José R. Matos-Souza

Sex-specific hemodynamic and non-hemodynamic determinants of aortic root size in hypertensive subjects with left ventricular hypertrophy

Aortic root (AoR) dilatation is more frequently observed in hypertensive individuals and is independently associated with left ventricular (LV) hypertrophy. Although the LV structure has sex-specific predictors, it remains unknown whether there are gender-related differences in the determinants of AoR size. We carried out a cross-sectional analysis of clinical, laboratory, anthropometric, funduscopic and echocardiographic features of 438 hypertensive patients with LV hypertrophy (266 women and 172 men). Women with enlarged AoR had higher cardiac output (P=0.0004), decreased peripheral vascular resistance (P=0.009), higher prevalence of mild aortic regurgitation (P=0.02) and increased waist circumference (P=0.04), whereas AoR-dilated men presented with a higher prevalence of concentric LV hypertrophy (P=0.0008) and mild aortic regurgitation (P=0.005) and increased log C-reactive protein levels (P=0.02), compared with sex-matched normal AoR subjects. In women, AoR dilatation associated with cardiac output, mild aortic regurgitation and waist circumference in a multivariate model including age, body surface area, height, homeostasis model assessment index, LV mass index, diastolic blood pressure, menopause status and use of antihypertensive medications as independent variables. Conversely, AoR dilatation associated with LV relative wall thickness, log C-reactive protein and mild aortic regurgitation without contributions from diastolic blood pressure, height, body surface area, LV mass index, peripheral vascular resistance and antihypertensive medications in men. Taken together, these results suggest that both volume overload and abdominal obesity are related to AoR dilatation in hypertensive women, whereas AoR enlargement is associated more with inflammatory and myocardial growth-related parameters in hypertensive men with LV hypertrophy.

Relationship between serum uric acid and internal carotid resistive index in hypertensive women: a cross-sectional study

BackgroundThe impact of serum uric acid (SUA) on arteries of hypertensive subjects remains to be fully established. This study investigated the relationship between SUA and carotid structural and hemodynamic parameters in hypertensive men and women.MethodsThree hundred and thirty eight patients (207 women and 131 men) were cross-sectionally evaluated by clinical, laboratory, hemodynamic and carotid ultrasound analysis. Common carotid diameters, circumferential wall tensions, Young’s Elastic Modulus, Stiffness Index, Arterial Compliance and intima-media thickness (IMT) were determined. Internal carotid artery resistive index (ICRI), a hemodynamic measure that reflects local vascular impedance and microangiopathy, was also assessed.ResultsUnivariate analysis showed no significant correlation of SUA with carotid diameters, elasticity/stiffness indexes, IMT and circumferential wall tensions in both genders. Conversely, SUA correlated with ICRI (r = 0.34; p < 0.001) in women, but not in men, and hyperuricemic women presented higher ICRI than normouricemic ones (0.684 ± 0.007 vs. 0.649 ± 0.004; p < 0.001). Stepwise and logistic regression analyses adjusted for potential confounding factors showed that ICRI was independently associated with SUA and hyperuricemia in women.ConclusionsThis study demonstrated that SUA was associated with ICRI in hypertensive women, suggesting that there might gender-related differences in the relationship between SUA and vascular damage in subjects with systemic hypertension.

Sodium Intake Is Associated with Carotid Artery Structure Alterations and Plasma Matrix Metalloproteinase-9 Upregulation in Hypertensive Adults

