Unheralded Myocardial Infarction Research Articles

Association between the diagnostic classification of newly diagnosed coronary artery disease and future heart failure development.

The first clinical manifestation of coronary artery disease (CAD) varies widely from unheralded myocardial infarction (MI) to mild, incidentally detected disease. The primary objective of this study was to quantify the association between different initial CAD diagnostic classifications and future heart failure. This retrospective study incorporated the electronic health record of a single integrated health care system. Newly diagnosed CAD was classified into a mutually exclusive hierarchy as MI, CAD with coronary artery bypass graft (CABG), CAD with percutaneous coronary intervention, CAD only, unstable angina, and stable angina. An acute CAD presentation was defined when the diagnosis was associated with a hospital admission. New heart failure was identified after the CAD diagnosis. Among 28 693 newly diagnosed CAD patients, initial presentation was acute in 47% and manifested as MI in 26%. Within 30 days of CAD diagnosis, MI [hazard ratio (HR) = 5.1; 95% confidence interval: 4.1-6.5] and unstable angina (3.2; 2.4-4.4) classifications were associated with the highest heart failure risk (compared to stable angina), as was acute presentation (2.9; 2.7-3.2). Among stable, heart failure-free CAD patients followed on average 7.4 years, initial MI (adjusted HR = 1.6; 1.4-1.7) and CAD with CABG (1.5; 1.2-1.8) were associated with higher long-term heart failure risk, but an initial acute presentation was not (1.0; 0.9-1.0). Nearly 50% of initial CAD diagnoses are associated with hospitalization, and these patients are at high risk of early heart failure. Among stable CAD patients, MI remained the diagnostic classification associated with the highest long-term heart failure risk, however, having an initial acute CAD presentation was not associated with long-term heart failure.

Physical Inactivity is Related to Unheralded Myocardial Infarction More Than Uncomplicated Stable Angina

ABSTRACT Background: Ischemic heart disease can vary substantially in its clinical presentation. Some patients have acute myocardial infarction (MI) without any previous signs of myocardial ischemia, whereas other patients may have stable angina pectoris for years without periods of acute instability; this suggests the possibility of different risk influence in these 2 groups of patients. Methods: Cardiovascular risk factors were compared in 112 consecutive patients with unheralded MIs (81 men; 59.9 ± 11.6 years) and in 168 consecutive patients with chronic stable angina (108 men; 58.2 ± 10.5 years) with at least 60% occlusion in lumen diameter in 1 of the coronary vessels. Results: Logistic-regression analysis revealed that physical inactivity (odds ratio [OR]: 4.32, 95% CI = 2.07, 8.99; P < 0.0001), the values of high sensitive-C-reactive protein levels (OR: 1.05, 95% CI = 1.00, 1.11; P = 0.043), diabetes (OR: 2.88, 95% CI = 1.42, 5.83; P = 0.003), and positive family history of premature coronary artery disease (OR: 1.96, 95% CI: 1.04, 3.71; P = 0.038) were independent predictors of unheralded MI versus chronic stable angina. Conclusion: In our subjects, sedentary life, diabetes mellitus, positive family history of premature coronary artery disease, and higher high sensitive-C-reactive protein levels were important independent predictors for unheralded MI, which suggests that these factors are involved in thrombosis, plaque rupture, or both.

Long-term prognosis of unheralded myocardial infarction vs chronic angina; role of sex and coronary atherosclerosis burden

BackgroundAngina pectoris (AP) and unheralded myocardial infarction (MI) are considered random clinical equivalents of ischemic heart disease (IHD). Aim of the study was to evaluate the long-term progression of AP as opposed to unheralded MI as alternative first clinical presentations of IHD and the effect of sex on prognosis.MethodsThe study included 2272 consecutive patients, 1419 MI and 1353 AP, hospitalized from 1995 to 2007 at CNR Clinical Physiology Institute, Pisa, Italy and followed up to December 2013, who fulfilled the following criteria: unheralded MI or AP as first manifestation of IHD; age < = 70 years; known coronary anatomy; at least 10-year follow-up. Fatal and non fatal MI, all-cause, and cardiac deaths were the end-points.ResultsMales were predominant in MI (86%) as compared to AP (77%). Females were predominantly affected by AP (61%, MI 39%), and older than men (61 ± 7 vs 59 ± 8 years, p < 0.001). Coronary stenoses were prevalent in MI. During 115 ± 58 months follow-up, 628 deaths (23%) were observed, including 269 cardiac (43%), and 149 cancer deaths (24%). Long-term prognosis was significantly better in AP than MI group. The lowest prevalence of future MI was recorded in female AP (p < 0.001).ConclusionsMI as first clinical manifestation of IHD implies a more adverse prognosis than AP; future MI is a rare event in AP; sex influences the first presentation of IHD and its course with possible implications for preventive strategy.

