjects with a mean age of 61 years and 246 (64%) men were included. The mean follow-up was 22 ± 7.4 months. At baseline, 41.3% of the T2DM subjects presented AD, this percentage decreasing to 34.8% with therapeutic intervention. AD prevalence varied in different age groups and appeared to be more prevalent in younger T2DM subjects. Those with AD had a more atherogenic lipid profile at baseline, with higher total cholesterol, triglyceride and non-(high-density lipoprotein) HDL cholesterol levels at baseline, together with lower HDL cholesterol concentrations, without achieving lipid subfraction goals during follow-up. Although almost 90% of the AD subjects were under lipid-lowering treatment, most were receiving only one drug, being statins the most used treatmentA high AD prevalence in T2DM subjects was observed, being age a determinant factor, with a modest decline during follow-up. Although almost 90% of the AD subjects were under lipid-lowering drugs, most were only receiving monotherapy with statins.

Beneficial effects of PCSK9 inhibition with alirocumab in familial hypercholesterolemia involve modulation of new immune players.

Familial hypercholesterolemia (FH) is associated with low-grade systemic inflammation, a key driver of premature atherosclerosis. We investigated the effects of inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) function on inflammatory state, endothelial dysfunction and cardiovascular outcomes in patients with FH. Fourteen patients with FH were evaluated before and 8 weeks after administration of a PCSK9 blocking monoclonal antibody (alirocumab, 150 mg/subcutaneous/14 days). In vivo and ex vivo analysis revealed that alirocumab blunted the attachment of leukocytes to TNFα-stimulated human umbilical arterial endothelial cells (HUAEC) and suppressed the activation of platelets and most leukocyte subsets, which was accompanied by the diminished expression of CX3CR1, CXCR6 and CCR2 on several leukocyte subpopulations. By contrast, T-regulatory cell activation was enhanced by alirocumab treatment, which also elevated anti-inflammatory IL-10 plasma levels and lowered circulating pro-inflammatory cytokines. Plasma levels of IFNγ positively correlated with levels of total and LDL-cholesterol, whereas circulating IL-10 levels negatively correlated with these key lipid parameters. In vitro analysis revealed that TNFα stimulation of HUAEC increased the expression of PCSK9, whereas endothelial PCSK9 silencing reduced TNFα-induced mononuclear cell adhesion mediated by Nox5 up-regulation and p38-MAPK/NFκB activation, concomitant with reduced SREBP2 expression. PCSK9 silencing also decreased endothelial CX3CL1 and CXCL16 expression and chemokine generation. In conclusion, PCSK9 inhibition impairs systemic inflammation and endothelial dysfunction by constraining leukocyte-endothelium interactions. PCSK9 blockade may constitute a new therapeutic approach to control the inflammatory state associated with FH, preventing further cardiovascular events in this cardiometabolic disorder.

Lipid metabolism and classification of hyperlipaemias. / Metabolismo lipídico y clasificación de las hiperlipemias.

This chapter summarises, and updates, lipid metabolism. Both pathways, exogenous metabolisms route via the chylomicrons, and the endogenous pathway of very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). The reverse cholesterol metabolism will also be mentioned. It also includes the current classification of hyperlipidaemias or hyperlipoproteinaemias, with a reminder of the phenotype classification, and further developments of the aetiological classification. Both parts have updated references, with which knowledge of this vast subject can be expanded.

Oral Unsaturated Fat Load Impairs Postprandial Systemic Inflammation in Primary Hypercholesterolemia Patients.

Context: Primary hypercholesterolemia (PH) is a lipid disorder characterized by elevated levels of cholesterol and low-density lipoprotein (LDL). Low-grade systemic inflammation is associated with PH, which might explain the higher incidence of cardiovascular diseases in this setting. Objective: To evaluate the effect of an oral unsaturated fat load (OUFL) on different immune parameters and functional consequences in patients with PH in postprandial state. Design: A commercial liquid preparation of long-chain triglycerides (Supracal®; ω6/ω3 ratio >20/1, OUFL) was administered to 20 patients and 10 age-matched controls. Whole blood was collected before (fasting state) and 4 h after administration (postprandial state). Flow cytometry was employed to determine platelet and leukocyte activation, and the levels of circulating platelet-leukocyte aggregates. Soluble markers were determined by ELISA, and the parallel-plate flow chamber was employed to study leukocyte adhesion to the dysfunctional arterial endothelium. Results: The PH group had a lower percentage of activated platelets and circulating type 1 monocytes, and blunted neutrophil activation after the OUFL, accompanied by a significant increase in the percentage of regulatory T lymphocytes. In this group, the OUFL led to a significant impairment of leukocyte adhesion to the dysfunctional [tumor necrosis factor α (TNFα)-stimulated] endothelium and reduced the plasma levels of soluble P-selectin, platelet factor-4 (PF-4)/CXCL4, CXCL8, CCL2, CCL5, and TNFα. Conclusion: The OUFL has a beneficial impact on the pro-thrombotic and pro-inflammatory state of PH patients and might be a promising macronutrient approach to dampen the systemic inflammation associated with PH and the development of further cardiovascular events.

