Age and sex
In 20 of 26 studies, overweight and/or obese patients were younger (1–10 years). Madala et al. [
43] observed that the first NSTEMI occurred 12 years earlier in severely obese than in normal BMI patients, whilst only 3.5 years earlier in less endangered overweight group. The finding of younger age of obese patients admitted for ACS therapy could be one of possible explanation for the better survival after ACS in people with BMI ≥ 25 kg/m
2. Peto et al. [
44] showed that in general population patients with BMIs above 25 kg/m
2 had an expected lifetime about 10 years shorter than people with normal BMI. Thus, the percentage of obese people in the population decreases with increasing age.
In patients aged 65 years or older, mortality was higher among obese patients in comparison with those with overweight (
p < 0.01) and normal weights (
p < 0.001). Obesity in this age group was an independent risk factor for in-hospital mortality [
17].
There are different reports on sex distribution across BMI groups. In some studies (Aronson, Eisenstein) more women, while in others [
18,
28,
30] more men were included in the obese groups. Rana et al. [
19] showed more women in normal-weight and class 1 and 2 obesity with nadir in the overweight ones (39, 33, 40 and 22 %, respectively,
p < 0.001). Similar differences were found for cardiogenic shock with occurrence 9.0; 4.1; 3.1; 2.9 and 5.4 % for underweight, normal weight, overweight, class 1 and class 2/3 obesity (
p = 0.006), respectively [
42].
Comorbidities and complications
Patients with BMI ≥ 25 kg/m
2 had higher cardiovascular risk. Diabetes mellitus (20 studies), hypertension (20 studies) or hyperlipidemia (10 studies) were more prevalent in obese than in normal-BMI group. Nevertheless, two studies showed lower GRACE risk score in obese patients [
35,
38].
Better survival in overweight or obese patients might be due to the relatively short follow-ups in the studies. During in-hospital stay or even in 5 years after MI, diabetes mellitus or hypertension had little chance to evoke complications and impact the mortality.
Although overweight or obese patients smoked rarely [
19‐
21,
28,
33,
35,
41], mortality risk among current smokers was higher in these groups and rose with increasing BMI–hazard ratio (HR) for BMI > 35 kg/m
2 was 4.51 (95 % CI, 1.42–14.3) in comparison to HR 1.18 (95 % CI, 0.42–2.58) for former smokers [
19]. Only 8 % of underweight patients smoked in the past in comparison to 15, 16 and 17 % found in normal-weight, overweight and obese subjects respectively (
p = 0.001) [
21].
Obese patients had higher concentrations of C-reactive protein [
27], lower troponin and NT-proBNP levels [
45]. The finding of lower natriuretic peptides levels in obese heart failure patients has been recognized recently was and could be explained by clearance function of adipose tissue on these peptides [
46].
Compared to normal-BMI group, in obese patients higher estimated glomerular filtration rates by both, MDRD or Cockroft-Gault formulas were observed [
25,
36,
47]. The choice of renal function estimation may be important because in patients with coronary artery disease and serum creatinine within normal range, CKD-EPI formula (Chronic Kidney Diseases Epidemiology Initiative) which was derived based on populations with vaster distribution of BMI, predicted long-term outcome more accurately, than MDRD equation [
48].
Patients with BMI < 25 had higher risk of bleeding [
25,
34]. Nikolsky et al. [
25] postulated that the difference had been determined by gastro-intestinal bleeding (2.7 vs 0.4,
p = 0.02 for normal weight and obesity, respectively). Moreover, overweight and obese more often had anemia [
41] and indication for blood transfusion [
25]. Noteworthy, the local groin bleeds (hematoma in the arterial puncture site) occurred also more frequently in patients with normal body weight, compared with overweight and obese (11, 6.8 and 7.6 %, respectively,
p = 0.014) [
28]. This phenomenon could be explained by ability of fat tissue to compress punctured femoral artery and staunch bleeding.
Obese patients had less often history of stroke [
18,
21] and rarely in-hospital stroke [
39], but this also could be explained by the differences in age.
Kragelund et al. [
21] showed that prevalence of cancer was more likely in underweight women group: 12 vs 5 %, 3 and 4 % in normal-weight, overweight and obese groups respectively (
p = 0.001). The observation was confirmed by Angerås et al. [
49] (from 8.7 % in underweight to 1.9 % in patients with BMI ≥ 35 kg/m
2,
p < 0.001).
Diagnosis and treatment
Angiotensin converting enzyme inhibitors (ACEI) were used more frequently in obese as compared to normal weight patients with ACS in 9 studies. Similarly beta-blockers (BB) or statins were given with higher probability to obese patients in 12 and 11 studies respectively. Better pharmacological treatment in obese patients might be caused by existence of other indications for these drugs such as hypertension (20 studies) among obese.
In four studies coronary angiography was reported more often in obese patients [
22,
23,
33,
34]. Additionally, six studies reported less frequent percutaneous coronary revascularization in underweight or normal-weight patients with ACS [
20,
22,
23,
31,
32,
34].
The door-to-balloon time was significantly longer in obese compared with normal weight patients. Moreover, they had more often final TIMI flow grade 0 compared to normal-weight individuals (2.0 vs. 0.4 %, respectively;
p = 0.04) [
28]. Initial TIMI flow grade 0 or 1 was also differs between in normal-weight and overweight patients (1.8 vs 0.7 %, respectively,
p = 0.04), as well as between overweight and obese subjects (0.7 vs 2.1 %, respectively,
p = 0.01) [
25].
