Diagnostic utility of MR-proANP and NT-proBNP in elderly outpatients with a high risk of heart failure: the Copenhagen heart failure risk study

Abstract

Background: Amino-terminal-pro-B-type-natriuretic-peptide (NT-proBNP) is a diagnostic biomarker for heart failure (HF), but plasma concentrations are influenced by numerous factors. Mid-regional-pro-atrial-natriuretic-peptide (MR-proANP) have comparable diagnostic value in acute HF. However, data are lacking in the non-acute setting. This study sought to assess the diagnostic utility of MR-proANP in outpatients with a high risk of HF.

Methods: This prospective study included 399 outpatients. Inclusion criteria were: age?≥?60?years, ≥1 risk factor for HF (diabetes, chronic kidney disease, vascular disease, atrial fibrillation, hypertension), without known or suspected HF. Unrecognized HF was diagnosed based on clinical signs, patient-reported symptoms and echocardiography. Plasma concentrations of MR-proANP and NT-proBNP were analysed.

Results: In total, 65 patients were diagnosed with HF or asymptomatic left ventricular systolic dysfunction (N?=?12 LVEF?≤?40%, N?=?7 LVEF?>?40% to ≤50%, N?=?46 LVEF?>?50%). Both MR-proANP (odds-ratio: 1.77; 95% CI:1.16–2.72; p?=?0.009) and NT-proBNP (odds-ratio: 1.49; 95% CI:1.22–1.82; p?<?0.001) were associated with HF. Area under receiver-operator characteristics curve (AUC) for the diagnosis of HF or asymptomatic left ventricular systolic dysfunction was higher for MR-proANP (AUC?=?0.886; p?<?0.001) and NT-proBNP (AUC?=?0.910; p?<?0.001) compared to patient-reported symptoms of HF (AUC?=?0.830), but NT-proBNP added more diagnostic information compared to MR-proANP (p?=?0.022).

Conclusions: Both NT-proBNP and MR-proANP are useful biomarkers in the diagnosis of HF or asymptomatic left ventricular systolic dysfunction in a non-acute setting. However, NT-proBNP added more diagnostic information compared to MR-proANP.     

SPARCL1 as a biomarker of maladaptive right ventricular remodelling in pulmonary hypertension

Abstract

Aim: This study assessed the utility of SPARC-like protein 1 (SPARCL1) as a biomarker of maladaptive right ventricular (RV) function in patients with pulmonary hypertension (PH).

Methods: In this prospective study, we examined SPARCL1 levels in 105 patients with adaptive (n?=?34) and maladaptive RV (n?=?32) pressure overload caused by PH, dilated cardiomyopathy (DCM, n?=?18) with LVEF < 35% and preserved RV function and controls without LV or RV abnormalities (n?=?21).

Results: The median SPARCL1 concentration in patients with maladaptive RV function was higher than in those with adaptive RV function (p?<?0.01), DCM (p?<?0.001) or controls (p?<?0.001). Patients with adaptive RV function had higher SPARCL1 concentrations than controls (p?<?0.05), whereas there was no difference between adaptive RV and DCM. SPARCL1 showed good predictive power for maladaptive RV (AUC 0.77, p?<?0.001) with an optimal cut-off value of 9.66?ng/ml. The TAPSE/PASP ratio was the only independent predictor of SPARCL1?≥?9.66?ng/ml in multivariable logistic regression analysis.

Conclusion: SPARCL1 shows potential as novel biomarker of RV pathological remodelling and is associated with RV maladaptation and ventriculoarterial uncoupling in PH.     

Maternal association and influence of DHFR 19 bp deletion variant predisposes foetus to anencephaly susceptibility: a family-based triad study

Abstract

Objective: Previous studies have not used family-based methods to evaluate maternal-paternal genetic effects of the folate metabolizing enzyme, dihydro folate reductase (DHFR) essential during embryogenesis. Present study focuses on evaluating the association and influence of parental genetic effects of DHFR 19?bp deletion in the development of foetal neural tube defects (NTDs) using family-based triad approach.

