The association of lipoprotein(a) and apolipoprotein(a) phenotypes with peripheral artery disease.

AIM: Lipoprotein(a) [Lp(a)] is an independent risk factor of coronary heart disease (CHD) and myocardial infarction. Data about the role of Lp(a) in the development of peripheral artery disease (PAD) is controversial and uncertain. The aim of the study was to evaluate the association between Lp(a), apolipoprotein(a) [apo(a)] phenotypes and PAD. MATERIALS AND METHODS: The study included 998 patients (707 male and 291 female, average age 60±12). The patients were divided into 4 groups depending on the presence or absence PAD and CHD: group I (n=188, PAD+CHD+), group II (n=78, PAD+CHD-), group III (n=407, PAD-CHD+), group IV (n=325, PAD-CHD-). RESULTS: The level of Lp(a) was significantly higher in groups I, II, III in comparison with patients of control group (group IV): 34 [15; 80], 30 [10; 49], 22 [8; 60] mg/dl vs. 15 [6; 35] mg/dl respectively, p<0.01 in all cases. Lp(a) level was higher in the group I than in the other groups (p<0.05). The prevalence of elevated Lp(a) level (≥ 30 mg/dl) was significantly higher in groups I, II, III than in control group: 54%, 50%, 43% respectively vs. 30%, p<0.01 in all cases. The prevalence of Lp(a) ≥ 30 mg/dl was more frequent in the group with PAD and CHD than in the group with CHD and without PAD (p=0.02). The odds ratio (OR) of PAD in the presence of elevated Lp(a) level was 1.9 (95%CI, 1.4-2.5, p<0.01). Low molecular weight (LMW) apo(a) phenotype was met more frequently in groups I, II, III compared to group IV: 46%, 56%, 52% respectively vs. 28%, p<0.01. LMW apo(a) in the patients without CHD was associated with PAD (OR 3.3; 95% CI, 1.6-6.8, p<0.01), and there was no association with the patients with CHD. In logistic regression analysis adjusted for age, sex, hypertension, obesity, smoking, diabetes, LDL-C, Lp(a) and LMW apo(a) phenotype were independent predictors of PAD when included separately. CONCLUSION: Elevated level of Lp(a) and LMW apo(a) phenotype are independent risk factors of PAD. The level of Lp(a) in the patients with PAD and CHD was higher than in the case of isolated lesion of each vascular pool. Higher level of Lp(a) is associated with more severe atherosclerosis involving more than one vascular pools.

Simultaneous quantitation and size characterization of apolipoprotein(a) by ultra-performance liquid chromatography/mass spectrometry.

RATIONALE: Apolipoprotein(a) is a polymorphic glycoprotein covalently bound to apoB100 in Lp(a) particles and has been described to be both atherogenic and prothrombotic, although its exact mechanism of action is not well defined. Apolipoprotein(a) is routinely measured by immunoassays. Unfortunately, the accuracy of the measurement can be affected by the apolipoprotein(a) size (number of kringles) polymorphism in Lp(a) particles. Here we describe an ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) assay that is capable of measuring apolipoprotein(a) concentrations while simultaneously determining the number of kringles present per protein. METHODS: Plasma samples were diluted and proteins de-lipidated with deoxycholate prior to tryptic digestion. Distinct tryptic peptides from different regions of apolipoprotein(a) were measured to determine both concentration and the number of kringles present per protein. Separation and quantitation of tryptic peptides is carried out at 700 µL/min using a 1.7 µm C18 column (2.1 × 100 mm) coupled to a Thermo Vantage triple quadrupole (QQQ) mass spectrometer with a heated electrospray ionization (HESI) source. RESULTS: This method was compared to established methods for measuring concentration (monoclonal antibody based ELISA) and size (gel-electrophoresis) using 80 plasma samples proved by NWLRL. The slope and r(2) value for the correlation of concentrations were determined to be 0.96 and 0.98, demonstrating excellent agreement of absolute values between the UPLC/MS and ELISA methods. As measured by UPLC/MS, the average kringle number or size is smaller than determined by the electrophoretic method. CONCLUSIONS: A single UPLC/MS method was developed capable of measuring apolipoprotein(a) concentration and size (by measuring the number of kringles per protein). This assay passes criteria required for 'fit for purpose' assays including sensitivity, intra and interday reproducibility and freeze/thaw stability. While the agreement between UPLC/MS and ELISA is excellent for concentration and may provide researchers with additional tools for studying apolipoprotein(a), the dissimilarities between UPLC/MS and the electrophoretic method may also be exploited for understanding apolipoprotein(a) structure and function.

