João Tiago Guimarães

Central obesity as a major determinant of increased high-sensitivity C-reactive protein in metabolic syndrome.

INTRODUCTION:Traditional cardiovascular risk factors such as central obesity, high blood pressure and insulin resistance, all constituents of metabolic syndrome, have been associated with increased levels of C-reactive protein (CRP). Therefore, this marker of low-grade inflammation may play a major role in the pathogenesis of cardiovascular diseases. In this study, data from a representative sample of urban adults was used to evaluate the association between CRP and metabolic syndrome, accounting for the type and number of its constituents.METHODS:Using random digit dialing, 1022 participants, aged 18–92 y, were selected. All participants completed a structured questionnaire comprising of information on social, demographic, behavioral and clinical aspects. Anthropometrics and blood pressure were recorded and a fasting blood sample collected. Metabolic syndrome was defined, according to the Third Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, as the presence of three or more of the following characteristics: waist circumference greater than 102 cm in men and 88 cm in women; triglyceride levels ≥150 mg/dl; high-density lipoprotein cholesterol levels <40 mg/dl in men and <50 mg/dl in women; blood pressure ≥130/85 mm Hg; and serum glucose ≥110 mg/dl. High-sensitivity CRP was assessed by immunonephelometric assay. After excluding 65 participants with CRP ≥10 mg/l, 957 subjects (599 women and 358 men) remained for analysis. Geometric means were compared after adjustment for age, sex, alcohol consumption and smoking.RESULTS:Higher mean levels of CRP (2.34 vs 1.36, P<0.001) were observed when metabolic syndrome was present. Also, mean CRP levels were significantly higher in the presence of central obesity (2.45 vs 1.24, P<0.001), high blood pressure (1.76 vs 1.12, P<0.001), hypertriglyceridemia (2.17 vs 1.32, P<0.001) and high fasting glucose (1.96 vs 1.46, P=0.032). We found a significant increasing trend (P<0.001) in mean levels of CRP as the number of features of metabolic syndrome increased. The major contributing features for high CRP levels were central obesity and high blood pressure.CONCLUSIONS:Present data show that increasing severity of metabolic syndrome is associated with increasing CRP. Additionally, we found that central obesity and high blood pressure are the most important determinants of the low-grade chronic inflammation present in metabolic syndrome.

Neutrophil Gelatinase-Associated Lipocalin in the Diagnosis of Type 1 Cardio-Renal Syndrome in the General Ward

BACKGROUND AND OBJECTIVES The early identification of acute heart failure (HF) patients with type 1 cardio-renal syndrome should be the first step for developing prevention and treatment strategies for these patients. This study aimed to assess the performance of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C in the early detection of type 1 cardio-renal syndrome in patients with acute HF. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS One-hundred nineteen patients admitted with acute HF were studied. NGAL and creatinine were measured in the first hospitalization morning; creatinine was also measured at least after 48 to 72 hours. Physicians were blinded to NGAL and cystatin C levels. Type 1 cardio-renal syndrome was defined as an increase in the creatinine level of at least 0.3 mg/dl or 50% of basal creatinine. RESULTS Type 1 cardio-renal syndrome developed within 48 to 72 hours in 14 patients (11.8%). Admission NGAL levels were higher in these patients: 212 versus 83 ng/dl. At a cutoff value of 170 ng/L, NGAL determined type 1 cardio-renal syndrome with a sensitivity of 100% and a specificity of 86.7%. The area under the receiver-operating characteristic curve of NGAL was 0.93 and that of cystatin C was 0.68. CONCLUSIONS Above a cutoff value of 170 ng/L, NGAL predicts 48- to 72-hour development of type 1 cardio-renal syndrome with a negative predictive value of 100% and a positive predictive value of 50%. NGAL independently associates with type 1 cardio-renal syndrome and might be a useful biomarker in the early recognition of these patients.