The mechanisms by which dietary sodium modulates cardiovascular risk are not fully understood. This study investigated whether sodium intake is related to carotid structure and hemodynamics and to plasma matrix metalloproteinase (MMP) activity in hypertensive adults. One hundred thirty-four participants were cross-sectionally evaluated by clinical history, anthropometry, carotid ultrasound, and analysis of hemodynamic, inflammatory, and metabolic variables. Daily sodium intake (DSI) was estimated by 24-h recall, discretionary sodium, and a FFQ. In 42 patients, plasma MMP-2 and MMP-9 activities were also analyzed. The mean DSI was 5.52 ± 0.29 g/d. Univariate analysis showed that DSI correlated with common carotid artery systolic and diastolic diameter (r = 0.36 and 0.34; both P < 0.001), peak and mean circumferential tension (r = 0.44 and 0.39; both P < 0.001), Youngs Elastic Modulus (r = 0.40; P < 0.001), intima-media thickness (r = 0.19; P < 0.05), and internal carotid artery resistive index (r = 0.20; P < 0.05). Multivariate analyses revealed that only artery diameter, circumferential wall tension, and Youngs Elastic Modulus were independently associated with DSI. Conversely, plasma MMP-9 activity was associated with DSI (r = 0.53; P < 0.001) as well as with common carotid systolic diameter (r = 0.33; P < 0.05) and Youngs Elastic Modulus (r = 0.38; P < 0.01). In conclusion, sodium intake is associated with carotid alterations in hypertensive adults independently of systemic hemodynamic variables. The present findings also suggest that increased MMP-9 activity might play a role in sodium-induced vascular remodeling.

Toll-like receptor 6 Ser249Pro polymorphism is associated with lower left ventricular wall thickness and inflammatory response in hypertensive women.

BACKGROUND Experimental data demonstrated that inactivation of toll-like receptor (TLR) pathway components attenuated left ventricular (LV) remodeling induced by pressure overload. This study investigated the impact of TLR6 Ser249Pro polymorphism on LV structure in hypertensive subjects. METHODS A sample of 443 patients (266 women and 177 men) was evaluated by clinical history, physical examination, analysis of inflammatory and metabolic parameters, echocardiography, and genotyping of the TLR6 variant. Moreover, the relationship between genotypes and in vitro responsiveness of peripheral blood monocytic cells to TLR agonists was also assessed. RESULTS Homozygous women for the TLR6 249Ser allele had lower LV posterior wall thickness (9.4 + or - 0.4 vs. 10.5 + or - 0.1 mm; P = 0.02), interventricular septum thickness (9.7 + or - 0.3 vs. 10.7 + or - 0.1 mm; P = 0.03), and LV relative wall thickness (0.39 + or - 0.02 vs. 0.44 + or - 0.01; P = 0.02) than women with other genotypes. These results were confirmed by stepwise regression analyses adjusted by potential confounders. Conversely, homozygous men for the 249Ser variant showed no differences in LV structure in comparison to males carrying the 249Pro allele. In addition, monocytes from hypertensive women homozygous for the 249Ser allele showed a lower release of tumor necrosis factor-alpha and interleukin-6 in response to zymosan (TLR6 agonist), but not to lipopolysaccharide (TLR4 agonist). CONCLUSION These data suggest that hypertensive women homozygous for the TLR6 249Ser polymorphism might exhibit lower LV wall thickness and reduced TLR6-mediated inflammatory response than females carrying the major allele.

The C242T polymorphism of the p22-phox gene (CYBA) is associated with higher left ventricular mass in Brazilian hypertensive patients.

BackgroundReactive oxygen species have been implicated in the physiopathogenesis of hypertensive end-organ damage. This study investigated the impact of the C242T polymorphism of the p22-phox gene (CYBA) on left ventricular structure in Brazilian hypertensive subjects.MethodsWe cross-sectionally evaluated 561 patients from 2 independent centers [Campinas (n = 441) and Vitória (n = 120)] by clinical history, physical examination, anthropometry, analysis of metabolic and echocardiography parameters as well as p22-phox C242T polymorphism genotyping. In addition, NADPH-oxidase activity was quantified in peripheral mononuclear cells from a subgroup of Campinas sample.ResultsGenotype frequencies in both samples were consistent with the Hardy- Weinberg equilibrium. Subjects with the T allele presented higher left ventricular mass/height2.7 than those carrying the CC genotype in Campinas (76.8 ± 1.6 vs 70.9 ± 1.4 g/m2.7; p = 0.009), and in Vitória (45.6 ± 1.9 vs 39.9 ± 1.4 g/m2.7; p = 0.023) samples. These results were confirmed by stepwise regression analyses adjusted for age, gender, blood pressure, metabolic variables and use of anti-hypertensive medications. In addition, increased NADPH-oxidase activity was detected in peripheral mononuclear cells from T allele carriers compared with CC genotype carriers (p = 0.03).ConclusionsThe T allele of the p22-phox C242T polymorphism is associated with higher left ventricular mass/height2.7 and increased NADPH-oxidase activity in Brazilian hypertensive patients. These data suggest that genetic variation within NADPH-oxidase components may modulate left ventricular remodeling in subjects with systemic hypertension.

