Non-alcoholic fatty liver disease fibrosis score and preclinical vascular damage in morbidly obese patients.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is strongly related with enhanced morbidity and mortality from cardiovascular disease. In obese patients with both NAFLD and features of the metabolic syndrome, the cardiovascular risk is further increased. AIM: The aim of this study is to investigate the relationship between severity of liver fibrosis evaluated by NAFLD fibrosis score (NAFLD-FS), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), other obesity-related markers and preclinical atherosclerosis in morbidly obese patients with previously diagnosed NAFLD. METHODS: Laboratory parameters, visceral fat area (VFA), flow-mediated dilatation (FMD), intima-media thickness (IMT), HOMA-IR and NAFLD-FS were determined in 196 morbidly obese patients. RESULTS: Patients with higher NAFLD-FS or HOMA-IR show higher left max-IMT and lower FMD (p<0.001). VFA and NAFLD-FS, but not HOMA-IR, were independent predictors of reduced FMD (respectively ß -0.268, p=0.001 and ß -0.165, p=0.039, p of the model<0.001) and increased left max-IMT (respectively ß 0.165, p=0.031 and ß 0.301, p<0.001, p of the model<0.001). CONCLUSIONS: In morbidly obese patients, NAFLD-FS correlates with markers of early vascular damage. NAFLD-FS, easier to obtain than VFA, seems to be a better score than HOMA-IR to categorize such subjects who are potentially at risk of future cardiovascular events.

Systemic inflammation and imbalance between endothelial injury and repair in patients with psoriasis are associated with preclinical atherosclerosis.

BACKGROUND: Systemic inflammation and imbalance between endothelial injury and repair, the latter referred to as vascular incompetence, are associated with atherosclerosis and cardiovascular risk. Psoriasis, an inflammatory disease of the skin, has been associated with atherosclerosis. We investigated whether, in psoriasis, inflammation and vascular incompetence are associated with carotid intima-media thickness (cIMT) irrespective of metabolic syndrome and other established cardiovascular risk factors. METHODS: High sensitivity C-reactive protein (hsCRP), the ratio between endothelial microparticles (EMPs) and progenitors (EPCs), a marker of vascular incompetence, and cIMT were measured in 84 patients with psoriasis and 90 healthy controls, balanced for age, gender and the prevalence of metabolic syndrome. RESULTS: Patients with psoriasis had higher hsCRP, EMP/EPC ratio and cIMT than controls. Patients with both psoriasis and metabolic syndrome had the highest hsCRP levels, psoriasis and metabolic syndrome being associated with a 3.1- and 2.6-fold increased risk of having high hsCRP levels, respectively. Logarithm transformed hsCRP and EMP/EPC ratio were predictors of high cIMT (odds ratio 3.8; 95% confidence interval 1.3-11.4; p = 0.02 and odds ratio 8.7; 95% confidence interval 2.7-27.5; p < 0.001, respectively) regardless of confounders. Patients with high hsCRP and EMP/EPC ratio had higher cIMT than those with none or at least one of risk variable. CONCLUSIONS: Patients with psoriasis have an increased burden of cardiovascular risk, including inflammation, vascular incompetence and early atherosclerosis. Increased hsCRP levels, possibly sustained by the inflammatory nature of psoriasis and metabolic syndrome, and vascular incompetence are associated with early carotid atherosclerosis, regardless of metabolic syndrome and other established cardiovascular risk factors.

Insulin resistance and not BMI is the major determinant of early vascular impairment in patients with morbid obesity.

AIM: Several factors contribute to the development of atherogenesis in patients with obesity. The aim of our study was to evaluate the different roles of insulin resistance, strictly correlated to visceral adiposity, and the body mass index (BMI), an estimate of overall adiposity, on early vascular impairment in patients with morbid obesity. METHODS: We enrolled 65 morbidly obese subjects (BMI 44.6 ± 7 kg/m(2)) who were free of previous cardiovascular events and 28 nonobese subjects (control group) in a cross-sectional study. The presence of glycemia and insulinemia, the levels of lipids and liver parameter and the ultrasonographic assessment of the flow-mediated dilatation (FMD), carotid intima-media thickness (IMT) and visceral fat area (VFA) were evaluated in all subjects. RESULTS: In the obese patients with a median HOMA value of ≥ 3.5, the FMD was significantly lower (p < .05) and the left carotid maximum-IMT was significantly higher (p < .05) than those observed in the group with lower HOMA values. No vascular differences were found between the two groups that were subdivided according to the BMI median value. Both the left max-IMT and FMD exhibited a significant correlation with HOMA-IR ("ρ" .292, p=0.02 , "ρ"-.292, p=0.02 respectively) but not with BMI. According to a multivariate analysis, the VFA was an independent predictor of a reduced FMD (ß - .541, p.002; p of the model .002), while age (ß .611 p < .0001) and HOMA-IR (ß .399 p < .001) were independent predictors of the left max-IMT (p of the model .002). CONCLUSIONS: The HOMA-IR, which is strictly related to visceral fat and is an index of metabolic impairment, and not BMI, which reflects of global adiposity, can be used to identify early vascular impairment in patients with morbid obesity.

On-treatment C-reactive protein and HDL cholesterol levels in patients at intermediate cardiovascular risk: impact on carotid intima-media thickness.

AIMS: Statin therapy is followed by reductions in carotid intima-media thickness (CIMT) and C-reactive protein (CRP) levels, but a significant number of treated patients still have increased CIMT. We investigated whether on-treatment levels of CRP are associated with CIMT in hypercholesterolemic patients receiving statin therapy. The influence of blood pressure and anti-hypertensive therapy on the association between CRP and CIMT was evaluated. MAIN METHODS: The assessment of cardiovascular risk factors, CRP and CIMT, was performed in a cross-sectional study of 240 hypercholesterolemic patients at intermediate cardiovascular risk under statin therapy; 125 patients received only a statin (statin group) and 115 also anti-hypertensive therapy (combined therapy group). KEY FINDINGS: Logarithmically transformed CRP (ß=0.17, p=0.01) and HDL cholesterol levels (ß=-0.27, p<0.001) were correlates of CIMT, irrespective of confounders. High CRP levels (>3mg/L) were associated with a 2.7-fold increased risk of having high CIMT (>1.25mm). High CIMT was present in a high percentage of patients not at target for cholesterol and blood pressure levels (61%). Patients in the statin group had lower Framingham risk and CIMT than those in the combined therapy group. In the statin group, logarithmically transformed CRP (ß=0.28, p=0.004) and HDL cholesterol (ß=-0.21, p=0.03) were associated with CIMT. In the combined therapy group, HDL cholesterol was the only significant CIMT correlate (ß=-0.33, p=0.001). SIGNIFICANCE: On-treatment CRP and HDL cholesterol levels are associated with CIMT among hypercholesterolemic patients under statin therapy. In patients receiving both statin and anti-hypertensive therapy, HDL cholesterol remains the main covariate of CIMT.

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.