Serum Leptin Levels and the Risk of Stroke: The Framingham Study.
OBJECTIVE
Leptin is a major adipokine that regulates weight balance and energy homeostasis. There is inconsistent evidence linking circulating leptin levels to risk of stroke. We tested the hypothesis that leptin levels are associated with risk of incident stroke in an elderly community based sample.


METHODS
Serum leptin levels were assayed in 757 stroke free individuals (mean age, 79 years; 62% women) from the Framingham Original Cohort at the 22nd examination cycle (1990-1994). Incidence of all -stroke and ischemic stroke were prospectively ascertained.


RESULTS
During a mean follow up of 10 years, 119 individuals developed stroke (99 ischemic strokes). In multivariable Cox regression models, log leptin levels were not associated with incidence of all -stroke or ischemic stroke (hazard ratios per SD increment in log leptin 0.90 [0.73-1.09] and 0.89 [0.72-1.11], respectively). The results were suggestive for potential effect modification by waist/hip ratio for the association between leptin and stroke (P=0.03). Adjusting for age, sex, and established stroke risk factors, analysis stratified by waist/hip ratio quartiles revealed a lower incidence of first-ever all-stroke and ischemic stroke associated with higher leptin levels among only subjects in the top waist/hip ratio quartile (hazard ratio, 0.64 [0.43, 0.95] versus 0.98 [0.77, 1.25] for incident all-stroke and 0.61 [0.39, 0.95] versus 0.96 [0.74, 1.26] for ischemic stroke).


