Roberto de Sá Cunha

Association between high heart rate and high arterial rigidity in normotensive and hypertensive subjects.

Background The dynamic elastic modulus of central arteries is very frequency-dependent. Although resting heart rate is a potent independent risk factor for morbidity and mortality both from cardiovascular and from noncardiovascular disease, no link between tachycardia and arterial stiffness has ever been established. Objective To relate arterial stiffness to heart rate in a population with relatively low cardiovascular risk. Methods Pulse-wave velocity measurements and highresolution echo-tracking techniques were used to determine the degree of arterial distension (of carotid and femoral arteries, and terminal aorta) and the velocity of the pulse wave (aorta and upper and lower limbs) at the same time as heart rate, in members of a large population of normotensive and hypertensive subjects in a multicenter study in Paris, Fleury-Merogis and Grenoble (France). Results A high heart rate was strongly associated with reduced distension and elevated pulse-wave velocity, even after adjustment for age and blood pressure. A high aortic pulse-wave velocity was also negatively associated with a low baroreflex sensitivity. The most significant associations between high heart rate and high arterial rigidity were found for the carotid artery, the thoracic aorta, and the lower limbs, but there was no significant result for the terminal aorta and the arm arteries. Conclusion This study demonstrates that there is a statistically significant positive link between high heart rate and high arterial stiffness measured at the site of central and lower limb arteries. Since an elevated heart rate has been shown to be associated with cardiovascular risk, such findings may be relevant for future cardiovascular studies in epidemiology.

Hipertensão arterial e consumo de sal em população urbana

OBJETIVO: Avaliar o consumo de sal e a relacao sodio/potassio urinario em amostra randomizada de populacao urbana etnicamente miscigenada. METODOS: Foi selecionada uma amostra randomica de 2.268 residentes de Vitoria, ES, entre 25 e 64 anos de idade. Os individuos foram escolhidos por amostragem domiciliar realizada em 1999/2000, dos quais 1.663 (73,3%) compareceram ao hospital para a realizacao de exames padronizados. O consumo estimado de sal, Na+ e K+ foi determinado por meio da coleta de urina de 12h no periodo noturno (19h as 7h) e do gasto mensal de sal domiciliar referido durante a entrevista. A pressao arterial clinica foi medida duas vezes por diferentes pesquisadores treinados em condicoes padronizadas, usando esfignomamometro de mercurio. Para analise estatistica foram utilizados o teste de Student e o teste de Tukey. RESULTADOS: A excrecao urinaria de Na+ foi mais alta em homens e em individuos de menores condicoes socioeconomicas (P<0,000). Nao foi observada diferenca entre os grupos etnicos. A excrecao de K+ nao se relacionou com nivel socioeconomico e raca, mas foi significativamente mais alta entre os homens (25±18 x 22±18 mEq/12h; P=0,002). Foi observada uma correlacao linear positiva entre a excrecao urinaria de Na+ e pressao arterial sistolica (r=0,15) e diastolica (r=0,19). Individuos hipertensos apresentaram maior excrecao urinaria de Na+ e relacao Na/K, quando comparados com individuos normotensos. O consumo de sal relatado foi aproximadamente 50% do consumo estimado pela excrecao urinaria de 12h (em torno de 45% da excrecao urinaria de 24h). CONCLUSOES: A ingestao de sal e fortemente influenciada pelo nivel socioeconomico e pode, parcialmente, explicar a alta prevalencia de hipertensao arterial nas classes socioeconomicas mais baixas.

