Heno Ferreira Lopes

DASH Diet Lowers Blood Pressure and Lipid-Induced Oxidative Stress in Obesity

Abstract—Evidence suggests that obesity may raise blood pressure (BP) through oxidative stress–sensitive mechanisms and that the Dietary Approaches to Stop Hypertension combination diet (DASH-CD) may decrease BP by enhancing antioxidant capacity. To address this question, 12 obese patients with high-normal–to–stage 1 hypertension (hypertensives) and 12 lean normotensives were studied on their usual diets and after following the DASH-CD and a low-antioxidant diet in random sequence for 4 weeks each. Acute oxidative stress was induced by a 4-hour infusion of intralipid and heparin. Ferric-reducing activity of plasma (FRAP) and plasma F2-isoprostanes were measured as biomarkers of antioxidant capacity and oxidative stress, respectively. BP was lower in obese hypertensives on the DASH-CD than on the usual and low-antioxidant diets (−8.1±1.5/−7.4±1.6 mm Hg, P <0.05). BP did not change significantly in lean normotensives after 4 weeks on the DASH-CD but tended to rise on the low-antioxidant diet. FRAP on usual diets was higher in lean subjects than in obese subjects. FRAP increased in obese but not lean volunteers on the DASH-CD compared with usual diet, and the group difference disappeared. F2-isoprostanes increased from baseline during intralipid and heparin in both groups on the low-antioxidant diet but not in obese hypertensives on the DASH-CD. Among free-living obese hypertensives, the DASH-CD raises antioxidant capacity, lowers BP, and reduces oxidative stress induced by acute hyperlipidemia. The findings are consistent with evidence that elevated BP in obese subjects may reflect an imbalance between antioxidant capacity and oxidative stress that is improved by the DASH-CD.

The impact of obstructive sleep apnea on metabolic and inflammatory markers in consecutive patients with metabolic syndrome.

Background Obstructive Sleep Apnea (OSA) is tightly linked to some components of Metabolic Syndrome (MetS). However, most of the evidence evaluated individual components of the MetS or patients with a diagnosis of OSA that were referred for sleep studies due to sleep complaints. Therefore, it is not clear whether OSA exacerbates the metabolic abnormalities in a representative sample of patients with MetS. Methodology/Principal Findings We studied 152 consecutive patients (age 48±9 years, body mass index 32.3±3.4 Kg/m2) newly diagnosed with MetS (Adult Treatment Panel III). All participants underwent standard polysomnography irrespective of sleep complaints, and laboratory measurements (glucose, lipid profile, uric acid and C-reactive protein). The prevalence of OSA (apnea-hypopnea index ≥15 events per hour of sleep) was 60.5%. Patients with OSA exhibited significantly higher levels of blood pressure, glucose, triglycerides, cholesterol, LDL, cholesterol/HDL ratio, triglycerides/HDL ratio, uric acid and C-reactive protein than patients without OSA. OSA was independently associated with 2 MetS criteria: triglycerides: OR: 3.26 (1.47–7.21) and glucose: OR: 2.31 (1.12–4.80). OSA was also independently associated with increased cholesterol/HDL ratio: OR: 2.38 (1.08–5.24), uric acid: OR: 4.19 (1.70–10.35) and C-reactive protein: OR: 6.10 (2.64–14.11). Indices of sleep apnea severity, apnea-hypopnea index and minimum oxygen saturation, were independently associated with increased levels of triglycerides, glucose as well as cholesterol/HDL ratio, uric acid and C-reactive protein. Excessive daytime sleepiness had no effect on the metabolic and inflammatory parameters. Conclusions/Significance Unrecognized OSA is common in consecutive patients with MetS. OSA may contribute to metabolic dysregulation and systemic inflammation in patients with MetS, regardless of symptoms of daytime sleepiness.

Increasing plasma fatty acids elevates F2-isoprostanes in humans: implications for the cardiovascular risk factor cluster

