Analysis of Geometric and Hemodynamic Profiles in Rat Arteriovenous Fistula Following PDE5A Inhibition

Arteriovenous fistula (AVF) is essential for chronic kidney disease (CKD) patients on hemodialysis, but treatment for AVF maturation failure remains an unmet clinical need. Successful AVF remodeling occurs through sufficient lumen expansion to increase AVF blood flow and lumen area. Aberrant blood flow is thought to impair AVF remodeling, but previous literature has largely focused on hemodynamics averaged over the entire AVF or at a single location. We hypothesized that hemodynamics is heterogeneous, and thus any treatment’s effect size is heterogeneous in the AVF. To test our hypothesis, we used the PDE5A inhibitor sildenafil to treat AVFs in a rat model and performed magnetic resonance imaging (MRI) based computational fluid dynamics (CFD) to generate a detailed spatial profile of hemodynamics in AVFs. 90 mg/kg of sildenafil was administered to rats in their drinking water for 14 days. On day 14 femoral AVFs were created in rats and sildenafil treatment continued for another 21 days. 21 days post-AVF creation, rats underwent non-contrast MRI for CFD and geometrical analysis. Lumen cross-sectional area (CSA) and flow rate were used to quantify AVF remodeling. Parameters used to describe aberrant blood flow include velocity magnitude, wall shear stress (WSS), oscillatory shear index (OSI), and vorticity. Geometrical parameters include arterial-venous (A-V) distance, anastomosis angle, tortuosity, and nonplanarity angle magnitude. When averaged across the entire AVF, sildenafil treated rats had significantly higher CSA, flow rate, velocity, WSS, OSI, and vorticity than control rats. To analyze heterogeneity, the vein was separated into zones: 0–5, 5–10, 10–15, and 15–20 mm from the anastomosis. In both groups: 1) CSA increased from the 0–5 to 15–20 zone; 2) velocity, WSS, and vorticity were highest in the 0–5 zone and dropped significantly thereafter; and 3) OSI increased at the 5–10 zone and then decreased gradually. Thus, the effect size of sildenafil on AVF remodeling and the relationship between hemodynamics and AVF remodeling depend on location. There was no significant difference between control and sildenafil groups for the other geometric parameters. Rats tolerated sildenafil treatment well, and our results suggest that sildenafil may be a safe and effective therapy for AVF maturation.

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Korelasi Blood Flow Rate Intraoperasi dan Enam Minggu Pascaoperasi Arteriovenous Fistula Brakiosefalika Dihubungkan dengan Maturitas di RSUP Prof. Dr. R. D. Kandou Manado

JURNAL BIOMEDIK (JBM) ◽

10.35790/jbm.11.2.2019.23325 ◽

2019 ◽

Vol 11 (2) ◽

pp. 123

Author(s):

Aubrey W. Palin ◽

Djony E. Tjandra ◽

Richard M. Sumangkut

Keyword(s):

