Interrelationships between B-type natriuretic peptides and vitamin D in patients on maintenance peritoneal dialysis.

OBJECTIVE: Experimental evidence suggests that vitamin D deficiency impairs cardiac structure and function. Our objective was to observe relationships between circulating levels of the cardiac natriuretic peptides and vitamin D levels in patients on chronic peritoneal dialysis. METHOD: Measurements were made of circulating levels of 25-hydroxyvitamin D [25(OH)D] and plasma B-type natriuretic peptide (BNP) levels in patients receiving chronic peritoneal dialysis. RESULTS: Both BNP and the 1-76 amino-terminal fragment of pro-BNP correlated inversely with 25(OH)D levels (rs = -0.60, p = 0.007, and rs = -0.64, p = 0.003, respectively) in patients on peritoneal dialysis. CONCLUSIONS: Vitamin D deficiency in chronic renal failure may impair cardiac function, as manifested by elevated levels of B-type cardiac natriuretic peptides.

Potential benefits of controlling coronary heart disease risk factors in the United Arab Emirates.

BACKGROUND: Cardiovascular risk factors including obesity, diabetes, hypertension, and dyslipidemia, are highly prevalent in the United Arab Emirates. In spite of significant awareness initiatives, little is known about the potential benefits of controlling these risk factors. AIMS: To assess the prevalence of preventable risk factors for coronary heart disease (CHD), and the likely benefits of controlling these risk factors. METHODS: In a health survey stratified by self-reported hypertension, we enrolled 349 hypertensive and 641 normotensive subjects of diverse ethnicity in Al-Ain city, and measured CHD risk factors. We used the Framingham risk score to estimate the proportion of CHD potentially preventable by controlling hypertension, dyslipidemia, diabetes mellitus (DM), and smoking. RESULTS: Smoking was similar in the two groups (hypertensives 13.2% vs. normotensives 14.2%). The prevalence of diabetes, dyslipidemia [mean (SD) triglycerides, high-density lipoprotein-cholesterol (HDL-C)], overweight/obesity, and thus the 10-year Framingham risk were all significantly (p < 0.001) higher among hypertensive than normotensives. CONCLUSION: Prevention of type 2 DM, aggressive control of hypertension and dyslipidemia, and smoking cessation could potentially reduce the 10-year incidence of CHD. Barriers include lack of awareness of this problem among the general population and health care providers.

Prevalence and determinants of microalbuminuria among diabetic patients in the United Arab Emirates.

BACKGROUND: Microalbuminuria (MA) represents the earliest clinical evidence of diabetic nephropathy and is a predictor of increased cardiovascular morbidity and mortality. The aim of this study was to determine the prevalence of MA among diabetic patients in the Al-Ain district of the United Arab Emirates (UAE). METHODS: The study was part of a general cross-sectional survey carried out to assess the prevalence of diabetes mellitus (DM) complications in Al-Ain district, UAE and was the first to assess the prevalence of MA among diabetic patients. A sample of 513 diabetic patients with a mean age of 53 years (SD: +/- 13) was randomly selected during 2003/2004. All patients completed an interviewer-administered questionnaire and underwent medical assessment. First morning urine collections were obtained and were tested for clinical proteinuria using urine dipsticks and for MA using the single Micral-Test II strips. RESULTS: MA was found in 61% (95% CI: 56.7-65.7) of the sample and the rate was significantly higher among males, positively related to body mass index (BMI), type 2 DM and presence of other DM complications such as diabetic retinopathy and neuropathy. Of the total sample population, 12.5% (95% CI: 8.1-14.1) had clinical proteinuria. CONCLUSION: The prevalence rate of MA was considerably high ( 61%) among diabetic patients in the UAE. Therefore, regular screening for MA is recommended for all diabetic patients, as early treatment is critical for reducing cardiovascular risks and slowing the progression to late stages of diabetic nephropathy (overt proteinuria and end-stage renal disease).

Low IGF-1 levels are associated with cardiovascular risk factors in haemodialysis patients.