Physical Activity and Improved Diastolic Function in Spinal Cord-Injured Subjects.

PURPOSE Subjects with spinal cord injury (SCI) have been reported to present impaired left ventricular (LV) diastolic function in comparison with able-bodied (AB) ones. The present study investigated the effect of regular physical activity on the cardiac structure and function of SCI subjects. METHODS Fifty-eight SCI men (29 sedentary [SCI-S] and 29 athletes [SCI-A]) and 29 AB men were cross-sectionally evaluated by clinical, laboratory, hemodynamic, and echocardiographic analysis. All enrolled subjects were normotensive, nondiabetic, nonsmoker, and normolipemic, and the studied groups presented similar age and body mass index. RESULTS SCI-S presented similar LV structural and systolic parameters but higher E/Em (8.0 ± 0.5) and lower Em/Am (1.18 ± 0.09) ratios than SCI-A and AB (E/Em = 6.4 ± 0.3 and 5.9 ± 0.3, respectively; Em/Am = 1.57 ± 0.12 and 1.63 ± 0.08, respectively; all P < 0.05 compared with SCI-S). Analysis of SCI individuals according to injury level revealed that tetraplegic athletes had similar features compared with sedentary tetraplegic subjects, except for higher Em (10.9 ± 0.6 vs 8.6 ± 0.7 cm s, P < 0.05) and lower E/Em ratio (6.3 ± 0.4 vs 8.8 ± 0.8, P < 0.05), whereas paraplegic athletes had similar features compared with sedentary paraplegic individuals, except for higher LV end-diastolic diameter (49.4 ± 1.4 vs 45.0 ± 1.0 mm, P < 0.05) and Em/Am ratio (1.69 ± 0.20 vs 1.19 ± 0.08, P < 0.05) and lower LV relative wall thickness (0.330 ± 0.012 vs 0.369 ± 0.010, P < 0.05) and heart rate (67.1 ± 4.2 vs 81.9 ± 2.8 bpm, P < 0.05). CONCLUSION Regular physical activity is associated with improved LV diastolic function in SCI subjects and might exert distinct cardiac structural effects in tetraplegic and paraplegic subjects.

Physical activity is associated with improved subclinical atherosclerosis in spinal cord injury subjects independent of variation in traditional risk factors.

injury subjects independent of variation in traditional risk factors☆ Jose R. Matos-Souza , Anselmo A. Silva , Luis F. Campos , Debora Goulart , Roberto Schreiber , Guilherme de Rossi , Jose A. Pio-Magalhaes , Mauricio Etchebehere , Jose I. Gorla , Alberto Cliquet Jr. , Wilson Nadruz Jr. a,⁎ a Department of Internal Medicine, School of Medical Sciences, State University of Campinas, Campinas, SP, Brazil b School of Physical Education, State University of Campinas, Campinas, SP, Brazil c Department of Orthopaedics, School of Medical Sciences, State University of Campinas, Campinas, SP, Brazil d Department of Electrical Engineering, University of Sao Paulo (USP), Sao Carlos, SP, Brazil

Upper Arm Circumference Is an Independent Predictor of Left Ventricular Concentric Hypertrophy in Hypertensive Women

Upper arm circumference (UAC) measurement is necessary for the proper sizing of cuffs and is recommended for accurate blood pressure (BP) assessment. The aim of this report is to identify and quantify the relationships between UAC and the usual anthropometric measurements of body fat distribution and cardiac structure in hypertensive subjects. We evaluated 339 patients (202 women and 137 men) by medical history, physical examination, anthropometry, metabolic and inflammatory parameters, and echocardiography. Partial correlation analyses adjusted for age and body mass index revealed that anthropometric variables were significantly associated with echocardiographic parameters exclusively in women. In this regard, UAC correlated with interventricular septum thickness, posterior wall thickness, and relative wall thickness ≥0.45, while waist circumference was related to left cardiac chamber diameter. Multivariate analyses including age, body mass index, systolic BP, homeostasis model assessment index, and use of antihypertensive medications demonstrated that UAC was an independent predictor of left ventricular wall thickness and concentric hypertrophy in women. Further linear regression analyses revealed that waist circumference was an independent predictor of left ventricular end-diastolic and left atrial diameters in this gender. Overall, these findings suggest that UAC determination might serve not only as a routine approach preceding BP evaluation but also as a simple and feasible predictor of adverse LV remodeling in hypertensive women.

