In this large survey of patients with ACS from Europe and the Mediterranean area, where only a small proportion of patients had no conventional risk factors, we found that presenting with ST elevation was strongly associated with smoking but inversely related to BMI and hypertension. Prior manifestations of coronary disease, with concomitant treatment, were associated with less ST elevation, but the associations between presenting with ST elevation and risk factors were independent of prior disease and medication. Thus, shifts in coronary risk factor pattern, with reduced smoking rates and an increase in the prevalence of obesity and obesity related disorders such as hypertension, may be contributing to a shift in the clinical presentation in ACS and perhaps to improved outcomes.
Several studies have reported decreasing severity of AMI and ACS.5–7,22
In a study from Finland, the proportion of patients who had an AMI with definite ECG findings decreased by about one third between 1983 and 1990,22
together with a significant decrease in the incidence of increased cardiac enzymes. In the US based ARIC (atherosclerosis risk in the communities) study, mean peak creatine kinase concentration decreased 5% per year between 1987 and 1994 among patients with ACS; however, at the same time the proportion with ST elevation increased, providing mixed support for decreases in the severity of AMI.6
Nonetheless, two other population based studies from the USA have indicated decreased disease severity in AMI. One study showed that the proportion of Q wave AMIs, as part of all AMIs, decreased from about one half to one third from the mid 1980s to the mid 1990s.5
The other study, from Olmsted County, Minnesota, examined several indicators of AMI severity between 1983 and 1994. The proportion of patients presenting with ST elevation declined, as well as the occurrence of Q waves and peak creatine kinase concentrations, independently of time to presentation and differences in reperfusion treatment.7
Contributing to the evidence of less severe AMIs are the numerous studies that report decreasing mortality from coronary disease in the USA,8
and in large parts of Europe3
and reports of decreasing case fatality.11,23
In studies investigating trends in fatal and non-fatal AMI, several studies have found that mortality decreased more than the incidence.4,8,10
The increasing survival of patients admitted to hospital has generally been attributed to better hospital care, but changes in risk factor patterns have also been implicated.4
Trends in out-of-hospital coronary mortality probably reflect changes in cardiovascular risk factors, whereas in-hospital mortality is more tied to medical care. However, judging from the results of the present study, and because ST elevation has the most adverse short term prognosis, it is possible that in-hospital mortality is also influenced by risk factor pattern.
Overall, the prevalence of risk factors was high in the Euro heart survey of ACS, with only 12% of the men and women lacking any of the conventional risk factors for the disease. This is a lower proportion than in the dataset from 14 international randomised clinical trials reported by Khot et al
probably in part because patients taking part in trials are selected. Even so, the proportion with no risk factors is probably underestimated because some patients with diabetes, hyperlipidaemia, or hypertension may be unaware of these conditions. Few studies have investigated risk factors in relation to the various manifestations of ACS. Although Khot et al24
did not comment on this, in their study current smoking was more prevalent among patients with ST elevation AMI than among patients with non-ST elevation AMI or unstable angina, particularly among women, whereas hypertension was more common among patients with non-ST elevation AMI. In a recent study of women hospitalised with AMI or unstable angina, current cigarette smoking (OR 1.60) and diabetes mellitus (OR 1.44) predicted AMI, whereas prior coronary disease (OR 0.70) independently predicted unstable angina.25
Other studies have also found smoking to be more prevalent among patients with ST elevation AMI.26,27
Paradoxically, smoking has been found to be associated with lower short term mortality among patients admitted with AMI, particularly after thrombolysis.28–30
Smoking is associated with a hypercoagulable state, particularly with respect to increased concentrations of plasma fibrinogen,31,32
but the propensity for intracoronary clot formation associated with smoking is also due to effects on platelet activation.32
Smokers have also been shown to have better outcome in ACS without ST elevation, but this was shown to be due to a more favourable clinical profile.33
The role of obesity in ACS is much less clear. Obesity is a risk factor for AMI34
but is also strongly associated with other factors in the development of coronary disease, such as hypertension, diabetes mellitus, and decreased glucose tolerance, as well as dyslipidaemia and inflammation. We found that BMI was inversely related to the risk of ST elevation but also that this effect was attenuated if correlates of obesity such as hypertension and diabetes (among men) were taken into account, indicating that the association between BMI and ST elevation was partly mediated by these intermediary factors. The effect was significant only among the women in the study. Among patients with stable and unstable coronary disease undergoing coronary angiography, obesity was recently shown to be strongly related to instability, independently of correlated risk factors and markers of inflammation.35
How this relates to our finding of less ST elevation in obese patients is not clear.
Hypertension is common among patients with AMI and unstable angina, but not many studies have evaluated the role of hypertension in patients with ACS. One recent study showed that more hypertensive patients with ACS were women and that they were older, had more co-morbidities,36
and slightly less often had AMI diagnosed. Hypertensive patients have also been shown to have more non-Q wave AMI but similar infarct sizes compared with non-hypertensive patients.37
The findings from the present study may tentatively help to explain the changes in clinical presentation of ACS in parts of the world. Decreasing rates of smoking, particularly among men, may be resulting in a lower proportion of patients presenting with ST elevation. The worldwide epidemic of overweight and obesity may be counteracting the beneficial effect of the decreasing trends in smoking but may be resulting in milder coronary events, with lower short term mortality. However, despite the increasing trend worldwide of overweight and obesity, blood pressure levels have decreased over the past decades in some countries,38
illustrating the complexity of these issues.
AMI and unstable angina diagnoses were not strictly validated. Even though atherosclerosis is probably the main causative factor for ACS even in patients without an angiographically obvious coronary stenosis, a proportion of the patients with diagnosed unstable angina may have had chest pain of non-cardiac origin. However, among the 5437 patients in the study who underwent a coronary angiography only 5% of these were normal. Only a small minority of patients with a diagnosis of unstable angina and no ST elevation had no prior cardiovascular disease or diabetes. Accordingly, the proportion of patients without any form of coronary disease is likely to be low. Limiting our analysis to patients with confirmed AMI or angiographically confirmed coronary disease would have excluded an important subset of the ACS population.
The main finding of this large survey of patients with ACS from 25 countries in Europe and the Mediterranean basin was that different risk factors were related to different ACS diagnoses. Smoking was related to patients presenting with ST elevation, whereas obesity and hypertension were more common among patients who presented without ST elevation. These differences suggest variations in pathophysiology associated with risk factor pattern, but they may also help to explain some of the temporal trends with respect to disease severity and decreasing mortality from coronary disease in areas where the epidemic of coronary disease seems to be receding.
The Euro heart survey of acute coronary syndromes was sponsored by Schering-Plough and Centocor. The Swedish participation was supported by the Swedish Heart and Lung Foundation.