Cardiovascular diseases (CVD) constitute a significant risk and may, in part, explain the high morbidity and mortality rates among haemodialysis (HD) patients. Several studies have implicated reduced insulin like growth factor (IGF-1) levels in the development of CVD. However, it is not clear whether IGF-1, and its relationship with other hormones such as leptin, insulin, and growth hormone (GH), as well as anthropometric variables may explain the high incidence of vascular complications in chronic kidney disease (CKD) patients. This study was designed to measure total serum IGF-1, leptin, insulin and GH levels in CKD patients and in age-matched control subjects and to elucidate the relationship between IGF-1 and GH, leptin, and insulin as well as other known aetiological risk factors for CVD including blood pressure, body mass index (BMI), and age. The study consisted of 50 CKD patients [36 M and 14 F; mean age; 41.8 +/- 10.3 years) on maintenance haemodialysis and 50 healthy control subjects (36 M and 14 F; mean age 41.6 +/- 10.2 years) matched for age and sex. None of the subject among patients and controls reported either smoking or history of diabetes mellitus. The circulating levels of IGF-1 were significantly lower (P < 0.001) in both male and female patients compared to the control subjects. Moreover, IGF-1 was strongly and inversely correlated with both systolic blood pressure (SBP) (r = -0.360; P < 0.01) and diastolic blood pressure (DBP) (r = -0.512; P < 0.001) in the CKD group, and when the two groups were combined SBP (r = -0.396; P < 0.001) and DBP (r = -0.296; P < 0.01). When adjusted for age, the correlation was more significant, however, when adjusted for BMI no significant correlation was observed between IGF-1 and blood pressure. IGF-1 was inversely correlated with age (r = -0.367; P < 0.01) and BMI (r = -0.310; P < 0.05) in the control group, but not the patient group. In controls and patients, respectively, a positive correlation between leptin and BMI (r = 0.358; P < 0.01; r = 0.640, P < 0.001) was observed. The results show that circulating levels of IGF-1 were significantly lower in CKD patients as compared to healthy normal subjects and were inversely correlated with SBP and DBP independent of age, but not BMI indicative of a strong relationship between cardiovascular risk factors and low IGF-1 levels. Although, the data do not clearly indicate low IGF-1 levels as a cause or an effect of these cardiovascular risk factors, they do point to an interesting relationship between low IGF-1 levels and increased cardiovascular risk factors among CKD patients as compared to age-matched healthy control subjects.

Alterations in atrial natriuretic peptide and its receptor levels in long-term, streptozotocin-induced, diabetes in rats.

Diabetes mellitus (DM) shows a markedly increased incidence of cardiovascular pathology that leads to hypertension, endothelial macro- and microangiopathy, diabetic nephropathy, and myocardial infarction. Atrial natriuretic peptide (ANP), is a 28 amino acid peptide hormone synthesized mainly by the heart atria and ventricles. It has potent diuretic and natriuretic properties. In this article the effect of long-term DM on blood plasma, kidney, and heart atrial and ventricular ANP concentrations were evaluated in streptozotocin (STZ)-induced 8-month diabetic and control rats by using radioimmunoassay (RIA). Moreover, ANP receptors in STZ-induced, 8-month diabetic rat kidneys were studied by receptor autoradiography. In addition, the expression of ANP concentrations in the kidney of diabetic and control rats was evaluated by means of immunohistochemistry. Body weight loss and increased blood glucose levels were used as indices of DM in the STZ-induced diabetic rats. Our results showed significantly higher ANP concentrations in diabetic plasma (P < 0.05), kidney (P < 0.01), heart atria (P < 0.05), and ventricles (P < 0.01) compared to controls. We also demonstrated a significant decrease in ANP receptors in the outer cortex (P < 0.05), juxtaglomerular medulla (P < 0.05), and papilla (P < 0.05) of 8-month diabetic rat kidneys compared to controls. The observed increase in ANP levels in plasma and kidney could play a role in the development of diabetic nephropathy: probably by reducing the levels of ANP receptors in diabetic kidney. Furthermore, the role of ANP in the STZ-induced diabetic heart merits additional study.

Circulating levels of endothelin-1 in a homogenous Gulf Arab population with untreated essential hypertension.

