Gene expression profile following an oral unsaturated fat load in abdominal obese subjects.

PURPOSE: Our aim was to evaluate the postprandial effect of an oral fat load test (OFLT) rich in unsaturated fatty acids on gene expression profile in peripheral blood mononuclear cells (PBMC) from subjects with abdominal obesity as an insulin resistance model and controls. METHODS: A total of 20 controls and 20 abdominal obese patients were studied. Metabolic parameters and oxidative stress markers were measured with standardized protocols. The whole gene expression at fasting state and after the OFLT (0, 4 and 8 h) was analysed using human HT-12-v4 expression beadchips, from Illumina. RESULTS: We found a significant decrease in plasma glucose, insulin and oxidative stress markers in abdominal obese patients and controls. We found beneficial metabolic postprandial gene expression in three genes: FKBP5, DDIT4 and DHRS9. Following an OFLT, the postprandial mRNA expression of FKBP5, and DDIT4 was downregulated while that of DHRS9 was overexpressed, both in nondiabetic normolipidemic subjects and in insulin-resistant subjects with abdominal obesity. CONCLUSIONS: Our results suggest that an OFLT rich in unsaturated fatty acids downregulates the expression of FKBP5, coding for the glucocorticoid receptor pathway, and that of DDIT4, involved in the oxidative stress response. These changes could favourably influence the insulin resistance and oxidative stress status in the postprandial state.

Establishing cut-off values for apolipoprotein B and non-HDL-C according to LDL-C values in a South European population.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) remains the primary target of therapy in most strategies of dyslipidaemia management focused on cardiovascular disease prevention. Different guidelines have identified specific LDL-C cut-off points as targets for therapeutic intervention. Many clinical situations characterised by dyslipidaemia and elevated triglycerides are common in our environment and in overall industrialised countries. Thus, lipid goals based only on LDL-C could misclassify an important percentage of subjects. The objective of the present study was to establish cut-off point values for apoB and non-HDL-C in relation to the identified LDL-C cut-off points for cardiovascular risk in a South European population. METHODS: We performed a cross-sectional study including 1501 subjects (770 women and 731 men) between 18 and 80 years of age. Samples were collected after 12-14 h of fasting. Cholesterol, HDL-C, triglycerides and apoB levels were measured using direct methods. LDL-C was calculated by the Friedewald formula. Non-HDL-C was calculated as total cholesterol minus HDL-C. RESULTS: The Spearman's rank correlations between apoB and LDL-C (r 0.86, p < 0.0001), and between apoB and non-HDL-C (r 0.91, p < 0.0001) were both significant. The proposed cut-off points for apoB, according to LDL-C goals (70, 100, 130 and 160 mg/dl) in our population are 70, 80, 100 and 115 mg/dl respectively. The proposed cut-off values for non-HDL-C are 100, 120, 150 and 190 mg/dl respectively. CONCLUSION: The established LDL-C cut-off values could not be accurate to estimate cardiovascular risk in subjects with mild hypertriglyceridaemia, as frequently occurs in our Mediterranean population. To take into consideration the burden of atherogenic particles and better classify patients at risk we propose cut-off values for apoB or the equivalent for non-HDL-C. Prospective trials including cardiovascular variables are needed to validate our assumption.

SEA 2022 Standards for Global Control of Cardiovascular Risk. / Estándares SEA 2022 para el control global del riesgo cardiovascular.

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to better knowledge of vascular disease, its prevention and treatment. It is well known that cardiovascular diseases are the leading cause of death in our country and entail a high degree of disability and health care costs. Arteriosclerosis is a multifactorial disease and therefore its prevention requires a global approach that takes into account the different risk factors with which it is associated. Therefore, this document summarizes the current level of knowledge and includes recommendations and procedures to be followed in patients with established cardiovascular disease or at high vascular risk. Specifically, this document reviews the main symptoms and signs to be evaluated during the clinical visit, the laboratory and imaging procedures to be routinely requested or requested for those in special situations. It also includes vascular risk estimation, the diagnostic criteria of the different entities that are cardiovascular risk factors, and makes general and specific recommendations for the treatment of the different cardiovascular risk factors and their final objectives. Finally, the document includes aspects that are not usually referenced in the literature, such as the organization of a vascular risk consultation.

Circulating mononuclear cells nuclear factor-kappa B activity, plasma xanthine oxidase, and low grade inflammatory markers in adult patients with familial hypercholesterolaemia.