Materials and methods: The study population (n?=?924) including 124 NTD case-parent trios (n?=?124?×?3?=?372) and 184 healthy control-parent trios (n?=?184?×?3?=?552) from Telangana, India, was genotyped for DHFR 19?bp deletion. Statistical analysis was used by SPSS and parent-of-origin effects (POE).

Results: Foetuses with deletion genotype (DD) were at risk of developing anencephaly (OR =?3.26, p?=?0.020). Among parents, increased maternal risk of having an anencephaly foetus (OR =?2.66, p?=?0.028) was observed in mothers with DD genotype. In addition, POE analysis also demonstrated higher risk of maternal transmission of the deletion allele to anencephaly foetus compared with paternal transmission (OR =?6.00, p?=?0.016). Interestingly, maternal-paternal-offspring genotype incompatibility revealed maternal deletion genotype (DD) in association with paternal heterozygous deletion genotype (WD) significantly increased risk for NTDs (OR =?5.29, p?=?0.013).

Conclusions: This study, using family-based case-parent and control-parent triad approach, is the first to report influence of maternal transmission of DHFR 19?bp deletion in the development of anencephaly in the foetus.     

Potential CD34 signaling through phosphorylated-BAD in chemotherapy-resistant acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) constitutively express growth factors and cytokines for survival. Chemotherapy alters these signals to induce cell death. However, drug resistance in AML remains a major hindrance to successful treatment and early warning is unavailable. Modulation of signaling pathways during chemotherapy may provide a window to detect response and predict treatment outcome. Blood samples collected from AML patients before and at day-3 of induction therapy were compared for changes in expression of CD117, CD34, pro-inflammatory cytokines and mediators of Akt and MAPK pathways, using multi-color flow cytometry. Nine patients were diagnosed as drug-resistant and seven sensitive to chemotherapy. Twelve were paired. Average percentages of CD34 (66.8?±?11.7% vs. 26.2?±?5.8%, p?=?0.033) and pBAD (66.9?±?8.2% vs. 28.9?±?8.2%, p?=?0.016) were significantly increased in chemo-resistant (N?=?9) compared to chemo-sensitive (N?=?5) samples. Percentages of CD34 were strongly correlated with pBAD (R?=?0.785; p?=?0.001; N?=?14) and pFKHR (R?=?0.755; p?=?0.002; N?=?14) at day-3 induction. Chemo-sensitive cases expressed significantly higher percentages of IL-18Rα (71.9?±?9.6% vs. 29.8?±?5.8%, p?=?0.016). Though not significantly different in the outcome, IL-1β was strongly associated with activated Akt-S473, IL-6 with phosphorylated JNK and FKHR while TNF-α appeared to trigger Bim, in treated samples. These preliminary results suggested AML cells resistant to chemotherapy increased expression of CD34 and may signal through pBAD while cells sensitive to chemotherapy-induced IL18Rα expression. These were observed early during induction therapy. Identifying CD34 is interesting as it is a convenient marker to monitor drug-resistance in AML patients. Inhibition of CD34 and pBAD signaling may be important in treating drug-resistant AML.     

Angiotensin-converting enzyme and metals in untreated essential hypertension

Hpertension is an important health problem throughout the world and a risk factor for many diseases. Angiotensin-converting enzyme (ACE), a component of the renin-angiotensin system, has an important role in the regulation of blood pressure. Zinc (Zn), a trace element with important biological functions, is located in the catalytic site of ACE. Calcium (Ca), magnesium (Mg), sodium (Na), and potassium (K) also appear to be involved in hypertension pathogenesis. In this study, plasma ACE activities and Ca_t, Ca_i, Mg, Na, K, and plasma/erythrocyte Zn levels of 20 untreated patients with essential hypertension and 28 helthy individuals were evaluated. Plasma ACE activities (p<0.05) and erythrocyte Zn concentrations (p<0.001) were significantly higher in patients with essential hypertension than values of the control group. No significant difference was found between plasma Zn concentrations of the groups (p>0.05). Plasma Ca_t (p<0.001) and Mg levels (p<0.05) in essential hypertension were significantly lower than those of controls. Plasma Na, K, and Ca_i levels remained normal in essential hypertension. There are complex associations between metals and arterial pressure. Ca and Mg deficiencies seem to be associated with increased prevalence of hypertension. Increases in erythrocyte Zn may have a future potential use for diagnosis of hypertension.     

