The Functional Polymorphism of DDAH2 rs9267551 Is an Independent Determinant of Arterial Stiffness

Background: The association of circulating asymmetric dimethylarginine (ADMA) levels with cardiovascular risk and arterial stiffness has been reportedly demonstrated, although the causal involvement of ADMA in the pathogenesis of these conditions is still debated. Dimethylaminohydrolase 2 (DDAH2) is the enzyme responsible for ADMA hydrolysis in the vasculature, and carriers of the polymorphism rs9267551 C in the 5′-UTR of DDAH2 have been reported to have higher DDAH2 expression and reduced levels of serum ADMA.Approach and Results: We genotyped rs9267551 in 633 adults of European ancestry and measured their carotid–femoral pulse wave velocity (cfPWV), the gold-standard method to estimate arterial stiffness. cfPWV resulted significantly lower in rs9267551 C allele carriers (Δ = −1.12 m/s, P < 0.01) after correction for age, sex and BMI, and a univariate regression showed that the presence of rs9267551 C variant was negatively associated with cfPWV (β = −0.110, P < 0.01). In a multivariable regression model, subjects carrying the rs9267551 C allele manifested significantly lower cfPWV than GG carriers (β = −0.098, P = 0.01) independently from several potential confounders. We measured circulating ADMA levels in a subset of 344 subjects. A mediation analysis revealed that the effect of DDAH2 rs9267551 genotype on cfPWV was mediated by the variation in ADMA levels.Conclusions: These evidences hint that the presence of rs9267551 C allele may explain, at least in part, a reduction in vessel rigidity as measured by cfPWV, and support the attribution of a causative role to ADMA in the pathogenesis of arterial stiffness.

Peripheral vascular involvement in transthyretin cardiac amyloidosis. A comparative analysis with AL amyloidosis

Background The pattern of peripheral vascular involvement in the wild type transthyretin-related cardiac amyloidosis (ATTRwt) and its diagnostic utility in differentiating this infiltrating cardiomyopathy from light chain (AL) cardiac amyloidosis (AL-CA) and heart failure with preserved ejection fraction (HFpEF) of different origin have not been explored. Aims To characterize the pattern of peripheral vascular involvement in ATTRwt and evaluate its value in differentiating ATTRwt from AL-CA and HFpEF. Methods Newly diagnosed patients with ATTRwt (n=42) were consecutively recruited from our amyloidosis center. These patients were matched 1:1 for age and sex to patients with AL-CA (n=32) and subjects without amyloidosis (n=32) and also matched 2:1 to HFpEF patients (n=16). All subjects underwent a series of non-invasive vascular examinations for the assessment of: 1. subclinical carotid atherosclerosis with B-mode ultrasonography, 2. Arterial stiffness with measurement of carotid-femoral pulse wave velocity, 3. Reactive vasodilation with flow-mediated dilation (FMD) and 4. Aortic blood pressures and arterial wave reflections with augmentation index (AI) and return time of reflected wave (Tr). Results ATTRwt patients had lower peripheral (pBP) and aortic blood pressure (aBP) markers compared to non-AL controls (p<0.05 for all). ATTRwt grouping was an independent determinant of these markers, after adjustment for cardiovascular risk factors (CVRF), including history of hypertension, hyperlipidemia and diabetes, glomerular filtration rate, body mass index and smoking status (core model). ATTRwt had lower aDBP and increased Tr compared to AL subjects. In a comparison between ATTRwt and AL patients with cardiac involvement, AI and Tr were higher and FMD lower in ATTRwt patients. ATTRwt was an independent determinant of these markers, after adjustment for the core model (p<0.05 for all). Compared to HFpEF, patients with ATTRwt had lower peripheral and central BP and higher Tr (p<0.05 for all). By ROC analysis, Tr provided high diagnostic value for ATTRwt vs. AL-CA (Area Under the Curve, AUC=0.809, CI: 0.65–0.96) and for ATTRwt vs combined AL-CA and HFpEF (AUC=0.880, CI: 0.79–0.97). Finally, AI was closely correlated with posterior (Spearman's Rho=−0.30) and intraventricular wall thickness (Rho=−0.329) and left ventricular global longitudinal strain (Rho=−0.4) and lower cDBP with higher Gilmore and New York Heart Association stage (p<0.05). Conclusion ATTRwt patients present differential characteristics of peripheral vascular function and aortic hemodynamics as compared to AL, HFpEF and healthy controls. The clinical value of these characteristics merit further investigation since differential diagnosis among amyloidosis types is clinically challenging, while it may have prognostic implications. FUNDunding Acknowledgement Type of funding sources: None.

