Treatment of elderly patients with isolated systolic hypertension with isosorbide dinitrate in an asymmetric dosing schedule.

Nitrates decrease pulse pressure more than mean arterial pressure (MAP) and are advocated for the treatment of isolated systolic hypertension (ISH). Nitrates show drug tolerance during chronic treatment so an asymmetric dosing regimen may prevent loss of effect of nitrates. This study investigates the anti-hypertensive effect of isosorbide dinitrate (ISDN) given in a twice daily asymmetric dosing regimen in elderly patients with ISH. After a 6-week placebo run-in period, patients entered the double-blind study. Ten patients received placebo and 11 patients ISDN 20 mg b.i.d. for 8 weeks. This dose could be doubled once. Office systolic and diastolic blood pressures (SBP/DBP) and ambulatory BP were measured. Pulse pressure was calculated as SBP-DBP. Office pulse pressure was more reduced during ISDN (17.9%) than with placebo (5%; P < 0.05). SBP and MAP decreased compared to baseline, but the changes were not statistically significant between the two groups. DBP tended to increase with ISDN compared to placebo. Mean 24-h, mean daytime and mean night-time pulse pressure decreased after treatment with ISDN (10.7%, 12.1%, 7.9%, respectively). Pulse pressure tended to decrease more during the day than during the night with ISDN. No changes could be demonstrated with placebo. In conclusion, pulse pressure decreased with ISDN, resulting in a lower SBP without a decrease in DBP. The latter may preserve coronary perfusion in ISH. With the asymmetric dosing regimen the decrease in pulse pressure was not clear at night. Whether a decrease in nocturnal BP, in addition to the spontaneous decrease, is advisable in ISH remains a matter of debate.

Successful recovery of a patient with thallium poisoning.

We describe a patient suffering from protracted and life-threatening thallium poisoning. She was treated with Prussian blue and forced diuresis, and made a good recovery. Cisapride may be effective in improving gastric emptying and relieving constipation resulting from the thallium and the treatment. Haematological abnormalities occurred in the early phase of the poisoning, with a prolonged fall in the CD4/8 lymphocyte ratio during recovery.

The influence of perindopril and the diuretic combination amiloride+hydrochlorothiazide on the vessel wall properties of large arteries in hypertensive patients.

OBJECTIVE: To compare the cardiovascular effects of 6 months of treatment with the angiotensin converting enzyme inhibitor perindopril and with the diuretic combination amiloride+hydrochlorothiazide, and to study possible persistence of observed treatment effects after discontinuation of antihypertensive therapy. DESIGN: A placebo run-in period preceded a 6-month active-treatment phase in 41 patients with essential hypertension, according to a double-blind, randomized, parallel-group design. Patients received either 4 mg perindopril or 2.5/25 mg amiloride+hydrochlorothiazide once a day. Patients were then studied for a 3-month single-blind placebo run-out period. RESULTS: After 6 months of treatment, systolic blood pressure was reduced significantly by perindopril (supine by 11%, sitting by 10%) and by amiloride+hydrochlorothiazide (supine by 8%, sitting by 12%). Diastolic blood pressure was also decreased significantly by perindopril (supine by 8%, sitting by 11%) and by amiloride+hydrochlorothiazide (supine by 4%, sitting by 9%). Mean arterial pressure decreased significantly during treatment with perindopril (by 9%) and with amiloride+hydrochlorothiazide (by 6%). Cardiac index increased with perindopril (by 6%), because of an increased stroke index (by 5%), but amiloride+hydrochlorothiazide did not change cardiac function. Systemic vascular resistance index decreased significantly more with perindopril (by 14%) than with amiloride+hydrochlorothiazide (by 8%). The distensibility of the common carotid artery was significantly enhanced by perindopril (by 16%), but not changed by amiloride+hydrochlorothiazide (1% difference). The difference between perindopril and amiloride+hydrochlorothiazide for carotid distensibility was statistically significant. The compliance of the common carotid artery tended to be increased more by perindopril (by 7%) than by amiloride+hydrochlorothiazide, which induced a 5% decrease in carotid compliance. After withdrawal of therapy, for both drugs, all treatment-induced changes were reversed to pretreatment values within 7 weeks. CONCLUSION: The distensibility of the elastic common carotid artery was increased by perindopril, but not by amiloride+hydrochlorothiazide. Large-artery properties of the muscular arteries and systemic vascular resistance improved with both drugs, but in general the changes were more pronounced with perindopril than with amiloride+hydrochlorothiazide. The present results indicate a more pronounced effect of perindopril at both macro- and microcirculatory levels, which will consequently lead to a larger decrease in cardiac afterload. After discontinuation of therapy all parameters returned to baseline values within 7 weeks.

