Clinical characterization and detection of subclinical atherosclerosis in subjects with extreme hyperalphalipoproteinemia. / Caracterización clínica y detección de arteriosclerosis subclínica en sujetos con hiperalfalipoproteinemia extrema.

INTRODUCTION AND OBJECTIVES: The association between HDL cholesterol (HDL-C) levels and death from cardiovascular disease follows a U-shaped pattern, increasing at the extremes. The objective of the study was to characterize a sample of subjects with extreme hyperalphalipoproteinemia (HAE). MATERIAL AND METHODS: 53 cases with HAE were recruited, 24 women (HDL-C>135mg/ dL) and 29 men (HDL-C>116mg/ dL). A detailed medical history was taken and questionnaires on adherence to the Mediterranean diet and physical activity were collected. Carotid ultrasounds were performed to detect the presence of suclinical atherosclerosis. RESULTS: The most prevalent cardiovascular risk factor (CVRF) was dyslipidemia (64%) with no significant differences between men and women, unlike hypertension (21% in women, versus 55% in men, p=0.01) and others CVRF, for example, diabetes. 7% of the series had previous cardiovascular disease, women had higher LDL cholesterol (p=0.002) and HDL-C than men (without significant differences). Plaque was detected in 53% of cases, being more prevalent in men. Patients with plaque were older, drank more alcohol and smoked more (p<0.05). CONCLUSIONS: Men had a higher prevalence of CVRF than women, except for dyslipidemia. Subclinical atherosclerosis occurred in more than half of the series. Age, alcohol consumption and smoking were independently associated with the presence of plaque, however, our data do not show a significant influence of HDL-C levels.

Acuerdo intra-interobservador en las pruebas Minimental State Examination (MMSE) y Montreal Cognitive Assessment (MoCA test) aplicados por personal en entrenamiento / Intra and interrater reliability of the Minimental State Exmination (MMSE) and Montréal Cognitive Assessment (MoCA test) applied by health personnel in training

Introducción: en el proceso del diagnóstico neuropsicológico, los instrumentos de tamizaje cognitivo, son una herramienta útil en la identificación de cambios mentales del sujeto, en momentos puntuales o a través del tiempo. Su uso se fundamenta en el análisis psicométrico. Objetivo: determinar el acuerdo inter e intra-observador en el MoCA test y el MMSE, aplicado por profesores y estudiantes en procesos de entrenamiento de tamización cognitiva. Materiales y métodos: a los estudiantes y profesores en entrenamiento en la puntuación del MoCA test y el MMSE, se les presentó un video en dos sesiones, con un intervalo de 5 meses, mostrando el desempeño de dos adultos mayores, respondiendo el MoCA test y el MMSE, previo consentimiento informado. Se compararon los puntajes dados en las dos sesiones por los sujetos en entrenamiento, con los de ellos mismos (intra-observador), usando el coeficiente de concordancia y correlación de Lin(rho) y con los del grupo restante (inter-observador) usando el coeficiente de correlación intra-clase (ICC). Resultados: participaron 46 evaluadores. Se encontró alta confiabilidad inter-observador para el MoCA (ICC=0.86), pero baja para el MMSE (ICC=0.24) y baja confiabilidad intra-observador tanto para el MoCA (rho paciente 1=0.012 y rho paciente 2=0.152) como para el MMSE (rho paciente 1=0.008 y rho paciente 2=0.012). Aunque los puntajes difirieron, las clasificaciones diagnósticas realizadas por los evaluadores fueron similares a las del patrón de oro. Conclusión: la correcta aplicación del test, requiere varios entrenamientos, y aunque hubo pocas diferencias entre los puntajes, los errores cuando se está cerca del punto de corte propuesto, aumentan el riesgo de sesgo.

Introduction: The instruments for screening cognitive functions, applied to subjects in clinical settings and research, are useful for determining if this person has any trouble in cognition or show changes in the time. The usefulness of these instruments is defined with the evaluation of their psychometrics properties. Objective: This study allows to determine the intra and inter-observer agreement, when the MoCA test and MMSE were applied by a group in training process Materials and methods: The study group who attended two training sessions, with an interval of 5 months, scored the MoCA test and MMSE, from two patients which were filmed responding the tests, previous informed consent signature. We compared how close were the scores of participants among themselves by concordance correlation coefficient of Lin (rho) and with those given from the others by intra-class correlation coefficients (ICC). Results: In total, 46 participants were included. Intra-rater reliability was high for MoCA test (ICC = 0.86), but it was poor for MMSE (ICC=0.24). Inter-rater was poor for MoCA test (rho patient 1= 0.012, rho patient 2= 0.152) and MMSE (rho patient 1 = 0.008, rho patient 2 = 0.012). Although the scores between participants and gold standard were different, the diagnoses were similar. Conclusion:The correct scoring of the test, requires several trainings to clinical and research groups, and although they can be found few differences between scores applied by non-expert personnel, if the scores mistakenly given, are close to the cut-of point proposed for each test, the bias increases.

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.

Association of the -250G/A promoter polymorphism of the hepatic lipase gene with the risk of peripheral arterial disease in type 2 diabetic patients.

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.

Smoking and postprandial triglycerides are associated with vascular disease in patients with type 2 diabetes.

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.