Context:
Subclinical hypothyroidism (SCH) is associated with cardiovascular (CV) risk factors, and possibly CV disease. However, its management remains controversial. Endothelial progenitor cells (EPC), expressing both endothelial and stem cell markers, are known to offer a novel CV risk marker.

Objective:
The aim of the study was to ascertain whether EPC count or function is reduced in SCH and whether it improves with T₄ therapy.

Design and Intervention:
EPC were studied in peripheral blood by fluorescence-activated cell sorter and following in vitro cultures before and after T₄ together with CV risk factors in 20 SCH and healthy controls (HC).

Main Outcome Measure:
EPC count was measured at baseline and after T₄ replacement in SCH.

Results:
EPC count was significantly reduced in SCH compared to HC: median (range)—CD133+/VEGFR-2+, 0.09 (0.02–0.44) vs. 0.47 (0.17–2.12), P<0.001; CD34+/VEGFR-2+, 0.10 (0.04–0.46) vs. 0.39 (0.11–2.13), P<0.001; whereas EPC function was similar. There was a significant positive correlation between CD133+/VEGFR-2+ with free T₄ levels (r=0.38; P=0.02); high-density lipoprotein cholesterol levels (r=0.51; P=0.001); and negative correlation with TSH concentrations (r=−0.64; P<0.001). After adjustment for conventional CV risk factors, SCH predicted lower EPC count, β coefficient/P value: CD133+/VEGFR-2+ (−0.77/<0.001), and CD34+/VEGFR-2+ (−0.71/<0.001). In SCH participants, EPC count increased and was similar to HC after T₄; CD133+/VEGFR-2+, 0.32 (0.03–0.94) vs. 0.09 (0.02–0.44), P<0.001; and CD34+/VEGFR-2+, 0.26 (0.06–0.88) vs. 0.10 (0.04–0.46), P<0.001.

Conclusion:
SCH predicted lower EPC count, which improved with T₄ treatment, independent of other CV risk factors, providing additional evidence that T₄ replacement may improve CV risk in SCH.