Differential proteome profile in ischemic heart disease: Prognostic value in chronic angina versus myocardial infarction. A proof of concept

The initial clinical manifestation of ischemic heart disease (IHD) i.e. unheralded myocardial infarction (MI) versus chronic angina pectoris (AP) is statistically associated with adverse or mild disease progression respectively in the long-term follow-up. Here, we subjected AP and MI patients to blood proteomic analysis by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) in order to investigate putative new prognostic biomarkers of IHD manifestation. We found several differentially expressed peaks but four of them (4176, 4475, 14,158m/z and 8922m/z for AP and MI, respectively) were most reliable. Two of them were identified; 14,158m/z peak was the double-charged form of Apolipoprotein A-I and its vasoprotective action accords with prominence in AP. The 4176m/z peak was related to FAM83C protein, while neither the 4475m/z peak nor the MI-linked 8922m/z peak could be identified. We conclude that SELDI-TOF-MS analysis may yield a panel of molecular signals able to retrospectively classify patients according to their clinical and molecular features, exploitable for predicting the natural course of IHD.

Impact of Family History of Coronary Artery Disease in Young Individuals (from the CONFIRM Registry)

Although family history (FH) of coronary artery disease (CAD) is considered a risk factor for future cardiovascular events, the prevalence, extent, severity, and prognosis of young patients with FH of CAD have been inadequately studied. From 27,125 consecutive patients who underwent coronary computed tomographic angiography, 6,308 young patients (men aged <55 years and women aged <65 years) without known CAD were identified. Obstructive CAD was defined as >50% stenosis in a coronary artery >2 mm diameter. Risk-adjusted logistic regression, Kaplan-Meier, and Cox proportional-hazards models were used to compare patients with and without FH of CAD. Compared with subjects without FH of CAD, those with FH of CAD (FH+) had higher prevalences of any CAD (40% vs 30%, p <0.001) and obstructive CAD (11% vs 7%, p <0.001), with multivariate odds of FH+ increasing the likelihood of obstructive CAD by 71% (p <0.001). After a mean follow-up period of 2 ± 1 years (42 myocardial infarctions and 39 all-cause deaths), FH+ patients experienced higher annual rates of myocardial infarction (0.5% vs 0.2%, log-rank p = 0.001), with a positive FH the strongest predictor of myocardial infarction (hazard ratio 2.6, 95% confidence interval 1.4 to 4.8, p = 0.002). In conclusion, young FH+ patients have higher presence, extent, and severity of CAD, which are associated with increased risk for myocardial infarction. Compared with other clinical CAD risk factors, positive FH in young patients is the strongest clinical predictor of future unheralded myocardial infarction.

Diagnosis of Coronary Artery Disease in Persons with Diabetes Mellitus

Coronary heart disease (CHD) is the leading cause of morbidity and mortality in patients with diabetes. Asymptomatic CHD in these patients is elusive and carries a poor prognosis given the fact that an unheralded acute myocardial infarction or sudden cardiac death frequently constitutes its first presentation. Because effective screening for asymptomatic patients with type 2 diabetes for both the presence and severity of CHD is intuitively appealing, we have summarized the utility and prognostic value of various diagnostic modalities (both functionally and anatomically) in enhancing risk stratification and leading to improved and more aggressive management of the risk factors. There exist some evidence and recommendations for screening of asymptomatic persons with diabetes using certain modalities. More research is needed to define potential subsets of patients with diabetes who may benefit from additional testing for asymptomatic CHD.

What does the clinical cardiologist need from noninvasive cardiac imaging: Is it time to adjust practices to meet evolving demands?

