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Association between admission blood pressure and spontaneous reperfusion and long-term prognosis in STEMI patients: an observational and multicenter study

BMC Cardiovascular Disorders volume 24, Article number: 500 (2024) Cite this article

Abstract

Background

This study aims to assess the associations of admission systolic blood pressure (SBP) level with spontaneous reperfusion (SR) and long-term prognosis in ST-elevation myocardial infarction (STEMI) patients.

Methods

Data from 3809 STEMI patients who underwent primary percutaneous coronary intervention within 24 h, as recorded in the Chinese STEMI PPCI Registry (NCT04996901), were analyzed. The primary endpoint was SR, defined as thrombolysis in myocardial infarction grade 2–3 flow of IRA according to emergency angiography. The second endpoint was 2-year all-cause mortality. The association between admission BP and outcomes was evaluated using Logistic regression or Cox proportional hazards models with restricted cubic splines, adjusting for clinical characteristics.

Results

Admission SBP rather than diastolic BP was associated with SR after adjustment. Notably, this relationship exhibits a nonlinear pattern. Below 120mmHg, There existed a significant positive correlation between admission SBP and the incidence of SR (adjusted OR per 10-mmHg decrease for SBP ≤ 120 mm Hg: 0.800; 95% CI: 0.706–0.907; p<0.001); whereas above 120mmHg, no further improvement in SR was observed (adjusted OR per 10-mmHg increase for SBP >120 mm Hg: 1.019; 95% CI: 0.958–1.084, p = 0.552). In the analysis of the endpoint event of mortality, patients admitted with SBP ranging from 121 to 150 mmHg exhibited the lowest mortality compared with those SBP ≤ 120mmHg (adjusted HR: 0.653; 95% CI: 0.495–0.862; p = 0.003). In addition, subgroups analysis with Killip class I-II showed SBP ≤ 120mmHg was still associated with increased risk of mortality.

Conclusion

The present study revealed admission SBP above 120 mmHg was associated with higher SR,30-d and 2-y survival rate in STEMI patients. The admission SBP could be a marker to provide clinical assessment and treatment.

Trial registration

ClinicalTrials.gov (NCT04996901), 07/27/2021.

Peer Review reports

Introduction

With the considerable advancements in interventional cardiology, there has been a continuous reduction in mortality and recurrent ischemic events during the last 20 years in ST-elevation myocardial infarction (STEMI) patients [1, 2]. However, data from the SWEDEHEART national registry indicate that the improved outcome was most dramatic between 1994 and 2008 and then leveled out at a new level with about 14% risk of mortality from around 2008 and onwards [3]. In other registry studies, the lack of further reduction in mortality was also observed in recent years [4, 5]. Thus, new effective therapeutic strategies were needed to further improve outcomes in STEMI patients despite receiving the full evidence-based treatments.

In acute atherothrombotic STEMI, the severity of cardiomyocyte necrosis largely depends on the duration of occluded epicardial coronary artery [6]. Interestingly, spontaneous reperfusion (SR), defined as initial thrombolysis in myocardial infarction (TIMI) grade 2–3 flow before undergoing reperfusion therapy, would likely represent 15% of patients with acute STEMI [7]. Angiographically confirmed SR correlates with smaller final infarct size, fewer heart failure admission as well as lower mortality [8,9,10]. Pre-hospital antithrombotic therapies were important for SR occurrence, but the results were paradoxical. The MONAMI study highlighted that aspirin and clopidogrel administration prior to interventional hospital transfer could contribute to SR in STEMI patients [4]. Similar results have also been observed in STEMI patients with early administration of heparin or bivalirudin [11, 12]. In contrast, data from the ATLANTIC trial and SCAAR showed that pre-treatment with ticagrelor failed to ameliorate SR rates [13, 14]. The heterogeneity of SR in some patients, but not others, is not understood.

Based on the principle that the delivery of thrombolytic medication to coronary thrombosis is directly related to the arterial blood pressure [15], several studies have demonstrated that arterial pressure augmentation could enhance the efficiency of coronary thrombolysis [15,16,17]. According to these findings, the relationship between admission BP and SR and long-term mortality would be identified in this study.