Objective To determine whether raised concentrations of non-esterified fatty acids (NEFAs) may contribute to the cardiovascular risk factor cluster by increasing oxidative stress in vivo. Design and Methods Plasma and urine F2-isoprostanes, biomarkers of oxidative stress, were measured after an overnight fast and during a 4 h infusion of Intralipid and heparin to increase NEFAs in 10 obese hypertensive patients with and 12 healthy normotensive individuals without evidence of insulin resistance. A time-control group of nine healthy normotensive individuals received saline and heparin. Results Plasma F2-isoprostanes increased more in obese hypertensive individuals than in lean normotensive individuals after 2 h (14.9 ± 2.8 ng/ml compared with 4.6 ± 2.8 ng/ml;P < 0.05) but not after 4 h (10.3 ± 2.5 ng/ml compared with 8.1 ± 4.1 ng/ml; NS) of the Intralipid and heparin infusion. When obese and lean individuals were combined, plasma (+9.1 ± 2.5 ng/ml;P < 0.05) and urine (+0.7 ± 0.3 ng/mg creatinine;P < 0.05) F2-isoprostanes increased by about 20% after 4 h of Intralipid and heparin, whereas plasma F2-isoprostanes decreased by approximately 20% (−9.7 ± 4.5 ng/ml;P < 0.05) after 4 h of saline and heparin. When individuals from both infusions were combined, the correlation between changes in plasma NEFAs and F2-isoprostanes after 4 h persisted after controlling for changes in triglyceride concentrations (partial r = 0.49;P < 0.01), whereas the correlation between changes in triglycerides and F2-isoprostanes did not persist after controlling for changes in NEFA concentrations (partial r = 0.33, NS). Conclusions The findings indicate that an acute increase in plasma lipids increases the concentration of F2-isoprostanes, biomarkers of oxidative stress, especially in obese hypertensive individuals. The observations raise the possibility that increased concentrations of NEFAs contribute to the cardiovascular risk factor cluster through oxidative-stress-sensitive mechanisms.

Obstructive sleep apnea is highly prevalent and correlates with impaired glycemic control in consecutive patients with the metabolic syndrome.

Obstructive sleep apnea (OSA) and the metabolic syndrome (MS) are independently associated with increased cardiovascular risk. The objective of the present study was to determine the prevalence of OSA among consecutive patients with MS and to determine whether OSA is associated with impaired glycemic control. Fifty consecutive patients with a recent diagnosis of MS and no previous diagnosis of OSA underwent a polysomnography and anthropometric and laboratory measurements. The prevalence of OSA (apnea-hypopnea index >or=15 events per hour of sleep) was 68% and in the same range of all other individual components of MS. Moreover, OSA was associated with increased levels of glucose (P=.03) and glycosylated hemoglobin (P=.03) but not with body mass index (P=.30). Glycosylated hemoglobin was independently associated with glucose (P<.001) and apnea-hypopnea index (P=.03). The prevalence of OSA is in the same range as all the individual components of MS and is independently associated with impaired glycemic control.

Lipid Metabolism Alterations in Normotensive Subjects With Positive Family History of Hypertension

Metabolic abnormalities are usually reported in hypertensive patients. These metabolic alterations seem to begin in childhood. The young offspring of hypertensive parents have not been studied thoroughly for metabolic alterations. The aim of this study was to examine the level of total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol, uric acid, glycemia, aldosterone, and plasma renin activity in a population of 42 young, slender normotensive subjects with positive family history of hypertension (FH+) or negative family history of hypertension (FH-). Measurements were made in 20 young normotensive subjects (age 21.1+/-2.2 years, 11 males, 15 white, 5 oriental, body mass index of 22.1+/-2.3 kg/m2) with FH+ and 22 young normotensive subjects (age 19.9+/-1.4 years, 17 males, 17 white, 5 oriental, body mass index of 22.1+/-2.3 kg/m2) with FH-. The total cholesterol (4.47+/-0.8 versus 3.95+/-0.6 mmol/L), LDL cholesterol (2.74+/-0.63 versus 2.36+/-0.61 mmol/L), VLDL cholesterol (0.5+/-0.25 versus 0.35+/-0.09 mmol/L), and triglycerides (2.52+/-1.26 versus 1.76+/-0.5 mmol/L) were significantly elevated (P<.05) in the FH+ group compared with the FH- group. The total cholesterol/HDL cholesterol ratio was significantly higher in the group with a positive family history of hypertension (3.75+/-0.02 versus 3.11+/-0.02, P<.05). Glycemia was slightly elevated in the FH+ group (2.16+/-0.29 mmol/L) but was not significantly different from that of the FH- group (2+/-0.2 mmol/L). Uric acid, plasma renin activity, and aldosterone were similar in both groups. We conclude that young, slender normotensive subjects with a positive history of hypertension show alterations in lipid metabolism, suggesting a positive correlation between lipid metabolism and hypertension heredity.

Blood pressure and the risk of complex arrhythmia in renal insufficiency, hemodialysis, and renal transplant patients☆

