Low plasma adiponectin is associated with coronary artery disease but not with hypertension in high-risk nondiabetic patients.

OBJECTIVE: To investigate the association of plasma adiponectin levels with coronary artery disease (CAD), arterial hypertension (HT), and insulin resistance (IR) in nondiabetic Caucasian patients. DESIGN: We measured plasma adiponectin levels, IR (HOMA index), and the CAD atherosclerotic burden (angiography-based modified Duke Index score) in 400 nondiabetic patients undergoing coronary angiography. HT was diagnosed by the European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines or if patients were on antihypertensive treatment. RESULTS: Coronary artery disease was found in 62% of the patients and ruled out in the rest (non-CAD group). Plasma adiponectin levels were inversely related to the CAD score (beta = -0.12, P = 0.029) and predicted the coronary atherosclerotic burden independent of other cardiovascular risk factors. However, they were similar in NT and HT and showed no correlation with blood pressure values. In non-CAD, but not in CAD patients, they were lower in patients with than without IR (8.3 +/- 1.2 vs. 11.3 +/- 1.3, respectively; P = 0.007). CONCLUSIONS: In nondiabetic high-risk Caucasian patients plasma adiponectin levels are inversely related to CAD severity and IR; however, they are not strongly related to blood pressure values.

Glomerular hyperfiltration predicts the development of microalbuminuria in stage 1 hypertension: the HARVEST.

Factors related to the development of microalbuminuria in hypertension are not well known. We did a prospective study to investigate whether glomerular hyperfiltration precedes the development of microalbuminuria in hypertension. We assessed 502 never-treated subjects screened for stage 1 hypertension without microalbuminuria at baseline and followed up for 7.8 years. Creatinine clearance was measured at entry. Urinary albumin and ambulatory blood pressure were measured at entry and during the follow-up until subjects developed sustained hypertension needing antihypertensive treatment. Subjects with hyperfiltration (creatinine clearance >150 ml/min/1.73 m2, top quintile of the distribution) were younger and heavier than the rest of the group and had a greater follow-up increase in urinary albumin than subjects with normal filtration (P<0.001). In multivariable linear regression, creatinine clearance adjusted for confounders was a strong independent predictor of final urinary albumin (P<0.001). In multivariable Cox regression, patients with hyperfiltration had an adjusted hazard ratio for the development of microalbuminuria based on at least one positive measurement of 4.0 (95% confidence interval (CI), 2.1-7.4, P<0.001) and an adjusted hazard ratio for the development of microalbuminuria based on two consecutive positive measurements of 4.4 (95% CI, 2.1-9.2, P<0.001), as compared with patients with normal filtration. Age, female gender, and 24 h systolic blood pressure were other significant predictors of microalbuminuria. In conclusion, stage 1 hypertensive subjects with glomerular hyperfiltration are at increased risk of developing microalbuminuria. Early intervention with medical therapy may be beneficial in these subjects even if their blood pressure falls below normal limits during follow-up.

Albumin excretion in diabetic patients in the setting of acute myocardial infarction: association with 3-year mortality.

