Pathophysiological processes underlying emotional triggering of acute cardiac events

Acute negative emotional states may act as triggers of acute coronary syndrome (ACS), but the biological mechanisms involved are not known. Heightened platelet activation and hemodynamic shear stress provoked by acute stress may contribute. Here we investigated whether patients whose ACS had been preceded by acute anger, stress, or depression would show heightened hemodynamic and platelet activation in response to psychophysiological stress testing. We studied 34 male patients an average of 15 months after they had survived a documented ACS. According to an interview conducted within 5 days of hospital admission, 14 men had experienced acute negative emotion in the 2 h before symptom onset, and 20 men had not experienced any negative emotion. Hemodynamic variables and platelet activation were monitored during performance of challenging color-word interference and public speaking tasks and over a 2-h poststress recovery period. The emotion trigger group showed significantly greater increases in monocyte-platelet, leukocyte-platelet, and neutrophil-platelet aggregate responses to stress than the nontrigger group, after adjusting for age, body mass, smoking status, and medication. Monocyte-platelet aggregates remained elevated for 30 min after stress in the emotion trigger group. The emotion trigger group also showed poststress delayed recovery of systolic pressure and cardiac output compared with the nontrigger group. These results suggest that some patients with coronary artery disease may be particularly susceptible to emotional triggering of ACS because of heightened platelet activation in response to psychological stress, coupled with impaired hemodynamic poststress recovery.     

Assessment of biochemical aspirin resistance at rest and immediately after exercise testing.

Some aspirin-treated patients experience thromboembolic events, a phenomenon termed 'aspirin resistance', which may be clinical or biochemical by definition. Physical exercise is known to enhance platelet secretion and aggregability. To evaluate the presence of biochemical aspirin resistance at rest and immediately after exercise in individuals with stable coronary artery disease or coronary artery disease risk factors. We prospectively enrolled 101 patients who had received 100 or 300 mg/day enteric-coated aspirin for at least 7 days. Biochemical aspirin resistance (defined as normal collagen-epinephrine closure time < 165 s) was studied using the standardized platelet function analyzer. Of the 101 patients, 63 were aspirin sensitive both at rest and immediately after exercise, 18 exhibited biochemical aspirin resistance both at rest and after exercise, and 20 were aspirin sensitive at rest but exhibited biochemical aspirin resistance immediately after exercise. The results of exercise testing were similar in all three groups (each P > 0.05). Our results indicate that in almost 20% of the patients, aspirin did not seem to protect against exercise-induced platelet activation, despite the presence of aspirin sensitivity at rest. We did not, however, determine the extent to which the biochemical aspirin resistance noted in our study applied to clinical events.     

The thienopyridines

Platelet adhesion, activation, and aggregation are key processes in the pathogenesis of coronary disease. Inhibition of these processes forms the cornerstone of therapy for coronary artery disease and particularly of acute coronary syndromes (ACS). Aspirin was the only available antiplatelet therapy for over 100 years, and it improves clinical outcome in a wide range of clinical situations. However, aspirin only inhibits platelet activation mediated by thromboxane A2, allowing platelet activation to occur through innumerable other pathways. As a result, adverse ischemic events are common when aspirin alone is used for the treatment of coronary disease, including ACS, during coronary interventions (particularly during stent implantation), and following coronary vascular brachytherapy (VBT). In these clinical situations, the presence of either thrombus, deep injury to the vessel wall, or delayed vascular reendothelialization leads to intense and often prolonged platelet activation, overwhelming the relatively weak effects of aspirin. The development of the thienopyridines, a class of antiplatelet drugs that reduce adenosine diphosphate-(ADP) mediated platelet activation, has significantly improved clinical outcomes in many coronary conditions. Widespread use of ticlopidine, the first available thienopyridine, was limited by frequent side-effects, including life-threatening neutropenia and thrombotic thrombocytopenic purpura. Following the introduction of clopidogrel, a thienopyridine with an excellent safety profile, dual antiplatelet therapy with aspirin and clopidogrel has become standard therapy following coronary stent implantation and coronary VBT. In patients presenting with ACS, the addition of clopidogrel to aspirin has now been proven to reduce ischemic events. The most important limitation of dual antiplatelet therapy is the increased bleeding risk as compared with aspirin alone, particularly in patients undergoing coronary artery bypass grafting during the index hospitalization. However, for many patients with ACS, combination therapy is appropriate.     

