What is the best predictor of the atherogenic LDL subclass phenotype 'pattern B' in patients with type 2 diabetes mellitus?

BACKGROUND: The atherogenic lipoprotein phenotype 'pattern B' comprises a predominance of small-dense low-density lipoprotein (sdLDL). Gradient gel electrophoresis (GGE) is considered a 'gold standard' method for identifying this phenotype, but is impractical for routine laboratory use. The low-density lipoprotein cholesterol:apolipoprotein-B (LDL-C:Apo-B) ratio has been advocated as a surrogate marker for sdLDL and a direct assay for sdLDL has recently become available. We compared the sdLDL assay and LDL-C:Apo-B with more established lipid parameters to predict the presence of 'pattern B' phenotype. METHOD: Blood was collected from 97 fasted subjects on three separate occasions. Total cholesterol, triglyceride, Apo-B and sdLDL were measured; LDL- and HDL-cholesterol were determined after ultracentrifugation. The predominant LDL particle size and phenotype were assigned by GGE. RESULTS: 'Pattern B' phenotype was identified in 36% of samples. Peak particle size showed a positive correlation with HDL-cholesterol and a negative correlation with triglyceride and Apo-B. Receiver operating curve (ROC) analysis showed triglyceride:HDL-C ratio and triglyceride alone to be the best predictors of 'pattern B' phenotype, with area under the curve (AUC) being 0.87 and 0.84, respectively. AUCs for sdLDL (0.74) and LDL-C:Apo-B (0.71) were significantly lower (P < 0.05). A high sdLDL concentration had the greatest specificity (95%) and positive predictive value (74%) for 'pattern B' phenotype, but low sensitivity (43%). CONCLUSION: Direct measurement of sdLDL provided the most specific predictor of 'pattern B' phenotype, whereas triglyceride:HDL-C ratio or triglycerides alone, parameters readily available in most laboratories, were the best predictors by ROC analysis.

Plasma sex hormone-binding globulin, corticosteroid-binding globulin, cortisol, and free cortisol levels in outpatients attending a lipid disorders clinic: a cross-sectional study of 1137 subjects.

We measured plasma sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), and total cortisol, and calculated free plasma cortisol in 1 137 subjects attending a hospital outpatient lipid disorders clinic to investigate whether or not these analytes correlated with the degree of insulin resistance and the presence of the metabolic syndrome. In both males and females, plasma SHBG correlated inversely with anthropometric measures and with fasting glucose, insulin, insulin resistance, and triglycerides, and positively with HDL-cholesterol. However, in males with the metabolic syndrome, unlike females, the relationship between SHBG, some anthropometric measures, fasting glucose, insulin, and HDL-cholesterol were lost, which suggests that in males SHBG may not co-cluster with other components of the metabolic syndrome. In males and males with the metabolic syndrome, total plasma cortisol and calculated plasma free cortisol correlated positively with fasting glucose. Corticosteroid-binding globulin correlated inversely with percentage body fat and positively with HDL-cholesterol in males with and without the metabolic syndrome. CBG correlated negatively with age in both sexes. Overall, the results confirm the finding that SHBG is a marker of insulin resistance in males and females and that SHBG is associated with fasting triglycerides in males with the metabolic syndrome. Importantly, SHBG could be considered a stronger component of the metabolic syndrome in females than in males. However, the aetiological role of CBG and cortisol in insulin resistance is uncertain, although in males, cortisol and CBG could be subtly related to the degree of insulin resistance.

Comparison of indices of insulin resistance with metabolic syndrome classifications to predict the development of impaired fasting glucose in overweight and obese subjects: a 3-year prospective study.

