A randomized, placebo-controlled study of loop diuretics in patients with essential hypertension: the bumetanide and furosemide on lipid profile (BUFUL) clinical study report.

This study was conducted to determine whether loop diuretics are more effective than placebo in reducing blood pressure without raising serum lipid levels, and whether bumetanide is more effective than furosemide in this respect. In a double-blind, 24-week placebo-controlled crossover study, 27 patients with essential hypertension were treated in four periods of 6 weeks each, including placebo twice, furosemide 40 mg daily, and bumetanide 1 mg daily. Several metabolic parameters, including serum lipid levels, and blood pressure were assessed. Overall levels of total cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol were 5%, 12.4%, and 4.8% higher, respectively, during loop diuretic therapy than during placebo treatment. Overall systolic and diastolic blood pressure measurements were 12 mmHg and 4 mmHg lower, respectively, during loop diuretic therapy than during placebo treatment. Any added effect of bumetanide on serum lipid levels and blood pressure compared with furosemide, however, could not be confirmed. Our results indicate that the loop diuretics bumetanide and furosemide are effective in reducing blood pressure, and influence serum lipid levels markedly less than do thiazide diuretics or chlorthalidone. In addition, these results indicate that differences in blood pressure reduction and serum lipid levels between the two compounds were small and nonsignificant.

Nephrogenic diabetes insipidus in a lethargic lithium-treated patient.

We report on a patient who developed severe lithium-induced nephrogenic diabetes insipidus (NDI) and neurotoxicity, despite recommended serum lithium levels. Hydrochlorothiazide and indomethacin appeared effective antipolyuric drugs, which led to a normalization of serum osmolality. After re-initiating lithium therapy, with lithium levels around 0.3 mmol/l, recurrence of NDI or neurotoxicity was not observed, despite discontinuation of indomethacin and hydrochlorothiazide. Together with hypothyroidism, NDI and neurotoxicity must be considered in lethargic lithium-treated patients.

Prothrombin fragment 1.2 in both treated and untreated hypertensive patients.

The coagulation parameters factor VII, fibrin monomers, thrombin-antithrombin III (TAT) complexes and fragment 1.2 (F 1.2) were studied in 43 treated and 11 untreated patients (27 males, 27 females age range 19-70 years) with hypertension of moderate severity. The patients included in this study who were treated with antihypertensive drugs were still hypertensive in spite of their treatment. The median F 1.2 concentrations (interquartile range) in the hypertensive patients were more than double those of the reference group: 1.47 (0.79) nmol/l as against 0.74 (0.49) nmol/l (p < 0.0001). Median concentrations of TAT complexes 2.9 (1.7) micrograms/l versus 2.6 (1.6) micrograms/l (p < 0.02) as well as those of fibrin monomers 14.2 (4.6) nmol/l as against 10.6 (2.0) nmol/l (p < 0.01) also were significantly elevated in the hypertensive patients, but to a lesser extent. For factor VII a significant difference was found between males and females. The median factor VII value in the male patients was 137% (32%) compared with 100% (33%) in the male reference group (p < 0.001). In the hypertensive female patients this median value was 147% (36%) in comparison with 139% (60%) in the female reference group (p < 0.01). By the Spearman rank test, no correlations were found between the coagulation parameters and systolic or diastolic blood pressure, age or duration of hypertension. F 1.2 values were correlated with fibrin monomers (r = 0.33, p < 0.03) but not with the other coagulation parameters studied. The elevated F 1.2 values, together with elevated concentrations of TAT complexes and fibrin monomers, are signs of an activated coagulation system in these hypertensive patients.

The effect of microalbuminuria on glycaemic control, serum lipids and haemostasis parameters in non-insulin-dependent diabetes mellitus.

Microalbuminuria is an important risk factor for cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM) patients although the pathogenic mechanism between microalbuminuria and cardiovascular disease has not yet been established. Microalbuminuria in insulin-dependent diabetes mellitus (IDDM) patients has been related to abnormalities in haemostasis, poor glycaemic control, disadvantageous alterations in the lipid spectrum and elevated concentrations of lipoprotein(a), another independent risk factor for cardiovascular disease. In this study the interrelations between microalbuminuria and metabolic control, lipoprotein(a), other blood lipids and several haemostasis parameters were studied in 96 NIDDM patients (50 women, 46 men). Forty-three patients showed microalbuminuria. No significant differences were found in blood lipids (Lp(a), serum cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides), glycaemic control (HbA1c) and several haemostasis parameters (factor VII, VIII, fibrin monomer, thrombin-antithrombin III, D-dimer, tissue plasminogen activator antigen and plasminogen activator inhibitor-1) between the micro- and normoalbuminuric subgroups. In the microalbuminuric subgroup increased concentrations for plasminogen and alpha 2-antiplasmin were measured. In general, the presence of microalbuminuria was not associated with significant alterations in glycaemic control, blood lipids or haemostasis parameters in this group of 96 NIDDM patients. Further investigation is required to explain the excess cardiovascular mortality in patients with an elevated urinary albumin excretion rate.

