Blood group A: a risk factor for heart rupture after acute myocardial infarction

Introduction Studies have been performed to identify the association between ABO blood groups and coronary artery disease. However, data is scarce about the impact of ABO blood groups on heart rupture (HR) after acute myocardial infarction (AMI). Methods We conducted a retrospective case–control study that included 61 consecutive patients with HR after AMI during a period from 1 January 2012 to 1 December 2019. The controls included 600 patients who were selected randomly from 8143 AMI patients without HR in a ratio of 1:10. Univariate and multivariate logistic regression analysis were used to identify the association between ABO blood groups and HR. Results Patients with blood group A had a greater risk of HR after AMI than those with non-A blood groups (12.35% vs 7.42%, P < 0.001). After adjusting for age, gender, heart rate at admission, body mass index (BMI), and systolic blood pressure (SBP), blood group A was independently related to the increased risk of HR after AMI (OR = 2.781, 95% CI 1.174–7.198, P = 0.035), and remained as an independent risk factor of HR after AMI in different multivariate regression models. Conclusion Blood group A is significantly associated with increased HR risk after AMI.


Introduction
Heart rupture (HR) was one of the fatal complications after acute myocardial infarction (AMI) though its incidence decreased dramatically in reperfusion era nowadays [1][2][3]. HR was specified as free wall rupture (FWR), ventricular septal rupture (VSR) and papillary muscle rupture (PMR). In the pre-perfusion time, the incidence of FWR was about 2-6%, accounting for up to 30% of the in-hospital death after AMI [3][4][5]. VSR happened in approximately 1-3% AMI population before the reperfusion time, with 45% and 90% death rates each for surgical and conservative treatment [6][7][8]. PMR often causes mitral regurgitation (MR) and present in < 1% of AMI patients who undergo early revascularization according to recent data [9]. Several previous studies have verified the association between blood group A and the increased risk of vascular diseases including coronary artery disease (CAD) [10][11][12][13][14][15]. Non-O blood groups were also determined to be a significant prognostic indicator of poor prognosis in AMI patients [16][17][18]. However, there is scarce or even no data about the impact of ABO blood groups on the risk of HR after AMI. Therefore, we conducted a retrospective case-control study to investigate whether there is a potential connection between ABO blood groups and the risk of HR after AMI. Fu et al. BMC Cardiovasc Disord (2020) 20:471

Patient population and study design
We retrospectively analyzed 61 consecutive patients with HR after AMI referred to Beijing Chao-Yang Hospital from 1 January 2012 to 31 December 2019. The controls included 600 patients who were selected randomly from 8143 AMI patients without HR in a ratio of 1:10 (n = 610 after excluding 10 cases with an incomplete record, Fig. 1). HR was specified as FWR, VSR and PMR.
AMI was classified as ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI), the diagnostic criteria refer to our previous study [19].
FWR was defined as: (1) echo-free space can be seen on echocardiography in patients with sudden cardiogenic shock, low blood pressure or indistinct consciousness; (2) Sudden cardiac shock, low blood pressure or indistinct consciousness that associated with massive pericardial effusion confirmed by pericardiocentesis [20]. VSR was characterized by: (1) abnormal physical examination findings such as cardiac systolic murmur and cardiac tremor; (2) Ventricular septal discontinuity can be seen on echocardiography [21]. The diagnostic criteria of PMR were as follows: (1) abnormal physical examination findings such as new systolic murmur; (2) Echocardiography shows a mobile mass in either the left atrium or ventricle; (3) flail or ruptured chordae with an abnormal-looking papillary muscle [9].

Data collection Anthropometric measurements and data collection
The demographics, medical and family history, height, weight, status of medications and smoking data were collected upon admission. Estimated glomerular filtration rate (eGFR) was calculated by using Modification of Diet in Renal Disease (MDRD) formula (Chinese version) [22].
The Global Registry of Acute Coronary Events risk score (GRACE RS) is developed for risk stratification in acute coronary syndromes (ACS) patients. It is calculated from several variables: age, history of myocardial infarction, history of heart failure, systolic blood pressure (SBP), heart rate and serum creatinine level at admission, ST-segment depression, elevated myocardial necrosis markers or enzymes, and lack of percutaneous coronary revascularization during admission [23][24][25].