AIMS/HYPOTHESIS: Diabetes mellitus is associated with increased mortality in subjects with acute myocardial infarction (AMI). We aimed to estimate the risk of mortality in AMI patients with and without diabetes using the urinary albumin : creatinine ratio (ACR). METHODS: This is a prospective study of 121 consecutive, non-selected diabetic AMI patients, 121 age- and sex-matched non-diabetic AMI patients and 61 diabetic non-AMI outpatients as control subjects. All data were obtained during the first 7 days of hospitalisation and each AMI patient was followed for a period of exactly 3 years. Baseline ACR RIA measurements were made on the 1st, 3rd and 7th days of admission. RESULTS: Adjusted ACR values were significantly higher in the diabetic AMI patients than in the diabetic control outpatients ( p<0.0001), and a significant difference was observed between the weekly ACR slopes for these two groups ( p<0.0001). Microalbuminuria was more prevalent in the diabetic AMI patients than in the non-diabetic AMI patients on the 1st day (62% vs 46%, p=0.01) and 3rd day (41% vs 29%, p=0.04). Among the AMI patients with normoalbuminuria (ACR <30 microg/mg), the mortality rate was 11.6% for the patients without diabetes and 33.8% for those with diabetes ( p=0.001). The mortality rate was much higher among the AMI patients with microalbuminuria (ACR >/=30 microg/mg) and similar for the diabetic (68.0%) and non-diabetic patients (74.3%). In a multivariable Cox model, ACR ( p<0.0001) and diabetes status ( p=0.01) were associated with adverse outcome even when several other clinical variables were included in the model. Furthermore, a negative interaction was found between diabetes and ACR ( p=0.01). CONCLUSIONS/INTERPRETATION: Microalbuminuria frequently occurs in diabetic and non-diabetic AMI patients during the first 3 days of admission to hospital and can be used to identify subjects at high risk of mortality.

Microalbuminuria during acute myocardial infarction; a strong predictor for 1-year mortality.

AIMS: Urinary albumin excretion increases during acute myocardial infarction but little is known on the prognostic significance and the pathophysiological mechanisms of microalbuminuria in this clinical setting. The primary aim of the study was to examine whether urinary albumin excretion has predictive power for 1-year mortality after acute myocardial infarction. A secondary objective was to gain insight into the pathophysiological mechanisms of increased urinary albumin in myocardial infarction. METHODS AND RESULTS: This is a prospective cohort study conducted in three coronary care units (Northeast Italy). Four hundred and thirty-two unselected, consecutively enrolled patients with acute myocardial infarction (66.3+/- 12.3 years of age) were studied. The incidence of mortality was related to the baseline urinary albumin:creatinine ratio. The best cut-off for total mortality approximated to 50 mg x g(-1)on the first day after myocardial infarction, 30 mg x g(-1)on the third day, and to 20 mg x g(-1)on the seventh day. At multivariable Cox analysis, the albumin:creatinine ratio was the strongest among several independent predictors of mortality (adjusted relative risks: 3.6 (95% CI, 2.1--6.2) on the first day, 4.9 (95% CI, 2.9--8.2) on the third day and 4.0 (95% CI, 2.3--6.8) on the seventh day). Independent determinants of urinary albumin were plasma aldosterone on the first day, and inflammatory markers on the third and seventh days. CONCLUSION: Urinary albumin assessed in the first week after acute myocardial infarction is a strong prognostic marker for 1-year mortality.

Identification of the etiology of primary aldosteronism with adrenal vein sampling in patients with equivocal computed tomography and magnetic resonance findings: results in 104 consecutive cases.

The objectives of this study were to investigate the usefulness of adrenal vein sampling in identifying the etiology of primary aldosteronism (PA) in patients with equivocal CT and MR findings. Between 1990 and 1999, 104 referred hypertensive patients (45 women and 59 men, aged 49.6 +/- 11.6 yr) were diagnosed to have PA with inconclusive computed tomography scan and magnetic resonance results, based on established criteria. Adrenal vein sampling (AVS) for measurement of plasma aldosterone (A) and cortisol (C) levels was performed in all. Selectivity of AVS was assessed by the ratio between C levels in each adrenal vein and in the infrarenal inferior vena cava plasma (C(side)/C(IVC)). A receiver operator characteristics analysis was carried out to establish 1) the best AVS-derived index, 2) the degree of selectivity that could provide an accurate diagnosis, and 3) whether a correct diagnosis could be made from a unilaterally selective AVS. An aldosterone-producing adenoma (average diameter, 12.2 +/- 0.08 mm) was eventually diagnosed in 41 patients (39.4%) and was excluded in the rest. Adrenal vein rupture leading to partial adrenal loss occurred in 1 patient (0.9% complication rate). By assuming a cut-off value of C(side)/C(IVC) > or = 1.1, AVS was selective in 85.7% and 94.1% of cases on the right and left sides, respectively, and bilaterally in 80.6% of cases. Of all AVS-derived indexes, the A/C of one over the A/C contralateral side [(A/C)(side)/(A/C)(contralateral side)] furnished the best diagnostic accuracy. With a bilaterally selective AVS, a value of (A/C)(side)/(A/C)(contralateral side) > or = 2 provided a conclusive etiological diagnosis of PA in 79.7% of cases. At variance, no accurate diagnosis could be made from unilaterally selective AVS. AVS was feasible and safe in most PA patients with inconclusive computed tomography and magnetic resonance scans. When bilaterally selective (i.e. C(side)/C(IVC) > or = 1.1) a ratio of (A/C)(side)/(A/C)(control) > or = 2 provided the best compromise of sensitivity and false positive rate for lateralization of the etiology of PA.

