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Biomedical subjects

J E Muller

Publications and source records attributed to J E Muller.

At least 37 records · Page 2Linked to original sources
PubMed2000

Factor VII gene polymorphism, factor VII levels, and prevalent cardiovascular disease: the Framingham Heart Study.

Elevated factor VII levels have been associated with increased cardiovascular risk in some studies. The arginine/glutamine (Arg/Gln) polymorphism of the factor VII gene has been previously shown to modify factor VII levels. However, the presence of a gene/environment interaction on factor VII levels or a link with cardiovascular disease (CVD) remains uncertain. We studied subjects from the Framingham Heart Study to determine (1) the extent to which this genetic polymorphism affects factor VII levels; (2) whether interactions exist between this polymorphism and environmental factors on factor VII levels; and (3) the association between the polymorphism and CVD. Genotype data and factor VII antigen levels were available in 1816 subjects. Factor VII levels differed significantly among genotypes in an additive fashion: Gln homozygous, 82.7+/-2.5%; heterozygous, 92.2+/-0.7%; and Arg homozygous, 100. 5+/-0.4% (P<0.0001). The polymorphism was the strongest, single predictor of factor VII levels, explaining 7.7% of the total variance of factor VII levels, whereas other traditional risk factors combined explained an additional 11.5% of the variance. There was an interaction (P=0.02) between the genotype and total cholesterol on factor VII levels, such that the correlation coefficient and slope (factor VII level/total cholesterol) were greatest in Gln/Gln subjects. Among 3204 subjects characterized for genotype and CVD, there was no significant relationship between the genotype and CVD (P=0.12). In the Framingham Heart Study, the Arg/Gln polymorphism was significantly associated with factor VII antigen levels. The strength of the association suggests that genetic variation plays an important role in determining factor VII levels. However, despite being associated with factor VII levels, the Arg/Gln polymorphism was not associated with prevalent CVD.

Amino Acid Sequence↗
PubMed1999

Sexual activity as a trigger for cardiovascular events: what is the risk?

An important component in the rehabilitation program of patients with cardiac disease is assisting them in resuming sexual activity. In many cases, cardiac disease creates fear, particularly in the spouse, that sexual activity will trigger a cardiac event. Assessment of the possibility that sexual activity may lead to cardiac disease has been aided by advances in the study of triggers of cardiovascular disease. The acute onset of cardiovascular disease has, in many cases, proved to result from the exposures and activities of patients. Nonfatal myocardial infarction, sudden cardiac death, stroke, transient myocardial ischemia, and most arrhythmias have a marked peak during the period between 6:00 A.M. and noon. Wake-time-adjusted data indicate that peak occurrence follows waking and rising. In addition to this marked dependence of disease onset on time of day and awakening, it has been established that there are numerous other triggers of cardiovascular events. For nonfatal infarction, the triggers of heavy exertion, anger, sexual activity, and awakening account for approximately 17% of all cases. Other triggers are still being identified. A new epidemiologic method, the case-crossover method, has greatly enhanced identification of triggering. Regular exertion can reduce the incidence of triggering. It is possible, though unproved, that an acute event can be triggered by rupture of a vulnerable atherosclerotic plaque. With regard to sexual activity, the low absolute risk generated by a potential trigger is useful information with which to reassure patients.

Adult↗
PubMed1999

Triggering of myocardial infarction by cocaine.