A patient with combined mediastinal, mesenteric and retroperitoneal fibrosis.

We report a patient with combined mediastinal, mesenteric and retroperitoneal fibrosis who first presented with signs of a superior vena cava syndrome. She was successfully treated with corticosteroids. The aetiology, clinical picture, and possible therapy of idiopathic fibrosclerosis are discussed.

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.

Nebivolol in hypertension: a double-blind placebo-controlled multicenter study assessing its antihypertensive efficacy and impact on quality of life.

Nebivolol is a selective beta 1-adrenoceptor antagonist with a particular hemodynamic profile, suggesting an ancillary vasodilating property. The nature of this ancillary property is still unknown. The present double-blind placebo-controlled multicenter study investigated the effect of 4 and 8 weeks treatment with nebivolol 5 mg once daily on blood pressure (BP), heart rate (HR), blood parameters, and ECG. The effect on quality of life perception and the adverse effect profile were also studied. Nebivolol 5 mg once daily had a good antihypertensive effect in supine (10/8 mm Hg) as well as in standing position (16/10 mm Hg). Of 114 patients studied, 65% had either normalization of or > 10% reduction in diastolic BP (DBP). No evidence of drug tolerance was observed during the 8-week treatment period. Quality of life perception, as measured with the Inventory of Subjective Health (ISH) and the perceived health rating scale, was not impaired with nebivolol during the entire 8-week study. Nebivolol showed a favorable adverse effect profile and appeared to be devoid of central nervous system (CNS) adverse effects. The total number of complaints with nebivolol treatment did not differ from the number of complaints with placebo treatment. ECG and blood analyses, also show that nebivolol is safe and well tolerated. This study also shows that absolute drug-induced changes in quality of life perception can be assessed only in a placebo-controlled study and that comparison with baseline might be incorrect and misleading.

Evaluation of the coagulation/fibrinolysis balance in patients with colorectal cancer.

The coagulation and fibrinolysis profile was evaluated in 40 patients with newly diagnosed untreated colorectal carcinoma (24 males, 16 females; 29 patients without and 11 patients with metastases). Fibrinogen, von Willebrand factor antigen, FVIII:C, thrombin-antithrombin III complex (TAT III), fibrin monomers (FM), plasminogen activator inhibitor-1 (PAI-1) and D-dimers were tested. None of the patients had clinical or laboratory evidence of serious hemorrhage or thrombosis. The results of global routine coagulation tests (aPTT, PT) were not significantly changed. Significant elevations were found for median fibrinogen, von Willebrand factor antigen, FVIII:C, TAT III and D-dimers, compared with a healthy reference group. These results confirm earlier reports of an enhanced level of both coagulation and fibrinolysis markers in carcinoma patients and might be helpful in trying to understand the impact of several relatively new sensitive coagulation and fibrinolysis parameters in colorectal cancer. Moreover the position of the coagulation/fibrinolysis balance might be an explanation for the elevated incidence of thrombotic events in patients with cancer.

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)

Porphyria cutanea tarda in a patient with AIDS.

