The oxidized low-density lipoprotein/ß2-glycoprotein I complex is associated with abdominal obesity in healthy middle-aged men.

BACKGROUND/AIMS: Oxidized low-density lipoprotein (oxLDL) in complex with ß2-glycoprotein I (ß2GPI) has been associated with autoimmune diseases, diabetes mellitus, chronic renal disease and coronary atherosclerosis. The aim of our study was to determine whether plasma levels of oxLDL/ß2GPI complexes are associated with insulin resistance, inflammation and markers of endothelial damage in obese middle-aged men and, if so, whether oxLDL/ß2GPI correlates better with insulin resistance parameters than oxLDL, advanced oxidation protein products (AOPP) or thioredoxin. METHODS: A total of 72 healthy men were recruited (41 obese and 31 nonobese individuals). Waist circumference >94 cm was used as the criterion for abdominal obesity. RESULTS: The obese men demonstrated higher oxLDL/ß2GPI levels (p < 0.001), homeostasis model assessment of insulin resistance (p < 0.01) and intima-media thickness of the common carotid artery (p < 0.01). oxLDL/ß2GPI correlated with more insulin resistance parameters compared to AOPP, thioredoxin or oxLDL. Furthermore, oxLDL/ß2GPI was associated with plasminogen activator inhibitor-I (PAI-I; r = 0.365, p < 0.001) and negatively with interleukin-8 (r = -0.297, p < 0.05). CONCLUSIONS: In summary, oxLDL/ß2GPI reflects the criterion for abdominal obesity and markers of insulin resistance in our study. The independent positive correlation with PAI-I indicates that oxLDL/ß2GPI may serve as an early marker of low-grade inflammation and atherosclerosis initiation.

Iron stores are associated with asymptomatic atherosclerosis in healthy men of primary prevention.

BACKGROUND: The aim of our study was to assess the impact of increased iron stores on the presence of asymptomatic atherosclerosis in a cohort of healthy men. We anticipated that higher iron stores would be associated with higher soluble cluster of differentiation 163 (sCD163) concentrations, elevated markers of oxidative stress, inflammation and higher common carotid intima-media thickness, independently of traditional risk factors of atherosclerosis. METHODS: In this cross-sectional study that included 72 healthy men, we measured the ultrasonography of common carotid intima-media thickness (IACC), the ratio of plasma-circulating transferrin receptors concentration to plasma ferritin concentration, certain inflammatory and oxidative stress markers, insulin sensitivity, plasma lipids and markers of endothelial dysfunction. RESULTS: The plasma-circulating transferrin receptor concentration to plasma ferritin concentration ratio (TfR/F) showed significant association with IACC (r=-0·310, P=0·008 vs. r=0·295, P=0·012). Multivariate analysis confirmed that the correlation of TfR/F with IACC is independent of traditional risk factors of atherosclerosis. The TfR/F ratio correlated with other indicators of atherosclerotic process fibrinogen (r=-0·292, P=0·013), von Willebrand factor (vWf; r=0·284, P=0·017), sCD163 (r=0·239, P=0·043) and IL-8 (r=0·233, P=0·049). In multivariate analysis, TfR/F independently correlated with haemoglobin (ß=-0·220, P=0·047), fibrinogen (ß=-0·290, P=0·009), IL-8 (ß=0·227, P=0·039) and sCD163 (ß=0·244, P=0·025); however, when vWf was added, significant independent correlation was seen only with fibrinogen (ß=-0·301, P=0·007) and IL-8 (ß=0·219, P=0·047). In addition, we demonstrated the independent correlation of sCD163 with vWf (ß=0·240, P=0·040). CONCLUSIONS: Our study showed a clear association of body iron stores expressed by the TfR/F ratio with asymptomatic carotid atherosclerosis. TfR/F further exhibited an independent positive correlation with fibrinogen and a negative correlation with sCD163 and IL-8.

Transpulmonary B-type natriuretic peptide uptake and cyclic guanosine monophosphate release in heart failure and pulmonary hypertension: the effects of sildenafil.