Coagulation factors and lipid composition of the blood in treated and untreated hypertensive patients.

The cardiovascular risk factors blood pressure, overweight, hyperlipidaemia and several coagulation parameters were studied in a group of 54 otherwise healthy patients with essential hypertension of moderate severity. Of the 54 hypertensive patients, 43 were treated with anti-hypertensive drugs and 11 were not. The patients included in this study who were treated with anti-hypertensive drugs were still hypertensive in spite of their treatment. Lipoprotein levels and coagulation parameters did not differ between the untreated and treated hypertensive patients. Substantial percentages of patients were found to have hypertriglyceridaemia (46%), elevated LDL-cholesterol (28%) and elevated lipoprotein(a) concentrations (43%). Coagulation factors F VIIIc, fibrin monomer and factor VII in males were significantly elevated in comparison with a healthy reference group. These data are compatible with a moderate activation of the coagulation system. Correlations were established between systolic blood pressure and serum cholesterol (r = 0.43, p = 0.003), LDL-cholesterol (r = 0.34, p = 0.02) and triglycerides (r = 0.35, p = 0.01); Quetelet-index with fibrinogen (r = 0.37, p = 0.02) and thrombin-antithrombin III (r = 0.30, p = 0.04); and triglycerides with F VIIc (r = 0.34, p = 0.03) and fibrin monomer (r = 0.29, p = 0.04) respectively. These data link hypertension and hyperlipidaemia with increased coagulation activity and may contribute to our understanding of why these two cardiovascular risk factors accelerate atherogenesis.

Glycometabolic control, lipids, and coagulation parameters in patients with non-insulin-dependent diabetes mellitus.

Diabetes mellitus and hyperlipidemia are associated with coronary heart disease and with hypercoagulability, another independent risk factor for coronary heart disease. In 65 non-insulin-dependent diabetes mellitus patients [41 females, 24 males, median age 66 years (range 43-81 years)] treated with antidiabetic agents glycometabolic control (HbA1c), lipids (Quetelet index and blood lipids), and several coagulation parameters were studied in comparison with a reference group. Serum triglycerides were elevated [median (interquartile range) 2.3 (1.3) mmol/l vs. 1.6 (0.7) mmol/l in the controls (P < 0.001)], whereas the median lipoprotein(a) concentration was 65 (157) mg/l in the diabetic patients versus 44 (114) mg/l in the control group (not significantly different). Median high-density lipoprotein-cholesterol concentrations were slightly decreased in the diabetic patients: 1.2 (0.3) mmol/l compared with 1.3 (0.4) mmol/l in the control group (P < 0.02). Elevated levels of fibrinogen, fibrin monomers, thrombin-antithrombin III complex, and factor VIIIc were found in the diabetic patients and factor VII in male diabetic patients. These elevated coagulation parameters are indicators of an activated coagulation system in this patient group. By Spearman's rank test, only HbA1c values correlated with anti-thrombin III (r = 0.27, P < 0.03) and showed a tendency towards a correlation with lipoprotein(a) (r = 0.23, P < 0.07). Triglycerides correlated with the Quetelet index (r = 0.27, P < 0.03), high-density lipoprotein-cholesterol (r = -0.41, P < 0.001), and factor VII (r = 0.35, P < 0.01), whereas serum cholesterol concentrations correlated with factor VII (r = 0.27, P < 0.04) and with fibrin monomers (r = 0.29, P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Low order correlations of lipoprotein(a) with other blood lipids and with coagulation and fibrinolysis parameters in hypertensive and diabetic patients.

Lipoprotein(a) (Lp(a)) has been established as an important independent risk factor for the development of cardiovascular disease. Apolipoprotein(a), together with apo B-100 the apolipoprotein of Lp(a), is homologeous to plasminogen but lacks fibrinolytic capacity and appeared to interfere with fibrinolysis in in vitro and ex vivo experiments. We determined the correlations between Lp(a) and other blood lipids (serum cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), coagulation parameters (fibrinogen, factor VII, factor VIII:C fibrin monomers, thrombin-antithrombin III) and fibrinolysis parameters (tissue plasminogen activator antigen, plasminogen activator inhibitor-1 and D-dimer) in 54 patients with essential hypertension, in 65 non-insulin-dependent diabetic patients and in 116 insulin-regulated diabetic patients. Signs of activated coagulation and increased reactive fibrinolysis were found in all three patient groups. In the hypertensive patients, Lp(a) was significantly correlated with LDL-cholesterol (r = 0.25, P = 0.04) and triglycerides (r = -0.30, P = 0.03), while in insulin-regulated diabetics, Lp(a) was also correlated with LDL-cholesterol (r = 0.20, P = 0.03). In the hypertensive patients and both diabetic groups there was no correlation of Lp(a) with coagulation or fibrinolysis parameters. These data show that Lp(a) concentrations are not related to coagulation or fibrinolysis parameters in hypertensive or diabetic patients and confirm the presence of an activated coagulation system in these patient groups.