Nutritional status and eating habits of bus drivers during the day and night

The aim of this study was to compare anthropometry and food intake patterns in bus drivers working during the day and night. One hundred and fifty males (81 night workers and 69 day workers) participated in the study. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. Measurements of height, weight, waist circumference (WC), systolic and diastolic blood pressure, blood glucose, and lipid profile were obtained. A significant difference between groups was observed for mean WC (98.5?±?10.7?cm in day workers versus 103.2?±?9.7?cm in night workers; p?=?0.005). Night workers had higher prevalence of being overweight and obese (BMI?≥?25?kg/m²) than day workers (78.2% day workers versus 90.2% night workers; p?=?0.004) and increased WC (>94?cm) (72.4% day workers versus 86.4% night workers; p?=?0.03). Significant differences were found for meat consumption (2.3 servings ±0.9 for night workers versus 2.0 servings ±0.7 day workers, p?=?0.04) and fruit intake (0.9 servings ±0.4 for night workers versus 0.7 servings for day workers ±0.5; p?=?0.006). Night workers had a lower intake of vegetables than recommended compared to day workers (100 versus 92.7%, respectively, p?=?0.01) and higher intake of oil (40.7 versus 24.6%, p?=?0.03). Multivariate logistic regression analysis indicated that night work was associated with being overweight (OR?=?2.94, 95% IC: 1.14–7.66, p?=?0.03) and abnormal values of WC (OR?=?2.82, 95% IC: 1.20–6.69, p?=?0.009) after adjusting for potential confounders. It is concluded that night workers had a higher prevalence and risk of being overweight/obese and increased WC compared with day workers. Night workers also presented a higher proportion of inappropriate intakes of food groups when compared to day workers, even though both groups were eating poor diets. These results demonstrate the need of lifestyle-intervention programs in these workers.     

Association between gestational diabetes and biomarkers: a role in diagnosis

Background: We investigated the association between markers of insulin resistance, chronic inflammation, and adipokines and GDM.

Methods: In our case-cohort study in Johannesburg we included women with GDM and controls. We tested the ability of biomarkers to identify women at high risk of GDM.

Results: Of the 262 pregnant women, 83 (31.7%) had GDM. Women with GDM were heavier (p?=?0.04) and had more clinical risk factors (p?=?0.008). We found a significant difference in fasting insulin (p?p?=?0.046), HOMA (p?p?Conclusions: Insulin sensitivity markers are promising tools to identify women at high risk of GDM.     

Blood Metals Concentration in Type 1 and Type 2 Diabetics

Mechanisms for the onset of diabetes and the development of diabetic complications remain under extensive investigations. One of these mechanisms is abnormal homeostasis of metals, as either deficiency or excess of metals, can contribute to certain diabetic outcomes. Therefore, this paper will report the blood levels of chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), mercury (Hg), nickel (Ni), lead (Pb), selenium (Se), and zinc (Zn) in subjects with type 1 diabetes (n?=?192, mean age 48.8 years, mean disease duration 20.6 years), type 2 diabetes (n?=?68, mean age 68.4 years, mean disease duration 10.2 years), and in control subjects (n?=?59, mean age 57.2 years), and discuss the results indicating their possible role in diabetes. The metal concentrations were measured by sector field inductively coupled plasma mass spectrometry after microwave-induced acid digestion of blood samples. The accuracy was checked using a blood-based certified reference material, and recoveries of all elements were in the range of 92–101 % of certified values. Type 1 diabetes was found to be associated with Cr (p?=?0.02), Mn (p?<?0.001), Ni (p?<?0.001), Pb (p?=?0.02), and Zn (p?<?0.001) deficiency, and type 2 diabetes with Cr (p?=?0.014), Mn (p?<?0.001), and Ni (p?<?0.001) deficiency. These deficiencies were appreciated also subdividing the understudied patients for gender and age groups. Furthermore, in type 1 diabetes, there was a positive correlation between Pb and age (p?<?0.001, ρ?=?0.400) and Pb and BMI (p?<?0.001, ρ?=?0.309), while a negative correlation between Fe and age (p?=?0.002, ρ?=??0.218). In type 2 diabetes, there was a negative correlation between Fe and age (p?=?0.017, ρ?=??0.294) and Fe and BMI (p?=?0.026, ρ?=??0.301). Thus, these elements may play a role in both forms of diabetes and combined mineral supplementations could have beneficial effects.     

