Monocytes of patients with unstable angina express high levels of chemokine and pattern-recognition receptors.

BACKGROUND AND AIMS: Macrophages derived from monocytes play an important role in atherosclerosis progression. Subpopulations of circulating classical, intermediate, and non-classical monocytes possess distinct functions and phenotypes, and participate in the pathogenesis of disease. The aim of this study was to compare the quantity and phenotypes of circulating monocyte subpopulations in patients with established atherosclerosis and healthy control individuals. Additionally, the study aimed to provide insight into the functional activity of monocytes against a heat shock protein (HSP60). METHODS: Chemokine and pattern recognition receptors in monocyte subsets obtained from peripheral blood of acute and chronic coronary artery disease patients and controls were quantified by flow cytometry. Furthermore, monocytes from healthy controls were stimulated in vitro with HSP60, and the cytokines produced by them were evaluated by flow cytometry. RESULTS: Eighteen controls (C), 34 individuals with risk factors for cardiovascular disease (RF), 32 patients with stable angina (SA), and 16 patients with unstable angina (UA) were enrolled in the study. The absolute count of intermediate monocytes was found to be increased in patients of the UA group; high frequencies of the chemokine receptors CCR2, CCR5, and CX3CR1 were also observed in this subpopulation. Moreover, the pattern recognition receptors TLR2 and TLR4 were more frequent in intermediate monocytes from the UA group. Furthermore, the intermediate monocytes from healthy individuals produced IL-12p70 after stimulation with HSP60. CONCLUSIONS: Our results show that intermediate monocytes of UA patients exhibited an enhanced expression of the receptors involved in the recognition of damage-associated molecular patterns (DAMPs) and enhancement of the migratory function. Hence, they might contribute to the propagation and progression of inflammation observed in atherosclerosis, especially in the acute setting.

Obesity and hypertension in Latin America: Current perspectives / Obesidad e hipertensión en Latinoamérica: Perspectivas actuales

In the countries of Central America, South America and the Caribbean, there has been a dramatic rise in obesity, the metabolic syndrome, hypertension and other cardiovascular risk factors in the last few decades. Epidemiological evidence highlights a consistent correlation between obesity and hypertension, and the presence of obesity predisposes an individual to a greater risk of hypertension although the mechanisms remain unclear. Obesity and hypertension are two key drivers of the cardio-renal disease continuum, and patients with uncontrolled cardiovascular risk in their mid-life will likely have an increased risk of clinical cardiovascular and renal outcomes in old age. This article summarizes the current status for the prevalence and consequences of obesity and hypertension in Latin America, with the aim of initiating a call to action to all stakeholders for greater implementation of primary prevention strategies, particularly in the young (AU)

En los países centroamericanos, sudamericanos y caribeños se ha producido un incremento alarmante en cuanto a obesidad, síndrome metabólico, hipertensión y otros factores de riesgo cardiovascular en las últimas décadas. La evidencia epidemiológica destaca una correlación consistente entre obesidad e hipertensión, y la presencia de obesidad predispone al individuo a un mayor riesgo de hipertensión, aunque los mecanismos siguen siendo inciertos. La obesidad y la hipertensión son claros impulsores esenciales de las cifras reales de las enfermedades cardio-renales, y los pacientes con riesgo cardiovascular descontrolado en la mediana edad tendrán, con toda probabilidad, un riesgo incrementado de resultados clínicos cardiovasculares y renales en la vejez. Este artículo resume el estatus actual de la prevalencia y consecuencias de la obesidad e hipertensión en Latinoamérica, con el objetivo de iniciar una llamada a la acción a todos los participantes, de cara a implementar unas mayores estrategias de prevención primaria, especialmente en los jóvenes (AU)

Obesity and hypertension in Latin America: Current perspectives.

In the countries of Central America, South America and the Caribbean, there has been a dramatic rise in obesity, the metabolic syndrome, hypertension and other cardiovascular risk factors in the last few decades. Epidemiological evidence highlights a consistent correlation between obesity and hypertension, and the presence of obesity predisposes an individual to a greater risk of hypertension although the mechanisms remain unclear. Obesity and hypertension are two key drivers of the cardio-renal disease continuum, and patients with uncontrolled cardiovascular risk in their mid-life will likely have an increased risk of clinical cardiovascular and renal outcomes in old age. This article summarizes the current status for the prevalence and consequences of obesity and hypertension in Latin America, with the aim of initiating a call to action to all stakeholders for greater implementation of primary prevention strategies, particularly in the young.

Myocardial remodeling in hypertension.

