Liver cancer risk after HCV cure in patients with advanced liver disease without non-characterized nodules.

BACKGROUND & AIMS: Recognition of non-characterized liver nodules (NCLN) prior to direct-acting antivirals (DAAs) is associated with increased hepatocellular carcinoma (HCC) risk in patients with HCV. The risk of HCC has not been defined in F3/F4 patients in whom NCLN have been ruled-out before starting DAAs and at sustained virological response (SVR). This study aimed to estimate HCC incidence in this population. METHODS: We performed a prospective study including HCV-infected patients with F3/F4 fibrosis, without a history of HCC, and who achieved SVR after DAAs. Patients were only included if they had undergone ultrasound imaging that excluded the presence of HCC/NCLN within 30 days after SVR. All patients were evaluated every 6 months until developing primary liver cancer, death or withdrawal of informed consent. HCC incidence was expressed per 100 patient-years (/100PY). Adherence to screening program was calculated every 6 months for the first 48 months. RESULTS: A total of 185 patients (63/122, F3/F4) were included. Among those with cirrhosis, 92% were Child-Pugh A and 42.7% had clinically significant portal hypertension (CSPH). Albumin-bilirubin score was 1 in 84.9% and 2 in 15.1% of patients, respectively. The median clinical and radiologic follow-up was 52.4 months and 48 months, respectively. Ten patients developed HCC: HCC incidence was 1.46/100PY (95% CI 0.79-2.71) in the whole cohort, 2.24/100PY (95% CI 1.21-4.17) in F4 only and 3.63/100PY (95% CI 1.95-6.74) in patients with CSPH. No HCC was registered in patients with F3. Median time between SVR and HCC occurrence was 28.1 months; 12 non-primary liver cancers were also identified. CONCLUSIONS: Patients with cirrhosis without NCLN at SVR remain at risk of HCC development. The absence of HCC in patients with F3 reinforces their marginal cancer risk, but prospective studies are needed to exclude them from screening programs. LAY SUMMARY: Patients with HCV-related cirrhosis, without non-characterized liver nodules at sustained virologic response, remain at risk of hepatocellular carcinoma despite viral cure. However, the cancer risk after successful direct-acting antiviral treatment is marginal in patients with F3 fibrosis without non-characterized liver nodules. If confirmed in larger prospective studies, current screening recommendations may need to be revisited in this group of patients.

Predicting portal thrombosis in cirrhosis: A prospective study of clinical, ultrasonographic and hemostatic factors.

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a relatively frequent event in patients with cirrhosis. While different risk factors for PVT have been reported, such as decreased portal blood flow velocity (PBFV) and parameters related with severity of portal hypertension, these are based on retrospective studies assessing only a discrete number of parameters. The aim of the current study was to evaluate the incidence and risks factors for non-tumoral PVT development in a large prospective cohort of patients with cirrhosis. METHODS: We performed an exhaustive evaluation of clinical, biochemical, inflammatory and acquired/hereditary hemostatic profiles in 369 patients with cirrhosis without PVT who were prospectively followed-up. Doppler ultrasound was performed at baseline and every 6 months or whenever clinically indicated. PVT development was always confirmed by computed tomography. RESULTS: Twenty-nine patients developed non-tumoral PVT, with an incidence of 1.6%, 6% and 8.4% at 1, 3 and 5 years, respectively. Low platelet count, PBFV <15 cm/sec and history of variceal bleeding were factors independently associated with a high PVT risk. No relationship between PVT development and any other clinical biochemical, inflammatory and acquired or hereditary hemostatic parameter was found. CONCLUSIONS: In patients with cirrhosis, the factors predictive of PVT development were mainly those related to the severity of portal hypertension. Our results do not support the role of hemostatic alterations (inherited or acquired) and inflammatory markers in the prediction of PVT in patients with cirrhosis. LAY SUMMARY: Patients with cirrhosis and more severe portal hypertension are at higher risk of non-tumoral portal vein thrombosis development. Acquired or inherited hemostatic disorders, as well as inflammatory status, do not seem to predict the development of portal vein thrombosis in patients with cirrhosis.