BACKGROUND: Cocaine has been implicated as a trigger of acute myocardial infarction in patients with and those without underlying coronary atherosclerosis. However, the magnitude of the increase in risk of acute myocardial infarction immediately after cocaine use remains unknown. METHODS AND RESULTS: In the Determinants of Myocardial Infarction Onset Study, we interviewed 3946 patients (1282 women) with acute myocardial infarction an average of 4 days after infarction onset. Data were collected on the use of cocaine and other potential triggers of myocardial infarction. We compared the reported use of cocaine in the hour preceding the onset of myocardial infarction symptoms with its expected frequency by using self-matched control data based on the case-crossover study design. Of the 3946 patients interviewed, 38 (1%) reported cocaine use in the prior year and 9 reported use within the 60 minutes preceding the onset of infarction symptoms. Compared with nonusers, cocaine users were more likely to be male (87% vs 67%, P=0.01), current cigarette smokers (84% vs 32%, P<0.001), younger (44+/-8 vs 61+/-13 years, P<0.001), and minority group members (63% vs 11%, P<0.001). The risk of myocardial infarction onset was elevated 23.7 times over baseline (95% CI 8.5 to 66.3) in the 60 minutes after cocaine use. The elevated risk rapidly decreased thereafter. CONCLUSIONS: Cocaine use is associated with a large abrupt and transient increase in the risk of acute myocardial infarction in patients who are otherwise at relatively low risk. This finding suggests that studying the pathophysiological changes produced by cocaine may provide insights into the mechanisms by which myocardial infarction is triggered by other stressors.

Adult↗
PubMed1999

Lack of effect of recent alcohol consumption on the course of acute myocardial infarction.

BACKGROUND AND OBJECTIVE: Alcohol has marked effects on hemodynamic and hemostatic variables that might alter the presentation of acute myocardial infarction that follows its use. We sought to determine whether recent alcohol consumption alters the course or complications of acute myocardial infarction. METHODS: In the Determinants of Myocardial Infarction Onset Study, we performed chart reviews and face-to-face interviews with 2161 patients who did not receive thrombolytic therapy. We assessed alcohol use before infarction, peak creatine kinase levels (1043 patients), electrocardiographic interpretations (1408 patients), and the presence of ventricular arrhythmias or congestive heart failure (all patients). RESULTS: Among the 2161 patients, 399 (18.5%) drank alcohol within 24 hours before myocardial infarction. We found no significant difference in mean peak creatine kinase level between those who had recently used alcohol and those who had not in an adjusted comparison (-6.1% difference; 95% confidence interval [CI] -20.3%-10.7%; P =.46). We also found no differences in adjusted risk for Q-wave infarction, congestive heart failure, or ventricular arrhythmias (odds ratios 1.03 [95% CI, 0.73-1.45; P =.88], 1.01 [95% CI, 0.67-1.54; P =.95], and 1.04 [95% CI, 0.66-1.65; P =.86]). Categorization of the duration since last alcohol use into 6-hour intervals revealed no trends between time since last use of alcohol and any of these outcomes. CONCLUSIONS: Recent alcohol use is not associated with changes in infarct size or risk for Q-wave infarction, congestive heart failure, or ventricular arrhythmia among this population.

Aged↗
PubMed1999

Recent aspirin use is associated with smaller myocardial infarct size and lower likelihood of Q-wave infarction.

BACKGROUND: Controversy exists about the effect of recent aspirin use on infarct size and the likelihood of Q-wave infarction in patients who sustain myocardial infarction. METHODS: We performed face-to-face interviews and chart reviews on 3665 patients with acute myocardial infarction for the Determinants of Myocardial Infarction Onset Study. For the 2206 patients who did not receive thrombolytic therapy, we assessed aspirin use, peak creatine kinase levels (in 1043 patients), and electrocardiographic interpretations (in 1447 patients). RESULTS: Of the initial 1043 patients, 317 (30. 3%) subjects reported aspirin use in the 4 days before their infarction. The mean +/- SD peak creatine kinase level for aspirin users was 701 +/- 570 IU/mL versus 851 +/- 727 IU/mL for nonusers, an 18% difference (95% confidence interval [CI], 8% to 26%; P <.001). After adjustment for confounding factors, the difference was 12% (95% CI, 2% to 21%; P =.03). Similarly, 38.9% of the aspirin users and 48.7% of the nonusers sustained a Q-wave infarction, an odds ratio of 0.67 (95% CI, 0.54 to 0.83, P <.001). The adjusted odds ratio was 0.77 (95% CI, 0.61 to 0.97, P =.03). CONCLUSIONS: Recent aspirin use was associated with smaller infarct size and fewer Q-wave infarctions among this population of early survivors of acute myocardial infarction who did not receive thrombolytic therapy.