Blood Flow ◽

Arteriovenous Fistula ◽

Flow Rate ◽

Significant Relationship ◽

Blood Flow Rate ◽

National Kidney Foundation ◽

Av Fistula ◽

Factors Affecting ◽

Significant Difference ◽

Venous Diameter

Abstract: American National Kidney Foundation (2002) states that end-stage kidney disease is an indication for renal replacement therapy, one of which is hemodialysis. Vascular access comprises a fundamental component of hemodialysis therapy (HD), facilitating the patient’s blood flow to the dialyzer. However, there are some factors affecting the maturity of an arteriovenous fistula (AVF), inter alia the patient, comorbidities, and anatomical and functional conditions of the blood vessels involving the blood flow rate (BFR). This study was aimed to establish the differences between intra-operative BFR and BFR six weeks after surgery as well as any correlations between intraoperative BFR, venous diameter, and skin to vein distance with maturity of brachiocephalic AVF. This was prospective cohort study conducted at the Department of Surgery, Prof. Dr. R. D. Kandou General Hospital Manado. Subjects were 41 CKD patients who underwent brachiocephalic AVF surgery. The vein diameter, skin to vein distance, and BFR were measured immediately as intra-operative data using a Doppler USG and all were re-measured at six-week-follow-up examination as six-week-postoperative data. The results showed that there was a significant increase in BFR at six weeks postoperation compared to intraoperation (t=-19.215; P <0.0001). Bi-serial point correlation analysis revealed that there was a significant correlation between intraoperative venous diameter and maturity (rpb=0.276; P=0.04) as well as a significant correlation between intraoperative BFR and maturity (rpb=0.615; P=0.002). No significant correlation was observed between intra-operative skin to vein distance and maturity (rpb=0.093; P=0.281). Conclusion: There was a significant difference in BFR between intraoperation and 6 weeks postoperation in the mature AV fistula. There was a significant relationship between intraoperative BFR and maturity as well as between intraoperative venous diameter and maturity, while no significant relationship between skin-vein distance and maturity was found.Keywords: brachiocephalic AVF, BFR, maturityAbstrak: American National Kidney Foundation (2002) menyatakan bahwa penderita dengan penyakit ginjal tahap akhir diindikasikan untuk dilakukan terapi pengganti ginjal, salah satunya hemodialisis (HD). Akses vaskular merupakan komponen penting pada terapi HD karena melalui akses vaskular darah dari tubuh pasien dapat dialirkan menuju dialyzer. Terdapat banyak faktor yang memengaruhi maturitas suatu arteriovenous fistula (AVF), yaitu pasien itu sendiri, komorbid, serta keadaan anatomi dan fungsional pembuluh darah termasuk nilai blood flow rate (BFR). Penelitian ini bertujuan untuk mengetahui perbedaan BFR intraoperasi dan BFR enam minggu pascaoperasi serta adanya korelasi antara BFR intraoperasi, diameter vena, dan jarak kulit-vena dengan maturitas AVF brakiosefalika. Penelitian ini dilaksanakan di Bagian Bedah RSUP Prof. Dr. R. D. Kandou Manado dengan desain kohort prospektif. Subyek penelitian ialah 41 pasien PGK yang menjalani operasi pembuatan AVF brakiosefalika. Setelah selesai operasi dihitung diameter vena, jarak kulit-vena, dan BFR sebagai data intraoperasi menggunakan USG Doppler. Penghitungan dilakukan kembali 6 miggu pascaoperasi. Hasil penelitian mendapatkan peningkatan BFR yang sangat bermakna pada enam minggu pascaoperasi dibandingkan intraoperasi (t =-19,215, P<0,0001). Dengan analisis korelasi point biserial didapatkan hubungan bermakna antara diameter vena intraoperasi dengan maturitas (rpb=0,276; P=0,04), tidak terdapat hubungan bermakna antara jarak kulit-vena intraoperasi dengan maturitas (rpb=0,093; P=0,281), dan terdapat hubungan bermakna antara BFR intraoperasi dengan maturitas (rpb=0,615; P=0,002). Simpulan: Terdapat perbedaan bermakna antara BFR intraoperasi dan BFR 6 minggu pascaoperasi pada AVF matur. Terdapat hubungan bermakna antara BFR intraoperasi dan diameter vena intraoperasi dengan maturitas namun tidak terdapat hubungan bermakna antara jarak kulit-vena dengan maturitas.Kata kunci: AVF brakiosefalika, BFR, maturitas

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Peak expiratory flow rate among smokers and non-smokers working in Kathmandu Medical College

Journal of Chitwan Medical College ◽

10.3126/jcmc.v10i2.29667 ◽

2020 ◽

Vol 10 (2) ◽

pp. 33-35

Author(s):

Preetu Gurung

Keyword(s):

