OBJECTIVE Prediction of clinical outcome in diabetic patients with critical limb ischemia (CLI) is unsatisfactory. This prospective study investigates if the abundance and migratory activity of a subpopulation of circulating mononuclear cells, namely, CD45dimCD34posCXCR4posKDRpos cells, predict major amputation and cardiovascular death in type 2 diabetic patients undergoing percutaneous transluminal angioplasty for CLI. RESEARCH DESIGN AND METHODS A consecutive series of 119 type 2 diabetic patients with CLI was enrolled. CD45dimCD34posCXCR4posKDRpos cells were assessed by flow cytometry upon isolation and also after spontaneous or stromal cell-derived factor 1a2directed migration in an in vitro assay. The association between basal cell counts and migratory activity and the risk Q:3 of an event at 18-month follow-up was evaluated in a multivariable regression analysis. RESULTS Time-to-event analysis of amputation (n = 13) showed no association with the candidate predictors. Sixteen cardiovascular deaths occurred during 18 months of follow-up. Abundance of CD45dimCD34posCXCR4posKDRpos cells was not associated with cardiovascular mortality. Interestingly, in vitro migration of CD45dim CD34posCXCR4posKDRpos cells was higher in patients with cardiovascular death compared with event-free subjects (percentage of migrated cells median value and interquartile range, 0.03 (0.02–0.07) vs. 0.01 (0.01–0.03); P = 0.0095).Multivariable regression model analysis showed that cell migration forecasts cardiovascular mortality independently of other validated predictors, such as age, diagnosed coronary artery disease, serum C-reactive protein, and estimated glomerular filtration rate. In this model, doubling of migrated cell counts increases the cardiovascular death hazard by 100% (P < 0.0001). CONCLUSIONS The new predictor could aid in the identification of high-risk patients with type 2 diabetes requiring special diagnostic and therapeutic care after revascularization.
Migratory Activity of Circulating Mononuclear Cells Is Associated With Cardiovascular Mortality in Type 2 Diabetic Patients With Critical Limb Ischemia.
SPECCHIA, Claudia;
2014-01-01
Abstract
OBJECTIVE Prediction of clinical outcome in diabetic patients with critical limb ischemia (CLI) is unsatisfactory. This prospective study investigates if the abundance and migratory activity of a subpopulation of circulating mononuclear cells, namely, CD45dimCD34posCXCR4posKDRpos cells, predict major amputation and cardiovascular death in type 2 diabetic patients undergoing percutaneous transluminal angioplasty for CLI. RESEARCH DESIGN AND METHODS A consecutive series of 119 type 2 diabetic patients with CLI was enrolled. CD45dimCD34posCXCR4posKDRpos cells were assessed by flow cytometry upon isolation and also after spontaneous or stromal cell-derived factor 1a2directed migration in an in vitro assay. The association between basal cell counts and migratory activity and the risk Q:3 of an event at 18-month follow-up was evaluated in a multivariable regression analysis. RESULTS Time-to-event analysis of amputation (n = 13) showed no association with the candidate predictors. Sixteen cardiovascular deaths occurred during 18 months of follow-up. Abundance of CD45dimCD34posCXCR4posKDRpos cells was not associated with cardiovascular mortality. Interestingly, in vitro migration of CD45dim CD34posCXCR4posKDRpos cells was higher in patients with cardiovascular death compared with event-free subjects (percentage of migrated cells median value and interquartile range, 0.03 (0.02–0.07) vs. 0.01 (0.01–0.03); P = 0.0095).Multivariable regression model analysis showed that cell migration forecasts cardiovascular mortality independently of other validated predictors, such as age, diagnosed coronary artery disease, serum C-reactive protein, and estimated glomerular filtration rate. In this model, doubling of migrated cell counts increases the cardiovascular death hazard by 100% (P < 0.0001). CONCLUSIONS The new predictor could aid in the identification of high-risk patients with type 2 diabetes requiring special diagnostic and therapeutic care after revascularization.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
