Consumption of sugar-sweetened soft drinks and risk of metabolic syndrome and its components: results of the ELSA-Brasil study (2008-2010 and 2012-2014).

AIM: To estimate the association between consumption of sugar-sweetened soft drinks and unsweetened fruit juice with metabolic syndrome (MetS) and its components in participants of the Brazilian Longitudinal Adult Health Study (ELSA-Brasil) after 4 years of follow-up. METHODS: We used data from ELSA-Brasil cohort (N = 15,105). The sample consisted of 6,124 civil servants free of the MetS at baseline (35 to 74 years, both sexes). The consumption of sugar-sweetened soft drinks and unsweetened fruit juice was estimated by a food frequency questionnaire previously validated. The outcome was MetS and its components (Joint Interim Statement criteria). To test the association between beverage consumption at baseline (2008-2010) and MetS and its components at follow-up (2012-2014), we used Poisson regression models with robust variance adjusting for potential confounders. RESULTS: After 4-year follow-up, the higher consumption of sugar-sweetened soft drinks (≥ 1 serving/day = 250 mL/day) increased the relative risk of MetS (RR = 1.22; 95% CI 1.04-1.45), high fasting glucose (RR = 1.23; 95% CI 1.01-1.48), and high blood pressure (RR = 1.23; 95% CI 1.00-1.54). Moderate consumption of this beverage (0.4 to < 1 serving/day) increased the relative risk of high waist circumference (WC) (RR = 1.21; 95% CI 1.02-1.42). After adjustment for confounding variables, the consumption of unsweetened fruit juice was not associated with the MetS and its components. CONCLUSION: Higher sugar-sweetened soft drinks consumption was associated with a higher risk relative of MetS, high fasting glucose, and high blood pressure, while moderate consumption of this beverage increased the relative risk of high WC in Brazilian adults.

Association of coronary artery calcium with heart rate variability in the Brazilian Longitudinal Study of Adult Health - ELSA-Brasil

Current data shows that the autonomic and vascular systems can influence each other. However, only a few studies have addressed this association in the general population. We aimed to investigate whether heart rate variability (HRV) was associated with coronary artery calcium (CAC) in a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We examined baseline data from 3138 participants (aged 35 to 74 years) without previous cardiovascular disease who underwent CAC score assessment and had validated HRV recordings. Prevalent CAC was defined as a CAC score>0, and HRV analyses were performed over 5-min segments. We detected CAC score>0 in 765 (24.4%) participants. Subgroup analyses in older participants (≥49 years) adjusted for sociodemographic and clinical variables revealed that CAC score>0 was associated with lower values of standard deviation of NN intervals (SDNN) (odds ratio [OR]=1.32; 95%CI: 1.05,1.65), root mean square of successive differences between adjacent NN intervals (RMSSD) (OR=1.28; 95%CI: 1.02,1.61), and low frequency (LF) (OR=1.53, 95%CI: 1.21,1.92). Interaction analysis between HRV indices and sex in age-stratified groups revealed significant effect modification: women showed increased OR for prevalent CAC in the younger group, while for men, the associations were in the older group. In conclusion, participants aged ≥49 years with low SDNN, RMSSD, and LF values were more likely to present prevalent CAC, suggesting a complex interaction between these markers in the pathogenesis of atherosclerosis. Furthermore, our results suggested that the relationship between CAC and HRV might be sex- and age-related.