Cigarette Smoking ◽

Peak Expiratory Flow ◽

Flow Rate ◽

Peak Expiratory Flow Rate ◽

Cross Sectional Study ◽

P Value ◽

Cross Sectional ◽

Medical College ◽

Significant Difference ◽

Expiratory Flow

Background: Cigarette smoking has remained a popular habit since ages. Most people are well aware of the deleterious effects of cigarette smoking yet continue to give a blind eye which deteriorates overall public health. The purpose of the present study was to assess Peak Expiratory Flow Rate among smoking and nonsmoking staffs who work in Kathmandu Medical College. Methods: In this comparative cross-sectional study Peak Expiratory Flow Rate was obtained using Mini Wright’s Peak Flow Meter of 108 smokers and 108 nonsmokers in the age group ranging from 25-45 years. Those who never smoked or who have quit smoking for the past 2 years were grouped as nonsmokers and the smokers with history of smoking at least five or more cigarettes per day for at least two years were included in the study for measuring their Peak Expiratory Flow Rate. Data was collected, compiled and analyzed by using Statistical Package of Social Science (SPSS) software version16. Student ‘t’ test was used for group comparison. Results: The Peak Expiratory Flow Rate value was significantly reduced in the smokers (p value< 0.05). Mean Peak Expiratory Flow Rate was reduced with increasing age of the smokers. However, no significant difference was observed in Peak Expiratory Flow Rate with increase in the number of cigarettes smoked (p value> 0.05). Conclusions: In the study Peak Expiratory Flow Rate among smokers (367.13 ± 74.182) was lower than nonsmokers (471.39±60.842), which was statistically significant proving that cigarette smoking reduced peak expiratory flow rate.

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How to carry out monthly blood flow surveillance of fistula in large-scale hemodialysis units: A cross-sectional study

The Journal of Vascular Access ◽

10.1177/1129729820923939 ◽

2020 ◽

pp. 112972982092393

Author(s):

Ya-wen Mo ◽

Chun-yan Sun ◽

Li Song ◽

Li-fang Zhou ◽

Ting-ting Zhuang ◽

...

Keyword(s):

Blood Flow ◽

Arteriovenous Fistula ◽

Doppler Ultrasound ◽

Radial Artery ◽

Brachial Artery ◽

Dilution Technique ◽

Cross Sectional ◽

Duplex Doppler Ultrasound ◽

Duplex Doppler ◽

Artery Flow

Background: The important effect of regular blood flow surveillance on arteriovenous fistula maintenance is emphasized. The ultrasonic dilution technique for blood flow surveillance can be performed during hemodialysis, but there are some limitations. Blood flow is traditionally measured by duplex Doppler ultrasound during the nondialysis period. However, the surveillance workload for arteriovenous fistula has increased with the rapid increase in the hemodialysis population size. Efficient methods for blood flow surveillance during hemodialysis are needed. Methods: Eighty-four hemodialysis patients with a forearm radiocephalic arteriovenous fistula were enrolled in this cross-sectional study. Each received blood flow measurements using ultrasonic dilution technique and duplex Doppler ultrasound during hemodialysis. Duplex Doppler ultrasound measurements included the blood flow of the brachial artery and radial artery. The correlations between these variables were analyzed. Results: The correlation coefficients ( r) between flow measured by ultrasonic dilution technique and brachial artery flow measured by duplex Doppler ultrasound, between flow measured by ultrasonic dilution technique and radial artery flow measured by duplex Doppler ultrasound, and between brachial artery flow and radial artery flow measured by duplex Doppler ultrasound were 0.724, 0.784, and 0.749, respectively (all p < 0.001). Conclusion: Blood flow measured by ultrasonic dilution technique was positively correlated with blood flow measured by duplex Doppler ultrasound during hemodialysis, suggesting that duplex Doppler ultrasound can be used to monitor the trends in the blood flow of the brachial artery and radial artery for timely intervention to improve patency during hemodialysis.

