Valeria Costa-Hong

Oxidative stress and endothelial dysfunction in chronic kidney disease

FUNDAMENTO: La enfermedad renal cronica (ERC) se caracteriza por la alta prevalencia de aterosclerosis Siendo el estres oxidativo y la disfuncion endotelial promotores de la aterosclerosis, es interesante verificar si las dos condiciones estan asociadas en pacientes con ERC, aun sin enfermedad cardiovascular (ECV) clinica. OBJETIVO: Evaluar las relaciones entre el estres oxidativo y la funcion endotelial en pacientes con ERC estado 5, sin ECV. METODOS: Se estudiaron 22 pacientes con ERC, no diabeticos, no fumadores, sin ECV y tratados por hemodialisis; ademas de 22 individuos normales. En todos los individuos se evaluaron la reactividad vascular, dependiente e independiente de endotelio (ecografia de alta resolucion de la arteria braquial), y el estres oxidativo (niveles plasmaticos de sustancias reactivas al acido tiobarbiturico - TBARS). RESULTADOS: La reactividad vascular dependiente de endotelio (6,0 ± 4,25% vs. 11,3 ± 4,46%, p <0,001) y la reactividad independiente de endotelio (11,9 ± 7,68% vs. 19,1 ± 6,43%, p <0,001) se redujeron en la ERC, mientras el estres oxidativo (2,63 ± 0,51 vs. 1,49 ± 0,43, p <0,001) se vio aumentado. Los niveles de TBARS, cuando se utiliza en la totalidad de individuos del estudio (pacientes y controles), se correlacionaron con la reactividad vascular dependiente de endotelio (r = -0,56, p<0,001) y con la presion arterial sistolica (r = 0,48, p = 0,002). CONCLUSION: El estres oxidativo esta asociado a la disfuncion endotelial. Pacientes con ERC presentan aumento del estres oxidativo y compromiso de la reactividad vascular. Los resultados sugieren ademas que el estres oxidativo y la disfuncion endotelial pueden estar involucrados en la susceptibilidad exagerada de la ERC a las complicaciones cardiovasculares.BACKGROUND Chronic kidney disease (CKD) is characterized by the high prevalence of atherosclerosis. Considering that endothelial dysfunction and oxidative stress are promoters of atherosclerosis, it is of interest to verify whether the two conditions are associated in CKD patients still free of clinical cardiovascular disease (CVD). OBJECTIVE To evaluate the association between oxidative stress and endothelial function in end-stage CKD patients without clinically evident CVD. METHODS We studied 22 nondiabetic, nonsmoker CKD patients without clinical CVD treated by maintenance hemodialysis and 22 healthy controls. Endothelium- dependent and independent vascular reactivity and oxidative stress, as determined by the plasma levels of thiobarbituric acid-reactive substances--TBARS, were evaluated in all subjects. RESULTS Endothelium-dependent (6.0 +/- 4.25 vs. 11.3 +/- 4.46%, p<0.001) and endothelium-independent (11.9 +/- 7.68 vs. 19.1% +/- 6.43%, p<0.001) vascular reactivity were reduced, while TBARS (2.63 +/- 0.51 vs. 1.49 +/- 0.42 nmols/mL) was increased in CKD patients when compared to controls. TBARS levels were significantly related to endothelium-dependent vascular reactivity (r=-0.56, p<0.001) and to systolic blood pressure (r=-0.48, p=0.002). CONCLUSION Oxidative stress is increased in CKD patients free of CVD and is associated with endothelial dysfunction in patients and controls. The results suggest that oxidative stress and endothelial dysfunction may be involved in the increased susceptibility of CKD patients to CVD and cardiovascular complications.