Peripheral blood levels of CXCL10 are a useful marker for diabetic polyneuropathy in subjects with type 2 diabetes.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus associated with high morbidity and mortality. Major risk factors for DPN include metabolic changes, duration of diabetes, nerve ischaemia and derangements in regeneration and nerve repair programmes. Chemokines have been previously implicated in the pathogenesis of various neuropathies and neuropathic pain processes. The aim of this pilot study was to evaluate the association between the plasma levels of chemokines (CXCL9, CXCL10 and CXCL11) in the presence of DPN in a cohort of type 2 diabetes (T2D) patients. MATERIALS AND METHODS: We studied 73 patients with T2D: 36 with DPN and 37 without DPN. DPN was established through the Semmes-Weinstein test (SW). Plasma levels of circulating chemokines CXCL9, CXCL10 and CXCL11 were determined using DuoSet ELISA kits (Abingdon, UK). RESULTS: We found that levels of CXCL10 were significantly higher in patients with DPN than amongst patients without DPN (57.6 ± 38.3 vs 38.1 ± 33.4 pg/mL, respectively; P = .034). Serum levels of chemokine CXCL9 were also higher amongst patients with DPN but did not reach a statistical significance (188.1 ± 72.7 and 150.4 ± 83.6 pg/mL, respectively, P = .06). CONCLUSIONS: Increased circulating levels of CXCL10 were associated with DPN in T2D patients, suggesting a role of this chemokine in the DPN. Determination of CXCL10 levels could be used as a marker for the early detection and implementation of therapeutic strategies in order to reverse and prevent the DPN.

Postprandial triglyceridaemia is modulated by insulin resistance but not by grade of obesity in abdominal and morbid obese subjects.

BACKGROUND: Obesity is associated with high cardiovascular risk. Postprandial lipidaemia has been associated with cardiovascular disease risk. Our aim was to identify whether anthropometric parameters, insulin resistance (IR) and/or fasting plasma triglycerides may determine postprandial changes in lipoprotein concentrations in abdominal and morbid obese subjects. METHODS: We have studied 20 non-diabetic, normolipidaemic subjects with abdominal obesity, 20 morbid obese subjects and 20 healthy individuals, that have similar age and gender. In all of them a standardised oral fat load test (OFLT) with unsaturated fat was performed. RESULTS: During the OFLT, the postprandial triglycerides response was significantly higher in subjects with abdominal obesity compared with morbid obese subjects (4 hours triglycerides pick value and AUC of triglycerides). Both obese groups showed significantly higher postprandial triglycerides response compared with healthy subjects. Dividing the obesity group according to the presence of IR, we found that IR was an important factor related with postprandial lipaemia but not BMI or waist circumference. In addition, postprandial glycaemia and insulinaemia significantly decreased in all studied subjects, being the highest decrease in morbid obese subjects and in subjects with IR. Postprandial triglyceridaemia significantly correlated with IR parameters and not with anthropometric parameters in AO and MO subjects. CONCLUSION: In subjects with AO and MO, postprandial triglycerides values are higher than healthy individuals and independently predicted by fasting IR parameters. Furthermore, unsaturated fat improved IR state.

