Relación entre modelado miocárdico y función diastólica en pacientes con hipertensión esencial / Relationship between myocardial modelling and diastolic function in patients with essential hypertension

Fundamento y objetivo: Analizar la relación entre las citoquinas antiapoptóticas, sFas y receptor soluble tipo 1 del factor de necrosis tumoral (sTNF-R1) con el fragmento aminoterminal del propéptido de procolágeno tipo iii (PIIINP) y tipo i (PINP) y la función diastólica en la hipertensión arterial (HTA). Pacientes y método: Se estudió un grupo de 253 pacientes con HTA, con una edad media (DE) de 60 (13) años; 139 eran varones. Se les realizó un examen físico, estudio eco-Doppler y determinación sérica de las moléculas. Resultados: Los valores séricos de PINP y PIIINP estuvieron elevados en pacientes hipertróficos frente a no-hipertróficos (media de 41 [extremos 31-52] frente a 35 [28-47] μg/l, p=0,010; y 4,33 [3,71-5,29] frente a 3,98 [3,49-4,58] μg/l, p=0,005, respectivamente). Además, se encontraron elevadas las concentraciones de sFas y sTNF-R1 (media de 1,47 [extremos 1,2-1,77] frente a 1,37 [1,1-1,59] ng/ml, p=0,012; y 466 [331-657] frente a 317 [260-427] pg/ml, p<0,0001, respectivamente). Por otra parte, los valores de PIIINP se relacionaron con sFas (r=0,386, p<0,0001) y sTNF-R1 (r=0,298, p<0,001); también se asoció PINP con estas citoquinas (r=0,158, p=0,011 y r=0,241, p<0,0001, respectivamente). En el análisis multivariable, sFas (p<0,0001) y sTNF-R1 (p<0,0001) fueron factores independientes de PIIINP. Por último, las concentraciones de los marcadores se relacionaron significativamente con los parámetros de función diastólica del ventrículo izquierdo. Conclusión:Las concentraciones de procolágeno y de citoquinas antiapoptóticas estuvieron elevadas en pacientes con hipertrofia ventricular. Además, sFas y sTNF-R1 son factores independientes de los valores en suero de PIIINP y se relacionan con los parámetros de función diastólica ventricular (AU)

Background and objectives: To analyze the relationship between sFas and soluble TNF receptor 1 (sTNF-R1) with type iii (PIIINP) and i (PINP) amino-terminal propeptide procollagens, and diastole in hypertension (HT). Patients and methods: A group of 253 Caucasian asymptomatic hypertensive patients (age 60±13 years, 139 males) were studied, in whom a physical examination, laboratory analyses (determination of serum PIIINP, PINP, sFas and by radioimmunoassay and ELISA, respectively), and echo-Doppler study were performed. Results: Serum PINP and PIIINP were increased in left ventricular hypertrophy compared to non-hypertrophy [41 (31-52) vs. 35 (28-47) μg/l, P=.010; and 4.33 (3.71-5.29) vs. 3.98 (3.49-4.58) μg/l, P=.005, respectively]. Furthermore, sFas and sTNF-R1 were also elevated [1.47 (1.2-1.77) vs. 1.37 (1.1-1.59), P=.012; and 466 (331-657) vs. 317 (260-427) μg/l, P<.0001, respectively]. Moreover, serum PIIINP was associated with sFas (r=.386, P<.0001) and sTNF-R1 (r=.298, P<.001); PINP was also associated with these cytokines (r=0.158, P=.011 and r=.241, P<.0001, respectively). Multivariable analyses included sFas (P<.0001) and sTNF-R1 (P<.0001) as independent factors related with serum PIIINP. Finally, marker concentrations were significantly related with left ventricular diastolic function parameters. Conclusion: Procollagen and anti-apoptotic cytokine levels were increased in our hypertrophic patients. Furthermore, sFas and sTNF-R1 are independent related factors of serum PIIINP. Diastolic parameters were associated with myocardial fibrosis and anti-apoptotic cytokines (AU)

MMP-2 and sTNF-R1 Variability in Patients with Essential Hypertension: 1-Year Follow-Up Study.

