P-selectin and subclinical and clinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA).
OBJECTIVE
P-selectin is a cellular adhesion molecule that has been shown to be crucial in development of coronary heart disease (CHD). We sought to determine the role of P-selectin on the risk of atherosclerosis in a large multi-ethnic population.


METHODS
Data from the Multi-Ethnic Study of Atherosclerosis (MESA), including 1628 African, 702 Chinese, 2393 non-Hispanic white, and 1302 Hispanic Americans, were used to investigate the association of plasma P-selectin with CHD risk factors, coronary artery calcium (CAC), intima-media thickness, and CHD. Regression models were used to investigate the association between P-selectin and risk factors, Tobit model for CAC, and Cox regression for CHD events.


RESULTS
Mean levels of P-selectin differed by ethnicity and were higher in men (P<0.001). For all ethnic groups, P-selectin was positively associated with measures of adiposity, blood pressure, current smoking, LDL, and triglycerides and inversely with HDL. A significant ethnic interaction was observed for the association of P-selectin and prevalent diabetes; however, P-selectin was positively associated with HbA1c in all groups. Higher P-selectin levels were associated with greater prevalence of CAC. Over 10.1 years of follow-up, there were 335 incident CHD events. There was a positive linear association between P-selectin levels and rate of incident CHD after adjustment for traditional risk factors. However, association was only significant in non-Hispanic white Americans (HR: 1.81, 95% CI 1.07 to 3.07, P=0.027).


CONCLUSIONS
We observed ethnic heterogeneity in the association of P-selectin and risk of CHD.
Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. Electronic address: bielinski.suzette@mayo.edu.
Suzette J
SJ
Bielinski
Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; Montefiore Medical Center, Bronx, NY, USA. Electronic address: ceci.berardi@gmail.com.
Cecilia
C
Berardi
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. Electronic address: Decker.Paul@mayo.edu.
Paul A
PA
Decker
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. Electronic address: Phillip_kirsch@uhc.com.
Phillip S
PS
Kirsch
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. Electronic address: Larson.Nicholas@mayo.edu.
Nicholas B
NB
Larson
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA. Electronic address: pankow@umn.edu.
James S
JS
Pankow
Center for Public Health Genomics, University of Virginia, VA, USA. Electronic address: msale@virginia.edu.
Michele
M
Sale
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. Electronic address: mandrade@mayo.edu.
Mariza
M
de Andrade
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. Electronic address: Sicotte.Hugues@mayo.edu.
Hugues
H
Sicotte
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA. Electronic address: tang0097@umn.edu.
Weihong
W
Tang
Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA. Electronic address: hanso047@umn.edu.
Naomi Q
NQ
Hanson
Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: cwassel@pitt.edu.
Christina L
CL
Wassel
Department of Radiology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA. Electronic address: jpolak@tufts-nemc.org.
Joseph F
JF
Polak
Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA. Electronic address: tsaix001@umn.edu.
Michael Y
MY
Tsai
D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D001213:Asian; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology; D059168:Carotid Intima-Media Thickness; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D012737:Sex Factors; D014481:United States / Q000453:epidemiology; D061205:Vascular Calcification / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology; D044465:White People
D015415:Biomarkers; D019007:P-Selectin; C546937:SELP protein, human
Atherosclerosis; Cardiovascular risk factors; Coronary artery calcium; P-selectin