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Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influence on cardiovascular disease and drugs used in the control of cardiovascular risk factors showing a beneficial effect on the liver disease will be reviewed., (Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the association of NAFLD with cardiovascular disease., (Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Lowe density lipoproteins (LDL) are the causal agent of cardiovascular diseases. In practice, we identify LDL with cholesterol transported in LDL (cLDL). So, cLDL has become the major target for cardiovascular prevention. Howewer, we have progressive evidences about the role of triglycerides rich lipoproteins, particularly those very low density lipoprotein (VLDL) in promotion and progression of atherosclerosis, that leads cholesterol in VLDL and its remanents as a potential therapeutic target. This feature is particularly important and of a great magnitude, in patients with hypertiglyceridemia. We can to considere, that the non-HDL cholesterol -cLDL+cVLDL+c-remmants+Lp(a)- is the real measurement of atherogenic cholesterol. In addition, non-HDL-cholesterol do not show any variations between postprandial states. In fact, non-HDL-cholesterol should be an excellent marker of atherogenic cholesterol, and an major therapeutic target in patients with atherogenic dyslipidaemia. According with different clinical trials and with the epidemiological and mendelian studies, in patients with high cardiovascular risk, optimal level of cLDL will be under 70mg/dl, and under 100 ng/dl for non-HDL-cholesterol; and in high risk patients, 100mg/dl and 130mg/dl, respectively., (Copyright © 2016. Publicado por Elsevier España, S.L.U.)

To control lipid factors risk, beyond proper management of LDL cholesterol according to individual risk, detection and treatment of atherogenic dyslipidemia and abnormal levels of triglycerides or HDL cholesterol it should be considered for address a global cardiovascular protection, both in primary and secondary prevention. In this sense, these recommendations collect data on efficacy and safety about the combination statin with fibrates, often necessary for total control of dyslipidemia, particularly in patients with metabolic disorders such as diabetes mellitus, metabolic syndrome or visceral obesity. Reference to control and monitoring of treatment is also done, as well as benefits of fenofibrate not linked directly to their lipid-lowering effect., (Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aim: To study the association between adiponectin plasma levels, and gray matter brain volume and cerebral glucose metabolism in a group of type 2 diabetes patients., Methods: We studied 25 type 2 diabetes patients and 25 age- and gender-matched healthy control participants. Biochemical analysis and structural cerebral magnetic resonance imaging, including voxel-based morphometry and (18)-fluorodeoxyglucose positron emission tomography, were performed. The gray matter volumes and metabolism changes were analyzed using statistical parametric mapping (SPM8)., Results: Lower levels of adiponectin correlated with a lower gray matter volume in temporal regions and with reduced cerebral glucose metabolism in temporal regions (p<0.001), adjusted for age, gender, education, and the presence of at least one epsilon 4 allele for the apolipoprotein E (APOEε4 genotype)., Conclusions: Positive correlations between adiponectin plasma levels and both gray matter volume and cerebral glucose metabolism were found, predominantly in temporal regions, as in Alzheimer's disease. Adiponectin might be a biomarker for the cognitive decline associated with type 2 diabetic patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Objective: Atherogenic dyslipidaemia is underdiagnosed, undertreated, and under-controlled. The aim of the present study was to assess the positioning of clinical guidelines as regards atherogenic dyslipidaemia., Material and Method: The major clinical guidelines of scientific societies or official agencies issued between January 1, 2012 and March 31, 2015 were collected from the MEDLINE database. High-density lipoprotein (HDL) cholesterol, triglycerides, atherogenic dyslipidaemia, non-HDL cholesterol, and apolipoprotein (apo) B were gathered from the 10 selected guidelines, and it was assessed whether these parameters were considered a cardiovascular risk factor, a therapeutic target, or proposed a pharmacological strategy., Results: American guidelines, except the National Lipid Association (NLA), do not consider HDL cholesterol and triglycerides in cardiovascular prevention. The NLA emphasises the relevance of atherogenic dyslipidaemia. The Canadian guidelines introduced non-HDL cholesterol and ApoB as alternative targets, and proposes non-statin treatment in the presence of low HDL cholesterol and hypertriglyceridaemia. The International Atherosclerosis Society (IAS) and National Institute for Health and Care Excellence (NICE) guidelines promote the importance of non-HDL cholesterol. European, Brazilian and Japanese guidelines highlight HDL cholesterol and triglycerides, but with the limitation that the main evidence comes from sub-analysis of clinical studies., Conclusions: The clinical guidelines analysed do not consider, or unconvincingly address, the importance of atherogenic dyslipidaemia., (Copyright © 2016 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.)

