Preclinical vascular damage in white postmenopausal women: the relevance of osteoprotegerin.

Osteoprotegerin (OPG) has recently been implicated in human atherogenesis. Abdominal obesity represents an established risk factor for the onset and development of atherosclerotic damage. The aim of the present study was to investigate the link between OPG and abdominal fat and the relationship to precocious features of atherosclerotic disease such as brachial flow-mediated vasodilation (FMV) and the intima-media thickening (IMT) in 195 white postmenopausal women (age range, 43-75 years). The study population was divided into 2 groups: group 1-waist circumference <80 cm and group 2-waist circumference > or = 80 cm. Group 2 had higher menopausal years, body mass index, low-density lipoprotein cholesterol, triglycerides, C-reactive protein, and carotid IMT. High-density lipoprotein cholesterol was higher in group 1. Afterward, these groups were divided on the basis of a cutoff value of OPG (6.85 pmol/L) that was the median of its distribution: patients with OPG < or = 6.85 pmol/L were OPG(-), and those with OPG >6.85 pmol/L were OPG(+). The OPG(+) subjects in both had lower brachial FMV and higher carotid IMT in comparison with OPG(-) subjects. At the multivariate regression analysis, waist circumference, high-density lipoprotein cholesterol, C-reactive protein, and OPG were predictors of carotid mean IMT (beta = 0.55, P = .001; beta = -0.14, P = .001; beta = 0.16, P = .001; and beta = 0.14, P = .05, respectively) and age, OPG, low-density lipoprotein cholesterol, and brachial diameter of brachial FMV (beta = -0.13, P = .05; beta = -0.25, P = .001; beta = -0.14, P = .024; and beta = 0.48, P = .001, respectively). The conclusions are as follows: first, OPG levels did not appear to be conditioned by a risk factor such as abdominal obesity; and second, OPG levels are mainly linked to the evidence of vascular damage. On this basis, we could speculate that OPG levels may be considered not a cardiovascular risk condition but a defense against atherosclerotic progression.

Racial difference in endothelial function: role of the infective burden.

There is much evidence to suggest the existence of racial differences between blacks and whites in the behaviour of endothelial function. Infective state, sustained by viral or bacterial agents, may injure the endothelial surface favouring the onset and progression of atherosclerotic process, mainly by an inflammatory mechanism. The aim of the study was to investigate endothelial function, expressed as brachial flow-mediated vasodilation (FMV), in black and white healthy subjects, along with antibody titer to cytomegalovirus, hepatitis virus (B, C), herpes virus-1 and 2, Epstein-Barr, Chlamydia pneumoniae and the expression of adhesion molecules. We enrolled 22 young (mean age 27+/-8 years) healthy subjects of black race (10 males) and 20 healthy young subjects (10 males, mean age 28+/-9 years) of white race. Total infectious burden (TIB) was defined as the number of serological positive infections. Black subjects have a reduced brachial FMV (6.9+/-3.5% versus 11.6+/-3.0%, p<0.01) and increased values of hsCRP (0.35+/-0.15 mg/dL versus 0.07+/-0.08 mg/dL, p<0.05), white cells (8578+/-1041/mmc versus 5833+/-998/mmc, p<0.01) and adhesion molecules (respectively: sVCAM-1 945+/-142 versus 779+/-93, sICAM-1 534+/-107 ng/mL versus 325+/-80 ng/mL; both p<0.01) in comparison to white subjects. The total infectious burden in black race was significantly higher than in white race (5+/-1 versus 2+/-1, p<0.01). At the univariate analysis, brachial FMV was significantly related to the levels of adhesion molecules (respectively: sVCAM-1 r=-0.49; sICAM-1 r=-0.50, both p<0.05), hsCRP (r=-0.47, p<0.05) and white blood cells (r=-0.43, p<0.05). TIB was associated with brachial FMV (r=-0.64, p<0.05), sVCAM-1 (r=0.55, p<0.05) and hsCRP (r=0.47, p<0.05). At the multivariate analysis the only predictive variables for brachial FMV were hsCRP, TIB and brachial diameter (respectively: beta=-0.49, -0.19, -0.54, all p<0.05). This study confirms that endothelial reactivity is impaired in young African black patients; moreover its behavior is strictly related to the inflammatory state and to the total infectious burden.

Metabolic syndrome and preclinical atherosclerosis: focus on femoral arteries.