OBJECTIVE: To compare the ability of biochemical indices of insulin resistance (IR) with metabolic syndrome (MetS) classifications to predict changes in blood glucose control over a 3-year period in overweight and obese subjects. DESIGN: This was a longitudinal, prospective study, with data collected at baseline, 18 and 36 months. SUBJECTS AND METHODS: A total of 175 overweight (body mass index (BMI)>25 kg m(-2)) and obese (BMI>30 kg m(-2)) subjects were enrolled in the study. The IR indices assessed included fasting insulin concentration, the insulin/glucose-derived indices, homeostasis assessment model of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI), the insulin/triglyceride-derived McAuley index, plasma adiponectin concentration and the triglyceride (trig) and high-density lipoprotein (HDL)-cholesterol ratio (trig:HDL). The two MetS classifications were assessed according to the definitions of the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) and the International Diabetes Federation (IDF). The potential of the IR indices and MetS classifications at baseline to predict the development of impaired fasting glucose (IFG) was examined using receiver-operator characteristic (ROC) curve analysis and analysis of variance. RESULTS: Complete data were collected on 158 subjects. In all, 51 (32%) subjects developed IFG during the study. The analysis of variance showed significant differences between the IFG and normoglycaemic group in the baseline values of the McAuley index, trig:HDL, plasma adiponectin concentration and prevalence of the MetS. The ROC curve analysis confirmed this result and showed that the strongest predictors of IFG were baseline trig:HDL and IDF MetS classification, followed in order by the McAuley index, plasma adiponectin concentration and NCEP-ATPIII MetS classification. In contrast, the baseline values of fasting insulin, HOMA-IR and QUICKI did not predict IFG. DISCUSSION: This study showed that the IR indices, derived, in part, from plasma triglyceride concentration, were sensitive predictors for the development of IFG in normoglycaemic overweight and obese subjects. Indices derived from glucose and insulin did not identify this at-risk group. The study also showed that the presence of MetS and its abnormalities of an increased trig:HDL ratio and low plasma adiponectin concentration were all sensitive predictors of IFG.

Plasma levels of sex hormone-binding globulin, corticosteroid-binding globulin and cortisol in overweight subjects who develop impaired fasting glucose: a 3-year prospective study.

Circulating sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), and total and calculated free cortisol were measured in 206 overweight subjects to investigate whether or not they were markers of insulin resistance. Measurements were carried out on two occasions 36 months apart and subjects were grouped according to fasting plasma glucose. Fifty-one subjects, with a normal basal fasting glucose (<5.6 mmol/l) developed impaired fasting glucose 3 years later (> or = 5.6 mmol/l). Analysis either in toto or based on gender showed a highly significant increase in fasting insulin and insulin resistance, a modest increase in body mass index (BMI), but importantly no change in plasma SHBG, CBG, or cortisol concentrations. Subjects (n=101) with a normal fasting glucose both at baseline (<5.6 mmol/l) and at 36 months showed no significant change in fasting insulin, insulin resistance, SHBG, CBG, cortisol, or BMI. Cross-sectional analysis of the study population showed that plasma SHBG correlated negatively with insulin resistance both in men and women. Overall SHBG at baseline was not predictive of changes in fasting glucose. In females, plasma CBG correlated negatively with BMI. The major finding is that overweight subjects who developed impaired fasting glucose showed no significant change in plasma SHBG, CBG or cortisol, and therefore these indices are probably not early markers of insulin resistance in overweight subjects.

Plasma variation of corticosteroid-binding globulin and sex hormone-binding globulin.

Sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) circulate in plasma and bind their cognate ligands with high affinity, offering a steroid delivery system to target tissues by a variety of mechanisms. Analysis of these steroid-binding proteins is gaining importance in the clinical setting, although more information is warranted on their diurnal and biological variation. This study shows that plasma SHBG (in normal subjects) exhibits little diurnal or biological variation over the 30 day period studied, in contrast to CBG, where plasma levels peak in the early afternoon. This leads to attenuation of the diurnal free cortisol level rhythm compared to total cortisol. We also show that plasma CBG is significantly lower in male subjects with the metabolic syndrome compared to age-matched lean counterparts, and may therefore act as a surrogate marker of insulin resistance. The consequence of lower levels of CBG in these obese male subjects is reflected by higher levels of circulating free cortisol, potentially offering a more favourable environment for adipogenesis.

The postprandial state does not impair endothelial function in women with type 2 diabetes irrespective of glycaemic control.