Shared decision making in breast cancer treatment guidelines: Development of a quality assessment tool and a systematic review.

BACKGROUND: It is not clear whether clinical practice guidelines (CPGs) and consensus statements (CSs) are adequately promoting shared decision making (SDM). OBJECTIVE: To evaluate the recommendations about SDM in CPGs and CSs concerning breast cancer (BC) treatment. SEARCH STRATEGY: Following protocol registration (Prospero no.: CRD42018106643), CPGs and CSs on BC treatment were identified, without language restrictions, through systematic search of bibliographic databases (MEDLINE, EMBASE, Web of Science, Scopus, CDSR) and online sources (12 guideline databases and 51 professional society websites) from January 2010 to December 2019. INCLUSION CRITERIA: CPGs and CSs on BC treatment were selected whether published in a journal or in an online document. DATA EXTRACTION AND SYNTHESIS: A 31-item SDM quality assessment tool was developed and used to extract data in duplicate. MAIN RESULTS: There were 167 relevant CPGs (139) and CSs (28); SDM was reported in only 40% of the studies. SDM was reported more often in recent publications after 2015 (42/101 (41.6 %) vs 46/66 (69.7 %), P = .0003) but less often in medical journal publications (44/101 (43.5 %) vs 17/66 (25.7 %), P = .009). In CPGs and CSs with SDM, only 8/66 (12%) met one-fifth (6 of 31) of the quality items; only 14/66 (8%) provided clear and precise SDM recommendations. DISCUSSION AND CONCLUSIONS: SDM descriptions and recommendations in CPGs and CSs concerning BC treatment need improvement. SDM was more frequently reported in CPGs and CSs in recent years, but surprisingly it was less often covered in medical journals, a feature that needs attention.

Backpack weight and back pain reduction: effect of an intervention in adolescents.

BACKGROUND: To assess if an educational intervention is effective to reduce backpack weight and back pain in schoolchildren. METHODS: We designed an intervention study in schoolchildren aged between 12 and 16 years aimed to reduce the weight of backpacks and back pain. The intervention was multifaceted, including an educational intervention with practical examples, advising on performing sports, postural habits, leaflets, stickers, and so on. The comparison group did not receive any intervention. RESULTS: A total of 1668 schoolchildren took part in the study. We observed a high prevalence of carrying heavy backpacks, with 66-80% of schoolchildren carrying backpacks surpassing 10% of their body weight. Back pain prevalence was 30%. We observed that the intervention was significant in reducing the backpack weight in first-year schoolchildren but not in second-year. The intervention was also significant in reducing back pain in third-year schoolchildren but only in girls. CONCLUSION: This study shows that an inexpensive intervention directed to reduce the backpack weight and back pain might have a positive effect in schoolchildren.

Relationship Between Total Serum Bilirubin Levels and Carotid and Femoral Atherosclerosis in Familial Dyslipidemia.

OBJECTIVE: Bilirubin is a potent antioxidant that has been inversely related to cardiovascular disease. There is little information on serum total bilirubin (TB) in relation to atherosclerosis in familial dyslipidemia. We assessed the association between TB and carotid and femoral atherosclerosis in this high-risk group. APPROACH AND RESULTS: We evaluated 464 individuals with familial dyslipidemia (56% men; median age, 48 years), 322 with familial hypercholesterolemia, and 142 with familial combined hyperlipidemia. Carotid and femoral arteries were imaged bilaterally with a standardized ultrasonographic protocol. Mean and maximum intima-media thickness and plaque presence (≥1.2 mm) and height were recorded. Cross-sectional associations between TB and atherosclerosis variables were investigated in multivariable-adjusted models, including lipid values and hypolipidemic drug use. Inflammatory markers (C-reactive protein, total leukocyte count, and lipoprotein[a]) were also determined. Increasing TB levels were associated with decreasing intima-media thickness of all carotid segments (P<0.05, all). TB also related to carotid plaque, present in 78% of individuals, and to plaque burden (≥3 plaques), with odds ratios (95% confidence interval) 0.59 (0.36-0.98) and 0.57 (0.34-0.96) for each increase of 0.5 mg in TB, respectively. Findings were confirmed in a validation cohort of 177 subjects with nonfamilial dyslipidemia. Only the familial combined hyperlipidemia group, with higher inflammation-related markers, showed an inverse association between TB and femoral plaque height (ß=-0.183; P=0.030). CONCLUSIONS: TB was inversely and independently associated with carotid plaque burden in familial and nonfamilial dyslipidemia. These findings support the use of TB as a biomarker of atherosclerosis in this high-risk group.