Aged↗
PubMed1999

Circadian variation and triggering of acute coronary events.

The recognition that the onset of cardiovascular events follows a circadian periodicity and is frequently triggered by physical or mental stresses has created new possibilities for disease prevention. Morning peaks in occurrence are now well-documented for acute myocardial infarction, sudden cardiac death, transient myocardial ischemia, and ischemic stroke. The morning increase in events begins after subjects assume an upright posture and start the day's activities, during a time of sympathetic nervous system activation. Additional triggers of onset include heavy physical exertion, sexual activity, and anger, the risks of which have been quantified in the Determinants of Myocardial Infarction Onset Study. A general hypothesis of the triggering of coronary thrombosis has been proposed. The process begins with the development of a vulnerable atherosclerotic plaque, which may become disrupted by internal forces or by external hemodynamic or vasoconstrictive changes. Once disrupted, the plaque becomes a thrombogenic focus. An occlusive thrombus is more likely to form if other factors come into play to increase coagulability and vasoconstriction. From a clinical standpoint these findings provide theoretical support for the use of long-acting agents to provide adequate anti-ischemic protection during the higher risk morning hours in patients already taking anti-ischemic medications. From a research standpoint this new information on triggering provides clues to a mechanism of onset that might lead to more effective preventive therapy. Because most deaths from coronary artery disease occur before any type of acute therapy can be given, further efforts to explore this new field are warranted.

Anger↗
PubMed1999

A perspective on the potential problems with aspirin as an antithrombotic agent: a comparison of studies in an animal model with clinical trials.

Aspirin is the most widely prescribed agent to reduce the platelet-mediated contributions to atherosclerosis, coronary thrombosis and restenosis after angioplasty. While aspirin treatment has led to significant reductions in morbidity and mortality in many clinical trials, there are several scenarios in which aspirin may fail to provide a full antithrombotic benefit. The cyclic flow model of experimental coronary thrombosis suggests that elevations of plasma catecholamines, high shear forces acting on the platelets in the stenosed lumen and the presence of multiple, input stimuli can activate platelets through different mechanisms that may lead to thrombosis despite aspirin therapy. Aspirin therapy is limited because it only blocks some of the input stimuli, leaving aspirin-independent pathways through which coronary thrombosis can be precipitated. These include thrombin and thrombogenic arterial wall substrates such as tissue factor. New agents that block the adenosine diphosphate (ADP) receptor, or regulate platelet free cytosolic calcium, such as direct nitric oxide donors, may be more potent overall than aspirin. Agents that block the platelet integrin GPIIb-IIIa receptor inhibit the binding of fibrinogen to platelets regardless of which input stimuli activate the platelet and, thus, as demonstrated in the cyclic flow model, would be much more potent than aspirin as an antithrombotic agent. The cyclic flow model has been useful in predicting which agents are likely to be of benefit in clinical trials.

Animals↗
PubMed1999

Circadian variation in cardiovascular events.

Serious adverse cardiovascular events, including myocardial infarction, sudden cardiac death, and stroke, frequently result from thrombotic processes and rupture of atherosclerotic plaques. These events exhibit a pronounced circadian rhythmicity, with a marked peak in the morning hours when the patient assumes an upright posture and begins daily activities. However, it is not known if plaques rupture more frequently in the morning. This review will examine the epidemiologic evidence documenting this circadian phenomenon, consider its physiologic underpinnings, and discuss the implications of this pattern for rational pharmaceutical development. Finally, some practical implications regarding potential triggers of cardiovascular events will be discussed.

Cardiovascular Diseases↗
PubMed1999

Upright posture and maximal exercise increase platelet aggregability and prostacyclin production in healthy male subjects.