AIMS/HYPOTHESIS: The postprandial state has been shown to be associated with endothelial dysfunction, a predictor of cardiovascular morbidity. In type 2 diabetes, postprandial metabolic excursions are prolonged and exaggerated, but less pronounced if glycaemic control is optimised. We investigated the impact of improved glycaemic control on endothelial function in the postprandial state. METHODS: We studied 19 postmenopausal women with type 2 diabetes and ten non-diabetic subjects. Participants with diabetes were re-studied 3 months after intensive glucose regulation. We measured forearm blood flow by strain gauge plethysmography during rest, during acetylcholine infusion and post ischaemia in the fasting state, and again 3 hours after a mixed meal (660 kcal, 55% fat). RESULTS: Endothelium-dependent vasodilation was impaired in the diabetic group (p<0.005) and improved following an HbA1c reduction of 0.96% (p<0.05 for high-dose acetylcholine infusion). Postprandial metabolic excursions were higher in the diabetic group (p<0.001, p<0.01 and p<0.05 for glucose, insulin and triglycerides respectively). Resting forearm blood flow increased in all groups after the meal (p<0.005). There was no difference in fasting and postprandial endothelium-dependent vasodilation before and after improved glucose regulation in either group. CONCLUSIONS/INTERPRETATION: The postprandial state does not impair endothelial function in non-diabetic women and does not make pre-existing endothelial dysfunction worse in women with type 2 diabetes, irrespective of glycaemic control.

Plasma sex hormone-binding globulin rather than corticosteroid-binding globulin is a marker of insulin resistance in obese adult males.

AIM: Plasma levels of corticosteroid-binding globulin (CBG) and sex hormone-binding globulin (SHBG) may be regulated by insulin. The aim of this study was to test the hypothesis that these steroid-binding proteins are markers of insulin resistance and obesity in adult patients with the metabolic syndrome. METHODS: Fasting blood samples were obtained from 108 male and 88 female overweight adult patients who had varying degrees of dyslipidaemia, adiposity and insulin resistance. We measured plasma levels of SHBG and CBG and investigated their correlation with insulin resistance [homeostasis model assessment (HOMA) % sensitivity] and anthropometric markers of adiposity. RESULTS: In male patients, plasma SHBG correlated positively with HOMA (% sensitivity) and negatively with anthropometric measurements, including body mass index, waist circumference (cm) and percentage body fat. There was no correlation with CBG and any other parameter in the male patients. The female patients were treated as two groups, those not using oral contraceptives or hormone replacement therapy (n = 67) and those taking steroid medications (n = 21). Female patients using steroid medications had significantly higher SHBG levels but neither group showed any correlation between SHBG, insulin resistance and adiposity. Correlation studies of CBG with other parameters in the female subgroups did not reach statistical significance. CONCLUSIONS: We conclude that plasma SHBG is another surrogate marker for insulin resistance in obese males but not in obese females. It also appears that plasma CBG is not a useful marker of insulin resistance in patients with the metabolic syndrome.

Plasma adiponectin in overweight, nondiabetic individuals with or without insulin resistance.

AIM: Adiponectin is a protein produced exclusively by adipocytes with putative insulin-sensitizing and anti-atherogenic properties. This cross-sectional study investigated the relationship between plasma adiponectin and a range of anthropometric, glycaemic, lipid and inflammatory parameters in overweight and obese subjects expressing characteristics of the metabolic syndrome. METHODS: Subjects were selected for the study from a clinical database, if they were non-diabetic, overweight [body mass index (BMI) > 25] and had features of the metabolic syndrome. The subjects were grouped according to BMI (25-30, 31-35 and >35 kg/m2) and then stratified for insulin resistance [homeostasis model assessment (HOMA) %S]. One hundred and ninety-seven patients (109 males and 88 females) were selected for the study by taking an equal number with the highest and lowest HOMA indices from each of the three BMI groups. Plasma adiponectin concentration was measured in duplicate by radioimmunoassay, and the relationship between these levels and the other parameters was investigated using correlation and multiple linear regression analyses. RESULTS: Plasma adiponectin concentration was higher in females than males (median 10.3 vs. 7.1 micro g/ml, p < 0.001) despite being matched for BMI. In both genders, adiponectin levels were inversely related to BMI, waist circumference, percentage body fat, insulin resistance and the fasting plasma concentration of leptin. A direct correlation in both sexes was found between adiponectin levels and high-density lipoprotein (HDL)-cholesterol, apolipoprotein A1 and age. Multiple linear regression analyses showed that the independent determinants of low plasma adiponectin concentrations were gender, age, BMI, insulin resistance and HDL-cholesterol. An association between reduced adiponectin and increased high-sensitivity plasma C-reactive protein concentration was observed only in female subjects and was independent of anthropometric variables. Our observation that adiponectin levels increase with age differs from the majority of other studies and may simply reflect the demographics of the population studied. CONCLUSIONS: This study shows that adiponectin is an important molecular link between obesity, insulin resistance and atherogenic lipoproteins. It is possible that plasma adiponectin concentration may be a convenient marker for identifying subjects with the metabolic syndrome who may progress to impaired glucose tolerance. Longitudinal studies are required in order to verify this clinical application of adiponectin.