Circulating biomarkers of hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy assessed by cardiac magnetic resonance

Abstract

Background: Myocardial fibrosis in hypertrophic cardiomyopathy (HCM) is associated with worse clinical outcomes. The availability of circulating biomarkers of myocardial fibrosis and hypertrophy would be helpful in clinical practice.

Objective: The aim of this study was to evaluate usefulness of various biomarkers of myocardial fibrosis and hypertrophy in HCM.

Methods: Levels of biomarkers: soluble ST2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15), NT-proBNP and high-sensitivity cardiac troponin T (hs-cTnT) were measured in 60 patients with HCM. All patients underwent cardiac magnetic resonance imaging to calculate parameters of hypertrophy and fibrosis.

Results: We observed positive correlations among sST2 levels and left ventricular mass (LVM) (r?=?0.32, p?=?0.012), LV mass indexed for the body surface area (LVMI) (r?=?0.27, p?=?0.036) and maximal wall thickness (MWT) (r?=?0.31, p?=?0.015). No correlation was found between Gal-3 and GDF-15 levels and hypertrophy and fibrosis parameters. We observed positive correlations among hs-cTnT levels and LVM (r?=?0.58, p?<?0.0001), LVMI (r?=?0.48, p?=?0.0001), MWT (r?=?0.31, p?=?0.015) and late gadolinium enhancement (LGE) mass (r?=?0.37, p?=?0.003). There were positive correlations between NT-proBNP levels and LVM (r?=?0.33, p?=?0.01), LVMI (r?=?0.41, p?=?0.001), MWT (r?=?0.42, p?<?0.001) and LGE mass (r?=?0.44, p?<?0.001).

Conclusions: Although no correlation between sST2 levels and myocardial fibrosis was found, sST2 may provide some additional information about hypertrophy extension. NT-proBNP and hs-cTnT are useful biomarkers in assessment of hypertrophy and fibrosis in HCM.     

Stability and Fragmentation of the Activity Rhythm Across the Sleep-Wake Cycle: The Importance of Age,Lifestyle, and Mental Health

The rhythms of activity across the 24-h sleep-wake cycle, determined in part by the circadian clock, change with aging. Few large-scale studies measured the activity rhythm objectively in the general population. The present population-based study in middle-aged and elderly persons evaluated how activity rhythms change with age, and additionally investigated sociodemographics, mental health, lifestyle, and sleep characteristics as determinants of rhythms of activity. Activity rhythms were measured objectively with actigraphy. Recordings of at least 96?h (138?±?14?h, mean?±?SD) were collected from 1734 people (age: 62?±?9.4?yrs) participating in the Rotterdam Study. Activity rhythms were quantified by calculating interdaily stability, i.e., the stability of the rhythm over days, and intradaily variability, i.e., the fragmentation of the rhythm relative to its 24-h amplitude. We assessed age, gender, presence of a partner, employment, cognitive functioning, depressive symptoms, body mass index (BMI), coffee use, alcohol use, and smoking as determinants. The results indicate that older age is associated with a more stable 24-h activity profile (β?=?0.07, p?=?0.02), but also with a more fragmented distribution of periods of activity and inactivity (β?=?0.20, p?<?0.001). Having more depressive symptoms was related to less stable (β?=??0.07, p?=?0.005) and more fragmented (β?=?0.10, p?<?0.001) rhythms. A high BMI and smoking were also associated with less stable rhythms (BMI: β?=??0.11, p?<?0.001; smoking: β?=??0.11, p?<?0.001) and more fragmented rhythms (BMI: β?=?0.09, p?<?0.001; smoking: β?=?0.11, p?<?0.001). We conclude that with older age the 24-h activity rhythm becomes more rigid, whereas the ability to maintain either an active or inactive state for a longer period of time is compromised. Both characteristics appear to be important for major health issues in old age.     

