Frida Liane Plavnik

Lipid peroxidation and antioxidants in hyperlipidemia and hypertension

Lipid peroxidation and lipid-derived oxidized products have been implicated in the pathogenesis of a variety of human diseases. To clarify the role of oxidative stress in essential hypertension and hypercholesterolemia the in vitro oxidative susceptibility of LDL, the antioxidant status and the lipid peroxide content of blood plasma were examined in hypercholesterolemic (HC), hypertensive (H), hypercholesterolemic/hypertensive (HH) and normolipidemic/normotensive subjects (N). Plasma ascorbate and lipid-soluble antioxidants were lower, while LDL oxidizability, CE-OOH and TL-OOH were higher in H, HC, and HH groups than in the N group. No difference was observed among groups for PL-OOH and isoprostanes. In summary, the results show that: 1) lipid- and water-soluble antioxidants are lower in hypercholesterolemic and hypertensive patients as compared to normal subjects, whereas the lipid peroxide content and the LDL susceptibility to oxidation were higher; 2) total cholesterol, LDL-cholesterol, apoB and CE-OOH were negatively correlated with the content of a-tocopherol; 3) there was a positive correlation between the content of lipid-soluble antioxidants and the resistance of LDL to oxidation; and 4) CE-OOH and TL-OOH were positively correlated with total cholesterol and LDL-cholesterol.

Effect of blood glucose on left ventricular mass in patients with hypertension and type 2 diabetes mellitus

The aim of our prospective study was to evaluate the influence of blood glucose (BG) on left ventricular mass and diastolic function in patients with hypertension and type 2 diabetes mellitus (DM). Fifty-six hypertensive patients with type 2 DM and 26 healthy controls were investigated. They were submitted to echocardiography (ECHO) with Doppler and we calculated the mean of their fasting BG values, office blood pressure (OBP), cholesterol and fractions, and triglycerides during the previous 4 years. The diabetic patients were then followed-up for 1 year with OBP, fasting BG, and lipids measured every 2 months. After this period, the patients were again submitted to ECHO and in 22 patients (group I [GI]), reductions greater than 10% in left ventricular mass index (LVMI) were observed (122 +/- 35 v 89 +/- 23 g/m2, P < .01), whereas increases greater than 10% (group II [GII], n = 17) (94 +/- 18 v 115 +/- 27 g/m2, P < .01) or no changes (group III [GIII], n = 17) (98 +/- 16 v 99 +/- 18 g/m2, NS) in LVMI were detected in the remaining patients. The OBP values did not change during the follow-up. In GI the reduction of LVMI was associated with a BG fall from 178 +/- 36 to 147 +/- 30 mg/dL (P < .01) and a correlation was observed between BG and LVMI percent variations (delta) (r = 0.48, P < .01). No important changes in left ventricular diastolic function were observed during the follow-up. We concluded that the improvement in glycemic control may contribute to LVH regression in hypertensive patients with type 2 DM.

Nitric oxide, cholesterol oxides and endothelium-dependent vasodilation in plasma of patients with essential hypertension

The objective of the present study was to identify disturbances of nitric oxide radical (.NO) metabolism and the formation of cholesterol oxidation products in human essential hypertension. The concentrations of.NO derivatives (nitrite, nitrate, S-nitrosothiols and nitrotyrosine), water and lipid-soluble antioxidants and cholesterol oxides were measured in plasma of 11 patients with mild essential hypertension (H: 57.8 +/- 9.7 years; blood pressure, 148.3 +/- 24.8/90.8 +/- 10.2 mmHg) and in 11 healthy subjects (N: 48.4 +/- 7.0 years; blood pressure, 119.4 +/- 9.4/75.0 +/- 8.0 mmHg). Nitrite, nitrate and S-nitrosothiols were measured by chemiluminescence and nitrotyrosine was determined by ELISA. Antioxidants were determined by reverse-phase HPLC and cholesterol oxides by gas chromatography. Hypertensive patients had reduced endothelium-dependent vasodilation in response to reactive hyperemia (H: 9.3 and N: 15.1% increase of diameter 90 s after hyperemia), and lower levels of ascorbate (H: 29.2 +/- 26.0, N: 54.2 +/- 24.9 micro M), urate (H: 108.5 +/- 18.9, N: 156.4 +/- 26.3 micro M), beta-carotene (H: 1.1 +/- 0.8, N: 2.5 +/- 1.2 nmol/mg cholesterol), and lycopene (H: 0.4 +/- 0.2, N: 0.7 +/- 0.2 nmol/mg cholesterol), in plasma, compared to normotensive subjects. The content of 7-ketocholesterol, 5alpha-cholestane-3beta,5,6beta-triol and 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol in LDL, and the concentration of endothelin-1 (H: 0.9 +/- 0.2, N: 0.7 +/- 0.1 ng/ml) in plasma were increased in hypertensive patients. No differences were found for.NO derivatives between groups. These data suggest that an increase in cholesterol oxidation is associated with endothelium dysfunction in essential hypertension and oxidative stress, although.NO metabolite levels in plasma are not modified in the presence of elevated cholesterol oxides.

