MicroRNA profiling identifies miR-7-5p and miR-26b-5p as differentially expressed in hypertensive patients with left ventricular hypertrophy

Recent evidence suggests that cell-derived circulating miRNAs may serve as biomarkers of cardiovascular diseases. However, a few studies have investigated the potential of circulating miRNAs as biomarkers for left ventricular hypertrophy (LVH). In this study, we aimed to characterize the miRNA profiles that could distinguish hypertensive patients with LHV, hypertensive patients without LVH and control subjects, and identify potential miRNAs as biomarkers of LVH. LVH was defined by left ventricular mass indexed to body surface area >125 g/m2 in men and >110 g/m2 in women and patients were classified as hypertensive when presenting a systolic blood pressure of 140 mmHg or more, or a diastolic blood pressure of 90 mmHg or more. We employed miRNA PCR array to screen serum miRNAs profiles of patients with LVH, essential hypertension and healthy subjects. We identified 75 differentially expressed miRNAs, including 49 upregulated miRNAs and 26 downregulated miRNAs between LVH and control patients. We chose 2 miRNAs with significant differences for further testing in 59 patients. RT-PCR analysis of serum samples confirmed that miR-7-5p and miR-26b-5p were upregulated in the serum of LVH hypertensive patients compared with healthy subjects. Our findings suggest that these miRNAs may play a role in the pathogenesis of hypertensive LVH and may represent novel biomarkers for this disease.

Addition of N-terminal Pro-B-type Natriuretic Peptide Levels to Electrocardiography Criteria for Detection of Left Ventricular Hypertrophy: The ARIRANG Study

The utility of electrocardiography (ECG) in screening for left ventricular hypertrophy (LVH) in general populations is limited mainly because its low sensitivity. B-type natriuretic peptide (BNP) is released due to the remodeling processes of LVH and could improve the diagnostic accuracy for the ECG criteria for LVH. We hypothesized that addition of BNP levels to ECG criteria could aid LVH detection compared with ECG alone in a general population. We enrolled consecutive 343 subjects from a community-based cohort. LVH was defined as LV mass index > 95 g/m2 for females and > 115 g/m2 for males according to echocardiography. The area under the receiver operator characteristic (ROC) curve to detect LVH was 0.55 (95% confidence interval [CI], 0.50-0.61) in Sokolow-Lyon criteria and 0.53 (0.47-0.59) in the Cornell voltage criteria. After addition of N-terminal-proBNP levels to the model, the corresponding areas under the ROC were 0.63 (0.58-0.69) and 0.64 (0.59-0.69), respectively. P values for the comparison in areas under the ROC for models with and without N-terminal-proBNP levels were < 0.001. These data suggest that addition of N-terminal-proBNP levels to ECG criteria could significantly improve the diagnostic accuracy of LVH in general populations.

Hipertrofia ventricular e mortalidade cardiovascular em pacientes de hemodiálise de baixo nível educacional / Ventricular hypertrophy and cardiovascular mortality in hemodialysis patients with low educational level / Hipertrofia ventricular y mortalidad cardiovascular en pacientes de hemodiálisis de bajo nivel educativo

FUNDAMENTO: A hipertrofia ventricular esquerda é potente preditor de mortalidade em renais crônicos. Estudo prévio de nosso grupo mostrou que renais crônicos com menor escolaridade têm hipertrofia ventricular mais intensa. OBJETIVO: Ampliar estudo prévio e verificar se a hipertrofia ventricular esquerda pode justificar a associação entre escolaridade e mortalidade cardiovascular de pacientes em hemodiálise. MÉTODOS: Foram avaliados 113 pacientes entre janeiro de 2005 e março de 2008 e seguidos até outubro de 2010. Foram traçadas curvas de sobrevida comparando a mortalidade cardiovascular, e por todas as causas dos pacientes com escolaridade de até três anos (mediana da escolaridade) e pacientes com escolaridade igual ou superior a quatro anos. Foram construídos modelos múltiplos de Cox ajustados para as variáveis de confusão. RESULTADOS: Observou-se associação entre nível de escolaridade e hipertrofia ventricular. A diferença estatística de mortalidade de origem cardiovascular e por todas as causas entre os diferentes níveis de escolaridade ocorreu aos cinco anos e meio de seguimento. No modelo de Cox, a hipertrofia ventricular e a proteína-C reativa associaram-se à mortalidade por todas as causas e de origem cardiovascular. A etiologia da insuficiência renal associou-se à mortalidade por todas as causas e a creatinina associou-se à mortalidade de origem cardiovascular. A associação entre escolaridade e mortalidade perdeu significância estatística no modelo ajustado. CONCLUSÃO: Os resultados do presente trabalho confirmam estudo prévio e demonstram, ademais, que a maior mortalidade cardiovascular observada nos pacientes com menor escolaridade pôde ser explicada por fatores de risco de ordem bioquímica e de morfologia cardíaca.