Irregular 24-hour activity rhythms and the metabolic syndrome in older adults

Circadian rhythms – near 24?h intrinsic biological rhythms – modulate many aspects of human physiology and hence disruption of circadian rhythms may have an important impact on human health. Experimental work supports a potential link between irregular circadian rhythms and several key risk factors for cardiovascular disease including hypertension, obesity, diabetes and dyslipidemia, collectively termed the metabolic syndrome. While several epidemiological studies have demonstrated an association between shift-work and the components of the metabolic syndrome in working-age adults, there is a relative paucity of data concerning the impact of non-occupational circadian irregularity in older women and men. To address this question, we studied 7 days of actigraphic data from 1137 older woman and men participating in the Rush Memory and Aging Project, a community-based cohort study of the chronic conditions of aging. The regularity of activity rhythms was quantified using the nonparametric interdaily stability metric, and was related to the metabolic syndrome and its components obesity, hypertension, diabetes and dyslipidemia. More regular activity rhythms were associated with a lower odds of having the metabolic syndrome (OR?=?0.69, 95% CI?=?0.60–0.80, p?=?5.8?×?10^?7), being obese (OR?=?0.73, 95% CI?=?0.63–0.85, p?=?2.5?×?10^?5), diabetic (OR?=?0.76, 95% CI?=?0.65–0.90, p?=?9.3?×?10^?4), hypertensive (OR?=?0.78, 95% CI?=?0.66–0.91, p?=?2.0?×?10^?3) or dyslipidemic (OR?=?0.82, 95% CI?=?0.72–0.92, p?=?1.2?×?10^?3). These associations were independent of differences in objectively measured total daily physical activity or rest, and were not accounted for by prevalent coronary artery disease, stroke or peripheral artery disease. Moreover, more regular activity rhythms were associated with lower odds of having cardiovascular disease (OR?=?0.83; 95% CI?=?0.73–0.95, p?=?5.7?×?10^?3), an effect that was statistically mediated by the metabolic syndrome. We conclude that irregular activity rhythms are associated with several key components of the metabolic syndrome in older community-dwelling adults, and that the metabolic syndrome statistically partially mediates the association between activity rhythms and prevalent cardiovascular disease. Although additional longitudinal and experimental studies are needed to conclusively delineate the causal relationships underlying these associations, these findings are consistent with preclinical data, and add further support for investigations of the irregularity of activity rhythms as a potential therapeutic target to decrease the burden of cardiovascular disease in older adults.     

Association between circulating irisin levels and epicardial fat in patients with treatment-naïve overt hyperthyroidism

Abstract

Background: Hyperthyroidism is associated with increased metabolic activity and thermogenesis. Irisin is a key molecule in thermogenesis and energy expenditure via adipose tissue browning. Epicardial fat was previously defined as brown-like fat. Thus, here we aimed to evaluate the association between serum irisin level and epicardial fat thickness (EFT) in patients with hyperthyroidism.

Methods: A total of 25 hyperthyroid patients and 24 age-, sex- and BMI-matched healthy controls were enrolled. Serum irisin levels, thyroid hormone levels, and body compositions were compared. EFT was measured via transthoracic echocardiography.

