Pulse pressure and subclinical cardiovascular damage in primary hypertension.

BACKGROUND: High pulse pressure (PP) values have recently been implicated in the development and progression of large vessel atherosclerosis, small vessel disease, and in the occurrence of cardiovascular events. The aim of the present study is to investigate the relationship between PP and subclinical cardiovascular damage in a cohort of unselected middle-aged patients (204 male, 129 female) with untreated primary hypertension. METHODS: PP was calculated as the difference between systolic (SBP) and diastolic blood pressure (DBP). Left ventricular mass index (LVMI) was assessed by M-B mode echocardiography (LVH=LVMI>51 g/m(2.7)), and carotid intima-media thickness (IMT) by high-resolution US scan. Albuminuria was measured as the albumin to creatinine ratio (ACR) in three non-consecutive first morning urine samples. RESULTS: PP was positively correlated to gender (P<0.05), duration of disease (P<0.001), age (P<0.0001), LDL cholesterol (P=0.007), and to early signs of target organ damage (TOD), namely LVMI (P<0.0001), IMT (P<0.0001), and ACR (P=0.036). Patients in the upper quartile of PP showed higher LVMI (P<0.001), thicker carotid walls (P<0.001), as well as higher ACR (P<0.04). Multiple linear regression analysis showed that PP and ACR independently influence LVMI (F=26.476, r(2)=0.29, P<0.0001) and IMT (F=17.813, r(2)=0.26, P<0.0001). Patients with LVH, increased carotid IMT and microalbuminuria showed higher PP values as compared with those with lesser degrees of target organ involvement (F=4.97, P<0.003 inter-group comparison). Moreover, the risk of having the simultaneous occurrence of various signs of TOD increases significantly with each SD increase in PP or SBP, but is not influenced by DBP. CONCLUSIONS: PP is an independent marker of preclinical cardiovascular damage in relatively young patients with primary hypertension and, therefore, can be useful for identifying those at higher risk of cardiovascular events.     

Does microalbuminuria in diabetic patients affect the postoperative course after coronary artery bypass surgery?

OBJECTIVES: Microalbuminuria is a predictor of microvascular disease and a marker for multiorgan damage in diabetic patients. It has been proposed that in diabetic patients who would undergo coronary artery bypass surgery (CABG), microalbuminuria is associated with poor postoperative outcome, higher incidence of early and late morbidity and mortality. METHODS: Microalbuminuria was prospectively studied preoperatively in 24-h urinary collections for 257 consecutive diabetic patients in a 2-year period. One hundred and sixty-eight patients (65.4%) were defined as microalbuminuria negative (Group A), and 89 (34.6%) were microalbuminuria positive (Group B) with respect to the cut-off point 30 mg/24 h. RESULTS: The two groups did not differ with respect to preoperative and operative data, except that preoperative blood glucose levels (P=0.046), blood urea nitrogen (P=0.001), and creatinine (P=0.001) were higher and creatinine clearance was lower (P=0.025) in Group B. Postoperative serum creatinine levels on different days were higher in microalbuminuria positive patients (P=0.04). Also, positive inotropic agent usages at the time of leaving the operating room (21.3 vs. 10.1%; P=0.013) and on the 1st day in the intensive care unit (ICU; 29.2 vs. 14.9%; P=0.014), ICU stay day (2.3+/-2 vs. 2.4+/-1.6; P=0.02) and also atrial fibrillation rate (30.3 vs. 17.9%) were higher in Group B (P=0.019). Total hospital stay (7.5+/-2.9 vs. 7.2+/-1.3) was similar. The 30-day mortality was 5.6 times higher (3.4 vs. 0.6%) but statistically not significant (P=0.088) in Group B. The mean follow-up was 30.6+/-16. 2 months in total (30.9+/-16.2 in Group A and 30.1+/-16.5 in Group B). There were 12 late deaths, nine were cardiac, and no differences were detected between groups. CONCLUSIONS: Our findings suggest that postoperative period may be more problematic in diabetic patients with microalbuminuria, but microalbuminuria does not seem to have a major effect on the postoperative course in patients undergoing CABG.     

