Susceptible bacteria can survive antibiotic treatment in the mammalian gastrointestinal tract without evolving resistance.

Antibiotic resistance and evasion are incompletely understood and complicated by the fact that murine interval dosing models do not fully recapitulate antibiotic pharmacokinetics in humans. To better understand how gastrointestinal bacteria respond to antibiotics, we colonized germ-free mice with a pan-susceptible genetically barcoded Escherichia coli clinical isolate and administered the antibiotic cefepime via programmable subcutaneous pumps, allowing closer emulation of human parenteral antibiotic dynamics. E. coli was only recovered from intestinal tissue, where cefepime concentrations were still inhibitory. Strikingly, "some" E. coli isolates were not cefepime resistant but acquired mutations in genes involved in polysaccharide capsular synthesis increasing their invasion and survival within human intestinal cells. Deleting wbaP involved in capsular polysaccharide synthesis mimicked this phenotype, allowing increased invasion of colonocytes where cefepime concentrations were reduced. Additionally, "some" mutant strains exhibited a persister phenotype upon further cefepime exposure. This work uncovers a mechanism allowing "select" gastrointestinal bacteria to evade antibiotic treatment.

Prediction of Potential MicroRNA-Disease Association Using Kernelized Bayesian Matrix Factorization.

MicroRNA (miRNA) molecules, which are effective in the formation and progression of many different diseases, are 18-22 nucleotides in length and make up a type of non-coding RNA. Predicting disease-related microRNAs is crucial for understanding the pathogenesis of disease and for diagnosis, treatment, and prevention of diseases. Many computational techniques have been studied and developed, as the experimental techniques used to find novel miRNA-disease associations in biology are costly. In this paper, a Kernelized Bayesian Matrix Factorization (KBMF) technique was suggested to predict new relations among miRNAs and diseases with several information such as miRNA functional similarity, disease semantic similarity, and known relations among miRNAs and diseases. AUC value of 0.9450 was obtained by implementing fivefold cross-validation for KBMF technique. We also carried out three kinds of case studies (breast, lung, and colon neoplasms) to prove the performance of KBMF technique, and the predictive reliability of this method was confirmed by the results. Thus, KBMF technique can be used as a reliable computational model to infer possible miRNA-disease associations.

Prediction of miRNA-disease associations based on Weighted [Formula: see text]-Nearest known neighbors and network consistency projection.

MicroRNAs (miRNA) are a type of non-coding RNA molecules that are effective on the formation and the progression of many different diseases. Various researches have reported that miRNAs play a major role in the prevention, diagnosis, and treatment of complex human diseases. In recent years, researchers have made a tremendous effort to find the potential relationships between miRNAs and diseases. Since the experimental techniques used to find that new miRNA-disease relationships are time-consuming and expensive, many computational techniques have been developed. In this study, Weighted [Formula: see text]-Nearest Known Neighbors and Network Consistency Projection techniques were suggested to predict new miRNA-disease relationships using various types of knowledge such as known miRNA-disease relationships, functional similarity of miRNA, and disease semantic similarity. An average AUC of 0.9037 and 0.9168 were calculated in our method by 5-fold and leave-one-out cross validation, respectively. Case studies of breast, lung, and colon neoplasms were applied to prove the performance of our proposed technique, and the results confirmed the predictive reliability of this method. Therefore, reported experimental results have shown that our proposed method can be used as a reliable computational model to reveal potential relationships between miRNAs and diseases.

Visible light nearly perfect absorber: an optimum unit cell arrangement for near absolute polarization insensitivity.

In this work, we propose an optimum unit cell arrangement to obtain near absolute polarization insensitivity in a metal-insulator-metal (MIM) based ultra-broadband perfect absorber. Our findings prove that upon utilizing this optimum arrangement, the response of the absorber is retained and unchanged over all arbitrary incidence light polarizations, regardless of the shape of the top metal patch. First, the impact of the geometry of the top nanopatch resonators on the absorption bandwidth of the overall structure is explored. Then, the response of the MIM design for different incidence polarizations and angles is scrutinized. Finally, the proposed design is fabricated and characterized.

Effects of restoration of the euthyroid state on epicardial adipose tissue and carotid intima media thickness in subclinical hypothyroid patients.