Triglicéridos, colesterol HDL y dislipidemia aterogénica en la guía europea para el control de las dislipidemias 2019 / Triglycerides, HDL cholesterol and atherogenic dyslipidaemia in the 2019 European guidelines for the management of dyslipidaemias

En general, las guías de práctica clínica tanto europeas con americanas han abordado el control de la dislipidemia aterogénica de forma poco convincente e incluso superficial, en gran medida por las limitaciones terapéuticas disponibles. En consecuencia, esta dislipidemia está infradiagnosticada, infratratada e infracontrolada. Dada la reciente aparición de la guía 2019 de la European Atherosclerosis Society y de la European Society of Cardiology sobre el control de las dislipidemias, parece oportuno examinar su posicionamiento con respecto a la dislipidemia aterogénica y/o sus principales componentes, el aumento en las lipoproteínas ricas en triglicéridos y la disminución del colesterol de las lipoproteínas de alta densidad

In general, both European and American clinical guidelines have addressed the management of atherogenic dyslipidaemia in an unconvincing and even superficial way, largely because of the available therapeutic limitations. Consequently, this type of dyslipidaemia is underdiagnosed, under-treated, and under-controlled. Given the recent presentation of the 2019 guidelines of the European Atherosclerosis Society and the European Society of Cardiology on the management of dyslipidaemias, it seems appropriate to examine its position with respect to atherogenic dyslipidaemia and/or its main components, the increase in triglyceride-rich lipoproteins, and the decrease of high-density lipoprotein cholesterol

Diferencias clínicas y genéticas de los pacientes con hipercolesterolemia familiar heterocigota con y sin diabetes mellitus tipo 2 / Clinical and genetic differences between heterozygous familial hypercholesterolemia patients with and without type 2 diabetes

INTRODUCCIÓN Y OBJETIVOS: La menor prevalencia de diabetes mellitus tipo 2 (DM2) en pacientes con hipercolesterolemia familiar heterocigota (HFHe) podría explicar por qué la DM2 no siempre se ha descrito como un predictor de enfermedad cardiovascular (ECV) en estos pacientes. El objetivo del presente estudio fue evaluar los aspectos clínicos y genéticos de pacientes con HFHe y DM2 del registro de dislipidemias de la Sociedad Española de Arteriosclerosis. MÉTODOS: Los pacientes con HFHe se clasificaron según la presencia/ausencia de DM2. Se compararon las características clínicas, bioquímicas y genéticas de ambos grupos. RESULTADOS: De los 2.301 casos de hipercolesterolemia primaria del registro, se incluyeron 1.724 casos con el diagnóstico cierto o probable según la Dutch Lipid Clinic Network para la hipercolesterolemia familiar. Los pacientes con HFHe y DM2 presentaron una tasa más elevada de ECV y un perfil lipídico menos favorable, con niveles más elevados de colesterol total (366,9±86,7 mg/dl frente a 342,0±74,7 mg/dl; diferencia media 24,894; IC95%, 5,840-43,949) y colesterol no-unido a lipoproteínas de alta densidad (316,9±87,8 mg/dl frente a 286,4±75,4 mg/dl; diferencia media 30,500; IC95%, 11,211-49,790). No se encontraron diferencias significativas entre los grupos con respecto al tipo de mutación (p = 0,720). Después de ajustar por los principales factores de riesgo, el análisis de regresión logística confirmó una relación entre la DM2 y la ECV (OR=2,01; IC95%, 1,18-3,43; p = 0,010). CONCLUSIONES: Los pacientes con HFHe y DM2 presentan una tasa más elevada de ECV y un perfil lipídico menos favorable, independientemente del tipo de mutación. La diabetes mellitus es un factor asociado a la presencia de ECV en estos pacientes

INTRODUCTION AND OBJECTIVES: The lower prevalence of type 2 diabetes mellitus (T2DM) in patients with heterozygous familial hypercholesterolemia (HeFH) could explain why T2DM has not always been identified as an independent predictor of cardiovascular disease (CVD) in different familial hypercholesterolemia cohort studies. The aim of the present study was to evaluate clinical and genetic aspects of HeFH patients with T2DM in the dyslipidemia registry of the Spanish Arteriosclerosis Society. METHODS: HeFH patients were classified according to the presence or absence of T2DM. The clinical, biochemical and genetic characteristics of the 2 groups were compared. RESULTS: Of the 2301 patients with primary hypercholesterolemia included in the registry, 1724 with a probable or definite diagnosis according to the Dutch Lipid Clinic Network score were finally included. HeFH patients with T2DM had a higher rate of CVD and a less favorable lipid profile, with higher total cholesterol (366.9±86.7mg/dL vs 342.0±74.7mg/dL; mean difference 24.894; 95%CI, 5.840-43.949) and non-high-density lipoprotein cholesterol (316.9±87.8mg/dL vs 286.4±75.4mg/dL; mean difference 30.500; 95%CI, 11.211-49.790) levels. No significant differences were found between the groups concerning the specific type of HeFH-causing mutation (P=.720). After adjustment for major risk factors, logistic regression analysis confirmed a relationship between T2DM and the presence of CVD (OR, 2.01; 95%CI, 1.18-3.43; P=.010). CONCLUSIONS: HeFH patients with T2DM have a higher rate of CVD and a less favorable lipid profile, regardless of genetic mutation type. In these patients, T2DM is associated with the presence of CVD

