TY - JOUR
T1 - Association of Exhaled Carbon Monoxide with Stroke Incidence and Subclinical Vascular Brain Injury
T2 - Framingham Heart Study
AU - Nayor, Matthew
AU - Enserro, Danielle M.
AU - Beiser, Alexa S.
AU - Cheng, Susan
AU - DeCarli, Charles
AU - Vasan, Ramachandran S.
AU - Seshadri, Sudha
N1 - Funding Information:
This work was supported by the Framingham Heart Study contract from the National Heart, Blood, and Lung Institute: N01-HC-25195 (R.S.V.) and by National Institute of Health (NIH) grant R01-NS-17950, which funded the stroke surveillance in the FHS. In addition, M.N. was supported by NIH grant T32-HL007604 and training grant U10HL110337 from the National Heart, Lung, and Blood Institute. C.D. was supported by NIH grants P-30-AG10129 and R01-AG-08122.
Publisher Copyright:
© 2016 American Heart Association, Inc.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Background and Purpose-Exhaled carbon monoxide (CO) is associated with cardiometabolic traits, subclinical atherosclerosis, and cardiovascular disease, but its specific relations with stroke are unexplored. We related exhaled CO to magnetic resonance imaging measures of subclinical cerebrovascular disease cross-sectionally and to incident stroke/transient ischemic attack prospectively in the Framingham Offspring study. Methods-We measured exhaled CO in 3313 participants (age 59±10 years; 53% women), and brain magnetic resonance imaging was available in 1982 individuals (age 58±10 years; 54% women). Participants were analyzed according to tertiles of exhaled CO concentration. Results-In age-and sex-adjusted models, the highest tertile of exhaled CO was associated with lower total cerebral brain volumes, higher white-matter hyperintensity volumes, and greater prevalence of silent cerebral infarcts (P<0.05 for all). The results for total cerebral brain volume and white-matter hyperintensity volume were consistent after removing smokers from the sample, and the association with white-matter hyperintensity volume persisted after multivariable adjustment (P=0.04). In prospective analyses (mean follow-up 12.9 years), higher exhaled CO was associated with 67% (second tertile) and 97% (top tertile) increased incidence of stroke/transient ischemic attack relative to the first tertile that served as referent (P<0.01 for both). These results were consistent in nonsmokers and were partially attenuated upon adjustment for vascular risk factors. Conclusions-In this large, community-based sample of individuals without clinical stroke/transient ischemic attack at baseline, higher exhaled CO was associated with a greater burden of subclinical cerebrovascular disease cross-sectionally and with increased risk of stroke/transient ischemic attack prospectively. Further investigation is necessary to explore the biological mechanisms linking elevated CO with stroke.
AB - Background and Purpose-Exhaled carbon monoxide (CO) is associated with cardiometabolic traits, subclinical atherosclerosis, and cardiovascular disease, but its specific relations with stroke are unexplored. We related exhaled CO to magnetic resonance imaging measures of subclinical cerebrovascular disease cross-sectionally and to incident stroke/transient ischemic attack prospectively in the Framingham Offspring study. Methods-We measured exhaled CO in 3313 participants (age 59±10 years; 53% women), and brain magnetic resonance imaging was available in 1982 individuals (age 58±10 years; 54% women). Participants were analyzed according to tertiles of exhaled CO concentration. Results-In age-and sex-adjusted models, the highest tertile of exhaled CO was associated with lower total cerebral brain volumes, higher white-matter hyperintensity volumes, and greater prevalence of silent cerebral infarcts (P<0.05 for all). The results for total cerebral brain volume and white-matter hyperintensity volume were consistent after removing smokers from the sample, and the association with white-matter hyperintensity volume persisted after multivariable adjustment (P=0.04). In prospective analyses (mean follow-up 12.9 years), higher exhaled CO was associated with 67% (second tertile) and 97% (top tertile) increased incidence of stroke/transient ischemic attack relative to the first tertile that served as referent (P<0.01 for both). These results were consistent in nonsmokers and were partially attenuated upon adjustment for vascular risk factors. Conclusions-In this large, community-based sample of individuals without clinical stroke/transient ischemic attack at baseline, higher exhaled CO was associated with a greater burden of subclinical cerebrovascular disease cross-sectionally and with increased risk of stroke/transient ischemic attack prospectively. Further investigation is necessary to explore the biological mechanisms linking elevated CO with stroke.
KW - Biomarkers
KW - Carbon monoxide
KW - Heme oxygenase (decyclizing)
KW - Ischemic attack, transient
KW - Stroke
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U2 - 10.1161/STROKEAHA.115.010405
DO - 10.1161/STROKEAHA.115.010405
M3 - Article
C2 - 26696648
AN - SCOPUS:84969373528
VL - 47
SP - 383
EP - 389
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 2
ER -