Several evidences revealed the relationship between the earliest stages of atherosclerosis and the components of metabolic syndrome. The aim of this study was to disclose preclinical atherosclerotic lesions in a cross-sectional observational study involving 147 patients with metabolic syndrome by the assessment of brachial flow-mediated vasodilation (FMV) and intima-media thickening at both carotid and femoral sites. The purpose was to investigate the association of this metabolic disorder with prevalent atherosclerotic damage in different vascular sites. A control group of 87 healthy subjects was also investigated. Patients had lower values of FMV and a higher mean intima-media thickness (IMT) at both the carotid and femoral sites with respect to controls. Flow-mediated vasodilation had a positive correlation with high-density lipoprotein (HDL) cholesterol and a negative one with low-density lipoprotein (LDL) cholesterol, glycemia, and insulinemia. Carotid mean IMT was directly related to LDL cholesterol and age, and inversely with HDL cholesterol; femoral mean IMT had a direct association with LDL cholesterol, triglycerides, glycemia, and insulinemia and an inverse correlation with HDL cholesterol and LDL size. LDL cholesterol, HDL cholesterol, insulin, and brachial artery diameter were predictive of brachial FMV (beta=-0.17, 0.21, -0.27, and -0.29, respectively; P<.05), whereas age, LDL cholesterol, and HDL cholesterol were independent predictors of mean carotid IMT (beta=0.19, 0.37, and -0.27, respectively; P<.05); on the other hand, LDL cholesterol, triglycerides, and insulin were independent predictors of mean femoral IMT (beta=0.32, 0.26, and 0.25, respectively; P<.05). In conclusion, the present study documented an altered endothelial function and intima-media thickening in patients with metabolic syndrome without overt cardiovascular disease. Moreover, it focused on the strong influence of metabolic syndrome on preclinical atherosclerotic lesions at the femoral site.

Bone mineral density in haemophilia patients. A meta-analysis.

Osteoporosis is caused by bone mineral density (BMD) reduction. Haemophilia patients are at increased risk of osteoporosis because of decreased physical activity and blood-borne virus infections. This systematic review of the literature aims at evaluating BMD reduction in severe haemophilia patients and its correlation with patients' characteristics. Seven case-control studies evaluating lumbar BMD values [g/cm2] (all studies), BMI (5/7 studies), and hepatitis C virus (HCV) seropositivity (6/7 studies) in severe haemophilia patients and controls were meta-analysed. Standardised mean difference (SMD) of BMD was used to compare cases and controls. The effect of body mass index (BMI) and HCV infection was investigated by meta-regression. One hundred one adult cases (age 33 +/- 8.9) with 101 controls and 111 paediatric cases (age 8 +/- 3.6) with 307 controls were available for analysis. Lumbar BMD was significantly lower in severe haemophilia patients than in controls, both in adult (pooled SMD -1.379, 95% confidence interval [CI] -2.355 to -0.403, p=0.006) and children (pooled SMD -0.438, 95% CI -0.686 to -0.189, p=0.001). The reduction in BMD in patients versus controls was not significantly correlated with the reduction in BMI or with the percentage of HCV-infected patients. This meta-analysis confirms the association between severe haemophilia and low BMD. Future studies should investigate fracture rates and interventions to prevent bone loss in persons with haemophilia.

The use of osteopathic manipulative treatment as adjuvant therapy in patients with peripheral arterial disease.

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis associated with impaired endothelial function and intermittent claudication is the hallmark symptom. Hypothesizing that osteopathic manipulative treatment (OMT) may represent a non-pharmacological therapeutic option in PAD, we examined endothelial function and lifestyle modifications in 15 intermittent claudication patients receiving osteopathic treatment (OMT group) and 15 intermittent claudication patients matched for age, sex and medical treatment (control group). Compared to the control group, the OMT group had a significant increase in brachial flow-mediated vasodilation, ankle/brachial pressure index, treadmill testing and physical health component of life quality (all p<0.05) from the beginning to the end of the study. At univariate analysis in the OMT group there was a negative correlation between changes in brachial flow-mediated vasodilation and IL-6 levels (r=-0.30; p=0.04) and a positive one between claudication pain time and physical function score (r=0.50; p=0.05). In conclusion, despite the relatively few patients in our study, these results suggest that OMT significantly improves endothelial function and functional performance in intermittent claudication patients along with benefits in quality of life. This novel treatment combined with drug and lifestyle modification might be an effective alternative to traditional training based on exercise.

Human endothelial impairment in sepsis.

The onset of sepsis is often non-specific, and its severity is cryptic. The pathophysiological mechanism of sepsis development involves vascular alteration and, in particular, the impairment of endothelial function. Aim of the study was to evaluate the potential implications of brachial endothelial function assessment in patients affected by Gram-negative sepsis. Forty-five young patients (mean age 41+/-8 years, 18 males) with Gram-negative sepsis were included; at admission time (T0) signs and symptoms, clinical and laboratory data were collected; the Sequential Organ Failure Assessment (SOFA) score was assessed at the time of the access along with the evaluation of brachial flow-mediated vasodilation (FMV). The same parameters were repeated 3 days after hospitalization (T1). Study population at the hospitalization time was divided on the basis of a brachial FMV cut off: at the T0 subjects with FMV<7.5% had lower white blood cell count in comparison to subjects with FMV> or =7.5% (6693+/-1559 mmc versus 14,270+/-2399 mmc); subjects with FMV<7.5% had a significant increase in SOFA score at T1 (4+/-1 versus 6+/-1) and a significant reduction of brachial FMV at T1 (4.8+/-2.7% versus 3.7+/-2.6%) (all p<0.05). FMV at the admission time was predicted by white blood cells (beta=0.65; p<0.001) and brachial diameter (beta=-0.292; p<0.05); Delta changes in FMV were predicted by changes in SOFA score (beta=-0.41; p<0.05). In conclusion, the present study indicates that in the initial phase of sepsis an impairment of brachial FMV anticipated the progression in organ failures; these considerations support the potential utility of brachial FMV in clinical practice in acute pathologies as septic state.