Microalbuminuria in children with primary and white-coat hypertension

Microalbuminuria serves as an early marker of hypertension-related renal damage in adults. However, data on the prevalence of microalbuminuria in paediatric hypertensive patients in general and in children with white-coat hypertension (WCH) specifically are lacking. The aim of our study was to investigate the prevalence of microalbuminuria in children with primary hypertension (PH) and WCH, respectively. This was a retrospective case review of children with PH and WCH treated at three paediatric nephrology centres. Untreated children with either form of hypertension for whom measurements of urinary albumin excretion (UAE) had been performed were enrolled in the study. The study cohort comprised 52 children (39 boys) with hypertension (26 children with PH, 26 with WCH). Microalbuminuria (>3.2 mg/mmol creatinine) was present in 20% of children with PH and none of the children with WCH (p < 0.01). Children with PH had a higher median UAE than those with WCH (1.27 ± 1.92 vs. 0.66 ± 0.46 mg/mmol creatinine, p < 0.05). Based on these results, we suggest that children with PH have an increased prevalence of microalbuminuria, while children with WCH show no signs of hypertension-related renal damage.     

The impact of visceral fat on multiple risk factors and carotid atherosclerosis in chronic haemodialysis patients.

BACKGROUND: There has been recent interest in the importance of visceral fat (VF) for the development of atherosclerosis. The purpose of this study was to examine associations between VF and multiple risk factors as well as the prevalence of carotid atherosclerosis in chronic haemodialysis patients. METHODS: We classified 77 non-diabetic haemodialysis patients into 'low VF', 'middle VF' and 'high VF' groups after determining VF area using computed tomography. Systemic atherosclerosis was assessed from intima-media thickness (IMT), plaque score (PS) and stiffness parameter beta (stiffness-beta) measured by high-resolution B-mode ultrasonography. RESULTS: Compared with the low VF group, the high VF group exhibited (i) significantly higher fasting plasma insulin (11.0 +/- 6.8 vs 7.1 +/- 2.9 micro U/ml, P = 0.0061); (ii) significantly higher plasma triglycerides (141.8 +/- 94.0 vs 86.5 +/- 32.5 mg/dl, P = 0.0032); and (iii) significantly lower plasma high-density lipoprotein cholesterol (42.1 +/- 14.5 vs 53.0 +/- 15.7mg/dl, P = 0.0134). Moreover, the high VF group had a higher prevalence and extent of carotid atherosclerosis: IMT was 0.69 +/- 0.13 vs 0.61 +/- 0.12 mm (P = 0.0239), PS was 4.8 +/- 3.2 vs 2.4 +/- 3.6 (P = 0.0236) and stiffness-beta was 11.4 +/- 3.1 vs 8.5 +/- 3.0 (P = 0.0082) in the high and low VF groups, respectively. CONCLUSION: We show that VF is associated with the prevalence of carotid atherosclerosis as well as with hyperinsulinaemia and lipid abnormalities in chronic haemodialysis patients.     

Genetic polymorphism of the renin-angiotensin system and organ damage in essential hypertension

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) plays a significant role in the development of hypertensive cardiac and vascular remodeling. Recently, several genetic variants of its key components, which may be clinically relevant and thus prove to be useful in the evaluation of cardiovascular risk, have been described. We therefore investigated the association between ACE I/D, AGT M235T, and AT1 A1266C gene polymorphisms and early signs of target organ damage in 215 untreated patients with essential hypertension (EH). METHODS: Genotyping was based on the polymerase chain reaction technique, with further restriction analysis when required. Albuminuria was measured as the albumin-to-creatinine ratio (ACR). The left ventricular mass index (LVMI) was assessed by echocardiography (LVH = LVMI > or = 125 g/m2), carotid wall thickness (IMT) by an ultrasonographic (US) scan, and retinal vascular changes by direct ophthalmoscopy (Keith-Wagener classification). RESULTS: The prevalence of microalbuminuria (Mi), LVH, and retinal vascular changes was 14, 46, and 74%, respectively. ACE, AGT, and AT1 genotype distribution was in agreement with the Hardy-Weinberg equilibrium. There was no difference in age, duration of disease, body mass index (BMI), blood pressure, and lipid profile when data were analyzed on the basis of genotype. Serum levels of angiotensin-converting enzyme (ACE) were related to the ACE genotype (10.2 +/- 0.5, DD; 8.2 +/- 0.3, ID; 6.5 +/- 0.4 IU/mL, II; P < 0. 0001 by analysis of variance). The ACE genotype independently influences serum ACE levels and accounts for approximately 14% of its variations (F = 26.7, r2 = 0.1393, df 1 to 214, P < 0.0001). Patients with DD and ID genotypes showed higher levels of ACR (1.59 +/- 0.2, DD + ID; 0.8 +/- 0.2 mg/mmol, II; P < 0.006 by ANOVA) and bigger LVMI (124.1 +/- 2.3, DD + ID vs. 117.8 +/- 3.6 g/m2, II; P < 0.01 by ANOVA). No differences in the prevalence and degree of target organ damage (TOD) were found when data were analyzed on the basis of the AGT and AT1 genotypes, respectively. Potentially unfavorable combinations of genotypes were also investigated by K-means cluster analysis. Two subgroups of patients were identified (cluster 1, N = 70; cluster 2, N = 57), and each differed significantly with regards to the presence and degree of TOD and patterns of RAAS gene polymorphisms (F, 15.97 for ACR; F, 7.19 for IMT; F, 217.03 for LVMI; F, 3.91 for ACE; F, 4.06 for AGT; and F, 5. 22 for AT1; df 1 to 214, P < 0.02, for each one of the variables examined). CONCLUSION: The D allele of the ACE gene may be an independent risk factor for the development of target organ damage, and evaluating it could be useful for assessing cardiovascular risk in EH. Unfavorable patterns of RAAS genotypes seem to predispose patients to subclinical cardiovascular disease in EH.     