Left ventricular (LV) hypertrophy and remodeling are frequently seen in hypertensive subjects and result from a complex interaction of several hemodynamic and non-hemodynamic variables. Although increased blood pressure is considered the major determinant of LV structural alterations, ethnicity, gender, environmental factors, such as salt intake, obesity and diabetes mellitus, as well as neurohumoral and genetic factors might influence LV mass and geometry. The conventional concept of hypertensive LV remodeling has been that hypertension leads to concentric hypertrophy, as an adaptive response to normalize wall stress, which is then followed by chamber dilation and heart failure. However, several lines of evidence have challenged this dogma. Concentric hypertrophy is not the most frequent geometric pattern and is less usually seen than eccentric hypertrophy in hypertensive subjects. In addition, data from recent studies suggested that transition from LV concentric hypertrophy to dilation and systolic dysfunction is not a common finding, especially in the absence of coronary heart disease. LV hypertrophy is also consistently associated with increased cardiovascular morbidity and mortality, raising doubts whether this phenotype is an adaptive response. Experimental evidence exists that a blunting of load-induced cardiomyocyte hypertrophy does not necessarily result in LV dysfunction or failure. Furthermore, the hypertrophic myocardium shows fibrosis, alterations in the coronary circulation and cardiomyocyte apoptosis, which may result in heart failure, myocardial ischemia and arrhythmias. Overall, this body of evidence suggests that LV hypertrophy is a complex phenotype that predicts adverse cardiovascular outcomes and may not be necessarily considered as an adaptive response to systemic hypertension.

Behavioural determinants of salt consumption among hypertensive individuals.

BACKGROUND: High salt consumption among populations remains a challenge for health professionals dealing with prevention and control of hypertension. The present study aimed to identify the psychosocial predictors of salt consumption among hypertensive individuals, based on an extended version of the Theory of Planned Behaviour (TPB). Three salt consumption behaviours were studied: Behaviour 1- using <4 g of salt per day during cooking; Behaviour 2- avoiding adding salt/table salt use to the prepared foods; and Behaviour 3- avoiding the consumption of foods with high salt content. METHODS: At baseline (n = 108), TPB and additional variables (self-efficacy, habit, past behaviour, hedonic determinant, self-perceived diet quality) were measured. At 2-month follow-up (n = 95), the three behaviours were assessed. Behaviour and intention were sequentially regressed on the study variables, using polytomous logistic regression and hierarchical linear regression with rank transformation, respectively. RESULTS: Behaviour 1 was predicted by intention [odds ratio (OR) = 6.23; 95% confidence interval (CI) = 1.81-21.52], whereas self-efficacy and habit predicted intention. Behaviour 2 exhibited high score mean and low variation and was predicted by self-perceived diet quality (OR = 2.56; 95% CI = 1.03-6.36). Behaviour 3 was predicted by the hedonic determinant (OR = 1.42; 95% CI = 1.01-1.98). CONCLUSIONS: The results indicate that salt-related behaviours are explained by a variety of determinants. Among these determinants, special consideration should be given to motivational and hedonic aspects.

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.

Common matrix metalloproteinase 2 gene haplotypes may modulate left ventricular remodelling in hypertensive patients.

Matrix metalloproteinases (MMPs) are involved in cardiac remodelling. We examined whether MMP-2 genetic polymorphisms are associated with hypertension and left ventricular (LV) remodelling in hypertensive patients. We studied 160 hypertensive patients and 123 healthy controls. Echocardiography was performed in all patients and the C(-1306)T (rs243865) and C(-735)T (rs 2285053) MMP-2 polymorphisms were analysed. Haplo.stats analysis was used to evaluate whether MMP-2 haplotypes are associated with hypertension and with extremes in LV mass index (LVMI). Multiple linear regression analysis was performed to assess whether MMP-2 genotypes or haplotypes affect LVMI and other echocardiography parameters. The C(-1306)T 'CC' genotype was associated with reduced LVMI and LV end-diastolic diameter (EDD) (P=0.0365 and P=0.0438, respectively). The haplotype 'C, C' was associated with reduced LVMI and EDD (P=0.0278 and P=0.0322, respectively). The comparison of upper and lower extremes of the LVMI phenotype showed that the 'C, C' haplotype was more common in the lower LVMI group (P=0.0060), whereas the 'T, C' haplotype was more common in the higher quartile of LVMI (P=0.0187), and this haplotype was associated with increased risk of higher LVMI values (odds ratio=3.5121, 95% confidence interval=1.3193-9.3494). The findings suggest that MMP-2 polymorphisms affect hypertension-induced LV remodelling.