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Predicting Arteriovenous Fistula Maturation with Intraoperative Blood Flow Measurements

The Journal of Vascular Access ◽

10.1177/112972980800900404 ◽

2008 ◽

Vol 9 (4) ◽

pp. 241-247 ◽

Cited By ~ 21

Author(s):

S.S. Berman ◽

B. Mendoza ◽

A. Westerband ◽

R.C. Quick

Keyword(s):

Renal Failure ◽

Blood Flow ◽

Native American ◽

Arteriovenous Fistula ◽

Threshold Value ◽

Operating Characteristics ◽

Chi Square ◽

Flow Measurements ◽

Significant Difference ◽

Blood Flow Measurements

Objective To establish the criteria for intraoperative blood flow measurements taken at the time of autologous arteriovenous fistula (AVF) construction to predict future access maturation and thereby avoid waiting periods for futile fistulas to declare themselves. Methods From April 2006 through to March 2007 consecutive patients undergoing native AVF construction at one institution underwent intraoperative measurements of blood flow using transit-time ultrasound technology. No action was taken based upon the flow measurement at the time of surgery. Patients were followed and data collected comprising demographics and AVF maturation. A fistula was considered mature when it was successfully accessed for hemodialysis (HD) at least three times. Statistical analysis was performed including receiver operating characteristics (ROC), ANOVA, and Chi square using the JMP software package. Results During the 12-month period, 70 autologous AVFs were created including 41 antecubital brachiocephalic, 21 radiocephalic, and 8 basilic vein transpositions in 35 females and 33 males with a mean age of 58 ± 1.7 (mean ± SEM). The group included 37 Hispanic, 17 Native American, 10 Caucasian, 3 African American and 1 Asian patient. The etiology of renal failure comprised 53 diabetics, 13 hypertensives, 1 polycystic kidney disease and 1 congenital abnormality. Complete follow-up was available in 69/70 AVFs in 67 patients. Patients were excluded from analysis if they had not yet started dialysis (n=12), stopped or died (n=4) before their fistula was accessed. Patients whose AVFs were patent, but required a secondary procedure to achieve a functional access were considered non-functional. There was a significant difference between the maximal intraoperative flow rates between functional and non-functional AVFs (573.6 ± 103 mL/min vs. 216.8 ± 35.8 mL/min; p<0.05). There was no difference between groups in regard to age, gender, race or etiology of renal failure. ROC analysis suggested a threshold value of 140 mL/min for radiocephalic and 308 mL/min for brachiocephalic AVFs to predict maturation to a functional access. Conclusion Intraoperative blood flow measurements obtained at the time of autologous AVF construction can identify fistulas that are unlikely to mature; and therefore, that require immediate revision or abandonment which will ultimately expedite the establishment of a useful access in the HD patient. This is the first study to establish the minimal flow values uniquely needed for both radial artery and brachial artery AVFs to expect primary maturation to a functional access.

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Effect of a Surgically Created Side-to-Side Arteriovenous Fistula on Heat Elimination from the Human Hand and Forearm: Evidence for a Critical Role of Venous Resistance in Determining Fistular Flow

Clinical Science ◽

10.1042/cs0550349 ◽

1978 ◽

Vol 55 (4) ◽

pp. 349-353

Author(s):

W. F. M. Wallace ◽

J. P. Jamison

Keyword(s):

Blood Flow ◽

Cold Stress ◽

Arteriovenous Fistula ◽

Flow Rate ◽

Temperature Regulation ◽

Critical Role ◽

Human Hand ◽

Superficial Vein ◽

Heat Elimination

1. In eight patients with a unilateral fistula between the radial artery and a nearby superficial vein, heat elimination from both hand and forearm, as measured by calorimetry, was always substantially greater on the side of the fistula (mean excess from hand-plus-forearm 889 J/min). 2. Fistular blood flow measured by hand-plus-forearm plethysmography in these patients averaged 431 ml/min. Correlation between fistular blood flow and heat elimination was poor (r = 0.70, P < 0.06), probably because heat elimination due to the fistula takes place mainly from veins, whose pattern varies from patient to patient. 3. Approximately half of the total increased heat elimination due to the fistula is from the hand. Occlusion of the circulation to the hand caused fistular flow rate to be reduced by about half. This suggests that the main resistance to fistular flow is venous, proximal veins offering a similar resistance to distal veins. 4. The obligatory heat loss due to the fistula is unlikely to embarrass temperature regulation, except in severe cold stress.