Major clinical vascular events and aspirin-resistance status as determined by the PFA-100 method among patients with stable coronary artery disease: a prospective study.

Aspirin inhibits platelet activation and reduces major vascular events in patients with stable coronary artery disease. The extent of platelet inhibition, denoted as aspirin resistance, however, is not always sufficient. A correlation between aspirin resistance as measured by aggregometry and adverse clinical events has been demonstrated. The point-of-care platelet function analyzer PFA-100 is usually used to detect aspirin resistance, but the relation between PFA-100 results and the vascular prognosis is not assessed. We prospectively enrolled 97 patients with stable coronary artery disease who were on aspirin (160 mg per day since 1 month or longer). Aspirin resistance was measured by the PFA-100 analyzer. Median follow-up was 2.5 years and the primary outcome was the composite of death, myocardial infarction, and ischemic cerebral infarction or acute limb ischemia. In our study, 29 patients (29.9%) showed resistance to aspirin, with a higher percentage of female patients (38 vs. 15%; P=0.01). During the follow-up, aspirin resistance was not associated with an increased risk of death, myocardial infarction, or ischemic vascular event compared with the aspirin-sensitive patients (17 vs. 13%; P>0.60). In this cohort of stable coronary artery disease, patients on aspirin dose of 160 mg per day, the aspirin-resistance status based on the PFA-100 results is not associated with a significant increase in major vascular clinical events.     

Platelet function studies in coronary artery disease. VII. Effect of aspirin and tachycardia stress on aortic and coronary venous blood

The effects of orally administered aspirin (650 mg) on platelet aggregation patterns and counts in aortic and coronary venous blood were evaluated in patients with coronary artery disease. Studies were conducted at rest and during the stress of tachycardia. Before administration of aspirin, platelet aggregation and counts were lower (p < 0.01) in coronary venous blood than in aortic blood. The stress of tachycardia resulted in increased (p < 0.01) platelet aggregation only in coronary venous blood. After administration of aspirin, differences in platelet aggregation and counts between coronary venous and aortic blood at rest were eliminated, and the tachycardia-associated increase in coronary venous blood platelet aggregation was significantly reduced. These observations suggest that aspirin influences and abolishes the changes that occur in blood platelet function as platelets traverse the atherosclerotic myocardial vascular bed. The absence of an increase in platelet aggregation during the stress of tachycardia after administration of aspirin may have important pathophysiologic and therapeutic implications.     

Changes in platelet glycoprotein receptors after smoking – a flow cytometric study

Cigarette smoking is accepted to be one of the major factors which increase the risk of coronary artery disease, peripheral vascular disease and stroke. A number of studies have been carried out on the acute and chronic effects of tobacco smoking on platelet activation. An enhancing effect of high nicotine cigarette smoking on platelet aggregation has been reported. Since platelet receptors are involved in the final stage of platelet aggregation, the intention of this study was to investigate platelet receptors in acute and chronic smokers before and after smoking. Nineteen chronic smokers, 18 acute smokers and 18 healthy non-smoking controls were included in the present study. Platelet aggregation was carried out using ristocetin, adenosine diphosphate (ADP) and collagen both before and after smoking in acute and chronic smokers. Flow cytometric studies of platelets were carried out utilizing fluorescein isothiocyanate (FITC)-labelled anti-human fibrinogen antibody in unstimulated and ADP-stimulated platelets, FITC-labelled anti-GP IIb/IIIa antibody, FITC-labelled anti-GP Ib/IX antibody and FITC-labelled P-selectin antibody. The intensity of fluorescence was graded into three groups and expressed in arbitrary units. The interesting data generated in the present work is that in vivo platelet activation occurs immediately after smoking a cigarette which is detected by using FITC-labelled anti-human fibrinogen antibody binding to platelet and by P-selectin expression. It is also quite evident from the present study that a significant number of circulating platelets are in the activated state in chronic smokers. Therefore this study suggests that smoking-induced platelet activation may be an important contributory mechanism for acute coronary events in smokers.     