Hepatitis C seroprevalence in an at-risk population in the southwest Madrid region of Spain. / Seroprevalencia de hepatitis C en población con factores de riesgo del suroeste de la Comunidad de Madrid.

INTRODUCTION: The estimated seroprevalence of hepatitis C virus (HCV) in Spain is 1.7%, but is much higher in the at-risk population. The most efficient national screening strategy is unclear. AIMS: To estimate the prevalence of HCV among the at-risk population seen in primary care (PC), and to determine their epidemiological profile. MATERIALS AND METHODS: Cross-sectional descriptive prevalence study that included adult patients with risk factors for HCV infection seen in PC in the southwest Madrid region between 2010 and 2012. RESULTS: A total of 158 patients (men=51.3%), mean age 46 years (SD=16.6), were included. The most common risk factors were hypertransaminasaemia (44.3%) and major surgery (13.3%). Immigration, unsafe sexual practices, and tattoos or body piercing were more prevalent in patients younger than 45 years of age. Fifteen patients (9.5%) were positive for anti-HCV; 9 of these (5.7%) were HCV-ARN positive. Of the positive patients, 4 (44.4%) had significant fibrosis at diagnosis (F3-F4). Male patients had a higher rate of positive anti-HCV results (13.8 vs. 5.3%; P=.072), as did patients older than 45 years of age (12.8 vs. 6.3%; P=.167). Intravenous and intranasal drug use were associated with a higher rate of positive anti-HCV results (50 vs. 8.5%; P=.005 and 66.7 vs. 8.4%; P=.001, respectively). CONCLUSIONS: Patients with risk factors for HCV infection have high seroprevalence. Screening programmes must therefore be implemented to detect HCV infection in this population in PC.

Exon array analysis reveals genetic heterogeneity in atypical femoral fractures. A pilot study.

Atraumatic subtrochanteric and diaphyseal (atypical) femoral fractures are a rare, but important adverse event in patients treated with potent anti-resortive agents. The mechanisms involved are unknown and particularly the association with genetic variants has not been explored. The aim of the study was to identify rare genetic variants that could be associated with the occurrence of these fractures. We performed a genome-wide analysis of up to 300,000 variants, mainly distributed in gene coding regions, in 13 patients with atypical femoral fractures and 268 control women, either healthy or with osteoporosis. Twenty one loci were more frequent in the fracture group, with a nominal p value between 1 × 10(-6) and 2.5 × 10(-3). Most patients accumulated two or more allelic variants, and consequently the number of risk variants was markedly different between patients and controls (p = 2.6 × 10(-22)). The results of this pilot study suggest that these fractures are polygenic and are associated with the accumulation of changes in the coding regions of several genes.

Changes in ultrasound-assessed carotid intima-media thickness and plaque with a Mediterranean diet: a substudy of the PREDIMED trial.

