OBJECTIVE: Microalbuminuria is associated with an increased risk for all-cause 
and cardiovascular mortality, but the pathophysiologic mechanism underlying the 
association between urinary albumin excretion and cardiovascular disease remains 
unclear. Here, we tested the hypothesis that enhanced endothelial apoptotic 
microparticles and decreased endothelial progenitor cell (EPC) levels might 
contribute to the pathophysiology of microalbuminuria or macroalbuminuria in 
cardiovascular disease.
METHODS: Flow cytometry was used to assess endothelial cell apoptosis and 
circulating EPC levels by quantification of circulating CD31/annexin V apoptotic 
microparticles and EPC markers (defined as KDRCD133, CD34CD133, CD34KDR) in 
peripheral blood.
RESULTS: In total, 125 patients with hypertension were enrolled in the study, of 
whom 80 patients (64%) were with normoalbuminuria (albumin excretion rate of <20 
microg/min, overnight urine samples), 35 patients (28%) with microalbuminuria 
(an albumin excretion rate of 20-200 microg/min), and 10 patients (8%) with 
macroalbuminuria (an albumin excretion rate >200 microg/min). Compared to 
hypertensive patients with normoalbuminuria, patients with microalbuminuria or 
macroalbuminuria had significantly more diabetes (P = 0.005), higher systolic 
blood pressure (P = 0.018), and elevated serum creatinine levels (P < 0.001). 
Among the three groups, patients with microalbuminuria or macroalbuminuria had 
significantly increased CD31/annexin V apoptotic microparticles (1.8 +/- 2.2 
versus 3.0 +/- 4.3 versus 5.2 +/- 6.2%, P = 0.044) and decreased circulating EPC 
numbers (P < 0.05). By multivariate analysis, CD31/annexin V apoptotic 
microparticle level was an independent predictor of urinary albumin excretion 
rate in hypertensive patients (P < 0.001). Microparticles isolated from 
hypertensive patients with microalbuminuria or macroalbuminuria attenuated EPC 
proliferation, migration, and increased H2O2 production, cellular senescence and 
apoptosis in comparison with those from hypertensive patients with 
normoalbuminuria.
CONCLUSION: These findings suggest that hypertensive patients with 
microalbuminuria or macroalbuminuria have increased endothelial apoptotic 
microparticles and decreased circulating EPC levels, which may contribute to 
atherosclerotic disease progression and enhanced cardiovascular risk in 
hypertensive patients with nephropathy.