Mannose-binding lectin (MBL2) polymorphisms and inflammation in hypertensive patients.

We investigated the possible role of Mannose binding lectin 2 (MBL2) functional polymorphisms in the prevalence of hypertension and hypertensive end-organ damage in 300 hypertensive patients and 313 normotensive individuals from Southern Brazil. Hypertensive subjects with MBL2 AO/OO genotypes presented lower C-reactive protein levels than AA individuals and consequently lower inflammatory status.

Hip circumference is associated with high density lipoprotein cholesterol response following statin therapy in hypertensive subjects.

AIM: This report investigated the relationship between anthropometric measurements of body fat distribution and lipid response to statins in hypercholesterolemic hypertensive patients. METHODS: We prospectively examined 129 subjects who used either simvastatin 20 mg/day (no.=83) or atorvastatin 10 mg/day (no.=46) for 3 months. Anthropometry included evaluation of body mass index, waist and hip circumferences, and waist-to-hip-ratio. RESULTS: Significant decreases in LDL (p<0.001), total cholesterol (p<0.001), and triglycerides (p=0.04) levels were detected after 3 months of therapy in the whole sample. At baseline, only an inverse correlation between waist circumference and HDLcholesterol levels was detected (r=-0.18; p=0.04). Conversely, a direct relationship between hip circumference and HDLcholesterol response to statins was found in the whole sample (r=0.24; p=0.006), while no other anthropometric measurement displayed significant correlation with lipid changes. The association between HDL-cholesterol response and hip circumference was further confirmed by stepwise regression analysis adjusted for baseline HDL-cholesterol levels, metabolic syndrome, body mass index, and waist circumference. CONCLUSIONS: Hip circumference, a surrogate marker of peripheral adiposity, is associated with HDL-cholesterol changes following statin therapy in hypertensive patients.

Altered left ventricular diastolic function in subjects with spinal cord injury.

STUDY DESIGN: This is cross-sectional study. OBJECTIVES: The aim of this study is to investigate the cardiac structure and function of subjects with spinal cord injury (SCI) and the impact of metabolic, hemodynamic and inflammatory factors on these parameters. SETTING: São Paulo, Brazil. METHODS: Sixty-five nondiabetic, nonhypertensive, sedentary, nonsmoker men (34 with SCI and 31 healthy subjects) were evaluated by medical history, anthropometry, laboratory tests, analysis of hemodynamic and inflammatory parameters and echocardiography. RESULTS: Subjects with SCI had lower systolic blood pressure and higher levels of C-reactive protein and tumor necrosis factor receptors than the healthy ones. Echocardiography data showed that the SCI group presented similar left ventricular (LV) structural and systolic parameters, but lower initial diastolic velocity (Em) (9.2 ± 0.5 vs 12.3 ± 0.5 cm s(-1); P<0.001) and higher peak early inflow velocity (E)/Em ratio (7.7 ± 0.5 vs 6.1 ± 0.3; P = 0.009) compared with the able-bodied group, even after adjustment for systolic blood pressure and C-reactive protein levels. Furthermore, injured subjects with E/Em >8 had lower peak spectral longitudinal contraction (Sm) (9.0 ± 0.7 vs 11.6 ± 0.4 cm s(-1); P<0.001) and cardiac output (4.2 ± 0.2 vs 5.0 ± 0.2 l min(-1); P = 0.029), as well as higher relative wall thickness (0.38 ± 0.01 vs 0.35 ± 0.01; P = 0.005), than individuals with SCI with E/Em<8, but similar age, body mass index, blood pressure, injury level, metabolic parameters and inflammatory marker levels. CONCLUSION: Subjects with SCI presented impaired LV diastolic function in comparison with able-bodied ones. Moreover, worse LV diastolic function was associated with a pattern of LV concentric remodeling and subclinical decreases in systolic function among injured subjects. Overall, these findings might contribute to explain the increased cardiovascular risk reported for individuals with SCI.

Subclinical atherosclerosis is related to injury level but not to inflammatory parameters in spinal cord injury subjects.