Chronic kidney disease as a cardiovascular risk factor.

: Chronic kidney disease (CKD) is a public health threat with impact in cardiovascular risk. All forms of cardiovascular disease and mortality are more common in CKD. Treatment of cardiovascular risk factors, hypertension, dyslipidemia and diabetes is essential for cardiovascular and kidney protection. CKD is a marker of high or very high cardiovascular risk and its presence require early treatment and specific goals. Lifestyle is a pivotal factor, stopping smoking, reducing weight in the overweight or obese, starting regular physical exercise and healthy dietary pattern are recommended. Office BP should be lowered towards 130/80 mmHg or even lower if tolerated with sodium restriction and single pill combination, including angiotensin system blocker. Out-of-office BP monitoring, mainly 24-h assessment, is recommended. Diabetes requires treatment from the moment of diagnosis, but prediabetes benefits with lifestyle changes and metformin in patients stage 2 and 3a. iSGLT2 and GLP-1RA are initially recommended in T2D patients with high or very high cardiovascular risk. Concerning dyslipidemia, for patients in stage 4, LDL-C 55 mg/dl or less (1.4 mmol/l) and an LDL-C reduction of 50% or less from baseline is recommended. In stage 3, LDL-C goal is 70 mg/dl or less (1.8 mmol/l) and an LDL-C. reduction of at least 50% from baseline. Statins are the lipid-lowering therapy of choice with or without ezetimibe. Higher doses of statins are required as GFR declines. Available evidence suggests that combined PCSK9 inhibitors with maximally tolerated dose of statins may have an emerging role in treatment of dyslipidemia in CKD patients.

Gender differences on oxidative stress markers and complement component C3 plasma values after an oral unsaturated fat load test / Diferencias de género en los marcadores de estrés oxidativo y los valores plasmáticos del componente c3 del complemento tras una sobrecarga oral con grasa insaturada

OBJECTIVE: Post-prandial lipaemia (PL), oxidative stress (OS), and complement component C3 (C3) values are related to the atherosclerosis process. The post-prandial response of C3 after an oral fat load test (OFLT) using unsaturated fat is poorly addressed. The aim of this study was to analyze and compare the post-prandial response of OS markers and C3 values in men and women after an OFLT using unsaturated fat. METHODS: The study included a total of 22 healthy subjects with normal lipids and normal blood glucose (11 men and 11 pre-menopausal women). An oral unsaturated fat load test (OFLT: 50g fat per m2 body surface) was performed using a commercial liquid preparation of long chain triglycerides (Supracal®). OS markers and C3 were measured using standardized methods at fasting state and every 2h up to 8h after the OFLT. RESULTS: Men showed statistically significant higher C3, oxidized glutathione (GSSG), and oxidized-reduced glutathione (GSSG/GSH) ratio values at fasting state compared to that obtained in women. In addition, post-prandial C3 values and GSSG/GSH ratios were significantly higher in men compared to women. The GSSG value and GSSG/GSH ratio significantly decreased in men after the OFLT compared to fasting values. In contrast, the post-prandial OS markers decrease observed in women was not statistically significant. CONCLUSIONS: In fasting state, men showed higher statistically significant C3 values and OS markers than women. The post-prandial OS markers (GSSG and GSSG/GSH ratio) significantly decrease after the OFLT with unsaturated fat in men compared to women