BACKGROUND: Racial variations are reported in the natural history of hypertension. For example, hypertension is significantly more prevalent in blacks than whites. Endothelial cells are important regulators of vascular tone and homeostasis, in part through secretions of vasoactive substances including endothelin-1 (ET-1), a small peptide with potent vasopressor actions. In black hypertensives, ET-1 levels are higher than in normotensive blacks and in both hypertensive and normotensive whites. Since ET-1 might play a significant role in the development and severity of hypertension in the indigenous Arab population of the United Arab Emirates, we investigated the circulating levels of ET-1 in this homogenous population. PATIENTS AND METHODS: ET-1 levels were measured in plasma samples from 60 untreated hypertensive Arabs and compared with 60 age- and sex-matched normotensive controls. RESULTS: ET-1 levels were significantly higher in hypertensives (mean 10.1 +/- 1 pmol/L) than normotensives (mean 2.2 +/- 0.5 pmol/L). Body mass index (BMI) was slightly higher among the hypertensives. For all subjects these levels significantly (P < 0.001) correlated with systolic blood pressure and less significantly (P < 0.05) with diastolic blood pressure and body weight. The correlation between ET-1 and both systolic and diastolic blood pressure was persistently significant after adjusting for BMI. CONCLUSION: Plasma concentrations of ET-1 are significantly higher in hypertensive Gulf Arabs as compared with reported levels in white hypertensives and ET-1 could be a risk factor for cardiovascular diseases in this population. The endothelial system might be particularly important with respect to hypertension in this racial group and merits further study.

Under- treatment and under diagnosis of hypertension: a serious problem in the United Arab Emirates.

BACKGROUND: Hypertension, notably untreated or uncontrolled, is a major risk factor for cardiovascular diseases (CVD) morbidity and mortality. In countries in transition, little is known about the epidemiology of hypertension, and its biochemical correlates. This study was carried out in Al Ain, United Arab Emirates, to characterize self-reported (SR) normotensives and hypertensives in terms of actual hypertension status, demographic variables, CVD risk factors, treatment, and sequalae. METHODS: A sample, stratified by SR hypertensive status, of 349 SR hypertensives (Mean age +/- SD; 50.8 +/- 9.2 yrs; Male: 226) and 640 SR normotensives (42.9 +/- 9.3 yrs, Male: 444) among nationals and expatriates was used. Hypertensives and normotensive subjects were recruited from various outpatient clinics and government organizations in Al-Ain city, United Arab Emirates (UAE) respectively. Anthropometric and demographic variables were measured by conventional methods. RESULTS: Both under-diagnosis of hypertension (33%) and under-treatment (76%) were common. Characteristics of undiagnosed hypertensives were intermediate between normotensives and SR hypertensives. Under-diagnosis of hypertension was more common among foreigners than among nationals. Risk factors for CVD were more prevalent among SR hypertensives. Obesity, lack of exercise and smoking were found as major risk factors for CVD among hypertensives in this population. CONCLUSION: Hypertension, even severe, is commonly under-diagnosed and under-treated in the UAE. Preventive strategies, better diagnosis and proper treatment compliance should be emphasized to reduce incidence of CVD in this population.

Plasma BNP in patients on maintenance haemodialysis: a guide to management?

The number of patients requiring long-term haemodialysis is increasing throughout the world. Cardiovascular disease is much more common in these patients than in the general population and accounts for the majority of deaths. New approaches to management are clearly needed to reduce this excessive cardiovascular burden. We propose that circulating levels of the cardiac natriuretic peptides, B-type natriuretic peptide (BNP) in particular, might provide a useful, objective guide to the management of their hydration status and pharmacotherapy. An overview of the literature shows that plasma levels of the cardiac natriuretic peptides are increased in this patient population and reflect cardiac preload and afterload along with cardiac pathology, thereby providing an index of cardiovascular (especially cardiac) stress and distress. Circulating levels of the cardiac peptides change in parallel with cardiac load, especially across haemodialysis. Furthermore, there is robust evidence that natriuretic peptide levels are predictive of cardiovascular outcome in these patients. Accordingly, we hypothesize that management of their haemodialysis, and pharmacotherapy designed specifically to lower plasma BNP levels to, or close to, the normal range, will reduce the excessive burden on the cardiovascular system and thereby ultimately lower the incidence of cardiovascular disease. We outline, in broad terms, how a trial to test this hypothesis might be designed.

Plasma concentrations of non-esterified fatty acids in chronic renal failure in the United Arab Emirates.

