Future Myocardial Infarction Research Articles

Plasma C-Reactive Protein in Haemodialysis

In recent years, acute phase reactants have been reevaluated as not merely biochemical markers of inflammation but also as active modulators of the inflammatory response. C-reactive protein – which is normally present in serum in only trace amounts, but whose concentration may rise markedly with inflammatory stimuli – was the first human acute phase protein discovered. It is now clear that cytokines are the major mediators of acute phase protein induction: interleukin-6 currently is felt to be the principal cytokine influencing C-reactive protein acute changes. Several studies have provided convincing evidence that among normal men, base-line serum levels of C-reactive protein are predictive of future myocardial infarction and ischemic stroke. The relevance of acute phase reactants in morbidity and mortality of haemodialysis patients has not been fully elucidated until now: in fact a few studies have implicated C-reactive protein in malnutrition, EPO-resistance, as a cardiovascular risk factor and as a marker of chronic stimulation in haemodialysis. The authors suggest the hypothesis of the occurrence of long-term complications in patients exposed to contaminated dialysate and suggest that back-filtration may induce a chronic, slowly developing inflammatory state that may be abrogated by avoiding backfiltration of contaminated dialysate.

Prospective study of herpes simplex virus, cytomegalovirus, and the risk of future myocardial infarction and stroke.

It has been hypothesized that infection with either herpes simplex virus (HSV) or cytomegalovirus (CMV) is associated with atherogenesis. However, prospective data relating evidence of prior exposure to these agents with risks of future myocardial infarction (MI) and stroke are sparse. In a prospective, nested case-control study of apparently healthy men, the baseline prevalence of antibodies directed against HSV or CMV was similar among 643 men who subsequently developed a first MI or thromboembolic stroke and among 643 age- and smoking-matched men who remained free of reported vascular disease over a 12-year follow-up period. Specifically, the relative risks for future MI and stroke were 0.94 (95% CI, 0.7 to 1.2) for HSV seropositivity and 0.72 (95% CI, 0.6 to 0.9) for CMV seropositivity, after adjustment for other cardiovascular risk factors. These findings were not materially altered in comparisons of early versus late events or in analyses stratified by smoking status. There was no evidence of association between HSV or CMV antibodies and plasma concentration of C-reactive protein, a marker of inflammation that predicts vascular risk in this cohort. Among apparently healthy middle-aged men, IgG antibodies directed against HSV or CMV do not appear to be a marker for increased atherothrombotic risk. The observed possible inverse relationship of CMV with MI and stroke was unexpected and may well be due to chance, because the direction of association is not compatible with the a priori hypothesis based on proposed biological mechanisms or previous cross-sectional and retrospective data.

Risk factors in the offspring of women with premature coronary heart disease

Some studies suggest that first-degree relatives of female patients with premature coronary heart disease (CHD) are at greater risk for early disease than if the proband is a male patient. To examine coronary risk factors, related knowledge, attitudes, and beliefs concerning CHD risk, we screened a sample of 87 apparently healthy offspring (56 female subjects and 31 male subjects) of women with documented premature CHD. More than half of the offspring had total and low-density lipoprotein cholesterol levels above the recommended levels for primary prevention, 31% were current smokers, and 56% exercised fewer than three times a week. A high proportion were overweight with a high prevalence of central obesity. A total of 13% had only one major risk factor, a family history of premature CHD, 10% had two risk factors, 23% had three, and 54% had four or more CHD risk factors. When compared with the Framingham cohort, 29% of sons and 30% of daughters exceeded their age- and sex-specific average risk for having CHD in 10 years. Only 28% identified heredity as a major cause of CHD, and 47% perceived their risk for future myocardial infarction as less than or equal to that of others their age. These findings suggest that adult children of women with premature CHD have a high prevalence of modifiable risk factors and do not perceive themselves to be at risk for CHD. (Am Heart J 1998;135:428-34.)

Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men

The intercellular adhesion molecule ICAM-1 mediates adhesion and transmigration of leucocytes to the vascular endothelial wall, a step proposed to be critical in the initiation and progression of atherosclerosis. Whether concentrations of soluble ICAM-1 (sICAM-1) are raised in apparently healthy individuals who later suffer acute myocardial infarction is unknown. We obtained baseline plasma samples from a prospective cohort of 14,916 healthy men enrolled in the Physicians' Health Study. With a nested case-control design, we measured sICAM-1 concentrations for 474 participants who developed a first myocardial infarction, and 474 controls (participants who remained healthy throughout the 9-year follow-up). Cases were matched to controls according to age and smoking status at the time of myocardial infarction. We found a significant association between increasing concentration of sICAM-1 and risk of future myocardial infarction (p = 0.003), especially among participants with baseline sICAM-1 concentrations in the highest quartile (> 260 ng/mL; relative risk 1.6 [95% Cl 1.1-2.4], p = 0.02). This association was present overall as well as among non-smokers, and persisted after control for lipid and non-lipid risk factors. In multivariate analyses, the risk of future myocardial infarction was 80% higher for participants with baseline sICAM-1 concentrations in the highest quartile (relative risk 1.8 [1.1-2.8], p = 0.02). Similar risk estimates were seen among non-smokers. We found slight but significant correlations between sICAM-1 and fibrinogen, high-density-lipoprotein cholesterol, homocysteine, triglycerides, tissue-type plasminogen-activator antigen, and C-relative protein, but adjustment for these altered the risk little. The risk of myocardial infarction associated with raised concentrations of sICAM-1 seemed to increase with length of follow-up. Our data support the hypothesis that cellular mediators of inflammation have a role in atherogenesis and provide a clinical basis to consider antiadhesion therapies as a novel means of cardiovascular disease prevention.

Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study.

Noninvasive assessment of intima-media thickness (IMT) is widely used in observational studies and trials as an intermediate or proxy end point for cardiovascular disease. However, data showing that IMT predicts cardiovascular disease are limited. We studied whether common carotid IMT is related to future stroke and myocardial infarction. We used a nested case-control approach among 7983 subjects aged > or =55 years participating in the Rotterdam Study. At baseline (March 1990 through July 1993), ultrasound images of the common carotid artery were stored on videotape. Determination of incident myocardial infarction and stroke was predominantly based on hospital discharge records. Analysis (logistic regression) was based on 98 myocardial infarctions and 95 strokes that were registered before December 31, 1994. IMT was measured from videotape for all case subjects and a sample of 1373 subjects who remained free from myocardial infarction and stroke during follow-up. The mean duration of follow-up was 2.7 years. Results were adjusted for age and sex. Stroke risk increased gradually with increasing IMT. The odds ratio for stroke per standard deviation increase (0.163 mm) was 1.41 (95% CI, 1.25 to 1.82). For myocardial infarction, an odds ratio of 1.43 (95% CI, 1.16 to 1.78) was found. When subjects with a previous myocardial infarction or stroke were excluded, odds ratios were 1.57 (95% CI, 1.27 to 1.94) for stroke and 1.51 (95% CI, 1.18 to 1.92) for myocardial infarction. Additional adjustment for several cardiovascular risk factors attenuated these associations: 1.34 (95% CI, 1.08 to 1.67) and 1.25 (95% CI, 0.98 to 1.58), respectively. The present study, based on a short follow-up period, provides evidence that an increased common carotid IMT is associated with future cerebrovascular and cardiovascular events.