Introduction: The glucagon-like peptide-1 (GLP-1) mimetics are an established therapeutic option for patients with type 2 diabetes. However, the properties of the GLP-1 mimetics go beyond the strict metabolic control of the patients with diabetes. The neuroprotective effects of GLP-1 have been shown in recent studies opening new areas of research in neurodegenerative diseases such as Alzheimer's disease (AD), among others. AIM. Systematic review including experimental studies and human clinical trials demonstrating the neuroprotective properties of GLP-1 mimetics in AD., Development: The experimental studies that have been conducted in rodent models of AD have demonstrated the neuroprotective properties of GLP-1 in the central nervous system reducing beta-amyloid plaques, the oxidative stress and the inflammatory brain response. Clinical trials in patients with cognitive impairment and AD testing the effects of GLP-1 analogs have recently started., Conclusion: The GLP-1 analogs have neuroprotective properties. Considering that type 2 diabetes is a risk factor for cognitive impairment and dementia, the benefits of GLP-1 mimetics on cognition must be considered. Likewise, the GLP-1 mimetics represent a promising treatment for neurodegenerative diseases such as AD.

Objective: The aim of this study was to assess the prevalence of atherogenic dyslipidemia (AD) and the lipid triad (LT) in the working population in Spain, their associated variables and how far they are linked to cardiovascular risk (CVR)., Methods: Observational cross-sectional study of 70,609 workers (71.5% male (M), 28.5% female (F), mean age 39.2 ± 10), who attended medical checkups and agreed to participate. Plasma samples were analysed in a central laboratory. AD definition used was: triglycerides ≥150 mg/dl and HDL cholesterol <40 mg/dl (M)/<50 mg/dl (F) and LT when LDL cholesterol > 160 mg/dl is further added. Univariate comparisons in the absence and presence of AD and LT and the probability of AD according to different parameters and their possible association with CVR were assessed. CVR was stratified following the European SCORE model for low risk-population., Results: 5.7% (95% CI 4.7-6.9) of the working population have AD and 1.1% (95% CI 1.0-1.2) LT. In univariate analysis, workers with AD and LT had a higher prevalence of obesity, hypertension, smoking and diabetes than those who had not (p < 0.001). In multivariate analysis, BMI, sex, age 40-49, diabetes, tobacco, uric acid, LDL or blood pressure significantly influenced the risk of AD. AD was significantly associated with CVR after adjusting for alcohol and obesity. However, most of the AD subjects (91.8%) were classified as low risk., Conclusions: About 6% of the working population in Spain meets AD criteria. Assuming that these subjects have increased CVR, AD allows to identify additional 5% of subjects with increased CVR to that one the SCORE model detects, helping to improve cardiovascular risk stratification., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

With mixed dyslipidemia of the atherogenic dyslipidemia type, once the LDL-c objectives have been achieved through statin treatment, there is often a residual risk, for which the addition of a fibrate is recommended. The combination of statins and fibrates has been limited by the possibility of drug interactions, which mostly result in myopathy. Interactions between statins and other drugs are caused by pharmacokinetic mechanisms, mainly by changing the metabolism of statins in the CYP450 enzyme system, in the hepatic glucuronidation pathway or in the transporters responsible for statin distribution in tissues. The most significant adverse eff ect of statins is myopathy, which can also be induced by fibrates and is more frequent when the 2 drugs (statins and fibrates) are combined. This adverse eff ect manifests clinically as myalgia, muscle weakness, increased CK levels and, in its most severe form, rhabdomyolysis. This interaction mainly aff ects gemfibrozil due to its specific action on the CYP450 enzyme system and that interferes with the hepatic glucuronidation of statins by using the same isoenzymes and with organic anion transporters in the liver. When combining statins, we should use other fibric acid derivatives, preferably fenofibrate., (Copyright © 2014 Sociedad Española de Arteriosclerosis y Elsevier España, S.L. All rights reserved.)

Although the mortality associated to cardiovascular diseases (CVD) has been reduced in the last decades, CVD remains the main cause of mortality in Spain and they are associated with an important morbidity and a huge economic burden. The increasing prevalence of obesity and diabetes could be slowing down the mortality reduction in Spain. Clinicians have often difficulty making clinical decisions due to the multiple clinical guidelines available. Moreover, in the current context of economic crisis it is critical to promote an efficient use of diagnostic and therapeutic proceedings to ensure the viability of public health care systems. The Spanish Society of Internal Medicine (SEMI) has coordinated a consensus document to answer questions of daily practice with the aim of facilitating physicians' decision-making in the management of diabetes and cardiovascular risk factors from a cost-efficiency point of view., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