Fibronectin Expression and Aortic Wall Elastic Modulus in Spontaneously Hypertensive Rats

Recent studies have shown that large-artery wall remodeling per se does not reduce distensibility in hypertension, indicating qualitative or quantitative changes in arterial components. The aim of the study was to determine in 1-year-old spontaneously hypertensive rats (SHRs) the changes in the elastic properties of large arteries, as assessed by the incremental elastic modulus (E(inc)), and the changes in the extracellular matrix, including fibronectin (FN) and alpha5beta1-integrin. The relationship between E(inc) and circumferential wall stress was calculated from in vivo pulsatile changes in blood pressure and arterial diameter by using a high-resolution echo-tracking system at the site of the abdominal aorta and in vitro medial cross-sectional area. E(inc)-stress curves and FN and integrin alpha5-subunit contents were determined for each animal. Mean stress and E(inc) were higher in SHRs than in Wistar rats. However, in a common range of stress, E(inc)-stress curves for SHRs were superimposable on those for Wistar rats, indicating that wall materials in both strains have equivalent mechanical behavior. Immunohistochemistry indicated that total FN, EIIIA FN isoform, and alpha5-integrin increased in the SHRs aortas without changes in elastin and collagen densities. Total FN was also increased in SHRs as determined by Western blot analysis. No differences in FN and alpha5-subunit mRNAs were detected between SHRs and Wistar rats. These results indicate that the aortic wall material of SHRs and Wistar rats have equivalent mechanical properties, although in SHRs it is subjected to a higher level of stress. By increasing cell-matrix attachment sites, FN may participate in the mechanical adaptation of both cellular and matrix components in SHRs.

β2 Adrenoceptor Functional Gene Variants, Obesity, and Blood Pressure Level Interactions in the General Population

Abstract—We investigated the association of &bgr;2 adrenoceptor functional gene variants (Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms), obesity phenotypes, and blood pressure levels in a large, ethnically mixed urban population. The individuals (n=1576) were randomly selected for a cross-sectional study of cardiovascular risk factors in Vitória, Brazil. Statistically significant associations among systolic blood pressure and the Arg16Gly and Thr164Ile variants were identified in univariate analysis. The Gly16/Gly16 genotype was still associated with systolic blood pressure (SBP) in multivariate analysis adjusting for age, gender, ethnicity, total cholesterol, diabetes, and body mass index (BMI) (P =0.01). The Arg16 allele was the only genotypic variable associated with BMI, and, in a dominant model, it remained associated with an increased BMI even after adjustment for age, gender, ethnicity, triglycerides, HDL cholesterol, LDL cholesterol, diabetes, and hypertension status (P =0.02). Although the different polymorphisms did not interact in the determination of SBP, a significant interaction with BMI (P =0.02), not through linkage disequilibrium, was identified between the Gln27Glu and the Thr164Ile variants. Furthermore, a significant interaction among the Arg16Gly polymorphism and BMI (P =0.036) and waist-hip ratio (P =0.003) in determining SBP was disclosed by ANOVA factorial modeling, with SBP used as the dependent variable. An interaction between the Thr164Ile polymorphism and waist-hip ratio was also identified (P =0.018). Finally, multiple logistic regression models showed a 1.48-fold increase in the risk of hypertension in individuals harboring the Gly16/Gly16 genotype and a 1.31-fold (P =0.01) and a 1.49-fold (P =0.003) increased risk of obesity in individuals harboring the Gln27/Gln27 genotype or the presence of the Arg16 allele, respectively. Taken together, these data provide evidence for a strong but complex relation between &bgr;-adrenoceptor gene variants, hypertension, and obesity.

Angiotensinogen 235T Allele “Dosage” Is Associated With Blood Pressure Phenotypes

Abstract—The genetic mechanisms underlying interindividual blood pressure variation among humans may reflect, at least in part, clustering of functional gene variants belonging to complex blood pressure control systems. In this study, we investigated the association of specific functional gene variants of the renin-angiotensin system, ACE (I/D) and angiotensinogen (M/T) genes, with blood pressure phenotypes (systolic, mean, diastolic, and pulse pressure), in an ethnically mixed urban population in Brazil. Individuals (n=1421) were randomly selected from the general population of the Vitoria City Metropolitan area. Neither gender, age, smoking status, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, or diabetes was associated with ACE or AGT polymorphism in univariate analysis. No association was found between ACE variants and blood pressure phenotypes. However, a statistically significant association was revealed between the AGT 235T variant and all blood pressure phenotypes, consistent with an additive/codominant mode of action even after adjustment for age and gender (P <0.01). Genotypic analysis contemplating both ACE and AGT variants in the same model did not show any significant interaction between both genetic polymorphisms. In addition, the AGT 235T allele was significantly associated with hypertension in a recessive model, which remained as an independent risk factor for hypertension even after adjustment for age, gender, and ethnicity (OR, 1.33; 95% CI, 1.04 to 1.70). Taken together, these data indicate a linear relation between AGT 235T allele number (“dosage”) and blood pressure in an ethnically mixed urban population and confirmed its role as an independent risk factor for hypertension for men and women when in homozygosity.