With the recent emergence of multidetector computed tomography angiography, coronary anatomy can now be assessed noninvasively. Until this advancement, functional noninvasive imaging used to serve as a gatekeeper that governed access to invasive diagnosis by coronary angiography and subsequent therapy. In the current era the threshold for access to coronary anatomy will be lowered. Functional noninvasive imaging will often come second, while anatomy is known already. If appropriate use of revascularization procedures is to be promoted, functional evaluation shall play an even greater role than before as a guide for selection of therapy. In subjects screened while the atherosclerotic disease is still at a preclinical stage, the ability to image plaque activity in the absence of flow-limiting stenosis will be essential in our attempts to prevent sudden ischemic cardiac death and unheralded myocardial infarction. In patients with advanced age and extensive obstructive disease, the diagnostic performance of functional testing will have to be raised by shifting from "per-patient" to "per-vessel" accuracy. Reengineering of currently available methods or the development of novel technologies that provide an integrative evaluation of anatomy and function will be necessary. With the availability of an increasing number of imaging options, it is anticipated that the emphasis will be placed more than ever on cost-effectiveness on a population basis, as well as on segmental predictive accuracy in the individual subject.

Enhanced T-Helper-1 Lymphocyte Activation Patterns in Acute Coronary Syndromes

We sought to determine whether different stages of coronary artery disease (CAD) are associated with distinct differentiation patterns of activated T cells. Atherosclerosis is an inflammatory disease. However, little is known about specific inflammatory cell activation in atherosclerosis, for example, the T-helper (Th)1/Th2-balance. We studied 18 patients with stable angina (SA), 28 patients with acute coronary syndrome (ACS) (16 with unstable angina pectoris and 12 with ST-segment elevation myocardial infarction), 19 patients with unheralded myocardial infarction (UH), and 16 control patients. Cytokine patterns and transcription factor signaling pathways of circulating T cells were characterized using reverse transcription polymerase chain reaction and flow cytometry. Although interferon (IFN)-gamma(+)/CD3(+) T cells were approximately 2-fold greater in patients with SA or UH than in control subjects, there was a massive expansion of Th1 cells in patients with ACS (p < 0.001). This increase was paralleled by significantly increased mRNA transcript levels for signal-transducer-and-activator-4 (ACS 1.17 +/- 0.14 relative units [RU]; control patients 0.44 +/- 0.09 RU; SA 0.67 +/- 0.12 RU; UH 0.61 +/- 0.17 RU), interleukin-2 (ACS 1.55 +/- 0.51 RU; control patients 0.21 +/- 0.09 RU; SA 0.54 +/- 0.18 RU; UH 0.45 +/- 0.16 RU), and IFN-gamma in ACS (1.27 +/- 0.39 RU; control patients 0.35 +/- 0.09 RU; SA 0.58 +/- 0.11 RU; UH 0.53 +/- 0.24 RU; p < 0.002). Th2 and Th0 cells were not different across patient subsets. The burden of CAD was identical between SA (1.4 +/- 0.2 diseased vessels, 68 +/- 13% diameter stenosis) and ACS (1.4 +/- 0.2 diseased vessels, 64 +/- 17% diameter stenosis) but significantly greater in patients with UH (2.5 +/- 0.5 diseased vessels, 95 +/- 7% diameter stenosis; p < 0.05). Patients with UH have a greater burden of obstructive CAD than SA but no greater T-cell activation. Patients with ACS have the same extent of CAD than SA but significantly greater activation of Th1 cells that may contribute to the increasing instability. Differences in circulating Th1 cells might indicate different pathogenic components, leading to ACS and UH.

Cardiovascular risk factors for stable angina pectoris versus unheralded myocardial infarction

Background Ischemic heart disease can vary substantially in its clinical presentation. Some patients have acute myocardial infarction (MI) without any previous signs of myocardial ischemia, whereas other patients may have stable angina pectoris for years without periods of acute unstability. This study compared baseline risk factors between subjects in whom stable angina pectoris developed and subjects in whom unheralded fatal or nonfatal MI developed during the follow-up period. Methods In 1970 to 1973, all 50-year-old men in Uppsala, Sweden, were invited to participate in a health survey aimed at identifying risk factors for cardiovascular disease. The present study is a nested case-control study of subjects who were free of coronary heart disease (CHD) at baseline and who then underwent revascularization (percutaneous transluminal coronary angioplasty or coronary artery bypass grafting) because of angina pectoris without preceding MI (n = 70) or in whom fatal or nonfatal MI developed without prior known CHD (n = 372) during the period until 1998. Results In multivariate Cox proportional hazard models, low-density lipoprotein and high-density lipoprotein levels (protective) were significant independent risk factors for stable angina pectoris demanding revascularization, whereas smoking, diastolic blood pressure, serum proinsulin levels, and serum lipid levels were significant independent predictors of subsequent unheralded MI. When comparing hazard ratios (HR), significantly higher HR for diastolic blood pressure (1.40 vs 1.00, for 1 SD increase) and serum proinsulin (1.82 vs1.20, for 1 SD increase) were found in the group in which unheralded MI developed than in the group with stable angina pectoris. Conclusions Serum lipid levels were important risk factors for the development of both stable and acute coronary heart disease. In addition, proinsulin levels and blood pressure were independent predictors of unheralded MI only, which suggests that these factors are involved in thrombosis, plaque rupture, or both.

