Peripheral Blood Monocytes Are Activated In Patients With Well Controlled Hypertension: Implications For The Understanding Of The Residual Cardiovascular Risk

Hypertension is associated with significant risk of cardiovascular events which remains increased even in the setting of well controlled hypertension. This residual risk may be related to inflammation persisting in spite of sufficient blood pressure control. We have recently reported that monocytes show pro-inflammatory and pro-atherosclerotic phenotype (co-expression of the Fc-gamma receptor-CD16+ and LPS receptor-CD14+) in relation to atherosclerosis risk factors and that hypertension is the strongest independent predictor of CD16+CD14+ monocytes. It is thus possible that monocytes remain activated in spite of appropriate blood pressure control and thus may be in part responsible for residual risk. We studied 112 hypertensive subjects and 25 control non-hypertensive individuals matched for major risk factors. Hypertension was well controlled (<140/90) in 52 and poorly controlled in 60 pts. Cytokine production was assessed by ELISA. Results: The prevalence of CD14+CD16+ monocytes was significantly positively correlated with systolic and diastolic blood pressure (R=0.3; p<0.01). Both subpopulations CD14(high)CD16+ (R=0.4; p<0.01) and to the lesser extent CD14(dim)CD16+ (R=0.2; p<0.05) showed relationships to systolic but only the CD14(high)CD16+ to diastolic blood pressure. The percentage of total CD14+CD16+ and CD14(high)CD16+ monocytes were highest in subjects whose blood pressure was poorly controlled. A significant difference was also observed between normotensives and hypertensive subjects with well controlled blood pressure. Further analysis of monocyte subpopulations showed that levels of pro-atherosclerotic CD14(high)CD16+ monocytes, revealed a strong relationship to hypertension and greatest difference between well controlled hypertension and normotensives (6±0.2 vs 9±0.4 p<0.01). These monocytes showed significantly higher expression of activation markers HLA-DR and CD45RA and TNF-a production in patients with hypertension, even in the absence of high blood pressure at the time of the study. These results provide a novel marker of inflammation in hypertension which remains increased even in the setting of well controlled disease providing an inflammatory mechanism for the residual risk.