Urinary Albumin Excretion and the Risk of Graft Loss and Death in Proteinuric and Non-proteinuric Renal Transplant Recipients

BACKGROUND: Microalbuminuria and macroalbuminuria constitute risk factors for ESRD and death in non-transplanted populations. Whether microalbuminuria (especially in non-proteinuric patients) and macroalbuminuria constitute risk factors for graft loss and death is presently unknown in renal transplantation. METHODS: We retrospectively assessed the association between urinary albumin excretion (UAE) and ESRD and death in renal transplantation. RESULTS: UAE was measured in 616 (397 proteinuric; 219 non-proteinuric patients) renal transplant recipients. They were grafted for 62 months (range: 6-192). During the 40 months (3.7-99) thereafter, 31 patients underwent dialysis and 32 died. Microalbuminuria (vs. normoalbuminuria) and macroalbuminuria (vs. microalbuminuria) were powerful risk factors for graft loss [OR: 14.25 (2.88-52.3) and 16.41 (7.46-36.0), respectively, both p < 0.0001], even after adjustments on renal function and diabetes. Among the 219 non-proteinuric patients, microalbuminuria (vs. normoalbuminuria) was a significant risk factor for graft loss [OR: 23.09 (1.93-276.4), p = 0.0132]. Both microalbuminuria (vs. normoalbuminuria) [OR: 5.55 (2.43-12.66), p < 0.0001] and macroalbuminuria (vs. microalbuminuria) [OR: 4.12 (1.65-10.29), p = 0.0024] were predictive of death. CONCLUSIONS: Microalbuminuria and macroalbuminuria are powerful independent predictors of ESRD and death. Microalbuminuria is a risk factor for graft loss even in non-proteinuric patients. UAE provides additional information on renal and patient prognosis as compared to proteinuria and renal function.     

Insulin resistance and microalbuminuria: a cross-sectional, case-control study of 158 patients with type 2 diabetes and different degrees of urinary albumin excretion

Microalbuminuria is a risk factor for renal and cardiovascular disease. A role for insulin resistance in the pathogenesis of microalbuminuria has been suggested but is still unproven. In this case-control, cross-sectional study, we compared glucose disposal rate (GDR), measured by hyperinsulinemic-euglycemic clamp, in 50 pairs of matched type 2 diabetic patients with micro- or normoalbuminuria (main study) and in 29 matched pairs of diabetic patients with macro- or microalbuminuria (substudy). In the main study, GDR was approximately 25% lower in micro- than in normoalbuminuric patients (5.20 +/- 1.91 vs. 6.86 +/- 2.88 mg . kg(-1) . min(-1), P < 0.05) and was independently associated with microalbuminuria (P = 0.002), with each 1 mg . kg(-1) . min(-1) decrease predicting approximately 40% increased prevalence (odds ratio 1.37 [95% CI 1.14-1.70]). Microalbuminuria was threefold more frequent in patients with GDR < or =7.50 +/- 2.56 mg . kg(-1) . min(-1) than in those with higher GDR (60% vs. 20%, P < 0.005). In the substudy, GDR in macro- and microalbuminuric patients was comparable (5.52 +/- 2.56 vs. 5.16 +/- 1.61 mg . kg(-1) . min(-1)) and independent of macroalbuminuria. GDR was significantly correlated with urinary albumin excretion rate in the main study (P = 0.004) but not in the substudy (P = 0.60). In type 2 diabetes, more severe insulin resistance is independently associated with microalbuminuria. Longitudinal studies are needed to clarify the role of insulin resistance in the pathogenesis of microalbuminuria and related complications.     

Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis in middle-aged adults.