The impact of metabolic syndrome on metabolic, pro-inflammatory and prothrombotic markers according to the presence of high blood pressure criterion

OBJECTIVES: We explored whether high blood pressure is associated with metabolic, inflammatory and prothrombotic dysregulation in patients with metabolic syndrome. METHODS: We evaluated 135 consecutive overweight/obese patients. From this group, we selected 75 patients who were not under the regular use of medications for metabolic syndrome as defined by the current Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults criteria. The patients were divided into metabolic syndrome with and without high blood pressure criteria (≥130/≥85 mmHg). RESULTS: Compared to the 45 metabolic syndrome patients without high blood pressure, the 30 patients with metabolic syndrome and high blood pressure had significantly higher glucose, insulin, homeostasis model assessment insulin resistance index, total cholesterol, low-density lipoprotein-cholesterol, triglycerides, uric acid and creatinine values; in contrast, these patients had significantly lower high-density lipoprotein-cholesterol values. Metabolic syndrome patients with high blood pressure also had significantly higher levels of retinol-binding protein 4, plasminogen activator inhibitor 1, interleukin 6 and monocyte chemoattractant protein 1 and lower levels of adiponectin. Moreover, patients with metabolic syndrome and high blood pressure had increased surrogate markers of sympathetic activity and decreased baroreflex sensitivity. Logistic regression analysis showed that high-density lipoprotein, retinol-binding protein 4 and plasminogen activator inhibitor-1 levels were independently associated with metabolic syndrome patients with high blood pressure. There is a strong trend for an independent association between metabolic syndrome patients with high blood pressure and glucose levels. CONCLUSIONS: High blood pressure, which may be related to the autonomic dysfunction, is associated with metabolic, inflammatory and prothrombotic dysregulation in patients with metabolic syndrome.

Hypertension Severity Is Associated With Impaired Cognitive Performance

Background Most evidence of target‐organ damage in hypertension (HTN) is related to the kidneys and heart. Cerebrovascular and cognitive impairment are less well studied. Therefore, this study analyzed changes in cognitive function in patients with different stages of hypertension compared to nonhypertensive controls. Methods and Results In a cross‐sectional study, 221 (71 normotensive and 150 hypertensive) patients were compared. Patients with hypertension were divided into 2 stages according to blood pressure (BP) levels or medication use (HTN‐1: BP, 140–159/90–99 or use of 1 or 2 antihypertensive drugs; HTN‐2: BP, ≥160/100 or use of ≥3 drugs). Three groups were comparatively analyzed: normotension, HTN stage 1, and HTN stage 2. The Mini–Mental State Examination, Montreal Cognitive Assessment, and a validated comprehensive battery of neuropsychological tests that assessed 6 main cognitive domains were used to determine cognitive function. Compared to the normotension and HTN stage‐1, the severe HTN group had worse cognitive performance based on Mini–Mental State Examination (26.8±2.1 vs 27.4±2.1 vs 28.0±2.0; P=0.004) or Montreal Cognitive Assessment (23.4±3.7 vs 24.9±2.8 vs 25.5±3.2; P<0.001). On the neuropsychological tests, patients with hypertension had worse performance in language, processing speed, visuospatial abilities, and memory. Age, hypertension stage, and educational level were the best predictors of cognitive impairment in patients with hypertension in different cognitive domains. Conclusions Cognitive impairment was more frequent in patients with hypertension, and this was related to hypertension severity.