Epicardial adipose tissue (EAT) thickness is a novel cardiovascular risk indicator, whereas carotid intima media thickness (CIMT) is a known marker of subclinical atherosclerosis. The aim of this study was to measure EAT thickness and CIMT in subclinical hypothyroid (SCH) patients and to determine the effect of restoration of the euthyroid state on these variables. The study included 43 patients with SCH (mean age: 35.2±10.7 years; F-M ratio: 42:1) and 30 healthy controls (mean age: 34.5±8.2 years; F-M ratio: 25:5). EAT thickness and CIMT were measured via conventional echocardiography and ultrasonography. Among the patients, 23 were followed up with L-thyroxine replacement until restoration of the euthyroid state and re-evaluated 6 months after baseline. Basal EAT thickness was higher in the SCH patients than in the controls (3.2±0.7 vs. 2.3±0.3 mm-p<0.0001), whereas CIMT was similar in both groups (0.50±0.09 vs. 0.48±0.04 mm). EAT thickness was correlated with CIMT in the patient group (r=0.39, p=0.01), but this correlation was not evident based on multivariate analysis when corrected for age and body mass index (r2=0.47 and p=0.0001 for the model). In the follow-up patient subgroup, both EAT thickness and CIMT decreased significantly following L-thyroxine treatment, when normal TSH levels were attained (3.4±0.7 vs. 2.3±0.5 mm-p=0.007 and 0.51±0.09 vs. 0.46±0.07 mm-p=0.01, respectively). EAT thickness was greater in the SCH patients than in controls, whereas CIMT was similar in both groups. Restoration of the euthyroid state with L-thyroxine treatment was associated with significant decreases in EAT thickness and CIMT in the group of patients that received L-thyroxine treatment and, as such, might reduce the cardiovascular risk associated with SCH.

Prediction of right ventricular dysfunction from radiographic estimates of right descending pulmonary artery in hemodynamically stable pulmonary embolism patients.

BACKGROUND: The evaluation of right ventricular (RV) dysfunction by echocardiography is one of the most important established determinants of the prognosis of acute pulmonary embolism. The aim of the study was to investigate possible association between diameter of right descending pulmonary artery on chest X-rays and RV dysfunction by echocardiography in hemodynamically stable pulmonary embolism patients. METHODS: Eighty-nine patients with the diagnosis of hemodynamically stable pulmonary embolism were included. RESULTS: The frequency of RV dysfunction was significantly higher in patients with an enlarged right descending pulmonary artery on chest X-rays (p = 0.001). There was a significant positive correlation between the diameter of the right descending pulmonary artery on postero-anterior chest X-rays and the diameter of the RV (r = 0.469; p = 0.002). Diameter of right descending pulmonary artery on chest X-rays was also found as a significant predictor of RV dysfunction besides the troponin-T levels and systolic pulmonary arterial pressure (p < 0.05). CONCLUSIONS: Diameter of right descending pulmonary artery on chest X-rays may provide information about the risk for pulmonary embolism patients and may be used as a prognostic radiological parameter for the appropriate management of acute pulmonary embolism.

Impaired diastolic function and elevated Nt-proBNP levels in type 1 diabetic patients without overt cardiovascular disease.

Diabetic cardiomyopathy is an important complication of type 1 diabetes mellitus. Diastolic heart failure is an early manifestation of diabetic cardiac disease. Nt-proBNP is a valuable marker of ventricular dysfunction. The aim of this study was to determine Nt-proBNP concentrations in type 1 diabetic patients and determine their relationship with ventricular diastolic dysfunction (DD) and carotid artery intima media thickness (CIMT) measurements. Sixty-seven type 1 diabetic patients (30.2 ± 8.0 years; W/M: 24/43) without known cardiovascular disease and 48 healthy controls (30.5 ± 6.4 years; W/M: 19/29) were recruited. Nt-proBNP levels were measured. Conventional and tissue Doppler echocardiography were used to evaluate left ventricular diastolic function and CIMT. Nt-proBNP in diabetic patients was significantly higher than in controls (38 ± 34.8 vs. 15.1 ± 12.7 pg/ml) (P = 0.004). Ea level was higher (12.3 ± 3 vs. 10.3 ± 4 cm/s, P = 0.003) and E/Ea ratio was lower in patients (6.6 ± 2.5 vs. 9.7 ± 5.9, P = 0.001) compared with controls. Ratio of DD was higher in patients than controls (11.1 vs. 2.1%, P = 0.01). CIMT measurements in diabetic patients were higher than controls (0.54 ± 0.11 vs. 0.48 ± 0.05 mm, P = 0.02). Logistic regression revealed age and HbA1c to be independently associated with the presence of DD. Nt-proBNP levels are elevated in type 1 diabetic patients without overt cardiovascular disease and the presence of DD is increased in diabetic patients in comparison with controls. Nt-proBNP levels do not seem to be related to the presence of DD and subclinical atherosclerosis in this group of patients.