BACKGROUND: Cystatin C, a marker of renal function, has been shown to be an independent predictor of cardiovascular disease (CVD) in older adults, but few data are available in middle-aged adults. Moreover, no study has compared cystatin C and microalbuminuria as risk factors for CVD outcomes in middle-aged adults, and it is not known whether cystatin C is related to an early stage of atherosclerosis. METHODS: We evaluated the relationships between serum creatinine, estimated glomerular filtration rate (GFR), serum cystatin C (all divided into tertiles), microalbuminuria and carotid atherosclerosis in a population-based random sample of 523 adults aged 35-64 years from the Seychelles (Indian Ocean). GFR was estimated using the modification of diet in renal disease (MDRD) equation. Intima-media thickness (IMT) was assessed by B-mode ultrasound. RESULTS: The mean age of the study sample was 52 years, and 55% were women. Carotid IMT was higher in participants with microalbuminuria (802 vs 732 microm, P<0.001) and was inversely associated with GFR tertiles (from 728 to 809 microm, P for trend=0.002). IMT was not associated with cystatin C or creatinine (P for trend=0.10 and 0.16, respectively). In multivariate analyses adjusted for cardiovascular risk factors, the association between microalbuminuria and IMT remained (P=0.047), while the association between GFR and IMT disappeared (P for trend=0.33). CONCLUSIONS: Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis beyond traditional cardiovascular risk factors among middle-aged adults. Cystatin C does not have a stronger relationship with carotid atherosclerosis in middle-aged adults than creatinine.     

Urinary albumin excretion associated with arterial wall stiffness rather than thickness in type 2 diabetic patients

BACKGROUND: A close relationship has been reported between microalbuminuria and atherosclerosis in patients with diabetes mellitus. The aim of this study was to determine which of the 2 aspects of atherosclerosis, arterial thickening or stiffness, has more effect on levels of microalbuminuria in type 2 diabetic patients. METHODS: Twenty-four-hour urine samples of 167 Japanese type 2 diabetic patients (aged 58 +/- 12 years) without overt proteinuria were collected for quantitative analysis of urinary albumin excretion (UAE). Arterial stiffness was evaluated by measuring aortic pulse-wave velocity (PWV), and arterial thickness was measured by the intima-media thickness (IMT) of the carotid artery. RESULTS: The aortic PWV and carotid IMT were both significantly positively correlated with logarithmically transformed UAE (r=0.269, p<0.001; and r=0.188, p<0.05, respectively). Although there was a significant positive correlation between aortic PWV and carotid IMT (r=0.263, p<0.001), multiple regression analyses demonstrated that aortic PWV, but not carotid IMT, was a significant factor associated with log UAE, independent of other confounding factors (R2=0.246, p<0.0001). CONCLUSIONS: These results suggest that increased arterial stiffness, but not arterial thickness, is significantly associated with the increase in albuminuria, and that decreased arterial distensibility due to increased stiffness caused by atherosclerosis may be related to the progression of diabetic nephropathy in type 2 diabetic patients.     

Increased renal resistive index in patients with essential hypertension: a marker of target organ damage.

BACKGROUND: Increased renal resistance detected by ultrasound (US) Doppler has been reported in severe essential hypertension (EH) and recently was shown to correlate with the degree of renal impairment in hypertensive patients with chronic renal failure. However, the pathophysiological significance of this finding is still controversial. METHODS: In a group of 211 untreated patients with EH, we evaluated renal resistive index (RI) by US Doppler of interlobar arteries and early signs of target organ damage (TOD). Albuminuria was measured as the albumin to creatinine ratio (ACR) in three non-consecutive first morning urine samples. Left ventricular mass was evaluated by M-B mode echocardiography, and carotid wall thickness (IMT) by high resolution US scan. RESULTS: RI was positively correlated with age (r=0.25, P=0.003) and systolic blood pressure (SBP) (r=0.2, P=0.02) and with signs of early TOD, namely ACR (r=0.22, P=0.01) and IMT (r=0.17, P<0.05), and inversely correlated with renal volume (r=-0.22, P=0.01) and diastolic blood pressure (r=-0.23, P=0.006). Multiple linear regression analysis demonstrated that age, gender, ACR and SBP independently influence RI and together account for approximately 20% of its variations (F=8.153, P<0.0001). When clinical data were analysed according to the degree of RI, the patients in the top quartile were found to be older (P<0.05) and with higher SBP (P<0.05) as well as early signs of TOD, namely increased ACR (P<0.002) and IMT (P<0.005 by ANOVA), despite similar body mass index, uric acid, fasting blood glucose, lipid profile and duration of hypertension. Furthermore, patients with higher RI showed a significantly higher prevalence of microalbuminuria (13 vs 12 vs 3 vs 33% chi2=11.72, P=0.008) and left ventricular hypertrophy (40 vs 43 vs 32 vs 60%, chi2=9.25, P<0.05). CONCLUSIONS: Increased RI is associated with early signs of TOD in EH and could be a marker of intrarenal atherosclerosis.     