Estresse oxidativo e disfunção endotelial na doença renal crônica

FUNDAMENTO: La enfermedad renal cronica (ERC) se caracteriza por la alta prevalencia de aterosclerosis Siendo el estres oxidativo y la disfuncion endotelial promotores de la aterosclerosis, es interesante verificar si las dos condiciones estan asociadas en pacientes con ERC, aun sin enfermedad cardiovascular (ECV) clinica. OBJETIVO: Evaluar las relaciones entre el estres oxidativo y la funcion endotelial en pacientes con ERC estado 5, sin ECV. METODOS: Se estudiaron 22 pacientes con ERC, no diabeticos, no fumadores, sin ECV y tratados por hemodialisis; ademas de 22 individuos normales. En todos los individuos se evaluaron la reactividad vascular, dependiente e independiente de endotelio (ecografia de alta resolucion de la arteria braquial), y el estres oxidativo (niveles plasmaticos de sustancias reactivas al acido tiobarbiturico - TBARS). RESULTADOS: La reactividad vascular dependiente de endotelio (6,0 ± 4,25% vs. 11,3 ± 4,46%, p <0,001) y la reactividad independiente de endotelio (11,9 ± 7,68% vs. 19,1 ± 6,43%, p <0,001) se redujeron en la ERC, mientras el estres oxidativo (2,63 ± 0,51 vs. 1,49 ± 0,43, p <0,001) se vio aumentado. Los niveles de TBARS, cuando se utiliza en la totalidad de individuos del estudio (pacientes y controles), se correlacionaron con la reactividad vascular dependiente de endotelio (r = -0,56, p<0,001) y con la presion arterial sistolica (r = 0,48, p = 0,002). CONCLUSION: El estres oxidativo esta asociado a la disfuncion endotelial. Pacientes con ERC presentan aumento del estres oxidativo y compromiso de la reactividad vascular. Los resultados sugieren ademas que el estres oxidativo y la disfuncion endotelial pueden estar involucrados en la susceptibilidad exagerada de la ERC a las complicaciones cardiovasculares.BACKGROUND Chronic kidney disease (CKD) is characterized by the high prevalence of atherosclerosis. Considering that endothelial dysfunction and oxidative stress are promoters of atherosclerosis, it is of interest to verify whether the two conditions are associated in CKD patients still free of clinical cardiovascular disease (CVD). OBJECTIVE To evaluate the association between oxidative stress and endothelial function in end-stage CKD patients without clinically evident CVD. METHODS We studied 22 nondiabetic, nonsmoker CKD patients without clinical CVD treated by maintenance hemodialysis and 22 healthy controls. Endothelium- dependent and independent vascular reactivity and oxidative stress, as determined by the plasma levels of thiobarbituric acid-reactive substances--TBARS, were evaluated in all subjects. RESULTS Endothelium-dependent (6.0 +/- 4.25 vs. 11.3 +/- 4.46%, p<0.001) and endothelium-independent (11.9 +/- 7.68 vs. 19.1% +/- 6.43%, p<0.001) vascular reactivity were reduced, while TBARS (2.63 +/- 0.51 vs. 1.49 +/- 0.42 nmols/mL) was increased in CKD patients when compared to controls. TBARS levels were significantly related to endothelium-dependent vascular reactivity (r=-0.56, p<0.001) and to systolic blood pressure (r=-0.48, p=0.002). CONCLUSION Oxidative stress is increased in CKD patients free of CVD and is associated with endothelial dysfunction in patients and controls. The results suggest that oxidative stress and endothelial dysfunction may be involved in the increased susceptibility of CKD patients to CVD and cardiovascular complications.

Association of obstructive sleep apnea with arterial stiffness and nondipping blood pressure in patients with hypertension

Whether sex influences the association of obstructive sleep apnea (OSA) with markers of cardiovascular risk in patients with hypertension is unknown. In this study, 95 hypertensive participants underwent carotid‐femoral pulse wave velocity, 24‐hour ambulatory blood pressure monitoring, echocardiogram, and polysomnography after a 30‐day standardized treatment with hydrochlorothiazide plus enalapril or losartan. OSA was present in 52 patients. Compared with non‐OSA patients, pulse wave velocity values were higher in the OSA group (men: 11.1±2.2 vs 12.7±2.4 m/s, P=.04; women: 11.8±2.4 vs 13.2±2.2 m/s, P=.03). The proportion of diastolic dysfunction was significant in men and women with OSA. Compared with non‐OSA patients, nondipping systolic blood pressure in OSA was higher in men (14.3% vs 46.4%) and in women (41.4% vs 65.2%). OSA was independently associated with pulse wave velocity (β=1.050; P=.025) and nondipping systolic blood pressure (odds ratio, 3.03; 95% confidence interval, 1.08–8.55; P=.035) in the regression analysis. In conclusion, OSA is independently associated with arterial stiffness and nondipping blood pressure in patients with hypertension regardless of sex.