Calcium Channel Blockers as Inhibitors of Angiotensin I–Converting Enzyme

Using ion-exchange chromatography of dialyzed human urine from healthy and hypertensive patients, we detected two peaks of angiotensin I-converting enzyme (ACE) activity on hippuryl-His-Leu eluted at ionic strengths of 0.7 (F1 peak) and 1.25 (F2 peak) mS. These hydrolytic activities decreased gradually in the urine of patients submitted to isradipine treatment, F2 and F1 disappearing after 12 and 24 hours, respectively. By Western blot analysis, the urine fractions corresponding to both peaks from healthy and untreated patients presenting ACE activity and from treated patients (24 hours) without this activity were recognized by an ACE-specific antibody. These results indicated that ACE was present but inhibited in the urine of isradipine-treated patients. In vitro assays with ACE isolated from human urine and guinea pig plasma demonstrated that the enzyme is inhibited by isradipine and other commercially available calcium channel blockers, such as felodipine, nifedipine, and verapamil. A noncompetitive inhibition was observed with all calcium channel blockers studied. In conclusion, these results suggest that besides the primary effect on calcium channels, the more commonly used calcium channel blockers are also ACE inhibitors. The development of efficient calcium channel blockers with higher ACE inhibitory activity could result in interesting bifunctional antihypertensive drugs.

Association of Carotid Intima-media Thickness and Cardiovascular Risk Factors in Women Pre- and Post-bariatric Surgery

BackgroundObesity is associated with cardiovascular risk factors (CVRFs), such as hypertension, hypertriglyceridemia, and low levels of high-density cholesterol (HDL-C). In obese patients with a body mass index (BMI) of ≥40xa0kg/m2 or 35–40xa0kg/m2 associated with CVRFs, weight loss may be achieved more effectively by bariatric surgery on reducing several CVRFs. Carotid intima-media thickness (C-IMT) is an indicator of early atherosclerosis, and may be correlated with CVRFs. Our objective was to correlate C-IMT with CVRFs before (baseline data) and after surgery, and to observe whether weight loss is followed by a regression of C-IMT.MethodsEighteen women who had undergone bariatric surgery participated in this study. Assessments were carried out on the baseline date, and 3, 6, and 12xa0months after surgery. Some of the CVRFs analyzed were: total cholesterol (TC) levels, HDL-C, triglycerides to HDL-C ratio (TG/HDL-C) and fasting plasma glucose. C-IMT was measured by B-mode ultrasound.ResultsA positive correlation was found between C-IMT and age and triglyceride level (pu2009=u20090.002 and pu2009=u20090.02, respectively). Six months after surgery, we found a significant reduction in C-IMT (pu2009<u20090.05), which was significantly correlated with TG level and systolic pressure (pu2009<u20090.05).ConclusionThe weight loss achieved with bariatric surgery resulted in regression of C-IMT. This regression could be observed 6xa0months following surgery, with an additional benefit at 12xa0months. Also, this finding was correlated with a reduction in triglyceride levels and systolic blood pressure.

Hyperglycemia and nocturnal systolic blood pressure are associatedwith left ventricular hypertrophy and diastolic dysfunction in hypertensive diabetic patients