Prognostic significance of hypertension and albuminuria for early mortality after acute myocardial infarction.

OBJECTIVE: To assess the risk of mortality associated with hypertension and microalbuminuria in patients with acute myocardial infarction. DESIGN: A prospective study. SETTING: Intensive care units in three Italian general hospitals. PATIENTS: In total 309 consecutive patients (including 97 women) aged 66.6 +/- 12.5 years, admitted to hospital for acute myocardial infarction. MAIN OUTCOME MEASURES: Albumin excretion rate measured by radioimmunoassay of 24 h urine samples, on the first and third days after admission to hospital. In-hospital mortality rate among the patients stratified according to their history of hypertension and albumin excretion rate. RESULTS: Of the patients, 147 had histories of hypertension. Forty-four per cent of the normotensive and 43% of the hypertensive subjects had microalbuminuria on the first day. On the third day the percentages were 25 and 29%, respectively. Twenty-two patients died before discharge from hospital. Patients were divided into four groups according to whether they had microalbuminuria or not and likewise for hypertension. Mortality rate among the subjects with hypertension and microalbuminuria combined was greater than those among the other three groups (P < 0.0001 on the first and third days). The relative hazard ratio was 11.7 on the first day, and 15.6 on the third day. In a multivariate Cox's model hypertension and microalbuminuria combined had a greater predictive power for mortality than either variable alone. Killip class, age, and creatinine kinases MB level were other significant predictors of death. CONCLUSIONS: These results show that the combination of hypertension and microalbuminuria is associated with a greater risk of in-hospital mortality among subjects with acute myocardial infarction, independently of degree of heart failure and other possible confounders.

Acute effects of the oral administration of midodrine, an alpha-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites.