OBJECTIVE: In end-stage renal failure, dyslipoproteinemia is linked to risk of cardiovascular disease. Increased concentrations of triacylglycerol-rich, very low density lipoproteins (VLDL) and decreased concentrations of high density lipoproteins (HDL) are usual, whilst total cholesterol and low density lipoprotein (LDL) concentrations are not increased. Non-esterified fatty acids (NEFA) are not transported by lipoproteins, but increased concentrations may also be associated with cardiovascular disease risk. In this study, plasma concentrations of NEFA and other lipids were compared in healthy subjects and patients with end-stage chronic renal failure who were either undialyzed or undergoing peritoneal dialysis or hemodialysis. METHODS: Fasted blood samples for measurement of albumin, total, free and HDL-cholesterol, triacylglycerols and NEFA were taken from 56 apparently healthy subjects and from 48, 28 and 46 patients from the United Arab Emirates during 2002 who were either untreated or on peritoneal or hemodialysis. Hemodialysis subjects were studied immediately before and after a single treatment session. RESULTS: For all groups of patients, total, and LDL-cholesterol were unchanged, triacylglycerols and free cholesterol were raised and HDL-cholesterol concentrations and the percentage of esterified cholesterol were significantly decreased compared to controls. Plasma NEFA concentrations for untreated patients were similar to controls, but were decreased in peritoneal dialysis patients and markedly increased both before and, even more so, after dialysis in hemodialysis patients. CONCLUSION: Patients with end-stage renal failure share common features of dyslipoproteinemia irrespective of whether they are untreated or on peritoneal dialysis or hemodialysis. However, only hemodialysis patients show significantly increased concentrations of NEFA.

Alterations in atrial natriuretic peptide and its receptors in streptozotocin-induced diabetic rat kidneys.

In this study the effect of diabetes mellitus on atrial natriuretic peptide (ANP) receptors in streptozotocin- (STZ-) induced diabetic rat kidneys was studied. Moreover, plasma ANP concentration was evaluated in diabetic and control rats by using radioimmunoassay. In addition, the expression of ANP in the kidneys of control and diabetic rats was evaluated by immunohistochemistry. Body-weight loss and increased glucose levels were used as indices of diabetes mellitus in the STZ-induced rats. There was a significant loss in the body weight of the diabetic rats compared to controls. The efficacy of STZ administration was confirmed by rising blood glucose levels, which were significantly higher in diabetic rats compared to controls. Plasma ANP concentration was significantly greater in the diabetic rats in comparison with controls. Moreover, our immunohistochemical results show that the expression of ANP in diabetic rats was higher than that in age-matched controls. ANP was observed in the cells lining the proximal convoluted tubules in the cortex. The distribution and levels of ANP receptors in the kidneys of diabetic rats and age-matched controls were investigated using quantitative receptor autoradiography. Our results demonstrate significant decrease in ANP receptors in the kidneys of the diabetic rats compared to controls. The significant decrease was found in the juxtaglomerular medulla, inner medulla, and the papillae. The decrease in ANP receptors observed in the diabetic kidneys could have pathological consequences resulting in renal resistance to ANP in diabetes.

Association between an ANF Gene I/D dimorphism and left ventricular hypertrophy in a Gulf Arab population.

BACKGROUND: An association case-controlled study was carried out on a group of 151 United Arab Emirates nationals--62 normotensives with and without left ventricular hypertrophy (LVH) and 89 hypertensives, also with and without LVH--with a view to evaluating the value of an insertion/deletion (I/D) dimorphism located in the second intron of the human atrial natriuretic factor (ANF) gene in relation to left ventricular hypertrophy. SUBJECTS AND METHODS: Criteria used for LVH inclusion were: demonstration of Sokoloe and Lyon ECG criteria (sum of S wave in V(1), and tallest R wave in lead V5 or V6 > or =35 mm) and echocardiography findings (interventricular septum > or =1.2 cm; posterior LV wall > or =1.3 cm) in the long axis. ANF gene was obtained according to the usual methods by DNA extraction by means of polymerase chain reactions (PCR). The frequencies of this marker were performed according to the Hardy-Weinberg proportions. RESULTS: Our findings show that there was a significant difference in the distribution of the I and D alleles between the two groups (LVH vs non-LVH), with chi(2) = 12.34, 2df, P=0.002, making this a significant association of the D allele with LVH. CONCLUSION: Our results do suggest that variants of the ANF gene might be involved in the determination of left ventricular hypertrophy.