Prognostic value of neutrophil gelatinase-associated lipocalin in acute heart failure

BACKGROUND The identification of patients at risk for worse outcome is still a challenge. We hypothesized that cystatin C, a marker of renal function, and neutrophil gelatinase-associated lipocalin (NGAL), a marker of acute renal injury, would have a role in the prognostic stratification of these patients. METHODS We prospectively evaluated 121 patients admitted for acute HF. Serum NGAL and cystatin C levels were measured on the first morning after admission. The outcome measures used were the occurrence of death from all causes, and the combined endpoint defined as the first occurrence of either death or hospital admission. Patients were followed for up to 3 months. RESULTS The variables associated with a higher occurrence of death in a univariate approach were older age and higher levels of BNP, cystatin C and NGAL, and those associated with the occurrence of the combined endpoint were older age, Diabetes mellitus, lower GFR, type 1 cardio-renal syndrome, BNP, cystatin C and NGAL. BNP and NGAL remained independent predictors of the occurrence of both all-cause death and the combined endpoint. NGAL levels in the 75th percentile (>167.5 ng/mL) were associated with a 2.7-fold increase in the risk of death and a 2.9-fold increase in the risk of the first occurrence of either death or hospitalization. CONCLUSIONS Serum NGAL, a marker of acute renal injury, is an independent predictor of worse short term prognosis in patients with acute HF. This suggests a role of renal damage, apart from renal function, in the prognosis of these patients.

Aging, High Salt Intake, and Renal Dopaminergic Activity in Fischer 344 Rats

The present study examined renal dopaminergic activity and its response to high salt (HS) intake in adult (6-month-old) and old (24-month-old) Fischer 344 rats. Daily urinary excretion of L-3, 4-dihydroxyphenylalanine (L-DOPA), dopamine, and its metabolites 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid was similar in adult and old rats; by contrast, daily urinary excretion of norepinephrine in old rats was almost twice that in adult animals. HS intake (1% NaCl) over a period of 24 hours resulted in a 2-fold increase in the urinary excretion of dopamine, DOPAC, and norepinephrine in adult animals but not in old animals. Norepinephrine and L-DOPA plasma levels did not change during HS intake and were similar in both groups of rats. The natriuretic response to an HS intake in old rats (from 4.7+/-0.4 to 10.7+/-2.0 nmol. kg(-1). d(-1); Delta=6.0+/-0.9 nmol. kg(-1). d(-1)) was less than in adult rats (from 5.2+/-0.4 to 13.5+/-2.5 nmol. kg(-1). d(-1); Delta=8.3+/-0.8 nmol. kg(-1). d(-1)). A diuretic response to HS intake was observed in adult rats (from 20.9+/-2.3 to 37.6+/-2.8 mL. kg(-1). d(-1)) but not in old rats (from 37.7+/-5.7 to 42.3+/-6. 0 mL. kg(-1). d(-1)). Dopamine levels and dopamine/L-DOPA ratios in the renal cortex of old rats were greater than in adult rats. HS intake increased both dopamine levels and dopamine/L-DOPA ratios in the renal cortex of adult rats but not in old rats. Aromatic L-amino acid decarboxylase activity was higher in old rats than in adult rats; HS intake increased L-amino acid decarboxylase activity (nmol. mg protein(-1). l5 min(-1)) in adult rats (from 67+/-1 to 93+/-1) but not in old rats (from 86+/-2 to 87+/-2). Dopamine inhibited Na(+),K(+)-ATPase activity in proximal tubules obtained from adult rats, but it failed to exert such an inhibitory effect in old rats. It is concluded that renal dopaminergic tonus in old rats is higher than in adult rats but fails to respond to HS intake as observed in adult rats. This may be due in part to the inability of dopamine to inhibit Na(+),K(+)-ATPase activity in old rats.

Sociodemographic Determinants of Prevalence and Incidence of Helicobacter pylori Infection in Portuguese Adults

Understanding the determinants of Helicobacter pylori infection in adults is essential to predict the burden of H. pylori‐related diseases. We aimed to estimate the prevalence and incidence of H. pylori infection and to identify its major sociodemographic correlates in an urban population from the North of Portugal.

Hereditary ataxia and spastic paraplegia in Portugal: a population-based prevalence study.