The effects of the acute administration of arterial vasoconstrictors on renal plasma flow (RPF) and urinary sodium excretion (UNaV) in cirrhotic patients with ascites with or without hepatorenal syndrome (HRS) are still controversial. As a consequence, vasoconstrictors are not actually used in the treatment of renal sodium retention or HRS in these patients, regardless of the several lines of evidence suggesting that these renal functional abnormalities are related to a marked arterial vasodilation. The lack of an orally available effective arterial vasoconstrictor probably represents a further reason for this omission. Consequently, the present study was made to evaluate the acute effects of the oral administration of midodrine, an orally available -mimetic drug, on systemic and renal hemodynamics and on UNaV in cirrhotic patients with ascites. Mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), systemic vascular resistance (SVR), left forearm blood flow (LFBF), left leg blood flow (LLBF), RPF, glomerular filtration rate (GFR), UNaV, plasma renin activity (PRA), plasma concentration of antidiuretic hormone (ADH), and the serum levels of nitrite and nitrate (NOx) were evaluated in 25 cirrhotic patients with ascites (17 without HRS and 8 with type 2 HRS) before and during the 6 hours following the oral administration of 15 mg of midodrine. During the first 3 hours after the drug administration, a significant increase in MAP (89.6 +/- 1.7 vs. 81.80 +/- 1.3 mm Hg; P < .0001) and SVR (1, 313.9 +/- 44.4 vs. 1,121.2 +/- 60.1 dyn . sec . cm-5; P < .0001) accompanied by a decrease in HR (69 +/- 2 vs. 77 +/- 3 bpm; P < .005) and CI (2,932.7 +/- 131.4 vs. 3,152.5 +/- 131.4 mL . min-1 . m2 BSA; P < .0025) was observed in patients without HRS. No change was observed in LFBF and LLBF. The improvement in systemic hemodynamics, which was also maintained during the the 3- to 6-hour period after midodrine administration, was accompanied by a significant increase in RPF (541.5 +/- 43.1 vs. 385.7 +/- 39.9 mL . min-1; P < .005), GFR (93.1 +/- 6.5 vs. 77.0 +/- 6.7 mL . min-1; P < .025), and UNaV (92.7 +/- 16.4 vs. 72.2 +/- 10.7 microEq . min-1; P < .025). In addition, a decrease in PRA (5.33 +/- 1.47 vs. 7.74 +/- 2.17 ng . mL-1 . h; P < .05), ADH (1.4 +/- 0.2 vs. 1.7 +/- 0.2 pg . mL-1; P < .05), and NOx (33.4 +/- 5.0 vs. 49.3 +/- 7.3 micromol-1; P < .05) was found. In patients with HRS, the effects of the drug on the systemic hemodynamics was smaller and shorter. Accordingly, regardless of a significant decrease in PRA (15.87 +/- 3.70 vs. 20.70 +/- 4.82 ng . mL-1 . h; P < .0025) in patients with HRS, no significant improvement was observed in RPF, GFR, or UNaV. In conclusion, the acute oral administration of midodrine is associated with a significant improvement in systemic hemodynamics in nonazotemic cirrhotic patients with ascites. As a result, renal perfusion and UNaV also improve in these patients. By contrast, midodrine only slightly improves systemic hemodynamics in patients with type 2 HRS, with no effect on renal hemodynamics and renal function.

Albumin excretion rate increases during acute myocardial infarction and strongly predicts early mortality.

BACKGROUND: This study was undertaken to assess whether albumin excretion rate (AER) increases during acute myocardial infarction (AMI) and whether it predicts in-hospital mortality. METHODS AND RESULTS: The study was carried out in 496 subjects admitted to hospital for suspected AMI. Of these, 360 had evidence of AMI. The other 136 were studied as control subjects. AER was assessed by radioimmunoassay in three 24-hour urine collections performed on the first, third, and seventh days after admission. Left ventricular ejection fraction was measured by two-dimensional echocardiography in 254 subjects. AER adjusted for several confounders was higher in the AMI than the non-AMI group on the first (69.2+/-5.2 versus 27.3+/-8.5 mg/24 h, P<.0001) and third (30.3+/-2.7 versus 12.5+/-4.4 mg/24 h, P=.001) days, whereas no difference was present on the seventh day. When the subjects with heart failure were excluded, the difference between the two groups remained significant (first day, P<.0001; third day, P=.001). On the basis of classification of the 26 AMI patients who died in hospital according to whether they had normal AER, microalbuminuria, or overt albuminuria, mortality rate progressively increased with increasing levels of AER (P<.0001). In a Cox's proportional hazards model, AER was a better predictor of in-hospital mortality than Killip class or echocardiographic left ventricular ejection fraction. A cutoff value of 50 mg/24 h for first-day AER and 30 mg/24 h for third-day AER yielded a sensitivity of 92.3% and of 88.5% and a specificity of 72.4% and of 79.3%, respectively, for mortality. Adjusted relative risks for the two cutoff values were 17.3 (confidence limits, 4.6 to 112.7) and 8.4 (confidence limits, 2.4 to 39.3), respectively. CONCLUSIONS: These data show that AER increases during AMI and that it yields prognostic information additional to that provided by clinical or echocardiographic evaluation of left ventricular performance.