Hemorheological investigations in patients with polycystic kidney disease.

Polycystic kidney disease (PKD) is associated with an increased incidence of hypertension and cardiovascular abnormalities. As hemorheology is an important hemodynamic determinant and may contribute to vasculopathies we measured whole blood viscosity and red blood cell (RBC) and plasma rheological factors in 38 patients with PKD and compared this data with similar measurements in age- and sex-matched healthy controls. Renal function was assessed by plasma creatinine concentration. Analysis of the data showed that the PKD group had a significant reduction in mean hematocrit and an increase in mean plasma viscosity and mean plasma fibrinogen concentration. Intrinsic RBC rheology assessed by standardised viscosity measurements was impaired in patients with PKD compared to control subjects. The changes in plasma and RBC rheology did not however result in increased whole blood viscosity in the patients with PKD due to the reduction in hematocrit level. Correlation analyses demonstrated a significant relationship between increased plasma creatinine concentration and lower hematocrit, decreased whole blood viscosity and impaired RBC deformability but not with increased plasma viscosity or plasma fibrinogen concentration. This study shows that although PKD is associated with mild abnormalities in plasma rheology and intrinsic RBC rheology these changes are offset by a reduction in hematocrit. The changes in RBC rheological determinants in PKD appeared to be related to the degree of renal impairment.

A comparison of post-prandial changes in flow-mediated dilatation in patients with type 2 diabetes with and without macroalbuminuria.

During the post-prandial period there is a decrease in systemic vascular resistance. This study compared meal-induced changes in flow-mediated dilatation (FMD) in patients with Type 2 diabetes with and without evidence of diabetic nephropathy as defined by the presence of macroalbuminuria. The effects on FMD of other factors such as smoking history, antihypertensive treatment and insulin use were also examined. Twelve patients with macroalbuminuria (>300 mg albumin/day) and 12 age- and sex-matched patients with normoalbuminuria (<50 mg albumin/day) participated in the study. Following a 12-hr overnight fast, forearm basal and reactive hyperaemic blood flow was assessed by venous occlusion plethysmography before and 2-hr after ingestion of a meal (2750 kJ) consisting of 56% fat, 26% carbohydrate and 16% protein. Plasma lipid and glycaemic indices were measured at the same times. The combined and grouped data was analysed using paired t tests and correlation and regression analyses. The meal resulted in significant increases in plasma glucose and triglyceride concentrations. While the meal resulted in a similar increase in basal blood flow rate in both patient groups, post-meal reactive hyperaemic flow increased significantly (p=0.04) in normoalbuminuric patients (mean individual increase: 33%) but remained unchanged in patients with macroalbuminuria (mean individual increase: 4%). The use of antihypertensive agents and insulin was also associated with an attenuated post-prandial hyperaemic response. In summary, our study demonstrated that the degree of renal impairment in patients with Type 2 diabetes may influence vasoactivity following a meal. Patients with evidence of diabetic nephropathy had a decreased post-prandial hyperaemic response, a result that indicated a reduced vasodilator reserve. The mechanism of this reduction in vasodilatation of peripheral vessels during the post-prandial period is probably multifactorial. These changes in vasoactivity have the potential to combine with other cardiovascular risk factors to enhance the development of atheroma.

Haemorheological effects of losartan and enalapril in patients with renal parenchymal disease and hypertension.