Prevalence of microalbuminuria in a large population of patients with mild to moderate essential hypertension.

To determine the prevalence of increased urinary albumin excretion (UAE) in essential hypertension and to establish whether this abnormality is associated with deranged renal function, we have measured UAE in a group of 123 patients with essential hypertension and in 110 normal subjects. Mean arterial pressure (MAP) was 96 +/- 0.6 mm Hg in normal subjects and 121 +/- 0.3 mm Hg in patients with essential hypertension (p less than 0.01). Mean UAE was 8.6 +/- 0.5 in normal subjects and 32.9 +/- 3.3 mg/24 h in patients with essential hypertension (p less than 0.01). Forty percent of patients with essential hypertension manifested a UAE exceeding 30 mg/24 h and had an average UAE of 72.0 +/- 4.7 mg/24 h. MAP in patients with increased UAE was similar to that in subjects with normal UAE (121 +/- 0.5 vs. 121 +/- 0.4 mm Hg). Creatinine clearance was also not different between these two groups (91 +/- 1.8 vs. 94 +/- 1.5 ml/min). No correlation was found between UAE and MAP or creatinine clearance. Long-term prospective studies are needed to extablish whether an increase in UAE may predict future nephrosclerosis in essential hypertension.     

Subclinical atherosclerosis is increased in type 2 diabetic patients with microalbuminuria evaluated by intima-media thickness and pulse wave velocity

BACKGROUND: Microalbuminuria appears to be a risk marker for atherosclerosis. However, little is known about the direct association between microalbuminuria and vascular wall properties. METHODS: Subjects were 306 type 2 diabetic patients with normoalbuminuria (N= 200) and microalbuminuria (N= 106). Those who had macroalbuminuria, atherosclerotic vascular disease, and/or ankle brachial index being less than 0.9 were not included. Brachial-ankle pulse wave velocity (PWV) was measured by automatic oscillometric method. Intima-media thickness (IMT) of the common carotid artery was measured using high-resolution B-mode ultrasonography and a computerized image-analyzing system. RESULTS: Average IMT, maximum IMT, and PWV were significantly higher in patients with microalbuminuria than in patients with normoalbuminuria. Both average and maximum IMT increased significantly as albuminuria increased in the microalbuminuric range. Average IMT and maximum IMT correlated significantly with PWV (P < 0.0001), although some patients exhibited increased levels of only PWV or IMT. By a multiple linear regression, age and albuminuria were independent predictors of IMT and PWV. Waist circumference was an independent predictor of IMT. Hypertension and hemoglobin A(1c) (HbA(1c)) were independent predictors of PWV. After adjustment for conventional cardiovascular risk factors including age, sex, waist circumference, HbA(1c), hypertension, hyperlipidemia, and smoking, albuminuria revealed a significant association with average IMT, maximum IMT, and PWV (P < 0.05, P < 0.0001, and P < 0.05, respectively). CONCLUSION: A slight elevation of albuminuria is a significant determinant of IMT and PWV independent of conventional cardiovascular risk factors in type 2 diabetic patients with no clinical nephropathy or any vascular diseases. This significant association might point to a link in the pathogenesis of atherosclerosis and diabetic nephropathy.     

The alpha-adducin gene is associated with macrovascular complications and mortality in patients with type 2 diabetes

We examined the association between alpha-adducin 1 (ADD1) gene polymorphism (Gly460Trp) with macrovascular complications and mortality in type 2 diabetes in a Caucasian population aged >or=55 years. The study was part of the Rotterdam Study, a prospective population-based cohort study. ADD1 polymorphism was determined in 6,471 participants, including 599 patients with type 2 diabetes at baseline. The prevalence of hypertension in type 2 diabetic patients was 2.57 times higher in ADD1 TT carriers compared with GG carriers (95% CI 1.05-6.32, P = 0.03). Homozygous T carriers also had a higher mean common carotid intima media thickness (IMT) compared with GG carriers (mean difference 0.05 mm, P for trend = 0.03). In diabetic patients with hypertension, the risk of mortality was 1.83 times higher in homozygous T carriers compared with the GG genotype group (95% CI 1.07-3.16, P = 0.03). The increased risk was only present among TT carriers who did not use antidiabetes medication (hazard ratio 2.18 [95% CI 1.12-4.24], P = 0.02). The results of this population-based cohort study suggest that the ADD1 gene contributes to the risk of hypertension and increases mean common carotid IMT in patients with type 2 diabetes. Furthermore, the study indicates that the ADD1 polymorphism could be useful in identifying hypertensive type 2 diabetic patients with a high risk of mortality.     