Renovascular hypertension with low-to-normal plasma renin: clinical and angiographic features.

1. Low-to-normal renin renovascular hypertension (RVH) and the accuracy of renal vein renin ratios were investigated in 129 consecutive patients referred for suspected RVH. Forty-nine had essential hypertension, 24 unilateral renoparenchymal hypertension and 56 renal artery obstruction. Of the latter, 86% were diagnosed retrospectively as RVH, based on fall in blood pressure with correction of renal ischaemia. We measured baseline, captopril-stimulated and renal vein plasma renin activity (PRA) levels, as well as several other parameters. 2. PRA was low-to-normal in 37% of the RVH patients [low-to-normal renin (LNR-) RVH group] and elevated in the remaining 63% [high-renin (HR-) RVH group]. In the LNR-RVH group, low-to-normal renin levels, by immunoreactive active renin and plasma renin concentration measurements, and a blunted response of PRA to captopril, were seen. As compared with HR-RVH, LNR-RVH patients had a longer duration of hypertension (P < 0.05), higher serum K+ (P = 0.04) and lower diastolic blood pressure (P = 0.02). However, they did not differ for the other variables, including the fall in blood pressure after correction of renal ischaemia. Although the number of bilateral stenoses was similar in the two groups, no patient in the LNR-RVH group had total renal artery occlusion compared with 53% in the HR-RVH group (P = 0.00015). The accuracy of renal vein renin indices were high enough to justify their use only in the patients with total occlusion of a renal artery. 3. Thus LNR-RVH is common in patients with longstanding hypertension without a totally occluded renal artery. Since the sensitivity of renin measurements is low, cure of hypertension would be precluded for more than one third of RVH patients, if these tests were a prerequisite for identifying RVH.

Relationship of plasma renin activity with caffeine intake and physical training in mild hypertensive men. HARVEST Study Group.

UNLABELLED: To study the relationship between plasma renin activity (PRA) and coffee consumption, cigarette smoking, alcohol intake and physical activity habits. SETTING: The multicentre HARVEST trial, involving 17 Hospital Centres in Northeast Italy. SUBJECTS: 351 borderline to mild hypertensive men (mean age +/- SEM 22.7 +/- 0.47 years), never treated for hypertension. INTERVENTIONS: Office and 24-hour blood pressure measurement, supine and standing PRA levels, and urinary catecholamines output. MAIN OUTCOME MEASURES: PRA levels according to coffee intake and physical activity status. RESULTS: Coffee intake showed a major effect on PRA. Supine PRA levels were 40% higher in the subjects abstaining from coffee (n = 94) than in the coffee drinkers and was similar in the moderate (n = 223) and heavy (n = 34) drinkers. A weaker negative association was found between coffee use and PRA on standing. Office and whole-day blood pressure and heart rate, and urinary catecholamines did not differ according to coffee intake. Supine PRA was lower in the subjects performing regular physical activity than in the inactive subjects. Office and whole-day diastolic blood pressure and heart rate, and urinary norepinephrine were lower in the active than in the sedentary men. No relationship was found between PRA measured either in the supine or the upright posture and tobacco or alcohol use. In a multiple linear regression model supine PRA was negatively correlated with age, coffee consumption and physical activity habits. CONCLUSIONS: Chronic coffee intake and physical training showed an inverse relationship with PRA in mild hypertensive men, while tobacco and alcohol use were unrelated to PRA.

Immunoreactive endogenous ouabain in primary aldosteronism and essential hypertension: relationship with plasma renin, aldosterone and blood pressure levels.