OBJETIVO: Los valores de lipemia postprandial (PL), estrés oxidativo (OS) y componente C3 del complemento (C3) están relacionados con el proceso de aterosclerosis. La respuesta postprandial de C3 tras una sobrecarga oral de grasa (OFLT) utilizando grasa insaturada no es completamente conocida. Nuestro objetivo fue analizar y comparar la respuesta postprandial de los marcadores de OS y los valores de C3 en hombres y mujeres después de una OFLT utilizando grasa insaturada. MÉTODOS: Estudiamos 22 sujetos normolipidémicos y normoglicémicos (11 hombres y 11 mujeres premenopáusicas). Se realizó una sobrecarga oral con grasa insaturada (OFLT: 50g de grasa por m2 de superficie corporal) utilizando una preparación líquida comercial de triglicéridos de cadena larga (Supracal®). Los marcadores OS y C3 se midieron utilizando métodos estandarizados en estado de ayuno y cada 2 horas hasta 8 horas después de OFLT. RESULTADOS: Los hombres mostraron valores significativamente mayores de C3, glutatión oxidado (GSSG) y glutatión reducido (GSSG/GSH) en estado de ayuno en comparación con los obtenidos en mujeres. Además, los valores de C3 postprandiales y la relación GSSG/GSH fueron significativamente más altos en los hombres que en las mujeres. El valor GSSG y la relación GSSG/GSH disminuyeron significativamente en los hombres después de OFLT en comparación con los valores de ayuno. En contraste, la disminución de marcadores postprandiales de OS observada en mujeres no fue estadísticamente significativa. CONCLUSIONES: En ayunas, los hombres muestran valores estadísticamente mayores de C3 y marcadores OS que las mujeres. Los marcadores OS postprandial (GSSG y GSSG/GSH ratio) disminuyen significativamente tras OFLT con grasa insaturada en los hombres en comparación con las mujeres

Dislipidemia aterogénica 2019. Documento de consenso del Grupo de Dislipidemia Aterogénica de la Sociedad Española de Arteriosclerosis / Atherogenic Dyslipidaemia 2019. Consensus document of the Atherogenic Dyslipidaemia Group of the Spanish Arteriosclerosis Society

No disponible

Gender differences on oxidative stress markers and complement component C3 plasma values after an oral unsaturated fat load test.

OBJECTIVE: Post-prandial lipaemia (PL), oxidative stress (OS), and complement component C3 (C3) values are related to the atherosclerosis process. The post-prandial response of C3 after an oral fat load test (OFLT) using unsaturated fat is poorly addressed. The aim of this study was to analyze and compare the post-prandial response of OS markers and C3 values in men and women after an OFLT using unsaturated fat. METHODS: The study included a total of 22 healthy subjects with normal lipids and normal blood glucose (11 men and 11 pre-menopausal women). An oral unsaturated fat load test (OFLT: 50g fat per m2 body surface) was performed using a commercial liquid preparation of long chain triglycerides (Supracal®). OS markers and C3 were measured using standardized methods at fasting state and every 2h up to 8h after the OFLT. RESULTS: Men showed statistically significant higher C3, oxidized glutathione (GSSG), and oxidized-reduced glutathione (GSSG/GSH) ratio values at fasting state compared to that obtained in women. In addition, post-prandial C3 values and GSSG/GSH ratios were significantly higher in men compared to women. The GSSG value and GSSG/GSH ratio significantly decreased in men after the OFLT compared to fasting values. In contrast, the post-prandial OS markers decrease observed in women was not statistically significant. CONCLUSIONS: In fasting state, men showed higher statistically significant C3 values and OS markers than women. The post-prandial OS markers (GSSG and GSSG/GSH ratio) significantly decrease after the OFLT with unsaturated fat in men compared to women.

Triglycerides, HDL cholesterol and atherogenic dyslipidaemia in the 2019 European guidelines for the management of dyslipidaemias. / Triglicéridos, colesterol HDL y dislipidemia aterogénica en la guía europea para el control de las dislipidemias 2019.

In general, both European and American clinical guidelines have addressed the management of atherogenic dyslipidaemia in an unconvincing and even superficial way, largely because of the available therapeutic limitations. Consequently, this type of dyslipidaemia is underdiagnosed, under-treated, and under-controlled. Given the recent presentation of the 2019 guidelines of the European Atherosclerosis Society and the European Society of Cardiology on the management of dyslipidaemias, it seems appropriate to examine its position with respect to atherogenic dyslipidaemia and/or its main components, the increase in triglyceride-rich lipoproteins, and the decrease of high-density lipoprotein cholesterol.