Gender divergence on the impact of multiple cardiovascular risk factors on the femoral artery intima-media thickness in asymptomatic young adults: the Bogalusa Heart Study.

INTRODUCTION: Gender divergence on the impact of multiple cardiovascular risk factors on the femoral artery intima-media thickness (IMT) has not been studied in a biracial (black-white) community-based asymptomatic young adults. METHODS: Femoral IMT was measured by B-mode ultrasonography in 1080 individuals (age, 24-43 years; 71% white; 43% men) enrolled in the Bogalusa Heart Study. RESULTS: Femoral IMT showed a gender difference (men > women; P = 0.001), but no racial difference. In a multivariate model, age, cigarette smoking, systolic blood pressure and total cholesterol to high-density lipoprotein cholesterol ratio related independently, in that order, to IMT in women, and age and low-density lipoprotein cholesterol in men. In women, mean IMT increased with increasing number of risk factors defined as values above the age-, race- and gender-specific 75th percentile of systolic blood pressure, waist circumference, total cholesterol to high-density lipoprotein cholesterol ratio and insulin along with positive smoking status (P for trend = 0.001), with respective mean IMT (mm) values of 0.61, 0.65, 0.72 and 0.77, for 0, 1 to 2, 3 and 4 to 5 risk factors. There was no such significant trend in men. CONCLUSIONS: Although men versus women had thicker IMT, the observed increasing trend of femoral IMT with increasing number of risk factors in asymptomatic young women suggests that women may be relatively more susceptible to the burden of multiple risk factors.

Serum adipokine levels in type 1 diabetic patients: association with carotid intima media thickness.

BACKGROUND: Adipokines are markers of insulin resistance and play a role in the atherosclerotic process. The association of adipokines with the macrovascular complications of type 1 diabetes mellitus (DM) needs to be determined. The aim of this study was to measure serum adiponectin, leptin, and resistin levels in type 1 DM patients and investigate their relationship with carotid intima media thickness (CIMT), a clinical marker of atherosclerosis. METHODS: Seventy-five type 1 DM patients and 115 sex and age-matched healthy controls were included in the study. Serum adiponectin, leptin, and resistin levels were measured by the enzyme-linked immunosorbent assay (ELISA method). CIMT was assessed by Doppler ultrasonography. RESULTS: Adiponectin levels in diabetics were higher (25.8±14.8 µg/mL vs. 5.5±7.3 µg/mL; P<0.0001) and leptin levels were lower than controls (9.4±6.2 ng/mL vs. 12.8±8.6 ng/mL; P=0.01). Resistin levels were also higher in the diabetic group compared to controls (2.1±1.4 ng/mL vs. 1.6±0.8 ng/mL; P=0.04). Adiponectin was correlated negatively with CIMT (r=-0.24, P=0.03), age (r=-0.30, P=0.02), BMI (r=-0.33, P=0.02), waist-to-hip ratio (WHR) (r=-0.38, P=0.01) and positively with creatinine (r=0.44, P=0.004). Leptin levels were correlated with total cholesterol (r=0.53, P=0.01) and high-density lipoprotein (HDL) (r=0.67, P=0.001). Resistin was correlated with CIMT (r=0.24, P=0.03) and systolic blood pressure (r=0.48, P=0.009). Multivariate analysis revealed resistin and creatinine to be independent predictors of CIMT among adiponectin, leptin, resistin, WHR, glycosylated hemoglobin (HbA1c), and creatinine. CONCLUSIONS: Increased adiponectin correlates negatively and resistin positively with CIMT in type 1 diabetic patients, but adjusting for other known predictors reveals only resistin to be associated with subclinical atherosclerosis in this group of patients.