Association between dietary patterns and renal function in a cross-sectional study using baseline data from the ELSA-Brasil cohort

Previous analyses of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) identified four main dietary patterns (DP). The aim of this study was to explore the association between the previously defined DP and renal function (RF). A cross-sectional study using the ELSA-Brasil baseline data was carried out. DP ("traditional", "fruits and vegetables", "bakery", and "low sugar/low fat), metabolic syndrome (MS) using the Joint Interim Statement criteria, microalbuminuria (MA), and glomerular filtration rate (eGFR) through the CKD-EPI equation were evaluated. Abnormal RF was defined as eGFR<60 mL·min-1·(1.73 m2)-1 and MA≥3.0 mg/dL. Factors associated with RF were determined and mediation analysis was performed to investigate the association between DP, MS, and RF. A total of 15,105 participants were recruited, with a mean age of 52±9 years; 8,134 participants (54%) were females. The mediation analysis identified indirect associations between "bakery" and "fruits and vegetables", and both were associated with decreased eGFR and albuminuria in both genders, compared with "traditional" and "low sugar/low fat" patterns in the general population. There was a direct association of the "bakery" pattern with MA in men (OR: 1.17, 95%CI: 1.92-1.48). The "fruits and vegetables" pattern also showed a direct association with reduced eGFR in women (OR: 1.65, 95%CI: 1.28-2.12), although there was no significance after adjustment. The "fruits and vegetables" and "bakery" DPs were associated with renal dysfunction. The only independent, direct association was between "bakery" DP and MA in men, raising concerns about DP and renal damage in men.

Relationship between heart rate variability and subclinical thyroid disorders of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

The association between subclinical thyroid dysfunctions and autonomic modulation changes has been described by many studies with conflicting results. We aimed to analyze the association between subclinical hyperthyroidism (SCHyper), subclinical hypothyroidism (SCHypo), and heart rate variability (HRV) using the baseline from ELSA-Brasil. SCHyper and SCHypo were classified by use of medication to treat thyroid disorders, thyrotropin levels respectively above and under the reference range, and normal free thyroxine levels. For HRV, the participants underwent 10 min in supine position and the R-R intervals of the final 5 min were selected for analysis. We first used linear regression models to report crude data and then, multivariate adjustment for sociodemographic (age, sex, and race) and cardiovascular risk factors (hypertension, dyslipidemia, diabetes, smoking, body mass index, use of alcohol, and leisure physical activity) using the euthyroid group as reference. From 9270 subjects (median age, 50; interquartile range: 44-56), 8623 (93.0%) were classified as euthyroid, 136 (1.5%) as SCHyper, and 511 (5.5%) as SCHypo. Compared to euthyroid subjects, SCHyper participants presented significantly higher heart rate (68.8 vs 66.5 for euthyroidism, P=0.007) and shorter R-R intervals (871.4 vs 901.6, P=0.007). Although SCHyper was associated with lower standard deviation of NN interval (SDNN) (ß: -0.070; 95% confidence interval (95%CI): -0.014 to -0.009) and low-frequency (LF) (ß: -0.242, 95%CI: -0.426 to -0.058) compared to the euthyroid group, these differences lost significance after multivariate adjustment for confounders. No significant differences were found for HRV in SCHypo. No association was found between HRV and SCHyper or SCHypo compared to euthyroid subjects in this sample of apparently healthy subjects.

Relationship between heart rate variability and subclinical thyroid disorders of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

The association between subclinical thyroid dysfunctions and autonomic modulation changes has been described by many studies with conflicting results. We aimed to analyze the association between subclinical hyperthyroidism (SCHyper), subclinical hypothyroidism (SCHypo), and heart rate variability (HRV) using the baseline from ELSA-Brasil. SCHyper and SCHypo were classified by use of medication to treat thyroid disorders, thyrotropin levels respectively above and under the reference range, and normal free thyroxine levels. For HRV, the participants underwent 10 min in supine position and the R-R intervals of the final 5 min were selected for analysis. We first used linear regression models to report crude data and then, multivariate adjustment for sociodemographic (age, sex, and race) and cardiovascular risk factors (hypertension, dyslipidemia, diabetes, smoking, body mass index, use of alcohol, and leisure physical activity) using the euthyroid group as reference. From 9270 subjects (median age, 50; interquartile range: 44-56), 8623 (93.0%) were classified as euthyroid, 136 (1.5%) as SCHyper, and 511 (5.5%) as SCHypo. Compared to euthyroid subjects, SCHyper participants presented significantly higher heart rate (68.8 vs 66.5 for euthyroidism, P=0.007) and shorter R-R intervals (871.4 vs 901.6, P=0.007). Although SCHyper was associated with lower standard deviation of NN interval (SDNN) (β: -0.070; 95% confidence interval (95%CI): -0.014 to -0.009) and low-frequency (LF) (β: -0.242, 95%CI: -0.426 to -0.058) compared to the euthyroid group, these differences lost significance after multivariate adjustment for confounders. No significant differences were found for HRV in SCHypo. No association was found between HRV and SCHyper or SCHypo compared to euthyroid subjects in this sample of apparently healthy subjects.

Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats

In cardiomyocytes, calcium (Ca2+) release units comprise clusters of intracellular Ca2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F0), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F0, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes.

Correlation between sodium and potassium excretion in 24- and 12-h urine samples

Low-sodium and high-potassium diets have been recommended as an adjunct to prevention and treatment of hypertension. Analysis of these nutrients in 24-h urine has been considered the reference method to estimate daily intake of these minerals. However, 24-h urine collection is difficult in epidemiological studies, since urine must be collected and stored in job environments. Therefore, strategies for shorter durations of urine collection at home have been proposed. We have previously reported that collecting urine during a 12-h period (overnight) is more feasible and that creatinine clearance correlated strongly with that detected in 24-h samples. In the present study, we collected urine for 24 h divided into two 12-h periods (from 7:00 am to 7:00 pm and from 7:00 pm to 7:00 am next day). A sample of 109 apparently healthy volunteers aged 30 to 74 years of both genders working in a University institution was investigated. Subjects with previous myocardial infarction, stroke, renal insufficiency, and pregnant women were not included. Significant (P < 0.001) Spearman correlation coefficients (r s) were found between the total amount of sodium and potassium excreted in the urine collected at night and in the 24-h period (r s = 0.76 and 0.74, respectively). Additionally, the 12-h sodium and potassium excretions (means ± SD, 95% confidence interval) corresponded to 47.3 ± 11.2%, 95%CI = 45.3-49.3, and 39.3 ± 4.6%, 95%CI = 37.3-41.3, respectively, of the 24-h excretion of these ions. Therefore, these findings support the assumption that 12-h urine collected at night can be used as a reliable tool to estimate 24-h intake/excretion of sodium and potassium.

CYBA C242T polymorphism is associated with obesity and diabetes mellitus in Brazilian hypertensive patients.

AIMS: The CYBA C242T polymorphism has been associated with cardiovascular phenotypes such as hypertension and atherosclerosis, but available data are conflicting. This report investigated the impact of this variant on hypertension and metabolic determinants of cardiovascular risk in a large Brazilian sample. METHODS: We cross-sectionally evaluated 1856 subjects (826 normotensive subjects and 1030 hypertensive patients) by clinical history, anthropometry, laboratory analysis and genotyping of the CYBA C242T polymorphism. RESULTS: Genotype frequencies in the whole population were consistent with the Hardy-Weinberg equilibrium and genotype distributions were not different between hypertensive and normotensive subjects. Hypertensive patients with the CC genotype presented lower fasting plasma glucose levels (5.9 ± 0.1 vs. 6.2 ± 0.1 mmol/l, P = 0.020) and waist circumference (94.5 ± 0.6 vs. 96.3 ± 0.6 cm, P = 0.028) than CT + TT ones. Similarly, the prevalence of diabetes mellitus and obesity was also lower in hypertensive patients carrying the CC genotype (16% vs. 21%, P = 0.041; 36% vs. 43%, P = 0.029, respectively). In addition, multiple and logistic regression analysis demonstrated that the CYBA C242T polymorphism was associated with glucose levels, waist circumference, obesity and diabetes mellitus in hypertensive patients independently of potential confounders. Conversely, in normotensive subjects, no significant difference in studied variables was detected between the genotype groups. CONCLUSIONS: These data suggest that the T allele of the CYBA C242T polymorphism may be used as a marker for adverse metabolic features in Brazilian subjects with systemic hypertension.

