Shantsila, Eduard (2012)
Ph.D. thesis, University of Birmingham.
Introduction and Aims: The progressive nature of heart failure (HF) is reflected by its complex pathophysiology, featured by imbalance of damaging and reparative factors. The overall aim was to assess the implication of endothelial (dys)function, monocyte subsets, different types of endothelial progenitors and plasma microparticles in subjects with HF. A special focus was an investigation of possible ethnic differences in these parameters.
Methods: Parameters of vascular function, monocyte subsets, endothelial progenitors, and cellular microparticles were compared between South Asian subjects with systolic HF, and those with heart disease without HF and healthy controls. Ethnic differences in HF were assessed in three ethnic groups: South Asians, Whites, and African-Caribbeans. Additionally, leukocyte counts were compared between subjects with HF with reduced or preserved ejection fraction, whose outcome (mortality) was recorded during follow-up.
Results: South Asian subjects with HF had significantly impaired micro- and macrovascular endothelial function, reduced levels of endothelial progenitors, and monocytes with reparative potential, but increased levels of microparticles. In HF patients, a high count of monocyte microparticles was associated with low ejection fraction. There were significant ethnic differences in characteristics of microvascular endothelial function, counts of CD14++CD16+ and CD14+CD16++ monocytes and monocyte-derived endothelial progenitors. On multivariate analysis, a high monocyte count was a significant predictor of death in HF with preserved ejection fraction unlike in those with systolic HF.
Conclusions: Significant impairment of microvascular endothelial function is present in South Asian subjects with HF. High monocyte count is an independent predictor of death in HF with preserved ejection fraction. The value of the tested biological markers as therapeutic targets should be explored in future studies.
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