BackgroundThe aim of this study was to determine if hypertensive type 2 diabetic patients, when compared to patients with essential hypertension have an increased left ventricular mass index (LVMI) and a worse diastolic function, and if this fact would be related to 24-h pressoric levels changes.MethodsNinety-one hypertensive patients with type 2 diabetes mellitus (DM) (group-1 [G1]), 59 essential hypertensive patients (group-2 [G2]) and 26 healthy controls (group-3 [G3]) were submitted to 24-h Ambulatory Blood Pressure Monitoring (ABPM) and echocardiography (ECHO) with Doppler. We calculated an average of fasting blood glucose (AFBG) values of G1 from the previous 4.2 years and a glycemic control index (GCI) (percentual of FBG above 200 mg/dl).ResultsG1 and G2 did not differ on average of diurnal systolic and diastolic BP. However, G1 presented worse diastolic function and a higher average of nocturnal systolic BP (NSBP) and LVMI (NSBP = 132 ± 18 vs 124 ± 14 mmHg; P < 0.05 and LVMI = 103 ± 27 vs 89 ± 17 g/m2; P < 0.05, respectively). In G1, LVMI correlated with NSBP (r = 0.37; P < 0.001) and GCI (r = 0.29; P < 0.05) while NSBP correlated with GCI (r = 0.27; P < 0.05) and AFBG (r = 0.30; P < 0.01). When G1 was divided in tertiles according to NSBP, the subgroup with NSBP≥140 mmHg showed a higher risk of LVH. Diabetics with NSBP≥140 mmHg and AFBG>165 mg/dl showed an additional risk of LVH (P < 0.05; odds ratio = 11). In multivariate regression, both GCI and NSBP were independent predictors of LVMI in G1.ConclusionThis study suggests that hyperglycemia and higher NSBP levels should be responsible for an increased prevalence of LVH in hypertensive patients with Type 2 DM.

Reproducibility of ambulatory blood pressure monitoring in hypertensive patients with type 2 diabetes mellitus

OBJECTIVEnTo evaluate the reproducibility of ambulatory blood pressure monitoring (ABPM) (SpaceLabs-90207) and placebo effect on ABPM.nnnMETHODSnBlood pressure was measured in the office and over two ABPM periods with an interval from one to ten months (mean 4.9 months), in 26 patients with type 2 diabetes mellitus and hypertension. Eleven patients (G1) had two ABPMs without taking antihypertensive drugs for 15 days, whereas G2 (N=15) had the second ABPM after administration of a placebo for 15 days.nnnRESULTSnIn the evaluation of the coefficient of variation (CV) of diurnal (awake) systolic BP (DSBP), of diurnal (awake) diastolic BP (DDBP), of 24-hour systolic BP (24hSBP) and of 24-hour diastolic BP (24hDBP), the values found were 4.6%, 3.9%, 5.0%, 4.0% for G1 and 4.3%, 5.1%, 3.7%, 5.1% for G2 respectively. We also determined the CV of nocturnal (sleep) systolic and diastolic BP (NSBP and NDBP) for G1 (7.7%; 8.2%) and G2 (5.6%; 6.3%). Heart rate CV during alertness and sleep were: G1=5.9% and 9.0%; G2=6.9% and 5.8% respectively. When the total number of patients was analyzed, all variables showed a strong correlation between the first and second ABPM measurements (DSBP, r = 0.76; P < 0.001; DDBP, r = 0.65; p < 0.001; 24hSBP, r = 0.77; p < 0.001; 24hDBP, r = 0.70; p < 0.001; NSBP, r = 0.62; p < 0.001; NDBP, r = 0.52; p < 0.01). Office systolic and diastolic BP and 24hSBP and 24hDBP also showed correlation (r = 0.65; p < 0.001; r = 0.57; p < 0.01).nnnCONCLUSIONnMean of pressure levels measured by ABPM presented good reproducibility and were not affected by placebo.

N-domain isoform of Angiotensin I converting enzyme as a marker of hypertension: populational study.

The aim of this paper was to investigate the presence of the urinary 90u2009kDa N-domain ACE in a cohort of the population from Vitoria, Brazil, to verify its association with essential hypertension since this isoform could be a possible genetic marker of hypertension. Anthropometric, clinical, and laboratory parameters of the individuals were evaluated (n = 1150) and the blood pressure (BP) was measured. The study population was divided according to ACE isoforms in urine as follows: ACE 65/90/190, presence of three ACE isoforms (n = 795), ACE 90+ (65/90) (n = 186), and ACE 90− (65/190) (n = 169) based on the presence (+) or absence (−) of the 90u2009kDa ACE isoform. The anthropometric parameters, lipid profile, serum levels of uric acid, glucose, and the systolic and diastolic BP were significantly greater in the ACE 90+ compared with the ACE 90− and ACE 65/90/190 individuals. We found that 98% of individuals from the ACE 90+ group and 38% from the ACE 65/90/190 group had hypertension, compared to only 1% hypertensive individuals in the ACE 90− group. There is a high presence of the 90u2009kDa N-domain ACE isoform (85%) in the studied population. The percentile of normotensive subjects with three isoforms was 62%. Our findings could contribute to the development of new efficient strategy to prevent and treat hypertension to avoid the development of cardiovascular disease.

