Is the effect of antihypertensive drugs on platelet aggregability and fibrinolysis clinically relevant?

Hypertension is associated with decreased fibrinolytic potential, mainly expressed as elevated plasma plasminogen activator inhibitor type 1 (PAI-1) levels, and increased platelet aggregability, which may account in part for the increased risk of atherosclerosis and its clinical complications in hypertensive patients. The effects of antihypertensive drugs on this prothrombotic state have been investigated and controversial findings have been reported, possibly because of differences in study designs, patients selected, and methodology used. Scarce and conflicting data exist about the effects of diuretics and beta-adrenoceptor antagonists on the fibrinolytic system, whereas ACE inhibitors have generally been reported to improve the fibrinolytic balance by decreasing plasma PAI-1 levels, calcium channel antagonists have been shown to increase tissue plasminogen activator (tPA) activity, and angiotensin II type 1 (AT(1)) receptor antagonists seem to exert neutral effects.

Effect of telmisartan/hydrochlorothiazide combination versus nifedipine GITS on ambulatory blood pressure and sympathetic activation.

Background: This study compares the effects of telmisartan hydrochlorothiazide (HCTZ) combination versus nifedipine GITS on ambulatory blood pressure (BP) and sympathetic activity, in patients with mild-to-moderate hypertension.

Methods: One hundred twenty-four outpatients with sitting diastolic BP > or =95 mmHg and <110 mm Hg were randomized to telmisartan 80 mg/HCTZ 12.5 mg daily (n = 62) or nifedipine GITS 60 mg daily (n = 62) for 12 weeks, according to a prospective, open-label, blind end point, parallel-group design.

Effect of manidipine as compared to atenolol on platelet aggregation in elderly patients with isolated systolic hypertension and type II diabetes mellitus.

This study was done to evaluate the effect of treatment with manidipine as compared with atenolol on thrombin-mediated platelet aggregation in elderly patients with isolated systolic hypertension and type II diabetes mellitus. After a 2-week washout placebo period, 60 elderly patients (aged 65-80 years) with isolated systolic hypertension (SBP > 140 mm Hg and DBP < 90 mm Hg) were randomly assigned to manidipine 10 mg or atenolol 50 mg 6-week treatment according to a double-blind, crossover design. Thirty patients had a concomitant well-controlled type 2 diabetes mellitus (HbA1c < or = 6.

Efficacy and safety of delapril plus manidipine compared with enalapril plus hydrochlorothiazide in mild to moderate essential hypertension: results of a randomized trial.

Background: The use of combination therapy is required to achieve blood pressure targets in 40% to 75% of patients with hypertension. There have been few studies comparing the efficacy and tolerability of the new fixed combination of the angiotensin-converting enzyme (ACE) inhibitor delapril 30 mg and the calcium channel antagonist manidipine 10 mg with those of a standard combination of another ACE inhibitor and a diuretic.

Objective: The aim of this study was to compare the antihypertensive efficacy and tolerability of delapril 30 mg given alone or with manidipine 10 mg with those of enalapril 20 mg given alone or with hydrochlorothiazide (HCTZ) 12.

Effect of amlodipine-atorvastatin combination on fibrinolysis in hypertensive hypercholesterolemic patients with insulin resistance.

Background: The aim of this study was to evaluate the effect of the amlodipine-atorvastatin combination on plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) activity in hypercholesterolemic, hypertensive patients with insulin resistance.

Methods: The study population included 45 patients, aged 41 to 70 years, with mild to moderate essential hypertension (diastolic blood pressure [BP] > or = 95 and < or = 105 mm Hg), hypercholesterolemia (total cholesterol > 200 and < 350 mg/dL), and insulin resistance (HOMA index > 2.5) After a 4-week wash-out period, they were randomized to amlodipine (5 mg) or atorvastatin (20 mg) or their combination at the same oral dosage for 12 weeks in three cross-over periods each separated by a 4-week placebo period (3 by 3 latin square design).

Effect of antihypertensive agents on quality of life in the elderly.

Management of hypertension in the elderly should take into account, in particular, the possible negative impact of antihypertensive drugs on the patient's quality of life, the deterioration of which may result in a loss of independence and reduced treatment compliance. Quality of life is recognised as a multifactorial variable and can be subdivided into different domains (symptomatic well-being, emotional, physical, work-social, cognitive and life satisfaction), which are generally explored by means of specific questionnaires or scales. When evaluating elderly patients with hypertension, it is necessary to pay particular attention to specific domains such as symptomatic well-being, cognitive function, activity and sexual function, which have already been diminished by the age itself and the disease.