OBJECTIVE: The Prevención con Dieta Mediterránea (PREDIMED) trial showed that a Mediterranean diet (MedDiet) supplemented with either extra virgin olive oil or 30 g/d of mixed nuts reduced incident cardiovascular events compared with a control (low fat) diet. The mechanisms of cardiovascular protection afforded by MedDiets remain to be uncovered. We assessed the effect of both supplemented MedDiets on internal carotid intima-media thickness (ICA-IMT) and plaque height, the ultrasound features that best predict future cardiovascular events, in subjects at high cardiovascular risk. APPROACH AND RESULTS: In a PREDIMED subcohort (n=175), plaque height and carotid IMT of 3 prespecified segments (ICA, bifurcation, and common) were sonographically assessed at baseline and after intervention for a mean of 2.4 years. We evaluated 164 subjects with complete data. In a multivariate model, mean ICA-IMT progressed in the control diet group (mean [95% confidence interval], 0.052 mm [-0.014 to 0.118 mm]), whereas it regressed in the MedDiet+nuts group (-0.084 mm [-0.158 to -0.010 mm]; P=0.024 versus control). Similar results were observed for maximum ICA-IMT (control, 0.188 mm [0.077 to 0.299 mm]; MedDiet+nuts, -0.030 mm [-0.153 to 0.093 mm]; P=0.034) and maximum plaque height (control, 0.106 mm [0.001 to 0.210 mm]; MedDiet+nuts, -0.091 mm [-0.206 to 0.023 mm]; P=0.047). There were no changes in ICA-IMT or plaque after the MedDiet+extra virgin olive oil. CONCLUSIONS: Compared with a control diet, consumption of a MedDiet supplemented with nuts is associated with delayed progression of ICA-IMT and plaque. The results contribute mechanistic evidence for the reduction of cardiovascular events observed in the PREDIMED trial. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.

Influence of (11)C-choline PET/CT on radiotherapy planning in prostate cancer.

AIM: To evaluate the influence of (11)C-choline PET/CT on radiotherapy planning in prostate cancer patients. BACKGROUND: Precise information on the extension of prostate cancer is crucial for the choice of an appropriate therapeutic strategy. (11)C-choline positron emission tomography ((11)C-choline PET/CT) has two roles in radiation oncology (RT): (1) patient selection for treatment and (2) target volume selection and delineation. In conjunction with high-accuracy techniques, it might offer an opportunity of dose escalation and better tumour control while sparing healthy tissues. MATERIALS AND METHODS: We carried out a retrospective study in order to analyse RT planning modification based on (11)C-choline PET/CT in 16 prostate cancer patients. Patients were treated with hypofractionated step-and-shoot Intensity Modulated Radiotherapy (IMRT), or Volumetric Modulated Arc Therapy (VMAT), and a daily cone-beam CT for Image Guided Radiation Therapy (IGRT). All patients underwent a (11)C-choline-PET/CT scan prior to radiotherapy. RESULTS: In 37.5% of cases, a re-delineation and new dose prescription occurred. Data show good preliminary clinical results in terms of biochemical control and toxicity. No gastrointestinal (GI)/genitourinary (GU) grade III toxicities were observed after a median follow-up of 9.5 months. CONCLUSIONS: In our experience, concerning the treatment of prostate cancer (PCa), (11)C-choline PET/CT may be helpful in radiotherapy planning, either for dose escalation or exclusion of selected sites.

Femoral atherosclerosis in heterozygous familial hypercholesterolemia: influence of the genetic defect.

OBJECTIVE: The purpose of this study was to assess femoral atherosclerosis by ultrasound in patients with molecularly defined heterozygous familial hypercholesterolemia (FH) in comparison with matched control subjects and in relation to mutational class in the LDL receptor and apolipoprotein B (APOB) genes. METHODS AND RESULTS: Femoral intima-media thickness (IMT) and plaque were evaluated in 146 FH patients carrying null alleles (n=48), defective-receptor alleles (n=62), undetermined-function alleles (n=25), or APOB defects (n=11) and in 193 healthy subjects. Twenty-three patients had coronary heart disease (CHD). The frequency of both tendon xanthomas and CHD was approximately 2-fold higher and average LDL cholesterol was 30 mg/dL higher in null-allele genotype compared with receptor-defective mutations. All femoral measurements were increased in FH patients versus controls (P<0.001), and null-allele mutations showed higher age-, sex-, and LDL cholesterol-adjusted maximum IMT than receptor-defective or APOB defects (P for trend, 0.001). By multivariate analysis, independent associations of mean IMT, a measure of early atherosclerosis, were age, LDL cholesterol, sex, and systolic blood pressure. Age, null-allele genotype, sex, and smoking explained 42% of the variability of maximum IMT, a measure of advanced atherosclerosis. CONCLUSIONS: FH patients have increased femoral IMT in relation to mutational class. The findings support the usefulness of genetic testing in FH beyond securing the diagnosis.