BACKGROUND: Few data are available on circulating mononuclear cells nuclear factor-kappa B (NF-kB) activity and plasma xanthine oxidase (XO) activity in heterozygous familial hypercholesterolaemia (FH). The goal of the study was to analyse circulating mononuclear cells NF-kB and plasma XO activities in FH patients. MATERIALS AND METHODS: Thirty FH index patients and 30 normoglycaemic normocholesterolaemic controls matched by age, gender, body mass index, abdominal circumference and homeostasis model assessment index were studied. Plasma XO and inflammatory markers were measured by standard methods. NF-kB was assayed in circulating mononuclear cells. RESULTS: Familial hypercholesterolaemia patients showed a significantly higher NF-kB (75.0 +/- 20.7 vs. 42.7 +/- 16.8 relative luminiscence units) and XO (0.44 +/- 0.13 vs. 0.32 +/- 0.09 mU mL(-1)) activities than controls. In addition, interleukin-1, interleukin-6, high sensitivity C reactive protein (hsCRP) and oxidized LDL (LDL-ox) were also significantly higher in FH patients. In the total group (FH and controls), XO was significantly associated with LDL-cholesterol (LDL-C), apolipoprotein B (apoB), NF-kB and hsCPR, and NF-kB activity was significantly associated with XO, hsCPR, LDL-ox, LDL-C and apoB plasma values. Using multiple regression analysis, XO was independently associated with hsCPR and NF-kB, and NF-kB activity in circulating mononuclear cells was independently associated with apoB and LDL-ox plasma values. CONCLUSION: Familial hypercholesterolaemia patients show increased activities of NF-kB and XO, and higher values of low grade inflammatory markers related to atherosclerosis. NF-kB activity was independently associated with apoB plasma values. These data could explain in part the high cardiovascular disease risk present in these patients.

Plasma homocysteine levels are associated with ulceration of the foot in patients with type 2 diabetes mellitus.

BACKGROUND: To examine the association of biochemical markers of risk (plasma Hcy, microalbuminuria, lipoprotein (a)(Lp(a)) and diabetic dyslipidaemia) with the prevalence of diabetic foot ulceration in type 2 diabetic patients. METHODS: Case/control study conducted in 198 type 2 diabetic patients. 89 patients have foot ulcers and 109 have no foot ulcers (control group), in order to establish ORs for diabetic foot ulceration. In all subjects plasma Hcy, Lp(a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, HbA(1c) and microalbuminuria were measured using standard procedures. RESULTS: Plasma Hcy, microalbuminuria, HbA(1c) and apolipoprotein B levels were significantly higher in patients with foot ulceration compared with the control group. Plasma lipids, Lp(a), vitamin B12 and folic acid values were similar in both groups. In the logistic regression model, plasma Hcy (OR 1.09; 95% CI 1.04-1.69), microalbuminuria (OR 1,01; 95% CI 1.01-1.17) and HbA(1c) levels (OR 1.33; 95% CI 1.04-1.69) were independent risk factors for the presence of diabetic foot ulceration. CONCLUSIONS: In our study, for each micromol increase in plasma Hcy levels there was a 10% increase in the risk of diabetic foot ulceration. In addition, plasma homocysteine, HbA(1c) and microalbuminuria accounted for 50% prevalence risk of diabetic foot ulceration. Further prospective studies should be conducted to confirm the association of plasma Hcy levels with the risk of foot ulceration.

Increased plasma xanthine oxidase activity is related to nuclear factor kappa beta activation and inflammatory markers in familial combined hyperlipidemia.

BACKGROUND AND AIMS: Xanthine oxidase (XO) has been described as one of the major enzymes producing free radicals in blood. Oxidative stress and inflammatory processes have been implicated in the pathogenesis of endothelial dysfunction and the progression of atherosclerosis but until now, there is little data about the influence of vascular prooxidant systems and inflammation in familial combined hyperlipidemia (FCH). Our goal was to evaluate whether XO activity was altered in FCH and if it was related to the inflammatory process represented by NFkB, IL-6 and hsCRP, and assessing the correlation between XO activity and insulin resistance (IR). METHOD AND RESULTS: 40 Non-related subjects with FCH and 30 control subjects were included, all of them non-diabetic, normotensive and non-smokers. We measured lipid profile, glucose, insulin, uric acid, XO activity, malondialdehyde (MDA), IL-6 and hsCRP in plasma and NFkB activity in circulating mononuclear cells. Patients with FCH showed significantly higher levels of uric acid, XO activity, MDA, NFkB activity, IL-6 and hsCRP than controls. XO activity was independently related to NFkB activity with an odds ratio of 4.082; to IL-6 with an odds ratio of 4.191; and to IR with an odds ratio of 3.830. Furthermore, mean NFkB activity, IL-6 levels, and IR were highest in the highest percentile of XO activity. CONCLUSIONS: Subjects with FCH showed increased XO and NFkB activities and low grade inflammatory markers related to atherosclerosis. XO activity was correlated with higher inflammatory activity and IR. These data could explain, in part, the high cardiovascular disease risk present in these patients.

