What is the clinical evidence from this study?

Study design: Cohort. Population: Suspected myocardial ischemia (n=224). Intervention: Abnormal coronary reactivity (low coronary flow reserve) vs. Normal coronary reactivity (CFR ≥2.32). Primary outcome: 4-component MACE (cardiovascular death, nonfatal MI, nonfatal stroke, or heart failure hospitalization) (HR 1.06, 95% CI 1.01-1.12, p=0.021).

What does this research mean for the field?

In women with signs and symptoms of ischemia, impaired coronary microvascular function, including low coronary flow reserve, independently predicts increased long-term risk of major adverse cardiovascular events and mortality. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To prospectively determine the association between invasive coronary reactivity testing and long-term adverse cardiovascular outcomes in women with signs and symptoms of ischemia.

August 28, 2026Journal of the American College of CardiologyOpen Access

Impact of Abnormal Coronary Reactivity on Long-Term Clinical Outcomes in Women

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Key result

Low coronary flow reserve is linked to ~6% higher MACE risk in symptomatic women.

HR 1.06
95% CI 1.01-1.12
P=0.021
n=224

Why the study?

Many women with suspected myocardial ischemia have no obstructive CAD, and abnormal coronary reactivity is commonly found, but its relationship with long-term adverse cardiovascular outcomes required investigation.

Does abnormal coronary reactivity predict long-term adverse cardiovascular outcomes in women with signs and symptoms of ischemia?

Key Points

To prospectively determine the association between invasive coronary reactivity testing and long-term adverse cardiovascular outcomes in women with signs and symptoms of ischemia.
Prospective cohort of 224 women with signs and symptoms of ischemia enrolled in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE).
Coronary microvascular function was evaluated using coronary flow reserve (CFR) and coronary blood flow (CBF) response to intracoronary (IC) acetylcholine, while epicardial reactivity was assessed using IC-acetylcholine and IC-nitroglycerine.
Outcomes included all-cause mortality, major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, stroke, heart failure hospitalization), and angina hospitalizations over a median follow-up of 9.7 years.
Low CFR independently predicted 4-component MACE after adjusting for traditional risk factors and CAD status (HR=1.06; 95% CI 1.004–1.12, p=0.035), with higher MACE rates in women with CFR<2.32 compared to CFR≥2.32 (26% vs 13%, p=0.008).
Each 10% reduction in CBF response to IC-acetylcholine was associated with increased all-cause mortality (adjusted HR=1.12; 95% CI 1.01–1.24, p=0.038) and 4-component MACE (adjusted HR=1.11; 95% CI 1.03–1.20, p=0.006).
Epicardial vasoconstriction to IC-acetylcholine was associated with increased risk of hospitalization for angina (HR=1.05 per 1% decrease in cross-sectional area; 95% CI 1.02–1.07, p<0.0001), whereas IC-nitroglycerine dilation showed no association with clinical outcomes.

Study Design

Type

Cohort (n=224)

Multicenter

Yes

Structured PICO

Does abnormal coronary reactivity predict long-term adverse cardiovascular outcomes in women with signs and symptoms of ischemia?

Population

224 women with signs and symptoms of ischemia, evaluated for coronary reactivity, followed for a median of 9.7 years.

Exposure

Abnormal coronary reactivity (impaired coronary flow reserve [CFR <2.32], abnormal coronary blood flow [CBF change <50%] response to intracoronary acetylcholine, or abnormal epicardial cross-sectional area change to intracoronary acetylcholine/nitroglycerine)

Comparator

Normal coronary reactivity (CFR ≥2.32, CBF change ≥50%, epicardial cross-sectional area change >0% to acetylcholine and >20% to nitroglycerine)

Outcome

All-cause mortality, major adverse cardiovascular events (MACE) [cardiovascular death, myocardial infarction, stroke, and heart failure], and angina hospitalizations over a median follow-up of 9.7 yearscomposite

Main Result

Hazard Ratio: 1.06 (95% CI 1.01–1.12)

Absolute Event Rate: 26% vs 13%

p-value: p=0.021

Limitations

Cohort limited to patients pre-determined to undergo coronary angiography based on inclusion and exclusion criteria.
Coronary reactivity testing results were from a single testing period, which may not reflect the status of the coronary artery over time.
Most women underwent testing for multiple reactivity pathways, making it unknown which modality is the best predictor when multiple are impaired.
Absence of advanced intra-coronary imaging techniques to assess the extent of atherosclerosis.
Coronary reactivity testing is an invasive procedure that requires experienced operators.
Cohort limited to patients pre-determined to undergo coronary angiography based on inclusion and exclusion criteria
Coronary reactivity testing results were from a single testing period
Multiple reactivity pathways tested making it unknown which testing modality is the best predictor of adverse events
Absence of advanced intra-coronary imaging techniques to assess extent of atherosclerosis
Coronary reactivity testing is an invasive procedure that requires experienced operators

Discussion

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Key expert perspectives

Captured external expert commentary on this paper, strongest first. Original sources are linked where available.

AA Ahmed AlBadriCardiologist, Emory University School of Medicine

“This study provides evidence that impaired microvascular function involving endothelial-dependent or independent pathways, or even both, predicts the adverse cardiovascular outcomes in women with signs and symptoms of ischemia but no obstructive coronary artery disease.”

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Implication

Impaired coronary microvascular function predicts long-term adverse cardiovascular outcomes in women with signs and symptoms of ischemia, highlighting the prognostic value of coronary reactivity testing even in the absence of significant CAD.

Cite This Study

AlBadri et al. (2019) conducted a cohort in Suspected myocardial ischemia (n=224). Abnormal coronary reactivity (low coronary flow reserve) vs. Normal coronary reactivity (CFR ≥2.32) was evaluated on 4-component MACE (cardiovascular death, nonfatal MI, nonfatal stroke, or heart failure hospitalization) (HR 1.06, 95% CI 1.01-1.12, p=0.021). In women with signs and symptoms of ischemia, impaired coronary microvascular function indicated by low coronary flow reserve predicted an increased rate of major adverse cardiovascular events (HR 1.06).

synapsesocial.com/papers/6a90fe1973d671a805e3bb1e https://doi.org/10.1016/j.jacc.2018.11.040

Topics

Coronary artery disease Women and heart disease

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Impact of Abnormal Coronary Reactivity on Long-Term Clinical Outcomes in Women

Key Points

Study Design

Structured PICO

Main Result

Limitations

Discussion

Key expert perspectives

Implication

Cite This Study

Topics

Impact of Abnormal Coronary Reactivity on Long-Term Clinical Outcomes in Women

Key Points

Study Design

Structured PICO

Main Result

Limitations

Discussion

Key expert perspectives

Implication

Cite This Study

Also Consider

Topics

Also Consider