The aim of this study is to analyze MMP-2 and sTNF-R1 variability, potent predictors of cardiovascular events, in stable hypertensive patients during a 12-month followup. 234 asymptomatic patients (age 60 ± 13, 136 male) out of 252 patients with essential hypertension were followed up. MMP-2 and sTNF-R1 were measured at baseline and after 12 months (stage I). To compare MMP-2 and sTNF-R1 levels over time interval, we used the statistical method of Bland-Altman. MMP-2 and sTNF-R1 reproducibility was good in our patients for the two intervals with a coefficient of reproducibility of 8.2% and 11.3%, respectively. The percentages of patients within 1.96 × standard deviation of the mean were 93.6% and 92.7%. An elevated coefficient of correlation was obtained for MMP-2, basal versus stage I (r = 0.55, P < 0.0001) and for sTNF-R1 (r = 0.75, P < 0.0001). There is good stability in MMP-2 and sTNF-R1 levels in a followup study of patients with stable hypertension. As a consequence, assessment of its concentrations may be a useful tool for monitoring the follow-up of these patients. Measured variations in MMP-2 and sTNF-R1 levels, exceeding 8.2% and 11.3%, respectively, may indicate an increase in cardiovascular risk, thus, could be used to optimizing treatment than blood pressure control alone.

Impact of glomerular filtration rate on urinary BNP and NT-proBNP levels in heart failure.

B-type natriuretic peptide (BNP) and its inactive amino-terminal fragment (NT-proBNP) are diagnostic tools for heart failure (HF), but less is understood regarding the effects of renal function on their urinary concentrations. The objective was to analyze the influence of renal function, as estimated glomerular filtration rate (eGFR), on BNP and NT-proBNP concentrations in 90 HF outpatients (65 ± 12 years; 73% men), grouped according to eGFR below or above 60 mL/min. Patients with worse eGFR had higher serum NT-proBNP (p < 0.01) and BNP (p < 0.01) than patients with higher eGFR: NT-proBNP, but urinary levels did not reach statistical differences. In addition, a direct significant correlation between filtered load of serum NT-proBNP or BNP with their concentrations in urine was found in patients with eGFR above 60 mL/min (r = 0.66, p < 0.001 and r = 0.338, p < 0.05) and below 60 mL/min (r = 0.63, p < 0.001 and r = 0.406, p < 0.01). However, after normalizing urinary natriuretic peptide concentrations by their filtered load, we obtained a significant inverse and exponential relation in patients with worse renal function for NT-proBNP and BNP (r = -0.87, p = 0.001; and r = -0.71, p < 0.001, respectively) and in patients with eGFR>60 mL/min (r = -0.84, p < 0.001; and r = -0.72, p < 0.001, respectively). In conclusion, similar urinary NT-proBNP and BNP excretion was obtained in patients with high or low eGFR. Furthermore, despite the direct correlation between filtered load of serum natriuretic peptides with their urinary levels, an inverse an exponential relationship was obtained after normalizing urinary concentrations. Therefore, glomerular filtration does not seem to be the major determinant of both urinary peptide concentrations.

[Relationship between myocardial modelling and diastolic function in patients with essential hypertension]. / Relación entre modelado miocárdico y función diastólica en pacientes con hipertensión esencial.

