Apolipoprotein E polymorphism modulation of asymmetric dimethylarginine in hypertensive patients is determined by renal function.

BACKGROUND: Endothelial dysfunction is considered an early step of atherosclerotic vascular disease. Asymmetric dimethylarginine (ADMA), the main endogenous inhibitor of nitric oxide synthase (NOS), plays a critical role in the process of atherosclerosis in a uremic environment. Increased plasma ADMA not only works as a cardiovascular morbidity biomarker but it is also involved in the genesis of atherosclerosis in renal disease. Considering the relationships of apolipoprotein E(ApoE) polymorphism with LDL cholesterol (LDL-C) levels and coronary risk, it is possible that it brings on susceptibility to endothelial dysfunction and atherogenesis seen on uremia. METHODS: Six hundred twenty patients were stratified according to glomerular filtration rate (GFR) estimated by Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) formula: group I > 60 mL/min, group II ≤ 60 mL/min and > 15 mL/min, and group III ≤ 15 mL/min or in hemodialysis. Polymorphic ApoE analysis was performed by polymerase chain reaction amplification (PCR). Plasma ADMA levels were measured by high performance liquid chromatography (HPLC). Groups were compared on clinical and laboratory characteristics as well as allele and genotype distribution towards. RESULTS: The ε2 allele of ApoE was present in 62 (10.3 %) patients, ε3 allele in 581 (96.2 %), and ε4 allele in 114 (18.9 %). Their distribution among the 3 groups was uniform. Such uniformity was not observed when we considered endothelial function measured by asymmetric dimethylarginine. In group III, the frequency of ε4 allele was significantly lower in the third tertile compared with the first tertile (14.7 versus 53.3 %, P = 0.000; Pearson chi-square). In groups I and II, there was no difference in allele frequency according to ADMA levels. This association remained significant even after confouding factors corrections (OR 0.329, 95 % CI 0.155 - 0.699, P = 0.004). CONCLUSIONS: The results of this study shows that the frequency of ε4 allele of ApoE is significantly lower among hypertensive patients on hemodialysis with the highest levels of ADMA. Uremia is capable of determining lower plasma ADMA levels in hypertensive ε4 allele carriers.

Diversity of apolipoprotein E genetic polymorphism significance on cardiovascular risk is determined by the presence of metabolic syndrome among hypertensive patients.

BACKGROUND: Hypertension has a significant relevance as a cardiovascular risk factor. A consistent increase on world's Metabolic Syndrome (MetS) incidence has been associated with an epidemic cardiovascular risk in different populations. Dislipidemia plays a major role determining the epidemic CV burden attributed to MetS. Apolipoprotein E (ApoE) is involved on cholesterol and triglycerides metabolism regulation. Once ApoE polymorphism may influence lipid metabolism, it is possible that it brings on individual susceptibility consequences for the development of MetS and cardiovascular risk. The objective of the study is to measure the discriminatory power of ApoE polymorphism in determining cardiovascular risk stratification based on the presence MetS in a cohort of hypertensive patients. METHODS: It was enrolled 383 patients, divided in two groups, classified by MetS presence (IDF criteria): Group 1: 266 patients with MetS (MetS +) and Group 2: 117 patients without Mets (MetS -). Patient's data were collected by clinical evaluation, physical exam, file reviews and laboratory testing. Polymorphic ApoE analysis was performed by PCR amplification. Groups were compared on clinical and laboratory characteristics as well as allele and genotype distribution towards ApoE polymorphism. Mets CVD prevalence was analysed according to E4 allele prevalence. RESULTS: The results evidenced 184 men (48%), 63,7% whites, 45,1% diabetics and 11,7% of patients were smokers. Mean age was 64,0 ± 12,0 years. When genotypic distribution was analyzed, E3/3 genotype and E3 allele frequencies were more prevalent. Among patients with MetS, we observed an independent association between CVD prevalence and E4 allele frequency (OR 2.42 (1.17- 5.0, p < 0,05)). On the opposite direction, in those without MetS, there was lesser CVD burden in E4 allele carriers (OR 0,14 (0,02-0,75)). These associations remained significant even after confounding factor corrections. CONCLUSIONS: The results presented demonstrate that the association between ApoE gene and CVD may be modulated by the presence of MetS, with an increased CV burden observed among E4 allele carriers with the syndrome. On the opposite way, E4 allele carriers without visceral obesity had lesser prevalence of CVD.