Alu-repeat Polymorphism in the Gene Coding for Tissue-Type Plasminogen Activator (t-PA) and Risks of Myocardial Infarction Among Middle-aged Men

An Alu-repeat polymorphism in the gene coding for tissue-type plasminogen activator has been described recently, and it has been hypothesized that this polymorphism may predict risk of coronary thrombosis. In a prospective cohort of nearly 15,000 apparently healthy men, presence of an Alu-repeat insertion/deletion (I/D) polymorphism in the gene coding for tissue-type plasminogen activator was determined among 369 study participants who subsequently suffered a first myocardial infarction (cases) and among a group of 369 age- and smoking-matched study participants who remained free of reported cardiovascular disease during follow-up (controls). The distributions of the II, DI, and DD genotypes of the tissue-type plasminogen activator polymorphism among men who subsequently suffered myocardial infarction (0.30, 0.50, 0.21) were virtually identical to those who remained free of disease (0.29, 0.50, 0.21; P = .9). There was no evidence of association between the Alu insertion polymorphism and risks of future myocardial infarction in models assuming either allelic recessive (relative risk, 1.05; 95% confidence interval, 0.8 to 1.4, P = .8) or allelic dominant (relative risk, 1.04; 95% confidence interval, 0.7 to 1.5, P = .8) modes of inheritance, nor were associations found in analyses stratified by age, family history, hypercholesterolemia, or the presence of other risk factors for premature coronary disease. Multivariate analysis had no important effects on these relationships. In this cohort of middle-aged US men, the presence of the insertion allele of the Alu-repeat polymorphism of the tissue-type plasminogen activator gene is not associated with future risks of myocardial infarction.

Prognostic Significance of Spontaneous Echo Contrast in the Thoracic Aorta: Relation With Accelerated Clinical Progression of Coronary Artery Disease

Objectives. The purposes of this study were to identify the incidence of aortic smoke in an unselected cohort of patients and to determine the utility of this measurement as a clinical marker for future coronary events and long-term cardiac prognosis.Background. Although spontaneous echo contrast detected within the cardiac chambers has been associated with an increased risk of thromboembolism, less is known about “smoke” within the thoracic aorta and its relation to progression of coronary artery disease.Methods. We prospectively assessed 118 unselected, consecutive male patients (mean age 67 years, range 29 to 86) who underwent transesophageal echocardiography (TEE). The presence of aortic smoke was identified by swirling echodense shadows distinct from high gain artifact. A positive result required confirmation by two of three independent observers.Results. Aortic smoke without dissection was found in 25 of the patients (21%). Indications for TEE, coronary risk factors, the incidence of reduced left ventricular ejection fraction and mitral insufficiency and known coronary artery disease severity collectively did not differ significantly at baseline between the groups with and without smoke. Follow-up averaged 20.4 months (range 18 to 24) and was 100% complete for mortality and 98% complete for morbidity. The presence of aortic smoke was an independent predictor of myocardial infarction (16.0% vs. 2.2%, p < 0.005) and cardiac death (20.0% vs. 1.1%, p < 0.0001). These statistics remained significant after covarying for age, ejection fraction <50%, hypertension, diabetes, aortic dimension, the presence of an atheromatous plaque and smoke in the left atrium.Conclusions. Spontaneous echo contrast detected within the thoracic aorta by transesophageal echocardiography is a common and important clinical marker that is strongly associated with an increased risk for future myocardial infarction and cardiac mortality. Future studies will attempt to define the pathophysiology of this relation and assess whether aggressive revascularization strategies and antithrombotic therapy may aid in the reduction of this risk.(J Am Coll Cardiol 1997;30:71–75)

Does the Presence and Site of Myocardial Ischemia on Perfusion Scintigraphy Predict the Occurrence and Site of Future Myocardial Infarction in Patients With Stable Coronary Artery Disease?

In 47 patients who had undergone myocardial scintigraphy, reversible perfusion abnormality was detected in only 28 segments (60%) that were the site of future acute myocardial infarction.