OBJECTIVE: To investigate the role of ouabain in human hypertension and to establish whether immunoreactive endogenous ouabain is secreted by the adrenal gland under the influence of dopaminergic regulation. METHODS: We measured plasma levels of endogenous ouabain by immunoassay, together with other variables, including plasma renin activity and aldosterone levels, in 91 clinically selected hypertensives and 19 healthy volunteers. We also measured endogenous ouabain in adrenal venous blood and the effect of DA2 dopaminergic receptor blockade and stimulation. After a thorough clinical evaluation, 64 patients were diagnosed with essential hypertension and 24 with primary aldosteronism. RESULTS: Plasma levels of endogenous ouabain were higher in essential hypertensives than in controls. Multiple regression analysis showed a significant relationship of mean blood pressure with plasma endogenous ouabain, age and body mass index, but not with other measured parameters. The plasma levels of endogenous ouabain were more than two standard deviations above the mean value for normotensives in 45% of patients with essential hypertension in whom plasma renin activity was normal. Higher plasma levels of endogenous ouabain were found in patients with aldosterone excess, specifically affecting 56% of 17 patients with surgically confirmed adrenal cortical adenoma and one (14%) of seven patients with idiopathic causes. Removal of adenomas lowered blood pressure in half of the patients in whom plasma levels of endogenous ouabain normalized after surgery. Plasma endogenous ouabain levels were similar in venous blood from the adrenal and inferior vena cava, and plasma levels were not influenced by DA2 dopaminergic blockade and stimulation. CONCLUSION: Approximately half of Caucasian patients with essential hypertension and with hyperaldosteronism exhibit elevated circulating levels of endogenous ouabain. The latter do not appear to be secondary to hypertension, are unrelated to plasma renin activity, and may not involve adrenal type-2 dopaminergic receptors.

[Urinary albumin excretion increases during an acute myocardial infarct especially in patients who develop heart failure]. / L'escrezione urinaria di albumina aumenta durante infarto miocardico acuto soprattutto nei pazienti che sviluppano insufficienza cardiaca.

AIM OF THE STUDY: To evaluate the profile of albumin excretion rate (AER) in the first days of acute myocardial infarction (AMI), its relationship with serum enzymes and the presence of heart failure, and the effect of thrombolytic therapy. METHODS: Two hundred and thirty-one consecutive patients admitted to coronary care unit for suspected AMI were examined. Patients with diabetes mellitus, urinary tract infections or proteinuric diseases were excluded. In 135 patients (95 males, 40 females) AMI diagnosis was confirmed. The remaining 96 (56 males, 40 females) were considered as controls. AER was measured by radioimmunoassay in 24-hour urine samples at the first, third and seventh day after admission and expressed as mg/24h. Statistical analysis was performed after AER logarithmic transformation using repeated measure ANOVA: RESULTS: Mean age was 66.9 +/- 12.2 years (range = 35 -91) in the AMI group and 63.2 +/- 12.3 years (range = 33-91) in the controls (p = 0.023) Age-adjusted blood pressure was lower in the AMI group than in the controls (p < 0.0001 for both systolic and diastolic), while no difference was found in heart rate. Plasma cholesterol, triglycerides, creatinine and uric acid were similar in the 2 groups. Mean AER was 43.4 +/- 64.8, 26.9 +/- 51.2 and 23.9 +/- 52.7 mg/24h at 1st, 3rd and 7th day respectively in the AMI group and 24.9 +/- 58.2, 13.7 +/- 25.8 and 17.9 +/- 44.1 mg/24h respectively in the controls (p = 0.014). In the AMI group, first day AER significantly and positively correlated with CPK (r = 0.287, p = 0.001), CPK-MB (r = 0.239, p = 0.007) and GOT (r = 0.300, p = 0.001). Within the patients with AMI, those who developed heart failure (n = 57), had higher AER (48.6 +/- 68.4, 29.7 +/- 54.9 and 28.1 +/- 55.8 mg/24h at 1st, 3rd and 7th day in patients with mild heart failure -2nd Killip Class- and 100.0 +/- 141.7, 50.3 +/- 66.4 and 64.2 +/- 74.4 mg/24h in those with severe heart failure -3rd and 4th Killip Class-) than those who did not (31.0 +/- 41.7, 19.6 +/- 45.6 and 16.5 +/- 45.7 mg/24h respectively) (p = 0.004). In a multiple linear regression model AER was significantly related to peak values of GOT (1st day) and CPK (3rd day) and to presence of heart failure (3rd and 7th day). Thrombolytic therapy (n = 48) did not influence AER. CONCLUSIONS: The results of the present study show that AER increases following AMI, chiefly in the subjects who develop heart failure. AER correlates with serum enzymes peak levels at 1st and 3rd day and with presence of heart failure at 3rd and 7th day after admission, and is not influenced by thrombolytic therapy. These data suggest that in AMI the initial increase in AER is due to the inflammatory process which accompanies cardiac necrosis, while in a later phase its rise is mainly due to the increased intraglomerular capillary pressure consequent to heart failure.

