In Europe, the prevalence of obesity ranges from 4.0 to 36.5 % [
17] and it is also well known that obesity acts as an independent cardiovascular risk factor for the development of coronary artery disease as well as general atherosclerosis and is associated with increased overall morbidity and mortality [
18,
19]. There is evidence that this increased risk is mediated through obesity-related co-morbidities such as diabetes mellitus, hyperlipidemia, hypertension, increased insulin resistance, enhanced free fatty acid turnover, and promotion of systemic inflammation [
20]. However, despite this correlation there is an assumption of an inverse correlation of obesity with mortality post PCI and less pronounced with a smaller need for repeat revascularisation. This has been described as the “obesity paradox” [
10,
21]. An analysis of 9,633 patients being stratified in normal weight (n = 1,923), overweight (n = 4,813) and obese (n = 2,897) undergoing PCI revealed a higher incidence of major in-hospital complications, including cardiac death (1.0 % vs. 0.7 % vs. 0.4 %; p = 0.001) in normal weight than overweight and obese patients despite similar periprocedural data. This was driven by overall mortality (10.6 % vs. 5.7 % vs. 4.9 %; p < 0.0001). Cardiac mortality (4.8 % versus 3.3 % versus 2.5 %; p < 0.0001) was also significantly higher in normal weight patients; whereas rates of MI and TVR were similar [
10]. A large meta-analysis including 250,152 patients with established coronary artery disease and a mean follow-up of 3.8 years supported these findings with increased relative risk for overall mortality [RR 1.37 (95 % CI 1.32-1.43)], and cardiovascular mortality [RR 1.45 (1.16-1.81)] after revascularization in normal weight patients [
22]. These results persisted even after adjustment for potential confounders, including age, arterial hypertension, diabetes, and left ventricular function. Another analysis on patients with established coronary artery disease undergoing medical, interventional or surgical treatment showed an “obesity paradox” after revascularisation irrespective of the chosen strategy. In the whole cohort patients who were overweight or obese were more likely to undergo revascularization procedures compared with those with normal BMI, despite having lower risk coronary anatomy [
23]. The underlying mechanism of the “obesity paradox” is speculative. Obesity is associated with lower levels of plasma renin, epinephrine and high serum levels of low-density lipoproteins that bind circulating lipopolysaccharides [
24]. Coronary vessel diameters, as confirmed in out-patient cohorts, have been shown to correlate with the increase in body weight; thus a smaller coronary artery size in normal weight and lean patients could theoretically influence periprocedural outcome [
25]. The relationship between obesity and survival is characterized in the literature by a J- or U-shaped curve with increasing mortality in the very lean or severely obese group [
26,
27]; however, after adjustment for smoking and concurrent illness, the relationship has always been linear [
28,
29]. Contrasting with these findings our analysis of high-risk all-comers STEMI population including patients with cardiogenic shock does not support the presence of an “obesity paradox”. Although there is a trend for better one-year survival in obese patients, this difference did not reach statistical significance. However, with access site being femoral there might be more bleeding events in obese patients, which could be avoided by radial access. Nevertheless, we think that the term “obesity paradox” might predominantly reflect different degrees of bias that cannot be completely corrected for by statistical means. Inherent bias in all obesity analyses result from the fact that overweight and obese patients are usually younger and have larger culprit coronary vessel diameters than normal weight counterparts. In general younger patients have better clinical outcomes after acute MI regardless of reperfusion modality [
30,
31]. Additionally, the presence of co-morbidities in obese and overweight younger patients usually leads to more aggressive therapy of cardiovascular risk factors likely to improve outcomes despite obesity [
30,
31]. In a study of 130,139 patients hospitalized for coronary artery disease, higher BMI was associated with increased use of standard medical therapies such as aspirin, beta-blockers, renin-angiotensin inhibitors, and lipid lowering therapy, and an increased likelihood of undergoing diagnostic catheterization and revascularization [
32,
33]. The all-comer design of our registry with the majority of patients having had no established coronary artery disease before the index STEMI reduces the influence of potential confounders. Especially promotion of primary PCI in shock patients and after resuscitation (significantly more frequent in obese and overweight patients) avoided a severe pre-selection bias. Another point of discussion with respect to the obesity paradox is that underweight patients may receive standard anti-coagulation doses that are too high for their body size, making them more prone to post-procedural bleeding complications, which could be ruled out in our cohort by weight-adjusted doses [
3,
5]. In addition obesity was found to correlate with higher levels of factor VII, VIII, fibrinogen and plasminogen activator inhibitor-1, which were all associated with increased risk of thrombosis [
34]. Accordingly prospective investigations have shown that overweight and obese patients were more likely to suffer from suboptimal platelet response to clopidogrel and aspirin treatment [
35,
36]. In our cohort the use of GP IIb/IIIa inhibitor was high facing the nature of exclusively high-risk STEMI patients. Furthermore obesity as well as STEMI is considered a low-grade inflammatory state, as demonstrated by increased levels of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, and acute phase proteins such as C-reactive protein [
37]. This proinflammatory state may also directly and indirectly cause thrombosis by oxidative stress and endothelial dysfunction [
38]. Such findings could not be confirmed in our real-world setting with similar rates of stent thrombosis in all subsets. Since low BMI may be a marker of severe systemic illness [
18,
39], we defined in a separate analysis the normal-weight group from 18.5 kg/m
2-24.9 kg/m
2 and excluded 5 extremely underweight patients. However, this did not change the previous findings with lack of an “obesity paradox”. A separate analysis of patients with cardiogenic shock, which is associated with a prothrombic situation and systemic inflammation, also revealed no statistical differences in clinical endpoints for all three groups.