Introduction and Objectives: Although atherogenic dyslipidemia is a recognized cardiovascular risk factor, it is often underassessed and thus undertreated and poorly controlled in clinical practice. The objective of this study was to reach a multidisciplinary consensus for the establishment of a set of clinical recommendations on atherogenic dyslipidemia to optimize its prevention, early detection, diagnostic evaluation, therapeutic approach, and follow-up., Methods: After a review of the scientific evidence, a scientific committee formulated 87 recommendations related to atherogenic dyslipidemia, which were grouped into 5 subject areas: general concepts (10 items), impact and epidemiology (4 items), cardiovascular risk (32 items), detection and diagnosis (19 items), and treatment (22 items). A 2-round modified Delphi method was conducted to compare the opinions of a panel of 65 specialists in cardiology (23%), endocrinology (24.6%), family medicine (27.7%), and internal medicine (24.6%) on these issues., Results: After the first round, the panel reached consensus on 65 of the 87 items discussed, and agreed on 76 items by the end of the second round. Insufficient consensus was reached on 3 items related to the detection and diagnosis of atherogenic dyslipidemia and 3 items related to the therapeutic goals to be achieved in these patients., Conclusions: The external assessment conducted by experts on atherogenic dyslipidemia showed a high level of professional agreement with the proposed clinical recommendations. These recommendations represent a useful tool for improving the clinical management of patients with atherogenic dyslipidemia. A detailed analysis of the current scientific evidence is required for those statements that eluded consensus., (Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Background/objective: The aim was to assess the neuropsychological performance of a group of middle-aged patients with well-controlled type 2 diabetes mellitus (T2DM) and to examine whether the neuropsychological deficits correlate with structural and functional brain alterations., Methods: We compared 25 subjects with T2DM aged 45-65 years with 25 control participants matched for age, gender, and educational level. The neuropsychological battery was designed to examine executive functions, attention, information processing speed, and verbal memory. Severity of depression was assessed using the Hamilton Depression Rating Scale and cardiovascular risk factors were assessed using the Framingham Cardiovascular Risk Profile Score. The presence of at least one APOEε4 allele was determined. Reduced gray matter density was analyzed using voxel-based morphometry and brain glucose metabolic changes were assessed by 18FDG-PET., Results: T2DM subjects had significantly lower scores than subjects without T2DM in the Trail-making Test B (p < 0.004), Color-Word Stroop test (p < 0.005), Semantic Fluency (p < 0.006), Digit-Symbol modalities test (p < 0.02), Text Recall from the Wechsler Memory Scale (p < 0.0001), Rey-Osterrieth Complex Figure-copy (p < 0.004), and delayed reproduction (p < 0.03). Worse executive functions and memory functioning correlated predominantly with less gray matter density and reduced glucose metabolism in the orbital and prefrontal cortex, temporal (middle gyrus, parahippocampus and uncus), and cerebellum regions (p < 0.001)., Conclusions: T2DM subjects presented cognitive dysfunctions compared with controls. Clinical-neuroimaging correlations corresponded to brain changes (reduced gray matter density and glucose metabolism) mainly in fronto-temporal areas.

Background: Type 2 diabetes mellitus (T2DM) is an emerging risk factor for cognitive impairment. Whether this impairment is a direct effect of this metabolic disorder on brain function, a consequence of vascular disease, or both, remains unknown. Structural and functional neuroimaging studies in patients with T2DM could help to elucidate this question., Objective: We designed a cross-sectional study comparing 25 T2DM patients with 25 age- and gender-matched healthy control participants. Clinical information, APOE genotype, lipid and glucose analysis, structural cerebral magnetic resonance imaging including voxel-based morphometry, and F-18 fluorodeoxyglucose positron emission tomography were obtained in all subjects., Methods: Gray matter densities and metabolic differences between groups were analyzed using statistical parametric mapping. In addition to comparing the neuroimaging profiles of both groups, we correlated neuroimaging findings with HbA1c levels, duration of T2DM, and insulin resistance measurement (HOMA-IR) in the diabetic patients group., Results: Patients with T2DM presented reduced gray matter densities and reduced cerebral glucose metabolism in several fronto-temporal brain regions after controlling for various vascular risk factors. Furthermore, within the T2DM group, longer disease duration, and higher HbA1c levels and HOMA-IR were associated with lower gray matter density and reduced cerebral glucose metabolism in fronto-temporal regions., Conclusion: In agreement with previous reports, our findings indicate that T2DM leads to structural and metabolic abnormalities in fronto-temporal areas. Furthermore, they suggest that these abnormalities are not entirely explained by the role of T2DM as a cardiovascular risk factor.

Extremely low LDL-cholesterol concentrations are very unusual and generally related with comorbidities accompanying malnutrition. Less frequently low LDL-cholesterol levels result from mutations in the APOB, PCSK9, ANGPTL3, SAR1B and MTTP genes (primary hypobetalipoproteinemia). We investigated three patients with plasma LDL-cholesterol levels below the fifth percentile of the Spanish population. We recorded data on demographic and anthropometric characteristics, life style habits, physical examination, liver ultrasound and lipid and lipoprotein levels, in the probands and their first-degree relatives. Secondary causes of hypocholesterolemia were ruled out by clinical study, complementary tests and follow-up. The APOB, MTTP and SAR1B genes were sequenced. Patients were found to be heterozygotes for point mutations located in the exon 26 of the APOB gene. One patient, with fatty liver, carried a previously described mutation (c.7600C>T) (Arg2507X), causing the formation of truncated Apo B-55.25. The other two mutations producing truncations are new. One asymptomatic patient carried the Arg3672X (Apo B-80.93) and the other with fatty liver and steatorrhea carried the Ser2184fsVal2193X (Apo B-48.32). Our study reinforces the concept that in the heterozygous carriers of truncated Apo Bs, the clinical manifestations of FHBL are dependent on the size of the truncations., (© 2013 Elsevier B.V. All rights reserved.)