Results: Serum irisin level and EFT were significantly higher in the hyperthyroid group (p?<?0.001 and p?=?0.001, respectively). The distributions of fat-free mass, muscle mass and fat mass were similar between the study groups. Serum irisin level was negatively correlated with TSH (p?<?0.001) and positively correlated with fT3 (p?<?0.001), fT4 (p?<?0.001) and TSH receptor antibody (p?=?0.002) levels and EFT (p?=?0.001). In multivariate linear regression analysis, TSH (β?=??0.475, p?<?0.001) and EFT (β?=?0.290, p?=?0.023) levels were significantly associated with serum irisin levels.

Conclusions: An increased serum irisin level associated with EFT might contribute to metabolic derangement in hyperthyroidism. Further studies are needed to elucidate whether irisin levels and EFT are affected by hyperthyroidism or vice versa.     

Association between polymorphisms in AXIN1 gene and atrial septal defect

Abstract

Context: AXIN1 is a central component of Wnt signalling pathway which is essential for embryonic development.

Objective: To investigate whether polymorphisms of AXIN1 contribute to ASD susceptibility.

Materials and methods: Three tag SNPs (rs12921862, rs370681 and rs1805105) in AXIN1 were genotyped in 208 ASD patients and 302 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a Chinese population.

Results: Significantly increased ASD risk was observed to be associated with the A allele of rs12921862 (p?<?0.0001, OR?=?3.096, 95% CI?=?2.037–4.717). Increased ASD risk was observed to be associated with rs370681 in a codominant (p?=?0.043, OR?=?1.52, 95% CI?=?1.04–2.22) and overdominant model (p?=?0.016, OR?=?1.57, 95% CI?=?1.08–2.27).

Conclusion: rs12921862 and rs370681 may contribute to ASD susceptibility.     

Plasma Leptin and Blood Pressure in Men: Graded Association Independent of Body Mass and Fat Pattern

Objective: The role of leptin in the association between body mass, central adiposity, and blood pressure (BP) is controversial. This study evaluated the relationship between leptin and BP in relation to body mass index (BMI) and fat distribution in a large sample of untreated male adults. Research Methods and Procedures: The study population was made up of 457 untreated male employees of the Olivetti factory in Naples. Plasma leptin, complete anthropometry, BP, and relevant biochemical variables were measured. Results: Log‐transformed plasma leptin levels were directly associated with BMI (r = 0.661, p < 0.001) and waist circumference (r = 0.630; p < 0.001). Leptin also correlated with systolic (r = 0.258) and diastolic (r = 0.277) BP (p < 0.001). The association between leptin and BP was maintained after accounting for age, BMI (or waist circumference), log‐insulin, and serum creatinine (p < 0.01); this association was stronger than that with BMI. Logistic regression analysis showed that an increased prevalence of hypertension (BP ≥ 140 and/or 90 mm Hg) was associated with high plasma leptin levels when controlling for age and waist circumference (odds ratio, 1.99; 95%CI, 1.06 to 3.72) or for age and BMI (odds ratio, 1.92; 95%CI, 1.02 to 3.61). Discussion: A graded positive relationship between plasma leptin levels and BP was observed in this sample of untreated male adults. This association was independent of age, BMI, abdominal adiposity, and fasting plasma insulin. Moreover, elevated plasma leptin concentrations were associated with greater probability of hypertension, again independently of potential confounders.     

Biomarker-specific differences between transpulmonary and peripheral arterial–venous blood sampling in patients with pulmonary hypertension

Abstract

Purpose: Transpulmonary biomarkers may provide insight into pulmonary hypertension (PH) pathophysiology, but require cardiac catheterization. We investigated whether the peripheral arterial–venous ratio (PR) could substitute for the transpulmonary ratio (TPR).

Materials and methods: Blood from the pulmonary artery (PA), pulmonary arterial wedge (PAW), peripheral venous, and peripheral arterial positions was analysed for ET-1, NT-pro-BNP and cAMP levels in subjects with no PH (n?=?18) and PH due to left heart disease (PH-LHD), which included combined pre- and post-capillary PH (Cpc-PH; n?=?7) and isolated post-capillary PH (Ipc-PH; n?=?9). Bland–Altman comparisons were made between peripheral venous and PA samples and between peripheral arterial and PAW samples. TPR was defined as [PAW]/[PA].