STUDY DESIGN: Cross-sectional. OBJECTIVES: Individuals with spinal cord injury (SCI) exhibit increased carotid intima-media thickness (IMT) and are reported to be exposed to higher circulating levels of inflammatory mediators. This study evaluated the relationship between inflammatory markers and carotid surrogates of cardiovascular risk in subjects with SCI. SETTING: São Paulo, Brazil. METHODS: A total of 65 nondiabetic, nonhypertensive, sedentary, nonsmoker men (34 with SCI; 31 healthy subjects) were evaluated by medical history, anthropometry, routine laboratory tests, analysis of hemodynamic, inflammatory parameters and ultrasound examination of carotid arteries. RESULTS: Subjects with SCI (18 tetraplegic and 16 paraplegic) had lower systolic blood pressure (P = 0.009), higher serum C-reactive protein (P = 0.001), tumor necrosis factor (TNF) receptor-II (P = 0.02) and TNF receptor-I (P = 0.04) levels and increased in vitro production of interleukin-6 by mononuclear cells (P = 0.04), compared to able-bodied individuals. No differences in serum interleukin-6, e-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and transforming growth factor-ß levels, or in vitro release of interleukin-10, interleukin-17 and interferon-γ by mononuclear cells, were detected between the studied groups. Common carotid IMT, but not internal carotid resistive index, was significantly higher in subjects with SCI (P<0.0001 adjusted for C-reactive protein and TNF receptor-II levels). In addition, tetraplegic subjects exhibited increased IMT (P = 0.002 adjusted for systolic blood pressure and body mass index), but similar levels of inflammatory mediators compared to paraplegic ones. CONCLUSIONS: Individuals with SCI exhibit a clustering of vascular and inflammatory surrogates of increased cardiovascular risk. Nevertheless, subclinical carotid atherosclerosis is related to injury level but not to increased inflammatory status in these subjects.

Successful accomplishment of educational goals with clinical experience at public primary care facilities.

GOAL: To compare the spectrum of clinical encounters experienced by medical students at the primary level of care in six urban public health units, and to determine the extent to which these educational experiences were sufficient to meet learning objectives proposed for a teaching module. METHOD: During the 4th year of a new six- year curriculum, 113 students cared for adults, the elderly, women and children. They were supervised by faculty and trained supervisors during three 4-hours periods a week, every other week, from January to October at six primary health units. RESULTS: There were 7198 clinical encounters (2493 for adults, 2440 for women, and 2302 for children), during a total of 37 periods, averaging 1.8 cases/student per period. The top five primary diagnoses, similar at all primary health units, included: for adults--hypertension, diabetes, upper respiratory diseases, anxiety/depression, and obesity; for children--first-year follow up, upper respiratory diseases, dermatological, and infectious diseases; for women--antenatal care, vaginal discharge, cervical cancer screening, climacteric symptoms/menstrual disorders, and family planning. CONCLUSIONS: Students were exposed to and cared for the most common conditions observed at the primary level of care, with a sufficient homogeneous clinical spectrum among six primary health units, meeting essential learning objectives related to ambulatory care.

Non-effect of p22-phox -930A/G polymorphism on end-organ damage in Brazilian hypertensive patients.

The p22-phox subunit is an essential component of NAD(P)H oxidase enzymatic complex, which is considered the major source of oxidative stress products in the cardiovascular system. The -930G allele of p22-phox has been associated with higher promoter activity, increased NAD(P)H oxidase-mediated oxidative stress and hypertension. We recently reported that left ventricular hypertrophy is accompanied by increased myocardial p22-phox expression in aortic-banded rats, suggesting that this protein might be involved in hypertensive cardiac hypertrophy.

Immobilization of xanthine oxidase on a polyaniline silicone support.

A polyaniline silicone support to immobilize xanthine oxidase is proposed as a reactor coil to monitor the action of xanthine oxidase on hypoxanthine, xanthine and 6-mercaptopurine. A purified xanthine oxidase immobilized on this support lost 80% of the initial activity after 12 min of use. Co-immobilization of superoxide dismutase and catalase increased the stability of immobilized xanthine oxidase so that the derivative maintained 79% of its initial activity after 4.6 h of continuous use in which 1.5 mumol purine bases were converted by the immobilized enzyme system. There is no evidence of either polyaniline or protein leaching from the coil during 3 h of continuous use. When solutions (10 ml) of hypoxanthine, xanthine and 6-mercaptopurine were circulated individually through the xanthine oxidase-superoxide dismutase-catalase-polyaniline coil (1 mm internal diameter and 3 m in length, 3 ml internal volume) activities of 8.12, 11.17 and 1.09 nmol min-1 coil-1, respectively, were obtained. The advantages of the reactor configuration and the redox properties of the polymer, particularly with respect to immobilized oxidoreductases, make this methodology attractive for similar enzyme systems. This immobilized enzyme system using polyaniline-silicone as support converted 6-mercaptopurine to 6-thiouric acid with equal efficiency as resins based on polyacrylamide and polyamide 11.