Effective blood pressure treatment improves LDL-cholesterol susceptibility to oxidation in patients with essential hypertension. A. QUINÃ ONES-GALVAN1 , A.
Journal of Internal Medicine 2001; 250: 322±326
Effective blood pressure treatment improves LDL-cholesterol susceptibility to oxidation in patients with essential hypertension Ä ONES-GALVAN1, A. PUCCIARELLI1, A. FRATTA-PASINI2, U. GARBIN2, A. QUIN F. FRANZONI1, F. GALETTA1, A. NATALI1, L. COMINACINI2 & E. FERRANNINI1 From the 1 CNR Institute of Clinical Physiology and Department of Internal Medicine, University of Pisa; and University of Verona, Italy
Abstract. QuinÄones-Galvan A, Pucciarelli A, FrattaPasini A, Garbin U, Franzoni F, Galetta F, Natali A, Cominacini L, Ferrannini E (University of Pisa; and Istituto di Semeiotica Medica, University of Verona, Italy). Effective blood pressure treatment improves LDL-cholestrol susceptibility to oxidation in patients with essential hypertension. J Intern Med 2001; 250: 322±326. Objectives. LDL-cholesterol particles from hypertensive patients exhibit enhanced susceptibility to in vitro oxidation, an abnormality thought to increase cardiovascular risk. We tested whether blood pressure (BP) normalization can reverse this abnormality. Design. Double-blind, randomized pharmacological intervention trial. Setting. Clinical research centre. Subjects. A total of 29 nondiabetic, normolipidaemic patients with essential hypertension (BP 151 3/99 1 mmHg) and 11 normotensive controls (BP 125 3/85 1 mmHg) matched for gender, age, obesity, glucose tolerance and lipid pro®le. Intervention. Anti-hypertensive treatment for 3 months with a calcium-antagonist in randomized combination with either an ACE inhibitor or a b-blocker.
Introduction An excess of cardiovascular events occurs in otherwise well-controlled hypertensive individuals, suggesting that factors other than haemodynamics 322
2
Istituto di Semeiotica Medica,
Main outcome measures. Lag phase of copperinduced LDL oxidation, cell-mediated (human umbilical vein endothelium) generation of malondialdehyde (MDA) by LDL and vitamin E content in LDL. Results. At baseline in hypertensives versus controls, lag phase was shorter (89 3 vs. 107 6 min, P < 0.04), MDA generation was higher (5.8 0.1 vs. 5.1 0.2 nmol L±1, P 0.002), and vitamin E was reduced (6.40 0.05 vs. 6.67 0.11 lg mg±1, P 0.03). At 3 months, BP was normalized (124 3/81 1, P < 0.0001 vs. baseline, P ns versus controls), lag phase was prolonged (to 98 3 min, P 0.0005), MDA generation was reduced (5.6 0.1 nmol L±1, P = 0.001), and vitamin E was increased (6.53 0.05 lg mg±1, P 0.003), with no signi®cant differences between the randomized groups. Conclusions. In nondiabetic, nonobese, normolipidaemic patients with essential hypertension, LDL susceptibility to copper- and cell-mediated oxidation is increased. BP normalization is associated with a signi®cant improvement, but not a full reversal, of this abnormality. Keywords: atherosclerosis, essential hypertension, LDL oxidation, oxidative stress.
contribute to the development and progression of atherosclerosis in essential hypertension [1]. LDL-cholesterol particles isolated from hypertensive patients exhibit both enhanced susceptibility to in vitro oxidation and reduced vitamin E content. ã 2001 Blackwell Science Ltd
LDL OXIDATION AND HYPERTENSION Furthermore, higher plasma antioxidized-LDL antibody titres are found in some hypertensive patients, suggesting that the enhanced oxidizability observed under in vitro conditions re¯ects increased in vivo oxidative stress [2]. Thus, it has been postulated that increased oxidative stress may contribute to the excess atherosclerosis observed in essential hypertension. Little information is available on whether antihypertensive treatment modi®es the enhanced LDL susceptibility to oxidation. We tested whether effective blood pressure (BP) treatment is able to modify LDL susceptibility to oxidation in a group of patients with essential hypertension but free of other conditions ± diabetes, obesity, dyslipidaemia ± that may potentially increase oxidative stress.
Materials and methods Study population A total of 29 nonobese (body mass index [BMI] 4 mmol L±1 or HDL-cholesterol