[Apolipoprotein(a) isoforms immunoblotting detection: comparative study of two methods]. / Immunorévélation des isoformes d'apolipoprotéine(a) : étude comparée de deux méthodes.

This study reports the comparison between two methods (chemiluminescence and enzymatic colorimetry) for revelation of apolipoprotein(a) [apo(a)] isoforms by immunoblotting in 102 Ivorian healthy subjects. Apo(a) isoform sizes were determined by sodium dodecyl sulfate-agarose-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting using enzymatic colorimetry or chemiluminescence. Within-run precision was comprised between 4.9% and 9.2% for colorimetry and between 2.9% and 4.6% for chemiluminescence. Both methods have detected apo(a) isoforms in all patients, even when lipoprotein(a) concentrations were under detection limit (0.02 g/L). The two methods were significantly correlated (r = 0.96 to 0.98, p<0.0001). Even though the chemiluminescence method exhibited better performances than the colorimetric method, both techniques could be used indifferently.

Grasa epicárdica y su asociación con marcadores de aterosclerosis subclínica y otros factores de riesgo en pacientes con síndrome metabólico / Epicardial fat and its association with markers of subclinical atherosclerosis and other risk factors in patients with metabolic syndrome

Introducción La grasa epicárdica ha mostrado una estrecha asociación con diversos marcadores de aterosclerosis subclínica. Sin embargo, en pacientes con síndrome metabólico (SM) los estudios son escasos y ninguno ha sido realizado en pacientes hispanos. Por ello decidimos evaluar la posible relación de la grasa epicárdica con marcadores de aterosclerosis subclínica y otros factores de riesgo cardiovascular en pacientes con SM. Métodos Se estudiaron 115 pacientes (76 mujeres y 39 hombres, con una edad media de 56,9±8,6 vs 56,7±9,4 años, respectivamente) con diagnóstico de SM. Se recogieron variables clínicas (edad, sexo, antecedentes de tabaquismo, presión arterial sistólica [PAS] y diastólica [PAD]), antropométricas (índice de masa corporal [IMC] y circunferencia de la cintura) y hemoquímicas (glucemia, colesterol total, colesterol HDL, colesterol LDL, triglicéridos, apolipoproteína B [ApoB], apolipoproteína A-I [ApoA-I] y ratio ApoB/ApoA-I). Realizamos además un examen ecocardiográfico transtorácico y carotídeo a todos los participantes, y cuantificación del calcio arterial coronario en 79 pacientes. Resultados La grasa epicárdica mostró una asociación significativa e independiente con la presencia de un grosor íntima-media (GIM) carotídeo >75 percentil (OR: 1,51; IC: 1,22-1,86; p=0,000). Los valores de grasa epicárdica fueron significativamente mayores en los pacientes con presencia de placa ateromatosa carotídea (6,39±1,8 vs 5,14±2,4mm; p=0,007), incremento en los cuartiles de calcificación arterial coronaria (p=0,042) y con un ratio ApoB/ApoA-I elevado para hombres y mujeres (p=0,027, p=0,037, respectivamente).Conclusiones La grasa epicárdica mostró una asociación significativa e independiente con marcadores de aterosclerosis subclínica, así como el ratio ApoB/ApoA-I en pacientes con SM (AU)