Objective: To determine the incidence and prevalence of cancer in a cohort of patients with systemic lupus erythematosus (SLE) and identify associated risk factors., Patients and Methods: The study comprised a dynamic cohort of SLE patients (November 1989 to December 2006) at a tertiary referral centre. An adjusted external control from the hospital tumour registry was used., Results: The study included 175 SLE patients (90% women), with a mean time at risk of 1370.5 patient-years. Fourteen women (8%) died, mainly from cardiovascular events. No patient died due to malignancy. We found 35 tumours in 28 patients, 25 of them after the diagnosis of SLE, of which 5 were malignant. The rate of benign tumours was 14.6/1000 patient-years (95% CI, 8.9-22.5) and of malignant tumours 3.6/1000 patient-years (95% CI, 1.5-8.8), with a crude incidence odds ratio for malignant tumours of 3.5 (95% CI, 1.5-7.9). However, this significance was lost after standardizing the rates. Concerning associated risk factors, differences were found in the mean erythrocyte sedimentation rate [HR 1.4 (1.1-1.7)], and the presence of thrombosis [HR 6.9 (1.49-41.2)], especially arterial thrombosis., Conclusions: We found a crude incidence rate of cancer that was almost four times greater in our SLE patients as compared with the expected rate in the hospital area of western Malaga., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)

An earlier study showed that fasting and postprandial concentrations of apolipoprotein B48 were raised in patients with type 2 diabetes (DM2) and peripheral arterial disease (PAD) as compared with persons without DM2 or persons with DM2 but not PAD. The aim of this study was to confirm the association of PAD and B48 in a larger group of patients with DM2 and the relation of B48 with the preheparin lipoprotein lipase (LPL) mass. We studied 456 patients with DM2. PAD was defined as an ankle-brachial index (ABI) <0.9. Apolipoprotein B48 was quantified by ELISA. Apo B48 was significantly higher in the group with an ABI <0.9 than the groups with ABI of 0.9-1.3 and >1.3 (10.7 ± 6.28 vs. 9.24 ± 5.5 vs. 9.17 ± 8.8 mg/L, ANOVA test, p < 0.05). B48 was independently associated with an ABI <0.9 (OR 1.053; 95 % CI, 1.013-1.094; p < 0.05), together with smoking and duration of diabetes. The preheparin LPL mass was similar in the patients with and without PAD. In conclusion, we confirmed that fasting B48 is an independent marker of PAD in patients with DM2, unrelated to the preheparin LPL mass, statin therapy or glucose lowering treatment.

Introduction: The study of the neural networks involved in music processing has received less attention than work researching the brain's language networks. For the last two decades there has been a growing interest in discovering the functional mechanisms of the musical brain and understanding those disorders in which brain regions linked with perception and production of music are damaged., Discussion: Congenital and acquired musical deficits in their various forms (perception, execution, music-memory) are grouped together under the generic term amusia. In this selective review we present the "cutting edge" studies on the cognitive and neural processes implicated in music and the various forms of amusia., Conclusions: Musical processing requires a large cortico-subcortical network which is distributed throughout both cerebral hemispheres and the cerebellum. The analysis of healthy subjects using functional neuroimaging and examination of selective deficits (e.g., tone, rhythm, timbre, melodic contours) in patients will improve our knowledge of the mechanisms involved in musical processing and the latter's relationship with other cognitive processes., (Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.)