Afericoes e exames clinicos realizados nos participantes do ELSA-Brasil

The article describes assessments and measurements performed in the Brazilian Longitudinal Study for Adult Health (ELSA-Brasil). Some assessments including anthropometric assessment, casual blood pressure measurement, and ankle-brachial index have an established clinical application while others including pulse wave velocity, heart rate variability, and carotid intima-media thickness have no established application and do not have reference values for healthy Brazilian population but may be important predictors of cardiovascular outcomes. Blood pressure measurement following postural change maneuver was included in the ELSA-Brasil because it has not been much tested in epidemiological studies. Innovative approaches were developed for assessing the ankle-brachial index using an automatic device instead of the mercury column to measure blood pressure and for assessing the anterior-posterior diameter of the right lobe of the liver by ultrasound for quantitative assessment of nonalcoholic fatty liver disease. All ELSA-Brasil subjects were younger (35 years or more) than those included in other cohorts studying subclinical atherosclerosis. The inclusion of younger individuals and a variety of assessments make the ELSA-Brasil a relevant epidemiology study nationwide and worldwide.

Racial differences in aortic stiffness in normotensive and hypertensive adults.

OBJECTIVE To investigate whether differences exist in the mechanical properties of large arteries between white and black subjects. DESIGN Eighty-two white (49 normotensive and 33 untreated hypertensive) and 38 black (24 normotensive and 14 untreated hypertensive) adult male volunteers were studied in a cross-sectional study. METHODS Carotid-femoral pulse wave velocity was measured as an index of arterial stiffness, using a recently developed non-invasive automatic device, and compared between white and black subjects before and after the adjustment for age. The slope of regressions for pulse wave velocity and systolic blood pressure were also compared between racial groups. RESULTS In the normotensive group, white subjects presented higher mean values of pulse wave velocity than blacks while the opposite behavior was found in the hypertensive group. After adjustment for age, significant differences in pulse wave velocity between whites and blacks became evident in the normotensive (whites 8.15 +/- 0.04 versus blacks 7.75 +/- 0.02 m/s; P < 0.001) and hypertensive (whites 8.88 +/- 0.02 versus blacks 9.30 +/- 0.17 m/s; P < 0.001) groups. Linear regression analysis for age-adjusted pulse wave velocity and systolic blood pressure showed that the slope was significantly greater in blacks than in whites (0.040 +/- 0.002 versus 0.019 +/- 0.001 m/s; P < 0.001). CONCLUSION These data indicate that there is a greater pressure-dependent increase in aortic stiffness in blacks than in whites. This finding points towards major differences in mechanical properties of large arteries between these racial groups.

APOE polymorphism is associated with lipid profile, but not with arterial stiffness in the general population