IMPORTANCE Epidemiological data on hereditary cerebellar ataxia (HCA) and hereditary spastic paraplegia (HSP) are scarce. OBJECTIVE To present the prevalence and distribution of HCA and HSP in Portugal. DESIGN AND SETTING Population-based, nationwide, systematic survey, from January 1, 1994, through April 15, 2004, in Portugal. PARTICIPANTS Multiple sources of information were used (review of clinical files, active collaboration of neurologists and geneticists, and investigation of affected families), but the main source was active collaboration of general practitioners. Patients were examined by the same team of neurologists, using homogeneous inclusion criteria. The clinical data were registered, and all families were genetically tested. RESULTS Overall, 1336 patients from a population of 10,322 million were diagnosed as having HCA or HSP, a prevalence of 12.9 per 100,000 population. Hereditary cerebellar ataxia was more prevalent (prevalence, 8.9 per 100,000 population; 5.6 for dominant and 3.3 for recessive ataxias) than HSP (prevalence, 4.1 per 100,000 population; 2.4 for dominant and 1.6 for recessive). Machado-Joseph disease (spinocerebellar ataxia type 3) (prevalence, 3.1 per 100,000 population), Friedreich ataxia (prevalence, 1.0 per 100,000 population), and ataxia with oculomotor apraxia (prevalence, 0.4 per 100,000 population) were the most frequent HCAs. Spastic paraplegia types 4 (prevalence, 0.91 per 100,000 population), 3 (prevalence, 0.14 per 100,000 population), and 11 (prevalence, 0.26 per 100,000 population) were the most prevalent HSPs. CONCLUSIONS AND RELEVANCE This population-based survey covered all the Portuguese territory and mobilized most general practitioners and health centers. To our best knowledge, this survey was the largest ever performed for HCA and HSP. Prevalence of autosomal dominant ataxias was high, particularly for Machado-Joseph disease (spinocerebellar ataxia type 3). The genetic cause has not been identified in 39.7% of the patients studied.

Dietary treatment in phenylketonuria does not lead to increased risk of obesity or metabolic syndrome

BACKGROUND Little is known about the consequences of the special energy enriched diet used to treat patients with phenylketonuria (PKU) in terms of obesity and metabolic syndrome (MetSyn) development. OBJECTIVE To investigate the prevalence of overweight and obesity, and its consequences in terms of body composition and MetSyn in early treated patients with PKU compared to controls. DESIGN A sample of 89 patients with PKU (3-30 y; 14.4±6.6 y) and 79 controls (3-47 y; 16.3±7.9 y) were studied. In the fasted state, anthropometric, body composition, blood pressure and analytical parameters [amino acids, glucose, insulin, total and HDL-cholesterol (HDL-c), triglycerides (TG), high sensitivity c-reactive protein and uric acid] were performed. Data on dietary intake was collected. BMI was classified using WHO criteria, while the definition from International Diabetes Federation (IDF) was used for MetSyn. RESULTS Prevalence of overweight and obesity (32.6% vs. 24.1%; p=0.293), body fat percentage (22% vs. 23.1%, p=0.581) and central obesity (36.9% vs. 36.4%, p=0.999) were comparable to controls. Patients revealed a higher TG/HDL-c (p<0.001). The prevalence of MetSyn was 1.5% and 6.1% in patients and controls, respectively. Patients and not controls with central obesity revealed a further significant increase in TG/HDL-c compared with those without central obesity (p=0.023). CONCLUSION Patients and controls were similar in terms of overweight and obesity, body composition and MetSyn. However, the dyslipidemia in patients with PKU in relation to overweight and obesity may help us trying to understand the course and the etiology of MetSyn not only in PKU but also in the general population.