Background:   Postprandial accumulation of atherogenic remnants has been described in patients with type 2 diabetes mellitus (T2DM), familial combined hyperlipidaemia (FCH), familial hypercholesterolaemia (FH) and coronary artery disease (CAD). Scarce data are available on fasting plasma apolipoprotein (apo) B48 levels in relation to these conditions and atherosclerosis., Design:   Treated patients with FCH (18), FH (20), T2DM (26), CAD (65), T2DM with CAD (T2DM/CAD) (28) and 33 healthy controls were included. Intima-media thickness (IMT) measurements were carried out to investigate subclinical atherosclerosis., Results:   LDL-C and total apoB were lowest in patients with T2DM/CAD owing to the more frequent use of lipid-lowering medication. Fasting plasma apoB48 was elevated in patients with FCH (11·38 ± 1·50 mg/L) and T2DM/CAD (9·65 ± 1·14 mg/L) compared with the other groups (anova, P < 0·01). CAD patients (8·09 ± 0·57 mg/L) had higher apoB48 levels than controls (5·74 ± 0·55 mg/L) and FH patients (5·40 ± 0·51 mg/L) (P = 0·02). IMT was highest in subjects with T2DM/CAD (0·77 ± 0·03 mm) (P < 0·01). The lowest IMT was measured in controls (0·56 ± 0·02 mm) and FCH patients (0·60 ± 0·03 mm). In the total group, the best association for apoB48 was found with fasting triglyceride (Pearson's r = 0·72, P < 0·001). In the subjects not using statins (n = 74), the best correlation was found with IMT (r = 0·52; P < 0·001), whereas total apoB was not associated with IMT (r = 0·20, P = 0·12)., Conclusions:   ApoB48 concentrations are highest in patients with FCH and in atherosclerotic subjects with T2DM. In patients not using statins, the surrogate atherosclerosis marker IMT correlates best with apoB48, suggesting that fasting apoB48 may help to detect subjects at risk., (© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.)

Background and Aims: To investigate the prevalence of high cardiovascular risk in the Spanish working population, and its distribution among different occupations and gender., Methods and Results: Cross-sectional study of 309,955 workers (72.6% males, mean age 36.5 years, range 16-74 years), who underwent a routine medical check-up. Workers were classified as high, intermediate or low cardiovascular risk, according to the SCORE system. Workers with a relative risk greater than 4 were also considered as high-risk. The prevalence of high cardiovascular risk was 7.6% (95% CI 7.5-7.7) in males and 1.7% (95% CI 1.6-1.8) in females. After adjusting for age and gender, the prevalence of high cardiovascular risk was greater in workers from the Agriculture and Construction sectors than in those from Industry and Service sectors. The prevalence of high cardiovascular risk was higher in blue-collar than in white-collar occupations., Conclusions: A sizeable proportion of workers, especially blue-collar males, are at high cardiovascular risk. Knowledge of this risk for certain workers may serve as a basis for preventive strategies., (Copyright © 2009. Published by Elsevier B.V.)

Background: Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information., Methods: A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG > or = 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption., Results: We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-epsilon4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p < 0.001) or more (2 or 3 raising variants; OR = 2.90; 95% CI, 1.56-5.41; p < 0.001) were associated with HTG., Conclusion: Our results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the epsilon4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia.

Background: Postprandial hyperlipidemia is a common feature in type 2 diabetes; our aim was to investigate whether there is an association between subclinical peripheral arterial disease (PAD) and the levels of apolipoprotein B48, as a specific marker for postprandial lipidemia., Methods: We enrolled 101 patients with type 2 diabetes and 73 controls free from clinical cardiovascular disease. Main outcome measures were the presence of subclinical PAD, assessed by the ankle-brachial index, and the intestinal particles measured as the concentration of apolipoprotein B48 at fasting and 4h after a mixed breakfast., Results: No control had subclinical PAD. Of the 101 diabetic patients, 21 had subclinical PAD. The levels of apo B48, both fasting and postprandial, were only significantly raised in the diabetic patients who had PAD. The diabetic patients without vascular disease had similar concentrations of triglycerides and apo B48 to the controls. In binary logistic regression analyses, only smoking and postprandial B48 levels, in addition to diabetes, were independently associated with PAD. On the other hand, PAD but not diabetes was associated with the fasting and postprandial levels of apo B48., Conclusion: Our study suggests that apolipoprotein B48 levels might be a marker of occult PAD in patients suffering from type 2 diabetes mellitus. Accordingly, subclinical PAD should be taken into account in studies on postprandial lipidemia involving patients with diabetes., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background: Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia., Methods: Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases) and 31 patients with severe hypertriglyceridaemia (controls) were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed., Results: Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS)., Conclusion: Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during childhood.

Background and Objective: Detection of asymptomatic peripheral arterial disease increases the risk of vascular morbibity and mortality. We aimed to estimate the prevalence of clinical and subclinical peripheral arterial disease using the ankle-arm index (AAI) as diagnostic tool in a working population., Subjects and Method: We included 450 workers, older than 50 years old, attending voluntary regular health check-up at Centro de Prevención de Riesgos Laborales de la Junta de Andalucía in Málaga (Spain). We recorded clinical and anthopometrical data. Blood samples were taken after an overnight fast. Vascular risk was calculated using Framinghan and SCORE scales. Every participant was asked for symptoms of intermittent claudicatio and AAI was measured. AAI was considered normal within 0.9-1.3 values., Results: Most of our workers were at low- or moderate vascular risk. Only 48 (10.6%) of individuals had an abnormal AAI: 9 (2%) showed an AAI<0.9 and 39 (8.6%) showed an AAI>1.3. An AAI<0.9 was found in 19% of those with a SCORE risk > or = 5%, and in 11% of those having a Framinghan risk > or = 20%. Intermittent claudication was present in 4 out of 9 (44%) of those having an AAI<0.9 and in 7 out of 402 (1.7%) with a normal AAI., Conclusions: Systematic screening of peripheral arterial disease using the AAI is not recommended in active working population over 50 years-old of age. Thus, AAI measurement is indicated only for those individuals suffering from intermitent claudicatio and those who are at moderate- or high vascular risk.