The role of increased glucose on neurovascular dysfunction in patients with the metabolic syndrome

Metabolic syndrome (MetS) causes autonomic alteration and vascular dysfunction. The authors investigated whether impaired fasting glucose (IFG) is the main cause of vascular dysfunction via elevated sympathetic tone in nondiabetic patients with MetS. Pulse wave velocity, muscle sympathetic nerve activity (MSNA), and forearm vascular resistance was measured in patients with MetS divided according to fasting glucose levels: (1) MetS+IFG (blood glucose ≥100 mg/dL) and (2) MetS‐IFG (<100 mg/dL) compared with healthy controls. Patients with MetS+IFG had higher pulse wave velocity than patients with MetS‐IFG and controls (median 8.0 [interquartile range, 7.2–8.6], 7.3 [interquartile range, 6.9–7.9], and 6.9 [interquartile range, 6.6–7.2] m/s, P=.001). Patients with MetS+IFG had higher MSNA than patients with MetS‐IFG and controls, and patients with MetS‐IFG had higher MSNA than controls (31±1, 26±1, and 19±1 bursts per minute; P<.001). Patients with MetS+IFG were similar to patients with MetS‐IFG but had higher forearm vascular resistance than controls (P=.008). IFG was the only predictor variable of MSNA. MSNA was associated with pulse wave velocity (R=.39, P=.002) and forearm vascular resistance (R=.30, P=.034). In patients with MetS, increased plasma glucose levels leads to an adrenergic burden that can explain vascular dysfunction.

Determinants of Functional and Structural Properties of Large Arteries in Healthy Individuals

Background Changes in the properties of large arteries correlate with higher cardiovascular risk. Recent guidelines have included the assessment of those properties to detect subclinical disease. Establishing reference values for the assessment methods as well as determinants of the arterial parameters and their correlations in healthy individuals is important to stratify patients. Objective To assess, in healthy adults, the distribution of the values of pulse wave velocity, diameter, intima-media thickness and relative distensibility of the carotid artery, in addition to assessing the demographic and clinical determinants of those parameters and their correlations. Methods This study evaluated 210 individuals (54% women; mean age, 44 ± 13 years) with no evidence of cardiovascular disease. The carotid-femoral pulse wave velocity was measured with a Complior® device. The functional and structural properties of the carotid artery were assessed by using radiofrequency ultrasound. Results The means of the following parameters were: pulse wave velocity, 8.7 ± 1.5 m/s; diameter, 6,707.9 ± 861.6 μm; intima-media thickness, 601 ± 131 μm; relative distensibility, 5.3 ± 2.1%. No significant difference related to sex or ethnicity was observed. On multiple linear logistic regression, the factors independently related to the vascular parameters were: pulse wave velocity, to age (p < 0.01) and triglycerides (p = 0.02); intima-media thickness, to age (p < 0.01); diameter, to creatinine (p = 0.03) and age (p = 0.02); relative distensibility, to age (p < 0.01) and systolic and diastolic blood pressures (p = 0.02 and p = 0.01, respectively). Pulse wave velocity showed a positive correlation with intima media thickness (p < 0.01) and with relative distensibility (p < 0.01), while diameter showed a positive correlation with distensibility (p = 0.03). Conclusion In healthy individuals, age was the major factor related to aortic stiffness, while age and diastolic blood pressure related to the carotid functional measure. The carotid artery structure was directly related to aortic stiffness, which was inversely related to the carotid artery functional property.

Renal artery stenosis predicts coronary artery disease in patients with hypertension.