BackgroundCardiovascular diseases (CVD) are the main cause of death and disability in developed countries. In most cases, the progress of CVD is influenced by environmental factors and multifactorial inheritance. The purpose of this study was to investigate the association between APOE genotypes, cardiovascular risk factors, and a non-invasive measure of arterial stiffness in the Brazilian population.MethodsA total of 1493 urban Brazilian individuals were randomly selected from the general population of the Vitoria City Metropolitan area. Genetic analysis of the APOE polymorphism was conducted by PCR-RFLP and pulse wave velocity analyzed with a noninvasive automatic device.ResultsAge, gender, body mass index, triglycerides, creatinine, uric acid, blood glucose, blood pressure phenotypes were no different between ε2, ε3 and ε4 alleles. The ε4 allele was associated with higher total-cholesterol (p < 0.001), LDL-C (p < 0.001), total-cholesterol/HDL-C ratio (p < 0.001), LDL/HDL-C ratio (p < 0.001), lower HDL-C values (p < 0.001) and higher risk to obesity (OR = 1.358, 95% CI = 1.019-1.811) and hyperuricemia (OR = 1.748, 95% CI = 1.170-2.611). Nevertheless, pulse wave velocity (p = 0.66) measures were no different between genotypes. The significant association between APOE genotypes and lipid levels persisted after a 5-year follow-up interval, but no interaction between time and genotype was observed for lipids longitudinal behavior.ConclusionThe ε4 allele of the APOE gene is associated with a worse lipid profile in the Brazilian urban population. In our relatively young sample, the observed effect of APOE genotype on lipid levels was not translated into significant effects in arterial wall stiffness.

Ethnicity and Arterial Stiffness in Brazil

BACKGROUND The impact of increased central arterial stiffness as a predictor of morbidity and mortality, independently of other cardiovascular (CV) risk factors, has been established. The main aim of the present work was to investigate the association of ethnicity on arterial stiffness in different ethnic groups from the Brazilian population. METHODS A total of 1,427 individuals from the general population were randomly selected from the Vitoria City metropolitan area and 588 Amerindians from a native community in Brazil. The ethnicity of the general population was classified by a standard questionnaire as Caucasian descent, African descent, or Mulattos (considered racially mixed subjects). Pulse wave velocity (PWV) was measured with a noninvasive automatic device (Complior, Colson; Garges les Gonesses, France). RESULTS Hemodynamic data of PWV, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) was higher in African descent individuals than in the other groups (P < 0.001). These results were still observed after adjustment for age and mean arterial pressure (P < 0.001). In addition, studying only normotensive individuals, PWV adjusted levels were higher in African descent individuals, and lower in Amerindians when compared with other ethnic groups (P < 0.01), showing, without the possible confounder effects of time and severity of hypertension or medication use, that PWV is associated with ethnicity in our population. CONCLUSION The study of different ethnic groups from a highly admixtured population was able to demonstrate an association between ethnicity and arterial stiffness.

Body Mass Index Is Not Independently Associated With Increased Aortic Stiffness in a Brazilian Population

BACKGROUND Obesity has been described as a predictor of cardiovascular mortality, and some studies have reported an association with obesity and increased aortic stiffness. Other studies have not identified obesity to be an independent risk factor. Therefore, the purpose of our study was to determine the association between aortic stiffness and obesity in the Brazilian population. METHODS A cross-sectional study recruited 1,662 individuals aged 25-64 years from the population of Vitória, Brazil following the guidelines of the MONICA-WHO Project. Anthropometric, clinical, and hemodynamic measurements and analyses of aortic stiffness (using carotid-femoral pulse wave velocity <PWV) were obtained in 1,608 subjects. RESULTS PWV correlated positively with age, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure, heart rate (HR), body mass index (BMI), waist circumference (WC), cholesterol levels, triglyceride levels, and blood glucose levels. A multivariate regression analysis demonstrated that the mean BP (β = 0.405, P < 0.01), age (β = 0.314, P < 0.01), HR (β = 0.107, P < 0.01), BMI (β = -103, P < 0.01), and blood glucose levels (β = 0.093, P < 0.01) explained nearly 37% of the PWV variability. A multivariate regression analysis using the WC instead of the BMI failed to reveal any significant effect of this parameter on the PWV. CONCLUSIONS In conclusion, our study failed to provide evidence of a positive, blood pressure (BP)-independent association between obesity on aortic stiffness. Our data suggests that the previously reported finding of an association between obesity and aortic stiffness was probably confounded by the progressive increase in BP observed in obesity.