Left Ventricular Hypertrophy Evaluation in Obese Hypertensive Patients: Effect of Left Ventricular Mass Index Criteria

PURPOSEnTo evaluate left ventricular mass (LVM) index in hypertensive and normotensive obese individuals.nnnMETHODSnUsing M mode echocardiography, 544 essential hypertensive and 106 normotensive patients were evaluated, and LVM was indexed for body surface area (LVM/BSA) and for height2 (LVM/h2). The 2 indexes were then compared in both populations, in subgroups stratified according to body mass index (BMI): <27; 27-30; >/= 30kg/m2.nnnRESULTSnThe BSA index does not allow identification of significant differences between BMI subgroups. Indexing by height2 provides significantly increased values for high BMI subgroups in normotensive and hypertensive populations.nnnCONCLUSIONnLeft ventricular hypertrophy (LVH) has been underestimated in the obese with the use of LVM/BSA because this index considers obesity as a physiological variable. Indexing by height2 allows differences between BMI subgroups to become apparent and seems to be more appropriate for detecting LVH in obese populations.

Efeitos de diferentes graus de sensibilidade a insulina na função endotelial de pacientes obesos

BACKGROUNDnObesity derived from intra-abdominal fat deposition tends to increase hormonal and cytokine production, thus worsening insulin sensitivity and leading to endothelial dysfunction. Hyperinsulinemia is considered an independent risk factor for ischemic heart disease and cause of endothelial dysfunction in healthy individuals.nnnOBJECTIVEnTo assess the impact of different degrees of insulin resistance, measured by HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), on endothelial function in obese, non-diabetic patients without prior history of cardiovascular events and different metabolic syndrome components.nnnMETHODSnForty obese individuals were submitted to anthropometric measurements, BP measurements at office and ABPM and laboratory tests, in addition to non-invasive ultrasound assessment of endothelial function. Patients were divided into 3 groups according to the level of insulin resistance: patients with HOMA-IR values from 0.590 to 1.082 were assigned to Group 1 (n=13), from 1.083 to 1.410 to Group 2 (n=14) and from 1.610 to 2.510 to Group 3 (n=13).nnnRESULTSnWe found a significant difference in flow-mediated dilation in group 3 compared to group 1 (9.2 ± 7.0 vs 18.0 ± 7.5 %, p=0.006). There was a negative correlation between endothelial function and insulin, HOMA-IR and triglycerides.nnnCONCLUSIONnOur data suggest that mild changes in insulin resistance levels assessed by HOMA-IR may have an impact on vasodilatatory endothelial function in uncomplicated obese individuals with different cardiovascular risk factors.FUNDAMENTO: A obesidade derivada da deposicao de gordura intra-abdominal tende a aumentar a producao de hormonios e citoquinas, piorando a sensibilidade a insulina e levando a disfuncao endotelial. A hiperinsulinemia e considerada um fator de risco independente para doenca isquemica cardiaca e e uma causa de disfuncao endotelial em individuos saudaveis. OBJETIVO: Avaliar o impacto de diferentes graus de resistencia a insulina, medida pelo HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), sobre a funcao endotelial de obesos, pacientes nao diabeticos, sem historia previa de eventos cardiovasculares e diversos componentes da sindrome metabolica. METODOS: Um total de 40 individuos obesos foi submetido a medidas antropometricas, pressao arterial de consultorio, MAPA e exames laboratoriais, alem de avaliacao ultrassonografica nao invasiva da funcao endotelial. Os pacientes foram divididos em tres grupos de acordo com o grau de resistencia a insulina: pacientes com valores de HOMA-IR entre 0,590 e 1,082 foram incluidos no Grupo 1 (n = 13); entre 1,083 e 1,410 no Grupo 2 (n = 14); e entre 1,610 e 2,510 no Grupo 3 (n = 13). RESULTADOS: Encontramos uma diferenca significativa na vasodilatacao mediada por fluxo no Grupo 3 em relacao ao Grupo 1 (9,2 ± 7,0 vs 18,0 ± 7,5 %, p = 0,006). Houve uma correlacao negativa entre a funcao endotelial e insulina, HOMA-IR e triglicerides. CONCLUSAO: Nosso estudo sugere que leves alteracoes nos niveis de resistencia a insulina avaliada pelo HOMA-IR podem causar algum impacto sobre a funcao vasodilatadora do endotelio em individuos obesos nao complicados com diferentes fatores de risco cardiovascular.