Impact of acute kidney injury exposure period among liver transplantation patients.

BACKGROUND: Acute kidney injury is a common complication of liver transplantation. In this single-centre retrospective observational study, we investigated the impact of acute kidney disease on liver recipient survival. METHODS: The study population consisted of patients who underwent a liver engraftment between January 2002 and November 2006, at a single transplantation centre in São Paulo, Brazil. Acute kidney injury diagnosis and staging were according to the recommendations of the Acute Kidney Injury Network and consisted of scanning the daily serum creatinine levels throughout the hospital stay. Patients requiring renal replacement therapy prior to transplantation, those who developed acute kidney injury before the procedure or those receiving their second liver graft were excluded from the study. RESULTS: A total of 444 liver transplantations were performed during the study period, and 129 procedures (29%) were excluded. The remaining 315 patients constituted the study population. In 207 procedures, the recipient was male (65%). The mean age of the population was 51 years. Cumulative incidence of acute kidney injury within 48 h, during the first week after transplantation, and throughout the hospital stay was 32, 81 and 93%, respectively. Renal replacement therapy was required within a week after the transplantation in 31 procedures (10%), and another 17 (5%) required replacement therapy after that period. Mean follow-up period was 2.3 years. Time in days from acute kidney injury diagnosis to initiation of replacement therapy or reaching serum creatinine peak was associated with lower overall survival even when adjusted for significant potential confounders (HR 1.03; 95% CI 1.01, 1.05; p=0.002). Overall, patients experiencing acute kidney injury lasting for a week or more before initiation of replacement therapy experienced a threefold increase in risk of death (HR 3.02; 95% CI 2.04, 4.46; p<0.001). CONCLUSIONS: Acute kidney injury after liver transplantation is remarkably frequent and has a substantial impact on patient survival. Delaying the initiation of renal replacement therapy in such population may increase mortality by more than 20% per day.

Relationship among end-stage renal disease, hypertension, and sleep apnea in nondiabetic dialysis patients.

BACKGROUND: Cardiovascular diseases (CVD) are responsible for more than 50% of the deaths in patients with end-stage renal disease (ESRD). Sleep apnea (SA) has been recognized as a risk factor for CVD. Previous studies have shown a higher prevalence of SA among patients on dialysis. METHODS: Forty-five nondiabetics patients with ESRD underwent a polysomnographic analysis with concomitant clinical evaluation and laboratory tests. Fourteen patients (31.1%) presented with an apnea/hypopnea index (AHI) more than 5, confirming a high prevalence of SA. We observed abnormal sleep pattern with high percentages of sleep stage 1 and low percentages of sleep stages 3 and 4. RESULTS: Patients with AHI more than 5 presented higher levels of systolic, diastolic, and mean blood pressures (MBP) as compared with those with AHI less than 5 (P < .05). When other variables were compared (age, time of dialytic treatment, cause of ESRD, use of antihypertensive drugs, body mass index, serum levels of hemoglobin, hematocrit, creatinine, KT/V index, pH, bicarbonate, parathormone, and alkaline phosphatase), no differences were found between the two groups. In a logistic regression model, MBP and age more than 40 years were positively related to the presence of SA. CONCLUSIONS: Our study is in agreement with previous works and shows that patients with ESRD have a higher SA index compared to those with normal renal function. In spite of having higher levels of BP no other parameter was different among apneic and nonapneic patients. Hypertension may play a pivotal role linking SA and CVD.