Effect of delapril-manidipine combination vs irbesartan-hydrochlorothiazide combination on fibrinolytic function in hypertensive patients with type II diabetes mellitus.

The aim of this double-blind, double-dummy, parallel group study was to compare the effects of delapril-manidipine combination vs a irbesartan-hydrochlorothiazide combination on plasma tissue plasminogen activator (t-PA) and plasmogen activator inhibitor type I (PAI-l) activities in hypertensive patients with type II diabetes mellitus. After a 4-week run-in placebo period, 80 patients (37 male and 43 female), aged 41-65 years, were randomly allocated to an 8-week treatment with delapril 30 mg once daily or irbesartan 150 mg once daily. Thereafter, manidipine l0 mg once daily was added to delapril treatment and hydrochlorothiazide 12.

Effects of valsartan compared with enalapril on blood pressure and cognitive function in elderly patients with essential hypertension.

Objective: This prospective, randomised, open-label, blinded-endpoint study was to compare the effects of the angiotensin II (Ang II) AT1 receptor antagonist valsartan with those of the ACE inhibitor enalapril on blood pressure (BP) and cognitive functions in elderly hypertensive patients.

Methods: One hundred and forty-four patients aged 61-80 years with mild to moderate essential hypertension (DBP > or =95 mmHg and < or =110 mmHg at the end of a 2-week placebo run-in period) were randomly assigned to once daily (o.d.

Influence of losartan and atenolol on memory function in very elderly hypertensive patients.

The aim of this study was to compare the effect of the beta-adrenergic blocker atenolol and the Angiotensin II type 1 (AT1) receptor antagonist losartan on cognitive function in very elderly hypertensive patients. A total of 120 mild to moderate essential hypertensive (DBP >90 and <105 mmHg) patients, aged 75-89 years, were studied. After a 4-week wash-out period on placebo, they were randomized to receive atenolol 50 mg or losartan 50 mg for 24 weeks according to a parallel arm design.

[Therapeutic indications for acute venous thromboembolism. Current status and future perspectives].

Except for selected patients requiring aggressive therapies, the large majority of patients with acute venous thromboembolism are currently treated with full doses of unfractionated or low-molecular-weight heparins (LMWH) followed by oral anticoagulants for variable periods of time. LMWHs present a number of potential advantages over unfractionated heparin: a longer plasma half-life, improved subcutaneous bioavailability, and a more predictable dose-response relationship. As a result of these pharmacokinetic properties, these compounds have the potential to greatly simplify the initial treatment of venous thromboembolism, making the treatment of suitable patients feasible in an outpatient setting with considerable saving in costs and improvement in patients' quality of life.

Differential effects of lercanidipine and nifedipine GITS on plasma norepinephrine in chronic treatment of hypertension.

This study aimed to compare the effects of two long-acting dihydropyridine calcium channel blockers (CCBs) with different pharmacologic properties, lercanidipine and nifedipine Gastro-Intestinal Therapeutic System (GITS), in the chronic treatment of essential hypertension. After a 4-week placebo run-in period, 60 patients of both sexes were randomly treated with lercanidipine 10 to 20 mg or nifedipine GITS 30 to 60 mg taken orally for 48 weeks, according to a double-blind, parallel group design. For the first 4 weeks of treatment, the lowest dose of each drug was used, followed by higher doses if diastolic blood pressure (BP) was >90 mm Hg.

Effect of benazepril amlodipine combination on fibrinolysis in hypertensive diabetic patients.

Objective: The aim of this study was to compare the effects of benazepril and amlodipine in monotherapy versus in combination with plasma t-PA and PAI-1 activity in hypertensive type-2 diabetic patients.

Methods: After an initial 6-week wash-out, single-blind placebo period, 38 patients, 17 men and 21 females, were randomly assigned to receive benazepril 10 mg o.d.

Atherosclerosis and secondary deep vein thrombosis: a difficult correlation.

The aim of this study was to verify the degree of atherosclerosis in a group of subjects affected by secondary deep vein thrombosis and in a matched control group. Sixty-three patients were studied. Of these, 19 were cases (mean age 62.

Chronic viral hepatitis: a prospective factor against atherosclerosis. A study with echo-color Doppler of the carotid and femoral arteries and the abdominal aorta.

Objective: To evaluate if chronic viral hepatitis may be a protective factor for atherosclerosis.

