Association of Cardiovascular Risk Factors With MRI Indices of Cerebrovascular Structure and Function and White Matter Hyperintensities in Young Adults

Abstract

Importance: Risk of stroke and brain atrophy in later life relate to levels of cardiovascular risk in early adulthood. However, it is unknown whether cerebrovascular changes are present in young adults.

Objective: To examine relationships between modifiable cardiovascular risk factors and cerebrovascular structure, function, and white matter integrity in young adults.

Design, setting, and participants: A cross-sectional observational study of 125 young adults (aged 18-40 years) without clinical evidence of cerebrovascular disease. Data collection was completed between August 2014 and May 2016 at the University of Oxford, United Kingdom. Final data collection was completed on May 31, 2016.

Exposures: The number of modifiable cardiovascular risk factors at recommended levels, based on the following criteria: body mass index (BMI) <25; highest tertile of cardiovascular fitness and/or physical activity; alcohol consumption <8 drinks/week; nonsmoker for >6 months; blood pressure on awake ambulatory monitoring <130/80 mm Hg; a nonhypertensive diastolic response to exercise (peak diastolic blood pressure <90 mm Hg); total cholesterol <200 mg/dL; and fasting glucose <100mg/dL. Each risk factor at the recommended level was assigned a value of 1, and participants were categorized from 0-8, according to the number of risk factors at recommended levels, with higher numbers indicating healthier risk categories.

Main outcomes and measures: Cerebral vessel density, caliber and tortuosity, brain white matter hyperintensity lesion count. In a subgroup (n = 52), brain blood arrival time and cerebral blood flow assessed by brain magnetic resonance imaging (MRI).

Results: A total of 125 participants, mean (SD) age 25 (5) years, 49% women, with a mean (SD) score of 6.0 (1.4) modifiable cardiovascular risk factors at recommended levels, completed the cardiovascular risk assessment and brain MRI protocol. Cardiovascular risk factors were correlated with cerebrovascular morphology and white matter hyperintensity count in multivariable models. For each additional modifiable risk factor categorized as healthy, vessel density was greater by 0.3 vessels/cm3 (95% CI, 0.1-0.5; P = .003), vessel caliber was greater by 8 μm (95% CI, 3-13; P = .01), and white matter hyperintensity lesions were fewer by 1.6 lesions (95% CI, -3.0 to -0.5; P = .006). Among the 52 participants with available data, cerebral blood flow varied with vessel density and was 2.5 mL/100 g/min higher for each healthier category of a modifiable risk factor (95% CI, 0.16-4.89; P = .03).

Conclusions and relevance: In this preliminary study involving young adults without clinical evidence of cerebrovascular disease, a greater number of modifiable cardiovascular risk factors at recommended levels was associated with higher cerebral vessel density and caliber, higher cerebral blood flow, and fewer white matter hyperintensities. Further research is needed to verify these findings and determine their clinical importance.

Figure.. Comparison of White Matter Lesion Count and Vessel Morphology Based on Study Participants’ Modifiable Cardiovascular Score

The cardiovascular score was cumulative based on each of the following factors: high cardiovascular fitness (top tertile of peak oxygen uptake [≥110% predicted peak oxygen uptake] or participating in ≥75 minutes of vigorous physical activity per week); not smoking in last 6 months; alcohol intake <8 drinks/week; ambulatory awake blood pressure <130/80 mm Hg; body mass index <25; fasting total cholesterol <200 mg/dL; fasting blood glucose <100 mg/dL; and diastolic blood pressure at peak exercise ≤90 mm Hg. The figure presents a post-hoc comparison between groups of participants who scored 0 to 5 positive factors (n = 47), 6 factors (n = 36), and 7 to 8 positive factors (n = 42). The groupings were defined to approximate tertiles of the combined cardiovascular score. A, White matter lesion counts for individual participants. The group mean and 95% CI are shown with a point estimate and error bars. B and C, Participants with 7 to 8 healthier categories of risk factor had a mean vessel density 11% higher than participants with 0 to 5 healthier categories of risk factor (panel B, 8.6 vessels/cm³ [SD, 1.39] vs 7.8 vessels/cm³ [SD, 1.21], P = .007), a mean vessel caliber 3% higher (panel C, 538 μm [SD, 21] vs 522 μm [SD, 45] P = .02), and on average 20% lower white matter hyperintensity lesion counts (panel A, 19.6 lesions [SD, 7.8] vs 23.5 lesions [SD, 8.6] P = .03). Group means and 95% CI are shown with a point estimate and error bars and reported group differences are adjusted for age and sex.