The objective of this study was to compare the effects of the angiotensin II (ang II) antagonist, losartan and the angiotensin-converting enzyme inhibitor (ACEI), enalapril on haemorheology. Twenty-nine patients with renal parenchymal disease and hypertension were enrolled in the prospective, open, parallel study that involved a 14-day washout period followed by a 120-day treatment period. Patients were allocated randomly to receive either losartan 50-100 mg/day (n = 15) or enalapril 2.5-10 mg/day (n = 14) to achieve blood pressure control <140/90 mm Hg. Blood pressure, haemorheology profile and plasma fibrinogen concentration were measured after the washout phase and after 2, 10, 60, and 120 days of treatment. The data were analysed using ANOVA with repeated measures. Twenty-seven patients completed the study. Treatment with both losartan and enalapril was associated with a significant decrease (P < 0.05) in relative high shear rate whole blood viscosity, indicating an increase in blood cell deformability. In patients taking losartan, the increase in blood cell deformability did not result in a decrease in mean whole blood viscosity due to a concomitant, significant increase in mean plasma viscosity (P < 0. 01). In contrast, the improved cell deformability in patients treated with enalapril resulted in a small and statistically insignificant decrease in mean whole blood viscosity (P = 0.06; mean change = -0.15 mPa sec). The mechanism of the increase in blood cell deformability and the rise in plasma viscosity associated with losartan remain unclear. It is possible but unproven that the improvement in intrinsic blood cell rheology with losartan and enalapril may be the result of changes in cation transport systems and/or the consequence of the protective antioxidant properties of drug metabolites.

Effect of lacidipine, a dihydropyridine calcium antagonist on renal function of hypertensive patients with renal insufficiency.

There are few studies on the use of dihydropyridine calcium antagonists in hypertensive patients with moderate renal insufficiency. We undertook an open study on the effects on renal function, albumin excretion and blood pressure of the slow-onset, long-acting dihydropyridine calcium antagonist, lacidipine, in 14 patients with stable, chronic renal insufficiency (mean assessed GFR 0.78 ml/s, range 0.50-1.17 ml/s) and moderate hypertension. Following a 2 week washout phase, lacidipine was administered for 24 weeks in a dose of 2 mg/day with the dose being titrated at 2 weekly intervals to a maximum of 6 mg/day in order to achieve adequate blood pressure control. Frusemide was introduced if blood pressure was not controlled on the maximum lacidipine dose. Blood pressure, creatinine clearance, 24 h urinary albumin excretion and plasma creatinine and albumin concentrations were measured at regular intervals throughout the study. Isotopic GFR was determined at the end of the washout period and at week 24. Lacidipine was not very effective in controlling blood pressure and had an adverse effect on renal function. In 3 patients with an incipient nephrotic syndrome this necessitated withdrawal from the study. Mean GFR of the 10 patients who completed the study decreased from 0.69 ml/s/1.73 m2 at baseline to 0.56 ml/s/1.73 m2 at week 24 (p = 0.006) with a decline in GFR being observed in 9 of these patients. The decrease in GFR was greatest in patients with poorly controlled blood pressure. An insignificant increase in mean urinary albumin excretion occurred during the study with this increase being observed only in patients with albuminuria > 1 g/24 h at baseline. These findings indicated that systemic hypertension altered glomerular hemodynamics and that the vasodilatation of pre-glomerular vessels which followed introduction of the calcium antagonist may have exacerbated this situation. The withdrawal of an angiotensin converting enzyme inhibitor during the washout period may have contributed to these changes. We suggest that renal function should be monitored closely in patients with renal insufficiency when a calcium antagonist is being used to control blood pressure, particularly in those with either marginal blood pressure control, significant albuminuria or an incipient nephrotic syndrome.

Oral vanadyl sulphate does not affect blood cells, viscosity or biochemistry in humans.

Vanadyl sulphate (VOSO4) is used to improve performance in weight training athletes. Concerns about its safety have arisen because vanadium compounds may cause anaemia and changes in the leukocyte system. In this study, the effects of oral VOSO4 (0.5 mg/kg/day) on haematological indices (red and white cell and platelet counts, red cell mean cell volume and haemoglobin level), blood viscosity (haematocrit, plasma viscosity and blood viscosity at 10s-1 and 100s-1 shear rates) and biochemistry (lipids and indices of liver and kidney function) were investigated in a twelve week, double blind, placebo controlled trial in 31 weight training athletes. Blood viscosity was evaluated at 0, 2, 4, 8 and 12 weeks and haematological indices and biochemistry were measured before and at the end of treatment. Both the treatment group and placebo group showed increases in haematocrit (3.3-3.6%) and blood viscosity (9-11% at 100s-1 shear; 35-38% at 10s-1 shear) but there were no significant effects of treatment. Similarly there were no treatment effects on haematological indices and biochemistry. Concerns about the adverse effects of oral vanadyl sulphate on blood are not supported by the results of this trial.