Endogenous fibrinolytic function and risks of future myocardial infarction and stroke: observations from the Physicians' Health Study

Summary Employing plasma and DNA samples collected at baseline among 14,916 participants in the Physicians' Health Study who were free of reported vascular disease at study initiation and were then followed prospectively for the occurrence of myocardial infarction, stroke, and venous thrombosis, we have found that baseline evaluations of endogenous tissue-type plasminogen activator (tPA:ag) as well as cross linked fibrin degradation products (D-dimer) are highly predictive of risk of future coronary and cerebral thrombosis, but not venous thrombosis. We have also found that levels of tPA:ag directly correlate with body mass index and cigarette consumption and inversely correlate with alcohol consumption and HDL cholesterol. In contrast, we have found no association between Lp(a) and risk of future myocardial infarction or stroke. Despite strong associations between plasma levels of tPA:ag and thrombotic risk, we have not found significant relationships between specific genetic polymorphisms associated with PAI-1 or tPA production to be predictive of risk. Thus, environmental and behavioural factors are likely to be critical in determining the net fibrinolytic balance on a systemic and local basis. Data from the Physicians' Health Study, taken in context with other important prospective evaluations of fibrinolytic potential, strongly support the hypothesis that hemostatic and thrombotic risk factors for vascular disease can be detected reliably on a population basis, and raise the possibility that assessment of novel risk factors may prove valuable in the detection and prevention of cardiovascular disease.

Does stress echocardiography predict the site of future myocardial infarction? A large-scale multicenter study

Objectives. We sought to assess whether the site of future myocardial infarction can be predicted on the basis of induced dyssynergy (“area at risk”) recognized by stress echocardiography.Background. The severity and extent of stress-induced dyssynergy are strong predictors of subsequent major cardiac events. However, high grade stenotic lesions are not strictly associated with the site of future coronary occlusions.Methods. From the stress echocardiography multicenter trials data bank, we selected 70 patients (56 men; mean age ± SD 58 ± 11 years) meeting the following inclusion criteria: 1) dipyridamole (n = 53) or dobutamine (n = 17) stress echocardiography; 2) a spontaneously occurring infarction, with no intercurrent revascularization procedure between the initial study and the infarction; and 3) a follow-up rest echocardiogram obtained 41 ± 90 days after the infarction.Results. A complete ischemia-infarction mismatch (infarct-related dysfunction in a patient with negative stress test results) occurred in 29 patients (41%). A partial mismatch (ischemic dysfunction in a territory different from the infarct area) occurred in nine patients (13%). A match (ischemia-related and infarction-related dyssynergy involving the same region) occurred in 32 patients (46%). The average time interval between the stress examination and the occurrence of infarction or reinfarction was 144 ± 160 days in patients with a match and 439 ± 622 days in patients with a mismatch (p < 0.05).Conclusions. Induced ischemia (imaged as transient dyssynergy by pharmacologic stress echocardiography) inconsistently identifies the site of future infarction. The majority of spontaneous coronary occlusions leading to infarction unheralded by induced ischemia. However, most infarctions occurring within 1 year of stress testing are in the area identified as ischemic during testing.

The relationship between severity of coronary artery disease and vital exhaustion

The present study investigates the association between the severity of coronary artery disease (CAD) and feelings of exhaustion. Vital exhaustion consists of three major components: lack of energy, increased irritability, and demoralization. Previous studies showed that exhaustion is of predictive value for first myocardial infarction (MI). However, these studies could not rule out that the state of exhaustion prior to MI was the result of underlying CAD. To examine this issue, severity of CAD and cardiac pump function were related to feelings of exhaustion in 307 patients who underwent coronary angiography. It was found that exhaustion, as assessed by means of the Maastricht Questionnaire (MQ), was not related to the severity of CAD ( F = 1.17; p = 0.15). Furthermore, a poor left ventricular function did not relate to MQ scores ( N = 138; F<1; NS). On the other hand, clinical variables (duration of complaints, exercise performance, peripheral vascular disease, and dyspnea), use of medication (nitrates, β-blocking agents, calcium antagonists, and diuretics), and demographic characteristics (gender and education) were associated with MQ scores. Multiple regression analysis showed that demographic variables (lower education, younger age, and female gender) were the predominant predictors of exhaustion. In addition, dyspnea, peripheral vascular disease, and the use of medication related significantly to exhaustion scores ( R 2 = 0.13; F = 4.8; p<0.001). We conclude that neither the extent of CAD nor impaired cardiac pump function is related to feelings of exhaustion in patients referred for coronary angiography. Therefore, the previously reported association between exhaustion and future MI is not likely to be caused by underlying coronary disease.