Background: Mixed hyperlipidemia is common in patients with diabetes. Statins, the choice drugs, are effective at reducing lipoproteins that contain apolipoprotein B100, but they fail to exert good control over intestinal lipoproteins, which have an atherogenic potential. We describe the effect of prescription omega 3 fatty acids on the intestinal lipoproteins in patients with type 2 diabetes who were already receiving fluvastatin 80 mg per day., Methods: Patients with type 2 diabetes and mixed hyperlipidemia were recruited. Fasting lipid profile was taken when patients were treated with diet, diet plus 80 mg of fluvastatin and diet plus fluvastatin 80 mg and 4 g of prescription omega 3 fatty acids. The intestinal lipoproteins were quantified by the fasting concentration of apolipoprotein B48 using a commercial ELISA., Results: The addition of 4 g of prescription omega 3 was followed by significant reductions in the levels of triglycerides, VLDL triglycerides and the triglyceride/HDL cholesterol ratio, and an increase in HDL cholesterol (P < 0.05). Fluvastatin induced a reduction of 26% in B100 (P < 0.05) and 14% in B48 (NS). However, the addition of omega 3 fatty acids enhanced this reduction to 32% in B100 (NS) and up to 36% in B48 (P < 0.05)., Conclusion: Our preliminary findings therefore suggest an additional benefit on postprandial atherogenic particles when omega 3 fatty acids are added to standard treatment with fluvastatin.

Low-density lipoprotein (LDL) cholesterol concentration has been the prime index of cardiovascular disease risk and the main target for therapy. However, several lipoprotein ratios or "atherogenic indices" have been defined in an attempt to optimize the predictive capacity of the lipid profile. In this review, we summarize their pathophysiological aspects, and highlight the rationale for using these lipoprotein ratios as cardiovascular risk factors in clinical practice, specifying their cut-off risk levels and a target for lipid-lowering therapy. Total/high-density lipoprotein (HDL) cholesterol and LDL/HDL cholesterol ratios are risk indicators with greater predictive value than isolated parameters used independently, particularly LDL. Future recommendations regarding the diagnosis and treatment of dyslipidemia, including instruments for calculating cardiovascular risk or action guidelines, should include the lipoprotein ratios with greater predictive power which, in view of the evidence-based results, are none other than those which include HDL cholesterol.

Objective: To analyze endothelial function in systemic lupus erythematosus (SLE), and its relationship with disease activity and subclinical arteriosclerosis., Methods: We studied a group of 26 patients with SLE and 21 age- and sex-matched controls. None of the patients or controls had had any ischemic event. Data were recorded on medical history, anthropometrics, prior treatment and the lupus activity index (LAI). Endothelial function was quantified by flow-mediated dilatation in the brachial artery. The presence of subclinical arteriosclerosis was assessed by the average intima-media thickness (IMT) on carotid ultrasound., Results: The patients and the controls had a similar degree of carotid IMT (0.58+/-0.08 mm vs. 0.57+/-0.07 mm, NS) and a similar prevalence of carotid plaque (27% vs. 24%, NS). However, the SLE patients had worse endothelial function than the controls (FMD 12.4+/-4.4% vs. 16.9+/-5.5%, p<0.05). This difference remained after adjusting for age, smoking, body mass index, waist circumference, total cholesterol, triglycerides, HDL cholesterol, apolipoproteins A-1 and B100 and postmenopausal status. A significant association was found in the SLE patients between FMD and LAI (Spearman Rho -0.462, p<0.05)., Conclusion: SLE-associated endothelial dysfunction is present in patients who have no prior ischemic events and with the same degree of subclinical arteriosclerosis as controls. The endothelial dysfunction is significantly associated with the degree of disease activity.

Our objective was to analyze the prevalence of peripheral arterial disease (PAD) in HIV patients at risk and to compare them with the general population. All HIV patients older than 50 years who attended our unit from October 2005-July 2006 and all persons attending for an annual medical checkup at an employees' insurance association during the same period were invited to participate in the study. Of the latter (n = 407), a person of the same sex and age (+/-5 years) was included for each HIV patient. PAD was assessed by the ankle-brachial index (ABI) in all subjects, and all completed the Edinburgh questionnaire. Ninety-nine HIV patients and 99 persons from the general population of the same age and sex were included in the study. The HIV patients had a greater prevalence of dyslipidemia, diabetes, and PAD, which was symptomatic in five of them and in one subject from the general population. Patients with HIV infection older than 50 had a high prevalence of PAD, and as it was asymptomatic in half the cases, an ABI may be performed in this population to actively look for PAD. Control of cardiovascular risk factors and the use of such drugs as platelet antiaggregation agents should therefore be optimized in this population.

