Exploring the value of apoB48 as a marker for atherosclerosis in clinical practice.

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.

Triglyceride levels and apolipoprotein E polymorphism in patients with acute pancreatitis.

BACKGROUND: Hypertriglyceridemia is an unusual cause of acute pancreatitis and sometimes considered to be an epiphenomenon. This study aimed to investigate the clinical and analytical features and the APOE genotypes in patients with acute pancreatitis and severe hypertriglyceridemia. METHODS: We undertook a one-year, prospective study of patients with acute pancreatitis whose first laboratory analysis on admission to the emergency department included measurement of serum triglycerides. The APOE genotype was determined and the patients answered an established questionnaire within the first 24 hours concerning their alcohol consumption, the presence of co-morbidities and any medications being taken. The patients' progression, etiological diagnosis, hospital stay and clinical and radiological severity were all recorded. RESULTS: Hypertriglyceridemia was responsible for 7 of 133 cases of pancreatitis (5%); the remaining cases were of biliary (53%), idiopathic (26%), alcoholic (11%) or other (5%) origin. Compared with these remaining cases, the patients with hypertriglyceridemia were significantly younger, had more relapses, and more often had diabetes mellitus. They usually consumed alcohol or consumed it excessively on the days before admission. Also, the ε4 allele of the APOE gene was more common in this group (P<0.05). CONCLUSION: One of 20 episodes of acute pancreatitis is caused by hypertriglyceridemia and it is linked to genetic (ε4 allele) and comorbid factors such as diabetes and, especially, alcohol consumption.

Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study.

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.

Omega 3 fatty acids induce a marked reduction of apolipoprotein B48 when added to fluvastatin in patients with type 2 diabetes and mixed hyperlipidemia: a preliminary report.

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.

Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis.

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.

[Usefulness of the ankle-arm index for detection of peripheral arterial disease in a working population of Junta de Andalucía at Málaga]. / Rentabilidad del índice tobillo-brazo para la detección de enfermedad arterial periférica en población laboral de la Junta de Andalucía en Málaga.

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.

Management of dyslipidemia in the metabolic syndrome: recommendations of the Spanish HDL-Forum.

In order to characterize the metabolic syndrome it becomes necessary to establish a number of diagnostic criteria. Because of its impact on cardiovascular morbidity/mortality, considerable attention has been focussed on the dyslipidemia accompanying the metabolic syndrome. The aim of this review is to highlight the fundamental aspects of the pathophysiology, diagnosis, and the treatment of the metabolic syndrome dyslipidemia with recommendations to clinicians. The clinical expression of the metabolic syndrome dyslipidemia is characterized by hypertriglyceridemia and low levels of high-density lipoprotein-cholesterol (HDL-C). In addition, metabolic syndrome dyslipidemia is associated with high levels of apolipoprotein (apo) B-100-rich particles of a particularly atherogenic phenotype (small dense low-density lipoprotein-cholesterol [LDL-C]. High levels of triglyceride-rich particles (very low-density lipoprotein) are also evident both at baseline and in overload situations (postprandial hyperlipidemia). Overall, the 'quantitative' dyslipidemia characterized by hypertriglyceridemia and low levels of HDL-C and the 'qualitative' dyslipidemia characterized by high levels of apo B-100- and triglyceride-rich particles, together with insulin resistance, constitute an atherogenic triad in patients with the metabolic syndrome. The therapeutic management of the metabolic syndrome, regardless of the control of the bodyweight, BP, hyperglycemia or overt diabetes mellitus, aims at maintaining optimum plasma lipid levels. Therapeutic goals are similar to those for high-risk situations because of the coexistence of multiple risk factors. The primary goal in treatment should be achieving an LDL-C level of <100 mg/dL (or <70 mg/dL in cases with established ischemic heart disease or risk equivalents). A further goal is increasing the HDL-C level to >or=40 mg/dL in men or 50 mg/dL in women. A non-HDL-C goal of 130 mg/dL should also be aimed at in cases of hypertriglyceridemia. Lifestyle interventions, such as maintaining an adequate diet, and a physical activity program, constitute an essential part of management. Nevertheless, when pharmacologic therapy becomes necessary, fibrates and HMG-CoA reductase inhibitors (statins) are the most effective drugs in controlling the metabolic syndrome hyperlipidemia, and are thus the drugs of first choice. Fibrates are effective in lowering triglycerides and increasing HDL-C levels, the two most frequent abnormalities associated with the metabolic syndrome, and statins are effective in lowering LDL-C levels, even though hypercholesterolemia occurs less frequently. In addition, the combination of fibrates and statins is highly effective in controlling abnormalities of the lipid profile in patients with the metabolic syndrome.