BACKGROUND: Left ventricular hypertrophy is a strong predictor of mortality in chronic kidney patients. A previous study of our group has shown that chronic kidney patients with low educational level has more severe ventricular hypertrophy. OBJECTIVE: To extend a previous study and to assess whether left ventricular hypertrophy can explain the association between schooling and cardiovascular mortality in hemodialysis patients. METHODS: This study assessed 113 patients from January 2005 to March 2008 and followed them up until October 2010. Survival curves were built to compare all-cause and cardiovascular mortality of patients with up to three years of schooling (median schooling) and those with schooling of four years and over. Cox multiple models were built and adjusted to confounding variables. RESULTS: Association between educational level and ventricular hypertrophy was observed. Statistical difference in all-cause and cardiovascular mortality between the different educational levels was observed at 5.5 years of follow-up. In the Cox model, ventricular hypertrophy and C-reactive protein associated with all-cause and cardiovascular mortality. The etiology of kidney failure associated with all-cause mortality, and creatinine associated with cardiovascular mortality. The association between educational level and mortality lost statistical significance in the adjusted model. CONCLUSION: The results of this study confirm those of a previous study. In addition, they show that the higher cardiovascular mortality observed in patients with low educational level can be explained by risk factors of biochemical and cardiac morphological origin.

FUNDAMENTO: La hipertrofia ventricular izquierda es potente predictor de mortalidad en renales crónicos. Estudio previo de nuestro grupo mostró que renales crónicos con menor escolaridad tienen hipertrofia ventricular más intensa. OBJETIVO: Ampliar estudio previo y verificar si la hipertrofia ventricular izquierda puede justificar la asociación entre escolaridad y mortalidad cardiovascular de pacientes en hemodiálisis. MÉTODOS: Fueron evaluados 113 pacientes entre enero de 2005 y marzo de 2008 y seguidos hasta octubre de 2010. Fueron trazadas curvas de sobrevida comparando la mortalidad cardiovascular, y por todas las causas de los pacientes con escolaridad de hasta tres años (mediana de la escolaridad) y pacientes con escolaridad igual o superior a cuatro años. Fueron construidos modelos múltiples de Cox ajustados para las variables de confusión. RESULTADOS: Se observó asociación entre nivel de escolaridad e hipertrofia ventricular. La diferencia estadística de mortalidad de origen cardiovascular y por todas las causas entre los diferentes niveles de escolaridad ocurrió a los cinco años y medio de seguimiento. En el modelo de Cox, la hipertrofia ventricular y la proteína-C reactiva se asociaron a la mortalidad por todas las causas y de origen cardiovascular. La etiología de la insuficiencia renal se asoció a la mortalidad por todas las causas y la creatinina se asoció a la mortalidad de origen cardiovascular. La asociación entre escolaridad y mortalidad perdió significación estadística en el modelo ajustado. CONCLUSÓN: Los resultados del presente trabajo confirman estudio previo y demuestran, además, que la mayor mortalidad cardiovascular observada en los pacientes con menor escolaridad puede ser explicada por factores de riesgo de orden bioquímico y de morfología cardíaca.

