TY - JOUR
T1 - Soluble Fms-like tyrosine kinase-1 (sFlt-1) is associated with subclinical and clinical atherosclerotic cardiovascular disease
T2 - The Dallas Heart Study
AU - Mauricio, Rina
AU - Singh, Kavisha
AU - Sanghavi, Monika
AU - Ayers, Colby R
AU - Rohatgi, Anand
AU - Vongpatanasin, Wanpen
AU - de Lemos, James A.
AU - Khera, Amit
N1 - Funding Information:
Dr de Lemos has received grant support from Roche Diagnostics and Abbott Diagnostics and consulting income from Ortho Clinical Diagnostics, Siemen's Health Care Diagnostics, and Quidel. Dr. Vongpatanasin is supported by the UT Southwestern O'Brien Kidney Center, the Pak Center of Mineral Metabolism and Clinical Research, and R01 HL133179. The other authors have nothing to disclose.
Funding Information:
The Dallas Heart Study was funded by the Donald W. Reynolds Foundation, Las Vegas, Nevada .
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/4
Y1 - 2022/4
N2 - Background and aims: Soluble Fms-like tyrosine kinase-1 (sFlt-1) plays a role in angiogenesis, atherogenesis, and preeclampsia. The relationship of sFlt-1 with markers of subclinical atherosclerosis and future atherosclerotic cardiovascular disease (ASCVD) events in a generally healthy population is unknown. Methods: Participants in the Dallas Heart Study with sFlt-1 measured were included (n = 3292). Abdominal aortic atherosclerosis was measured by MRI and coronary artery calcium (CAC) by CT. The cohort was also followed for subsequent ASCVD events (CV death, MI, stroke, unstable angina, revascularization). Multivariable linear and logistic regression analyses and Cox regression analyses were performed adjusting for demographics and traditional cardiac risk factors. Results: sFlt-1 levels were higher in older individuals, males, and African Americans, and tracked with most traditional risk factors. sFlt-1 was significantly associated with higher prevalence of aortic plaque [OR 1.33 (95% CI 1.02–1.73)], greater abdominal aortic wall thickness (p<0.01) and aortic plaque area (p<0.02) but no difference in coronary artery calcification. There were 322 ASCVD events over 12 years of follow-up. Higher sFlt-1 levels associated with increased ASCVD events in unadjusted (16.1% vs. 8.9%, p<0.001, quartile 4 vs. quartile 1) and adjusted analyses (HR 1.58 [1.14–2.18], p<0.01, quartile 4 vs. quartile 1). Findings were unchanged when analyzing sFlt-1 as a continuous variable or when excluding those with a history of ASCVD. Conclusions: In a population-based cohort, sFlt-1 is associated with measures of subclinical aortic atherosclerosis and clinical ASCVD events. Future studies are warranted on the therapeutic potential of targeting sFlt-1 for atherosclerotic disease.
AB - Background and aims: Soluble Fms-like tyrosine kinase-1 (sFlt-1) plays a role in angiogenesis, atherogenesis, and preeclampsia. The relationship of sFlt-1 with markers of subclinical atherosclerosis and future atherosclerotic cardiovascular disease (ASCVD) events in a generally healthy population is unknown. Methods: Participants in the Dallas Heart Study with sFlt-1 measured were included (n = 3292). Abdominal aortic atherosclerosis was measured by MRI and coronary artery calcium (CAC) by CT. The cohort was also followed for subsequent ASCVD events (CV death, MI, stroke, unstable angina, revascularization). Multivariable linear and logistic regression analyses and Cox regression analyses were performed adjusting for demographics and traditional cardiac risk factors. Results: sFlt-1 levels were higher in older individuals, males, and African Americans, and tracked with most traditional risk factors. sFlt-1 was significantly associated with higher prevalence of aortic plaque [OR 1.33 (95% CI 1.02–1.73)], greater abdominal aortic wall thickness (p<0.01) and aortic plaque area (p<0.02) but no difference in coronary artery calcification. There were 322 ASCVD events over 12 years of follow-up. Higher sFlt-1 levels associated with increased ASCVD events in unadjusted (16.1% vs. 8.9%, p<0.001, quartile 4 vs. quartile 1) and adjusted analyses (HR 1.58 [1.14–2.18], p<0.01, quartile 4 vs. quartile 1). Findings were unchanged when analyzing sFlt-1 as a continuous variable or when excluding those with a history of ASCVD. Conclusions: In a population-based cohort, sFlt-1 is associated with measures of subclinical aortic atherosclerosis and clinical ASCVD events. Future studies are warranted on the therapeutic potential of targeting sFlt-1 for atherosclerotic disease.
KW - ASCVD
KW - Atherosclerosis
KW - sFlt-1
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U2 - 10.1016/j.atherosclerosis.2022.02.026
DO - 10.1016/j.atherosclerosis.2022.02.026
M3 - Article
C2 - 35276530
AN - SCOPUS:85126812364
SN - 0021-9150
VL - 346
SP - 46
EP - 52
JO - Atherosclerosis
JF - Atherosclerosis
ER -