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Effects of Arterial Needle Placement in Arteriovenous Fistula on Dialysis Adequacy of End-Stage Renal Disease Patients Undergoing Maintenance Hemodialysis

Journal of Nursing & Healthcare ◽

10.33140/jnh/01/02/00010 ◽

2016 ◽

Vol 1 (2) ◽

Keyword(s):

Blood Flow ◽

Arteriovenous Fistula ◽

Intervention Group ◽

Maintenance Hemodialysis ◽

Control Group ◽

Needle Placement ◽

Dialysis Adequacy ◽

Significant Difference ◽

Stage Renal Disease ◽

End Stage

Objective: The arterial needle placement in arteriovenous fistula (AVF) can either be antegrade (in the direction of blood flow or pointing towards the heart) or retrograde (against the direction of blood flow) while venous needle placement should always be in the same direction as the blood flow. This study determined the effects of arterial needle placement in the arteriovenous fistula on dialysis adequacy of End-Stage Renal Disease (ESRD) patients undergoing maintenance hemodialysis in United Candelaria Doctors Hospital - Nephro Synergies Inc. (UCDHNSI) Hemodialysis Center. Methods: A randomized controlled trial design was used in the study. A total of 20 non-diabetic, non-cardiac patients on maintenance hemodialysis for more than 6 months were randomized either to the intervention group (patients’ AVF were cannulated in a retrograde manner) or the control group (patients’ AVF were cannulated in an antegrade manner). Urea reduction ratio (URR) and Kt/V as well as access recirculation percentage were used to determine dialysis adequacy. Pre-dialysis, in the first 30 minutes of dialysis initiation and post-dialysis blood samples were obtained in each patient in 6 succeeding hemodialysis considering dialyzer reuse up to fifth reuse. Means were compared by independent t-test. Results: The findings of the study revealed that the mean URR and Kt/V of the subjects cannulated in retrograde manner and antegrade manner were 69.35% and 1.45, and 74.65% and 1.70, respectively. The mean access recirculation percentage of the subjects was 4.65% in the intervention group and 3.02% in the control group. There was a significant difference on URR and Kt/V of the subjects using retrograde and antegrade arterial needle placement in 6 succeeding hemodialysis sessions. There was no significant difference on access recirculation percentage of the subjects using retrograde and antegrade arterial needle placement in 6 succeeding hemodialysis sessions. Conclusions: Antegrade arterial needle placement provides more adequate hemodialysis than retrograde arterial needle placement in terms of URR and Kt/V values among non-diabetic, non-cardiac patients undergoing maintenance hemodialysis in 6 succeeding hemodialysis sessions. The directions of the arterial needle either retrograde and antegrade did not have significant effects on access recirculation.

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Characterization of Left Ventricle Main Flow Axis Line Using Echodynamography

INDONESIAN JOURNAL OF APPLIED PHYSICS ◽

10.13057/ijap.v11i2.51896 ◽

2021 ◽

Vol 11 (2) ◽

pp. 153

Author(s):

Sri Oktamuliani ◽

Kaoru Hasegawa ◽

Tadanori Minagawa ◽

Yoshifumi Saijo

Keyword(s):