Cardiotrofina-1 circulante puede diferenciar la hipertrofia ventricular fisiológica del atleta de la hipertrofia patológica del paciente hipertenso / Corculating cardiotrophyn-1 may help differenciate left ventricular hypertrophy seen in athletes from pathologic left ventricular hypertrophy associated to hypertension

Introducción: Cardiotrofina-1 (CT-1), una citoquina perteneciente a la superfamilia de la interleukina-6, se encuentra elevada en pacientes con hipertensión arterial (HTA) e hipertrofia ventricular izquierda (HVI). Sus niveles se correlacionan con el tamaño auricular izquierdo y con las presiones de llenado del ventrículo izquierdo. Los niveles de CT-1 en atletas con HVI fisiológica no han sido investigados. Métodos: Estudio transversal. Se incluyeron pacientes con HTA esencial con y sin evidencia ecográfica de cardiopatía hipertensiva (CH)(HVI y relación E/E´>10), recientemente diagnosticada y sin tratamiento. Un grupo de atletas normotensos con diagnóstico ecográfico de HVI y un grupo control de sujetos normotensos pareados por edad y sexo. En todos los sujetos se midieron los niveles plasmáticos de CT-1 (ELISA). Se definió HVI utilizando el índice de masa ventricular izquierda con ecocardiograma usando la fórmula de Devereux (hombres ≥ 115 gramos/m2, mujer ≥ 95 gramos/m2). Las presiones de llenado del VI se estimaron con la relación E/E’ (doppler tisular en el anillo mitral medial). Resultados: Se incluyeron 10 pacientes por grupo. Los atletas con HVI presentaron una relación E/E´ < a 10, y ésta no fue distinta al grupo control y a la de los hipertensos sin HVI y fue significativamente menor respecto de los hipertensos con CH (6,5 +/- 1 versus 12,9 +/- 1,1, p < 0,01). Respecto de los niveles de CT-1 los atletas con HVI presentaban niveles menores que los pacientes hipertensos con evidencia de CH (6,6 fmol/ml +/- 0,4 versus 18,2 fmol/ml +/- 5,6, p < 0,001) y niveles similares al grupo control y de hipertensos sin evidencia de CH. Conclusión: En atletas con HVI los niveles de CT-1 son similares a los de sujetos normotensos y a los de pacientes hipertensos sin HVI, y significativamente menores respecto a los de pacientes hipertensos con niveles similares de HVI y disfunción diastólica.

Background: Cardiotrophyn-1 (CT-1), is a cytokine which is increased in patients with hypertension (HT) and left ventricular hypertrophy (LVH). This increase occurs in proportion to left atrial size and left ventricular filling pressures. CT-I levels in athletes with LVH have not been investigated Methods:Crossectional study. We evaluated; a) hypertensive patients with LVH and E/E> 10 by echocardiography, recently diagnosed and receiving no medications; b) normotensive athletes with LVH as shown by echocardiography, and c) normotensive subjects, paired by age and sex. Plasma levels of CT-i (ELISA) were measured in all. L VH was defined as left ventricular mass index> 115 G/m2 (males) or> 95 G/m2 (females). Results: EIE’ was lower in athletes than hypertensive patients with LVH (6.5 +/- I vs 12.9 +/- II, p<0.01). EIE’ in both control subjects and patients with HTA but no LVH did not differ from EIE’ in athletes. CT-I was lower in athletes than patients with HTA and LVH (6.6 +/- 0.4 vs 18.2 +/- 5.6 fmol/ml, respectively, p<0.00l). CT-I levels in control subjects and hypertensive patients without LVH did not differ from that found in athletes. Conclusion: CT-I levels are similar in athletes compared to normal subjects and patients with HTA and no LVH. Hypertensive patients with similar grades of LVH and left ventricular diastolic dysfunction had significantly greater leves of CT-I. Thus, CT-I levels could help differentiate pathological HVI from physiologic LVH in athletes

A gravidade da lesão do fundo de olho e o padrão de hipertrofia ventricular esquerda na hipertensão arterial sistêmica refratária ao tratamento / Severity of retinopathy and left ventricular hypertrophy pattern in treatment-resistant systemic arterial hypertension