Remodeling in the ischemic heart: the stepwise progression for heart

Abstract Coronary artery disease is the leading cause of death in the developed world and in developing countries. Acute mortality from acute myocardial infarction (MI) has decreased in the last decades. However, the incidence of heart failure (HF) in patients with healed infarcted areas is increasing. Therefore, HF prevention is a major challenge to the health system in order to reduce healthcare costs and to provide a better quality of life. Animal models of ischemia and infarction have been essential in providing precise information regarding cardiac remodeling. Several of these changes are maladaptive, and they progressively lead to ventricular dilatation and predispose to the development of arrhythmias, HF and death. These events depend on cell death due to necrosis and apoptosis and on activation of the inflammatory response soon after MI. Systemic and local neurohumoral activation has also been associated with maladaptive cardiac remodeling, predisposing to HF. In this review, we provide a timely description of the cardiovascular alterations that occur after MI at the cellular, neurohumoral and electrical level and discuss the repercussions of these alterations on electrical, mechanical and structural dysfunction of the heart. We also identify several areas where insufficient knowledge limits the adoption of better strategies to prevent HF development in chronically infarcted individuals.

Reproducibility of heart rate variability parameters measured in healthy subjects at rest and after a postural change maneuver

Heart rate variability (HRV) provides important information about cardiac autonomic modulation. Since it is a noninvasive and inexpensive method, HRV has been used to evaluate several parameters of cardiovascular health. However, the internal reproducibility of this method has been challenged in some studies. Our aim was to determine the intra-individual reproducibility of HRV parameters in short-term recordings obtained in supine and orthostatic positions. Electrocardiographic (ECG) recordings were obtained from 30 healthy subjects (20-49 years, 14 men) using a digital apparatus (sampling ratio = 250 Hz). ECG was recorded for 10 min in the supine position and for 10 min in the orthostatic position. The procedure was repeated 2-3 h later. Time and frequency domain analyses were performed. Frequency domain included low (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.4 Hz) bands. Power spectral analysis was performed by the autoregressive method and model order was set at 16. Intra-subject agreement was assessed by linear regression analysis, test of difference in variances and limits of agreement. Most HRV measures (pNN50, RMSSD, LF, HF, and LF/HF ratio) were reproducible independent of body position. Better correlation indexes (r > 0.6) were obtained in the orthostatic position. Bland-Altman plots revealed that most values were inside the agreement limits, indicating concordance between measures. Only SDNN and NNv in the supine position were not reproducible. Our results showed reproducibility of HRV parameters when recorded in the same individual with a short time between two exams. The increased sympathetic activity occurring in the orthostatic position probably facilitates reproducibility of the HRV indexes.

Effects of chronic treadmill training on body mass gain and visceral fat accumulation in overfed rats

This study evaluated the effects of chronic treadmill training on body mass gain and visceral fat accumulation in overfed rats. Overfeeding was induced by reducing the litter size to 3 male pups per mother during the suckling period. The litter size of control rats was adjusted to 10 male pups per mother. Seven weeks after birth overfed and normally fed rats were selected and assigned to a sedentary protocol or to a low-intensity treadmill training protocol (60 min, 5 times/week, for 9 weeks). Four groups (overfed sedentary, N = 23; normally fed sedentary, N = 32; overfed exercised, N = 18, and normally fed exercised, N = 18) were evaluated at 18 weeks. Data are reported as means ± SEM. Initial body weight was similar in control and overfed rats [8.0 ± 0.2 g (N = 42) vs 8.0 ± 0.1 g (N = 50); P > 0.05] and body weight gain during the suckling period was higher in the overfed rats (30.6 ± 0.9 vs 23.1 ± 0.3 g; P < 0.05). Exercise attenuated the body weight gain of overfed compared to sedentary rats (505 ± 14 vs 537 ± 12 g; P < 0.05). The sedentary overfed rats showed higher visceral fat weight compared to normally fed animals (31.22 ± 2.08 vs 21.94 ± 1.76 g; P < 0.05). Exercise reduced visceral fat by 36.5 percent in normally fed rats and by 35.7 percent in overfed rats. Exercise attenuated obesity in overfed rats and induced an important reduction of visceral fat.