Differential effect of elevated blood pressure on left ventricular geometry types in black and white young adults in a community (from the Bogalusa Heart Study).

Hypertension and left ventricular (LV) hypertrophy are both more common in blacks than in whites. The aim of the present study was to test the hypothesis that blood pressure (BP) has a differential effect on the LV geometry types in black versus white asymptomatic young adults. As a part of the Bogalusa Heart Study, echocardiography and cardiovascular risk factor measurements were performed in 780 white and 343 black subjects (aged 24 to 47 years). Four LV geometry types were identified as normal, concentric remodeling, eccentric, and concentric hypertrophy. Compared to the white subjects, the black subjects had a greater prevalence of eccentric (15.7% vs 9.1%, p <0.001) and concentric (9.3% vs 4.1%, p <0.001) hypertrophy. On multivariate logistic regression analyses, adjusting for age, gender, body mass index, lipids, and glucose, the black subjects showed a significantly stronger association of LV concentric hypertrophy with BP (systolic BP, odds ratio [OR] 3.74, p <0.001; diastolic BP, OR 2.86, p <0.001) than whites (systolic BP, OR 1.50, p = 0.037; and diastolic BP, OR 1.35, p = 0.167), with p values for the race difference of 0.007 for systolic BP and 0.026 for diastolic BP. LV eccentric hypertrophy showed similar trends for the race difference in the ORs; however, the association between eccentric hypertrophy and BP was not significant in the white subjects. With respect to LV concentric remodeling, its association with BP was not significant in either blacks or whites. In conclusion, elevated BP levels have a greater detrimental effect on LV hypertrophy patterns in the black versus white young adults. These findings suggest that blacks might be more susceptible than whites to BP-related adverse cardiac remodeling.

C-reactive protein in acute pulmonary embolism.

BACKGROUND: Right ventricular dysfunction and N-terminal proB-type natriuretic peptide (NT-proBNP) are established determinants of prognosis in acute pulmonary embolism (PE). The aim of the study was to investigate the prognostic value of C-reactive protein (CRP) in PE. METHODS: Fifty-six patients (mean age, 64.4 T 14.8years; 22 male subjects) with acute PE were consecutively enrolled and followed for 36 months after discharge. Serum CRP, NT-proBNP, and troponin T levels were determined. Right ventricular function was evaluated by transthoracic echocardiography. RESULTS: Right ventricular dysfunction was present in 31 patients and was more frequent in patients with higher CRP and NT-proBNP levels (P = 0.020 and P = 0.045, respectively). During the 36-month follow-up, there were 15 terminal events (death due to recurrent PE). The mortality rate was 41.2% in patients with NT-proBNP levels greater than 1000 pg/mL, whereas it was 5.9% in patients with less than 500 pg/mL (P = 0.011). Mortality rates also were higher in patients with elevated CRP and troponin T levels, but the differences did not reach clinical significance. The survival rate of acute PE patients with lower NT-proBNP and CRP levels was better than that of patients with higher NT-proBNP and CRP levels. Receiver operating characteristic curve analysis demonstrated cutoff values for NT-proBNP as 1800 pg/mL (sensitivity, 93.3%; specificity, 68.2%; positive predictive values, 66.7%; and negative predictive values, 93.8%) and for CRP as 48 mg/L (sensitivity, 72.7%; specificity, 61.9%; positive predictive values, 50.0%; and negative predictive values, 81.3%) to predict mortality in PE patients. CONCLUSIONS: C-reactive protein is associated with right ventricular dysfunction, which is a predictor of prognosis in PE and may become a promising biomarker for risk stratification of PE, although CRP is not found superior to NT-proBNP.

Adiposity in childhood is related to C-reactive protein and adiponectin in young adulthood: from the Bogalusa Heart Study.