Methods

Study design and population

In this observational and multicenter study, data utilized were sourced from The Chinese STEMI PPCI Registry (CSPR) between December 2015 and April 2021 (ClinicalTrials.gov number, NCT04996901) within the framework of the China Chest Pain Center. This clinical trial was registered on 07/27/2021 and the design is detailed in prior publications [18, 19]. In brief, the CSPR trial is aimed at developing and validating a feasible risk score to identify patients at high risk of 30-day major adverse cardiac events in STEMI patients treated with primary percutaneous coronary intervention (PPCI). The population analyzed in our study aligns with that of the CSPR trial, focusing on a consecutive cohort of STEMI patients ≥ 18 years of age who underwent PPCI within 24 h after symptom onset from the seven largest interventional cardiology centers among the three economic-geographic regions of Mainland China (East, Central, and North).

Given potential benefit of PPCI for STEMI patients presenting both < 12 h and 12-24 h after symptom onset, patients finally diagnosed with STEMI within 24 h of symptom onset were enrolled [20]. Exclusion criteria comprised patients with symptom onset exceeding 24 h, patients who either did not receive PPCI or experienced unsuccessful PPCI, patients with missing admission BP values, and patients who suffered cardiac arrest between symptom onset and hospital admittance. A total of 3809 STEMI patients were eligible for further analysis (Fig. 1).

Fig. 1
figure 1

Study flow chart. STEMI, ST-elevation myocardial infarction; PPCI, primary percutaneous coronary intervention

Full size image

Patient baseline characteristics

Baseline characteristics, encompassing patient demographics, medical history, admission laboratory tests, procedural details, and medical therapy, were extracted from medical records. BP was measured using a non-invasive automatic bedside monitoring instrument at the first medical contact including community healthcare center, ambulance, and emergency department and recorded every 15 min from the FMC to the operating room. Admission BP was defined as the average BP value during the period. Laboratory characteristics refer to the first blood results obtained following analysis of samples drawn immediately upon admission. Procedural details, including vascular access approach, stent selection, antithrombotic therapy, and interventional strategy, were at the discretion of the individual operators and documented in medical records.

Clinical endpoints and follow-up

The primary endpoint was SR, which was defined as TIMI grade 2 or 3 flow of the infarct-related artery (IRA) during emergency angiography [21]. This definition excluded the resolution of ST-segment elevation due to the lack of post-PPCI electrocardiogram data in some cases. The second endpoint was all-cause mortality during a median follow-up of 48 months (interquartile range, 32–64 months), concluding on 31 August 2023. Detailed data on mortality was compiled through telephone interviews and hospital discharge summaries. For patients lost to follow-up, the Household Registration System was queried to ascertain death status. Data on long-term mortality were available for 3558 patients (93.4%).

Study definitions

STEMI was defined as new ST-segment elevation (measured at the J-point) in two contiguous leads or a new left bundle branch block on the electrocardiographic, coupled with an elevation in cardiac biomarkers, in line with the fourth universal definition of MI [22]. Multi-vessel coronary artery disease was defined based on angiography results: IRA plus at least one non-infarct-related artery (N-IRA) with a minimum of one lesion deemed angiographically significant (> 70% diameter stenosis in one plane or > 50% in two planes). The N-IRA had to be a major (> 2 mm) epicardial coronary artery or branch (> 2 mm) suitable for stent implantation [23]. Complete revascularization encompassed PPCI of the IRA and simultaneous or routine staged PCI of all suitable N-IRA during the index admission [24].

Statistical analysis

Differences between groups were evaluated using the Student’s t-test or Mann-Whitney U test for continuous data and the \(\:{\varvec{\upchi\:}}^{2}\) test or Fisher’s exact test for categorical data. Kaplan–Meier survival curves were constructed and compared using the log-rank test. Logistic regression models were employed to assess the correlation between admission BP and SR, while the association between admission BP and all-cause mortality was determined using Cox regression models. The associations were analyzed both in unadjusted (crude) and adjusted fashion. Covariates for adjustment included age, gender, diabetes mellitus, atrial fibrillation, symptom to balloon time, chronic kidney disease, multivessel disease, neutrophil-to-lymphocyte ratio * platelet, Killip class, and infarct-related artery, selected for their clinical relevance and prognostic association, as reported in previous studies. The relationship between admission BP and its variations, expressed as continuous variables, were also analyzed non-parametrically with restricted cubic splines, thereby enabling the exploration of non-linear relationships. To further evaluate the shape of the association between admission SBP and SR, multivariable spline, and regression models were repeated for patients with completed baseline data as sensitivity analyses. All statistical tests conducted were 2-sided, with p < 0.05 deemed statistically significant. The analyses were performed with R 4.2.2 (R Core Team) and SPSS 26.0 (IBM Crop).