Changes in platelet glycoprotein receptors after smoking--a flow cytometric study

Cigarette smoking is accepted to be one of the major factors which increase the risk of coronary artery disease, peripheral vascular disease and stroke. A number of studies have been carried out on the acute and chronic effects of tobacco smoking on platelet activation. An enhancing effect of high nicotine cigarette smoking on platelet aggregation has been reported. Since platelet receptors are involved in the final stage of platelet aggregation, the intention of this study was to investigate platelet receptors in acute and chronic smokers before and after smoking. Nineteen chronic smokers, 18 acute smokers and 18 healthy non-smoking controls were included in the present study. Platelet aggregation was carried out using ristocetin, adenosine diphosphate (ADP) and collagen both before and after smoking in acute and chronic smokers. Flow cytometric studies of platelets were carried out utilizing fluorescein isothiocyanate (FITC)-labelled anti-human fibrinogen antibody in unstimulated and ADP-stimulated platelets, FITC-labelled anti-GP IIb/IIa antibody, FITC-labelled anti-GP Ib/IX antibody and FITC-labelled P-selectin antibody. The intensity of fluorescence was graded into three groups and expressed in arbitrary units. The interesting data generated in the present work is that in vivo platelet activation occurs immediately after smoking a cigarette which is detected by using FITC-labelled anti-human fibrinogen antibody binding to platelet and by P-selectin expression. It is also quite evident from the present study that a significant number of circulating platelets are in the activated state in chronic smokers. Therefore this study suggests that smoking-induced platelet activation may be an important contributory mechanism for acute coronary events in smokers.     

The Role of Clopidogrel in the Management of Patients with Ischemic Heart Disease

Antiplatelet therapy plays a pivotal role in the treatment of patients across the entire spectrum of coronary artery disease. Platelets are believed to be integrally involved in both the development and progression of atherosclerotic heart disease, as well as in its acute thrombotic complications. While aspirin remains the traditional antiplatelet agent in patients with CAD, adverse vascular events continue to occur in patients on aspirin therapy. Clopidogrel is a relatively new antiplatelet agent and is currently one of the most widely prescribed drugs for the treatment of symptomatic coronary artery disease. As a member of the class of drugs known as the thienopyridines, clopidogrel irreversibly prevents platelet activation by blocking one of the three known adenosine 5'-diphosphate (ADP) receptors on its surface. The findings of a number of seminal clinical trials have expanded the indications for the use of clopidogrel in patients with coronary artery disease. When used in conjunction with aspirin, these studies have demonstrated an incremental benefit of clopidogrel above and beyond that of aspirin alone. This article reviews the data supporting the use of clopidogrel in patients with atherosclerotic heart disease, and makes recommendations for its use based on the available evidence.     

Effects of aspirin and propranolol on the acute psychological stress response in factor VIII coagulant activity: a randomized, double-blind, placebo-controlled experimental study.

Activity of clotting factor VIII has been shown to acutely increase with sympathetic nervous system stimulation. We investigated whether aspirin and propranolol affect the responsiveness of plasma clotting factor VIII activity levels to acute psychosocial stress. We randomized 54 healthy subjects double-blind to 5-day treatment with a single daily oral dosage of either 100 mg aspirin plus 80 mg propranolol combined, 100 mg of aspirin, 80 mg of propranolol, or placebo medication. Thereafter, subjects underwent a 13-min standardized psychosocial stressor. Plasma levels of clotting factor VIII activity were determined immediately before, immediately after, 45 min and 105 min after stress. Controlling for demographic, metabolic, and life style factors repeated measures analysis of covariance showed that the change in clotting factor VIII activity from prestress to 105 min poststress differed between medication groups (P = 0.023; partial eta = 0.132). The clotting factor VIII activity level decreased from prestress to immediately poststress in the aspirin/propranolol group relative to the placebo group (P = 0.048) and the aspirin group (P < 0.06). Between 45 min and 105 min poststress, clotting factor VIII levels increased in the aspirin/propranolol group relative to the placebo group (P = 0.007) and the aspirin group (P = 0.039). The stress response in clotting factor VIII activity levels was not significantly different between the aspirin/propranolol group and the propranolol group. Propranolol in combination with aspirin diminished the acute response in clotting factor VIII activity to psychosocial stress compared with placebo medication and aspirin alone. The effect of single aspirin on the acute clotting factor VIII stress response was indistinguishable from a placebo effect.     

