María Vela

Apolipoprotein E polymorphism and gallstones

BACKGROUND & AIMS Apolipoprotein (apo) E is a genetically polymorphic protein influencing lipoprotein metabolism and the risk of both atherosclerosis and Alzheimers disease. As opposed to common apo E3, apo E2 decreases and apo E4 increases hepatic lipoprotein uptake; hence, apo E4 could promote gallstone formation by increasing hepatic and biliary cholesterol concentrations. This study was designed to evaluate whether apo E polymorphism is related to gallstone risk. METHODS apo E phenotype was determined in subjects older than 40 years of age (160 with and 125 without gallstones) and in 61 patients with cholesterol gallstones who underwent cholecystectomy. Bile composition, nucleation time, and gallstone features were analyzed in surgical patients. RESULTS The E4/3 phenotype was enriched in both patients with gallstones and those who underwent cholecystectomy, with significantly (P < 0.006) higher epsilon 4 allele frequencies than in gallstone-free subjects (odds ratio, 2.67 [95% confidence limits, 1.23-5.93] and 3.62 [95% confidence limits, 1.49-8.91], respectively); women, but not men, accounted for these differences. The prevalence of the epsilon 4 allele increased with age in patients with gallstones, whereas the opposite occurred in gallstone-free subjects. Biliary lipid and gallstone cholesterol content tended to increase in the sequence E4 > E3 > E2 in patients who underwent cholecystectomy. CONCLUSIONS Carrying the apo E4 isoform is a genetic risk factor for cholelithiasis in humans, thus adding another adverse effect of apo E polymorphism on health.

OriginalesEcografía carotídea en la evaluación de aterosclerosis preclínica. Distribución de valores del grosor íntima-media y frecuencia de placas de ateroma en una cohorte comunitaria españolaCarotid ultrasound in the assessment of preclinical atherosclerosis. Distribution of intima-media thickness values and plaque frequency in a Spanish community cohort☆

BACKGROUND AND OBJECTIVE: High-resolution B-mode ultrasound measurements of carotid intima-media thickness (IMT) and determination of plaque presence are useful to assess preclinical atherosclerosis. Normal IMT values have not been reported in Spanish subjects. Our aim was to define normality data of carotid ultrasound by sex and age. SUBJECTS AND METHODS: We studied 250 healthy, normolipidemic subjects, 125 men and 125 women, with mean age 49 years (range, 20-81). We assessed cardiovascular risk factors and performed ultrasound determination of mean and maximum IMT in the far wall of the common carotid artery, plaque occurrence, and maximum plaque height. RESULTS: Reference values for carotid IMT, expressed as 25th, 50th, and 75th percentiles by sex and 5 age groups, have been obtained. The 50th percentiles of mean IMT ranged from 0.50 to 0.74 mm in men in the age groups 35 years or younger and 65 years or older, respectively. For women, corresponding IMT values ranged from 0.40 to 0.65 mm. IMT was strongly related (p < 0.001) to age, both in men (r = 0.57) and women (r = 0.61). From the regression equations, the estimated yearly increase in IMT was 0.005 mm in men and 0.007 mm in women. More than 50% of men aged 55 years and older, and of women aged 65 years and older, had carotid plaques. CONCLUSIONS: Both IMT and plaque frequency were associated with age in men and women. Carotid IMT values in a Spanish community cohort were lower than those reported for countries with higher cardiovascular risk, such as Northern European countries and the US.BACKGROUND AND OBJECTIVE High-resolution B-mode ultrasound measurements of carotid intima-media thickness (IMT) and determination of plaque presence are useful to assess preclinical atherosclerosis. Normal IMT values have not been reported in Spanish subjects. Our aim was to define normality data of carotid ultrasound by sex and age. SUBJECTS AND METHODS We studied 250 healthy, normolipidemic subjects, 125 men and 125 women, with mean age 49 years (range, 20-81). We assessed cardiovascular risk factors and performed ultrasound determination of mean and maximum IMT in the far wall of the common carotid artery, plaque occurrence, and maximum plaque height. RESULTS Reference values for carotid IMT, expressed as 25th, 50th, and 75th percentiles by sex and 5 age groups, have been obtained. The 50th percentiles of mean IMT ranged from 0.50 to 0.74 mm in men in the age groups 35 years or younger and 65 years or older, respectively. For women, corresponding IMT values ranged from 0.40 to 0.65 mm. IMT was strongly related (p < 0.001) to age, both in men (r = 0.57) and women (r = 0.61). From the regression equations, the estimated yearly increase in IMT was 0.005 mm in men and 0.007 mm in women. More than 50% of men aged 55 years and older, and of women aged 65 years and older, had carotid plaques. CONCLUSIONS Both IMT and plaque frequency were associated with age in men and women. Carotid IMT values in a Spanish community cohort were lower than those reported for countries with higher cardiovascular risk, such as Northern European countries and the US.

The use of Achilles tendon sonography to distinguish familial hypercholesterolemia from other genetic dyslipidemias.