The Association between Perceived Risk and Actual Cardiovascular Disease

We examined the association between self-rated risk of stroke or myocardial infarction and actual morbidity and mortality by gender among participants of the Pawtucket Heart Health Program Health Survey in a nested case-control study. We defined cases (N = 191) as survey participants who later had a cardiac event registered in the Pawtucket Heart Health Program cardiovascular disease morbidity and mortality surveillance system. We matched controls (N = 573) on age, sex, date of survey, and city of residence. Women reporting a high perceived risk of stroke or myocardial infarction were four times as likely as women who indicated low perceived risk to have a future cardiovascular event [adjusted odds ratio = 4.0; 95% confidence interval (CI) = 1.5-10.3]. Men who perceived their risk as average were twice as likely as those who rated their risk as low to have a future myocardial infarction or stroke (adjusted odds ratio = 1.9; 95% CI = 1.0-3.6), whereas those who perceived their risk as high were at only slightly higher risk of morbid or mortal events (adjusted odds ratio = 1.8; 95% CI = 0.9-3.9).

Prognostic significance of transient myocardial ischaemia after first acute myocardial infarction: five year follow up study.

To assess the five year prognostic significance of transient myocardial ischaemia on ambulatory monitoring after a first acute myocardial infarction, and to compare the diagnostic and long term prognostic value of ambulatory ST segment monitoring, maximal exercise testing, and echocardiography in patients with documented ischaemic heart disease. Prospective study. Cardiology department of a teaching hospital. 123 consecutive men aged under 70 who were able to perform predischarge maximal exercise testing. Echocardiography two days before discharge (left ventricular ejection fraction), maximal bicycle ergometric testing one day before discharge (ST segment depression, angina, blood pressure, heart rate), and ambulatory ST segment monitoring (transient myocardial ischaemia) started at hospital discharge a mean of 11 (SD 5) days after infarction. Relation of ambulatory ST segment depression, exercise test variables, and left ventricular ejection fraction to subsequent objective (cardiac death or myocardial infarction) or subjective (need for coronary revascularisation) events. 23 of the 123 patients had episodes of transient ST segment depression, of which 98% were silent. Over a mean of 5 (range 4 to 6) years of follow up, patients with ambulatory ischaemia were no more likely to have objective end points than patients without ischaemic episodes. If, however, subjective events were included an association between transient ST segment depression and an adverse long term outcome was found (Kaplan-Meier analysis; P = 0.004). The presence of exercise induced angina identified a similar proportion of patients with a poor prognosis (Kaplan-Meier analysis; P < 0.004). Both exertional angina and ambulatory ST segment depression had high specificity but poor sensitivity. The presence of exercise induced ST segment depression was of no value in predicting combined cardiac events. Indeed, patients without exertional ST segment depression were at increased risk of future objective end points (Kaplan-Meier analysis; P < 0.0045). These findings may be explained in part by a higher prevalence of left ventricular dysfunction in patients without ischaemic changes in the exercise electrocardiogram (P < 0.05). There seem to be limited reasons to perform ambulatory ST segment monitoring in survivors of a first myocardial infarction who can perform exercise tests before discharge. Patients at high risk of future myocardial infarction or death from cardiac causes are not identified. Ambulatory monitoring and exertional angina distinguish a small subset of patients who will develop severe angina pectoris demanding coronary revascularisation during follow up. Patients without exercise induced ST segment depression comprise a high risk subgroup in terms of subsequent objective end points. The role of ambulatory ST segment monitoring performed in unselected patients immediately after infarction when risk is maximal remains to be clarified.