OBJECTIVES: We sought to identify factors that discriminate heart failure (HF) patients with normal and elevated pulmonary vascular resistance (PVR) and to elucidate the role of cyclic guanosine monophosphate (cGMP)-dependent vasodilation. BACKGROUND: Mechanisms of PVR increase in patients with chronic HF are incompletely understood. METHODS: Twenty-two HF patients with high pulmonary vascular resistance (H-PVR) (>200 dyn.s.cm(-5)) were compared with 24 matched low pulmonary vascular resistance (L-PVR) patients of similar age, sex, body size, HF severity, and volume status who were undergoing invasive hemodynamic study. Pulmonary arterial (PA) and venous blood samples from a wedged PA catheter were used to calculate transpulmonary B-type natriuretic peptide (BNP) uptake and cGMP release. The H-PVR patients were re-examined 1 h after a 40-mg oral dose of sildenafil. RESULTS: Although transpulmonary BNP uptake was similar (p = 0.2), cGMP release was diminished in the H-PVR patients (-1.9 vs. 27.8 nmol.min(-1); p = 0.005). Transpulmonary BNP uptake and cGMP release correlated in the L-PVR patients (R = 0.6, p = 0.004) but not in the H-PVR. The H-PVR patients also had lower PA compliance, systemic arterial compliance (by 47% and 20%, p < 0.001 and p < 0.03), and cardiac index. Sildenafil reduced PVR (-47%), systemic resistance (-24%) and heart rate (-8%), increased cardiac index (+24%), and PA compliance (+87%, all p < 0.001), with a parallel increase of cGMP release (from -5.6 to 16.5 nmol.min(-1), p = 0.047), without affecting BNP uptake or norepinephrine(PA). The PVR response was not dependent on PA wedge pressure or pulmonary hypertension reversibility with prostaglandin E(1). CONCLUSIONS: The H-PVR patients have stiffening of both pulmonary and systemic arteries, preserved transpulmonary BNP uptake, but diminished cGMP release, which is reversible by the administration of sildenafil. This study provides in vivo evidence that phosphodiesterase 5A inhibition restores sensitivity of pulmonary vasculature to endogenous cGMP-dependent vasodilators.

Relationship between increased body iron stores, oxidative stress and insulin resistance in healthy men.

AIM: The aim of our cross-sectional study was to assess the relationships between body iron stores, oxidative stress, impaired insulin sensitivity and carotid atherosclerosis in a cohort of healthy men in primary prevention of cardiovascular disease. METHODS: We examined 151 volunteers, aged 35- 60 years. Anthropometric parameters, markers of metabolic syndrome, insulin resistance, inflammatory markers, parameters of oxidative stress and intima-media thickness of common carotid artery were measured. RESULTS: Ferritin correlated positively with waist circumference, body mass index, impaired insulin sensitivity, plasma triglycerides and inversely with high-density lipoprotein cholesterol. We observed positive correlations between ferritin, oxidized lowdensity lipoprotein and advanced oxidation protein products after adjustment for age, waist circumference, body mass index and measured inflammatory markers (high-sensitivity C-reactive protein, fibrinogen, interleukin-6 and tumor necrosis factor-alpha). There were no significant associations between ferritin and intima-media thickness or markers of endothelial dysfunction. In a stepwise multiple regression analysis, triglycerides, waist circumference and elevated transaminases were independent determinants of the serum ferritin level. CONCLUSION: Our results provide evidence for a relationship between plasma ferritin and oxidative modification of lipids as well as proteins in vivo. Higher body iron stores may contribute to impaired insulin sensitivity through increased oxidative stress in a cohort of healthy men.

Ghrelin variants influence development of body mass index and plasma levels of total cholesterol in dialyzed patients.

BACKGROUND: Ghrelin is an endogenous hormone expressed predominantly in the stomach. Ghrelin controls growth hormone secretion and also affects the body's energy balance. We analyzed the association of ghrelin variants with body mass index (BMI), albumin as a marker of malnutrition and plasma lipids as risk factors for atherosclerosis in hemodialyzed patients, in whom malnutrition and accelerated atherosclerosis are common complications. METHODS: Ghrelin variants Arg51>Gln and Leu72> Met were analyzed by PCR-RFLP in 210 hemodialyzed patients, prospectively followed up for 15 months. Changes in body mass index, triglycerides, total cholesterol and albumin over time (after 3, 6, 9, 12 and 15 months of dialysis) were analyzed in subgroups divided according to ghrelin genotypes. RESULTS: Carriers of at least one of the Gln51 and Met72 alleles lost body weight more quickly than Arg51Arg/Leu72Leu homozygotes (p<0.01). Carriers of the Gln51 allele were at higher risk of developing high cholesterol levels (p<0.01). CONCLUSIONS: Common ghrelin variants may have an effect on changes in biochemical and anthropometric parameters in hemodialyzed patients over time and could be used in the future to plan individualized therapy.