P2308 Coronary calcifications versus Framingham and PROCAM risk assessment in patients with a first, unheralded myocardial infarction

P2308 Coronary calcifications versus Framingham and PROCAM risk assessment in patients with a first, unheralded myocardial infarction

Coronary calcifications in young patients with first, unheralded myocardial infarction: a risk factor matched analysis by electron beam tomography

Coronary calcifications in young patients with first, unheralded myocardial infarction: a risk factor matched analysis by electron beam tomography

SAI-21: Coronary calcifications in “young” patients with first, unheralded myocardial infarction: a risk factor-matched analysis by electron-beam tomography

SAI-21: Coronary calcifications in “young” patients with first, unheralded myocardial infarction: a risk factor-matched analysis by electron-beam tomography

Enhanced inflammatory response in patients with preinfarction unstable angina

OBJECTIVESWe assessed the extent and the time course of the acute phase response following myocardial cell necrosis and its relationship with the presence of preinfarction unstable angina (UA).BACKGROUNDElevated levels of acute phase proteins have been reported in patients with UA and in patients with acute myocardial infarction (MI).METHODSC-Reactive Protein (CRP), serum amyloid A protein (SAA) and interleukin-6 (IL-6) were measured in 36 patients with MI admitted within 3 h from symptoms onset. All patients had normal levels of creatine kinase and of troponin T on admission, rising above diagnostic levels within 6 to 12 h. Blood samples for CRP, SAA and IL-6 measurements were taken on admission, at 6, 24, 48, 72 h and at discharge.RESULTSTwenty of the 36 patients studied presented an unheralded MI (Group 1); the remaining 16 patients had symptoms of unstable angina in the preceding 7 days (Group 2). Group 2 patients have much higher levels of CRP and SAA on admission (median values 8.8 vs. 3 mg/L and 28 vs. 3.4 mg/L, respectively, all p < 0.001). Following the necrotic insult, despite similar infarct size and clinical signs of reperfusion, Group 2 patients had strikingly higher peaks of IL-6 (median values 85.2 vs. 19 pg/ml, p < 0.05), CRP (50 vs. 31.4 mg/L, p < 0.05) and SAA (228 vs. 45 mg/L, p < 0.001).CONCLUSIONSOur data demonstrated that the acute phase response is greatly enhanced in patients with preinfarction UA compared with those presenting with an unheralded MI. The significant differences in acute phase response observed in these two clinical presentations of MI indicate a major difference in their underlying pathogenetic components.

Protein C resistance in severe peripheral atherosclerosis and in unheralded myocardial infarction

Protein C resistance in severe peripheral atherosclerosis and in unheralded myocardial infarction

Risk factors in schoolchildren associated with a family history of unheralded myocardial infarction or uncomplicated stable angina in male relatives

Objectives. The aim of this study was to compare risk factors for coronary atherosclerosis in children with a family history of unheralded myocardial infarction or uncomplicated stable angina.Background. In patients with unheralded myocardial infarction, coronary atherosclerosis might have a greater tendency to cause acute coronary occlusion than in patients with uncomplicated stable angina, suggesting the possibility of different risk factors in these two groups of patients.Methods. Serum lipid levels were compared in children with a family history of unheralded myocardial infarction (236 children) or uncomplicated stable angina (48 children) or no family history of ischemic heart disease (613 children).Results. Mean (± 1 SD) total serum cholesterol was higher in children with a family history of myocardial infarction than in control subjects (161 ± 28 vs. 154 ± 25 mg%, p < 0.01). In children with a family history of stable angina, mean total serum cholesterol (159 ± 25 mg%) was similar to that in children with family history of myocardial infarction. High density lipoprotein cholesterol and apolipoprotein A-I were higher in children with family history of stable angina than in children with family history of myocardial infarction and control subjects (69 ± 18 vs. 61 ± 13 and 60 ± 13 mg%, p < 0.01; 143 ± 23 vs. 130 ± 18 and 129 ± 18 mg%, p < 0.01, respectively). in children with a family history of myocardial infarction, the low density/high density lipoprotein cholesterol ratio was significantly higher than in control subjects (1.53 ± 0.64 vs. 1.44 ± 0.56, p < 0.05). Conversely, in children with a family history of stable angina, this ratio (1.24 ± 0.51) was significantly lower (p < 0.05) than in control subjects.Conclusions. Risk factors for coronary athersclerosis in children with a family history of unheralded myocardial infraction are different from those in children with a family history of uncomplicated stable angina. Higher levels of apolipoprotein A-I early in life might reduce the risk of acute coronary syndromes.