748-3 The Relationship Between the Location of Ischemic Perfusion Defects on Stress Technetium-99m Sestamibi SPECT Scintigraphy and the Location of a Subsequent Myocardial Infarction

While the presence of ischemia on stress myocardial perfusion imaging has been shown to correlate with a future myocardial infarction (MI), it is unknown whether the location of the ischemia predicts the location of the subsequent MI. Therefore, 24 patients (83% male, mean age: 66 ± 13 yrs, 46% exercise, 54% pharmacologic stress) who had an enzyme proven myocardial infarction following a stress Tc-99m sestamibi (MIBI) SPECT imaging study were analyzed. The location of the MI, as determined by either standard electrocardiographic criteria, or by a new wall motion abnormality on echocardiography or contrast ventriculography, was related to the location of a reversible defect on the preceding stress/rest MIBI images. Two territories per patient—anterior (including anterolateral and anteroseptal) and inferior (including inferolateral and inferoseptal)—were assessed for the presence of a reversible defect, and for the location of the subsequent MI. In 5 patients, the location of the MI could not be determined, leaving 38 territories in the remaining 19 pts for analysis: Of 19 territories with a reversible defect, 9 (47%) were the site of a subsequent MI, compared with 3 (50%) of 6 territories with a fixed defect, and 6 (46%) of 13 territories with no defect (p = NS). The remaining patient had a lateral MI after MIBI images had shown a reversible apical defect. Thus, 10 (53%) of the 19 Ml's occurred in a territory that did not show ischemia on the preceding MIBI images. The location of ischemia on a stress Tc-99m sestamibi SPECT imaging study does not consistently predict the location of a future myocardial infarction. This is in accord with previous findings from coronary angiography that the most severe stenoses frequently do not correlate with the locations of subsequent infarctions.

Plasma concentration of cross-linked fibrin degradation product (D-dimer) and the risk of future myocardial infarction among apparently healthy men.

Plasma levels of D-dimer, the primary degradation product of cross-linked fibrin, are elevated in several acute thrombotic disorders. However, whether elevated D-dimer levels among healthy individuals are associated with future coronary thrombosis is unknown. To evaluate whether levels of D-dimer are associated with the occurrence of future myocardial infarction (MI) among apparently healthy men, levels were measured in plasma samples collected at baseline from 296 participants in the Physicians' Health Study who later developed a first MI and from an equal number of age- and smoking status-matched control subjects who remained free of vascular disease during a mean follow-up period of 60.2 months. In univariate analyses, baseline plasma concentrations of D-dimer in the upper ranges of normal were associated with elevated risks of MI. Specifically, the relative risk of future MI for individuals with baseline D-dimer concentration exceeding the 95th percentile of the control distribution was two times higher than that of individuals with lower levels (relative risk [RR], 2.02; 95% confidence interval [CI], 1.04 to 4.02; P = .04). This association persisted in multivariate analyses controlling for nonlipid cardiovascular risk factors (RR, 2.12; 95% CI, 1.05 to 4.28; P = .04) and for lipoprotein(a) (RR, 2.02; 95% CI, 1.04 to 3.94; P = .03). In contrast, this association was attenuated and no longer statistically significant in analyses that controlled for total and high-density lipoprotein cholesterol (RR, 1.74; 95% CI, 0.78 to 3.91; P = .2) or for endogenous tissue-type plasminogen activator and its primary inhibitor, plasminogen activator inhibitor type 1 (RR, 1.58; 95% CI, 0.67 to 3.77; P = .3). Elevated levels of D-dimer are associated with increased risks of future MI, although they do not appear to be an independent predictor when other risk factors are considered. As the presence of D-dimer in plasma reflects ongoing fibrin degradation, these data support the hypothesis that activation of the endogenous fibrinolytic system occurs many years in advance of coronary arterial occlusion.