Results

Baseline characteristics of the study population

The clinical and demographic characteristics of the 3809 patients are delineated in Table 1, categorized according to non-SR and SR groups. SR was observed in 20.8% of patients according to emergency coronary angiography. Interestingly, patients with SR exhibited higher admission SBP, diastolic blood pressure (DBP), and longer symptom-to-balloon (S2B) time, belonging to lower Killip classes. The rate of left anterior descending artery as IRA was higher in the SR group. In addition, patients with SR exhibited a modest yet statistically significant reduction in inflammatory indices, as well as in alanine transaminase and aspartate aminotransferase levels. Other cardiovascular risk factors, such as hypertension and a history of atrial fibrillation, were also lower in the SR group. Most patients received prehospital dual antiplatelet therapy both in the ambulance and emergency department, with no difference observed across the groups.

Table 1 Baseline characteristics of the study groups
Full size table

Relationship between admission BP and SR

In the multivariate logistic regression analysis, admission SBP (adjusted OR:1.007; 95%CI: 1.001–1.013; p = 0.015) rather than DBP (adjusted OR:1.000; 95% CI: 0.991–1.008; p = 0.914) was found to be associated with SR (Table 2). In multivariable modeling, the shape of the association between admission SBP and SR appeared flat when admission SBP>120 mmHg, at which point the incidence of SR increased (Fig. 2). Below 120mmHg, There existed a significant correlation between admission SBP and the incidence of SR (adjusted OR per 10-mmHg decrease for SBP ≤ 120 mm Hg,: 0.800; 95% CI: 0.706–0.907; p<0.001); whereas above 120mmHg, no further improvement in SR was observed (adjusted OR per 10-mmHg increase for SBP >120 mm Hg: 1.019; 95% CI: 0.958–1.084, p = 0.552). Therefore, SBP of 120 mmHg was used as the cutpoint for the linear splines of SBP in the multivariable restricted cubic spline (RCS) analysis. The shapes of the associations between admission SBP and SR in sensitivity analysis were similar when applied to patients with complete baseline data (Figure S1).

Table 2 Independent predictors for SR in STEMI patients
Full size table
Fig. 2
figure 2

Restricted cubic splines for SR according to admission SBP with adjusted model (A) and unadjusted model (B). OR was adjusted for age, gender, diabetes mellitus, atrial fibrillation, symptom to balloon time, chronic kidney disease, multivessel disease, neutrophil-to-lymphocyte ratio * platelet, Killip class, and infarct-related artery. SBP, systolic blood pressure; OR, Odds ratio; CI, confidence interval

Full size image

Associations between admission SBP and SR in the subgroups analysis

SR before PPCI appeared to be at a higher rate in STEMI patients with an admission SBP>120 mmHg as compared with the group of admission SBP ≤ 120 mmHg (23.4% vs. 17.9%; p<0.001). After adjustment for baseline factors, there was an association between admission SBP>120mmHg and development of SR (adjusted OR: 1.293; 95%CI: 1.099–1.521; p = 0.002). This association was consistent in most of the 7 interesting subgroups, including age, gender, DM, chronic kidney disease, Killip class, multivessel disease, and IRA (Figure S2).

Association between admission SBP and mortality

Long-term mortality data were available for 3558 patients (93.4%). The median follow-up period was 48 months (interquartile range, 32–64 months). Kaplan-Meier estimates for survival at 30-day and 2-year are shown in Fig. 3, demonstrating that patients with admission SBP <120mmHg had the highest 2-year mortality (9.8% vs. 5.6% for other 2 groups, Log-rank p < 0.001). Furthermore, Cox-regression analysis revealed that admission SBP within 121-150mmHg was an independent protective factor of 2-year mortality (adjusted HR: 0.653; 95% CI: 0.495–0.862; p = 0.003; Table S1). Among the subgroups analysis, the association between group of 121-150mmHg and lower long-term mortality was consistent (Figure S3). Similar results were observed in sensitivity analysis (Table S2).

