Mild aortic regurgitation as an independent predictor of major adverse cardiovascular events in non-ST-elevation acute coronary syndrome: insights from a multicentre propensity score-matched cohort study

Q: What are the key findings of this study?

Mild aortic regurgitation was independently associated with a higher risk of major adverse cardiovascular events in patients with NSTE-ACS.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Non-ST-elevation acute coronary syndrome (NSTE-ACS) (n=5162). Intervention: Mild aortic regurgitation vs. No aortic regurgitation or other valvular heart disease. Primary outcome: Major adverse cardiovascular events (MACEs), a composite of cardiac death, heart failure rehospitalisation, and unplanned coronary revascularisation (HR 1.47, 95% CI 1.26-1.72, p=<0.001).

Q: What does this research mean for the field?

Mild aortic regurgitation is independently associated with an increased risk of major adverse cardiovascular events in patients with non-ST-elevation acute coronary syndrome. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To determine whether mild aortic regurgitation independently predicts major adverse cardiovascular events in patients presenting with non-ST-elevation acute coronary syndrome.

Peng Zhao; Wenqiang Fang; Hui Li; Bowen Zhou; Tongjian Zhu; Jiajun Zhu; Long Tang; Shili Wu; Bing Wu; Jun Wang; Jinjun Liu

doi:10.7189/jogh.16.04404

November 13, 2026Journal of Global HealthOpen Access

Mild aortic regurgitation as an independent predictor of major adverse cardiovascular events in non-ST-elevation acute coronary syndrome: insights from a multicentre propensity score-matched cohort study

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Key result

Mild aortic regurgitation linked to ~47% higher major cardiovascular events risk in NSTE-ACS.

HR 1.47
95% CI 1.26-1.72
P<0.001
n=5,162

Figures

Why the study?

Mild aortic regurgitation is frequently detected on routine echocardiography in patients with coronary artery disease, yet its prognostic significance in the high-risk context of NSTE-ACS remained poorly defined.

Does concomitant mild aortic regurgitation increase the risk of major adverse cardiovascular events in patients with non-ST-elevation acute coronary syndrome?

Key Points

To determine whether mild aortic regurgitation independently predicts major adverse cardiovascular events in patients presenting with non-ST-elevation acute coronary syndrome.
Multicentre retrospective cohort study across six tertiary cardiovascular centres in China including 1,290 patients with NSTE-ACS and mild aortic regurgitation alongside 3,872 propensity score-matched controls without valvular heart disease (1:3 ratio).
Covariates in the propensity-matching model included demographics, cardiovascular risk factors, medications, and ACS subtype, achieving adequate balance (absolute standardised mean difference <0.10).
The primary endpoint was major adverse cardiovascular events (composite of cardiac death, heart failure rehospitalisation, and unplanned coronary revascularisation) over a median follow-up of 50 months.
Mild aortic regurgitation was associated with a significantly higher risk of MACEs (HR = 1.47; 95% CI = 1.26–1.72, P < 0.001), remaining independent after multivariable adjustment (HR = 1.329; 95% CI = 1.144–1.545, P < 0.001).
Individual event rates were significantly increased with mild aortic regurgitation versus controls: cardiac death (6.2% vs. 4.2%; HR = 1.51; 95% CI = 1.13–2.02, P = 0.002), heart failure rehospitalisation (4.7% vs. 3.1%; HR = 1.57; 95% CI = 1.12–2.20, P = 0.004), and unplanned revascularisation (10.4% vs. 8.0%; HR = 1.34; 95% CI = 1.08–1.67, P = 0.004).
Mild aortic regurgitation was also associated with higher neutrophil-to-lymphocyte ratio (β = 0.56, P < 0.001), systemic immune-inflammation index (β = 161.73, P < 0.001), and remnant cholesterol (β = 0.21, P < 0.001).

Study Design

Type

Cohort (n=5,162)

Blinding

Blinded endpoint adjudication

Multicenter

Yes

Structured PICO

Does concomitant mild aortic regurgitation increase the risk of major adverse cardiovascular events in patients with non-ST-elevation acute coronary syndrome?

P

Population

5,162 propensity score-matched adults with non-ST-elevation acute coronary syndrome undergoing coronary angiography across six Chinese tertiary centres (1,290 with mild aortic regurgitation and 3,872 without valvular heart disease), followed for a median of 50 months.