Aim: This study aimed to investigate the association between a polymorphism in the hepatic lipase (LIPC) gene promoter and the presence of peripheral arterial disease (PAD) in persons with type 2 diabetes., Patient and Methods: We evaluated 120 type 2 diabetics and identified those with PAD according to the ankle-arm index. The G-250A polymorphisms in the promoter of the LIPC gene were studied by PCR restriction. A logistic regression analysis was performed to determine the association between the rare allele and PAD., Results: The prevalence of PAD was 19%. The frequency of the -250A allele was 0.211 in the group without PAD and 0.395 in the group with PAD (P<.05). Carriers of the -250A allele differed only in the ankle-arm index (0.92+/-0.12 for carriers vs. 1.00+/-0.12 for noncarriers, P<.05), with the difference remaining significant after adjustment for covariates (age; sex; waist-to-hip ratio; body mass index; duration of diabetes; smoking; hypertension; glycated hemoglobin; triglycerides; HDL cholesterol; LDL cholesterol; small, dense LDL cholesterol). Only smoking [odds ratio (OR)=6.93, 95% confidence interval (CI)=2.12-22.69, P=.001] and the -250A allele (OR=2.89, 95% CI=1.07-7.84, P=.036) were significantly associated with vascular disease in the logistic regression analysis., Conclusions: Patients with type 2 diabetes who are carriers of the rare -250A allele in the promoter of the hepatic lipase gene are susceptible to PAD.

Objective: To evaluate the effectiveness and safety of anti-tumor necrosis factor (anti-TNF) therapies in rheumatoid arthritis (RA), and to identify the factors involved in this response., Methods: Dynamic prospective cohort study of patients with RA treated with anti-TNF under clinical practice conditions. Effectiveness was evaluated using Disease Activity Score (DAS) 28, European League Against Rheumatism (EULAR) response, Health Assessment Questionnaire (HAQ), and time to treatment failure. Prior adherence was evaluated retrospectively and safety was evaluated by adverse events (AE). The analysis was restricted to anti-TNF-naive patients., Results: The study included 161 patients treated for RA during 6 years (60 infliximab, 79 etanercept, and 22 adalimumab). At 6 months, 15% reached a good EULAR response and 38% a moderate response. A mean decrease of -1.5 (p < 0.0001) was observed in the DAS28 and of -0.34 in the HAQ (p < 0.0001); however, women showed poorer progress in terms of DAS and HAQ. In the first year, 64.3% did not experience treatment failure and this figure was 50.5% after 2 years. In one-third, glucocorticoids were withdrawn and in the remainder the dose was reduced by 50%. Adherence to treatment, selection of etanercept, and intensification of infliximab were associated with a lower probability of premature failure in the multivariate model. AE were similar to other those in studies and no outstanding differences in safety were found between the 3 anti-TNF therapies., Conclusions: Anti-TNF treatments are effective and safe, reducing the activity of the disease, disability, and the need for corticosteroids. Patients who displayed good adherence prior to the anti-TNF treatment and were treated with etanercept or with increasing doses of infliximab had the best chance of displaying a response.

Aims: To determine whether postprandial lipid levels are markers of clinical and subclinical macrovascular disease in a select group of patients with type 2 diabetes., Methods: We recruited 119 local patients with type 2 diabetes and moderate metabolic control (HbA1c <8%). The patients were being treated with dietary measures and/or oral antihyperglycemic therapy. No patient was receiving lipid-lowering therapy. A history of cardiovascular events was recorded and the ankle-arm index was measured to assess subclinical peripheral artery disease. The patients underwent a lipid analysis after a 12-h fast and 4h after a mixed breakfast (50 g of fat, 40 g of carbohydrates)., Results: The patients with clinical and subclinical macrovascular disease had a greater history of smoking, a longer disease duration, and higher serum creatinine levels. The groups with macroangiopathy had lower postprandial concentrations of HDL cholesterol (p<0.05) and a trend towards lower fasting levels of HDL cholesterol (p=0.08) and higher fasting and postprandial levels of triglycerides (p=0.07). Multivariate analysis showed the presence of vascular (both clinical and subclinical) disease to be significantly associated with smoking (OR 3.06; 95% CI, 1.15-8.4), disease duration (for each year, OR 1.12; 95% CI, 1.03-1.22) and postprandial levels of triglycerides (for each 50mg, OR 1.73; 95% CI, 1.13-2.65)., Conclusions: In our diabetic patients, the postprandial level of triglycerides 4h after a fatty breakfast, though not fasting lipids, plus smoking and disease duration were independently associated to clinical and subclinical macrovascular disease.

