Prevalence of atherogenic dyslipidemia: association with risk factors and cardiovascular risk in Spanish working population. "ICARIA" study.

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.

Clinical decisions in patients with diabetes and other cardiovascular risk factors. A statement of the Spanish Society of Internal Medicine.

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.

Familial hypobetalipoproteinemia: analysis of three Spanish cases with two new mutations in the APOB gene.

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.

Model of music cognition and amusia.

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.

Fasting apolipoprotein B48 is a marker for peripheral arterial disease in type 2 diabetes.

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.

Childhood-onset chylomicronaemia with reduced plasma lipoprotein lipase activity and mass: identification of a novel GPIHBP1 mutation.

OBJECTIVES: Deficiency in the catabolism of triglyceride-rich lipoproteins is the main cause of childhood-onset chylomicronaemia syndrome. Missense mutations in lipoprotein lipase (LPL) or in proteins influencing LPL activity or stability have been shown to be critical determinants of chylomicronaemia syndrome. The main objective of this study was to assess the primary deficiency in five cases of childhood-onset chylomicronaemia syndrome. SETTING: Lipid clinic at a university hospital, SUBJECTS: Subjects presenting with severe hypertriglyceridaemia and chylomicronaemia syndrome in which reduced LPL activity and mass were observed. INTERVENTIONS: Analysis of LPL and GPIHBP1 genes. RESULTS: Amongst the five patients, one novel homozygous missense mutation (p.C68Y) in exon 3 of GPIHBP1 was identified. The other four patients were homozygous for the common LPL mutation p.G188E. CONCLUSION: These findings provide further evidence that GPIHBP1 is involved in the catabolism of triglyceride-rich lipoproteins and plays a role in childhood-onset chylomicronaemia.

High cardiovascular risk in Spanish workers.

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.

Postprandial apolipoprotein B48 is associated with asymptomatic peripheral arterial disease: a study in patients with type 2 diabetes and controls.

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.

Lupus-associated endothelial dysfunction, disease activity and arteriosclerosis.

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.

Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".

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.

[Hepatic amyloidosis as cause of severe intrahepatic cholestasis]. / Amiloidosis hepática como causa de colestasis severa intrahepática.

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.

Lessons from the "Euro-Lupus Cohort".

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.

Increment of the platelet count in temporal arteritis: response to therapy and ischemic complications.

Temporal arteritis (TA) is a vasculitis involving mainly cranial branches of the aorta that can lead to ischemic complications such as amaurosis or ischemic stroke. Increment in the platelet count has been described in the acute period of the disease. We studied retrospectively the platelet count in patients with TA, its association with ischemic complications and quantified its response to therapy. We found thrombocytosis in 44% of 34 patients with TA, with a mean reduction in the platelet count of 25.1% after therapy. We were also able to quantify the increment in the platelet count at the onset of the disease and its response to prednisone in a group of 5 patients. We did not find any relation between platelet count and ischemic complications of the disease or the result of the temporal artery biopsy. In conclusion TA is associated with an increase in the platelet count, with a 25% reduction after prednisone therapy. These two determinations are not related to ischemic complications of the disease.

[Incidence and natural history of hepatocellular carcinoma in patients with chronic hepatitis C virus infection]. / Incidencia e historia natural del carcinoma hepatocelular en los pacientes con infección crónica por el virus de la hepatitis C.

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.

Effects of interferon-beta on plasma lipid and lipoprotein composition and post-heparin lipase activities in patients with chronic hepatitis C.

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.