Laboratory parameters
Blood samples were collected in the emergency room before any therapies and analyzed by Dimension RxL Max ™ automated analyzer (Dimension, USA). Automatic analyzer Hitachi 7600 (Hitachi, Japan) was used for biochemical variables measurement. All parameters were tested by using blood serum.

Statistical analysis
All statistical analyses were conducted using SPSS 24.0 (IBM Corp, Armonk, NY). Kolmogorov-Smirnov test was used to test the normal distribution of continuous variables. Normally-distributed data are expressed as mean ± SD, and analyzed by Student's t-test. Non normally-distributed variables are presented as median (interquartile range), and analyzed by Mann-Whitney U test. Dichotomous variables were presented as frequencies and percentages, analyzed with Pearson's chisquared test. The analysis of variance (ANOVA) test was used to examine the distribution of HR events in each blood group. Univariable analysis was used to identify the risk factors for HR. The potential association between ABO blood groups and HR after AMI was identified by multivariate logistic regression analysis. A 2-sided P < 0.05 was considered statistically significant.

General characteristics
A total of 661 AMI patients (68.53% male) were included in data analyses ( Table 1). Selection of all participants is shown in Fig. 1

ABO blood groups and HR
Blood group B was most common (37.07%), followed by blood group A (36.76%), O (19.06%), and AB (7.11%) ( Table 3). The frequency of blood group A was significantly higher in HR patients (49.18% vs. 35.5% in non-TM group, P = 0.012, Table 1). However, in the ANOVA test, HR events did not differ from 4 other blood groups (F = 2.086, P = 0.105). In multivariate logistic regression analysis, compared to non-A blood groups, blood group A remained an independent predictor for HR after AMI, after the adjustment for anthropometric variables such as age, gender, heart rate at admission, BMI and SBP (OR = 2.781, 95% CI 1.174-7.198, P = 0.035, Table 4 model 1). The association between blood group A and an elevated risk of HR after AMI was also observed in different multivariate regression models (P < 0.05, Table 4).

