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Mauro Silvestrini, MD; Fabrizio Vernieri, MD; Patrizio Pasqualetti, PhD; Maria Matteis, PhD; Francesco Passarelli, MD; Elio Troisi, MD; Carlo Caltagirone, MD

JAMA. 2000;283:2122-2127.

Context  Standards for treating patients with asymptomatic carotid artery stenosis have been difficult to establish because of the lack of evidence for factors influencing these patients' prognoses. However, preliminary evidence suggests that an alteration in cerebral hemodynamic function may play a relevant role in the occurrence of stroke in patients with carotid artery disease.

Objective  To investigate the relationship between cerebrovascular reactivity to hypercapnia and cerebrovascular events in patients with severe unilateral asymptomatic carotid artery stenosis.

Design and Setting  Prospective, blinded longitudinal study conducted in an outpatient neurovascular department in Italy between June 1996 and April 1998, with a median follow-up of 28.5 months.

Patients  Ninety-four patients with asymptomatic carotid artery stenosis of at least 70% (74 men; mean age, 71 years).

Main Outcome Measures  Subsequent occurrence of cerebral ischemic events (transient ischemic attack or stroke) or death, analyzed by cerebrovascular reactivity to hypercapnia (measured by transcranial Doppler ultrasonography and calculated by the breath-holding index values in the middle cerebral arteries).

Results  The overall annual rate for all ischemic events was 7.9%. Seventeen patients (18%) had ischemic events, all but 1 of which were ipsilateral to the carotid artery stenosis. Among factors considered, only lower breath-holding index values in the middle cerebral artery ipsilateral to carotid artery stenosis were significantly associated with the risk of an event (hazard ratio, 0.09; 95% confidence interval, 0.02-0.38; P=.001, by multivariate analysis). Based on data from previously studied healthy subjects, the cutoff of the breath-holding index for distinguishing between impaired and normal cerebrovascular reactivity was determined to be 0.69. Using this cutoff, the annual ipsilateral ischemic event risk was 4.1% in patients with normal and 13.9% in those with impaired breath-holding index values.

Conclusions  These results suggest a link between impaired cerebrovascular reactivity and the risk of ischemic events ipsilateral to severe asymptomatic carotid stenosis.

Author Affiliations: Clinica Neurologica, Università di Roma "Tor Vergata" (Drs Silvestrini and Caltagirone), AFaR CRCCS, Dipartimento di Neuroscienze, Ospedale Fatebenefratelli, Isola Tiberina (Drs Vernieri, Pasqualetti, and Passarelli), and IRCCS "S. Lucia," (Drs Matteis, Troisi, and Caltagirone) Rome, Italy.

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