Microalbuminuria in single kidney patients: relationship with protein intake

Experimental models have shown that the reduction in renal mass induces an increase in glomerular filtration rate of the remnant nephrons, leading to proteinuria and glomerular sclerosis. Since the presence of microalbuminuria - increased urinary albumin excretion (UAE) undetectable by routine assays - can be an early sign of this phenomenon, UAE in the normo- and microalbuminuric range was measured in 24 single kidney patients with negative Albustix. Nephrectomy had been performed in 22 cases 1 to 28 years before, mostly because of renal lithiasis. Patients were selected as being normotensive, normoglycemic and free of recurrent urinary infections or stones. On regular diet (mean protein intake 1.2 g/kg/day), UAE mean values were significantly higher in single kidney patients than in 20 controls both in supine position during overnight rest (clinostatism) (37.71 +/- 56.32 vs 2.56 +/- 2.27 micrograms/min, p less than 0.001) and in erect position during moderate physical effort (orthostatism) (67.31 +/- 86.12 vs 4.59 +/- 5.73 micrograms/min, p less than 0.004). Microalbuminuria was observed in 18/24 single kidney patients in clinostatism and 15/24 in orthostatism. A subgroup of 14 patients was also studied on different protein dietetic regimens. After one month on a 0.6 g/kg/day protein containing diet, UAE mean levels significantly decreased in comparison to those found on regular diet (clinostatism: 26.15 +/- 35.93 vs 49.24 +/- 70.29 micrograms/min, p less than 0.02; orthostatism: 31.73 +/- 46.97 vs 68.92 +/- 83.53 micrograms/min, p less than 0.001). One month after a 1.6 g/kg/day protein diet UAE mean values significantly increased (clinostatism 83.99 +/- 88.04 micrograms/min, p less than 0.001; orthostatism: 117.19 +/- 116.12 micrograms/min, p less than 0.001). Our data indicate that microalbuminuria, detectable in the majority of patients with a single kidney, can be modulated by different protein intakes.     

Pulse wave velocity--a useful tool for cardiovascular surveillance in pre-dialysis patients.

BACKGROUND: Cardiovascular mortality is high among patients with chronic kidney disease. Pulse wave velocity (PWV) is a simple method used for arterial distensibility evaluation. Few data are available concerning PWV in pre-dialysis patients. The aim of this study was to evaluate the association between PWV and cardiovascular disease in pre-dialysis. METHODS: One hundred and four patients were submitted to PWV analysis, coronary artery calcium (CAC) determination with a multi-slice CT scan of the coronary arteries, echocardiogram and a carotid intima-media thickness (IMT) evaluation, with a high resolution ultrasound. The demographic characteristics and laboratory tests results were studied. RESULTS: The mean age of those studied was 54.4 +/- 11.5 years, 60% were males and the mean creatinine clearance was 40 ml/min/1.73 m(2). The mean PWV was 12.2 +/- 3.4 m/s and it was significantly higher in males, diabetics, those with creatinine clearance <60 ml/min and proteinuria > or =1 g/24 h. PWV was correlated with systolic blood pressure, age, triglycerides, total cholesterol and 24 h proteinuria. In the multiple regression analysis, PWV was significantly associated with diabetes, age, systolic blood pressure and cholesterol. Fifty-eight patients (56%) presented coronary calcification and PWV correlated with coronary calcium score (R = 0.48; P < 0.001) and calcium volume (R = 0.50; P < 0.001). Moreover, PWV was higher in patients with coronary calcification (13.4 +/- 3.6 m/s vs 10.7 +/- 2.4 m/s; P < 0.001). The mean left ventricular mass index (LVMI) was 106 +/- 31 g/m(2) and 24% of patients had left ventricular hypertrophy, while 19 (18.3%) patients had left ventricular dysfunction. PVW was correlated with LVMI (R = 0.25; P = 0.01) while no association could be seen between PWV and the ejection fraction or left ventricular dysfunction. A correlation between the IMT and PWV was observed (R = 0.27; P = 0.005). In addition, those with a thicker IMT had a higher PWV (13.2 +/- 3.4 m/s vs 11. 2 +/- 3.2 m/s; P = 0.003). CONCLUSION: PWV is associated with cardiovascular disease in pre-dialysis patients and can be a useful tool to identify patients with increased cardiovascular risk.     