Psychophysical responses to a speech stressor: Correlation of plasma beta-endorphin levels at rest and after psychological stress with thermally measured pain threshold in patients with coronary artery disease

Objectives. We tested the hypothesis that psychological stress alters plasma levels of opioid peptides and that these plasma levels are related to pain perception in patients with coronary artery disease.

Background. Public speaking psychological stress has previously been shown to be associated with silent ischemia.

Methods. After instrumentation and a 30-min rest period, venous blood samples for beta-endorphin were obtained before and immediately after psychological stress in 20 patients with coronary artery disease. Pain threshold was then assessed using a thermal probe technique at baselin and immediately after stress. Patients gave three brief speeches lasting a total of 15 min about real-life hassle situations.

Results. Psychological stress significantly increases plasma beta-endorphin levels (4.3 ± 0.9 pmol/liter [mean ± SE] at rest to 8.3 ± 2 pmol/liter after stress, p < 0.05). There was a significant positive correlation between pain threshold and beta-endorphin levels after stress (r = 0.577, p = 0.008). This significant positive correlation was still present while rest blood pressure and change in blood pressure during stress were controlled for by analysis of covariance techniques.

Conclusions. In patients with coronary artery disease and exercise-induced ischemia, public speaking produces psychological stress manifested by increased cardiovascular reactivity and causes an increase in plasma beta-endorphin levels that is significantly correlated with pain thresholds. These findings may explain the predominance of silent ischemia during psychological stress in patients with coronary artery disease.     

Role of platelet inhibitor therapy in myocardial infarction

Summary Atherosclerotic plaque disruption is the predominant pathogenetic mechanism underlying the acute coronary syndromes. Plaque rupture leads to the exposure of collagen and vessel media, resulting in platelet and clotting activation, and occlusive thrombus formation. While drugs that interfere with platelet activation and function have been available for years, more powerful agents with novel mechanisms of action are being developed. Of the available platelet inhibitor drugs, only aspirin, sulfinpyrazone, and dipyridamole have undergone extensive clinical testing in patients with cardiovascular disease. More recently ticlopidine, a new and potent platelet inhibitor, has been successfully tested in patients with coronary and vascular disease.In acute myocardial infaction, aspirin significantly reduces cardiovascular mortality and reinfarction. Furthermore, the combination of aspirin and a thrombolytic agent produces maximal benefit. A role for heparin in the prevention of early mortality and reinfaction is emerging. This drug is effective for the prevention of left ventricular thrombosis in patients with anterior myocardial infarction.In the secondary prevention of reinfarction and cardiovascular mortality, available data support the use of a platelet inhibitor. Trials have shown that aspirin is as effective alone as in combination with dipyridamole, and is probably more effective than sulfinpyrazone. Long-term anticoagulant therapy also appears to be beneficial, but is associated with a high cost, need for extensive monitoring, and potential for hemorrhagic side effects.The role of aspirin in primary prevention is controversial. It may be indicated for patients at high risk for coronary disease in whom the benefit of therapy may outweigh the potential risk of cerebral bleeding.Coronary atherosclerotic plaque rupture, associated with thrombus formation, is fundamental to the development of acute myocardial infarction. Based on this concept, the role of antithrombotic therapy for the prevention or treatment of ischemic events in patients with coronary artery disease has stimulated enormous interest among clinicians and basic investigators. In this review we will examine: a) the pathogenesis of coronary thrombosis, b) the pharmacology of plateletinhibitor agents, and c) their role in the management of patients with acute myocardial infarction and in primary and secondary prevention of cardiovascular disease.Platelets interact with both the coagulation and fibrinolytic systems in the pathogenesis of thrombosis. While the purpose of this review is to discuss the role of platelets and platelet inhibitors in coronary disease, the use of anticoagulant or thrombolytic agents will be analyzed briefly when pertinent.     

