Summary
The prevalence, incidence, risk factors and prognosis of silent myocardial infarction are less well known than those of silent myocardial ischaemia. The aims of this article are to evaluate the prevalence and incidence of silent myocardial infarction in subjects with or without a history of cardiovascular disease and in diabetic patients, and to identify potential risk factors and estimate prognosis through a review of the literature. A Medline search identified studies that provided data on the prevalence, incidence, potential risk factors and/or prognosis of silent myocardial infarction, among cohorts from the general population and large clinical studies of at-risk patients (with hypertension or a history of cardiovascular disease or diabetes). The search identified 15 studies in subjects from the general population, five in hypertensive patients, six in patients with a history of cardiovascular disease, and 10 in diabetic patients. The prevalence and incidence of silent myocardial infarction appear highly variable depending on the population studied, the patients’ ages, and the method used to detect silent myocardial infarction. In the general population, the prevalence of silent myocardial infarction increased markedly with increasing age (up to > 5% in elderly subjects). Hypertension causes only a moderate increase in prevalence, whereas underlying cardiovascular diseases and diabetes are associated with marked increases in prevalence. The incidence of silent myocardial infarction changes in the same way. The main predictive factors of silent myocardial infarction are hypertension, history of cardiovascular diseases and diabetes duration. Silent myocardial infarction is associated with as poor a prognosis as clinical myocardial infarction. The frequency of silent myocardial infarction and the poor prognosis in at-risk patients amply justify its systematic early detection and active management.
Résumé
Comparativement à l’ischémie myocardique silencieuse, la prévalence et l’incidence de l’infarctus du myocarde silencieux (IDMs), ses facteurs de risque et son pronostic sont mal connus. Évaluer la prévalence et l’incidence de l’IDMs chez des sujets avec/sans antécédents cardiovasculaires et chez des diabétiques, identifier ses facteurs de risque et estimer son pronostic, à partir des données de la littérature. La recherche a été effectuée dans Medline pour identifier, parmi les cohortes de sujets de population générale et les grandes études de patients à risque (hypertension, maladies cardio-vasculaires, diabète), celles évaluant la prévalence et l’incidence de l’IDMs, ses facteurs de risque et son pronostic. La recherche a identifié 15 études en population générale, cinq chez des patients hypertendus, six chez des patients avec antécédents cardiovasculaires et dix chez des patients diabétiques. La prévalence et l’incidence de l’IDMs apparaissent très variables selon la population étudiée, l’âge des patients et la méthode de détection. En population générale, la prévalence de l’IDMs augmente nettement avec l’âge (jusqu’à > 5 % chez les sujets âgés). L’hypertension augmente modérément la prévalence, tandis que les maladies cardiovasculaires sous-jacentes et le diabète induisent une nette augmentation de la prévalence de l’IDMs. L’incidence de l’IDMs varie parallèlement. Les principaux facteurs pronostiques sont l’hypertension, les maladies cardiovasculaires et la durée du diabète. Enfin, le pronostic de l’IDMs est aussi péjoratif que celui de l’IDMs clinique. La fréquence et le mauvais pronostic de l’IDMs chez les patients à risque justifient son diagnostic systématique précoce et une prise en charge active.
Background
A substantial number of myocardial infarctions (MIs) are asymptomatic or associated with minor and atypical symptoms, and are found accidentally during routine electrocardiogram (ECG) examinations that reveal the existence of abnormal Q waves. The possible causes of blunted MI perception in some patients remain ill defined, but there may be some impairment of the stimulation of cardiac receptors, impulse initiation, or conduction, or of cerebral pain perception . Symptoms are often atypical or even absent, especially in diabetic patients – a population particularly at risk for coronary artery disease (CAD) .
Compared with the frequency of silent myocardial ischaemia, which is defined as evidence of myocardial ischaemia in the absence of signs of angina , the frequency of silent MI, which is unequivocal objective signs of infarction accompanied by unrecognized minimal, atypical symptoms or no symptoms at all, is less well known. Data may be collected, however, from studies that followed subjects from the general population or subjects at risk for CAD, such as those with hypertension or a history of cardiovascular disease, and also from large clinical studies that have been conducted for the evaluation of antidiabetic or hypolipidaemic therapies.
The aim of the present study was to retrieve information on the prevalence, incidence, and predictive/prognostic factors of silent MI, and to assess the influence of potential factors such as age, hypertension, other cardiovascular disorders, and diabetes that may promote the occurrence of silent MI.
