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.

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.

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.

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

INTRODUCCIÓN: La seroprevalencia estimada del VHC en España es del 1,7%, cifra que es muy superior en la población con factores de riesgo. Se desconoce cuál sería la estrategia de cribado más eficiente en nuestro país. OBJETIVOS: Estimar la prevalencia del VHC en la población con factores de riesgo atendida en Atención Primaria (AP) y conocer su perfil epidemiológico. MATERIAL Y MÉTODOS: Estudio descriptivo transversal de prevalencia que incluyó a pacientes adultos con factores de riesgo de infección por VHC asistidos en AP de la zona suroeste de la Comunidad de Madrid entre 2010 y 2012. RESULTADOS: Se incluyó a 158 pacientes (H: 51,3%) con una edad media de 46 años (DE=16,6). Los factores de riesgo más frecuentes fueron la hipertransaminasemia (44,3%) y cirugía mayor (13,3%). La inmigración, las prácticas sexuales de riesgo y los tatuajes o piercing fueron más prevalentes en los menores de 45 años. Del total de pacientes, 15 (9,5%) presentaron anti-VHC positivo, de ellos 9 tenían ARN-VHC positivo (5,7%). De los pacientes positivos, 4 (44,4%) presentaron fibrosis significativa al diagnóstico (F3-F4). Los pacientes varones presentaron una mayor tasa de anti-VHC positivo (13,8 vs. 5,3%; p = 0,072), y también los pacientes mayores de 45 años (12,8 vs. 6,3%; p = 0,167). El uso de drogas parenterales se asoció a mayor tasa de anti-VHC positivo (50 vs. 8,5%; p = 0,005), así como el uso de drogas vía nasal (66,7 vs. 8,4%; p = 0,001). CONCLUSIONES: Los pacientes con factores de riesgo de infección por VHC presentan una elevada seroprevalencia. Por tanto, es necesario implantar programas de detección de la infección VHC en esta población en AP

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

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.

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.

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.

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.

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.

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.

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.

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.

Carotid and femoral plaque burden is inversely associated with the α-linolenic acid proportion of serum phospholipids in Spanish subjects with primary dyslipidemia.

OBJECTIVE: α-Linolenic acid (ALA), the vegetable n-3 fatty acid, appears to have antiatherosclerotic properties akin to those of marine n-3 fatty acids. A prior study in a US population with low fish intake showed an inverse association between ALA intake and carotid plaque. We examined the association between the ALA status and advanced carotid and femoral atherosclerosis in subjects at high cardiovascular disease risk from Spain, a country with low coronary heart disease (CHD) rates and high fish consumption. METHODS: Cross-sectional study of 211 patients with primary dyslipidemia, with determination of fatty acid composition of serum phosphatidylcholine by gas chromatography and plaque outcomes (frequency, number, maximum height and sum of plaque heights) in carotid and femoral arteries by sonography. RESULTS: In multivariate regression analyses after adjusting for age, gender, lipid genotype, BMI, smoking, hypertension, diabetes mellitus, APOE4 genotype, prior statin treatment, and serum proportions of other unsaturated fatty acids known to relate to atherosclerosis, the proportion of ALA showed an inverse association with the risk of carotid plaque (OR [95% CI] 0.66 [0.44-0.91]) and concomitant carotid and femoral artery plaque (0.57 [0.38-0.86]). CONCLUSION: The inverse relationship between ALA in serum phosphatidylcholine and plaque burden in carotid and femoral arteries supports its antiatherosclerotic effect independently of fish-derived n-3 fatty acids. However, whether ALA enrichment in phospholipids is beneficial per se or is a surrogate of the consumption of bioactive compounds in parent foods deserves further research.

Fatty acids in serum phospholipids and carotid intima-media thickness in Spanish subjects with primary dyslipidemia.

BACKGROUND: Low rates of incident ischemic heart disease (IHD) and cardiac death occur in Spain despite a high prevalence of cardiovascular risk factors. High consumption of unsaturated fatty acid-rich foods, such as olive oil, nuts, and seafood, might underlie this paradox. OBJECTIVE: We investigated whether serum phosphatidylcholine enrichment in oleic, linoleic, alpha-linolenic, and n-3 (omega-3) long-chain polyunsaturated fatty acids (as biomarkers of olive oil, seed oil, walnut, and fish intake, respectively) relate to carotid atherosclerosis in Spanish subjects at risk of IHD. DESIGN: In a cross-sectional study, we measured fatty acid concentrations in serum phosphatidylcholine and measured carotid intima-media thickness (IMT) by using ultrasound in 451 asymptomatic subjects (261 men, 190 women; mean age: 45 y) with primary dyslipidemia. Main and secondary outcomes were mean and maximum IMT in the common carotid artery (CCA) and other carotid segments, respectively. RESULTS: Phosphatidylcholine fatty acid composition was similar to that reported for other Spanish populations. Multiple regression analyses showed that proportions of oleic and docosahexaenoic acids were inversely related to mean CCA IMT (P < 0.02, all) after adjustment for several confounders. In similar models, alpha-linolenic acid related inversely to mean and maximum internal carotid artery IMT (P < 0.05 for all). Linoleic and eicosapentaenoic acids were unrelated to IMT. CONCLUSIONS: Higher phospholipid proportions of oleic, alpha-linolenic, and docosahexaenoic acids showed inverse associations with IMT at specific carotid segments in subjects with primary dyslipidemia. High intakes of healthy fats might explain, in part, the Spanish paradox of low IHD rates in the face of a high burden of cardiovascular risk factors.

Impact of low-density lipoprotein receptor mutational class on carotid atherosclerosis in patients with familial hypercholesterolemia.

BACKGROUND AND OBJECTIVES: Defects in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a highly atherogenic condition. The effect of different LDLR mutations on coronary heart disease (CHD) risk is insufficiently defined. We assessed carotid intima-media thickness (IMT), a surrogate marker of CHD, in relation to LDLR mutational class in FH. METHODS: In 436 Spanish FH patients (223 men and 213 women, age 44+/-14 years) with known LDLR mutations, alleles were classified by standard criteria as null (n=269), defective (n=162), or undetermined (n=5). LDLR defects were detected using a microarray (Lipochip) designed to uncover prevalent mutations in Spain and gene sequencing when no mutations were detected. Carotid IMT and plaque were assessed in FH patients and 268 healthy subjects. RESULTS: All carotid measurements were increased in FH patients versus controls (p<0.05), irrespective of genotype. After adjustment for gender and age, patients with null alleles compared with defective alleles had similar mean and maximum common carotid artery (CCA) IMT, but higher maximum IMT at any carotid segment, with median values (95% confidence interval) of 1.25 mm (1.19-1.31) and 1.11 mm (1.05-1.18), respectively. Multivariate analysis showed that null alleles were independently associated with maximum CCA-IMT (beta=0.09, p=0.033) with an impact similar to that of gender (beta=0.10, p=0.035). CONCLUSIONS: FH patients show advanced carotid atherosclerosis in relation to LDLR mutational class. The findings support the utility of genetic testing in FH beyond providing a secure diagnosis.

[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.