Introduction Epicardial fat has been shown to be strongly associated with several markers of subclinical atherosclerosis. However, few studies have been performed in patients with metabolic syndrome and none has been carried out in Hispanic patients. The purpose of our study was to determine the relationship between epicardial fat and markers of subclinical atherosclerosis and other cardiovascular risk factors in patients with metabolic syndrome. Methods A total of 115 patients (76 women and 39 men, mean age 56.9±8.6 vs 56.7±9.4 years, respectively) with metabolic syndrome were studied. We included clinical (age, sex, smoking history, systolic and diastolic blood pressure), anthropometric (body mass index and waist circumference) and biochemical variables (fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein [Apo] B, Apo A-I and the ApoB/ApoA-I ratio). We also performed a transthoracic echocardiography and ultrasonographic carotid examination in all participants as well as coronary artery calcium score quantification in 79 patients. Results Epicardial fat was significantly and independently associated with the presence of carotid intima-media thickness >75th percentile (OR: 1.51; CI: 1.22-1.86; P=.000). Epicardial fat values were significantly higher in patients with carotid plaque (6.39±1.8 vs 5.14±2.4mm, P=.007), an increase in coronary calcium score quartiles (P=.042) and a high ApoB/ApoA-I ratio in both men and women (P=.027 and P=.037, respectively).Conclusions Epicardial fat was significantly and independently associated with several markers of subclinical atherosclerosis, as well as with the ApoB/ApoA-I ratio in patients with metabolic syndrome (AU)

Conmoción cerebral en el deporte / Concussion in Sports an up to date

Realizamos una revisión y puesta al día del manejo del atleta que ha sufrido una conmoción cerebral hasta su regreso a la práctica del deporte, además de evaluar las diferencias entre distintos grupos de atletas, para explicar los mecanismos neuronales que intervienen tras una conmoción cerebral, así como los factores genéticos que puedan predisponer a sufrir una conmoción cerebral (AU)

This article is an up to date about concussions in athletes in the last 2 years. The revision includes the immediate response at the sideline and the return to play protocol with attention in the different population of athletes. There is a great interest in trying to understand the neurological mechanisms that intervene in the concussed athlete and the genetic factors that may predispose some athletes to suffer more concussions (AU)

Variabilidade interensaios de dislipidemias em pacientes hipertensos / Inter-assays variability of dislipidemias in hypertensive patients

INTRODUÇÃO E OBJETIVOS: Ensaios de diferentes procedências para avaliação das dislipidemia podem resultar em variações significativas nos resultados obtidos e consequente conduta inadequada pelo clínico. O estudo objetivou comparar resultados laboratoriais de colesterol total (CT), triglicérides (TG), colesterol da lipoproteína de alta densidade (HDL-C), colesterol da lipoproteína de baixa densidade (LDL-C), apolipoproteína A-1 (Apo A-1), apolipoproteína B (Apo B) e lipoproteína (a) (Lp[a]) e índices lipídicos (não-HDL-C, CT/HDL-C, LDL-C/HDL-C, TG/HDL-C e Apo B/HDL-C) de pacientes hipertensos e/ou diabéticos diagnosticados. MÉTODOS: Foram utilizados conjuntos reativos, e os respectivos analisadores Gold Analisa, Dia Sys (CCX - Abbott), Dade Behring (Nefelômetro BN 100) e Roche (COBAS Integra 400), para verificar a reprodutibilidade dos resultados obtidos. Participaram 99 pacientes (36 do sexo masculino e 63 do feminino). Comparando os resultados, verificamos que: todas as médias obtidas dos constituintes lipídicos apresentaram diferença significativa; número semelhante de pacientes apresentou níveis séricos elevados de CT, TG, Lp(a) e Apo A-1. O HDL-C, o LDL-C e a Apo B apresentaram discordância, assim como os índices de CT/LDL-C, LDL-C/HDL-C e TG/HDL-C. Para não-HDL-C e ApoB/HDL, houve semelhança no número de pacientes com valores não recomendados. Em consequência da diferença, em relação ao LDL-C, a decisão da conduta terapêutica poderá ser inadequada, enquanto o não-HDL-C, além de evidenciar partículas aterogênicas, apresentou número de hipertensos com valores séricos não referendados semelhantes, independente da metodologia e do equipamento utilizado. CONCLUSÃO: No grupo de hipertensos analisados, o não-HDL-C se caracterizou um importante fator de correção interensaios de parâmetros lipídicos. E sua associação à relação Apo B/HDL-C pode ser um fator adicional em relação às condutas hipolipemiantes a serem adotadas.