Ten-year prognosis of Puumala hantavirus-induced acute interstitial nephritis

Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome caused by Puumala hantavirus. Its long-term prognosis is considered favorable. There are, however, some reports about subsequent hypertension, glomerular hyperfiltration, and proteinuria after previous hantavirus infection. Therefore, we studied 36 patients 5 and 10 years after acute NE, with 29 seronegative controls. Office blood pressure, ambulatory 24-h blood pressure (ABP), glomerular filtration rate (GFR), and proteinuria were examined. Hypertensive subjects were defined as those patients having increased ambulatory or office blood pressure, or receiving antihypertensive therapy. Office blood pressure was used to define hypertension only if ABP was not determined. At 5 years, the prevalence of hypertension was higher among NE patients than in controls (50 vs 21%, P=0.020). At 10 years, the difference between the groups was no more significant (39 vs 17%, P=0.098). Five years after NE, patients showed higher GFR (121+/-19 vs 109+/-16 ml/min/1.73 m(2), P=0.012) and urinary protein excretion (0.19 g/day, range 0.12-0.38 vs 0.14 g/day, range 0.09-0.24, P=<0.001) than controls. At 10 years, there were no more differences in GFR or protein excretion between the groups (GFR: 113+/-20 vs 108+/-17 ml/min/1.73 m(2), P=0.370; proteinuria: 0.14 g/day, range 0.07-0.24 vs 0.13 g/day, range 0.06-0.31, P=0.610). In conclusion, the 10-year prognosis of NE is favorable, as glomerular hyperfiltration and slight proteinuria detected at 5 years disappeared during the longer follow-up. However, the possibility exists that NE may predispose some patients to the development of hypertension.     

Microalbuminuria after pregnancy complicated by pre-eclampsia.

BACKGROUND: Microalbuminuria is an important risk factor for underlying vascular disease. Its detection after pregnancy complicated by pre-eclampsia may have predictive value for the later development of chronic hypertension or renal disease. METHOD: The study group consisted of 48 women in whom pregnancy had been complicated by pre-eclampsia. Urinary albumin excretion rate, blood pressure, and renal function parameters were assessed 2-4 months and 3-5 years after the pregnancy. Results were compared with those in 44 women after normal pregnancy. RESULTS: Mean urinary albumin excretion rate was significantly higher in the study group than in the controls both at 2-4 months after delivery (27.0 +/- 33 vs 6.1 +/- 3.3 mg/24 h) and at 3-5 years after delivery (23.5 +/- 26.8 vs 6.7 +/- 2.8 mg/24 h) (P = 0.001). The rate of occurrence of microalbuminuria was not significantly different between the early (58%) and late (42%) time-points within the study group or between the nulliparous and the multiparous women. CONCLUSIONS: A history of pregnancy complicated by pre-eclampsia is associated with a high occurrence of microalbuminuria. Whether the presence of microalbuminuria reflects a possible underlying vascular disease in affected patients needs to be further investigated in large-scale studies.     

Relationship between carotid artery intima-media thickness and renal function in patients with diabetes mellitus

Objective To investigate the relationship between carotid artery intima-media thickness and renal function in patients with diabetes mellitus. Methods 424 patients of type 2 diabetes without dialysis were enrolled in a cross-sectional study. According to their artery intima-media thickness (IMT), the patients were divided into normal group and higher IMT group. All patients according to UAER or 24h urinary protein were divided into normal proteinuria group, micro-proteinuria group and clinical proteinuria group. The biochemical examination, eGFR, and atherosclerotic plaque of different groups were compared. Pearson or spearman correlation was used to analyze the relationship between eGFR, IMT and other parameters. Risk factors for eGFR decline were analyzed by binary logistic regression. Results Compared with normal group, patients in the higher IMT group were older [(63.3±10.2) year vs (52.5±10.6) year, P﹤0.05], and underwent longer duration of diabetes [(8.9±6.7) year vs (6.2±5.7) year, P﹤0.05]. Their level of eGFR was decreased [(75.92±28.00) ml/min vs (91.64±24.05) ml/min, P﹤0.05], while plaque incidence (71.3% vs 18.3%,χ2=112.42, P﹤0.01) and prevalence of hypertension (56.4% vs 29.6%, χ2=27.22, P﹤0.01) increased. Correlation analysis showed that IMT was positively correlated with age (r=0.503, P﹤0.01), duration of diabetes (r=0.204, P﹤0.01), 24 h urine protein (rs=0.175, P﹤0.05), plaque (rs=0.562, P﹤0.01), and hypertension (rs=0.193, P﹤0.01), but negatively correlated with eGFR (r=-0.307, P﹤0.01). Logistic regression analysis showed that age, serum uric acid, 24 h urine protein and carotid artery intima-media thickness were independent risk factors for eGFR decline [OR=1.115, 95%CI(1.053, 1.165), P﹤0.001; OR=1.008,95%CI (1.002, 1.014), P=0.006; OR=1.492, 95%CI(1.170,1.903), P=0.001; OR=1.619, 95%CI(1.121, 2.339), P=0.010]. Conclusion Carotid artery intima-media thickness is an independent risk factor for kidney function decline in patients of diabetes.     