Nonhuman primate welfare: Can there be a relationship between personality, lateralization and physiological indicators?

Measuring personality is being used to improved nonhuman primate welfare. To expand its use, it is important to identify traits that are shared between species and that measures are reliable, easy to use and less time consuming. Combining personality and other indicators strong validation of the results can be obtained. In the present study, we sought to determine if there is a link between physiological stress response (fecal cortisol metabolites), personality (ratings made by animal keepers and reaction to novel objects) and lateralization of the brain (hand preferences) on eight species of nonhuman primates: Callithrix jacchus, Callithrix geoffroyi, Cebuella Pygmaea, Saguinus imperator, Saguinus oedipus, Leontopithecus rosalia, Pithecia pithecia and Nycticebus pygmaeus. Personality assessments achieved good levels of interrater reliability and revealed three components of personality in our sample: fearfulness, activeness and aggressiveness. More exploratory individuals were more active, aggressive and showed higher cortisol metabolite levels. Right-handed subjects inspected novel objects sooner and the strength of the lateralization was linked with individual stress and the aggressiveness component. Our results highlight that there is a relation between personality, lateralization and physiological indicators in nonhuman primates, but although some aspects can be generalized across species and/or sexes others are species/sex dependent.

[Femoral ultrasound in the assessment of preclinical atherosclerosis. Distribution of intima-media thickness and frequency of atheroma plaques in a Spanish community cohort]. / 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.

Influence of HDL cholesterol on preclinical carotid atherosclerosis in familial hypercholesterolemia.

OBJECTIVE: The effect of risk factors on carotid atherosclerosis in heterozygous familial hypercholesterolemia (FH) is unclear. We evaluated carotid intima-media thickness (IMT) by sonography in relation to classical and emergent risk factors in a large FH cohort. METHODS AND RESULTS: Risk factors and carotid IMT were assessed in 196 asymptomatic subjects aged > or =25 years fulfilling strict diagnostic criteria for clinical FH who were either undertreated or treatment-naive. Conventional risk factors, but not lipoprotein(a), homocysteine, or apolipoprotein E (apoE) genotypes were univariately related to IMT. Age-adjusted and gender-adjusted IMT increased with increasing low-density lipoprotein (LDL) cholesterol and decreased with increasing high-density lipoprotein (HDL) cholesterol. Compared with a total cholesterol/HDL ratio >5.0, a ratio < or =5.0 was associated with a lower adjusted IMT, with a mean difference of -0. 09 mm (95% confidence interval, -0.13 to -0.04). By multivariate analysis, age, HDL cholesterol (negatively), physical exercise, family history of early-onset coronary heart disease, LDL cholesterol, and leukocyte count, in this order, were independent associations of IMT (r2=0.429, P<0.001). CONCLUSIONS: Traditional risk factors account for a sizeable proportion of variation in carotid IMT in FH. Because the HDL cholesterol level and the total cholesterol/HDL ratio are strong predictors of preclinical carotid atherosclerosis, HDL cholesterol-raising strategies should have an important therapeutic role in FH.

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. CONCLUSIONS: 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.

Effect of weight loss on abnormal 24-hour blood pressure patterns in severely obese patients.

