Cardiovascular Risk Factors are Associated with Cerebrovascular Reactivity in Young Patients

ABSTRACT Introduction Endothelial dysfunction represents the earliest detectable stage of atherosclerosis, is associated with an increased risk of cardiovascular events, and predicts cardiovascular disease (CVD) more effectively than traditional cardiovascular risk factors. Cerebrovascular reactivity (CVR) provides an index of endothelial function in the brain. Poor CVR is associated with stroke, cerebral small vessel disease, dementia, and even coronary artery disease. Traditional CVD risk factors are associated with low CVR in patients with known CVD and in older cohorts. However, the relationship between cardiovascular risk profile and reduced CVR in young adults who do not yet have CVD is uncertain. We hypothesized that in young adults undergoing routine clinical fMRI examinations for non-vascular disease low CVR measures would be associated with increased cardiovascular risk factors. Methods This cross-sectional study included adults who underwent a clinically indicated 3-Tesla fMRI scan of the brain for mapping of eloquent cortex including a “breath-hold task” as an imaging quality control measure. Individuals with intracranial masses and those with baseline CVD were excluded. The task consisted of 5½, 20-second blocks of normal breathing interspersed with 20-second blocks of continuous breath holding. In breath hold fMRI scans, a voxel-wise comparison of brain T2 signal to an expected hemodynamic response curve is used to generate maps of voxel-wise t-statistics, indicating the probability that blood flow within a specific voxel had increased in response to changes in blood carbon dioxide levels. Using an axial slice 8 mm superior to the corpus callosum, a mean cerebral t-statistic was calculated for the slice as a comparative global measure of CVR in each patient. We retrospectively reviewed the charts of all individuals to characterize their clinical profile at the time of the fMRI. Based on the distribution of mean t-statistic values the sample was divided into two groups: high t-statistic (“normal reactivity”) and low t-statistic value (“abnormal reactivity”). The distribution of cardiovascular risk factors was then compared across groups. Results Between January 2014 and December 2023, 76 individuals underwent brain fMRI employing a “breath hold task” with suitable image quality for the current analysis (mean ± SD age, 35.46 ± 12.09 yrs.; 31.6% female). Mean ± SD global CVR T-statistic was 3.97 ± 1.62. Low CVR was defined as a mean T-statistic ≤4.2 (n=44, 57.9%). Individuals with abnormal CVR were older (age: 45.1 ± 10.3 vs. 27.0 ± 3.4 yrs., p<0.001), had a higher frequency of hypertension (31.8% vs. 14.3%, p=0.0069) and hyperlipidemia (18.2% vs. 3.1%, p=0.0449), and had higher systolic (123.5 ± 13.2 vs. 116.9 ± 12.2 mmHg, p=0.0282) and diastolic blood pressures (77.9 ± 11.8 vs. 72.2 ± 8.9, p=0.0141). Age, systolic blood pressure and hyperlipidemia were significantly associated with abnormal CVR in univariable and multivariable analyses (age, increase by 10 years OR: 2.00, 95% CI 1.40 – 2.78, p=0.0078; hyperlipidemia OR: 8.54, 95% CI 1.07 – 184.9, p=0.0049, and systolic blood pressure (OR for an increase in 10 mmHg: 1.57, 95% CI 1.10 – 2.10, p=0.0084). Conclusion Traditional cardiovascular risk factors are significantly associated with abnormal CVR in young adults without baseline CVD or cerebrovascular disease undergoing fMRI for reasons related to a diagnosis of epilepsy. Thus, CVR using fMRI could provide an integrated index of the collective burden of cardiovascular risk factors that could form a therapeutic target to prevent cardiovascular events.