Doxazosin reduces prevalence of small dense low density lipoprotein and remnant-like particle cholesterol levels in nondiabetic and diabetic hypertensive patients

Abstract

Small dense low density lipoprotein (LDL) and remnant lipoproteins are potent atherogenic lipoproteins, often elevated in the plasma of patients with type 2 diabetes. The alpha1-blocker doxazosin has been reported to favorably affect the plasma lipid profile. We examined whether doxazosin could reduce these atherogenic lipoproteins in hypertensive subjects with and those without type 2 diabetes. Seventeen nondiabetic hypertensive patients and 33 hypertensive patients with type 2 diabetes were studied. Doxazosin (2 to 4 mg) was administered alone or with other previously received antihypertensive drugs for 6 months. Mean LDL size was measured by 2% approximately 16% gradient gel electrophoresis. Remnant-like particle (RLP)-cholesterol was measured with the use of an affinity column containing anti-apoA1 and B100 monoclonal antibodies. Doxazosin effectively decreased blood pressure (BP) without significantly affecting glucose, glycosylated hemoglobin (HbA1c), or C-peptide levels in both nondiabetic and diabetic patients. Doxazosin significantly reduced triglyceride, apo CIII, and apo B, but did not alter total-, LDL- or HDL-cholesterol. Mean LDL particle diameter was significantly increased from 25.6+/-0.6 nm to 25.9+/-0.4 nm (P < .001) by doxazosin treatment, regardless of the presence of diabetes. Consequently, the prevalence of small dense LDL (<25.5 nm) was halved in both groups. The increase in LDL size significantly correlated with decrease in triglyceride level (r=-0.798, P < .0001). Doxazosin significantly reduced RLP-cholesterol in both groups. These results suggest that doxazosin may help to prevent coronary artery disease by reducing atherogenic lipoproteins, including small dense LDL and remnant lipoproteins, in hypertensive patients, regardless of the presence of diabetes.