Blood Flow ◽

Cardiac Function ◽

Velocity Distribution ◽

Slope Angle ◽

Left Ventricular ◽

Main Flow ◽

Imaging Method ◽

Flow Axis ◽

Velocity Magnitude ◽

Significant Difference

<span>Left ventricular (LV) blood flow analysis may play an essential role in evaluating cardiac function besides the classical analysis of wall motion. Echodynamography is an imaging method in which two-dimensional (2D) blood flow vectors are deduced by blood flow information obtained by color Doppler echocardiography. Echodynamography has provided useful information on the blood flow pattern in healthy and abnormal LV. The main flow axis line (MFAL) is defined as a maximum velocity magnitude of blood flow from the LV's apex to LV's outflow, which is a new hemodynamic parameter for cardiac assessment. The present study's objective is to compare blood flow patterns between healthy and abnormal LV by investigating the MFAL and its correlation to vorticity and velocity distribution on MFAL. This study enrolled 12 participants, four healthy volunteers, and eight abnormal patients. Echodynamography analyzed frame by frame Doppler image of apical three-chamber views. The results showed MFAL superimposed on vorticity mapping during ventricular ejection and MFAL path coincide with the irrotational flow of zero vorticity path, ω = 0. A significant difference was observed in the velocity distribution curve (VDC) on the MFAL during early, mid, and late systoles compared to healthy and abnormal LV. VDC showed the linear upward curve and the highest velocity magnitude during the early systole phase in healthy LV. In contrast with abnormal LV, VDC showed the downward convex curve and the highest velocity magnitude during mid systole phase. Furthermore, the gradient and slope angle of the VDC on the MFAL was compared. The result showed that the maximum gradient and slope angle were not significantly different between healthy and abnormal LV. In conclusion, the study of MFAL and the correlation to vorticity based on the Echodynamography computational program provides additional insights for representing a cardiac function, and thus, the clinical implications of MFAL warrant further investigation.</span>

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Evaluation of hemodynamic impact of absorbable sutures in native arteriovenous fistulas: A retrospective study

The International Journal of Artificial Organs ◽

10.1177/0391398819877420 ◽

2019 ◽

Vol 43 (1) ◽

pp. 58-61

Author(s):

Savino Occhionorelli ◽

Fabio Fabbian ◽

Yuri Battaglia ◽

Tommaso Miccoli ◽

Dario Andreotti ◽

...

Keyword(s):

Blood Flow ◽

Arteriovenous Fistula ◽

Flow Rate ◽

Neointimal Hyperplasia ◽

Blood Flow Rate ◽

Absorbable Suture ◽

Absorbable Sutures ◽

The Mean ◽

Fistula Maturation ◽

Arteriovenous Fistula Maturation

One of the major causes of arteriovenous fistula failure is the venous stenosis due to aggressive neointimal hyperplasia. The aim of the study was to assess the arteriovenous fistula maturation comparing absorbable sutures and non-absorbable ones in native vessels. Surgeries performed during a period of 24 months by a single team of expert surgeons were evaluated. Surgeries that met the inclusion criteria, namely, age ⩾ 18 years and radio-cephalic arteriovenous fistula, were considered. According to type of suture, patients were classified as Max group (absorbable suture) and Prol group (non-absorbable). Data pertaining to 70 patients were collected; 51% were men and the mean age was 73 ± 12 years. In Max group, an increasing blood flow was observed during the first 4 weeks without post-operative complications. In Prol group, six patients had thrombosis that resulted in vascular access failure. After the first week, the duplex Doppler ultrasound of both groups showed a regular arteriovenous fistula maturation, with an increase of blood flow rate. Although pre-operative post-tourniquet mean vein diameters of Max group were not adequate, the mean vein diameter and mean blood flow rate increased after 4 weeks, respectively. On the contrary, in Prol group, mean vein diameters and blood flow rate decreased. The maturation of arteriovenous fistula and its functional performance were not altered by the type of suture (absorbable/non-absorbable). Absorbable sutures were associated with good results considering arteriovenous fistula maturation.

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Determinants for outcome of hypoplastic right ventricle with duct-dependent pulmonary blood flow presenting in the neonatal period

Cardiology in the Young ◽

10.1017/s1047951100007976 ◽

1992 ◽

Vol 2 (4) ◽

pp. 377-381 ◽

Cited By ~ 3

Author(s):

Michael L. Rigby ◽

Micelia Salgado ◽

Celia Silva

Keyword(s):

