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April 22, 2026European Heart Journal51 citationsOpen Access

Coronary microvascular dysfunction is associated with impaired cognitive function: the Cerebral-Coronary Connection study (C3 study)

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HMHernán Mejía‐RenteríaATAlejandro TraviesoJMJordi A. Matías‐Guiu

Key Result

Coronary microvascular dysfunction is associated with impaired cognitive function.

Key Points

  • This study aims to explore the connection between coronary microcirculatory dysfunction and cognitive function impairment in patients with coronary artery disease.
  • Prospective blinded study including 67 patients with documented coronary artery disease.
  • Physiological assessment of epicardial vessels and coronary microcirculation using intracoronary pressure and Doppler.
  • Brain imaging, transcranial Doppler, and neurocognitive assessments were conducted.
  • 55.2% of patients had abnormal coronary flow reserve (CFR) (<2.0), linked to higher white-matter hyperintensities (43.2% vs. 20.0%, P = 0.044).
  • Low CFR correlated with reduced grey matter volume (P = 0.024) and worse diffusion-tensor imaging parameters (P = 0.029 and P = 0.032).
  • Lower cognitive performance was observed with worse neurocognitive test scores (P = 0.025 and P = 0.034).

Structured PICO

Does coronary microcirculatory dysfunction correlate with cerebral small vessel disease and cognitive impairment in patients with coronary artery disease?

P
Population
67 patients with documented coronary artery disease (CAD), mean age 66 years, 73% female.
I
Intervention
Presence of coronary microcirculatory dysfunction (CMD), defined as abnormal coronary flow reserve (CFR < 2.0) measured via intracoronary pressure and Doppler.
C
Comparator
Normal coronary flow reserve (CFR ≥ 2.0).
O
Outcome
Burden of cerebral small vessel disease (white-matter hyperintensities, grey matter volume, microstructural damage on MRI), cerebral flow hemodynamics (transcranial Doppler), and cognitive function (neurocognitive examination).surrogate

Coronary microvascular dysfunction in patients with CAD is significantly associated with cerebral small vessel disease and cognitive impairment, suggesting a shared systemic microvascular pathology.

Abstract

BACKGROUND: It remains unknown whether the presence of coronary microcirculatory dysfunction (CMD) correlates with its equivalent condition in the brain, cerebral small vessel disease (CSVD). The cerebral-coronary connection (C3), a prospective blinded study, investigated the prevalence of CMD in patients with coronary artery disease (CAD) and its association with CSVD and cognitive function. METHODS AND RESULTS: Patients with documented CAD fulfilling inclusion criteria underwent physiological assessment of epicardial vessels and the microcirculation using intracoronary pressure and Doppler. Coronary microcirculation-related indices included coronary flow reserve (CFR) and hyperaemic microvascular resistance. Brain magnetic resonance imaging, transcranial Doppler (TCD), and neurocognitive examination were performed. Overall, 67 patients were included in the study (mean age 66 years, 73% female). Patients with abnormal CFR (<2.0) (55.2%) showed higher burden of white-matter hyperintensities: 43.2 vs. 20.0% (P = 0.044). After statistical adjustment, low CFR was associated with lower grey matter volume (P = 0.024) and with parameters of white-matter microstructural damage in diffusion-tensor imaging (lower fractional anisotropy and higher mean diffusivity, P = 0.029 and P = 0.032, respectively). Low CFR was associated with higher resistive (P = 0.027) and pulsatility (P = 0.043) values on TCD, and worse neurocognitive test scores (lower mini mental state examination, P = 0.025, and slower Trail Making Test A, P = 0.034). CONCLUSIONS: Coronary microcirculatory dysfunction is frequent in patients with CAD and correlates with CSVD, abnormal cerebral flow haemodynamics, and significant cognitive impairment. These findings support the hypothesis that microvascular dysfunction in the heart and the brain are part of a single pathological process affecting microcirculation in patients with CAD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04131075.

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Cite This Study

Mejía‐Rentería et al. (2022) studied this question. Coronary microvascular dysfunction is associated with impaired cognitive function.

synapsesocial.com/papers/69e8e6f05169eb7de91c9214https://doi.org/10.1093/eurheartj/ehac521
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