Aspirin inhibits ox-LDL-mediated LOX-1 expression and metalloproteinase-1 in human coronary endothelial cells

BACKGROUND: Aspirin is thought to exert salutary effects in vascular disease states by inhibiting platelet aggregation. Endothelial activation, accumulation of oxidized low-density lipoprotein (ox-LDL) and intense inflammation also characterize atherosclerotic plaque in acute myocardial ischemia. Ox-LDL induces expression of lectin-like receptors (LOX-1) on endothelial cells and leads to the expression of matrix metalloproteinases (MMPs), which destabilize the atherosclerotic plaque. We hypothesized that aspirin may interfere with LOX-1 expression and subsequent MMP activation. METHODS AND RESULTS: Cultured human coronary artery endothelial cells (HCAECs) were incubated with aspirin (1-5 mM), sodium salicylate (5 mM) or the cyclo-oxygenase inhibitor indomethacin (0.25 mM) before treatment with ox-LDL. Aspirin, in a dose- and time-dependent fashion, reduced ox-LDL-mediated LOX-1 expression (P<0.01). Ox-LDL also increased MMP-1 expression and activity, and treatment of HCAECs with aspirin decreased this effect (P<0.01). Ox-LDL also enhanced the activity of p38MAPK in HCAECs, and aspirin blocked this effect of ox-LDL (P<0.01). Treatment of HCAECs with salicylate, but not indomethacin, resulted in a suppression of LOX-1 expression, an effect similar to that of aspirin. Importantly, both aspirin and salicylate, but not indomethacin, decreased superoxide anion generation in ox-LDL-treated HCAECs (P<0.05). CONCLUSION: These observations suggest that aspirin inhibits ox-LDL-mediated LOX-1 expression and interferes with the effects of ox-LDL in intracellular signaling (p38MAPK activation) and subsequent MMP-1 activity. These novel effects of aspirin may complement its platelet inhibitory effect in acute myocardial ischemia.     

Salutary effects of aspirin in coronary artery disease are not limited to its platelet inhibitory effects

Aspirin is widely used in the treatment and prevention of coronary artery disease (CAD). However, other platelet inhibitory agents, which inhibit platelet activation, have not been found to be effective or as effective as aspirin. The discrepancy between the efficacy of these compounds and aspirin suggests that the therapeutic efficacy of aspirin may not be limited to its platelet inhibitory effect. in this review, the basis for a unique place for aspirin in the therapy of patients with CAD is discussed. The author believes that the nonplatelet-mediated effects of aspirin could be more important than the platelet inhibitory effect, or at least may complement the platelet inhibitory effects of aspirin in patients with acute myocardial ischemia and in others undergoing intra-coronary procedures.     

Aspirin and clopidogrel in acute coronary syndromes: therapeutic insights from the CURE study

Platelet adhesion, activation, and aggregation are central to thrombus formation, which follows atherosclerotic plaque disruption and causes acute coronary syndromes. Aspirin and clopidogrel exert their antiplatelet effects by inhibiting thromboxane A2 production and adenosine diphosphate-induced platelet aggregation pathways, respectively. Aspirin has proven benefits in primary and secondary prevention of coronary artery disease. Clopidogrel, an alternative antiplatelet agent used in patients with aspirin intolerance, is especially useful in combination with aspirin after coronary stent procedures. The CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) study demonstrates for the first time the benefit of adding clopidogrel to aspirin rather than using aspirin alone in patients having acute coronary syndromes without ST-segment elevation myocardial infarction. Patients who are resistant to aspirin (up to 10%) have higher rates of cardiovascular events and may derive special benefit from the combination therapy. Aspirin resistance can be assessed through platelet aggregometry testing, measurement of urinary thromboxane metabolites, and, possibly, genomic testing in the future.     