Change in blood pressure and 5-year risk of coronary heart disease among elderly men

To study the association between blood pressure and change in blood pressure with future coronary risk among elderly men. Cohort study. Finnish cohorts of the Seven Countries Study. Four hundred and seventy-six men aged 65-84 years and free of clinically manifested coronary heart disease at baseline, in 1984. Fatal myocardial infarction (n = 29), any myocardial infarction (n = 42), and incidence of any new signs and symptoms of coronary heart disease (n = 80) during a 5-year follow-up. In multivariate analysis, a significant inverse U-shaped relationship was observed between baseline diastolic blood pressure and future fatal myocardial infarction, any myocardial infarction and any coronary heart disease. In models predicting the risk of coronary heart disease during 1984-1989, there was a significant interaction between both systolic (SBP) and diastolic blood pressure (DBP) in 1969-1974 and change in blood pressure between 1969-1974 and 1984. In categorical analyses, men (n = 42) who experienced a decline in DBP of > or = 4 mmHg from initial levels of > or = 90 mmHg had a higher risk of any myocardial infarction than men (n = 112) with a change of < 4 mmHg (odds ratio 4.5). For a decline of > or = 10 mmHg or more in SBP from levels of > or = 160 mmHg the corresponding odds ratio was 2.9. Men who experienced a decline in DBP or SBP from normotensive levels or an increase in blood pressure had no excess risk compared with men with stabile (change in DBP < 4 mmHg and change in SBP < 10 mmHg) blood pressure values. The present results suggest that among elderly men a decline in DBP or SBP from previously hypertensive levels may be associated with increased coronary risk.

Vital exhaustion predicts new cardiac events after successful coronary angioplasty.

Excessive tiredness is one of the most prevalent premonitory symptoms of myocardial infarction and sudden cardiac death. This state is labelled as vital exhaustion and consists of three components: fatigue, increased irritability, and demoralization. Vital exhaustion has been found to be an independent risk-indicator of myocardial infarction in one prospective study and several case-control studies. It is as yet unclear whether the association between vital exhaustion and future myocardial infarction can be explained by confounding of (subclinical) coronary artery disease. Therefore, the present study investigates the predictive value of vital exhaustion for the occurrence of new cardiac events after percutaneous transluminal coronary angioplasty (PTCA), while explicitly controlling for the severity of coronary artery disease. Patients with a successful PTCA were followed during 1.5 years. A new cardiac event was defined as present if one of the following end points occurred: cardiac death, myocardial infarction, coronary bypass surgery, repeat-PTCA, increase of coronary atherosclerosis, or new anginal complaints with documented ischemia. Vital exhaustion was assessed using the Maastricht Questionnaire two weeks after hospital discharge. Participants of the present study were 127 patients (mean age 55.6 +/- 9.1; 105 men, 22 women). Fifteen (35%) of the 43 exhausted patients experienced a new cardiac event, whereas 14 (17%) of the 84 not exhausted patients had a new cardiac event (OR = 2.7; CI = 1.1-6.3; p = .02). Multiple logistic regression analysis revealed that vital exhaustion continued to be of predictive value when other significant risk factors for new cardiac events were controlled for (i.e., severity of coronary artery disease and hypercholesterolemia).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma Concentration of Endogenous Tissue Plasminogen Activator and the Occurrence of Future Cardiovascular Events.