Results: For ET-1, Bland–Altman analysis indicated negative bias (?24%) in peripheral arterial compared to PAW concentration and positive bias (23%) in peripheral venous compared to PA concentration. There was <10% absolute bias for NT-pro-BNP and cAMP. For ET-1, there was no difference in PR between Cpc-PH and Ipc-PH (0.87?±?0.4 vs. 0.94?±?0.6, p?=?0.8), whereas there was a difference in TPR (2.2?±?1.1 vs. 1.1?±?0.2, p?<?0.05).

Conclusions: In PH-LHD, peripheral samples may be inadequate surrogates for transpulmonary samples, particularly when measuring mediators with prominent pulmonary secretion or clearance, such as ET-1.     

The Association of IL-6, TNFα and CRP Gene Polymorphisms with Coronary Artery Disease in a Tunisian Population: A Case–Control study

Coronary artery disease is an inflammatory disease. Systemic markers of inflammation such as Interleukin-6, Tumor Necrosis Factor alpha and C-reactive protein have previously been shown to be associated with increased risk of cardiovascular events. The aim of the present study is to assess the role of variants in the IL-6 (??174 G/C), TNFα (??308 A/G) and CRP (+?1059G/C) genes as susceptibility markers for CAD in a Tunisian population. The investigation was conducted as a case–control study involving 204 patients and 400 age-gender matched controls. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism analysis. There are significant differences between CAD patients and the control group with regard to BMI (p?<?10^–3) and family history of CAD (p?<?10^–3). The CAD patients are more likely to have a history of smoking (p?<?10^–3), have a higher value of TC (p?=?0.003), LDLc (p?=?0.016), hs-CRP (p?=?0.01), IL6 (p?<?10^–3) and TNFα (p?=?0.038). Our analysis showed significant differences between cases and controls in genotypic distribution of IL6-174CC (p?=?0.003; OR?=?7.71 CI (1.58–37.56)), TNFα ??308 AA (p?=?0.004; OR?=?2.95 (1.57–5.51)) and CRP?+?1059 CC (p?<?10^–3; OR?=?5.40 (2.30–12.68)). However, we failed to find an association between the different genotypes and the inflammatory markers levels. Our results suggest that the presence of IL-6 (??174 G/C), TNFα (-308 A/G) and CRP (+?1059G/C) polymorphisms, may be considered to be a risk factor for CAD in Tunisian population.

     

A novel noninvasive index for nonalcoholic steatohepatitis: a pilot study

Abstract

Objective: The potential development of a noninvasive marker predicting nonalcoholic steatohepatitis (NASH).

Methods: Thirty patients with biopsy-proven nonalcoholic fatty liver disease were evaluated by numerous anthropometric, clinical and biochemical parameters.

Results: Serum glutamic oxaloacetic transaminase (SGOT; p?=?0.027), log (erythrocyte sedimentation rate) (ESR; p?=?0.034) and homocysteine (p?=?0.041) were associated with NASH independently from gender, age and body mass index. When combined, the regression model provided R²?=?0.563 (p?=?0.001) and area under the ROC curve?=?0.873?±?0.066 (p?<?0.001).

Conclusion: This noninvasive marker, named HSENSI (acronym of homocysteine, SGOT, ESR, Nonalcoholic Steatohepatitis Index), consists of three low cost, easily measurable parameters and may accurately predict NASH.     

Plasma levels of S100A4 in portopulmonary hypertension

We previously showed that a single nucleotide polymorphism in S100A4 was associated with portopulmonary hypertension (PPHTN) in patients with advanced liver disease. We aimed to determine the association between plasma levels of S100A4 and PPHTN. We performed a case–control study of patients with advanced liver disease. Cases with PPHTN had mean pulmonary artery pressure >25?mmHg, pulmonary vascular resistance >240 dynes s?cm^?5 and pulmonary capillary wedge pressure ≤15?mmHg. Controls with liver disease had right ventricular systolic pressure <40?mmHg and normal right atrial and ventricular morphology by echocardiography. Plasma samples were assayed for S100A4. The study sample included 14 cases with PPHTN and 32 controls with liver disease. There was no difference in mean age between cases and controls (p = 0.52). Seventy-nine percent of cases were female compared with 44% of controls (p?=?0.03). There was no difference in S100A4 levels between cases and controls (p?=?0.58). Both groups had significantly higher S100A4 levels than healthy volunteers (p?<0.05). There was no significant difference in plasma levels of S100A4 between PPHTN patients and controls with liver disease, although liver disease itself was associated with increased S100A4 levels.     

