What is the clinical evidence from this study?

Study design: Observational. Population: Adults diagnosed with acute coronary syndrome (ACS), subdivided into allergy-associated ACS with and without anaphylaxis (n=49). Primary outcome: Comparison of immune markers (serum IgE, plasma histamine) and autonomic nervous system activity (HRV parameters) in allergy-associated ACS (ACS-AL) vs. non-allergy-associated ACS (ACS-NA).

What does this research mean for the field?

Allergy-associated acute coronary syndrome, even in the absence of anaphylaxis, is characterized by significant immune activation with elevated IgE and histamine levels, as well as autonomic imbalance with sympathetic predominance. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to investigate allergy-associated acute coronary syndrome (ACS) without accompanying anaphylaxis and its immune markers.

March 8, 2026Open Access

Allergy-associated acute coronary syndrome without anaphylaxis in a prospective observational study

Key Result

Allergy-associated ACS patients had significantly higher serum IgE (213.6 ± 221.9 vs. 84.5 ± 73.7 IU/mL, P=0.02) and plasma histamine levels (11.4 ± 8.7 vs. 5.6 ± 3.2 ng/mL, P<0.01) and exhibited increased sympathetic activity with higher LF/HF ratios (daytime 3.5 ± 2.2 vs. 2.5 ± 1.3, P=0.04; nighttime 4.0 ± 2.6 vs. 2.1 ± 1.5, P<0.01) compared to non-allergic ACS patients.

Key Points

This research aims to investigate allergy-associated acute coronary syndrome (ACS) without accompanying anaphylaxis and its immune markers.
Prospective observational study of 375 ACS patients from April 2022 to March 2024.
Enrolled 49 patients classified into allergy-associated and non-allergy-associated ACS groups.
Measured serum IgE and plasma histamine at ACS onset.
Analyzed heart rate variability (HRV) using 24-hour monitoring post-intervention.
ACS-AL groups showed significantly higher levels of IgE and histamine compared to ACS-NA (P < 0.05).
HRV analysis indicated increased LF/HF ratios and reduced daytime HF, showing sympathetic nervous system predominance in both allergy-associated groups.
Findings suggest immune activation and autonomic imbalance even in non-anaphylactic ACS cases.

Study Design

Type

Observational (n=49)

Multicenter

Structured PICO

Does allergy-associated acute coronary syndrome (with or without anaphylaxis) alter immune markers and autonomic nervous system activity compared to non-allergy-associated ACS?

Population

49 patients treated for acute coronary syndrome (ACS) prospectively enrolled from a total of 375 ACS patients. Classified into non-allergy-associated ACS (n=32) and allergy-associated ACS (n=17, which included 11 non-anaphylactic and 6 anaphylactic patients).

Intervention

Allergy-associated acute coronary syndrome (ACS-AL), including both non-anaphylactic and anaphylactic presentations

Comparator

Non-allergy-associated acute coronary syndrome (ACS-NA)

Outcome

Serum IgE and plasma histamine levels at ACS onset, and heart rate variability (HRV) parameters (LF/HF ratio and HF power) measured via 24-h ambulatory monitoring within 1 week after percutaneous coronary interventionsurrogate

Allergy-associated ACS, even without overt anaphylaxis, is characterized by elevated immune markers (IgE, histamine) and sympathetic nervous system predominance compared to non-allergy-associated ACS.

Limitations

Small sample size with only 49 patients included and especially few patients with anaphylactic allergy-associated ACS (n=6), limiting generalizability and preventing multivariable adjustment.
Single-center study conducted in Japan, which may limit applicability to other populations.
Use of medications affecting autonomic function (e.g., β-blockers) was not controlled for, which could confound HRV results.
Serum tryptase, a marker of mast cell activation, was not measured, limiting confirmation of acute allergic activation.
The use of LF/HF ratio as a marker of sympathetic predominance is debated and may not fully represent autonomic balance.

Abstract

Abstract Kounis syndrome is an acute coronary syndrome (ACS) triggered by allergic reactions via mast cell activation, classically accompanied by anaphylaxis. However, ACS associated with mild or subclinical allergic reactions may be underrecognized. We investigated immune markers and autonomic nervous system activity in patients with ACS and characterized allergy-associated ACS without anaphylactic symptoms. Among 375 patients treated for ACS (April 2022 to March 2024), 49 were prospectively enrolled. Patients were classified into non-allergy-associated ACS (ACS-NA, n = 32) and allergy-associated ACS (ACS-AL, n = 17) groups. ACS-AL was subdivided into the non-anaphylactic (ACS-AL(nonA), n = 11) and anaphylactic (ACS-AL(withA), n = 6) groups. Allergic status was comprehensively assessed. Serum IgE and plasma histamine were measured at ACS onset. Heart rate variability (HRV) parameters were analyzed using 24-h ambulatory monitoring within 1 week after percutaneous coronary intervention. The ACS-AL(nonA) and ACS-AL(withA) groups showed significantly higher IgE and histamine levels than the ACS-NA group (P < 0.05), with overlapping distributions. HRV analysis revealed elevated LF/HF ratios and reduced daytime HF in both groups, indicating sympathetic predominance. ACS-AL, even without anaphylaxis, involves immune activation and autonomic imbalance. Combined assessment of IgE, histamine, and HRV may improve the identification of this phenotype.

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