To determine the association between cardiovascular (CV) risk factors in childhood and high-sensitivity C-reactive protein (hsCRP) and adiponectin in adulthood, 835 eligible white and African-American young adult subjects (age range 24-42 years, average 34 years, 43% men, 31% African Americans) who had CV risk-factor variable data from their childhood (20 years earlier, age range 5-18 years, average 14 years) were selected. Stepwise linear regression models revealed that mean logarithmic hsCRP level in adulthood was 0.02 greater with every increase of 1 mm in skinfold thickness in childhood, 0.25 greater for African Americans than whites, 0.36 greater for girls than boys, and 0.15 greater for every unit increase in BMI z score. Mean logarithmic adiponectin level in adulthood was 0.36 greater for girls than boys, 0.22 greater for whites than African Americans, and 0.01 less with every increase of 1 mm of childhood skinfold thickness. Seventy participants (8%) were overweight or obese in their childhood, and 64 of these (91%) remained obese in their young adulthood. In conclusion, childhood adiposity and African-American race were associated with higher hsCRP and lower adiponectin levels in their adulthood. Skinfold thickness and BMI z score in childhood were the main obesity determinants for higher hsCRP and lower adiponectin levels in young adulthood.

Toll-like receptor expression in monocytes in patients with chronic kidney disease and haemodialysis: relation with inflammation.

BACKGROUND: Inflammation is one of the main contributors to atherosclerosis in haemodialysis (HD) patients. Activation of Toll-like receptors (TLRs) leads to inflammatory response. In this study, we aimed to evaluate the expression of TLRs on monocytes and relate their expression with inflammation in chronic kidney disease (CKD) and HD patients. METHODS: Thirty-four age- and gender-matched controls and stage 3-4 CKD patients and thirty-two HD patients were included in each study group. The effect of HD on the expression of Toll-like receptor-2 (TLR-2) and Toll-like receptor-4 (TLR-4) on CD14( +) monocytes was determined at the beginning (baseline), during (120 min) and following (300 min and 24 h) HD and compared with control and stage 3-4 CKD groups. The HD procedure was performed by using low-flux polysulphone dialysers. In addition, serum IL-6 levels were evaluated in both groups at baseline and after a HD session. RESULTS: The percentage of CD14( +) monocytes expressing TLR-2 were similar in all of the study groups, whereas the percentage of CD14( +) monocytes expressing TLR-4 were significantly lower in both stage 3-4 CKD and HD patients at baseline than in controls. The mean fluorescence intensities (MFI) of TLR-2 were significantly lower in controls than in stage 3-4 CKD and HD patients at baseline. The MFI of TLR-4 was similar in all of the groups. The percentage of CD14( +) monocytes expressing TLR-2 did not change during and after HD. The MFI of TLR-2 decreased at 120 min of HD compared with baseline (1837 ± 672 vs 1650 ± 578, P < 0.05), and recovered back to baseline values at 300 min and at 24 h post-HD. MFI of TLR-4 increased at 24 h compared with baseline (941 ± 294 vs 1087 ± 441, P < 0.05). Serum IL-6 levels correlated with MFI of TLR-2 and TLR-4 in stage 3-4 CKD patients and in HD patients at baseline and after HD in univariate analysis. Stepwise multiple regression analysis revealed that MFI of TLR-2 was an independent determinant of serum IL-6 concentrations in stage 3-4 CKD and in HD patients at baseline, at 300 min and at 24 h post-HD. Conclusions. Our study demonstrates that TLR-2 is associated with the inflammatory response of non-dialysed and dialysed CKD patients.

C-reactive protein is an independent predictor for carotid artery intima-media thickness progression in asymptomatic younger adults (from the Bogalusa Heart Study).

BACKGROUND: Conflicting information exists regarding the association between hsCRP and the progression of early stages of atherosclerosis. The purpose of the study was to investigate the association of high sensitiviy c-reactive protein (hsCRP) along with major cardiovascular (CV) risk factors on early carotid atherosclerosis progression in a large, population-based cohort study. METHODS: The study cohort included 839 young adults (aged 24 to 43 years, 70% white, 42% men) enrolled in Bogalusa Heart Study, who in 2001-2002 attended baseline examination with measurements of CV risk factors. Progression of carotid artery intima-media thickness (IMT) was assessed during a mean follow-up of 2.4 years. RESULTS: Carotid artery IMT progression rates were as follows: composite carotid artery = 9.2 ± 52 µm/y, common carotid artery = 0.0 ± 51 µm/y, carotid bulb = 8.8 ± 103 µm/y, and internal carotid artery = 18.9 ± 81 µm/y. Elevated baseline hsCRP, reflecting an inflammatory state, showed independent association with composite carotid artery IMT progression. Increased age, systolic blood pressure, fasting glucose, LDL cholesterol, and current smoking were other risk associates of carotid artery IMT progression in young adults, indicating an underlying burden on the CV system by multiple risk factors. CONCLUSION: In this population-based study, we observed independent categorical association of increased hsCRP with carotid artery IMT progression in young adults. This study underlines the importance of assesssing hsCRP levels along with smoking and traditional CV risk factor profiles in asymptomatic young adults.