Kinetics of cardiac and vascular remodeling by spontaneously hypertensive rats after discontinuation of long-term captopril treatment

Angiotensin-converting enzyme inhibitors reduce blood pressure and attenuate cardiac and vascular remodeling in hypertension. However, the kinetics of remodeling after discontinuation of the long-term use of these drugs are unknown. Our objective was to investigate the temporal changes occurring in blood pressure and vascular structure of spontaneously hypertensive rats (SHR). Captopril treatment was started in the pre-hypertensive state. Rats (4 weeks) were assigned to three groups: SHR-Cap (N = 51) treated with captopril (1 g/L) in drinking water from the 4th to the 14th week; SHR-C (N = 48) untreated SHR; Wistar (N = 47) control rats. Subgroups of animals were studied at 2, 4, and 8 weeks after discontinuation of captopril. Direct blood pressure was recorded in freely moving animals after femoral artery catheterism. The animals were then killed to determine left ventricular hypertrophy (LVH) and the aorta fixed at the same pressure measured in vivo. Captopril prevented hypertension (105 ± 3 vs 136 ± 5 mmHg), LVH (2.17 ± 0.05 vs 2.97 ± 0.14 mg/g body weight) and the increase in cross-sectional area to luminal area ratio of the aorta (0.21 ± 0.01 vs 0.26 ± 0.02 ìm²) (SHR-Cap vs SHR-C). However, these parameters increased progressively after discontinuation of captopril (22nd week: 141 ± 2 mmHg, 2.50 ± 0.06 mg/g, 0.27 ± 0.02 ìm²). Prevention of the development of hypertension in SHR by using captopril during the prehypertensive period prevents the development of cardiac and vascular remodeling. Recovery of these processes follows the kinetic of hypertension development after discontinuation of captopril.

Ventricular performance and Na+-K+ ATPase activity are reduced early and late after myocardial infarction in rats

Myocardial infarction leads to compensatory ventricular remodeling. Disturbances in myocardial contractility depend on the active transport of Ca2+ and Na+, which are regulated by Na+-K+ ATPase. Inappropriate regulation of Na+-K+ ATPase activity leads to excessive loss of K+ and gain of Na+ by the cell. We determined the participation of Na+-K+ ATPase in ventricular performance early and late after myocardial infarction. Wistar rats (8-10 per group) underwent left coronary artery ligation (infarcted, Inf) or sham-operation (Sham). Ventricular performance was measured at 3 and 30 days after surgery using the Langendorff technique. Left ventricular systolic pressure was obtained under different ventricular diastolic pressures and increased extracellular Ca2+ concentrations (Ca2+e) and after low and high ouabain concentrations. The baseline coronary perfusion pressure increased 3 days after myocardial infarction and normalized by 30 days (Sham 3 = 88 ± 6; Inf 3 = 130 ± 9; Inf 30 = 92 ± 7 mmHg; P < 0.05). The inotropic response to Ca2+e and ouabain was reduced at 3 and 30 days after myocardial infarction (Ca2+ = 1.25 mM; Sham 3 = 70 ± 3; Inf 3 = 45 ± 2; Inf 30 = 29 ± 3 mmHg; P < 0.05), while the Frank-Starling mechanism was preserved. At 3 and 30 days after myocardial infarction, ventricular Na+-K+ ATPase activity and contractility were reduced. This Na+-K+ ATPase hypoactivity may modify the Na+, K+ and Ca2+ transport across the sarcolemma resulting in ventricular dysfunction.