Have the Government's prescription algorithm and the 2013 American College of Cardiology/American Heart Association guidelines for managing dyslipidaemia influenced the management of dyslipidaemia? The MEJORALO-CV Project. / ¿Han influido el algoritmo de prescripción de la Administración y las guías de manejo de la dislipemia de la ACC/AHA 2013 en el manejo de la dislipemia? Proyecto MEJORA-LO CV.

OBJECTIVE: To determine the management of dyslipidaemia in primary care after the publication of the American College of Cardiology/American Heart Association (ACC/AHA) 2013 guidelines and Valencian government's algorithm. METHOD: We conducted a cross-sectional descriptive study that employed a survey of primary care physicians of the Community of Valencia between January and October 2016. RESULTS: A total of 199 physicians (mean age, 48.9±11.0 years; experience, 21.3±11.1 years) participated in the survey. The most followed guidelines were those of the European Society of Cardiology (37.5% of respondents) and Valencian government (23.4% of respondents). Some 6.3% of the respondents followed the 2013 ACC/AHA guidelines, and 88.0% established objectives based on LDL cholesterol and cardiovascular risk. The choice of lipid-lowering drug was based on its LDL cholesterol lowering capacity (28.6% of respondents), on the Valencian government's algorithm (23.4%) and on the drug's safety (20.4%). Statins, ezetimibe and fibrates were the preferred hypolipemiant agents, and their combination (51% of respondents) and dosage increases (35%) were the strategies employed for poor control. Lipid profile and transaminase and creatine kinase levels were measured every 6 (59.5%, 52.3% and 54.3% of respondents, respectively) or 12 months (25.1%, 29.2% and 30.3%, respectively). Forty-one percent of the respondents were aware of the controversy surrounding the 2013 ACC/AHA guidelines. Although 60% of the respondents acknowledged its relevance, only 21% changed their daily practices accordingly. CONCLUSIONS: The Valencian government's algorithm had a greater impact than the 2013 ACC/AHA guidelines in primary care in Valencia. Areas for improvement included the low use of validated guidelines and risk tables and the streamlining of laboratory test periodicity.

[Difficult treatment of amiodarone-induced thyrotoxicosis: a case report]. / Dificultad en el tratamiento del hipertiroidismo por amiodarona. Presentación de un caso.

Amiodarone causes changes in thyroid function tests in about 15-20% of patients, inducing either hypothyroidism or thyrotoxicosis. The iodine load and the destructive thyroiditis caused by amiodarone produce thyrotoxicosis. We report a case of amiodarone-induced thyrotoxicosis diagnosed when investigating the reason for worsening of cardiac function. Prognosis and treatment of cardiac disorder were determined by thyrotoxicosis. The management needed a closed monitoring of thyroid function. Treatment was based on high doses of propylthiouracil and dexamethasone, but they couldn t control cardiac condition and surgery was warranted. When amiodarone-induced thyrotoxicosis is refractory to medical treatment, we believe surgery should be considered earlier.

[Effect of gender and obesity on postprandial lipemia in non-diabetic normolipidemic subjects and subjects with familial combined hyperlipidemia]. / Efecto del género y de la obesidad en la lipemia posprandial en sujetos sanos normolipidémicos no diabéticos y sujetos con hiperlipemia familiar combinada.

INTRODUCTION: A new method based on self-measurement of diurnal capillary triglycerides (TG) facilitates the study of postprandial lipemia (PL). The objectives of our study are: to evaluate the effect of gender and obesity on PL measured by self-determination of diurnal capillary TG with Accutrend GCT in normolipidemic non-diabetic subjects and subjects with familial combined hyperlipidemia (FCH). MATERIAL AND METHODS: We studied 23 FCH subjects (10 males) and 45 normolipidemic non-diabetic subjects (29 males). All subjects self-determine 3 diurnal capillary TG profiles during a week. RESULTS: In normolipidemic non diabetic subjects significantly higher diurnal TG profiles and area under the curve of TG (AUCTGc) (25.25 +/-9.09 vs 19.71 +/- 6.16 mmolh/l) were found in males compared to females. In FCH subjects these differences were not found and the AUCTGc correlated with BMI (r = 0.510, p < 0.05) and waist circumference (r = 0.453, p < 0.05). Obese subjects (BMI >or= 27 kg/m2) showed diurnal TG profiles and AUCTGc significantly higher than the non-obese. DISCUSSION: Normolipidemic non diabetic females showed a lower PL compared to males, probably due to the effect of estrogens in PL metabolism. Obesity negatively influences PL in normolipidemic non diabetic subjects and subjects with FCH.