Circulating Progenitor Cells Identify Peripheral Arterial Disease in Patients With Coronary Artery Disease.
BACKGROUND
Peripheral arterial disease (PAD) is a clinical manifestation of extracoronary atherosclerosis. Despite sharing the same risk factors, only 20% to 30% of patients with coronary artery disease (CAD) develop PAD. Decline in the number of bone marrow-derived circulating progenitor cells (PCs) is thought to contribute to the pathogenesis of atherosclerosis. Whether specific changes in PCs differentiate patients with both PAD and CAD from those with CAD alone is unknown.


OBJECTIVE
Determine whether differences exist in PCs counts of CAD patients with and without known PAD.


RESULTS
1497 patients (mean age: 65 years; 62% men) with known CAD were identified in the Emory Cardiovascular Biobank. Presence of PAD (n=308) was determined by history, review of medical records, or imaging and was classified as carotid (53%), lower extremity (41%), upper extremity (3%), and aortic disease (33%). Circulating PCs were enumerated by flow cytometry. Patients with CAD and PAD had significantly lower PC counts compared with those with only CAD. In multivariable analysis, a 50% decrease in cluster of differentiation 34 (CD34+) or CD34+/vascular endothelial growth factor receptor-2 (VEGFR2+) counts was associated with a 31% (P=0.032) and 183% (P=0.002) increase in the odds of having PAD, respectively. CD34+ and CD34+/VEGFR2+ counts significantly improved risk prediction metrics for prevalent PAD. Low CD34+/VEGFR2+ counts were associated with a 1.40-fold (95% confidence interval, 1.03-1.91) and a 1.64-fold (95% confidence interval, 1.07-2.50) increases in the risk of mortality and PAD-related events, respectively.


CONCLUSIONS
PAD is associated with low CD34+ and CD34+/VEGFR2+ PC counts. Whether low PC counts are useful in screening for PAD needs to be investigated.
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
Salim S
SS
Hayek
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
James
J
MacNamara
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
Ayman S
AS
Tahhan
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
Mosaab
M
Awad
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
Adithya
A
Yadalam
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
Yi-An
YA
Ko
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
Sean
S
Healy
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
Iraj
I
Hesaroieh
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
Hina
H
Ahmed
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
Brandon
B
Gray
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
Salman S
SS
Sher
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
Nima
N
Ghasemzadeh
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
Riyaz
R
Patel
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
Jinhee
J
Kim
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA.
Edmund K
EK
Waller
From the Division of Cardiology (S.S.H., M.A., A.Y., S.H., I.H., H.A., B.G., S.S.S., N.G., R.P., A.A.Q.) and Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA (J.M., A.S.T.); and Department of Biostatistics and Bioinformatics (Y.-A.K.) and Department of Hematology and Oncology, Winship Cancer Institute (J.K., E.K.W.), Emory University, Atlanta, GA. aquyyum@emory.edu.
Arshed A
AA
Quyyumi
D000368:Aged; D000369:Aged, 80 and over; D001772:Blood Cell Count / Q000379:methods; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D011446:Prospective Studies; D012042:Registries; D013234:Stem Cells / Q000378:metabolism*
aortic aneurysm; atherosclerosis; coronary artery disease; peripheral arterial disease; stem cells