Ventricular performance and Na+-K+ ATPase activity are reduced early and late after myocardial infarction in rats.

Myocardial infarction leads to compensatory ventricular remodeling. Disturbances in myocardial contractility depend on the active transport of Ca2+ and Na+, which are regulated by Na+-K+ ATPase. Inappropriate regulation of Na+-K+ ATPase activity leads to excessive loss of K+ and gain of Na+ by the cell. We determined the participation of Na+-K+ ATPase in ventricular performance early and late after myocardial infarction. Wistar rats (8-10 per group) underwent left coronary artery ligation (infarcted, Inf) or sham-operation (Sham). Ventricular performance was measured at 3 and 30 days after surgery using the Langendorff technique. Left ventricular systolic pressure was obtained under different ventricular diastolic pressures and increased extracellular Ca2+ concentrations (Ca2+e) and after low and high ouabain concentrations. The baseline coronary perfusion pressure increased 3 days after myocardial infarction and normalized by 30 days (Sham 3 = 88 +/- 6; Inf 3 = 130 +/- 9; Inf 30 = 92 +/- 7 mmHg; P < 0.05). The inotropic response to Ca2+e and ouabain was reduced at 3 and 30 days after myocardial infarction (Ca2+ = 1.25 mM; Sham 3 = 70 +/- 3; Inf 3 = 45 +/- 2; Inf 30 = 29 +/- 3 mmHg; P < 0.05), while the Frank-Starling mechanism was preserved. At 3 and 30 days after myocardial infarction, ventricular Na+-K+ ATPase activity and contractility were reduced. This Na+-K+ ATPase hypoactivity may modify the Na+, K+ and Ca2+ transport across the sarcolemma resulting in ventricular dysfunction.

TCF7L2 variant genotypes and type 2 diabetes risk in Brazil: significant association, but not a significant tool for risk stratification in the general population.

BACKGROUND: Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population. METHODS: We genotyped the single nucleotide polymorphisms (SNP) rs7903146 of the TCF7L2 gene in 560 patients with known coronary disease enrolled in the MASS II (Medicine, Angioplasty, or Surgery Study) Trial and in 1,449 residents of Vitoria, in Southeast Brazil. The associations of this gene variant to diabetes risk and metabolic characteristics in these two different populations were analyzed. To access the potential benefit of using this marker for diabetes risk prediction in the general population we analyzed the impact of this genetic variant on a validated diabetes risk prediction tool based on clinical characteristics developed for the Brazilian general population. RESULTS: SNP rs7903146 of the TCF7L2 gene was significantly associated with type 2 diabetes in the MASS-II population (OR = 1.57 per T allele, p = 0.0032), confirming, in the Brazilian population, previous reports of the literature. Addition of this polymorphism to an established clinical risk prediction score did not increased model accuracy (both area under ROC curve equal to 0.776). CONCLUSION: TCF7L2 rs7903146 T allele is associated with a 1.57 increased risk for type 2 diabetes in a Brazilian cohort of patients with known coronary heart disease. However, the inclusion of this polymorphism in a risk prediction tool developed for the general population resulted in no improvement of performance. This is the first study, to our knowledge, that has confirmed this recent association in a South American population and adds to the great consistency of this finding in studies around the world. Finally, confirming the biological association of a genetic marker does not guarantee improvement on already established screening tools based solely on demographic variables.

[A patient with feigned mental incompetence requiring medical treatment]. / Een patiënt die wilsonbekwaamheid simuleert en voor wie somatische behandeling is geïndiceerd.