Association of Increased Hair Calcium Levels and Enhanced Augmentation Index (AIx): a Marker of Arterial Stiffness

Arterial stiffness is involved in the pathophysiology of cardiovascular disease, and the degree of arterial stiffness is associated with the extent of vascular calcification. This study aimed to investigate the association of hair calcium levels with augmentation index (AIx), a simple, non-invasive measurement for arterial stiffness. Healthy Koreans (male, n?=?34, female, n?=?70) were enrolled in this study. Anthropometric parameters, lipid profiles, fasting glucose, hair mineral levels, and AIx were measured. Pearson/partial correlations and multivariate linear regression analyses were used to assess the relationship between hair calcium levels and AIx. AIx positively correlated with hair calcium levels (r?=?0.275, p?=?0.005), age (r?=?0.283, p?=?0.004), systolic blood pressure (r?=?0.282, p?=?0.004), low-density lipoprotein (LDL)-cholesterol (r?=?0.255, p?=?0.009), and hair magnesium (r?=?0.196, p?=?0.046), and negatively correlated with heart rate (r?=?-0.563, p?<?0.001) and fasting glucose (r?=?-0.262, p?=?0.005). Hair calcium levels significantly correlated with hair magnesium (r?=?0.926, p?<?0.001). Significant relationship between AIx and hair calcium levels was maintained after adjustment for sex, age, height, hear rate, blood pressure, total cholesterol, LDL-cholesterol, fasting glucose, and hair magnesium (r?=?0.244, p?=?0.018). Logistic regression model showed that AIx increased with the increment of hair calcium levels; log-AIx increased by 0.403% (95% CI: 0.139–0.515, p?=?0.001) per unit change in log-hair calcium level (sex-adjusted). After adjustment for all the variables above together with triglyceride and high-density lipoprotein-cholesterol, increased significance of the association was 0.513% (p?=?0.016)]. This study supports the presence of the independent positive relationship between hair calcium levels and AIx. It suggests the possibility that hair calcium levels may be a useful index for reflecting arterial stiffness.     

The severity of chewing disorders is related to gross motor function and trunk control in children with cerebral palsy

Abstract

Purpose: The frequency of chewing disorders increases with decreasing level of gross motor function in children with cerebral palsy (CP). Besides its frequency, the severity of chewing disorders is also important. The aim of this study was to determine the relationship between chewing performance level and gross motor function, and trunk postural control in children with CP.

Materials and methods: The study included 119 children with CP (age 2–10 years). Chewing performance level was determined by the Karaduman Chewing Performance Scale (KCPS). The Gross Motor Function Classification System (GMFCS) was used to determine the level of gross motor function. Segmental Assessment of Trunk Control (SATCo) was used to measure trunk control.

Results: Children with spastic CP with a median age of 4?years were evaluated, of which 50.4% were male. The percentages of patients classified to GMFCS levels I to V were 43.7%, 6.7%, 9.2%, 5.0%, and 35.3%, respectively. The median KCPS score was 3 (min?=?0, max?=?4). A good correlation was found between KCPS and GMFCS (p?<?.001, r?=?0.70). Negative, excellent correlations between KCPS and SATCo static, SATCo active, and SATCo reactive postural controls were found (p?<?.001, r?=?–0.75, r?=?–0.77, r?=?–0.79; respectively).

Conclusions: The severity of chewing disorders is related to the level of gross motor function and trunk postural control in children with CP.

Clinical trial number: NCT03241160