Comparison of coronary angiographic findings in acute and chronic first presentation of ischemic heart disease.

It is generally assumed that the clinical manifestations of ischemic heart disease occur randomly on the same underlying pathological process. Therefore, coronary angiographic findings should be similar whether the first presentation of ischemic heart disease is acute myocardial infarction or uncomplicated chronic stable angina. We studied 102 patients (men < or = 60 years old, women < or = 65 years old) presenting with either acute myocardial infarction as first manifestation of coronary artery disease with a concomitant coronary angiogram (55 patients; mean age, 50.2 years) or stable angina for at least 2 years with no history, ECG, or left ventriculographic evidence of any acute event and with an angiogram performed at least 2 years after initial symptoms (47 patients; mean age at symptom onset, 51.7 years). These angiograms were evaluated blindly for severity (number of vessels diseased, stenoses > or = 50%, occlusions), extent of disease (with an index derived by assigning a score of 0-3 per segment, depending on the proportion of lumen length irregularity and dividing the sum by the number of visualized segments), and pattern (discrete: three or fewer loci of disease never involving more than 50% of the length of any segment or diffuse: anything exceeding this). Patients with unheralded myocardial infarction had fewer vessels diseased, fewer stenoses and occlusion, and a lower extent index than those with uncomplicated stable angina (mean +/- SD of 1.3 +/- 0.8 versus 2.1 +/- 0.8, p < 0.001; 2.1 +/- 1.8 versus 3.9 +/- 1.8, p < 0.001; 0.6 +/- 0.6 versus 1.0 +/- 0.9, p < 0.02; and 0.6 +/- 0.5 versus 1.2 +/- 0.5, p < 0.001, respectively). A discrete pattern was present in 54.5% of patients with unheralded infarction and in only 8.5% of those with uncomplicated angina (p < 0.001). These very different angiographic findings suggest that unheralded acute myocardial infarction and uncomplicated chronic stable angina do not occur randomly on a common atherosclerotic background but rather that additional factors, such as a varying propensity to thrombosis, may predispose to one or the other of these two clinical syndromes.

Different coronary angiographic findings in unheralded acute myocardial infarction and uncomplicated chronic stable angina

Different coronary angiographic findings in unheralded acute myocardial infarction and uncomplicated chronic stable angina

Early unheralded myocardial infarction and chronic stable angina have different risk factors: A clue to a different pathogenesis

Early unheralded myocardial infarction and chronic stable angina have different risk factors: A clue to a different pathogenesis

Total ischemic burden in patients with coronary artery disease

In patients with coronary artery disease, angina pectoris provides an unreliable underestimation of disease activity and risk. Unheralded myocardial infarction and sudden death are common clinical presentations. Furthermore, objective testing, in hospital and more recently during the patient's normal daily activities, has demonstrated frequent and asymptomatic episodes of ischemia, as indicated by transient ST-segment depression. Since the underlying pathophysiologic disturbances of myocardial perfusion appear to be similar in painful and painless episodes, it seems appropriate to consider them together as the "total ischemic burden" on the myocardium. Research into this functional expression of coronary disease has indicated that active ischemia is associated with an increased risk of morbid events in all clinical subgroups of patients, including those with stable angina, unstable angina, peripheral vascular disease and following myocardial infarction. If this is confirmed in prospective trials, the assessment of total ischemic burden is likely to become part of the clinical investigation of patients with coronary disease. Clinical trials testing the efficacy of interventions will need to examine the effect on ischemic activity during normal daily life, in addition to symptoms and exercise tolerance. Evidence is still required to demonstrate whether therapy aimed at reducing the total ischemic burden will prolong life. The total ischemic burden provides a marker to follow the dynamic changes of the atherosclerotic lesion. Future research may have to concentrate on treatment aimed at altering the natural history of obstructive coronary atherosclerosis in order to affect the long-term outlook for patients with coronary artery disease.