Renal Dopaminergic System Activity in the Rat Remnant Kidney

Background: Renal dopamine exerts natriuretic and diuretic effects by activating D1-like receptors. Uninephrectomy results in increased renal dopaminergic activity and dopamine-sensitive enhanced natriuresis. Methods: The present study evaluated renal adaptations in sodium handling and the role of dopamine in rats submitted to ¾ nephrectomy: right nephrectomy and excision of both poles of the left kidney (¾nx rats). Results: Two weeks after surgery the absolute urinary levels of dopamine were markedly reduced in ¾nx rats whereas the urinary dopamine excretion per % of residual nephrons was significantly increased in the remnant kidney of ¾nx rats. The Vmax values for renal aromatic L-amino acid decarboxylase, the enzyme responsible for the synthesis of renal dopamine, were decreased in ¾nx rats. Renal catechol-O-methyltransferase activity, the enzyme responsible for the methylation of dopamine, was increased in ¾nx rats whereas the renal activities of monoamine oxidases A and B did not differ between ¾nx and Sham animals. Volume expansion (5% body weight) resulted in similar natriuretic responses in ¾nx and Sham rats. During D1 antagonist administration (Sch-23390, 30 µg·h–1·kg–1) the natriuretic response to volume expansion was reduced in ¾nx rats more pronouncedly than in Sham animals. Conclusion: The decrease in absolute renal dopamine output in ¾nx rats is related with reduced renal synthesis and enhanced O-methylation of the amine. However, this is accompanied in ¾nx rats by increased renal dopamine excretion per residual nephrons and dopamine-sensitive enhanced natriuresis.

Portuguese families with dentatorubropallidoluysian atrophy (DRPLA) share a common haplotype of Asian origin

Dentatorubropallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by a variable combination of progressive ataxia, epilepsy, myoclonus, choreoathetosis and dementia. This disease is caused by a (CAG)n expansion in the DRPLA gene, on chromosome 12p13. DRPLA is prevalent in Japan, but several families of non-Japanese ancestry have already been published. To identify the origin of expanded alleles in Portuguese families with DRPLA, we studied two previously reported intragenic SNPs in introns 1 and 3, in addition to the CAG repeat of the DRPLA gene. The results showed that all four Portuguese DRPLA families shared the same haplotype, which is also common to that reported for Japanese DRPLA chromosomes. This haplotype is also the most frequent in Japanese normal alleles, whereas it was rare in Portuguese control chromosomes. Thus, our findings support that a founder DRPLA haplotype of Asian origin was introduced in Portugal, being responsible for the frequency of the disease in this country.

Persistent organic pollutant levels in human visceral and subcutaneous adipose tissue in obese individuals-Depot differences and dysmetabolism implications

BACKGROUND The role of persistent organic pollutants (POPs) with endocrine disrupting activity in the aetiology of obesity and other metabolic dysfunctions has been recently highlighted. Adipose tissue (AT) is a common site of POPs accumulation where they can induce adverse effects on human health. OBJECTIVES To evaluate the presence of POPs in human visceral (vAT) and subcutaneous (scAT) adipose tissue in a sample of Portuguese obese patients that underwent bariatric surgery, and assess their putative association with metabolic disruption preoperatively, as well as with subsequent body mass index (BMI) reduction. METHODS AT samples (n=189) from obese patients (BMI ≥ 35) were collected and the levels of 13 POPs were determined by gas chromatography with electron-capture detection (GC-ECD). Anthropometric and biochemical data were collected at the time of surgery. BMI variation was evaluated after 12 months and adipocyte size was measured in AT samples. RESULTS Our data confirm that POPs are pervasive in this obese population (96.3% of detection on both tissues), their abundance increasing with age (RS=0.310, p<0.01) and duration of obesity (RS=0.170, p<0.05). We observed a difference in AT depot POPs storage capability, with higher levels of ΣPOPs in vAT (213.9 ± 204.2 compared to 155.1 ± 147.4 ng/g of fat, p<0.001), extremely relevant when evaluating their metabolic impact. Furthermore, there was a positive correlation between POP levels and the presence of metabolic syndrome components, namely dysglycaemia and hypertension, and more importantly with cardiovascular risk (RS=0.277, p<0.01), with relevance for vAT (RS=0.315, p<0.01). Finally, we observed an interesting relation of higher POP levels with lower weight loss in older patients. CONCLUSION Our sample of obese subjects allowed us to highlight the importance of POPs stored in AT on the development of metabolic dysfunction in a context of obesity, shifting the focus to their metabolic effects and not only for their recognition as environmental obesogens.