Progression of segment-specific carotid artery intima-media thickness in young adults (from the Bogalusa Heart Study).

Carotid intima-media thickness (CIMT) progression is predictive of future cardiovascular events in middle-age and older adults. However, information is scant on segment-specific CIMT progression by race (black vs white) and gender and its predictors during short-term follow-up in asymptomatic young adults. B-mode ultrasound images of the far walls of both carotid arteries were obtained in 842 subjects aged 24 to 43 years and enrolled in the Bogalusa Heart Study (70% whites and 42% men). The CIMT and cardiometabolic risk variables were measured at baseline and after an average of 2.4 years. The mean CIMT progression rates/year adjusted for age, race, and gender were greatest at the bulb, followed by the internal and common carotid segments (p <0.0001). In a multivariate logistic model, age, mean arterial pressure, and high-density lipoprotein cholesterol were significantly associated with common CIMT progression. Smoking, age, insulin resistance index, and mean arterial pressure were significantly associated with bulb CIMT progression; and the waist/height ratio, smoking, age, and mean arterial pressure were significantly associated with internal CIMT progression, independent of the baseline CIMT and traditional cardiometabolic risk variables, including adiponectin, C-reactive protein, and intercellular adhesion molecules. In addition, the status of progression was associated with a greater prevalence of metabolic syndrome (common and internal CIMT, p <0.05; bulb CIMT, p <0.0001) and diabetes (bulb CIMT only, p <0.001). In conclusion, in younger adults, the magnitude of progression of CIMT within a short period varied in a segment-specific manner, regardless of race or gender, and was predictable using modifiable traditional risk factors. This could have implications for preventive and interventional cardiology.

Framingham risk score is associated with femoral artery intima-media thickness in asymptomatic young adults (the Bogalusa heart study).

OBJECTIVE: Femoral artery intima-media thickness (IMT), like carotid IMT, is a surrogate indicator of atherosclerotic coronary and peripheral vascular diseases. The Framingham risk score (FRS) is widely being used in the early prediction of coronary artery disease (CAD). However, the association between FRS and femoral artery IMT has not been studied in asymptomatic younger black and white adult population. Our objective was to examine the association between FRS and femoral artery IMT in asymptomatic younger adults. METHODS: Subjects (n=1080; 71% white, 43% male) aged 24-43 years enrolled in the Bogalusa heart study. Femoral IMT was measured by B-mode ultrasonography. Age, gender, systolic blood pressure, diastolic blood pressure, low density lipoprotein cholesterol, high density lipoprotein cholesterol, cigarette smoking and type2 diabetes were used to calculate individual FRS. RESULTS: FRS was lower in females (p=0.001) than males. Age-adjusted femoral IMT showed gender differences (males>females, p=0.001) among whites only; and no race difference in both genders. A significant positive linear relationship between tertiles of FRS and IMT of femoral artery was noted in whites and blacks alike (p for trend<0.0001). In a multivariate analysis that included FRS, race, body mass index (BMI), log insulin, log triglycerides, exercise and alcohol intake; FRS, insulin and BMI were significantly and independently associated in that order with femoral IMT. CONCLUSIONS: The findings support the use of FRS in both white and black younger adults and underscore the importance of prevention and control of FRS variables in youth.

Relation of serum phosphorus levels to carotid intima-media thickness in asymptomatic young adults (from the Bogalusa Heart Study).