Objective—Achilles tendon (AT) xanthomas, specific for familial hypercholesterolemia (FH), may be clinically undetectable. We assessed the usefulness of AT sonography in the diagnosis of FH. Methods and Results—Sonographic AT characteristics were evaluated in 127 subjects with FH (81 genetically ascertained), 84 familial combined hyperlipidemia, 79 polygenic hypercholesterolemia, and 88 normolipidemic controls. Abnormal echostructure (sonographic xanthoma) was noted only in FH. AT thickness was higher (P<0.001) in FH men and women compared with all of the other groups and, in FH mutation carriers but not in others, correlated positively with low-density lipoprotein cholesterol (r=0.345; P<0.001) and negatively with high-density lipoprotein cholesterol (r=−0.265, P=0.015). Thickness thresholds for the diagnosis of FH with specificity >80%, as were derived from receiver operating curves, were 5.3 and 5.7 mm in men < and >45 years, and 4.8 and 4.9 mm in women < and >50 years, respectively. In FH mutation carriers, sonographic findings increased the clinical diagnosis of xanthomas from 35 (43%) to 55 (68%). Using thresholds in validation sets of 70 genetically identified FH and 54 dyslipidemic non-FH correctly classified 80% and 88%, respectively. Conclusion—Sonographic AT characteristics are normal in non-FH dyslipidemias. Identification of suspected FH by ultrasound using sex- and age-specific AT thickness thresholds is recommended.

Ecografía femoral en la evaluación de la aterosclerosis preclínica. Distribución de valores del grosor íntima-media y frecuencia de placas de ateroma en una cohorte comunitaria española

BACKGROUND AND OBJECTIVE High-resolution B-mode ultrasound measurements of intima-media thickness (IMT) and plaque presence are useful to assess preclinical atherosclerosis. Normal carotid IMT values, but not normal femoral IMT values, have been reported in Spanish subjects. Our aim was to define the normality data of femoral ultrasound by sex and age. SUBJECTS AND METHOD We studied 192 healthy subjects from a community cohort, 85 men and 107 women (mean age: 49 years; range: 20-81 years). We sonographically determined mean and maximum IMT in the far wall of the common femoral artery, plaque occurrence, and maximum plaque height. RESULTS Reference values for femoral IMT, expressed as 25th, 50th, and 75th percentiles by sex and 5 age groups, were obtained. The 50th percentiles of mean IMT ranged from 0.50 to 1.04 mm in men in the age groups < or = 35 years and > or = 65 years, respectively. For women, corresponding IMT values ranged from 0.40 to 0.53 mm. IMT was positively related to age in both men (r = 0.44; p < 0.001) and women (r = 0.23; p = 0.019). From the regression equations of IMT versus age, the estimated yearly increase in IMT was 0.016 mm in men and 0.008 mm in women. More than 50% of men aged > or = 55 years and women aged > or = 65 years had plaques. CONCLUSIONS Both IMT and plaque frequency are associated with age in men and women. Femoral IMT values in a Spanish community cohort are lower than those reported for geographical areas with higher cardiovascular risk, such as the Northern European countries and the US.

Application of focused-microwave wet digestion to the determination of trace metals in human gallstones by ICP/AES

We propose an analytical digestion method for trace metal determination (Co, Cr, Cu, Fe, Mn, Ni and Zn) in gallstones, in an attempt to facilitate detection of their origin. The method consists of sample digestion with HNO3 and H2O2 by means of focused microwave. Metals are quantified by inductively coupled plasma atomic emission spectroscopy. The effect of calcium concentration in the analytical solutions was studied. Cu, Fe, Mn and Zn were detected in all the samples analysed and the highest concentrations were obtained for Cu and Fe, especially in black-pigmented gallstones. The reproducibility in terms of %RSD, determined in the gallstones with the lowest metal content, was below 5% for Cu, between 10% and 15% for Mn and Zn and up to 25% for Fe.

Alteraciones cardiacas en la osteogénesis imperfecta. Estudio ecocardiográfico de casos y controles

BACKGROUND AND OBJECTIVES Osteogenesis imperfecta is a rare disease with abnormal synthesis of type 1 collagen that affects diverse extra-skeletal tissues. Aortic root dilatation and valvular dysfunction have been described. Our purpose was to evaluate the prevalence of cardiac abnormalities in patients with osteogenesis imperfecta in comparison with an age and sex-matched control group of healthy people. PATIENTS AND METHODS We prospectively studied 26 patients with osteogenesis imperfecta and compared them with 25 healthy people. All patients underwent a transthoracic standard M-mode, 2D and colour Doppler study. RESULTS We did not find significant differences between both groups in the left ventricular diastolic and systolic function and the incidence of valvulopathies. The dimensions of the aortic root, left atrium and left ventricle when indexed by body surface area were significantly larger in patients with osteogenesis imperfecta compared with the control group, which was probably due to the reduced body surface of these patients. However there was a significant difference in the aortic root/telediastolic diameter of left ventricle ratio independent of the body surface, which was higher in patients with osteogenesis imperfecta. CONCLUSIONS The incidence of valvular disease in osteogenesis imperfecta is similar to that of the normal population. However aortic root is larger in the former patients and is related to the left ventricular diastolic diameter.

Cambios estructurales y funcionales en el corazón de pacientes adultos con osteogénesis imperfecta: estudio de casos y controles

INTRODUCTION AND OBJECTIVES Osteogenesis imperfecta (OI) is a connective tissue disease characterised by an anomalous synthesis of type i collagen. Little is known about the cardiovascular affectation suffered by these patients. The most frequently described are valvular dysfunction and dilatation of the aorta. We wanted to analyse the structural and functional changes of the heart in adult patients with OI. METHODS We prospectively studied 82 patients with OI and compared them with 60 healthy subjects matched for age and sex. All of them underwent an echocardiographic study. RESULTS We found no differences in the incidence of valvulopathies compared to the control group. Our patients had a larger left atrium and larger left ventricle (LV) diameters adjusted for body surface area. Aortic root was significantly higher. LV ejection fraction in patients with OI was lower and they had higher pulmonary artery systolic pressure. CONCLUSIONS Patients with OI suffer structural and functional changes in the heart. A follow-up is recommended to observe the evolution of these changes.