The Effect of Beta-Blockers, Aspirin, and Natural Habituation on Procoagulant Activity, Expression of Cellular Adhesion Molecules, and Endothelial Activation in Response to Acute Mental Stress: a Randomized Controlled Trial.
试验速览
- 阶段
- 1 期
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Change scores in plasma levels of D-dimer determined by subtracting levels immediately after the stressor as compared to baseline levels prior to the stressor.
研究概览
简要总结
This randomized double-blinded controlled trial uses a factorial design to investigate whether application of beta-blockers (inderal 80 mg) or aspirin (100 mg) or a combination thereof has an effect on the activation of the hemostatic system, the platelets and the endothelium in response to acute mental stress. Specifically we test the hypothesis that inderal attenuates the activation of the hemostatic system as compared to placebo. The second hypothesis is that aspirin attenuates the activation of platelets as compared to placebo. Subjects will be randomly allocated to either of the four following study arms: placebo - inderal - aspirin - inderal plus aspirin. Subjects will receive the study medication for five days prior to the mental stress. The acute mental stress consists of a public speaking session of 10 min duration immediately followed by a mental arithmetic test of 5 min duration. Blood will be collected prior to the stress, immediately thereafter, at 45 min at at 1 hour and 45 min.
详细描述
Background: Population based studies have established hemostatic abnormalities as independent risk factors for atherosclerosis and related adverse outcomes. These abnormalities are characterized as prothrombotic by elevated plasma levels of e.g. fibrinogen or D-dimer. Prothrombotic states appear to aggravate the impact of other risk factors, e.g. hypertension. Other epidemiologic studies have shown a sizable association between chronic mental stress (e. g. marital discord in women) or acute mental stress (anger) and coronary heart disease. A large case-crossover study attributed a 2.3-fold increased relative risk of acute myocardial infarction during the 2 hours following outbursts of anger. This risk was modified by aspirin (risk ratio of 2.9 in non-users, risk-ratio of 1.4 with prior to aspirin intake). We have recently shown that acute mental stress is followed by profound rises of D-dimer and induction of a prothrombotic state. In real life, individuals are frequently and repetitively exposed to similar stressors (e.g. work or marital discord). Those who fail to habituate and to mitigate their adrenergic responses and hemostatic changes, may be at increased risk of rapid progression of atherosclerosis. These individuals might particularly benefit from preventive medication with beta-blockers or aspirin.
Objectives: To elucidate whether administration of non-specific beta-blockers, aspirin or both may abrogate the prothrombotic shift in the hemostatic balance in response to acute mental stress.
To elucidate the pathway leading from central nervous system arousal after acute mental stress to increases in plasma D-dimer levels by investigating intermediate steps in the process, including activation of mononuclear and endothelial cells, of platelets, and of hemostatic factors.
To show that some individuals do not habituate when repetitively being exposed to the same stressor or/and that habituation blunts the stress response as do beta-blocking medication, aspirin or both.
Subjects: 80 healthy male and nonpregnant female non-smokers aged 40 - 55 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- Double
入排标准
- 年龄范围
- 40 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Life-time non-smoker or non-smoker for more than a year,
- •native language Swiss-German,
- •systolic blood pressure <160 mm Hg, diastolic blood pressure <100 mm Hg.
- •Subjects must have a body mass index that is not considered to be a cardiovascular risk factor, i.e. ≤ 26.5 kg/m2.
排除标准
- •Individuals reporting cardiovascular disease, renal disorders, endocrine disorders, hepatopathy, psychiatric disorders or who take regular medication for any of these conditions.
- •Persons are excluded, who report to drink >5 cups (0.15 l each) of brewed coffee (> 500 mg caffeine) a day, or who report drink more than 1.0 l beer and 0.45 l wine per day, respectively.
- •All subjects on regular beta-blocking or aspirin medication are excluded from the study.
- •Participants will be required not to take aspirin or any other non-steroidal anti-inflammatory drug during the study period, beginning 10 days prior to the first study medication.
结局指标
主要结局
Change scores in plasma levels of D-dimer determined by subtracting levels immediately after the stressor as compared to baseline levels prior to the stressor.
次要结局
- Change scores of a) monocyte and T-lymphocyte expression of L-selectin, lymphocyte-function associated antigen (LFA-1), and CD40L
- monocyte tissue-factor antigen (CD 142) expression
- plasma levels of TAT, t-PA, and PAI-1
- plasma levels of soluble intercellular adhesion molecule (sICAM-1), soluble vascular adhesion molecule (sVCAM-1), endothelin-1, and vWF