Increased serum phosphorus has been associated with increased mortality from cardiovascular (CV) disease. However, information is scant regarding the influence of serum phosphorus within the normal range on vascular risk in subclinical atherosclerosis in asymptomatic young adults. Serum phosphorus and other CV risk factor variables were measured in 856 white and 354 black subjects without known CV disease or renal disease. Carotid intima-media thickness (IMT) was measured by B-mode ultrasonography. Significant race and gender differences were noted for serum phosphorus (blacks > whites) and carotid IMT (black women > white women; men > women). In bivariate analyses, serum phosphorus was correlated with carotid IMT (p <0.001), and smokers showed higher phosphorus levels than nonsmokers (p = 0.008). In multivariate regression analyses, carotid IMT was significantly associated with serum phosphorus (regression coefficient beta = 0.028, p <0.001) and smoking (beta = 0.032, p <0.001), adjusting for other CV risk factors and estimated glomerular filtration rate. In addition, a significant interaction effect of cigarette smoking and serum phosphorus on carotid IMT was noted, with a greater increasing trend of carotid IMT with phosphorus in smokers than in nonsmokers (p = 0.019 for interaction). In conclusion, serum phosphorus within the normal range is an important correlate of carotid IMT in asymptomatic young adults, with smoking potentiating this adverse association.

Epicardial fat tissue thickness correlates with endothelial dysfunction and other cardiovascular risk factors in patients with metabolic syndrome.

BACKGROUND: Epicardial adipose tissue has shown to be related to cardiovascular risk. The aim of this study is to investigate the relationship between epicardial adiposity and endothelial function in metabolic syndrome. METHODS: Fifty patients with metabolic syndrome were recruited. Anthropometric measurements, fasting blood glucose, insulin, lipid profile, high-sensitivity C-reactive protein (hsCRP), fibrinogen, apolipoprotein A (Apo A), Apo B1, and lipoprotein (a) [Lp(a)] were determined. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Epicardial fat thickness was measured via two-dimensional M-mode echocardiography. Endothelial function was assessed as flow-mediated dilatation at the brachial artery. RESULTS: Epicardial fat tissue thickness was shown to be correlated negatively with FMD and positively with age, diastolic blood pressure, hsCRP, fibrinogen, HOMA-IR, and lipid parameters. Multiple regression analysis showed epicardial fat tissue thickness to be an independent factor influencing the endothelial function. CONCLUSIONS: Epicardial fat tissue may be a useful parameter in the assessment of patients with metabolic syndrome.

Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects.

CONTEXT: Vitamin D receptors are present in many tissues. Hypovitaminosis D is considered to be a risk factor for atherosclerosis. OBJECTIVE: This study explores the effects of vitamin D replacement on insulin sensitivity, endothelial function, inflammation, oxidative stress, and leptin in vitamin D-deficient subjects. DESIGN, SETTING, AND PATIENTS: Twenty-three asymptomatic vitamin D-deficient subjects with 25-hydroxyvitamin D [25(OH)D] levels below 25 nmol/liter were compared with a control group that had a mean 25(OH)D level of 75 nmol/liter. The vitamin D-deficient group received 300,000 IU im monthly for 3 months. The following parameters were evaluated before and after treatment: vitamin D metabolites, leptin, endothelial function by brachial artery flow mediated dilatation (FMD), insulin sensitivity index based on oral glucose tolerance test, and lipid peroxidation as measures of thiobarbituric acid reactive substances (TBARS). RESULTS: FMD measurements were significantly lower in 25(OH)D-deficient subjects than controls (P = 0.001) and improved after replacement therapy (P = 0.002). Posttreatment values of TBARS were significantly lower than pretreatment levels (P < 0.001). A positive correlation between FMD and 25(OH)D (r = 0.45; P = 0.001) and a negative correlation between FMD and TBARS (r = -0.28; P < 0.05) were observed. There was a significant increase in leptin levels after therapy, and the leptin levels were positively correlated with 25(OH)D levels (r = 0.45; P < 0.05). CONCLUSIONS: This study shows that 25(OH)D deficiency is associated with endothelial dysfunction and increased lipid peroxidation. Replacement of vitamin D has favorable effects on endothelial function. Vitamin D deficiency can be seen as an independent risk factor of atherosclerosis. Hypovitaminosis D-associated endothelial dysfunction may predispose to higher rates of cardiovascular disease in the winter.