Data from recent prospective studies of hemostasis and thrombosis indicate that the plasma concentration of endogenous tissue-type plasminogen activator (tPA) is often elevated years in advance of a first arterial occlusion. Specifically, among healthy subjects with no prior cardiovasacular disease, the risk of future myocardial infarction and stroke appears to be three to four times higher among subjects with high baseline levels of tPA antigen as compared to subjects with lower levels. Whether this relationship represents activation of the endogenous fibrinolytic system in response to the presence of preclinical atherosclerosis or is a reflection of elevated concentrations of local plasminogen activator inhibitors is currently unresolved. However, cross-sectional data indicate that the plasma concentration of IPA antigen is related to several traditional atherosclerotic risk factors, including HDL cholesterol, findings that further support a direct relationship between endogenous IPA and vascular risk. In concert with data concerning the primary inhibitors of plasminogen activation, it has been hypothesizd that the endogenous fibrinolytic system varies within the general population such that certain individuals are prone to thrombosis, whereas others may be prone to hemorrhage. Thus, observations regarding fibrinolytic activation and inhibition raise the possibility that assessment of the intrinsic fibrinolytic system may prove useful in identifying individuals at increased risk for vascular thrombosis. In addition, available findings suggest that therapeutic agents capable of favorably shifting the net filerinolytic balance may provide a new strategy for cardiovascular disease prevention.

Sleep physiological characteristics of exhausted men.

Problems initiating and maintaining sleep, and waking up exhausted have been implicated as precursors of a first nonfatal myocardial infarction. These sleep problems are part of an array of complaints that we have labeled as reflecting a state of 'vital exhaustion.' Excess fatigue, loss of vigor, increased irritability, and feelings of demoralization are also characteristic of this state of vital exhaustion, which has been found to constitute a risk indicator for future myocardial infarction. In the present study, we tested the hypothesis that the sleep of exhausted subjects is characterized by a relative absence of slow wave sleep. To test this hypothesis, all-night recordings of the EEG, EOG, and submental EMG of nine exhausted and eight nonexhausted subjects were made for four nights. Sleep stages were rated according to standard criteria. Because these stages do not adequately reflect the essentially continuous aspect of slow wave sleep (SWS), a more detailed analysis of changes in frequencies of the EEG during sleep was also made, using spectral analysis. It seemed that SWS was significantly diminished in exhausted subjects. This suggests that the normal restoration processes that take place during sleep are impaired in exhausted subjects. Additional studies are required to determine the significance of this finding with respect to cardiovascular control during sleep.

A Prospective Study of Lipoprotein(a) and the Risk of Myocardial Infarction

To assess prospectively the risk of myocardial infarction (MI) associated with elevated levels of lipoprotein(a) (Lp[a]). Nested case-control study using prospectively collected plasma samples. Participants in the Physicians' Health Study. A total of 14,916 male physicians aged 40 to 84 years with no prior history of MI or stroke provided plasma samples at baseline and were followed up prospectively for an average period of 60.2 months. Samples from 296 physicians who subsequently developed MI were analyzed for Lp(a) level together with paired controls, matched for smoking status and age. Fatal or nonfatal acute MI. The distribution of Lp(a) level among cases was virtually identical to that of controls (P = .88), and there was no significant difference between groups for median Lp(a) levels (103.0 mg/L vs 102.5 mg/L; P = .73). In analyses controlling for age and smoking status, we found no evidence of association between increasing level of Lp(a) and risk of MI (relative risks from lowest to highest quintiles of Lp(a): 1.00, 0.97, 0.83, 0.88, and 1.07; P for trend = .93) or a threshold effect at any prespecified cutoff of Lp(a) level (relative risks associated with Lp[a] levels above the 25th, 50th, 75th, 90th, and 95th percentiles of the control distribution, respectively: 1.04, 1.00, 1.19, 1.00, and 1.07; all P values nonsignificant). Further adjustment for both lipid and nonlipid cardiovascular risk factors had no material impact. In this prospective study of predominantly middle-aged white men, we found no evidence of association between Lp(a) level and risk of future MI. These data do not support the use of Lp(a) level as a screening tool to define cardiovascular risk among this population.