[Pressure and metabolic effects of terazosin in essential hypertension]. / Effetti pressori e metabolici della terazosina nell'ipertensione essenziale.

To assess the efficacy and safety of different doses of the alpha-1 blocker terazosin on long-term therapy, 12 essential hypertensives (7 males, 5 females, aged 27-61) were investigated. The study was conducted according to the Latin square design and each patient underwent 4 periods of treatment with 2, 5, 10 mg/day terazosin and placebo, in a double-blind, randomized order. Each treatment lasted 4 weeks. In comparison to placebo, a fall in diastolic pressure was observed already with the 2 mg/daily dose, with a decrease > 10 mmHg in 7 patients (responders). Body weight increased in a dose dependent manner, while atrial natriuretic peptide, serum glucose and insulin during oral glucose tolerance test, total cholesterol, HDL and LDL cholesterol, triglycerides were unaffected. It is concluded that terazosin is effective and safe in essential hypertensives already at 2 mg daily dose. Further reduction in blood pressure at higher doses is likely to be counteracted by salt and water retention.

Interactions between insulin and sodium homeostasis in essential hypertension.

It has been proposed, therefore, that hyperinsulinemia may favor the development of hypertension through sodium retention, sympathetic nervous system activation, and vascular hypertrophy. In insulin-resistant hypertensive subjects, insulin infusion during euglycemic clamp promotes a transient sodium retention by stimulating proximal tubular Na+ reabsorption, but chronic hypertension usually is not associated with extracellular fluid and plasma volume expansion. In essential hypertensive subjects, intracellular potassium is decreased and intracellular sodium increased, which is consistent with insulin resistance. The latter is also associated with high red blood cell Li+/Na+ exchange, and chronic insulin treatment in insulin-dependent diabetics induces a slight increase in Li+/Na+ CT. This is a functioning mode of the Na+/H+ exchange, and its increase may reflect either an increased number of transport units or abnormal kinetic properties. Experiments in vitro and in vivo suggested that any change in insulin concentration and insulin sensitivity may affect Li+/Na+ and Na+/H+ counter-transport. High Li+/Na+ and Na+/H+ CT are associated with a significant cardiac and vascular remodeling in essential hypertension, insulin-dependent diabetes, and familiar hypertrophic cardiomyopathy. Reduced insulin sensitivity is associated with salt-sensitive hypertension. Finally, insulin potentiates the effects of other agonists (eg, thromboxane A2, angiotensin II) on vascular contraction and cell growth. These data indicate that insulin may play a role in the pathogenesis of hypertension and its major complications by amplifying the effects of sodium, vasoconstrictors, and growth factors.

Variability of atrial natriuretic peptide plasma levels in ascitic cirrhotics: pathophysiological and clinical implications.