Fibrinolysis factors and lipid composition of the blood in treated and untreated hypertensive patients.

The correlations between the cardiovascular risk factors hypertension, overweight, hyperlipidemia and fibrinolysis parameters were studied in a group of 54 otherwise healthy patients (age 19 to 70 years) with essential hypertension of moderate severity. Of the 54 patients 43 were treated with antihypertensive drugs and eleven were not. The patients included in this study who were treated with antihypertensive drugs were, in spite of their treatment, still hypertensive. Lipoprotein levels and fibrinolysis parameters did not differ between the untreated and treated patients. In the patient group we found significant incidence of hypertriglyceridemia (46%) elevated LDL-cholesterol (28%) and elevated lipoprotein (a) levels (43%). In comparison with a healthy control group the hypertensive patient group showed a decreased median tissue plasminogen activator activity (interquartile range): 0.23 (0.79) IU.10(3)/l vs 1.5 (0.47) IU.10(3)/l in the controls (p less than 0.0001), an increased tissue plasminogen activator antigen concentration: 8.2 (4.5) micrograms/l vs 5.1 (3.9) micrograms/l in the controls (p less than 0.0001), an elevated plasminogen activator inhibitor-1 level: 2.8 (2.5) AU.10(3)/l vs 1.1 (2.0) AU.10(3)/l in the controls (p less than 0.01) and a slightly increased alpha 2-antiplasmin concentration: 110 (8)% vs 98 (16)% in the controls (p less than 0.0001). Median D-dimer concentration levels were substantially increased in the hypertensive patients: 315 (263) micrograms/l vs 199 (146) micrograms/l in the controls (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Microalbuminuria in diabetic patients: relationship to lipid, glyco-metabolic, coagulation and fibrinolysis parameters.

One hundred and sixteen insulin treated diabetic patients were evaluated for the relationship between the presence of microalbuminuria and several lipid, glyco-metabolic, coagulation and fibrinolysis factors. A significant correlation existed only between microalbuminuria and HbA1c (r = 0.23, p = 0.008) and D-dimer (r = 0.28, p = 0.002). After the subdivision of the patients in a group without (n = 85) and a group with microalbuminuria (n = 31) significant differences were found between these two groups for the HDL-cholesterol content (p less than 0.05), the HbA1c level (p less than 0.01) and for the D-dimer concentration (p less than 0.01). Comparison of the patient groups without and with microalbuminuria separately with a healthy volunteers group without albuminuria resulted in significant differences for HDL-cholesterol, triacylglycerols, HbA1c, fructosamine, fibrin monomer and D-dimer, whereas fibrinogen also was significantly different between the diabetic group without microalbuminuria and the healthy volunteers group. Several factors predisposing for atherosclerosis (decrease of HDL-cholesterol, increase of triacylglycerols, coagulation activation with relatively insufficient fibrinolysis) were noticed in both diabetic groups without or with microalbuminuria, but more pronounced in the latter group. The appliance of a Receiver Operating Characteristic (ROC) curve for HbA1c against microalbuminuria (cut-off level 20 micrograms/min) reconfirmed the value of adequate glycaemic control in diabetics for the prevention of microalbuminuria. In conclusion the results of this study show a significantly poorer glycaemic control in insulin treated diabetics with microalbuminuria than in those without microalbuminuria. The presence of lower HDL-cholesterol, higher triacylglycerols and the elevation of fibrin monomers and D-dimers is more pronounced in the microalbuminuria group.(ABSTRACT TRUNCATED AT 250 WORDS)

Disparity of thyrotropin (TSH) and prolactin responses to TSH-releasing hormone in obesity.

The effect of TRH administration on TSH and PRL release was investigated in 11 obese women and 16 normal weight women. There were no differences in basal serum levels of estradiol, T3, T4, TSH, or PRL between the 2 groups. The increment of TSH levels in the obese group [mean maximum change (delta max), 19.3 +/- 3.0 (+/-SEM) mIU/liter] was significantly higher (P less than 0.025) than that in the control group (delta max, 11.3 +/- 1.3 mIU/liter), whereas PRL levels rose significantly less (P less than 0.025) in these obese women than in the control group (delta max, 738 +/- 132 and 1311 +/- 133 mIU/liter, respectively). Since serotonin is known to stimulate PRL and inhibit TSH release, deficiency of serotonin has been hypothesized as the cause of this disparity between TSH and PRL levels in obesity.