A woman at the presumed age of 60 years was suspected of malingering cognitive impairment, due to her social circumstances (illegal residency) and was consequently unable to give permission for treatment. She was suffering from locally advanced mammary carcinoma, diagnosed according to the Breast Imaging Reporting and Data System in stage 5. In order to assess mental incompetence, an algorithm from the Royal Dutch Medical Association (KNMG) is a useful tool. The algorithm contains questions for determining whether a patient is able to make choices, if he/she understands medical information and can apply this to his/her own situation and whether he/she is able to logically consider the choice. Mental incompetence is a legally defined status - there is no straightforward relation between mental incompetence and the underlying diagnosis, in this case malingering. Since feigning mental incompetence has its own limitations, the subjective judgment of the physician is important. In the case presented, medical treatment i.e. chemotherapy was started in accordance with the Dutch Medical Treatment Contracts Act (WGBO) for a patient with cognitive impairment. Compulsory treatment was not necessary because the patient did not resist either physically or verbally. If a critical situation is to be prevented or is threatening, then there is no difference between genuine or feigned mental incompetence.

Endothelial nitric oxide synthase gene variant modulates the relationship between serum cholesterol levels and blood pressure in the general population: new evidence for a direct effect of lipids in arterial blood pressure.

BACKGROUND: A causal relationship between plasma cholesterol and blood pressure remains poorly understood. It has been postulated that the decrease in nitric oxide (NO) availability is a potential mechanism by which hypercholesterolemia may stimulate blood pressure elevation. However, evidence supporting the role of the L-arginine-NO pathway on the relationship between hypertension and hypercholesterolemia is still lacking. METHODS AND RESULTS: We tested for an association of the expressed NO synthase (eNOS) Glu298Asp gene variant and plasma levels of lipids and lipoproteins in the determination of systolic blood pressure levels in a 1577 individuals randomly selected from the general population. Significant interactions could be disclosed either between the Glu298Asp gene variant and total-cholesterol (p = 0.02), log-transformed triglycerides (p = 0.004) or non-HDL-cholesterol (p = 0.003) in the determination of systolic blood pressure. In addition, although the presence of the AspAsp genotype did not significantly increase the risk of hypertension in individuals in the 50% lowest percentile of total-cholesterol, presence of this genotype significantly increased the risk of hypertension in individuals in the 50% highest percentile. Finally, in a multiple logistic regression model adjusting for age, sex, diabetes, ethnicity, smoking status and BMI, the AspAsp genotype significantly increased the risk of hypertension only in individuals with total-cholesterol above 209 mg/dL (p = 0.05, odds ratios (OR) = 2.0). CONCLUSION: Taken together, these results provide evidence supporting the role of the eNOS Glu298Asp gene variant in modulating blood pressure through a relationship with lipid levels.

Chronic experimental myocardial infarction produces antinatriuresis by a renal nerve-dependent mechanism

The present study focused on the role of sympathetic renal nerve activity, in mediating congestive heart failure-induced sodium retention following experimental chronic myocardial infarction. Groups of male Wistar rats (240-260 g) were studied: sham-operated coronary ligation (CON3W, N = 11), coronary ligation and sham-operated renal denervation (INF3W, N = 19), 3 weeks of coronary ligation and sympathetic renal nerve denervation (INF3WDX, N = 6), sham-operated coronary ligation (N = 7), and 16 weeks of coronary ligation (INF16W, N = 7). An acute experimental protocol was used in which the volume overload (VO; 5 percent of body weight) was applied for 30 min after the equilibration period of continuous iv infusion of saline. Compared to control levels, VO produced an increase (P < 0.01, ANOVA) in urine flow rate (UFR; 570 percent) and urinary sodium excretion (USE; 1117 percent) in CON3W. VO induced a smaller increase (P < 0.01) in USE (684 percent) in INF3W. A similar response was also observed in INF16W. In INF3WDX, VO produced an immediate and large increase (P < 0.01) in UFR (547 percent) and USE (1211 percent). Similarly, in INF3W VO increased (P < 0.01) UFR (394 percent) and USE (894 percent). Compared with INF3W, VO induced a higher (P < 0.01) USE in INF3WDX, whose values were similar to those for CON3W. These results suggest that renal sympathetic activity may be involved in sodium retention induced by congestive heart failure. This premise is supported by the observation that in bilaterally renal denervated INF3WDX rats myocardial infarction was unable to reduce volume expansion-induced natriuresis. However, the mechanism involved in urinary volume regulation seems to be insensitive to the factors that alter natriuresis.