Facilitating Optimal Care of Acute Coronary,Cerebrovascular and Peripheral Vascular Syndromes in the Emergency Department: The Role of Oral Antiplatelet Therapy

The benefits of aspirin use in the emergent care of MI and stroke have been well established. Recent studies have further demonstrated the importance of antiplatelet therapy in the acute setting, primarily with the use of intravenous glycoprotein IIb/IIIa receptor inhibitors. Aspirin and the thienopyridines (ticlopidine and clopidogrel) are oral antiplatelet agents that interfere with platelet activation in complementary, but separate pathways. Combination therapy of clopidogrel and aspirin has demonstrated benefit for the management of acute coronary syndromes, ischemic cerebrovascular disease and peripheral vascular disease in several large trials. This article reviews the pathophysiology of platelet activation, landmark trials on oral antiplatelet agents, and the current recommendation for the use of oral antiplatelet agents in the emergency department.     

Platelet activation in stable coronary artery disease

To elucidate the role of physical activity in the pathogenesis of acute ischemic syndromes in patients with coronary artery disease (CAD), we hypothesized that platelet activation occurs when coronary blood flow velocity and shear stress increase across an atherosclerotic vascular bed. We measured platelet aggregation by using angiologic catheterization to obtain simultaneous samples of whole blood from the coronary sinus and the aorta white at rest, 2 minutes after the onset of rapid atrial pacing, and 10 minutes after termination of pacing. Of 82 consecutive patients included in our study, 36 had stenosis of the left coronary artery, 12 had stenosis of the right coronary artery only, and 34 had no evidence of CAD. Samples taken at rest revealed no arteriovenous difference in platelet aggregation between patients with CAD and those without CAD. In patients with significant stenosis (≥50%) of the left coronary artery, atrial pacing caused platelet aggregation to increase in samples from the coronary sinus (64 ± 9% increase; p < 0.01) but not in blood from the aorta (2 ± 8% decrease; difference not significant). This increase was transient, with aggregation returning almost to resting values 10 minutes after pacing ended. Atrial pacing elicited no change in platelet aggregation in samples from either the coronary sinus or aorta of patients with nonsignificant stenosis (<50%) of the left coronary artery, patients with significant stenosis of the right coronary artery only, and patients free of CAD. Thus, under resting conditions, no evidence of platelet activation across the coronary bed was seen regardless of CAD status. However, significant stenosis was associated with heightened platelet activation and aggregation when coronary blood flow was increased with atrial pacing.     

Protection against epinephrine-induced myocardial necrosis by drugs that inhibit platelet aggregation

To investigate the possibility that the myocardial necrosis seen after epinephrine infusion is related to the platelet aggregating effects of epinephrine, 10 dogs pretreated with aspirin, 10 dogs pretreated with dipyridamole and 10 dogs not pretreated were infused with epinephrine, 4 μg/kg per min; their hearts were studied histologically after sacrifice 1 week later. All of the control animals had necrosis, 6 with 3+, 2 with 2+, and 2 with 1+ necrosis. Seven of the 10 dogs pretreated with aspirin and 7 of the 10 pretreated with dipyridamole had no evidence of myocardial necrosis. Three dogs pretreated with aspirin had 1+ necrosis; 3 pretreated with dipyridamole had 2+, 1+ and trace degrees of necrosis, respectively. This demonstration of a protective effect of antiplatelet aggregating agents suggests that intravascular platelet aggregation plays a role in catecholamine-induced myocardial necrosis. Clinical acute myocardial infarction seen after prolonged stress (during which catecholamine secretion is increased) may be related to similar intravascular platelet thrombosis induced by catecholamines occluding a coronary artery previously narrowed by atherosclerosis.     