Fundamentos:A avaliação dos órgãos-alvo na hipertensão arterial refratária ao tratamento(HRT) permite uma estratificação prognóstica. Objetivo:Relacionar a lesão no fundo de olho (FO) com o padrão de hipertrofia ventricular esquerda(HVE) e os níveis médios de pressão sistólica nas 24h, na HRT. Métodos:Estudo transversal com 194 sujeitos do ambulatório de hipertensão arterial(INC-MS), sendo 42(21,6 por cento) com HRT. A retinopatia foi classificada de acordo com keith-wagener-backer(KWB); as variáveis analisadas ecocardiograficamente foram: índice de massa do VE(IMVE), para o diagnóstico de HVE; e a espessura relativa de parede do VE(ERP), para avaliar o padrão, se concêntrica(C) ou excêntrica(E). Foi estudada a pressão sistólica média de 24 hs(PSM24H) obtida pela MAPA. A análise dos dados foi testada por t de student, oneway ANOVA e quiquadrado ou exato de fisher para tabelas de contingência(a<0,05). Resultados: Todos os pacientes com HRT apresentavam lesão no FO e HVE. Foram estratificados em quatro grupos, segundo o FO(KWBII e KWBIII) e o ecocardiograma(HVEC e HVE E). Não houve diferença nos parâmetros antropométricos entre os grupos (p=NS) e na distribuição de HVE C e E entre os sujeitos com KWB II e KWB III (x=1,84; p=0,17). Nos indivíduos com HVE E(p<0,001) o que não foi observado nos KWB II e KWB III(p=NS). Conclusão: Nos sujeitos com HRT, lesões de FO e HVE foram dominantes. Os níveis de PSM24H elevados estão associados ao HVE C, mas não ao FO.

Relación entre hiperinsulinemia, disfunción diastólica e hipertrofia del ventrículo izquierdo en pacientes con hipertensión arterial sistémica / Association of hyperinsulinemia with left ventricular hypertrophy and diastolic dysfunction in patients with hypertension

Background: Hypertension is the main independent cardiovascular risk factor. However, there are additional factors that induce organic damage. Aim: To assess the association between hyperinsulinemia, ventricular hypertrophy and left ventricular diastolic function. Patients and Methods: Seventy-four patients aged 30 to 65 years, with mild or moderate systemic hypertension, with overweight or mild obesity and normal glucose tolerance curve (GTC), were studied. Serum insulin was measured during GTC. The maximum levels of insulin and glucose were observed 60 minutes after the oral glucose load and they were expressed as rG/1. Patients were stratified in three groups according to their glucose and insulin fasting levels (I0) and post-glucose challenge levels (rG/I): Group 1 (normoinsulinemic patients) I0 <17 mU/mL and rG/I >2 (2.45+0.4). Group 2 (post-prandial hyperinsulinemic patients) I0 <17 mU/mL and rG/I <2> 1 (1.34+0.3). Group 3 (persistently hyperinsulinemic patients) I0 >17 mU/mL and <1 (0.7+0.3). Left ventricular mass and its diastolic function were measured by Doppler echocardiography. Results: No differences in blood pressure or age were observed between groups. There was a negative correlation between ventricular mass and rG/1 (r =-0.282, p =0.015). Left ventricular diastolic dysfunction was significantly more deteriorated in group 3, as compared with group 1 (p <0.001 ANOVA). There was a significant correlation between g/GI and diastolic dysfunction (r =0.232 p =0.047). Conclusions: Fasting, post challenge hyperinsulinemia and a rG/I <1 are associated with higher ventricular mass and left ventricular diastolic dysfunction, independent of blood pressure and age.

Relations of serum aldosterone and microalbuminuria to left ventricular hypertrophy in patients with essential hypertension

Left ventricular hypertrophy [LVH] is an independent risk factor for cardiovascular morbidity and mortality in hypertensive patients. The identification of risk factors for the initiation of LVH in patients with hypertension [HTN] is important including microalbuminunuria [MAU] and hyperaldosteronism. Evaluation of the relationship of MAU and plasma aldosterone to blood pressure [BP] and LVH in patients with essential HTN. Thirty male patients with essential HTN and 15 healthy subjects as a control group were subjected to thorough clinical examination, transthoracic echocardiography, lipid profile, serum potassium, and serum aldosterone estimation. MAU was evaluated with dipstick Micral-II Test of fasting midstream morning urine on two successive days. Left ventricular mass index [LVMI] was calculated and values >134gm/m[2] were considered as LVH. Patients with LVMI >134 gm/m[2] had higher serum aldosterone, BMI, Interventricular septal thickness [IVST], Posterior wall thickness [PWT] and Relative wall thickness [RWT]. Serum aldosterone was significantly higher among the test hypertensive group and was positively correlated correlated with LVMI, RWT, PWT, IVST, LVM and negatively correlated with LV diastolic dimensions. MAU was positively correlated with systolic BP, Pulse pressure, BMI and LVMI and a strong relationship between MAU and serum aldosterone was detected. Aldosterone is an important contributor to the development of LVH and hypertensive nephropathy and strong relation between microalbuminuria and aldosterone is detected. The Value of selective aldosterone blockers in preventing target organ damage [TOD] awaits further investigation