Ambulatory blood pressure and Doppler echocardiographic indexes of borderline hypertensive men presenting an exaggerated blood pressure response during dynamic exercise

Borderline hypertension (BH) has been associated with an exaggerated blood pressure (BP) response during laboratory stressors. However, the incidence of target organ damage in this condition and its relation to BP hyperreactivity is an unsettled issue. Thus, we assessed the Doppler echocardiographic profile of a group of BH men (N = 36) according to office BP measurements with exaggerated BP in the cycloergometric test. A group of normotensive men (NT, N = 36) with a normal BP response during the cycloergometric test was used as control. To assess vascular function and reactivity, all subjects were submitted to the cold pressor test. Before Doppler echocardiography, the BP profile of all subjects was evaluated by 24-h ambulatory BP monitoring. All subjects from the NT group presented normal monitored levels of BP. In contrast, 19 subjects from the original BH group presented normal monitored BP levels and 17 presented elevated monitored BP levels. In the NT group all Doppler echocardiographic indexes were normal. All subjects from the original BH group presented normal left ventricular mass and geometrical pattern. However, in the subjects with elevated monitored BP levels, fractional shortening was greater, isovolumetric relaxation time longer, and early to late flow velocity ratio was reduced in relation to subjects from the original BH group with normal monitored BP levels (P<0.05). These subjects also presented an exaggerated BP response during the cold pressor test. These results support the notion of an integrated pattern of cardiac and vascular adaptation during the development of hypertension

Effects of mercury on the arterial blood pressure of anesthetized rats

The available data suggests that hypotension caused by Hg2+ administration may be produced by a reduction of cardiac contractility or by cholinergic mechanisms. The hemodynamic effects of an intravenous injection of HgCl2 (5 mg/kg) were studied in anesthetized rats (N = 12) by monitoring left and right ventricular (LV and RV) systolic and diastolic pressures for 120 min. After HgCl2 administration the LV systolic pressure decreased only after 40 min (99 +or - 3.3 to 85 + or - 8.8 mmHg at 80 min). However, RV systolic pressure increased, initially slowly but faster after 30 min (25 + or - 1.8 to 42 + or - 1.6 mmHg at 80 min). Both right and left diastolic pressures increased after HgCl2 treatment, suggesting the development of diastolic ventricular dysfunction. Since HgCl2 could be increasing pulmonary vascular resistance, isolated lungs (N = 10) were perfused for 80 min with Krebs solution (continuous flow of 10 ml/min) containing or not 5 µM HgCl2. A continuous increase in pulmonary vascular resistance was observed, suggesting the direct effect of Hg2+ on the pulmonary vessels (12 + or - 0.4 to 29 + or - 3.2 mmHg at 30 min). To examine the interactions of Hg2+ and changes in cholinergic activity we analyzed the effects of acetylcholine (Ach) on mean arterial blood pressure (ABP) in anesthetized rats (N = 9) before and after Hg2+ treatment (5 mg/kg). Using the same amount and route used to study the hemodynamic effects we also examined the effects of Hg2+ administration on heart and plasma cholinesterase activity (N = 10). The in vivo hypotensive response to Ach (0.035 to 10.5 µg) was reduced after Hg2+ treatment. Cholinesterase activity (µM h-1 mg protein-1) increased in heart and plasma (32 and 65 percent, respectively) after Hg2+ treatment. In conclusion, the reduction in ABP produced by Hg2+ is not dependent on a putative increase in cholinergic activity. HgCl2 mainly affects cardiac function. The increased pulmonary vascular resistance and cardiac failure due to diastolic dysfunction of both ventricles are factors that might contribute to the reduction of cardiac output and the fall in arterial pressure