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

Williamson W, Lewandowski AJ, Forkert ND, Griffanti L, Okell TW, Betts J, Boardman H, Timo Siepmann T, McKean D, Huckstep O, Francis JM, Neubauer S, Phellan R, Jenkinson M, Doherty A, Dawes H, Frangou E, Malamateniou C, Foster C, Leeson P (2018) JAMA.  2018;320(7): 665-673. doi:10.1001/jama.2018.11498 

Web URL: Read this abstract on jamanetwork here


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.


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