Blood Flow ◽

Right Ventricle ◽

Pulmonary Blood Flow ◽

Pulmonary Valve ◽

Pulmonary Atresia ◽

Cross Sectional ◽

Mitral Valves ◽

Significant Difference ◽

The Right ◽

Pulmonary Valvar Stenosis

SummaryA retrospective study was undertaken of patients with hypoplastic right ventricles, either with pulmonary atresia and intact ventricular septum or critical pulmonary valvar stenosis, and duct-dependent pulmonary blood flow who were investigated at the Royal Brompton Hospital between January 1976 and December 1990. The diagnosis was made on the basis of at least one diagnostic method (cross-sectional echocardiography, cardiac catheterization and angiography, or autopsy). Of the patients, 56 (82%) were found to have an imperforate pulmonary valve or infundibulum (pulmonary atresia), while 12(18%) had critical pulmonary valvar stenosis. The ratio of the diameters of the tricuspid and mitral valvar orifices was measured angiographically during diastole, and the right ventricle was analyzed according to the presence or overgrowth of the inlet, apical trabecular and outlet components. A correlation was made between the severity of the disease and the outcome. The overall mortality was 53% when those not undergoing any surgery were excluded, and significant differences were found between the group dying and those who survived. The incremental risk factors for death were a ratio between the diameter of the tricuspid and mitral valves of less than 0.6; the presence of fistulous communications with the coronary arteries; and obliteration of the apical trabecular component of the right ventricle. There was no significant difference between the group with pulmonary valvar atresia and the group with critical stenosis of the pulmonary valve.

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Associations Between Genetic Variants near the CHREBP Locus and Lipoprotein Concentrations May Be Modified by Sugar-Sweetened Beverage Consumption

Current Developments in Nutrition ◽

10.1093/cdn/nzaa058_014 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1256-1256

Author(s):

Danielle Haslam ◽

Gina Peloso ◽

Caren Smith ◽

Josee Dupuis ◽

Hassan Dashti ◽

...

Keyword(s):

Effect Size ◽

Genetic Variants ◽

Multiple Testing ◽

Random Effect ◽

Nucleotide Polymorphisms ◽

Aging Research ◽

Cross Sectional ◽

Sugar Sweetened Beverage ◽

Genomic Epidemiology ◽

Significant Difference

Abstract Objectives Carbohydrate responsive element binding protein (ChREBP) is a transcription factor that responds to sugar consumption. Consumption of sugar-sweetened beverages (SSB) and genetic variants at the CHREBP (also known as MLXIPL) locus have separately been linked to dyslipidemia. We hypothesized that SSB intake may modify the associations between CHREBP variants and HDL-C and TG concentrations. Methods We conducted a cross-sectional analysis of data from 11 Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium cohorts (N = 63,599). A total of 1606 single-nucleotide polymorphisms (SNPs) were selected within or near the CHREBP locus. SSB intake (sodas, fruit punches, lemonades, or other fruit drinks) was estimated from food-frequency questionnaires. Participants were grouped by five categories of SSB intake (ranging from < 1 serving/month to > 1 serving/day). Inverse-variance weighted fixed- and random-effect meta-analyses were used to quantify the following associations: 1) SSB consumption and HDL-C and TG concentrations; 2) selected SNPs and HDL-C and TG concentrations; and 3) interactions between SSB consumption and selected SNPs, and HDL-C and TG concentrations. Results were corrected for multiple testing to achieve a global p < 0.05. Results SSB intake was inversely associated with HDL-C and positively associated with TG concentrations (ptrend < 0.0001). We replicated previously observed GWAS associations between one distinct SNP on HDL-C (rs71556736) and two distinct SNPs (rs71556736 and rs13225660) on TG concentrations (Bonferroni-corrected P < 0.0001). Additionally, we identified two distinct novel SNP associations with TG concentrations (rs42124 and rs10245965). One distinct SNP displayed a statistically significant difference in effect size by category of SSB intake with HDL-C, where each additional minor allele at rs71556729 was significantly associated with HDL-C concentrations only among the highest SSB consumers [>1 serving/day: β (SE) = 4.47 (1.10) mg/dl, P = 5.0E-05; pinteract = 0.0001]. Additional SNPs displayed a suggestive difference in effect size for both HDL-C and TG concentrations. Conclusions Our results indicate that high SSB consumption may modify the association between genetic variants within or near the CHREBP locus and HDL-C and TG concentrations. Funding Sources NIH, AHA, USDA-ARS.

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