Cardiovascular risk factors in renal artery stenosis : Effects of renal angioplasty and angiotensin II receptor antagonism

Abstract: Renovascular hypertension (RVH) caused by atherosclerotic renal artery stenosis (ARAS) is one of the most common forms of secondary hypertension. The prognosis for patients with RVH is much worse compared to patients with primary hypertension, and caused by a high cardiovascular morbidity. The aim of this thesis was to increase our knowledge about the pathophysiology of RVH and to identify novel treatment targets that could reduce cardiovascular risk in these patients. We investigated: 1) whether systemic inflammation and endothelin-1 (ET-1) are increased in patients with RVH and evaluated how treatment with percutaneous transluminal renal angioplasty (PTRA) affected these variables; 2) lipoprotein abnormalities in patients with atherosclerotic renovascular disease (ARVD) and analyzed whether angiotensin II (Ang II) receptor antagonism with candesartan influenced lipoprotein levels; 3) whether plasma levels of brain natriuretic peptides (BNP) are increased in patients with ARAS and may predict favorable outcome of PTRA; and 4) the long-term effects of candesartan on kidney function, inflammatory biomarkers and ET-1 in patients with ARVD and residual hypertension after PTRA. In patients with significant renal artery stenosis (RAS) we found increased plasma levels of inflammatory biomarkers and ET-1 compared to healthy subjects. Intervention with PTRA triggered a rapid, transient increase in hs-CRP and IL-6. However, one month after PTRA, both IL-6 and ET-1 had decreased compared to before intervention. Patients with ARVD had elevated levels of atherogenic, triglyceride-rich, ApoC-III-containing lipoproteins in spite of ongoing treatment with statins. Treatment with candesartan did not correct these abnormalities. Patients with ARAS had increased plasma levels of BNP compared to healthy controls, but BNP concentrations were not affected by PTRA. Plasma levels of BNP could not be used to predict the outcome of PTRA on blood pressure. Candesartan did not have any significant effects on kidney function, inflammatory biomarkers or ET-1 in patients with ARVD during 35 months of follow up. In conclusion, patients with ARAS had increased levels of inflammatory biomarkers, ET-1, and ApoC-III-containing lipoproteins that may contribute to progressive atherosclerosis and accelerated cardiovascular disease. Intervention with PTRA reduced plasma levels of IL-6 and ET-1 indicating beneficial effects on inflammation and the endothelin system. Plasma concentrations of BNP could not be used to identify patients with a favorable outcome to PTRA.