BACKGROUND AND OBJECTIVES: To analyze the relationship between sFas and soluble TNF receptor 1 (sTNF-R1) with type iii (PIIINP) and i (PINP) amino-terminal propeptide procollagens, and diastole in hypertension (HT). PATIENTS AND METHODS: A group of 253 Caucasian asymptomatic hypertensive patients (age 60±13 years, 139 males) were studied, in whom a physical examination, laboratory analyses (determination of serum PIIINP, PINP, sFas and by radioimmunoassay and ELISA, respectively), and echo-Doppler study were performed. RESULTS: Serum PINP and PIIINP were increased in left ventricular hypertrophy compared to non-hypertrophy [41 (31-52) vs. 35 (28-47) µg/l, P=.010; and 4.33 (3.71-5.29) vs. 3.98 (3.49-4.58) µg/l, P=.005, respectively]. Furthermore, sFas and sTNF-R1 were also elevated [1.47 (1.2-1.77) vs. 1.37 (1.1-1.59), P=.012; and 466 (331-657) vs. 317 (260-427) µg/l, P<.0001, respectively]. Moreover, serum PIIINP was associated with sFas (r=.386, P<.0001) and sTNF-R1 (r=.298, P<.001); PINP was also associated with these cytokines (r=0.158, P=.011 and r=.241, P<.0001, respectively). Multivariable analyses included sFas (P<.0001) and sTNF-R1 (P<.0001) as independent factors related with serum PIIINP. Finally, marker concentrations were significantly related with left ventricular diastolic function parameters. CONCLUSION: Procollagen and anti-apoptotic cytokine levels were increased in our hypertrophic patients. Furthermore, sFas and sTNF-R1 are independent related factors of serum PIIINP. Diastolic parameters were associated with myocardial fibrosis and anti-apoptotic cytokines.

Impact of cardiovascular risk factors and inflammatory status on urinary 8-OHdG in essential hypertension.

BACKGROUND: The urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) reflect the oxidation status of hypertensive subjects and it can be used for monitoring oxidative stress changes. However, the influence of cardiovascular risk factors and inflammation on the urinary levels of this marker in hypertension (HT) has never evaluated. The purpose of this study was to analyze the impact of cardiovascular risk factors, and established inflammatory markers on 8-OHdG in essential HT. METHODS: We studied 149 asymptomatic hypertensive patients (61 ± 14 years). A routine physical examination, laboratory analyses, and echo-Doppler study were performed. Urinary 8-OHdG and plasma tumor necrosis factor-α (TNF-α), soluble TNF receptor 1 (sTNF-R1), soluble TNF receptor 2 (sTNF-R2), and interleukin-6 (IL-6) were determined. RESULTS: 8-OHdG/creatinine levels were higher in hypertrophic patients (P = 0.022) and correlated with left ventricular mass index (P < 0.01). When 8-OHdG/creatinine was compared according to obesity and diabetes in our hypertensive subjects, no significant differences were found. 8-OHdG/creatinine was increased in hypertensive smokers (P = 0.032) and women (P = 0.006). Furthermore, 8-OHdG/creatinine correlated with TNF-α, sTNF-R1, sTNF-R2 (P < 0.0001), and with IL-6 (P < 0.05). A multivariate linear regression analysis showed that gender, smoking, and TNF-α were independent factors of 8-OHdG/creatinine. CONCLUSIONS: Urinary 8-OHdG was increased in hypertensive patients with hypertrophy even under medical treatment. The presence of other cardiovascular risk factors on top of HT do not alter the concentrations of this oxidative stress marker, only smoking increasing its levels. TNF-α is an independent factor of 8-OHdG. These data suggest that this urinary marker gives specific additional information, further than blood pressure control alone, when evaluating hypertensive patients.

Urinary NT-proBNP. A valuable marker in the assessment of patients with essential hypertension.

The aim was to evaluate the usefulness of urinary N-terminal fragment of B-type natriuretic peptide (NT-proBNP) measurement for predicting the presence of left ventricular hypertrophy (LVH) in 160 asymptomatic patients with essential hypertension. The urinary NT-proBNP/creatinine ratio was higher in patients with LVH than in either those without LVH (P< .0001) or control subjects (P< .0001). Multivariate linear regression analysis identified age (P=.034), left ventricular mass index (P=.026) and serum NT-proBNP level (P=.001) as predictors of the urinary peptide level. The area under the curve for the NT-proBNP/creatinine ratio was 0.71+/-0.04 (P< .0001) for identifying LVH. Logistic regression analysis showed that the NT-proBNP: creatinine ratio was a predictor of LVH (odds ratio=4.074; P=.009). In conclusion, the urinary NT-proBNP concentration is a new marker that could be useful for identifying LVH in subjects with essential hypertension.