In hypertensive patients with indication of renal arteriography to investigate renal artery stenosis (RAS) there are no recommendations regarding when to investigate coronary artery disease (CAD). Moreover, the predictors of CAD in patients with RAS are not clear. We aimed to evaluate the frequency and the determinants of CAD in hypertensive patients referred to renal angiography. Eighty-two consecutive patients with high clinical risk suggesting the presence of RAS systematically underwent renal angiography and coronary angiography during the same procedure. Significant arterial stenosis was defined by an obstruction≥70% to both renal and coronary territories. Significant CAD was present in 32/82 (39%) and significant RAS in 32/82 (39%) patients. Both CAD and RAS were present in 25.6% from the 82 patients. Patients with severe CAD were older (63±12 vs. 56±13 years; p = 0.03) and had more angina (41 vs. 16%; p = 0.013) compared to patients without severe CAD. Significant RAS was associated with an increased frequency of severe CAD compared to patients without significant RAS (66% vs. 22%, respectively; p<0.001). Myocardial scintigraphy showed ischemia in 21.8% of the patients with CAD. Binary logistic regression analysis showed that RAS≥70% was independently associated with CAD≥70% (OR: 11.48; 95% CI 3.2–40.2; p<0.001), even in patients without angina (OR: 13.48; 95%CI 2.6–12.1; p<0.001). Even considering a small number of patients with significant RAS, we conclude that in hypertensive patients referred to renal angiography, RAS≥70% may be a strong predictor of severe CAD, independently of angina, and dual investigation should be considered.

Higher arterial stiffness is associated with lower cognitive performance in patients with hypertension

Cognitive impairment and elevated arterial stiffness have been described in patients with arterial hypertension, but their association has not been well studied. We evaluated the correlation of arterial stiffness and different cognitive domains in patients with hypertension compared with those with normotension. We evaluated 211 patients (69 with normotension and 142 with hypertension). Patients were age matched and distributed according to their blood pressure: normotension, hypertension stage 1, and hypertension stage 2. Cognitive function was assessed using the Mini‐Mental State Examination, Montreal Cognitive Assessment, and a battery of neuropsychological evaluations that assessed six main cognitive domains. Pulse wave velocity was measured using a Complior device, and carotid properties were assessed by radiofrequency ultrasound. Central arterial pressure and augmentation index were obtained using applanation tonometry. The hypertension stage 2 group had higher arterial stiffness and worse performance either by Mini‐Mental State Examination (26.8±2.1 vs 27.3±2.1 vs 28.0±2.0, P=.003) or the Montreal Cognitive Assessment test (23.4±3.5 vs 24.9±2.9 vs 25.6±3.0, P<.001). On multivariable regression analysis, augmentation index, intima‐media thickness, and pulse wave velocity were the variables mainly associated with lower cognitive performance at different cognitive domains. Cognitive impairment in different domains was associated with higher arterial stiffness.

Does Obstructive Sleep Apnea Influence Blood Pressure and Arterial Stiffness in Response to Antihypertensive Treatment

Untreated obstructive sleep apnea (OSA) is common in patients with hypertension and may impair blood pressure (BP) and target-organ damage responses to antihypertensive therapy. In this study, we recruited hypertensive patients who underwent treatment with a 30-day regimen of hydrochlorothiazide 25 mg plus enalapril (20 mg BID) or losartan (50 mg BID) and were assessed with a baseline clinical evaluation, polysomnography, 24-hour ambulatory BP monitoring, and carotid-femoral pulse wave velocity. All the examinations except for polysomnography were repeated at 6 and 18 months of follow-up. We studied 94 hypertensive patients (mean age, 55±9 years). The frequency of OSA was 55%. Compared with baseline, we did not observe significant differences between groups in 24-hour BP, daytime systolic and diastolic BPs, or night-time systolic BP at 6 and 18 months. The BP control rate at 24 hours (<130/80 mm Hg) was similar between the groups (baseline, 42.3% versus 45.2%; 6 months, 46.9% versus 57.5%; 18 months, 66.7% versus 61.5%). However, patients with OSA had higher night-time diastolic BP decrease than did the non-OSA group (6 months, −4.9±11.8 versus −0.3±10.3 mm Hg; 18 months, −6.7±11.1 versus −1.2±10.6 mm Hg; P=0.027). There were no differences in the number and class of antihypertensive medications prescribed during follow-up. In terms of arterial stiffness, patients with OSA had higher pulse wave velocity than did patients without OSA at baseline (10.3±1.9 versus 9.2±1.7 m/s; P=0.024), but both groups had similar decreases in pulse wave velocity during follow-up. In conclusion, with combined antihypertensive treatment aimed at controlling BP, hypertensive patients with OSA had similar 24-hour BP and arterial stiffness to those without OSA.