BACKGROUND: It is well accepted that heavy physical exertion can trigger the onset of myocardial infarction, but the mechanism is uncertain. As platelet and endothelial function play an important role in thrombotic events, platelet and prostacyclin responses to maximal treadmill exercise were studied. METHODS/RESULTS: The study subjects were 40 healthy men, mean (SEM) age 29 (5) years. Platelet aggregation was measured on a four channel aggregometer. Plasma 6-keto-prostaglandin F1alpha was analysed using an enzyme immunoassay technique. Upright posture and exercise produced an increase in platelet aggregability, as indicated by a fall in the threshold concentration of adrenaline (epinephrine) from 7.6 (1.5) microM at rest to 4.3 (1.0) microM after exercise (p = 0.002). The collagen lag time became significantly shorter with exercise (from 79.1 (3.1) seconds at rest to 71.9 (2.6) seconds after exercise, p = 0.003). Exercise was also associated with a 55% increase in plasma 6-keto-prostaglandin F1alpha (from 38.1 (75%CI 29.0 to 46.5) pg/ml at rest to 59.2 (47.3 to 66.8) pg/ml after exercise, p<0.001). CONCLUSIONS: In healthy male subjects, upright posture and maximal exercise increased platelet aggregability but this increase was counteracted by an increase in prostacyclin production. In patients with endothelial dysfunction, a reduced prostacyclin response to exercise may promote a transient prothrombotic imbalance that may trigger cardiovascular disease onset.

Adult↗
PubMed1999

Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism: the Framingham Offspring Study.

The platelet glycoprotein IIb/IIIa (GP IIb/IIIa) plays a pivotal role in platelet aggregation. Recent data suggest that the PlA2 polymorphism of GPIIIa may be associated with an increased risk for cardiovascular disease. However, it is unknown if there is any association between this polymorphism and platelet reactivity. We determined GP IIIa genotype and platelet reactivity phenotype data in 1422 subjects from the Framingham Offspring Study. Genotyping was performed using PCR-based restriction fragment length polymorphism analysis. Platelet aggregability was evaluated by the Born method. The threshold concentrations of epinephrine and ADP were determined. Allele frequencies of PlA1 and PlA2 were 0.84 and 0.16, respectively. The presence of 1 or 2 PlA2 alleles was associated with increased platelet aggregability as indicated by incrementally lower threshold concentrations for epinephrine and ADP. For epinephrine, the mean concentrations were 0.9 micromol/L (0.9 to 1.0) for homozygous PlA1, 0.7 mmol/L (0.7 to 0.9) for the heterozygous PlA1/PlA2, and 0.6 micromol/L (0.4 to 1.0) for homozygous PlA2 individuals, P=0.009. The increase in aggregability induced by epinephrine remained highly significant (P=0.007) after adjustment for covariates. For ADP-induced aggregation, the respective mean concentrations were 3.1 micromol/L (3.0 to 3.2), 3.0 micromol/L (2.9 to 3.2), and 2.8 micromol/L (2.4 to 3.3); P=0.19 after adjustment for covariates. Our findings indicate that molecular variants of the gene encoding GP IIIa play a role in platelet reactivity in vitro. Our observations are compatible with and provide an explanation for the reported association of the PlA2 allotype with increased risk for cardiovascular disease.

Adenosine Diphosphate↗
PubMed1998

Effects of therapy with nifedipine GITS or atenolol on mental stress-induced ischemic left ventricular dysfunction.

