Antibodies against oxidized LDL and atherosclerosis in rheumatoid arthritis patients treated with biological agents: a prospective controlled study.

OBJECTIVES: The aim of this study was to investigate the relation among atherosclerosis, antibodies against oxidized LDL (anti-oxLDL), and inflammation in rheumatoid arthritis (RA) patients treated with biological (b) disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Fifty-nine patients who were receiving conventional synthetic DMARDs and were eligible for treatment with a biological agent were included in the study. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and IgG antibodies against oxidized LDL (anti-oxLDL) as well as carotid intima-media thickness (cIMT) were determined before and after 6 months of treatment. Thirty-one healthy individuals were used as a control group. RESULTS: At baseline, RA patients had lower TC and HDL-C levels and increased cIMT compared to controls. After a 6-month follow-up, the re-evaluation of carotids revealed a statistically important decrease of cIMT values. This observation was accompanied by a statistically important elevation of HDL-C levels and a reduction of the titer of anti-oxLDL antibodies regardless of the bDMARD that was administered. No statistically significant association was found between the cIMT and anti-oxLDL, HDL-C, CRP, or DAS28 score neither before nor 6 months after treatment using linear regression analyses adjusted for age and gender. CONCLUSIONS: We provide evidence that atherogenic lipid profile and ongoing atherosclerosis which characterize RA patients appear to improve after biological therapy, and we also suggest a possible atherogenic effect of IgG anti-ox LDL antibodies.

Distinct effects of fixed combinations of valsartan with either amlodipine or hydrochlorothiazide on lipoprotein subfraction profile in patients with hypertension.

The effect of antihypertensive drugs on lipoprotein subfraction profile is still under investigation. In this study the effects of fixed combination of valsartan with either amlodipine (V-A) or hydrochlorothiazide (V-H) on low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) subfraction profile of patients with stage 2 or 3 hypertension were assessed. A total of 60 drug-naive patients were randomized to either V-A (160/5 mg, n=30) or V-H (160/12.5 mg, n=30). At baseline as well as 16 weeks post-treatment analysis of the LDL and HDL subfraction profile was conducted by using LDL Lipoprint System. Both V-A and V-H effectively reduced blood pressure (BP) to similar levels. An increase in the cholesterol concentration of small-dense LDL subfractions (by 18.2%, P<0.05) was observed in the V-H group, whereas this parameter remained unchanged in the V-A group. Therefore, mean LDL particle size was decreased in the V-H group (from 267 ± 5 to 266 ± 5Å, P<0.05). HDL-Cholesterol (HDL-C) levels were reduced by 4.7% (P<0.05) in the V-H group, mirrored by a reduction in the cholesterol mass of small and intermediate HDL particles. In conclusion, despite similar reductions in BP, V-H combination may adversely affect serum lipids as well as LDL and HDL subfraction profile as compared with V-A.

Influence of high-density lipoprotein and paraoxonase-1 on platelet reactivity in patients with acute coronary syndromes receiving clopidogrel therapy.

BACKGROUND: The paraoxonase activity of the enzyme paraoxonase-1 (PON-1) associated with high-density lipoprotein (HDL) may significantly influence clopidogrel's antiplatelet and clinical efficacy as a result of its involvement in the clopidogrel biotransformation to the pharmacologically active thiol metabolite. We evaluated the possible relationships of HDL levels as well as PON-1 activities and the Q192R genotype with clopidogrel's antiplatelet efficacy in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: The platelet aggregation, P-selectin expression and platelet/leukocyte conjugates as well as the clopidogrel response variability (evaluated by the VASP phosphorylation test and expressed as platelet reactivity index, PRI) were assessed in 74 ACS patients undergoing percutaneous coronary intervention (PCI) in relation to the PON-1 Q192R genotype and to serum HDL-cholesterol levels, and PON-1 (paraoxonase and arylesterase) activities. Patients were loaded with 600 mg of clopidogrel followed by 75 mg per day. HDL-cholesterol levels and PON-1 activities at baseline (before clopidogrel loading) were not altered at 5- and 30-day post-clopidogrel loading, whereas baseline platelet activation parameters were significantly attenuated. At 5 days, 17 patients were clopidogrel non-responders (PRI: 64.2 ± 11.1%). HDL-cholesterol was inversely associated with platelet activation parameters independently on platelet response variability to clopidogrel whereas a negative association between platelet activation parameters and paraoxonase activity was observed in patients adequately responding to clopidogrel but not in clopidogrel non-responders. Similarly, the platelet activation markers were significantly higher in PON-1 Q192Q genotype carriers compared with those having one or two R alleles only in patients adequately responding to clopidogrel. CONCLUSIONS: PON-1 is an important determinant of clopidogrel antiplatelet efficacy only in patients adequately responding to clopidogrel. These findings may be clinically important in ACS patients receiving clopidogrel therapy, especially the first days after the episode.