Clinical and genetic differences between heterozygous familial hypercholesterolemia patients with and without type 2 diabetes.

INTRODUCTION AND OBJECTIVES: The lower prevalence of type 2 diabetes mellitus (T2DM) in patients with heterozygous familial hypercholesterolemia (HeFH) could explain why T2DM has not always been identified as an independent predictor of cardiovascular disease (CVD) in different familial hypercholesterolemia cohort studies. The aim of the present study was to evaluate clinical and genetic aspects of HeFH patients with T2DM in the dyslipidemia registry of the Spanish Arteriosclerosis Society. METHODS: HeFH patients were classified according to the presence or absence of T2DM. The clinical, biochemical and genetic characteristics of the 2 groups were compared. RESULTS: Of the 2301 patients with primary hypercholesterolemia included in the registry, 1724 with a probable or definite diagnosis according to the Dutch Lipid Clinic Network score were finally included. HeFH patients with T2DM had a higher rate of CVD and a less favorable lipid profile, with higher total cholesterol (366.9±86.7mg/dL vs 342.0±74.7mg/dL; mean difference 24.894; 95%CI, 5.840-43.949) and non-high-density lipoprotein cholesterol (316.9±87.8mg/dL vs 286.4±75.4mg/dL; mean difference 30.500; 95%CI, 11.211-49.790) levels. No significant differences were found between the groups concerning the specific type of HeFH-causing mutation (P=.720). After adjustment for major risk factors, logistic regression analysis confirmed a relationship between T2DM and the presence of CVD (OR, 2.01; 95%CI, 1.18-3.43; P=.010). CONCLUSIONS: HeFH patients with T2DM have a higher rate of CVD and a less favorable lipid profile, regardless of genetic mutation type. In these patients, T2DM is associated with the presence of CVD.

Non-HDL cholesterol as a therapeutic goal. / Colesterol-no HDL como objetivo terapéutico.

Although cholesterol linked to low-density lipoproteins (c-LDL) is well established as a risk factor for cardiovascular disease, there is often a more complex dyslipidaemia pattern that contributes to the formation of atherosclerotic plaque. Non-HDL cholesterol (c-NO-HDL) is used to estimate the total amount of atherogenic lipoproteins in plasma, some of which are not usually determined in daily clinical practice. c-NO-HDL is easily calculated from the subtraction of total plasma cholesterol from the cholesterol content carried by high density lipoproteins. The c-NO-HDL has a predictive value superior to that of C-LDL to estimate the risk of major cardiovascular events in epidemiological studies. Genetic studies by analysis of the complete genome, together with those based on Mendelian randomisation, point to the aetiological character of c-NO-HDL on ischaemic heart disease (IHD). Intervention studies, and the meta-analyses derived from them, close the causal circle between c-NO-HDL and IHD, by demonstrating that any intervention that decreases the concentrations of the former reduces the incidence of arteriosclerotic heart disease. The European ESC/EAS 2016 guide for the management of dyslipidaemia considers c-NO-HDL as a therapeutic target with a Class IIa recommendation (should be performed) Level B (data from a single randomised clinical trial [RCT]) or from several non-RCTs), and sets its target at less than 100 or 130mg/dL for those patients with very high risk or high risk, respectively. These achievable c-NO-HDL values are easily calculated by adding 30mg/dL to the c-LDL targets.

Control of the overall lipid profile. / Control del perfil lipídico global.

The importance of overall lipid control in cardiovascular prevention is reviewed. Several studies and meta-analyses show that the control of LDL cholesterol (LDL-C) still maintains a high cardiovascular risk, which is related to the presence of triglyceride-rich lipoproteins, and therefore with an increase in plasma triglycerides and the values of apolipoprotein B (apoB) containing these lipoproteins. The importance of this relationship is due to the change in the lipid profile of our population in recent years. This is related to the increase in obesity and insulin resistance, and is called atherogenic dyslipidaemia. Thus, hypertriglyceridaemia should be considered a cardiovascular risk factor, especially when the desirable objectives of LDL-C have been achieved. The indications for treatment with fibrates in primary and secondary prevention, using the medical evidence-based recommendations, are described, along with its importance in the reduction of cardiovascular risk. Finally, the established indications of the combined statin-fibrate treatment are presented, always after changes in lifestyle.