Can Neutrophil-To-Lymphocyte Ratio (Nlr) be a simple predictive marker for differentiating gastric intestinal metaplasia and gastric atrophy from non-atrophic non-metaplastic chronic gastritis?

Background: Gastric İntestinal Metaplasia (GIM) and Gastric Atrophy (GA) are pre-neoplastic lesions that can lead to gastric cancer. Nowadays, there are no recognized good biomarkers of GIM and GA. The neutrophil-to-lymphocyte ratio (NLR) is an economical, effective, and repetitive indicator of inflammation. We aimed to comparatively evaluate Red Cell Distribution Width (RDW) and the NLR. Methods: 88 patients with GIM and 48 patients with GA and 64 patients with non-atrophic-non-metaplastic gastritis were included in the study. NLR and RDW levels were measured in patients and controls. Results: NLR levels were significantly higher in patients with GIM than in controls (p < 0.05). NLR level was correlated positively with presence of GIM (p < 0.05), H.pylori presence in GIM and GA (p < 0.05), and menopause (p < 0.05). A multiple logistic regression analysis showed the GIM was predictor for elevated NLR (p < 0.05). According to the ROC curve analysis, the best cut-off NLR value to differentiate between patients with GIM from GA and/or controls was >2.92 (p < 0.05). In this study, we mainly found a significant association between GIM and NLR. Conclusions: NLR is significantly higher in patients with GIM. NLR can be an independent determinant factor for GIM. Keywords: Intestinal metaplasia; gastric atrophy; biomarker.

Prevalence and characteristics of isolated nocturnal hypertension in the general population

Background/Aims: Ascertaining the prevalence of isolated nocturnal hypertension (INHT) in the general population and identifying the characteristics of patients with INHT may be important to determine patients who should receive 24- hour ambulatory blood pressure (BP) measurements. This study aimed to evaluate the prevalence and characteristics of INHT in the general population.Methods: Of 1,128 participants (aged 20 to 70 years), we analyzed 823 who had valid 24-hour ambulatory BP measurements and were not on antihypertensive drug treatment.Results: The prevalence of INHT in the study was 22.8%. Individuals with INHT had a higher office, 24-hour, and daytime and nighttime ambulatory systolic and diastolic BPs compared to individuals with sustained day-night normotension. INHT was more prevalent in individuals with masked hypertension (MH) than in those with sustained hypertension (59.8% vs. 15.6%, p < 0.001). Among individuals with INHT, 92.6% had MH. Among individuals with office BP-based prehypertension, 34.5% had both INHT and MH. The prevalence of INHT was highest in individuals with office BP-based prehypertension. INHT was an independent determinant of MH after adjustment for age, sex, body mass index, diabetes, low-density-lipoprotein cholesterol, 24-hour systolic and diastolic BP, systolic and diastolic BP dipping, and systolic and diastolic BP non-dipping.Conclusions: The present study showed that INHT is not uncommon and is a major determinant of MH. Our findings strongly suggest the use of 24-hour ambulatory BP measurement for individuals within the prehypertension range of office BP owing to the high prevalence of INHT and MH in this population.

Metabolic Syndrome, Homocysteine and uric acid in patients with obesity; experience from obesity and work centre

BACKGROUND: Uric acid (UA) and homocysteine (HCys) are involved in cardiovascular diseases. Patients with obesity (PwO) are characterized by elevated cardiovascular risk. OBJECTIVE: To evaluate the relationship between HCys and UA concentrations in 1141 overweight patients and PwO with and without metabolic syndrome (MS). METHODS: MS was defined according to IDF criteria (2005). Anthropometric data were recorded and blood biochemical parameters were assessed with routine methods on fasting blood samples. Statistics: Spearman correlation and multiple regression analysis. RESULTS: Gender, obesity and MS influenced both UA and HCys levels, which were increased in males, MS patients, PwO with MS and positively correlated (p < 0.001). Patients without MS had normal or slightly high levels. Hypertension, hyperuricemia and hyperhomocysteinemia were found in PwO with MS. UA concentration correlated with systolic blood pressure, triglycerides and HDL (all p < 0.05). Multivariate analysis showed that HCys concentration was an independent determinant factor affecting UA levels (T value 3.5, p < 0.001). CONCLUSIONS: HCys and UA levels positively and significantly correlated in PwO, especially in those with MS. The significant correlation between UA and hypertension, triglycerides, HDL suggests the clinical usefulness of monitoring UA together with HCys concentrations as cardiovascular risk marker in these patients.