Multi-vessel coronary artery disease was more common in patients with a normal body weight than in obese with BMI ≥ 40 kg/m
2, according to studies of Das et al. (28.4 vs 22.4 %) and Diercks et al. (30.0 vs 24.6 %) [
22,
36]. Nikolsky et al. [
25] did not confirm the higher occurrence of multi-vessel coronary artery disease in normal-weight with STEMI and showed the same frequency of percutaneous (and surgical) revascularization in all BMI ranges.
Despite the lack of differences in the effect of angioplasty, patients with normal weight required a longer hospital stay: 7.1, 6.9, and 6.7 days for normal weight, overweight, and obese, respectively;
p = 0.014. Major adverse cardiovascular events (MACE) at 6 months was also observed more often in the normal BMI range in comparison with overweight and obese cases: 8.8, 6.6, and 5.0 % respectively;
p = 0.031 [
28]. Major adverse cardiovascular or cerebrovascular events (MACCE) was also more frequent in normal-weight patients, comparing to overweight and obese subjects: 14.7, 12.7, 10.0 %, respectively for in-hospital outcome (
p < 0.001) and 12.6, 9.3, 8.7 %, respectively (
p < 0.001) for long-term follow-up [
31].
Central obesity and weight loss
Only four studies highlighted the prognostic role of central obesity. Zeller et al. divided patients with myocardial infarction (MI) into the tertiles of BMI and waist circumference (WC). The group of lower or middle tertile of BMI and upper tertile of WC had 1-year mortality risk above 20 % in women and more than 18 % in men, whilst in lower WC and upper BMI tertiles mortality was 7.6 and 7.7 %, respectively [
50]. This finding was confirmed by Kadakia et al. [
45]. It may indicate the special significance of central obesity. Unfortunately, most of the studies did not report parameters allowing more detailed description of obesity phenotype. Kragelund et al. [
21] confirmed abdominal obesity assessed by waist-to-hip ratio, to be independent predictor of all-cause mortality in men (adjusted RR 1.22 (1.07–1.38),
p < 0.01), but not in women subgroup after ACS [adjusted RR 1.13 (0.95–1.34,
p = 0.2)].
Guidelines of European Society of Cardiology (ESC) for the prevention of cardiovascular disease in clinical practice, highlights that obesity in the general population is associated with an increased incidence of cardiovascular disease and cardiovascular mortality. Therefore, the recommendation (class I, level of evidence A) exists for a weight reduction of overweight or obese individuals who have not undergone any cardiovascular event. Body weight reduction to the normal range (BMI 20–24.9 a kg/m
2) has a positive effect on blood pressure and plasma lipids, which is reflected in a lower incidence of cardiovascular disease [
51]. So far, no studies have confirmed the mortality reduction after MI in patients who reduced their body weight [
52]. On the contrary, weight loss of more than 5 % after MI in patients with depression (found in 27 % of patients) was related to 70 % higher risk of all-cause and cardiovascular mortality and those finding were not associated with depression nor social support [
29]. Weight loss of more than 5 % in a South Korean population of patients following acute MI was associated with a higher 1-year rate of MACEs. Patients who gained weight also have a greater 1-year mortality risk [
7]. On the other hand, intentional weight loss during cardiac rehabilitation in patients with CAD (not MI) was a marker for favourable long-term (6.4 years) outcomes, in both subgroups with initial BMI < 25 or ≥25 kg/m
2 [
53].
Comparison to general population
The collected data showed that in a population of patients with ACS, an obesity paradox may occur. However, a meta-analysis of 97 studies about mortality in the general population, published in January 2013, indirectly calls into question the existence of the obesity paradox in patients with ACS and chronic diseases. In the general population, the risk of death (HR) in people who were overweight and in the 1st class of obesity (BMI 25–35 kg/m
2) was lower than in individuals with normal weights (BMI 18.5–25 kg/m
2). Only patients with BMIs 35 kg/m
2 and greater had a higher risk of death [
54]. To compare the results of the studies about BMI and mortality in chronic diseases with the work of Flegal et al. [
54], the obesity paradox exists also in the general population. In the ACS, chronic diseases and the general population the lowest mortality was observed among individuals with BMI values above the normal WHO range.
Although results of our study seem to be clear and quite obvious, outcomes should be interpreted with caution. Despite obese patients more often had diabetes mellitus and/or hypertension, they were younger and had less bleeding complications. Therefore, to compare the mortality of obese patients with people with normal BMIs, the age of the patients and associated diseases should be taken into account in long enough follow-up. In other cases, the relationship between BMI and mortality may be disturbed.
In unadjusted analyses performed on data assessed from the studies, better survival in overweight, obesity and severe obesity group was confirmed in 16 out of 26 studies, 19 of 26 and 5 of 10 studies, respectively. In Low BMI group 7 of 9 studies showed worse survival, comparing to Normal BMI group. After adjustment, both for multivariate analysis (BMI as continuous variable) or models adjusted for various covariables (BMI groups), significant relation between lower BMI and worse survival was found in 15 out of 25 studies.