OBJECTIVES: We sought to determine the effect of nifedipine gastrointestinal therapeutic system (GITS) or atenolol on ischemic left ventricular dysfunction induced by mental stress. BACKGROUND: The efficacy of conventional antianginal therapy in preventing myocardial ischemia induced by mental stress is unknown. METHODS: Nifedipine GITS, atenolol and placebo were administered to 15 subjects with stable angina in a double-blind crossover trial. Subjects underwent a series of mental stressors at the end of each treatment. Radionuclide ventriculography was performed at baseline and at peak mental stress. Other measured variables included time to ischemia on exercise treadmill testing, ischemia on 48-h ambulatory electrocardiogram (ECG) monitoring, and resting and mental stress-induced levels of plasma catecholamines, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 and platelet aggregability. RESULTS: Mental stress resulted in a significant increase in plasma epinephrine and norepinephrine levels during each treatment phase. Atenolol therapy was associated with lower baseline and postmental stress rate-pressure product compared with nifedipine or placebo. Therapy with either nifedipine GITS or atenolol prevented the development of wall-motion abnormalities and the decline in regional ejection fraction (EF) in the segment with the largest deterioration in wall motion during placebo therapy. Both medications prevented the decrease in global EF in subjects who demonstrated at least a 5% fall in global EF on placebo therapy. No therapy exerted a statistically significant benefit on exercise performance or frequency of ischemia during ambulatory ECG monitoring. CONCLUSIONS: Both nifedipine GITS and atenolol are effective at preventing mental stress-induced wall-motion abnormalities, although the mechanisms may be different.

Adrenergic beta-Antagonists↗
PubMed1998

Fibrinolytic potential is significantly increased by oestrogen treatment in postmenopausal women with mild dyslipidaemia.

OBJECTIVE: To study the effects of oestrogen replacement treatment on fibrinolytic potential in postmenopausal women. DESIGN: Randomised, double blind, placebo controlled trial of oral 17 beta-oestradiol. SETTING: Subjects were evaluated in the outpatient setting. PATIENTS: Nineteen postmenopausal women with mild dyslipidaemia, aged 44 to 69 years (mean (SD) 55.7 (6.7)). MAIN OUTCOME MEASURES: Fibrinolytic activity (fibrin plate assay) and tissue plasminogen activator (t-PA) antigen were measured at baseline and after three, six, and nine weeks of each treatment. RESULTS: After nine weeks of 2 mg oestradiol treatment, there was a significant increase in fibrinolytic potential compared with placebo, as indicated by an increase in fibrinolytic activity (mean (SEM), 80 (9) v 54 (5) mm2 of lysis in the fibrin plate, 2 mg v placebo, p = 0.002) and a decrease in t-PA antigen (5.8 (0.9) v 8.4 (1.2) ng/ml, 2 mg v placebo, p < 0.001). There was a similar trend with the 1 mg dose but the changes were less noticeable. CONCLUSIONS: Hormone replacement treatment with 17 beta-oestradiol for nine weeks significantly increased fibrinolytic potential in postmenopausal women with mild dyslipidaemia. This suggests that the cardioprotective effect of oestrogen may be mediated, in part, by an increase in fibrinolytic potential.

Adult↗
PubMed1997

Nonuniform nighttime distribution of acute cardiac events: a possible effect of sleep states.

BACKGROUND: Although 250,000 myocardial infarctions and 38,000 sudden cardiac deaths occur at night annually, this public health problem is underappreciated and poorly understood. We examined whether the incidence of myocardial infarction, sudden cardiac death, and automatic implantable cardioverter-defibrillator (AICD) discharge was nonuniform, a result that may implicate physiological triggers such as sleep-state dependent changes in autonomic nervous system activity. METHODS AND RESULTS: We conducted a review of the circadian pattern of the onset of myocardial infarction (n=19), sudden cardiac death (n=12), and AICD discharge (n=7). The nighttime period was chosen a priori as midnight to 5:59 AM. These reports documented 11,633 nocturnal myocardial infarctions (20% of the total myocardial infarctions), 1981 nocturnal sudden cardiac deaths (14.6% of the total sudden cardiac deaths), and 1200 nocturnal AICD discharges (15.0% of the total discharges). The distributions of myocardial infarction, sudden cardiac death, and AICD discharge were each significantly nonuniform (P<.001). The peak incidence of myocardial infarction and AICD discharge occurred between midnight and 0:59 AM, whereas the peak incidence of sudden cardiac death was between 1:00 and 1:59 AM. The trough in incidence occurred between 4:00 and 4:59 AM for sudden cardiac death and between 3:00 and 3:59 AM for myocardial infarction and AICD discharge. CONCLUSIONS: Nocturnal myocardial infarction, sudden cardiac death, and AICD discharge exhibit nonuniform distributions. This finding is consistent with the hypothesis that sleep-state dependent fluctuations in autonomic nervous system activity may trigger the onset of major cardiovascular events and provides further impetus for more directly testing this hypothesis at population, individual, and mechanistic levels. A better understanding of nocturnal triggers may make it possible to reduce the incidence of myocardial infarction, ventricular tachyarrhythmias, and sudden cardiac death during the nocturnal period.