E

Exposure

Concomitant mild aortic regurgitation (AR) diagnosed by standardised multiparametric transthoracic echocardiography (vena contracta width, pressure half-time, and colour Doppler jet area)

C

Comparator

Propensity score-matched controls (approximately 1:3 ratio) with NSTE-ACS but without echocardiographically diagnosed aortic regurgitation or other valvular heart disease (both groups received standardised diagnostic and treatment protocols for ACS)

O

Outcome

Composite of major adverse cardiovascular events (MACEs), comprising cardiac death, heart failure rehospitalisation (unplanned admission requiring intravenous therapy), and unplanned coronary revascularisation (unscheduled repeat PCI or CABG), over a median follow-up of 50 months, independently reviewed by blinded assessorscomposite

Main Result

Hazard Ratio: 1.47 (95% CI 1.26–1.72)

Absolute Event Rate: 21.3% vs 15.3%

p-value: p=<0.001

Limitations

Retrospective observational design with potential for selection bias (complete-case analysis excluding 7.2% of eligible patients) and unmeasured confounding
Single baseline transthoracic echocardiographic assessment of aortic regurgitation without central core laboratory rereading or serial follow-up assessments
Lack of competing risk analyses for nonfatal outcomes such as heart failure rehospitalisation and unplanned revascularisation
Absence of data on natriuretic peptides, coronary microvascular resistance, and serial inflammatory biomarkers during follow-up
Concurrent baseline measurement of mild aortic regurgitation, inflammatory markers, and left atrial diameter precludes establishing temporal directionality or causal mediation
Limited generalisability as the study was conducted exclusively across six tertiary centres in China
Cardiac structural and functional parameters (LVEF, LVEDD, LAD) were not included in the propensity-score matching model
Lack of formal multiplicity adjustment across numerous secondary, subgroup, biomarker, and mediation analyses
Complete-case approach excluding 417 (7.2%) patients with missing data without imputation
Did not formally assess variable-specific pattern and mechanism of missingness

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Implication

In patients with NSTE-ACS, concomitant mild aortic regurgitation is an independent predictor of long-term MACEs (cardiac death, heart failure rehospitalisation, and unplanned revascularisation) and is associated with elevated systemic inflammatory indices and remnant cholesterol.

Abstract

Background: Non-ST-elevation acute coronary syndrome (NSTE-ACS) remains a leading cause of cardiovascular morbidity and mortality worldwide, making accurate risk stratification beyond conventional clinical parameters a critical need. Mild aortic regurgitation (AR) is frequently detected on routine echocardiography in patients with coronary artery disease, yet its prognostic significance in the high-risk context of NSTE-ACS remains poorly defined. Methods: This multicentre retrospective cohort study included 1,290 patients with NSTE-ACS and mild AR from six tertiary cardiovascular centres in China. Propensity score matching targeting an approximately 1:3 ratio identified 3,872 matched controls without AR or other valvular heart disease. The primary endpoint was major adverse cardiovascular events (MACEs), comprising cardiac death, heart failure rehospitalisation, and unplanned coronary revascularisation, over a median follow-up of 50 months. Results: Covariates included in the propensity-score model were adequately balanced after propensity score matching (absolute standardised mean difference <0.10). Mild AR was associated with higher risks of MACEs (HR = 1.47; 95% CI = 1.26-1.72, P < 0.001), cardiac death (HR = 1.51; 95% CI = 1.13-2.02, P = 0.002), heart failure rehospitalisation (HR = 1.57; 95% CI = 1.12-2.20, P = 0.004), and unplanned coronary revascularisation (HR = 1.34; 95% CI = 1.08-1.67, P = 0.004). After multivariable adjustment, mild AR remained independently associated with MACEs (HR = 1.329; 95% CI = 1.144-1.545, P < 0.001). Mild AR was also associated with higher neutrophil-to-lymphocyte ratio (β = 0.56; 95% CI = 0.37-0.74, P < 0.001), systemic immune-inflammation index (β = 161.73; 95% CI = 119.36-204.10, P < 0.001), and remnant cholesterol (β = 0.21; 95% CI = 0.16-0.26, P < 0.001). Exploratory mediation analyses showed modest statistical indirect associations between mild AR and MACEs (~6.8%) and between mild AR and cardiac death (~10.0%), operating through left atrial diameter. Conclusions: In patients with NSTE-ACS, mild AR was independently associated with MACEs and modest differences in inflammatory indices and remnant cholesterol. Mild AR may, therefore, be a readily available marker for risk stratification in this high-risk population.

Discussion

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Cite This Study

Zhao et al. (2026) conducted a cohort in Non-ST-elevation acute coronary syndrome (NSTE-ACS) (n=5,162). Mild aortic regurgitation vs. No aortic regurgitation or other valvular heart disease was evaluated on Major adverse cardiovascular events (MACEs), a composite of cardiac death, heart failure rehospitalisation, and unplanned coronary revascularisation (HR 1.47, 95% CI 1.26-1.72, p=<0.001). Mild aortic regurgitation was independently associated with a higher risk of major adverse cardiovascular events in patients with NSTE-ACS.

synapsesocial.com/papers/6af88c530e4d8f4b089c1bd3 https://doi.org/10.7189/jogh.16.04404

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Mild aortic regurgitation as an independent predictor of major adverse cardiovascular events in non-ST-elevation acute coronary syndrome: insights from a multicentre propensity score-matched cohort study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Mild aortic regurgitation as an independent predictor of major adverse cardiovascular events in non-ST-elevation acute coronary syndrome: insights from a multicentre propensity score-matched cohort study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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