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium--the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

In the approach to lipid-related risk factors for cardiovascular diseases, serum high density lipoprotein-cholesterol (HDL-C) levels bear a particular significance as this lipoprotein is considered to be an antiatherogenic factor mainly, but not only, because of its influence and impact on reverse cholesterol transport. Hence the need and requirement to consider serum HDL-C levels for both primary and secondary prevention of cardiovascular disease. A particularly important aspect is the association of the 'low HDL syndrome' with the metabolic syndrome. These factors force us to consider serum HDL-C level as a therapeutic target by itself, or even in association with low density lipoprotein-cholesterol (LDL-C) levels when the latter are increased. This review stresses the aspects connecting serum HDL-C levels and cardiovascular risk, and looks at the populations that should be considered amenable to therapeutic management because of low serum HDL-C levels. We review therapeutic strategies, both pharmacological and nonpharmacological. The aim of this review is to present therapeutic management recommendations for correcting the proportion of cardiovascular risk that is attributable to changes in HDL-C. Serum HDL-C levels of >40 mg/dL must be a therapeutic target in primary and secondary prevention. This goal is particularly important in patients with low serum HDL-C levels and ischemic heart disease (IHD) or its equivalents, even if the therapeutic target for serum LDL-C levels (<100 mg/dL) has been achieved. The first choice for this clinical condition is fibric acid derivates. The same therapeutic option should be considered in patients without IHD with low serum HDL-C levels and high cardiovascular risk (>20%), hypertriglyceridemia, type 2 diabetes mellitus, or metabolic syndrome.

The liver is frequently involved by amyloidosis, but hyperbilirubinemia and liver failure are uncommon features. A mild elevation of the serum alkaline phosphatase value and, less frequently, hepatomegaly are the most common findings. Usually the patients have no symptoms related with the liver involvement; the clinical manifestation and the long term prognosis depends on the renal and cardiac disease. We report an unusual clinical presentation of primary amyloidosis in a previously asymptomatic 65 years old woman who was admitted to the hospital because of ictericia and ascitis mimicking a drug induced acute hepatic failure.

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Objective: To report the natural history of patients with hepatitis C virus (HCV) infection and hepatocarcinoma (HCC) and to define clinico-biological variables with prognostic and predictive value of this complication., Materials and Methods: A total of 543 patients consecutively diagnosed of chronic infection with HCV were included and followed prospectively and observationally regarding the development of HCC by means of semestral abdominal ultrasonography and measurement of serum alpha-fetoprotein (AFP). To determine variables with predictive value of HCC, the parameters determined at the start were compared, and all subjects diagnosed of hepatoma during the first twelve months after admission were excluded from the analysis. The Kaplan-Meier method was used to evaluate both survival and accumulated probability of HCC., Results: During a mean follow-up period of 28.9 months, an incidence density of HCC of 2.6 per 100 inhabitants-year was obtained (n = 35). 52.6% of those with HCC in the first year were asymptomatic. The only initial variables associated with further development of HCC were age (64.6 vs 58.4 years; p = 0.0039) and alkaline phosphatase (373.5 vs 259 U/l; p = 0.001). Patients with cirrhosis at the start of the study had a higher risk of developing hepatoma than non-cirrhotic patients (RR: 11.5; 95% CI: 4.25-29.9; p < 0.0001). The presence of HCC decreased the survival of patients with cirrhosis (median 20 vs 75 months; log rank < 0.0001), with the exception of patients in stage C of the Child-Pugh classification., Conclusions: a) In the chronic infection with HCV, HCC showed to be an oligosymptomatic complication affecting almost exclusively patients with long-lasting cirrhosis. b) Survival in patients in the stage C of the Child-Pugh classification is independently associated with the coexistence of hepatoma; therefore, the early diagnosis of this complication should be restricted to those with a better liver functional reserve.

Background: Interferon therapy has been shown to induce lipid abnormalities., Aim: We assessed the effects of interferon-beta on the lipoprotein profile and post-heparin lipase activities in 26 normolipaemic patients with chronic hepatitis C., Methods: Interferon-beta was administered subcutaneously at doses of 6 x 106 U (units) three times a week, over 6 months, and lipoproteins and post-heparin lipases were measured at baseline and at the end of therapy., Results: Plasma triglycerides increased by 21% due to preferential enrichment in those contained in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions. The concentration of cholesterol decreased slightly in the high density lipoprotein (HDL) subfractions. Lipoprotein lipase, but not hepatic lipase activity decreased by a 36%, and this change showed a significant negative correlation with changes in plasma triglycerides. Five patients (19.5%) responded to interferon-beta therapy. The lipoprotein profile was no different between responders and non-responders to therapy., Conclusions: Interferon-beta treatment in normolipaemic patients with chronic hepatitis C induced moderate disturbances in plasma lipoproteins, associated with inhibition of lipoprotein lipase activity.