Methods: Echo-doppler of the carotid and femoral arteries and the abdominal aorta was used to examine 48 patients with a histological diagnosis of chronic viral hepatitis (42 hepatitis C virus-related, 6 hepatitis B virus-related), with a low degree of activity and preserved hepatic function, and 50 controls matched for age, sex and exposure to the main risk factors of atherosclerosis.

Results: The prevalence of atherosclerosis in patients was clearly lower than in controls in all investigated sites, although the difference was statistically significant only for the carotid arteries.

APC-dependent impairment of T cell proliferation in aging: role of CD28- and IL-12/IL-15-mediated signaling.

The age-related impairment of phytohaemagglutinin (PHA)-triggered peripheral blood mononuclear cell (PBMC) proliferation was paralleled by an expansion of CD28 (-) T lymphocytes with a poor capacity to undergo lectin-induced blastogenesis. However, both CD28 (-) and CD28 (+) T cells isolated from aged individuals exhibited a significant reduction of proliferative response to PHA in comparison with young controls, this implies that the CD28-mediated signaling is not the only defective pathway in the elderly. Thus, PBMC or T cell subsets plus monocytes from aged donors were stimulated with PHA and assayed for the production of, or the response to cytokines known to regulate T cell functions.

Cancer and thromboembolic disease: how important is the risk of thrombosis?

The overall incidence of postoperative DVT in patients with cancer is twice as high as in cancer-free patients. Immobilisation and chemotherapy increase the risk of thrombosis as does the insertion of central venous lines. Patients with cancer who have established thrombosis exhibit a remarkably high risk of recurrent thromboembolism, particularly in the first months after the interruption of anticoagulant treatment: the risk is double that of non-cancer patients.

Risk factors for thrombosis in patients with immune mediated heparin-induced thrombocytopenia.

Background: As reported by major clinical series in the literature, about 2% of patients receiving unfractionated heparin (UFH) develop immune-mediated (type II) heparin-induced thrombocytopenia (HIT) that may be complicated in 30-75% of cases by a paradoxical thrombotic syndrome (HITTS), either arterial or venous. HITTS carries relevant rates of mortality and morbidity, amongst which cerebral and/or myocardial infarction and limb amputations. It is unclear as yet why some patients suffer from isolated thrombocytopenia (HIT), whilst others have HITTS.

Effects of antihypertensive therapy on sexual activity in hypertensive men.

Sexual dysfunction has a high prevalence among hypertensive men, and hypertension per se, regardless of drugs, has been suggested to affect sexual function. The available studies have not clarified which factors play a major role in the pathogenesis of sexual dysfunction in hypertensive men. Neurovascular factors, however, seem to be especially important, (in particular defective nitric oxide activity), although hormonal and psychogenic factors cannot be excluded.

Leukaemic transformation in a case of thrombocythaemia. Case report and review of the literature.

The authors describe a case of thrombocythaemia, with subsequent leukaemic transformation. Cytochemical and immunocytochemical investigations indicated a trilineage involvement of the myeloid series, compatible with a leukaemic transformation at the level of the colony-forming unit granulocytes, erythrocytes, macrophages, megakaryocytes. No cytogenetic abnormalities were observed.

[Association between motoneuron disease and Waldenström macroglobulinemia].

The authors describe the case of a patient who was referred to their Unit because of polyneuropathy and was subsequently found to be affected by Waldenström's macroglobulinemia. A monoclonal paraproteinemia is frequently described in the serum of subjects with motor neuron disease. The association between motor neuron disease (MND) and lymphoproliferative disease (LPD) could be the result of a coincidence, but LPD seems to be disproportionally frequent in patients with MND, compared to the population in general.

Venous thromboembolism as first manifestation of cancer.

Since Trousseau's time numerous studies have addressed the relationship between cancer and venous thromboembolism (VTE) providing firm evidence of the increased risk of subsequent clinically overt malignancy during the follow-up of patients with idiopathic VTE. These malignancies are not limited to certain subtypes, but involve virtually all body systems. This knowledge has led to a long-standing debate on the need to screen for occult malignancies patients with idiopathic VTE with no clinical evidence of cancer at the time of the index thrombotic event.

Heparins and venous thromboembolism: current practice and future directions.

Unfractionated heparin (UFH) in adjusted doses and low-molecular-weight heparins (LMWH) in fixed doses are the chosen therapy for the initial treatment of venous thromboembolism. The use of UFH protocols ensures that virtually all patients will promptly achieve the therapeutic range for the activated partial thromboplastin time. However, proper use of UFH requires considerable expertise, can cause inconvenience and has limitations.