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment (II). The treatment of nonalcoholic fatty liver disease. / Enfermedad del hígado graso no alcohólico, asociación con la enfermedad cardiovascular y tratamiento (II). Tratamiento de la enfermedad del hígado graso no alcohólico.

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.

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment. (I). Nonalcoholic fatty liver disease and its association with cardiovascular disease. / Enfermedad del hígado graso no alcohólico, asociación con la enfermedad cardiovascular y tratamiento (I). Enfermedad del hígado graso no alcohólico y su asociación con la enfermedad cardiovascular.

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.

[The real measurement of non-HDL-cholesterol: Atherogenic cholesterol]. / La auténtica dimensión del colesterol-no-HDL: colesterol aterogénico.

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.

[Fibrates therapy: Rational use fenofibrate 2016. Executive summary]. / Terapia con fibratos: uso racional del fenofibrato 2016. Resumen ejecutivo.

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.

Alzheimer's like brain changes correlate with low adiponectin plasma levels in type 2 diabetic patients.

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.

[The role of atherogenic dyslipidaemia in clinical practice guidelines]. / El papel de la dislipemia aterogénica en las guías de práctica clínica.

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.

Significance of high density lipoprotein-cholesterol in cardiovascular risk prevention: recommendations of the HDL Forum.

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 combinations of statins and fibrates: pharmacokinetic and clinical implications]. / Combinaciones de estatinas y fibratos: implicaciones farmacocinéticas y clínicas.

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.

[Glucagon-like peptide-1 (GLP-1) mimetics: a new treatment for Alzheimer's disease?]. / Análogos del glucagon-like peptide-1 (GLP-1): ¿una nueva estrategia de tratamiento para la enfermedad de Alzheimer?

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.

TITLE: Analogos del glucagon-like peptide-1 (GLP-1): una nueva estrategia de tratamiento para la enfermedad de Alzheimer?Introduccion. Los analogos del glucagon-like peptide-1 (GLP-1) son una opcion terapeutica establecida en los pacientes con diabetes tipo 2. Sin embargo, las propiedades de los analogos del GLP-1 van mas alla del control estrictamente metabolico del paciente diabetico. Los efectos neuroprotectores de los analogos del GLP-1 se han puesto de manifiesto en estudios recientes y han abierto nuevos campos de investigacion en trastornos neurodegenerativos como la enfermedad de Alzheimer (EA), entre otros. Objetivo. Revision sistematica de los estudios experimentales y ensayos clinicos en humanos que demuestran las propiedades neuroprotectoras de los analogos del GLP-1 en la EA. Desarrollo. Los estudios experimentales que se han llevado a cabo en modelos de roedores con EA demuestran las propiedades neuroprotectoras de los analogos del GLP-1 sobre el sistema nervioso central que reducen las placas de beta-amiloide, el estres oxidativo y la respuesta inflamatoria cerebral. Recientemente se han puesto en marcha estudios con analogos del GLP-1 en humanos con deterioro cognitivo y EA. Conclusiones. Los analogos del GLP-1 presentan propiedades neuroprotectoras. Al considerarse la diabetes tipo 2 un factor de riesgo para el deterioro cognitivo y la demencia, deben considerarse los beneficios de los analogos del GLP-1 sobre la cognicion. Del mismo modo, los analogos del GLP-1 suponen un tratamiento prometedor en la EA.

Use of expert consensus to improve atherogenic dyslipidemia management.

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.

Cognitive dysfunctions in middle-aged type 2 diabetic patients and neuroimaging correlations: a cross-sectional study.

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.

Structural and functional brain changes in middle-aged type 2 diabetic patients: a cross-sectional study.

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.

Incidence of cancer in a cohort of Spanish patients with systemic lupus erythematosus.

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.