Complex arrhythmia is frequent in hemodialysis patients but it is not clear if this is a consequence of dialysis or uremia or is secondary to the hemodynamic and cardiovascular alterations often associated with chronic renal failure. The incidence of complex ventricular arrhythmia (frequent multiform premature beats, couplets, and runs) in 31 subjects who had their uremic status recently corrected by renal transplant (Group 1) and in 23 predialysis (Group 2) and 73 hemodialysis (Group 3) chronic renal failure patients were studied with 24-h Holter monitoring. Patients were not receiving antiarrhythmic drugs or digitalis and significant coronary artery disease was excluded by clinical and noninvasive methods. Complex arrhythmia was two times more frequent in dialysis patients but the difference did not reach statistical significance (Group 1: 16%; Group 2: 17%; Group 3: 34%; chi2 4.9, P = .086). The stepwise model of logistic regression analysis identified systolic blood pressure (odds ratio 1.015, 95% confidence interval [CI] 1.001-1.027, P = .03) and left ventricular systolic dysfunction (odds ratio 7.04, 95% CI 1.3-36.7, P = .02) as the only factors that independently influenced the probability of complex arrhythmia. Age, gender, race, diabetes, smoking status, body mass index, diastolic blood pressure, serum creatinine, hematocrit, left ventricular mass index, and use of diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, sympatolytics, and calcium channel blockers did not influence the occurrence of complex arrhythmia. The data indicate that blood pressure and myocardial dysfunction are more important determinants of complex arrhythmia than dialysis or uremia in chronic renal disease patients.

Blood Pressure Influences the Occurrence of Complex Ventricular Arrhythmia in Hemodialysis Patients

We investigated the relationship between blood pressure and the occurrence of complex ventricular arrhythmias (multiform, couplets, or runs) as assessed by 48-hour Holter monitoring in 74 stable long-term hemodialysis patients (44.5 +/- 12 years old; 54% men; 74% whites; dialysis duration, 51.3 +/- 36.1 months; systolic pressure, 146.6 +/- 19.3 mm Hg; diastolic pressure, 89.2 +/- 12.1 mm Hg; prevalence of arterial hypertension, 33.8%). Systolic and diastolic pressures represented the average of all predialysis determinations during the 3 months preceding the tests. Hemodialysis was performed midway through the Holter monitoring period. M-mode and bidimensional echocardiograms and myocardial perfusion tests were also obtained from all patients. Complex arrhythmias were observed in 37 individuals (50%). Univariate analysis showed that systolic pressure (P < .001), diastolic pressure (P < .05), age (P < .001), left ventricular posterior wall thickness (P < .01), left ventricular mass index (P < .05), and ischemic alterations on myocardial perfusion tests (P < .005) were significantly associated with complex arrhythmias. With the use of a multivariate model (stepwise logistic regression analysis) only systolic pressure (P < .01) and age (P < .05) were independently associated with complex arrhythmias. Sex; angina; dialysis duration; New York Heart Association functional class; use of digitalis; plasma levels of creatinine, sodium, potassium, calcium, and phosphate; hematocrit; left ventricular fractional shortening; left ventricular diastolic diameter; and ST segment deviation were not correlated with complex arrhythmias. The severity and frequency of complex arrhythmias were not influenced by hemodialysis. At follow-up (5 to 80 months) 5 patients had died of sudden death, 4 of whom were hypertensive and older than 45 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic abnormalities demonstrable in young normotensive subjects who are children of hypertensive parents

Although a slightly elevated office blood pressure (BP) has been reported in several studies, little is known about the prolonged resting blood pressure, heart rate (HR) and baroreflex sensitivity (BRS) of prehypertensive subjects with a family history of hypertension. Office blood pressure, prolonged resting (1 h) BP and HR were measured in 25 young normotensives with a positive family history of hypertension (FH+) and 25 young normotensives with a negative family history of hypertension (FH-), matched for age, sex, and body mass index. After BP and HR measurements, blood samples were collected for the determination of norepinephrine, plasma renin activity and aldosterone levels, and baroreflex sensitivity was then tested. Casual BP, prolonged resting BP and heart rate were significantly higher in the FH+ group (119.9 +/- 11.7/78.5 +/- 8.6 mmHg, 137.3 +/- 12.3/74.4 +/- 7.9 mmHg, 68.5 +/- 8.4 bpm) compared to the FH- group (112.9 +/- 11.4/71.2 +/- 8.3 mmHg, 128.0 +/- 11. 8/66.5 +/- 7.4 mmHg, 62.1 +/- 6.0 bpm). Plasma norepinephrine level was significantly higher in the FH+ group (220.1 +/- 104.5 pg/ml) than in the FH- group (169.1 +/- 63.3 pg/ml). Baroreflex sensitivity to tachycardia (0.7 +/- 0.3 vs 1.0 +/- 0.5 bpm/mmHg) was depressed in the FH+ group (P<0.05). The FH+ group exhibited higher casual blood pressure, prolonged resting blood pressure, heart rate and plasma norepinephrine levels than the FH- group (P<0.05), suggesting an increased sympathetic tone in these subjects. The reflex tachycardia was depressed in the FH+ group.