A 53-yr-old man, known to have had AIDS for 6 months, developed the clinical signs and symptoms of porphyria cutanea tarda (PCT) preceding deterioration of his illness. Urinary porphyrin analysis confirmed the diagnosis of PCT. At the time the cutaneous blistering and scars developed, he was taking zidovudine and fluconazole. Reviewing the literature suggested that association of the two disorders is not purely coincidental. Anaemia, due to chronic immune activation and therapeutic options in the light of AIDS, could play an important role in the development of PCT. We recommend analysing the urine for porphyrins in HIV-positive patients who have chronic photosensitivity of the skin.

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.

The extent of diffuse intravascular coagulation and fibrinolysis in patients with liver cirrhosis.

Twenty-five patients with different stages of liver cirrhosis were evaluated with regard to the degree of liver synthesis reduction, the extent of the decrease of blood coagulation factors and/or alterations of the fibrinolytic system. For the assessment of the residual level of liver synthesis we used pseudo-cholinesterase and serum albumin as references. We did not find a correlation between these quantities and antithrombin III or fibrinogen, but highly significant inverse correlations with tissue plasminogen activator activity and D-dimer concentration. We found considerable alterations in the concentrations of the coagulation and fibrinolysis factors, with the exception of fibrinogen and plasminogen activator inhibitor. Significant increases were seen for thrombin-antithrombin III complex, tissue plasminogen activator activity and D-dimer, while significant decreases were seen for antithrombin III and alpha 2-antiplasmin, compared with a group of healthy volunteers. In the group of patients with liver cirrhosis and reduced liver synthesis, as documented by lowered pseudo-cholinesterase and serum albumin, the reduction of both antithrombin III and alpha 2-antiplasmin was most prominent. Intravascular coagulation was negligibly small. For the fibrinolytic system, the increase of tissue plasminogen activator, the decrease of the fibrinolysis inhibitor (alpha 2-antiplasmin) and the elevated D-dimer concentration seem to be important. These results suggest an acceleration of fibrinolysis and the prolonged presence of cross-linked fibrin degradation products.

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)

Plasma concentration of coagulation and fibrinolysis factors and platelet function in hypertension.

Fifty-one patients with mild hypertension were evaluated in relation to the plasma concentrations of coagulation and fibrinolysis factors as well as for the aggregability of their platelets. In a considerable number of the patients (18/51), a significantly enhanced in vitro ADP (2 mumol/l)-induced aggregation was found. In the coagulation line significant increases could be demonstrated in fibrinogen, fibrin monomers and thrombin-antithrombin III. The fibrinolysis system showed significant increases for D-dimers, tissue plasminogen activator antigen and plasminogen activator inhibitor, whereas the tissue plasminogen activator activity was significantly diminished. Remarkably, there seems to be a discrepancy between the (low) tissue plasminogen activator activity and the (higher) plasminogen activator antigen concentration. Alterations in the plasma concentrations of the investigated coagulation and fibrinolysis factors and in the aggregability of the platelets are indicative of an involvement of coagulation, fibrinolysis and platelets in hypertension, which can be considered as partial risk factors for thrombophilia.

Comparison of the appropriateness of the latex and Elisa plasma D-dimer determination for the diagnosis of deep venous thrombosis.

Thirty-two patients suspected of deep venous thrombosis (DVT) of the leg were evaluated after simple plasma tests (latex D-dimer and Elisa D-dimer) against echography and phlebography as the gold standard of DVT. Seven patients showed negative results in the latter test. The classification conformity between the D-dimer methods amounted 84.4%. With regard to the diagnostic classification a high specificity of 100% was found for the latex D-dimer test at the cut-off level of 450 ng/ml, whereas for sensitivity, 96% was reached. The Elisa D-dimer test was striking by its high sensitivity of 100%, but its low specificity of 28.5%. In summary, these results demonstrate that when there is a suspicion of DVT according to the clinical symptoms, a negative latex test may reject the diagnosis, whereas the latex test is less useful to establish the diagnosis. On the contrary, the Elisa D-dimer test has a too high false-positive rate. The latex D-dimer test seems to be a reliable tool to exclude the diagnosis after which an ascending contrast venography can be omitted.