Acute infection with Epstein-Barr virus is associated with atherogenic lipid changes.

OBJECTIVE: To evaluate the effects of acute infection with Epstein-Barr virus (infectious mononucleosis, IM) on lipids and lipoproteins. METHODS: Fasting serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), apolipoproteins (apo) A-I, B, E, C-II, C-III and lipoprotein (a) [Lp(a)] were determined in patients with IM on diagnosis and 4 months after the resolution of febrile illness and in age- and sex-matched controls. Activities of cholesteryl-ester transfer protein (CETP), lipoprotein-associated phospholipase A2 (Lp-PLA2) and paraoxonase 1 (PON1) as well as levels of several cytokines were determined. LDL subclass analysis was performed with the Lipoprint LDL System. RESULTS: Twenty-nine patients (16 males, aged 24.3±14.6 years) and 30 controls were included. TC, HDL-C, LDL-C, apoA-I, apoB, apoC-III and Lp(a) levels were lower at baseline whereas apoB/apoA-I ratio, TG levels and CETP activity were elevated compared with 4 months later. At baseline, higher levels in cytokines and the cholesterol concentration of small-dense LDL particles (sdLDL-C) were noticed, whereas LDL particle size was lower compared with follow-up. Activities of Lp-PLA2 and PON1 were similar at baseline and 4 months later. Four months after the resolution of IM levels of TGs, apoE, apoC-III, Lp(a), sdLDL-C and cytokines as well as LDL particle size, apoB/apoA-I ratio, CETP and Lp-PLA2 activities were similar to controls. PON1 activities both at baseline and 4 months later were lower in patients compared with controls. CONCLUSIONS: IM is associated with atherogenic changes of lipids and lipoproteins that are partially restored 4 months after its resolution.

Persistence of an atherogenic lipid profile after treatment of acute infection with Brucella.

Serum lipid changes during infection may be associated with atherogenesis. No data are available on the effect of Brucellosis on lipids. Lipid parameters were determined in 28 patients with Brucellosis on admission and 4 months following treatment and were compared with 24 matched controls. Fasting levels of total cholesterol (TC), HDL-cholesterol (HDL-C), triglycerides, apolipoproteins (Apo) A, B, E CII, and CIII, and oxidized LDL (oxLDL) were measured. Activities of serum cholesterol ester transfer protein (CETP), paraoxonase 1 (PON1), and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and levels of cytokines [interleukins (IL)-1beta, IL-6, and tumor necrosis factor (TNFa)] were also determined. On admission, patients compared with controls had 1) lower levels of TC, HDL-C, LDL-cholesterol (LDL-C), ApoB, ApoAI, and ApoCIII and higher LDL-C/HDL-C and ApoB/ApoAI ratios; 2) higher levels of IL-1b, IL-6, and TNFa; 3) similar ApoCII and oxLDL levels and Lp-PLA(2) activity, lower PON1, and higher CETP activity; and 4) higher small dense LDL-C concentration. Four months later, increases in TC, HDL-C, LDL-C, ApoB, ApoAI, and ApoCIII levels, ApoB/ApoAI ratio, and PON1 activity were noticed compared with baseline, whereas CETP activity decreased. LDL-C/HDL-C ratio, ApoCII, and oxLDL levels, Lp-PLA(2) activity, and small dense LDL-C concentration were not altered. Brucella infection is associated with an atherogenic lipid profile that is not fully restored 4 months following treatment.