AB0194 ASSOCIATION OF MALNUTRITION WITH QUALITY OF LIFE IN ELDERLY RA PATIENTS

Background:Rheumatoid arthritis (RA) is a progressive joint condition that leads to joints destruction and complications in the internal organs and significantly affects the a patient’s functional ability. Elderly patients with RA complain of pain, mood and sleep disturbances, fatigue, and insomnia in addition to weakness, decreased appetite and weight loss. Chronic use of medications results in the risk of comorbidities and decreased physical functioning. All this together significantly contributes to a negative assessment of quality of life (QoL).Objectives:Due to the chronic nature of RA and the high risk of malnutrition in this group of patients, an attempt was made to assess the QoL, activities of daily living and severity of frailty syndrome according to the results of the MNA questionnaire in a group of elderly patients with RA.Methods:The study included 98 patients (age over 60 years) with a diagnosis of RA according to ARA. Standardized tools were used in the study: the WHOQOL-BREF to assess quality of life, the Edmonton Frailty Scale to assess frailty syndrome, MNA to assess nutritional status and MMSE to assess cognitive function. Medical data were taken from the hospital records.Results:Patients significantly differed in the extent of limitations in basic (ADL) and advanced activities of daily living (IADL) according to their nutritional status. The higher the level of malnutrition, the greater the limitations of undertaken activities. In addition, an adverse effect of reduced body weight on the occurrence of cognitive dysfunction was observed (33.33% of malnourished patients were diagnosed with dementia vs. 1.79% in normal weight patients). Similarly, frailty syndrome or vulnerability to frailty syndrome was associated with malnourished patients (33.3% mild, 16.67% moderate, and 16.67% severe frailty syndrome). Malnourished patients had significantly lower QoL scores in all domains of the WHOQOL-BREF questionnaire compared to normal weight patients and multivariate analysis of the effect of selected variables on QoL in the domains of the WHOQOL-BREF questionnaire showed that a significant independent determinant of lower QoL in all domains was the presence of frailty syndrome, respectively: Perception of QoL (R=-0. 069), Self-perception of health (R=-0.172), Physical domain (R=-0.425), Psychological domain (R=-0.432), Social domain (R=-0.415), Environmental domain (R=-0.317). Malnutrition was a significant independent determinant of QoL in the self-perception of health domain (R=-0.08). Additionally, in the regression analysis, a positive effect of male gender was observed on the assessment of QoL in the psychological (R=1.414) and environmental (R=1.123) domains.Table 5.Comparative analysis of quality of life in terms of each domain of the WHOQOL-BREF questionnaire according to nutritional status.WHOQOL BREFMNApMalnutrition (Mean±SD)Risk of malnutrition (Mean±SD)Normal nutrition (Mean±SD)Perception of quality of life3,33±1,033,33±0,683,68±0,580,029Self-perception of health2,67±0,822,47±0,843,14±0,980,004Physical health10,83±3,4911,31±2,3912,68±2,270,02Psychological domain12,5±3,8913,28±2,7314,45±2,240,056Social domain12,33± 2,8612,67±2,9314,29±2,610,007Environmental domain13,83±2,8613,22±2,2813,96±2,170,34Conclusion:Malnourished people have a lower quality of life than people of normal weight. Malnutrition is a factor that negatively affects daily functioning, cognitive functioning, and the severity of frailty syndrome. A significant independent determinant of reduced quality of life across all domains of the WHOQOL-BREF questionnaire is frailty syndrome.References:[1]Marcora SM, Chester KR, Mittal G et al. Randomizedphase 2 trial of anti-tumor necrosisfactortherapy for cachexia in patients with earlyrheumatoidarthritis. Am J ClinNutr 2006;84:1463–72. 24 .[2]Kremers HM, Nicola PJ, Crowson CS, et al. Prognosticimportance of low body mass index in relation to cardiovascularmortality in rheumatoidarthritis. ArthritisRheum. 2004;50:3450–7.Disclosure of Interests:None declared