Discussion
In the present study, A significant association was observed between blood group A and an increased risk of HR after AMI, in both univariate and multivariate analyses. As far as we know, this is the first study to reveal that blood group A is an independent risk factor for HR in Chinese AMI patients. HR was still one of the most serious complications after AMI, even with the worldwide use of PCI or some other modern therapies [1][2][3]26]. In the pre-reperfusion era, HR occurred in about 6% of all admitted AMI patients [2,5].   The incidence of HR after AMI is less than 1% reported in modern studies and similar results can be seen in the present study (0.75%) [1,27,28]. HR, especially FWR, is known as a desperate complication after AMI. The in-hospital mortality of HR patient remains very high in spite of the rapid advances in diagnostic and treatment methods. In this study, the in-hospital death rate of patients with HR was 81.97%, with 95%, 66.67% and 33.33% in FWR, VSR and PMR patients, respectively. Similar or a little lower hospital mortality rates have been reported in previous studies [7,[29][30][31].
The antigens of ABO blood groups are mainly expressed on the surface of red blood cells (RBC), and are also expressed on vascular endothelium, gastrointestinal, oral and bronchopulmonary epithelium, platelets (PLT) and neurocytes [10,18,32]. There is conflicting data about the association between ABO blood groups and CAD. A number of studies have proved the important role of the ABO blood groups in the prognosis of CAD patients. Carpeggiani et al. [11] showed that blood group A is associated with increased mortality in patients with CAD, particularly in younger females. Cetin et al. [18] reported that ABO blood groups were determined to be significant prognostic indicators of short and long-term cardiovascular adverse events and mortality in patients with STEMI undergoing pPCI. A study by Ketch et al. [16] showed that compared to blood group O, patients with non-O blood groups have larger infarct sizes but similar 1 year outcomes. However, the association between ABO blood groups and CAD or cardiovascular risk factors had not been confirmed by some other studies [14,33,34]. None of these previous studies demonstrated the association between ABO blood groups and HR after AMI, the current study was designed to provide evidence.
The underlying mechanisms through which ABO blood groups may participate in the pathogenesis of HR after AMI remain unclear. Patients with non-O compared to O blood group have more myocardial necrosis, larger myocardial infarct size and reduced pre-procedural thrombolysis in myocardial infarction (TIMI) flow of coronary, accounting for the higher level of von Willebrand factor (VWF) and factor VIII in non-O blood groups, especially in A and B blood groups [16,17,21]. This may be one potential reason for the increased HR risk in AMI patients with blood group A. Higher CTnI and lower LVEF are two major clinical indicators related to a larger myocardial infarct size [35]. In our study, however, there was no statistical difference in CTnI or LVEF between blood group A and other blood groups. The bias caused by small sample size of our study may be responsible for this. However, whether blood type A increases the risk of HR after AMI by causing a larger myocardial infarct size should be further studied in larger cohort with the help of cardiac magnetic resonance. Moreover, genome-wide association studies (GWAS) have identified that ABO blood groups gene as a locus for diabetes mellitus and many inflammatory biomarkers, such as IL-10, soluble E-selectin, P-selectin and intercellular adhesive molecule 1 (ICAM-1) [17,36,37]. Therefore, blood group antigens may increase thrombus burden and inflammatory substances level in circulation, which can increase the risk of HR [37,38]. HR were more prevalent in older and female patients. Longer Time from symptom onset to admission, higher heart rate at admission, KILLIP class, BNP, ESR, WBC, CTNI, CK-MB and blood group A, were also seen in patients with HR after AMI. Moreover, HR group had significantly lower BMI, RBC, Hb, LVEF, eGFR, and had lower chance to receive pPCI treatment. Most of these HR related factors, such as age, female gender, BNP, heart rate at admission and no pPCI treatment, have also been reported previously, except blood group A [21,26,30,39,40]. According to the principle of 10 outcome events per variable, multivariate logistic regression analyses included less than 6 variables was conducted [41]. After adjusting anthropometric risk factors of HR (age, gender, heart rate at admission, BMI and SBP), blood group A was associated with HR after AMI independently (OR = 2.781, 95% CI 1.174-7.198, P = 0.035). We then conducted another multivariate logistic regression model that included age, gender and blood biomarkers related to HR (ESR, BNP and CTnI). After adjusting these variables, blood group A remained as an independent predictor for HR after AMI (OR = 2.488, 95% CI 1.121-5.869, P = 0.045). The association between blood group A and an elevated risk of HR after AMI was also observed in different multivariate regression models that included echocardiographic index (LVEF) and treatment strategy (received pPCI treatment or not).
The GRACE RS has been recognized as a validated tool to predict mortality risk of ACS patients and it has been recommend by current clinical guidelines [42][43][44][45]. The value of the GRACE RS in predicting HR after AMI was rarely reported, and might be able to predict HR [21]. The GRACE RS of patients with HR was significantly higher than patients without HR (199.14 ± 41.03 vs 164 ± 36.54, P < 0.001).We then conducted a logistic regression analysis that included the GRACE RS as an independent variable, the analysis also indicated that blood group A is a risk factor of HR (OR = 2.212, 95% CI 1.064-5.168, P = 0.039). To the best of our knowledge, this is the first study proving the association between ABO blood groups and HR after AMI.
There were 3 limitations to the current study. First, this a single-center research with a relatively small population. Second, as a retrospectively case-control study, the potential cause-effect relationship was unknown. Finally, we only observed an independent association between blood group A and HR after AMI, the underlying mechanisms should be studied in the future.

Conclusion
Blood group A is an independent risk factor for HR in Chinese AMI patients. Evaluation of this parameter may help with risk stratification of HR in AMI patients.