Association of IL-6 polymorphism -174G/C and metabolic syndrome in hypertensive patients.

INTRODUCTION: Visceral obesity, the central core of metabolic syndrome (MetS), is conceived as the pathogenic basis of an increased cardiovascular burden and is related with changes in cytokines. We investigated whether IL-6-174G/C gene polymorphism is associated with MetS prevalence in hypertensive patients. METHOD: A population of hypertensive patients was included and stratified by the presence of MetS according to IDF criteria and evaluated by Framingham risk score. The IL-6-174G/C genotyping was performed by polymerase chain reaction and the prevalence of MetS was compared between "C" carrier and "non-C" carrier groups. RESULTS: From an original sample of 664 patients, 612 (34.2% men, age 57.3 ± 10.1, 30.4% diabetics) were included. MetS was diagnosed in 51.3% of total population and "C" carriers demonstrated high prevalence of MetS (P < 0.05) and each of its components. On binary logistic regression, it was observed that the IL-6 polymorphism was independently associated with occurrence of MetS, even after adjusting for covariates (OR 1.13-2.37, 95% CI, P < 0.05). CONCLUSION: The C allele at the -174 locus of IL-6 gene is independently associated with the occurrence of metabolic syndrome, emphasizing the importance of inflammatory genetic background in the pathogenesis of visceral obesity and related cardiovascular burden.

Cholesterol goal attainment in hypertensive patients: the impact of metabolic syndrome components.

BACKGROUND: Hypertension and dyslipidemia are potentially modifiable cardiovascular risk factors. METHODS: We studied hypertensive outpatients regarding goal attainment in controlling dyslipidemia, according to individual cardiovascular risk profile, following the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines. Factors of goal attainment for low-density lipoprotein cholesterol (LDL-C) were determined. RESULTS: Of the 1,202 patients, this study included 886 (73.8% female, 59.9±11.1 years) with available data to determine cardiovascular risk. Overall, 544 (61.4%) had LDL-C within the goal. Individuals with inappropriate LDL-C were older, had higher systolic blood pressure (SBP), and were more likely to have metabolic syndrome, diabetes, and cardiovascular disease (CVD) and were less likely to show a controlled blood pressure. There was a progressive worsening of LDL-C control as the number of components of metabolic syndrome increased. There was also a progressive increase in the percentage of patients with inappropriate LDL-C with the increase in cardiovascular risk. In a logistic regression model including LDL-C inadequacy as a dependent variable, only age, diabetes, and CVD were predictors of inappropriate LDL-C. Moreover, even with correction for demographic and clinical variables, the inappropriate LDL-C was an independent predictor of CVD. CONCLUSIONS: The control of dyslipidemia in hypertensive patients is far from ideal and results are even worse in individuals with CVD.

Síndrome da apnéia do sono: causa de hipertensão arterial e de refratariedade ao tratamento anti-hipertensivo / Sleep apnea syndrome as a cause of hypertension and its clinical relevance

A síndrome da apnéia do sono tem sido considerada causa de hipertensão arterial secundária, caracterizada pela ausência de descenso noturno da pressão arterial e típica refratariedade ao tratamento medicamentoso. O principal mecanismo de desenvolvimento de hipertensão relaciona-se à hiperatividade simpática, determinada pelos episódios recorrentes de apnéia e hipoxemia, com subsequentes despertares. O tratamento da SAS com o uso do CPAP nasal corrige de maneira importante as principais conseqüências do quadro de apnéias e hipopnéias repetidas. O efeito do CPAP sobre os níveis tensionais é controverso, porém parece haver uma redução do risco cardiovascular, principalmente quando associado ao tratamento não-farmacológico, principalmente representado pela redução do peso em obesos, e à intensificação do tratamento medicamentoso, destacadamente com drogas bloqueadoras do sistema nervoso simpático. A consideração da possibilidade de SAS é essencial em pacientes com hipertensão arterial refratária, principalmente obesos e com alto risco cardiovascular