Impact of vertebral artery hypoplasia on cerebrovascular reactivity

Vertebral artery hypoplasia (VAH) is one of the most common anomalies of cerebrovascular structure and is present among healthy asymptomatic individuals. The prevalence of VAH is estimated to be between 15% and 35%. Although VAH has been associated with regional hypoperfusion in the brain, less is known about the impact of VAH on cerebrovascular reactivity, which is a sensitive measure of microvascular function and reflects the ability of cerebral arteries to dilate in response to vasoactive stimuli such as carbon dioxide (CO 2 ). Therefore, the purpose of this study was to determine the impact of VAH on cerebrovascular reactivity of regional arteries including the vertebral arteries (VAs) and basilar artery (BA) among cognitively unimpaired middle-aged and older adults. We hypothesized that in response to hypercapnia, individuals with VAH (VAH+) would have lower VA and BA reactivity compared with individuals without VAH (No VAH). Sixty-three cognitively unimpaired middle-aged and older adults underwent 4D flow magnetic resonance imaging (MRI) in a 3T scanner to determine blood flow of the VAs and BA during normocapnia and a stepped hypercapnia protocol (+5 mmHg and +8 mmHg CO 2 ). Individuals were categorized as VAH+ if they met all three criteria: (1) left or right VA diameter < 2.5 mm, (2) left or right VA flow < 50 mL/min, and (3) flow ratio between the hypoplastic and contralateral VAs < 1:2. Mean arterial blood pressure (MAP) and end-tidal CO 2 (ETCO 2 ) were continually monitored during the MRI scan. Cerebrovascular conductance (CVC) was calculated as flow/MAP for each condition. Cerebrovascular reactivity was calculated as the slope of the relationship between the absolute changes in ETCO 2 and CVC of the VAs and BA. In the VAH+ group, paired t-tests were used to evaluate differences between the hypoplastic and contralateral VAs. Independent t-tests were used to evaluate group differences (VAH+ vs. No VAH) in the BA. Twenty participants were categorized as VAH+ (15F/5M, 63 ± 4 years old) and 43 were No VAH (34F/9M, 64 ± 4 years old). As expected, the hypoplastic VA had significantly lower flow than the contralateral VA (32.74 ± 11.85 mL/min vs. 107.45 ± 29.26 mL/min, p < 0.001) among the VAH+ group during normocapnia. Additionally, the hypoplastic VA had significantly lower CVC reactivity than the contralateral VA (0.03 ± 0.02 mL/min/mmHg2 vs. 0.07 ± 0.04 mL/min/mmHg2, p < 0.001) in the VAH+ group. Contrary to our hypothesis, there were no group differences in BA flow during normocapnia between the VAH+ and No VAH groups (123.05 ± 37.93 mL/min vs. 129.71 ± 32.21 mL/min, p = 0.480). There were also no group differences in BA CVC reactivity between the VAH+ and No VAH groups (0.09 ± 0.04 mL/min/mmHg2 vs. 0.08 ± 0.04 mL/min/mmHg2, p = 0.182). Our results suggest that, among cognitively unimpaired middle-aged and older VAH+ adults, although the hypoplastic VA has a lower reactivity, the contralateral VA appears to compensate for this blunted reactivity. This may in part explain why VAH+ and No VAH adults have comparable BA flow and reactivity. Funding Source: National Institute of Neurological Disorders and Stroke Grant (R01NS117746, JNB), National Institute on Aging Grant (K00AG083283, ZZ), and the Alzheimer’s Association Research Fellowship (AARF-22-924325, BGF). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.