BACKGROUND: Nocturnal hypertension (night systolic [S]/diastolic [D] blood pressure [BP]≥120/70 mm Hg), nondipper status (nocturnal BP fall<10% of daytime values), and pulse pressure ([PP]; difference between 24-h SBP and DBP readings) are associated with increased risk of cardiovascular disease. We evaluated the 1-year effect of significant surgical weight loss (WL) on abnormal BP patterns in patients with and without hypertension and identified the factors involved. SETTING: University hospital, Spain. METHODS: This prospective study included 42 patients (28 normotensive [NT] and 14 hypertensive [HT]), 71% women with a mean age (standard deviation [SD]) of 48 (11) years undergoing bariatric surgery (BS): 22 laparoscopy Roux-en-Y gastric bypass (LRYGB) and 20 sleeve gastrectomy (SG). SG: 20. Before and 12 months post-BS, anthropometric data, BP (24-h ambulatory BP measurement), and metabolic parameters were determined. At 12 months post-BS ultrasonographic carotid assessment was performed in a subgroup of patients (22). RESULTS: Both groups experienced significant WL (percent of excess body weight loss [%EBWL] 68%), a fall in 24-h SBP of-13 (11)/DBP-3 (7) mm Hg, and improvement in all the metabolic parameters evaluated and the homeostatic model assessment of insulin resistance (HOMA-IR). However, nondipper status remained high in NT (54%) and HT (64%) as well as 60% of the patients with carotid plaque. Additionally, in HT patients nocturnal hypertension and PP remained significantly higher, and basal fasting insulin values and the HOMA-IR score were significantly higher in those not normalizing dipper status. CONCLUSION: Surgery-induced WL was associated with a sizeable decline in BP and metabolic parameters improvement. However, independent of the presence of hypertension, the prevalence of abnormal 24-h BP patterns remained high, and thus, cardiovascular risk continued to be high in these patients.

A walnut diet improves endothelial function in hypercholesterolemic subjects: a randomized crossover trial.

BACKGROUND: Epidemiological studies suggest that nut intake decreases coronary artery disease (CAD) risk. Nuts have a cholesterol-lowering effect that partly explains this benefit. Endothelial dysfunction is associated with CAD and its risk factors and is reversed by antioxidants and marine n-3 fatty acids. Walnuts are a rich source of both antioxidants and alpha-linolenic acid, a plant n-3 fatty acid. METHODS AND RESULTS: To test the hypothesis that walnut intake will reverse endothelial dysfunction, we randomized in a crossover design 21 hypercholesterolemic men and women to a cholesterol-lowering Mediterranean diet and a diet of similar energy and fat content in which walnuts replaced approximately 32% of the energy from monounsaturated fat. Participants followed each diet for 4 weeks. After each intervention, we obtained fasting blood and performed ultrasound measurements of brachial artery vasomotor function. Eighteen subjects completing the protocol had suitable ultrasound studies. Compared with the Mediterranean diet, the walnut diet improved endothelium-dependent vasodilation and reduced levels of vascular cell adhesion molecule-1 (P<0.05 for both). Endothelium-independent vasodilation and levels of intercellular adhesion molecule-1, C-reactive protein, homocysteine, and oxidation biomarkers were similar after each diet. The walnut diet significantly reduced total cholesterol (-4.4+/-7.4%) and LDL cholesterol (-6.4+/-10.0%) (P<0.05 for both). Cholesterol reductions correlated with increases of both dietary alpha-linolenic acid and LDL gamma-tocopherol content, and changes of endothelium-dependent vasodilation correlated with those of cholesterol-to-HDL ratios (P<0.05 for all). CONCLUSIONS: Substituting walnuts for monounsaturated fat in a Mediterranean diet improves endothelium-dependent vasodilation in hypercholesterolemic subjects. This finding might explain the cardioprotective effect of nut intake beyond cholesterol lowering.

[Carotid ultrasound in the assessment of preclinical atherosclerosis. Distribution of intima-media thickness values and plaque frequency in a Spanish community cohort]. / Ecografía carotídea en la evaluación de 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 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.

Longitudinal changes of blood pressure after weight loss: factors involved.