Decreased Cardiopulmonary Baroreflex Sensitivity in Chagas’ Heart Disease

No study has been performed on reflexes originating from receptors in the heart that might be involved in the pathological lesions of Chagas’ heart disease. Our study was undertaken to analyze the role of cardiopulmonary reflex on cardiovascular control in Chagas’ disease. We studied 14 patients with Chagas’ disease without heart failure and 12 healthy matched volunteers. Central venous pressure, arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance were recorded during deactivation of cardiopulmonary receptors. By reducing central venous pressure by applying −10 and −15 mm Hg of negative pressure to the lower body, we observed (a) a similar decrease of central venous pressure in both groups; (b) a marked increase in forearm vascular resistance in the control group but a blunted increase in the Chagas’ group; and (c) no significant changes in blood pressure and heart rate. To analyze cardiopulmonary and arterial receptors, we applied −40 mm Hg of lower-body negative pressure. As a consequence, (a) central venous pressure decreased similarly in both groups; (b) blood pressure was maintained in the control group, whereas in patients with Chagas’ disease, a decrease in systolic and mean arterial pressure occurred; (c) heart rate increased in both groups; and (d) forearm vascular resistance increased significantly and similarly in both groups. Unloading of receptors with low levels of lower-body negative pressure did not increase forearm vascular resistance in patients with Chagas’ disease, which suggests that the reflex mediated by cardiopulmonary receptors is impaired in patients with Chagas’ disease without heart failure. Overall control of circulation appears to be compromised because patients did not maintain blood pressure under high levels of lower-body negative pressure.

Body mass index has a good correlation with proatherosclerotic profile in children and adolescents

FUNDAMENTO: Recentemente, uma associacao de diferentes fatores de risco foi descrita como a sindrome metabolica. Diferentes definicoes estao sendo utilizadas para a mesma sindrome. Independente do nome ou da classificacao, estabeleceu-se que um agrupamento de fatores de risco cardiovasculares incluindo sobrepeso/obesidade, aumento da pressao arterial e anormalidade lipidicas e glicemicas esta associado com aumento do risco de aterosclerose em adultos. OBJETIVO: O objetivo desse estudo foi correlacionar os percentis do indice de massa corporal com a pressao arterial (PA), indice de resistencia a insulina (HOMA-ir) e perfis lipidicos em criancas e adolescentes, os quais caracterizam um perfil pro-aterosclerotico. METODOS: Agrupamentos de fatores de risco cardiovasculares foram avaliados em 118 criancas e adolescentes, divididos de acordo com os quartis do percentil de indice de massa corporal (PIMC): Q1 (n=23) com PIMC 93%. Estatisticamente, diferencas significantes nao foram observadas para idade (F=2,1; p=0,10); sexo (teste Qui-quadrado=3,0; p=0,38), e etnia (teste do Qui-quadrado = 4,7; p=0,20) entre diferentes quartis. RESULTADOS: Uma diferenca estatisticamente significante foi observada para PA sistolica (F=15,4; p<0,0001), PA diastolica (F=9,5; p<0,0001), glicemia (F=9,6; p<0,0001), insulina (F=12.9; p<0.0001), HOMA-ir (F=30,8; p<0,0001), e niveis de triglicerides (F=2,7; p=0,05) entre os diferentes quartis. CONCLUSAO: O excesso de peso avaliado pelo PIMC foi associado ao aumento de PA, triglicerides, indice HOMA-ir, e HDL - colesterol baixo, o que configura um perfil pro-aterosclerotico em criancas e adolescentes.BACKGROUND More recently, the association of different risk factors has been described as the metabolic syndrome. Different definitions are being used for the same syndrome. Regardless of the name or classification, it has been well established that a cardiovascular cluster including overweight/obesity, increased blood pressure, and lipid and glucose abnormalities are associated with an increased risk of atherosclerosis in adults. OBJECTIVE The aim of this study was to correlate body mass index percentiles with blood pressure, insulin resistance index, and lipid profiles in children and adolescents, which characterize a proatherosclerotic profile. METHODS Cardiovascular risk factor clusters were evaluated in 118 children and adolescents divided according to body mass index percentile (BMIP) quartiles: Q1 (n=23) with BMIP <50%, Q2 (n=30) with BMIP between 50 and 85%, Q3 (n=31) with BMIP between 85 and 93%, and Q4 (n=34) with the BMIP > 93%. Statistically significant differences were not observed for age (F=2.1; p=0.10); sex (chi-square test=3.0; p=0.38), and ethnicity (chi-square test=4.7; p=0.20) between different quartiles. RESULTS A statistically significant difference was observed for systolic BP (F=15.4; p<0.0001), diastolic BP (F=9.5; p<0.0001), glycemia (F=9.6; p<0.0001), insulin (F=12.9; p<0.0001), HOMAir (F=30.8; p<0.0001), and triglyceride levels (F=2.7; p=0.05) between the different quartiles. CONCLUSION Excess weight evaluated by BMIP was associated with increased blood pressure, triglycerides, HOMAir index, and low HDL-cholesterol, a proatherosclerotic profile in children and adolescents.