NT-proBNP urinario. Su valor en la caracterización de pacientes con hipertensión esencial / Urinary NT-proBNP. A valuable marker in the assessment of patients with essential hypertension

El objetivo fue evaluar el poder predictivo para diagnosticar hipertrofia del ventrículo izquierdo (HVI) de la concentración urinaria del fragmento N-terminal del propéptido natriurético tipo B (NT-proBNP) en 160 pacientes asintomáticos diagnosticados de hipertensión esencial (HT). Las concentraciones urinarias de NT-proBNP/creatinina estuvieron incrementadas en pacientes con HVI al compararlos con no hipertróficos (p < 0,0001) y controles (p < 0,0001). El análisis de regresión lineal múltiple mostró que la edad (p = 0,034), el índice de masa del ventrículo izquierdo (IMVI) (p = 0,026) y el NT-proBNP sérico (p = 0,001) predicen la concentración urinaria del péptido. El área bajo la curva de NT-proBNP/creatinina fue 0,71 ± 0,04 (p < 0,0001) para la detección de HVI, y el análisis de regresión logística mostró que NT-proBNP urinario/ creatinina predice la HVI (odds ratio = 4,074; p = 0,009). En conclusión, la concentración de NT-proBNP en orina es un nuevo marcador que puede ser de utilidad para detectar HVI en sujetos con HT esencial (AU)

The aim was to evaluate the usefulness of urinary N-terminal fragment of B-type natriuretic peptide (NT-proBNP) measurement for predicting the presence of left ventricular hypertrophy (LVH) in 160 asymptomatic patients with essential hypertension. The urinary NT-proBNP/creatinine ratio was higher in patients with LVH than in either those without LVH (P < .0001) or control subjects (P < .0001). Multivariate linear regression analysis identified age (P=.034), left ventricular mass index (P=.026) and serum NT-proBNP level (P=.001) as predictors of the urinary peptide level. The area under the curve for the NT-proBNP/creatinine ratio was 0.71±0.04 (P < .0001) for identifying LVH. Logistic regression analysis showed that the NT-proBNP: creatinine ratio was a predictor of LVH (odds ratio=4.074; P=.009). In conclusion, the urinary NT-proBNP concentration is a new marker that could be useful for identifying LVH in subjects with essential hypertension (AU)

Obese and nonobese patients with essential hypertension show similar N-terminal proBNP plasma levels.

BACKGROUND: Multiple studies have focused on the influence of obesity on natriuretic peptide levels. However, the effect of obesity on amino-terminal propeptide of B-type natriuretic peptide (NT-proBNP) levels in hypertensive (HT) patients remains uncertain. METHODS: We studied 252 asymptomatic patients (60 +/- 13 years, 136 men) with essential HT. A routine physical examination, anthropometry, laboratory analyses, echo-Doppler study, and NT-proBNP level determination were performed. RESULTS: NT-proBNP levels were similar in both obese and nonobese HT (median 56 (25-130) pg/ml vs. median 51 (26-129) pg/ml, P = 0.488). No significant differences were found in obese or nonobese patients with left ventricular hypertrophy (LVH) (median 135 (73-425) pg/ml vs. median 151 (64-274) pg/ml, P = 0.597). The area under the curve was 0.89 +/- 0.03 for NT-proBNP to diagnose LVH in the obese HT patients and 0.88 +/- 0.03 in the nonobese. A logistic regression analysis showed that age, gender, and left ventricular mass index (LVMI) were independent predictors of NT-proBNP levels. Body mass index (BMI) was not significantly associated with NT-proBNP in LVH HT patients. CONCLUSIONS: Obesity is not statistically associated with NT-proBNP levels in HT asymptomatic patients. The same results were observed in our group of patients with LVH. These data are in contrast with those previously found in heart failure, and raise questions about the role of obesity per se as primary cause of decreased NT-proBNP levels in other pathophysiological conditions.