Ascitic cirrhotic patients are a heterogenous population with respect to factors that may affect plasma human atrial natriuretic peptide levels (such as degree of plasma volume and plasma levels of angiotensin II, vasopressin and norepinephrine). Thus the proven variability of plasma human atrial natriuretic peptide values in ascitic cirrhotic patients may be due also to the selection of patients, not only to the study conditions. The response to standardized stepped-care medical treatment of ascites makes it possible to characterize ascitic cirrhotic patients with different patterns of renal sodium excretion, intrarenal sodium handling, plasma renin activity, plasma aldosterone and thus, probably, effective circulating volume. Consequently, we evaluated human atrial natriuretic peptide plasma levels in controls (n = 23), in ascitic cirrhotic patients who underwent spontaneous diuresis (group A, n = 7) and in cirrhotic patients who required diuretic treatment (group B, n = 44). The last group was then divided into two subgroups. Subgroup B-R (n = 25) included patients who responded to spironolactone alone, whereas subgroup B-NR (n = 19) included patients who did not respond to 500 mg/day spironolactone. All patients were maintained on identical normocaloric restricted sodium intake (80 mEq/day) throughout the study. Ascitic cirrhotic patients, as a whole, had higher values of human atrial natriuretic peptide than did controls (70.8 +/- 46.6 pg/ml vs. 41.7 +/- 16.3 pg/ml, p < 0.025). No difference was found in human atrial natriuretic peptide/plasma renin activity between the two groups (87 +/- 160 pg/ng/hr vs. 44 +/- 73 pg/ng/hr, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of thrombin-antithrombin III complexes in the diagnosis of deep vein thrombosis.

Plasma thrombin-antithrombin III (T-AT) complexes are reputed to be an indirect manifestation of thrombin generation, and a role for their determination in the diagnosis of deep vein thrombosis (DVT) has been advocated. In order to evaluate the accuracy of T-AT complexes assay for DVT diagnosis, in 166 consecutive outpatients with clinical suspicion of the disease, plasma concentration of T-AT complexes was measured immediately before venography by means of an enzyme-linked immunosorbent assay kit. The result of the T-AT complexes assay was elevated in 29 of the 48 patients with DVT (sensitivity, 60%). The T-AT complexes levels were within the normal range in 104 of the 118 patients with normal venograms (specificity, 88%). The positive and the negative predictive value were 67% and 85%, respectively. The authors conclude that the T-AT complexes assay is of little value for the diagnosis of DVT in outpatients.

Tubular site of renal sodium retention in ascitic liver cirrhosis evaluated by lithium clearance.

Renal tubular sodium handling was evaluated in 27 non-azotemic cirrhotic patients with ascites and positive sodium balance and in 17 controls after at least 5 days of a constant sodium intake using the lithium clearance as an index of fluid delivery to the distal tubule. Plasma renin activity and plasma aldosterone were also evaluated. Sodium fractional excretion, filtered sodium load, absolute sodium distal delivery, lithium fractional excretion and absolute distal sodium reabsorption were significantly lower in cirrhotics than in controls (0.58 +/- 0.11 vs. 1.29 +/- 0.12%, P less than 0.001; 12529 +/- 677 vs. 15707 +/- 796 microEq min-1 1.73 m-2 BSA, P less than 0.005; 2384 +/- 135.2 vs. 3685 +/- 219.3 microEq min-1 1.73 m-2 BSA, P less than 0.001; 19.5 +/- 1.0 vs. 24.2 +/- 1.3%, P less than 0.01; 2299 +/- 127 vs. 3485 +/- 214 microEq min-1 1.73 m-2 BSA, P less than 0.001, respectively). A correlation was found between lithium clearance and sodium clearance only in cirrhotic patients (r = 0.62; P less than 0.01). Distal sodium reabsorption evaluated as a per cent of filtered sodium load was lower in cirrhotics than in controls (19.1 +/- 1.0 vs. 22.4 +/- 1.2%, P less than 0.05) while distal sodium reabsorption evaluated as a per cent of sodium distal delivery was higher in cirrhotics than in controls (96.7 +/- 0.4 vs. 94.4 +/- 0.5%, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)