Fig. 3
figure 3

Kaplan-Meier survival estimates for 30-day (A) and 2-year (B) all-cause mortality by admission systolic blood pressure

Full size image

Discussion

To our best knowledge, the current study pioneered the investigation of the relationship between admission SBP and SR in STEMI patients. Our data demonstrated that admission SBP but not DBP was associated with SR in STEMI patients. Notably, this relationship exhibits a nonlinear pattern, characterized by a positive correlation when SBP is below 120 mmHg, whereas above this threshold, the association becomes statistically insignificant. In the analysis of the endpoint event of mortality, patients admitted with SBP ranging from 121 to 150 mmHg exhibited the lowest mortality. This finding adds depth to our comprehension of the association between SBP and SR and long-term prognosis in STEMI patients.

Previous studies have shown that prehospital antithrombotic therapy might influence the occurrence of SR [4]. Noteworthy, in our study, prehospital DAPT did not differ significantly between groups of SR and non-SR. Unlike other organs, numerous studies have shown that coronary perfusion is more dependent on diastolic blood pressure [25]. In several earlier studies, arterial diastolic pressure augmentation by IABP or norepinephrine could impact thrombolytic agent delivery to thrombi by directly affecting coronary blood flow in severe coronary stenosis in animal and clinical practice [15, 17, 26]. However, in our study, we did find admission SBP but not DBP was associated with SR in STEMI patients. Observational data have shown that groups with higher SBP were prone to a higher prevalence of TIMI grade 2–3 flow in IRA prior to PPCI [27, 28]. Similar effects were observed by moderately increasing SBP (from 64 mmHg to 102 mmHg) in STEMI patients with cardiogenic shock [16]. It is noteworthy that BP is an indirect reflection of blood flow and perfusion pressure is not equal to blood flow [29]. Regulation of coronary blood flow involves multiple mechanisms, including tissue pressure, coronary perfusion pressure, metabolic factors, and hemodynamics etc [30]. It is known that the increase of heart rate or systemic vascular resistance may significantly reduce coronary blood flow in spite of good DBP [29]. Reduced coronary blood flow may indicate poorer cardiac output and yield low SBP [29], thus there is a vicious circle of low blood pressure and coronary blood flow. Maintaining SBP may provide good organ perfusion as well as coronary blood flow [29]. Patients with SR, characterized by blood flow restoration, typically present with smaller infarct size and superior cardiac contractility [8, 9]. SBP is considered to reflect a combination of cardiac output and systemic peripheral resistance, implying that optimal SBP might be a manifestation of efficient coronary flow as compared with DBP or mean aortic pressure [29]. In contrast to previous studies, our data further investigated that admission SBP>120 mmHg was associated with a higher rate of SR development.

Target of SBP management before PPCI in AMI patients is unclear. Several studies have revealed that intensively lowering SBP below 130 mmHg led to cardiovascular risk reduction across a variety of cohorts, including older patients (60–80 years) and those with diabetes or CAD [31,32,33,34]. Contradictorily, findings from subgroups of AMI patients challenged the “lower is better” hypothesis. The Acute Coronary Syndrome Israel Survey, comprising 7645 patients diagnosed with AMI, delved into the link between admission SBP and all-cause mortality. In contrast to patients with normal admission SBP (110–140 mm Hg) and low SBP (< 110 mm Hg), those with high admission SBP (> 140 mm Hg) presented with a lower 1‐year mortality risk [35]. Accordingly, in another study of 3943 acute MI patients treated at a tertiary hospital, admission SBP > 160 mmHg was correlated with the most favorable outcome compared to SBP ranging from 121 mmHg to 140 mmHg [36]. Our conclusions essentially proved the studies we mentioned previously. The present study showed that admission SBP of 121-150mmHg was associated with higher 2-year survival rate compared with those of SBP ≤ 120mmHg. Subsequently, we also performed a subgroup analysis based on patients with Killip class I-II and similar results were obtained. Elevation of admission SBP could result in increased myocardial oxygen consumption, exacerbating the imbalance between oxygen supply and myocardial metabolic demand in STEMI patients [37]. However, our finding showed that patients with SBP >150mmHg presented an upward trend in 2-year mortality compared with those SBP of 121-150mmHg but was not statistically significant. We suspect that the sample size was not large enough or that there were other errors. As sample size increases, we believe that there will be different changes to the curve.