Mean Platelet Volume and Exercise Stress Test

BACKGROUND: Long-term moderate or strenuous physical activity is associated with a considerable reduction in cardiovascular morbidity and mortality. However acute exercise leads to a transient activation of the thrombotic system. Healthy individuals can react this by increasing their fibrinolytic capacity acutely. However, patients with ischemic heart disease, lacking fibrinolytic potential, may be at considerable risk for acute ischemic events if exposed to heavy physical exertion. Platelet size has been shown to reflect platelet activity. The mean platelet volume (MPV) can reflect changes in either the level of platelet stimulation or rate of platelet production. DESIGN AND METHODS: We evaluated Treadmill exercise test (TMET) and compared MPV values (fl) before and after TMET in 63 consecutive patients who, then, underwent coronary angiography and found to have significant coronary artery disease in more than one coronary artery (>70% diameter stenosis in left anterior descending, right coronary or circumflex artery and >50% diameter stenosis in left main coronary artery). Sixty-three male patients were enrolled as a patient group with a mean age of 52.43 +/- 4.08 years and with strongly positive exercise test (> or =2 mm ST segment depression, horizontal or down-sloping). Thirty-five patients without significant coronary artery disease were selected as a control group with a mean age of 52.66 +/- 4.39 years having undergone TMET. RESULTS AND DISCUSSION: In the patient and control groups, mean MPV values before TMET were the same, 8.52 +/- 0.63 and 8.45 +/- 0.58 respectively. Following TMET within 30 minutes, mean MPV were 10.03 +/- 0.96 and 8.50 +/- 0.45 respectively ( p < 0.001). When pre and post-TMET MPV values were evaluated together, the patient group had a significant increase in the MPV ( p < 0.001), whereas, the control group had no significant increase in the MPV ( p = 0.379). It was concluded that exercise possibly makes patients with significant coronary artery disease, more susceptible to a thrombotic event through various routes, one of that is platelet activation that could be measured indirectly via MPV. Healthy subjects react this thrombotic process by increasing their fibrinolytic capacity acutely. Patients with ischemic heart disease, particularly those with significantly narrowed coronary arteries, known to lack fibrinolytic capacity and have high shear stress, on the other hand, might face ischemic events, including sudden death following acute exercise.     

Clinical and prognostic implications of the initial response to aspirin in patients with acute coronary syndrome

Increased platelet reactivity and decreased response to antiplatelet drugs may result in recurrent ischemic events after acute coronary syndrome (ACS). We evaluated laboratory response to aspirin in patients with ACS before and after percutaneous coronary intervention (PCI) and assessed its effect on major adverse clinical events. Sixty-three consecutive patients with ACS were tested for response to aspirin by light transmittance aggregometry (LTA) and the IMPACT-R test (with arachidonic acid) before and 2 to 4 days after PCI and clopidogrel loading. Patients were followed for clinical events up to 15 months from PCI. Response to aspirin improved significantly after PCI and clopidogrel treatment (mean arachidonic acid-induced LTA decreased from 34.9 ± 3.35% before PCI to 15.2 ± 2.2% and surface coverage increased from 2.2 ± 0.27% to 6.2 ± 0.6%, p <0.0001 for the 2 methods). Improved response to aspirin after PCI correlated with response to clopidogrel (LTA and IMPACT-R, p <0.01). Patients with good laboratory response to aspirin before but not after PCI had a significantly lower major cardiovascular event rate during 15-month follow-up in multivariate analysis. In conclusion, laboratory response to aspirin is highly dynamic in patients with ACS. Improved response to aspirin after PCI may result from stabilization of coronary artery disease and/or clopidogrel treatment. Laboratory response to aspirin before PCI and clopidogrel loading is a sensitive marker for platelet reactivity that correlates with clinical outcome in patients with ACS.     

Antiplatelet agents in acute coronary syndromes

Plaque disruption, platelet activation, and intracoronary artery thrombus formation are the key events in the pathogenesis of acute coronary syndromes. Antiplatelet therapies significantly reduce the risk of ischemic complications both during the acute phase and in the long term in patients with acute coronary syndromes. Aspirin remains the cornerstone of antiplatelet therapy, but there is incremental benefit when clopidogrel or ticlopidine is added to aspirin. Dual antiplatelet therapy with the combination of clopidogrel and aspirin is becoming the new standard of care for the management of patients with non-ST-segment elevation acute coronary syndrome and undergoing percutaneous coronary intervention and is currently being further evaluated in ST-segment elevation acute coronary syndrome.