Fluvastatin for dyslipoproteinemia, with or without concomitant chronic renal insufficiency.

Renal insufficiency is frequently associated with both quantitative and qualitative abnormalities in lipid and hemorheologic profiles. Although this may lead to increased risk of cardiovascular disease, a number of studies have also shown dyslipidemia to be a significant risk factor for the progression of renal insufficiency in human chronic renal disease. This double-blind, placebo-controlled trial aimed to assess the effect of fluvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on these parameters in dyslipidemic patients with or without chronic renal insufficiency. After a 6-week placebo run-in, 42 patients who had been previously stratified into 2 groups on the basis of creatinine clearance levels (0.5-1.0 mL/sec or > 1.0-1.5 mL/sec) were randomized to treatment with fluvastatin (40 mg daily) or matching placebo. Significant differences (on analysis of variance with repeated measures) were seen between fluvastatin and placebo treatment groups for changes in total cholesterol (-15% vs 1%, respectively; p < 0.001), low density lipoprotein cholesterol (LDL-C; -21% vs -5%; p < 0.001), very low density lipoprotein cholesterol (-14% vs 14%; p = 0.017), very low density lipoprotein triglycerides (-1% vs 29%; p = 0.014) and total triglycerides (-7% vs 24%; p < 0.001). These effects on cholesterol levels were reflected in a significant decrease in apolipoprotein B levels with fluvastatin therapy (p < 0.001). Apolipoprotein A-I levels increased (p = 0.054) despite no significant change in the levels of high density lipoprotein cholesterol. Response to therapy did not differ between the 2 renal function groups for any of the lipid, lipoprotein, and apolipoprotein variables. Hemorheologic parameters were not altered with fluvastatin therapy, regardless of renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of enalapril on erythrocytosis in hypertensive patients with renal disease.

Treatment of hypertension with an angiotensin converting enzyme inhibitor (ACEI) may be associated with a decrease in haemoglobin concentration especially in patients with renal insufficiency. This open study in 19 patients with a variety of renal diseases with complicating hypertension investigated the effects of the ACEI, enalapril, on haemoglobin and plasma erythropoietin (EPO) concentrations. Blood samples were obtained at baseline and 2, 60 and 120 days after starting treatment with enalapril. By day 60 there was a significant decrease in mean haemoglobin concentration (mean decrease 7.4 g/l) that was sustained until day 120. Apart from a small, but significant, reduction by day 2, mean plasma EPO concentration remained constant throughout the study. The magnitude of the decrease in haemoglobin concentration was, however, significantly correlated with the baseline plasma creatinine concentration and creatinine clearance. These results suggested that the degree of renal insufficiency was important in determining the haematological response to ACE inhibition. While the mechanism of these changes remains unclear, our findings suggest that inhibition of the renin-angiotensin system, rather than decreasing EPO production, may reduce the erythropoietic activity of the hormone.

Effect of enalapril on hemorheology in hypertensive patients with renal disease.

An open, prospective study was undertaken to investigate the effects of enalapril on hemorheology in patients with renal disease and complicating hypertension. Cellular and plasma determinants of blood viscosity and renal function were measured in 19 patients at baseline and 2, 60 and 120 days after treatment with enalapril (mean dose 5.4; range 2.5-20 mg/day). Within 2 days of starting enalapril there was a significant decrease in apparent blood viscosity measured at high shear rate (-0.15 mPa.s; p < 0.05) which fell further by day 60. The decrease in blood viscosity was primarily the result of hemodilution, as evidenced by a concurrent fall in plasma albumin concentration and plasma viscosity. A small, but significant decrease, in hemoglobin concentration (-7.4g/l; p = 0.03), and a trend of improved red blood cell (RBC) and white blood cell (WBC) rheological properties may have also contributed to the decrease in blood viscosity. We conclude that enalapril had a beneficial effect on hemorheology in patients with renal disease. The mechanism of the rheological changes appeared to be multifactorial and would be expected to decrease vascular resistance to blood flow.