Circadian Rhythm↗
PubMed1997

Effect of aspirin dosage and enteric coating on platelet reactivity.

Although aspirin is effective in the prevention and treatment of cardiovascular diseases, the optimal dose remains uncertain. The purpose of this study was to compare the platelet inhibitory and prostacyclin-sparing effects of 2 doses (81 and 325 mg) and forms (enteric-coated and regular) of aspirin. Since platelet reactivity has been reported to increase after strenuous exercise, a known trigger of myocardial infarction, subjects were studied following maximal treadmill exercise as well as at rest. Forty male healthy subjects were evaluated using a randomized, double-blind, parallel study design. Blood samples were obtained before and after maximal treadmill exercise at baseline and after 7 days on aspirin therapy. Both enteric and regular aspirin in 81- and 325-mg dosages markedly inhibited adenosine diphosphate and epinephrine-induced aggregation at rest and after exercise. Aspirin also inhibited the platelet response to collagen as assessed by a longer lag time to aggregation. The prolongation of lag time was greater for 325 mg than for 81 mg (100 +/- 7 vs 91 +/- 7; p = 0.04, after exercise). There were no significant dose-related differences in plasma 6-keto-prostaglandin F1alpha level; however, enteric-coated aspirin inhibited the exercise-induced increase in 6-keto-prostaglandin F1alpha to a lesser extent than regular aspirin. Although both doses (81 and 325 mg) and types (regular and enteric-coated) of aspirin inhibited adenosine diphosphate and epinephrine-induced aggregation equally, the 325-mg dose inhibited collagen-induced aggregation to a greater extent than 81 mg. The greater platelet inhibition observed with 325 mg may be clinically relevant in acute coronary syndromes characterized by plaque rupture with extensive collagen exposure and platelet activation.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Meta-analysis of the morning excess of acute myocardial infarction and sudden cardiac death.

To evaluate the impact of elimination of the morning peak of cardiovascular events, we performed a meta-analysis of studies of circadian variation of myocardial infarction and sudden cardiac death. The impact would be significant because approximately 1 of every 11 acute myocardial infarctions and 1 of every 15 sudden cardiac deaths are attributable to the morning excess incidence.

Circadian Rhythm↗
PubMed1997

Effect of sustained-release Verapamil on the morning systemic arterial pressure surge during daily activity in patients with systemic hypertension.

In a placebo-controlled study of 13 subjects with systemic hypertension, sustained-release verapamil reduced the morning surge in systolic pressure by 10.2 mm Hg (p = 0.04), diastolic pressure by 11.1 mm Hg (p = 0.008), and heart rate by 3.3 beats/min (p = 0.17). Blunting of the morning hemodynamic surge may be a mechanism by which verapamil could reduce the risk of plaque disruption and acute coronary events in the morning.

Adult↗
PubMed1997

Angioscopic assessment of coronary lesions underlying thrombus.

This study examines the characteristics of coronary lesions in which thrombus is found as assessed by angioscopy before percutaneous transluminal coronary angioplasty in patients with various coronary syndromes. Our findings demonstrate that the plaque underlying intracoronary thrombus is usually yellow and/or disrupted, and support in vitro observations that lipid-rich plaques are highly thrombogenic and that disruption of these plaques is associated with in situ thrombosis.

Angioscopy↗