BACKGROUND: The combination of obesity and hypertension (HT) places patients at a higher risk for adverse cardiovascular outcomes and raises the need to establish the pathogenic mechanisms of this relationship. The aim of this study was to assess the effects of important weight loss on longitudinal changes in blood pressure (BP) and investigate the pathogenic factors associated with these changes. METHODS: We performed a prospective, open-label study including 37 obese hypertensive patients (28 females, mean age 52±8 yr) undergoing BS. Before BS, and at 4 and 12 months postoperatively, the body mass index (BMI), 24-h ambulatory BP, renin-angiotensin-aldosterone system (RAAS: plasma rennin activity, aldosterone, angiotensin II, and angiotensin converting enzyme), sympathetic nervous system (SNS: metanephrines, normetanephrines, and norepinephrine) components, leptin, insulin, and abdominal fat were measured. RESULTS: Before BS, HT-duration was 6±6 years, the BMI 45±5 kg/m2 and excess weight (EBW) was 53±12 kg. At 12 months, the excess BMI loss was 14 kg/m2 and the EBW loss was 70 %; HT remission was observed in 70%; 24-h (systolic 19±13/diastolic 7±9 mm Hg), day and night BP levels and aldosterone, norepinephrine, leptin, insulin, subcutaneous and visceral abdominal fat (VAT) significantly decreased (P<.05). Mixed models for repeated measures revealed that HT-duration, baseline BP, BMI, and VAT area were the main variables associated with longitudinal changes in BP. CONCLUSION: These results demonstrate that the hypotensive response after weight loss in severely hypertensive obese patients is mainly regulated by HT-duration, baseline BP, BMI and VAT area, independently of suppression of hyperinsulinemia or changes in RAAS and SNS components.

White blood cell count is associated with carotid and femoral atherosclerosis.

OBJECTIVE: Chronic low-grade inflammation is associated with atherosclerosis. Ultrasound imaging allows measurement of intima-media thickness (IMT) and plaque. We investigated the association between inflammatory markers and carotid and femoral atherosclerosis. METHODS: We studied 554 subjects with primary dyslipidemia (57% men, median age 49 years) and 246 age- and sex-matched normolipidemic subjects. Carotid and femoral arteries were imaged bilaterally with a standardized protocol. Mean and maximum common carotid IMT (CC-IMT and MaxCC-IMT) and common femoral IMT (F-IMT and MaxF-IMT), and carotid and femoral plaque were assessed. Carotid atherosclerosis was defined by CC-IMT and/or plaque height >75th percentile of a reference population. White blood cell count (WBCC) was measured in all subjects. High-sensitivity C-reactive protein (CRP) was measured in 330 dyslipidemic subjects. RESULTS: The age- and sex-adjusted probability of carotid atherosclerosis and femoral plaque increased by 20% (odds ratio [OR] 1.20; 95% CI, 1.10-1.31) and 25% (1.25; 1.13-1.38), respectively, for each 1000/mm(3) WBCC increment. WBCC was associated with age- and sex-adjusted CC-IMT and MaxCC-IMT (p<0.05, both), and F-IMT and MaxF-IMT (p<0.001, both). Adjustment for cardiovascular risk factors did not influence these associations. CRP was associated with CC-IMT and MaxCC-IMT (p<0.05, both), but the associations disappeared after adjustment for body mass index. CRP was unrelated to carotid plaque or measures of femoral atherosclerosis. CONCLUSIONS: WBCC, but not CRP, related to early and advanced measures of atherosclerosis independently of risk factors. Our findings support using the heretofore undervalued WBCC as an easy-to-measure, low-cost diagnostic marker of atherosclerosis.

School children's backpacks, back pain and back pathologies.

OBJECTIVE: To investigate whether backpack weight is associated with back pain and back pathology in school children. DESIGN: Cross-sectional study. SETTING: Schools in Northern Galicia, Spain. PATIENTS: All children aged 12-17. INTERVENTIONS: Backpack weight along with body mass index, age and gender. MAIN OUTCOME MEASURES: Back pain and back pathology. RESULTS: 1403 school children were analysed. Of these, 61.4% had backpacks exceeding 10% of their body weight. Those carrying the heaviest backpacks had a 50% higher risk of back pain (OR 1.50 CI 95% 1.06 to 2.12) and a 42% higher risk of back pathology, although this last result was not statistically significant (OR 1.42 CI 95% 0.86 to 2.32). Girls presented a higher risk of back pain compared with boys. CONCLUSIONS: Carrying backpacks increases the risk of back pain and possibly the risk of back pathology. The prevalence of school children carrying heavy backpacks is extremely high. Preventive and educational activities should be implemented in this age group.