Methods
Articles meeting the study objectives were identified by searching the MEDLINE database. Only relatively recent studies (from 1980 onwards) were retained for analysis, given that the detection and management of infarction may have changed considerably over time. Furthermore, studies essentially focused on the treatment of coronary heart disease were excluded.
A general search was first performed using the following keywords: “silent myocardial infarction” and “unrecognized myocardial infarction”. Furthermore, a manual search was conducted from the bibliographic references quoted in the selected publications, and also from the “related citations” in PubMed. The information gathered was then analysed to estimate the prevalence of silent MI in the populations considered and the incidence over the follow-up period in each study.
Hereafter, the prevalence of silent MI is expressed as the proportion of patients with silent MI detected by the presence of a Q wave on the ECG or of abnormalities at stress echocardiography, delayed gadolinium-enhanced cardiac magnetic resonance imaging (DGE-MRI), or scintigraphy in the absence of a previous history or obvious clinical symptoms of MI. The prevalence of silent MI is also expressed as the proportion relative to all clinical MIs or all non-fatal MIs. The incidence of silent MI is either reported as the number of incident cases per 1000 patient-years, or estimated from the cumulative number of cases observed referred to the duration of the follow-up period and expressed as the number of cases per 1000 patient-years.
Results of the bibliographic search
The search in MEDLINE allowed the initial identification and selection of:
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23 general publications on silent MI;
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134 articles on studies conducted in patients with hypertension;
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nine articles on studies conducted in patients with CAD (five studies), thrombosis (two studies), or cardiac dyskinesia (two studies);
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73 articles on clinical studies conducted in diabetic patients;
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eight articles in patients with diabetic neuropathy;
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24 articles on clinical studies conducted in patients with dyslipidaemia;
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14 articles on studies conducted in patients with nephropathy.
In addition to these 285 publications, 16 articles were identified by the manual search. Analysis of all these articles finally allowed the selection of 36 articles reporting data on silent MI: 15 in healthy subjects from the general population, five in hypertensive patients, six in patients with a history of cardiovascular disease, and 10 in diabetic patients.
Methods of silent MI diagnosis
In most studies, diagnosis of silent MI was based on the existence of a Q wave on ECG, and in some cases on R-wave reduction or abnormalities of the ST segment and/or T wave as coded according to the Minnesota classification . In some studies, silent MI was detected by stress echocardiography (one study), dipyridamole/exercise stress scintigraphy (two studies) or delayed DGE-MRI (three studies) which in addition detected non-Q-wave silent MIs.
The choice of the detection method may have had an impact on silent MI diagnosis, as there may be a relationship between the knowledge of a patient’s medical history at the time of examination, the choice of the detection method, and the accuracy of the diagnosis. An ECG is indeed the preferred detection method for patients with no obvious sign of MI, but may show low sensitivity, whereas more sophisticated methods used in patients with a stronger suspicion of MI may show greater sensitivity (e.g. DGE-MRI), possibly at the cost of lower selectivity (e.g. stress methods may erroneously detect reversible ischaemia).
Results
Prevalence of silent MI in the general population
Data on the prevalence of silent MI were obtained from 10 studies conducted in Europe, North America and India in healthy subjects from the general population, either adults (eight studies) or elderly subjects (two studies) ( Table 1 ). In all these studies, silent MI was detected by ECG (Q wave and/or ST-T abnormalities in two studies) ( Table 1 ). The patient populations comprised only low proportions of diabetic patients (0–7.6% of subjects aged < 65 years; 9.8–12.4% of those aged > 65 years).