The role of secondary hyperparathyroidism in left ventricular hypertrophy of patients under chronic hemodialysis

End-stage renal disease (ESRD) patients frequently develop structural cardiac abnormalities, particularly left ventricular hypertrophy (LVH). The mechanisms involved in these processes are not completely understood. In the present study, we evaluated a possible association between parathyroid hormone (PTH) levels and left ventricular mass (LVM) in patients with ESRD. Stable uremic patients on intermittent hemodialysis treatment were evaluated by standard two-dimensional echocardiography and their sera were analyzed for intact PTH. Forty-one patients (mean age 45 years, range 18 to 61 years), 61 percent males, who had been on hemodialysis for 3 to 186 months, were evaluated. Patients were stratified into 3 groups according to serum PTH: low levels (<100 pg/ml; group I = 10 patients), intermediate levels (100 to 280 pg/ml; group II = 10 patients) and high levels (>280 pg/ml; group III = 21 patients). A positive statistically significant association between LVM index and PTH was identified (r = 0.34; P = 0.03, Pearson's correlation coefficient) in the sample as a whole. In subgroup analyses, we did not observe significant associations in the low and intermediate PTH groups; nevertheless, PTH and LVM index were correlated in patients with high PTH levels (r = 0.62; P = 0.003). LVM index was also inversely associated with hemoglobin (r = -0.34; P = 0.03). In multivariate analysis, after adjustment for age, hemoglobin, body mass index, and blood pressure, the only independent predictor of LVM index was PTH level. Therefore, PTH is an independent predictor of LVH in patients undergoing chronic hemodialysis. Secondary hyperparathyroidism may contribute to the elevated cardiovascular morbidity associated with LVH in ESRD.

Disminución de receptores cardíacos para el factor de crecimiento análogo a la insulina tipo I en la hipertrofia ventricular hipertensiva experimental / Decrease of type I insulin-like growth factor cardiac receptors of the hypertensive experimental ventricular hypertrophy

La hipertrofia ventricular es una respuesta celular a la sobrecarga de presión. Se ha sugerido que el factor de crecimiento análogo a la insulina, tipo I (IGF-I), un polipéptido con mecánismo de acción paracrino y/o endocrino, puede participar como estímulo para el crecimiento celular cardiaco. Usando RIA determinamos los niveles séricos de IGF-I en ratas hipertensas por el mecánismo de Goldblatt de 2 riñones-1 clamp, 9 semanas después de la operación. La hipertrofia ventricular fue evaluada por peso ventricular en relación a peso corporal y por la relación de peso del ventrículo izquierdo al ventrículo derecho. El número de receptores cardiacos de IGF-I de alta afinidad fue determinado por la unión de 125-I IGF-I a las membranas ventriculares a las 3, 6 y 9 semanas siguientes a la cirugía. En relación a los controles, se observó una significativa (p< 0,05) hipertensión sistólica en cada punto: 184 vs 136, 196 vs 131 y 197 vs 136 mmHg, respectivamente. Se documentó hipertrofia ventricular izquierda (relación de peso con VD): 4,8 vs 3,7, 4,6 vs 3,6 y 4,4 vs 3,7. El número de receptores de IGF-I (fmol/mg protein) en los mismos periodos fue 1,6 vs 4,1, 2,3 vs 7,5 y no detectable vs 3,0. Los niveles séricos de IGF-I fueron determinados sólo a las 9 semanas y fueron similares en los animales tratados que en los controles (452 vs 469). Los errores estándar de todos los valores dados fueron menores de 5 por ciento del promedio. La progresiva disminución de los receptores cardiacos de IGF-I puede reflejar un aumento de los niveles tisulares de IGF-I, más aún cuando el nivel sérico de IGF-I no difirió entre los animales tratados y los controles