INTRODUCTION AND OBJECTIVES: Different assays to evaluate dyslipidemia may show significant variations in the obtained results and a consequent inappropriate clinical approach may be adopted. This study aimed to compare the results of total cholesterol (CT), triglycerides (TG), HDL-C, Apo A1, Apo B, lipoprotein (a) and lipidic indexes (not-HDL-C, CT/HDL-C, LDL-C/HDL-C, TG/HDL-C and Apo B/HDL-C) of hypertensive and/or diabetic patients. METHODS: The following reactive kits and respective analyzers were applied to verify the reproducibility of results: Gold Analisa, DiaSys (CCX-ABBOTT), Dade Behring (Nephelometer BN 100) and Roche (COBAS Integra 400). Ninety nine patients (36 male and 63 female gender) were investigated. Comparing the results, we observed that all mean numbers of lipid constituents showed a significant difference. A similar number of patients had high CT, TG, Lp (a) and Apo A-1 serum levels. There was also disagreement in HDL-C, LDL-C, ApoB, CT/LDL-C, LDL-C/HDL-C and TG/HDL-C indexes. For not-HDL-C and ApoB/HDL, there was similarity in the number of patients with not recommended values. As a consequence of this difference, the choice of therapeutic approach may be inappropriate as to LDL-C levels, whereas Not-HDL-C not only showed atherogenic particles but also a number of hypertensive patients with similar not recommended serum values, regardless of the methodology and the equipment used. CONCLUSION: In the analyzed group of hypertensive patients, not-HDL-C was an important inter assay correction factor of lipidic parameters. The association with Apo B/HDL-C relation may be an additional factor as to the choice of hypolipemiant treatments.

Adiponectin levels and cardiovascular risk factors in hypothyroidism and hyperthyroidism.

OBJECTIVE: Adiponectin, an adipose tissue-derived hormone, has been reported to have anti-inflammatory and anti-atherogenic effects. The physiological effect of adiponectin on the metabolic changes and its relation with cardiovascular risk factors in thyroid dysfunction states is still not clear. The aim of the study was to evaluate plasma adiponectin level and its relation to cardiovascular risk factors in patients with thyroid dysfunction. PATIENTS AND MEASUREMENTS: Sixty-seven patients with hypothyroidism, 56 patients with hyperthyroidism and 52 age- and sex-matched euthyroid subjects were enrolled in the study. Adiponectin, C-reactive protein (CRP), homocysteine (Hcy), lipid parameters, Lipoprotein(a) [Lp (a)], Apolipoprotein (Apo) A, Apo B and fibrinogen levels were measured in all subjects. Insulin sensitivity was determined using the Homeostasis Model Assessment (HOMA-IR). RESULTS: Circulating adiponectin levels were not different between the groups (16.2 +/- 5.0, 15.1 +/- 3.7, 15.9 +/- 4.8 ng/ml; hypothyroid, hyperthyroid, euthyroid group, respectively). Plasma adiponectin levels correlated negatively with body mass index (BMI) and HOMA-IR index and positively with high-density lipoprotein cholesterol (HDL-C) in all groups. There was a significant correlation between adiponectin and CRP levels in both hypothyroid and hyperthyroid groups. In all groups, adiponectin levels did not correlate with age, systolic blood pressure, diastolic blood pressure and thyroid hormones. Multiple regression analysis revealed BMI and HDL-C levels to be the most important predictors of circulating adiponectin levels. CONCLUSIONS: Plasma adiponectin levels are associated with BMI and HDL-C levels in patients with hypothyroidism and hyperthyroidism. But there is not a direct relation of adiponectin with thyroid hormones in these patients.