Risk Of Future Myocardial Infarction Research Articles

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.

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)

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.

A Prospective Study of Triglyceride Level, Low-Density Lipoprotein Particle Diameter, and Risk of Myocardial Infarction

To test whether a predominance of small, dense low-density lipoprotein (LDL) particles and elevated triglyceride levels are independent risk factors for myocardial infarction (MI). Nested case-control study with prospectively collected samples. Prospective cohort study. Blood samples were collected at baseline (85% nonfasting samples) from 14916 men aged 40 to 84 years in the Physicians' Health Study. Myocardial infarction diagnosed during 7 years of follow-up. Cases (n=266) had a significantly smaller LDL diameter (mean [SD], 25.6 [0.9] nm) than did controls (n=308) matched on age and smoking (mean [SD], 25.9 [8] nm; P<.001). Cases also had higher median triglyceride levels (1.90 vs 1.49 mmol/L [168 vs 132 mg/dL]; P<.001). The LDL diameter had a high inverse correlation with triglyceride level (r=-0.71), and a high direct correlation with high-density lipoprotein cholesterol (HDL-C) level (r=0.60). We observed a significant multiplicative interaction between triglyceride and total cholesterol (TC) levels (P=.01). After simultaneous adjustment for lipids and a variety of coronary risk factors, LDL particle diameter was no longer a statistically significant risk indicator, with a relative risk (RR) of 1.09 (95% confidence interval [CI], 0.85-1.40) per 0.8-nm decrease. However, triglyceride level remained significant with an RR of 1.40 (95% CI, 1.10-1.77) per 1.13 mmol/L (100-mg/dL) increase. The association between triglyceride level and MI risk appeared linear across the distribution; men in the highest quintile had a risk about 2.5 times that of those in the lowest quintile. The TC level, but not HDL-C level, also remained significant, with an RR of 1.80 (95% CI, 1.44-2.26) per 1.03-mmol/L (40-mg/dL) increase. These findings indicate that nonfasting triglyceride levels appear to be a strong and independent predictor of future risk of MI, particularly when the total cholesterol level is also elevated. In contrast, LDL particle diameter is associated with risk of MI, but not after adjustment for triglyceride level. Increased triglyceride level, small LDL particle diameter, and decreased HDL-C levels appear to reflect underlying metabolic perturbations with adverse consequences for risk of MI; elevated triglyceride levels may help identify high-risk individuals.

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.

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.

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.

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.

Complex and simple coronary artery stenoses: a new way to interpret coronary angiograms based on morphologic features of lesions.

For many years, atherosclerotic coronary artery lesions have been described by angiographers only in terms of location and degree of narrowing. However, it has become apparent that coronary stenoses generally have distinct morphologic features that can be recognized at angiography and that allow them to be classified as either "simple" or "complex" plaques. Complex plaques are those characterized by ulcerated or ruptured surfaces, subintimal hemorrhage, superimposed partially occluding thrombi, recanalized thrombi, or some combination. Pathologic studies have shown a very high frequency of these lesions at sites of total thrombotic occlusion of coronary arteries. Clinical and angiographic studies have demonstrated a high frequency of such lesions in living patients with both unstable angina and acute myocardial infarction. The presence of complex stenoses has also been found to increase the risk of future myocardial infarction. Plaque morphology thus appears to significantly affect the prognosis of patients with coronary disease and should be carefully evaluated in interpretation of all coronary angiograms.

Diet in the prevention and treatment of myocardial infarction

1. (1) The increase in risk of future myocardial infarction associated with elevation of lipoproteins of the S f o 0–12, 12–20, 20–100, and 100–400 classes provides the basis for a rational application of dietary measures in this disease. 2. (2) The prospect for dietary management of the coronary disease problem lies primarily in the ability of dietary measures to lower these lipoprotein levels. 3. (3) Animal fat contains some factor (or factors) which provokes elevation in the serum level of S f o 0–12 and S f o 12–20 lipoproteins. 4. (4) No valid evidence exists that any protective factor is present in vegetable oils which will lower S f o 0–12 or S f o 12–20 lipoprotein levels. 5. (5) Dietary carbohydrate intake is a prime factor in controlling the serum level of the S f o 20–100 and S f o 100–400 lipoprotein classes. Restriction of dietary carbohydrate can provoke marked falls in the serum level of these lipoproteins. 6. (6) The effect of caloric restriction and weight reduction can be largely explained on the basis of the alteration in animal fat intake and carbohydrate intake in such diets. 7. (7) The serum cholesterol measurement can be a dangerously misleading guide in evaluation of the effect of diet upon the serum lipids. 8. (8) Rational management of patients with coronary heart disease or of individuals attempting to avoid coronary disease depends upon knowledge of the lipoprotein distribution in the individual patient.