Oxidized low-density lipoprotein, matrix-metalloproteinase-8 and carotid atherosclerosis in spinal cord injured subjects.

OBJECTIVE Previous reports have indicated that subjects with chronic spinal cord injury (SCI) exhibit increased cardiovascular risk compared to able-bodied individuals. This study investigated the relationship between plasmatic oxidized low-density lipoprotein (OxLDL), matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) levels and vascular remodeling in SCI subjects and the role of physical activity in this regard. METHODS We studied 42 men with chronic (≥2 years) SCI [18 sedentary (S-SCI) and 24 physically active (PA-SCI)] and 16 able-bodied men by clinical, anthropometric, laboratory, and carotid intima-media thickness (IMT) analysis. All enrolled subjects were normotensive, non-diabetics, non-smokers and normolipemic. Plasmatic OxLDL, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 levels were determined by enzyme-linked immunosorbent assay. RESULTS Carotid IMT, IMT/diameter ratio and OxLDL levels of PA-SCI and able-bodied subjects were statistically similar. Conversely, S-SCI subjects exhibited higher IMT, IMT/diameter ratio and OxLDL levels compared to PA-SCI (p < 0.01, p < 0.001 and p = 0.01, respectively) and able-bodied (p < 0.001 for all) individuals. Results of bivariate correlation analysis including all injured subjects showed that carotid IMT and IMT/diameter ratio only correlated with OxLDL, MMP-8 and MMP-8/TIMP-1 ratio. Further stepwise regression analysis adjusted for the presence or not of physical activity and age showed that OxLDL was associated with carotid IMT and IMT/diameter ratio, while MMP-8 was associated with IMT/diameter ratio in SCI individuals. CONCLUSIONS Plasmatic OxLDL and MMP-8 levels are associated with carotid atherosclerosis and there is an interaction among physical inactivity, atherosclerosis and OxLDL in SCI individuals.

A simplified ultrasound-based edema score to assess lung injury and clinical severity in septic patients

BACKGROUND Lung ultrasound (US) is an excellent tool to assess lung edema in a myriad of different clinical situations. We hypothesized that lung US might also be a good prognostic and management instrument in septic patients, regardless of disease severity. METHODS This was a prospective observational cohort study at an urban academic emergency department (ED). Inclusion criteria were as follows: septic patients, at least 18 years old, admitted at the ED of a tertiary hospital. A simplified lung edema scoring system (SLESS) was developed, and 6 thoracic regions were evaluated. Four different lung US patterns were considered, from normal aeration to total consolidation. To evaluate disease severity, the SLESS was compared with the Mortality in Emergency Department Sepsis Score and the third version of the Simplified Acute Physiology Score scoring systems. Aiming to assess the effect of the lung edema in the gas exchange, the SLESS was compared with the Pao2/fraction of inspired oxygen ratio. RESULTS Sixty-one patients were enrolled in a 3-month period. The SLESS had a good correlation with the Mortality in Emergency Department Sepsis Score and Simplified Acute Physiology Score (r = 0.53 and r = 0.55, respectively; P < .001 for both) and a negative correlation with the Pao2/fraction of inspired oxygen ratio (r = -0.62; P < .001). The SLESS also showed correlation with the respiratory rate (r = 0.45; P = .0003). The odds ratio for death related to the SLESS was 1.370 (95% confidence interval, 1.109-1.691; P = .0035). CONCLUSION The SLESS is an easy and practical scoring system. It might be a useful tool to predict severity of disease in sepsis patients. The SLESS might also be able to be correlated with the oxygen exchange.