Renal and cardiac effects of antihypertensive treatment with ramipril vs metoprolol in autosomal dominant polycystic kidney disease.

BACKGROUND: Hypertension is a common complication in autosomal dominant polycystic kidney disease (ADPKD). This prospective randomized double-blind study was performed to compare the renal and cardiac effects of the ACE inhibitor ramipril and the beta-blocker metoprolol as first line therapy in ADPKD patients with hypertension. METHODS: Forty-six hypertensive ADPKD patients were randomized to either ramipril (n = 23) or metoprolol (n = 23). Twenty-four hour (24-h) ambulatory blood pressure (BP), glomerular filtration rate (GFR) as calculated by the Cockcroft and Gault formula, urinary albumin excretion (albumin/creatinine ratio), and left ventricular mass index (LVMI) were established at baseline and at yearly intervals. The total follow-up was 3 years. Baseline characteristics were similar in both groups. RESULTS: Mean arterial pressure (MAP) decreased significantly in both the ramipril and the metoprolol group (-8 +/- 2 and -6 +/- 2 mmHg; both P < 0.01). There was a significant decline in renal function during follow-up which was similar in patients treated with ramipril or metoprolol (-2.5 +/- 0.7 vs -2.9 +/- 0.8 ml/min/year; P = NS). After the 3 years follow-up, no differences in GFR, LVMI and urinary albumin excretion were observed between the ramipril and the metoprolol group (80.7 +/- 10.7 vs 78.0 +/- 7.6 ml/min, 102.6 +/- 6.8 vs 100.3 +/- 5.4 g/m(2); and 42.6 +/- 12.3 vs 70.3 +/- 32.5 mg/g, respectively; all P = NS). A post-hoc analysis evaluating the effects of BP control, revealed that LVMI increased in patients with standard BP control while it remained stable in patients with rigorous BP control with a significant difference in LVMI between the groups after 3 years of follow-up (110.5 +/- 6.3 vs 90.9 +/- 4.7 g/m(2); P = 0.017). Also, by the end of the study albuminuria was lower in patients with rigorous vs standard BP control (23.5 +/- 6.7 vs 94.8 +/- 35.4 mg/g; P = 0.05). CONCLUSIONS: In our study population of hypertensive ADPKD patients, no differences in renal function, urinary albumin excretion and LVMI were detected between those treated with ramipril or metoprolol, respectively, during a 3 years follow-up. Rigorous BP control prevented an increase in LVMI and reduced urinary albumin excretion, suggesting a crucial role of BP control for slowing progression of cardiac and renal organ damage in ADPKD.     

Intima-media thickening of common carotid arteries is a risk factor for severe erectile dysfunction in men with vascular risk factors but no clinical evidence of atherosclerosis

PURPOSE: The association of erectile dysfunction (ED) with vascular damage in men without clinical atherosclerosis is unknown. By B-mode ultrasound we evaluated intima-media thickness (IMT) of common carotid arteries, a measure of vascular damage, in men reporting ED with or without vascular risk factors (VRFs) but no clinical atherosclerosis. MATERIALS AND METHODS: IMT of common carotid arteries was evaluated in 270 men with ED. A total of 50 men (mean age +/- SD 39.84 +/- 12.5 years) had no VRFs, 100 (mean age 47.92 +/- 10.94 years) were overweight and/or had hyperlipidemia, and 120 (mean age 53.95 +/- 9.73 years) were affected by type 2 diabetes and/or essential arterial hypertension. RESULTS: IMT was significantly lower in men with no VRFs compared to men with VRFs (p <0.05), and correlated with the severity of ED evaluated through the Sexual Health Inventory for Men (p = 0.0008). Of men with VRFs 17.7% (39 of 220) showed an IMT score indicative of vascular damage (1.00 mm or greater), while only 1 man with no VRFs had a high IMT. Men with VRFs and a high carotid IMT score demonstrated more severe ED, were older and had a higher serum level of C-reactive protein compared to men with VRFs and an IMT of less than 1.00 mm (p <0.05). A high IMT score but not an increased measure for each VRF, including aging, significantly increased the risk of severe ED (odds ratio 2.6, confidence interval 1.1 to 5.9) even after controlling for smoking and drugs associated with ED. CONCLUSIONS: ED in men with VRFs was the only clinical correlate of unrecognized atherosclerosis of common carotid arteries.