| Cohort name and/or year | Region | n | Sex | Mean or range age (years) | Method of diagnosis | Prevalence (%) | Proportion of all MIs (%) |
|---|---|---|---|---|---|---|---|
| Bronx AS 1990 | USA | 390 | M/F | 79 | ECG Q wave | 6.4 | 35 |
| 1992 | India | 5621 | M/F | 25–64 | ECG Q wave | 1.4 | – |
| Reykjavik 1995 | Europe | 9141 | M | 33–60 at entry | ECG | 0.5 at age 50 to > 5 at age 75 | 54 |
| Reykjavik 1998 | Europe | 9773 | F | 32–59 at entry | ECG | < 1 at age 60 to 1.9% at age 75 | 42 |
| BRHS 2000 | Europe | 7735 | M | 50 | ECG | 1.7 | 46 |
| CHS 2000 | USA | 5888 | M/F | 72 | ECG Q wave a | 3.4 | 22 |
| MONICA 2003 | Europe | 771 | M/F | 45 | ECG Q wave | 4.8 | 64 |
| Olmsted 2005 | USA | 2042 | M/F | 62 | ECG Q wave a | 3.9 | 44 |
| Rochester 2005 | USA | 603 | M/F | 58 | ECG | 0.3 | – |
| Rotterdam 2008 | Europe | 6347 | M/F | 69 | ECG Q wave | 5.4 | 45 |
These data suggest a strong relationship between subjects’ age and prevalence of silent MI. The prevalence of silent MI was lowest (0.3–0.5%) in the studies that included young subjects (Rochester cohort and Reykjavik male cohort) and highest (3.4–6.4%) in those that included older subjects (Rotterdam, Olmsted, Cardiovascular Health Study [CHS], and Bronx Aging Study [AS] cohorts) . The prevalence of silent MI was also high among the young subjects included in the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) cohort (4.8%) . This is probably because this particular ethnic group is more likely to develop CAD (8.6% of subjects had impaired glucose tolerance). The direct relationship between age and the prevalence of silent MI was well assessed in the two Reykjavik cohorts: in middle age (∼ 60 years), the prevalence of silent MI was estimated at 1–1.5% in men and women, but this was much higher (> 5%) in men aged > 75 years . Geographic location does not seem to exert a notable influence. In the studies in relatively young people, silent MIs accounted for 42–64% of all MIs , whereas this proportion was lower (22–35%) in older subjects (CHS and Bronx AS cohorts) ( Table 1 ).
Prevalence of silent MI in high-risk populations: patients with hypertension or a history of CAD
The two studies of hypertensive subjects that provided prevalence data reported somewhat conflicting results. In the Medical Research Council (MRC) trial, which included mildly hypertensive patients , hypertension did not seem to be associated with increased prevalence of silent MI, whereas in the International Prospective Primary Prevention Study in Hypertension (IPPPSH)-Italia study , the prevalence of silent MI appeared moderately elevated compared with that in normotensive subjects of similar age (except for the MONICA study and the Olmsted study ; see above) from the general population ( Table 2 ).
| Cohort name and/or year | Region | n | Sex | Mean or range age (years) | Method of diagnosis | Prevalence (%) |
|---|---|---|---|---|---|---|
| Patients with arterial hypertension | ||||||
| MRC trial 1988 | Europe | 17 354 | M/F | 35–64 | ECG Q wave | M/F 1.3/1.5 |
| IPPPSH 1988 | Europe | 746 | M/F | 40–64 | ECG Q wave | M/F 2.4/3.3 |
| Patients with a history of cardiovascular disease | ||||||
| 2006 | USA | 579 | M/F | – | Exercise stress scintigraphy | 7.1 (diabetics 18.4) |
| 2006 | USA | 195 | M/F a | 59 | DGE-MRI | 22.6 |
| 2007 | Europe | 1092 | M/F b | 64 | Stress echocardiography | 23.4 (diabetics 34) |
| 2009 | USA | 185 | M/F a | 60 | ECG Q wave/DGE-MRI | ECG/MRI 8.1/27.0 |
a Subjects with suspected or known CAD.
The four studies in patients with a history of cardiovascular disease showed a notably higher prevalence of silent MI ( Table 2 ). In patients with a history of cardiovascular disease, including those with a clinical suspicion of CAD or with non-cardiac vascular surgery, the observed prevalence of silent MI reached 23% in both a European and a North American study where silent MI was detected by stress echocardiography or DGE-MRI . The prevalence of silent MI was similar (27%) in a study of patients with suspected CAD in whom silent MI was detected by DGE-MRI (compared with only 8.1% by ECG) . It was found to be lower, however, in a study that included a high proportion of diabetic patients in whom silent MI was detected by exercise stress scintigraphy . In two studies where both types of data were available, the proportion of silent MI patients was notably higher amongst diabetic patients compared with their non-diabetic counterparts .
Prevalence of silent MI in diabetic patients
Data on the prevalence of silent MI in diabetic patients were retrieved from four articles ( Table 3 ) . One of them concerned the Australian Fremantle cohort, which included 1269 patients with type 2 diabetes of median 4-year duration . The three other studies were smaller series of 30–107 diabetic patients that were carried out in North America. In addition to diabetes, patients included in two studies had a cardiovascular disease (suspicion of CAD based on recent suggestive symptoms or peripheral artery disease ) or, in another study, peripheral or cardiac neuropathy characterized by the Valsalva test . Some patients (25%) of the Fremantle cohort also had CAD .