Limitations

Notable limitations of the current study included, first, its observational nature, encompassing both design and data collection. Second, data on medical therapy and blood pressure control levels during follow-up, potentially related to prognosis, were unavailable. Last, this analysis shows an association between SBP level and SR and long-term mortality. This association is often referred uncritically to as reverse causation without direct proofs. In contrast, reverse causation could be present and cannot be ruled out in association of risk to admission SBP. Further randomized controlled trials are necessitated to validate these hypotheses.

Perspective

BP is one of the most readily available physiological indices that can be obtained within the first few minutes of STEMI patients at FMC, and it is even more easily obtained than other clinical data such as troponin level. BP control is a recognized strategy for primary prevention of cardiovascular disease and a growing body of literature advocates for intensive BP-lowering strategies. However, there could be novel targets for SBP control in STEMI patients. Both high and low BP have been associated with an increased risk of all-cause mortality. Our findings might reveal the effect of admission SBP on the occurrence of SR and all-cause mortality in patients with STEMI, and we hope it will provide some new tips for clinical assessment and treatment Consequently, clinicians should be cognizant of SBP control therapy for STEMI patients at the first medical contact. Further randomized controlled trials are necessitated to validate these hypotheses.

Conclusion

The present study revealed admission SBP above 120 mmHg was associated with higher SR,30d and 2-y survival rate in STEMI patients. The admission SBP could be a marker to provide clinical assessment and treatment.

Data availability

The data that support the findings of this study are available from Renmin Hospital of Wuhan University but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the corresponding author upon reasonable request and with permission of Renmin Hospital of Wuhan University.

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Acknowledgements

Not applicable.

Funding

This study received funding from the Chinese Society of Cardiology Foundation (Grant No. CSCF2021A02), the Young Talents Project of Hubei Provincial Health Commission (Grant No. WJ2021Q033), the National Natural Science Foundation of China (Grant No. 82100287), and the National Natural Science Foundation of China Hubei Province (Grant No. 2021CFB110).

Author information

Author notes

  1. Zheng Hu, Da Luo and Wen-jie Zhou contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University,Hubei Key Laboratory of Cardiology, Wuhan, China

    Zheng Hu, Da Luo, Wen-jie Zhou, Chang-wu Xu, Bo-fang Zhang, Hong Jiang & Jing Chen

  2. Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China

    Xiang-zhou Chen

  3. Tong Liao City Hospital, Tongliao, China

    Xing Jin

  4. Wuhan No.1 Hospital, Wuhan, China

    Yun Wang

  5. Three Gorges University and Yichang Central People’s Hospital, Yichang, China

    Jing Zhang & Hui Wu

  6. The No. 1 People’s Hospital of Xiangyang, Xiangyang, China

    Fu-yuan Liu

  7. The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China

    Yu-hua Lei

  8. Wuhan Third Hospital and Tongren Hospital of Wuhan University, Wuhan, China

    Dong-sheng Li

  9. Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, China

    Xin-yong Cai

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  1. Zheng Hu
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  14. Xin-yong Cai
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  15. Hong Jiang
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  16. Jing Chen
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Contributions

Da Luo and Wen-jie Zhou designed the research and devised the study plan. Zheng Hu and Da Luo were instrumental in data analysis and interpretation. The manuscript revision was undertaken by Zheng Hu and Jing Chen. Chang-wu Xu, Xiang-zhou Chen, Bo-fang Zhang, Xing Jin, Yun Wang, Jing Zhang, Hui Wu, Fu-yuan Liu, Yu-hua Lei, Dong-sheng Li, Xin-yong Cai, and Hong Jiang contributed to the The Chinese STEMI PPCI Registry data we studied. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Hong Jiang or Jing Chen.

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Ethics approval and consent to participate

This study was approved by the institutional Ethics Research Committee of Renmin Hospital of Wuhan University (WDRY2021-K504). The study was performed according to the declaration of Helsinki. Informed consent was waived for the post hoc analysis of the observational, multicenter trial.

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Not applicable.

Competing interests

The authors declare no competing interests.

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Hu, Z., Luo, D., Zhou, Wj. et al. Association between admission blood pressure and spontaneous reperfusion and long-term prognosis in STEMI patients: an observational and multicenter study. BMC Cardiovasc Disord 24, 500 (2024). https://doi.org/10.1186/s12872-024-04168-4

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  • DOI: https://doi.org/10.1186/s12872-024-04168-4

Keywords

BMC Cardiovascular Disorders

ISSN: 1471-2261

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