CONCLUSIONS
Leptin levels were not directly related to the risk of incident stroke overall but there was an inverse association with stroke in the top waist/hip ratio quartile. Further investigations are required to confirm these findings and explore possible mechanisms for the observed association.
From the Framingham Heart Study, MA (H.S., A.B., J.R.R., C.S.K., R.S.V., S.S.); Department of Biostatistics, Boston University School of Public Health, MA (A.B.); Division of Neurology, Department of Medicine, McMaster University/Population Health Research Institute, Hamilton, ON, Canada (A.S.); Department of Neurology, University of Toronto, Toronto, ON, Canada (A.P.); Geriatric Epidemiology section, National Institute on Aging, National Institute of Health, Bethesda, MD (T.B.H.); Friedman School of Nutrition Science and Policy, Tufts University School of Medicine, Boston, MA (R.R.); and Department of Neurology, Boston University School of Medicine, MA (H.S., J.J.H., A.B., J.R.R., C.S.K., R.S.V., S.S.). Hsaber@bu.edu.
Hamidreza
H
Saber
From the Framingham Heart Study, MA (H.S., A.B., J.R.R., C.S.K., R.S.V., S.S.); Department of Biostatistics, Boston University School of Public Health, MA (A.B.); Division of Neurology, Department of Medicine, McMaster University/Population Health Research Institute, Hamilton, ON, Canada (A.S.); Department of Neurology, University of Toronto, Toronto, ON, Canada (A.P.); Geriatric Epidemiology section, National Institute on Aging, National Institute of Health, Bethesda, MD (T.B.H.); Friedman School of Nutrition Science and Policy, Tufts University School of Medicine, Boston, MA (R.R.); and Department of Neurology, Boston University School of Medicine, MA (H.S., J.J.H., A.B., J.R.R., C.S.K., R.S.V., S.S.).
Jayandra J
JJ
Himali
From the Framingham Heart Study, MA (H.S., A.B., J.R.R., C.S.K., R.S.V., S.S.); Department of Biostatistics, Boston University School of Public Health, MA (A.B.); Division of Neurology, Department of Medicine, McMaster University/Population Health Research Institute, Hamilton, ON, Canada (A.S.); Department of Neurology, University of Toronto, Toronto, ON, Canada (A.P.); Geriatric Epidemiology section, National Institute on Aging, National Institute of Health, Bethesda, MD (T.B.H.); Friedman School of Nutrition Science and Policy, Tufts University School of Medicine, Boston, MA (R.R.); and Department of Neurology, Boston University School of Medicine, MA (H.S., J.J.H., A.B., J.R.R., C.S.K., R.S.V., S.S.).
Ashkan
A
Shoamanesh
From the Framingham Heart Study, MA (H.S., A.B., J.R.R., C.S.K., R.S.V., S.S.); Department of Biostatistics, Boston University School of Public Health, MA (A.B.); Division of Neurology, Department of Medicine, McMaster University/Population Health Research Institute, Hamilton, ON, Canada (A.S.); Department of Neurology, University of Toronto, Toronto, ON, Canada (A.P.); Geriatric Epidemiology section, National Institute on Aging, National Institute of Health, Bethesda, MD (T.B.H.); Friedman School of Nutrition Science and Policy, Tufts University School of Medicine, Boston, MA (R.R.); and Department of Neurology, Boston University School of Medicine, MA (H.S., J.J.H., A.B., J.R.R., C.S.K., R.S.V., S.S.).
Alexa
A
Beiser
From the Framingham Heart Study, MA (H.S., A.B., J.R.R., C.S.K., R.S.V., S.S.); Department of Biostatistics, Boston University School of Public Health, MA (A.B.); Division of Neurology, Department of Medicine, McMaster University/Population Health Research Institute, Hamilton, ON, Canada (A.S.); Department of Neurology, University of Toronto, Toronto, ON, Canada (A.P.); Geriatric Epidemiology section, National Institute on Aging, National Institute of Health, Bethesda, MD (T.B.H.); Friedman School of Nutrition Science and Policy, Tufts University School of Medicine, Boston, MA (R.R.); and Department of Neurology, Boston University School of Medicine, MA (H.S., J.J.H., A.B., J.R.R., C.S.K., R.S.V., S.S.).
Aleksandra
A
Pikula
From the Framingham Heart Study, MA (H.S., A.B., J.R.R., C.S.K., R.S.V., S.S.); Department of Biostatistics, Boston University School of Public Health, MA (A.B.); Division of Neurology, Department of Medicine, McMaster University/Population Health Research Institute, Hamilton, ON, Canada (A.S.); Department of Neurology, University of Toronto, Toronto, ON, Canada (A.P.); Geriatric Epidemiology section, National Institute on Aging, National Institute of Health, Bethesda, MD (T.B.H.); Friedman School of Nutrition Science and Policy, Tufts University School of Medicine, Boston, MA (R.R.); and Department of Neurology, Boston University School of Medicine, MA (H.S., J.J.H., A.B., J.R.R., C.S.K., R.S.V., S.S.).
Tamara B
TB
Harris
From the Framingham Heart Study, MA (H.S., A.B., J.R.R., C.S.K., R.S.V., S.S.); Department of Biostatistics, Boston University School of Public Health, MA (A.B.); Division of Neurology, Department of Medicine, McMaster University/Population Health Research Institute, Hamilton, ON, Canada (A.S.); Department of Neurology, University of Toronto, Toronto, ON, Canada (A.P.); Geriatric Epidemiology section, National Institute on Aging, National Institute of Health, Bethesda, MD (T.B.H.); Friedman School of Nutrition Science and Policy, Tufts University School of Medicine, Boston, MA (R.R.); and Department of Neurology, Boston University School of Medicine, MA (H.S., J.J.H., A.B., J.R.R., C.S.K., R.S.V., S.S.).
Ronenn
R
Roubenoff
From the Framingham Heart Study, MA (H.S., A.B., J.R.R., C.S.K., R.S.V., S.S.); Department of Biostatistics, Boston University School of Public Health, MA (A.B.); Division of Neurology, Department of Medicine, McMaster University/Population Health Research Institute, Hamilton, ON, Canada (A.S.); Department of Neurology, University of Toronto, Toronto, ON, Canada (A.P.); Geriatric Epidemiology section, National Institute on Aging, National Institute of Health, Bethesda, MD (T.B.H.); Friedman School of Nutrition Science and Policy, Tufts University School of Medicine, Boston, MA (R.R.); and Department of Neurology, Boston University School of Medicine, MA (H.S., J.J.H., A.B., J.R.R., C.S.K., R.S.V., S.S.).
Jose Rafael
JR
Romero
From the Framingham Heart Study, MA (H.S., A.B., J.R.R., C.S.K., R.S.V., S.S.); Department of Biostatistics, Boston University School of Public Health, MA (A.B.); Division of Neurology, Department of Medicine, McMaster University/Population Health Research Institute, Hamilton, ON, Canada (A.S.); Department of Neurology, University of Toronto, Toronto, ON, Canada (A.P.); Geriatric Epidemiology section, National Institute on Aging, National Institute of Health, Bethesda, MD (T.B.H.); Friedman School of Nutrition Science and Policy, Tufts University School of Medicine, Boston, MA (R.R.); and Department of Neurology, Boston University School of Medicine, MA (H.S., J.J.H., A.B., J.R.R., C.S.K., R.S.V., S.S.).
Carlos S
CS
Kase
From the Framingham Heart Study, MA (H.S., A.B., J.R.R., C.S.K., R.S.V., S.S.); Department of Biostatistics, Boston University School of Public Health, MA (A.B.); Division of Neurology, Department of Medicine, McMaster University/Population Health Research Institute, Hamilton, ON, Canada (A.S.); Department of Neurology, University of Toronto, Toronto, ON, Canada (A.P.); Geriatric Epidemiology section, National Institute on Aging, National Institute of Health, Bethesda, MD (T.B.H.); Friedman School of Nutrition Science and Policy, Tufts University School of Medicine, Boston, MA (R.R.); and Department of Neurology, Boston University School of Medicine, MA (H.S., J.J.H., A.B., J.R.R., C.S.K., R.S.V., S.S.).
Ramachandran S
RS
Vasan
From the Framingham Heart Study, MA (H.S., A.B., J.R.R., C.S.K., R.S.V., S.S.); Department of Biostatistics, Boston University School of Public Health, MA (A.B.); Division of Neurology, Department of Medicine, McMaster University/Population Health Research Institute, Hamilton, ON, Canada (A.S.); Department of Neurology, University of Toronto, Toronto, ON, Canada (A.P.); Geriatric Epidemiology section, National Institute on Aging, National Institute of Health, Bethesda, MD (T.B.H.); Friedman School of Nutrition Science and Policy, Tufts University School of Medicine, Boston, MA (R.R.); and Department of Neurology, Boston University School of Medicine, MA (H.S., J.J.H., A.B., J.R.R., C.S.K., R.S.V., S.S.).
Sudha
S
Seshadri
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D020738:Leptin / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011863:Radioimmunoassay; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D049629:Waist-Hip Ratio
D015415:Biomarkers; D020738:Leptin
adipokines; leptin; obesity; risk; stroke