Diet-Dependent and Diet-Independent Hemorheological Alterations in Celiac Disease: A Case-Control Study

INTRODUCTION: Hemorheology is the study of the flow properties of the blood and its elements, which, together with natural anticoagulants, are important determinants of cardiovascular events. This study aimed to assess hemorheological and natural anticoagulant profiles of patients with celiac disease (CeD) comprehensively. METHODS: Our study is a case-control study (registered under ISRCTN49677481) comparing patients with CeD with age- and sex-matched control subjects (1:1). We measured erythrocyte deformability (ED) at high (3–30 Pa) and low shears (0.3–3 Pa), erythrocyte aggregation, whole blood viscosity, plasma viscosity, and natural anticoagulants (protein C, protein S, and antithrombin activity). Adherence to gluten-free diet was estimated through dietary interview and urine gluten immunogenic peptide (urine GIP) detection. RESULTS: After matching, we analyzed the data of 100 study participants. ED at high shears was impaired in CeD (P < 0.05 for all shears, confirmed by random forest analysis) independently of findings on CeD-specific serological assessment and urine GIP detection but slightly dependently on dietary adherence (P = 0.025 for 30 Pa shear). ED at low shears seemed to be impaired only in urine GIP+ CeD patients (P < 0.05 for all comparisons with urine GIP− CeD patients and control subjects). All parameters describing erythrocyte aggregation and whole blood viscosity were shifted toward a prothrombotic direction in patients with CeD with poor dietary adherence compared with those with good dietary adherence. Plasma viscosity and activity of natural anticoagulants did not differ across groups. DISCUSSION: We observed diet-dependent and diet-independent prothrombotic hemorheological alterations in CeD, which can contribute to the elevated cardiovascular risk. The untoward metabolic changes during gluten-free diet, which can further aggravate hemorheological status, may indicate the implementation of prevention strategies.

[1]  J. Ludvigsson,et al.  Association Between Celiac Disease and Mortality Risk in a Swedish Population. , 2020, JAMA.

[2]  P. Hegyi,et al.  A Call for Research on the Prognostic Role of Follow-Up Histology in Celiac Disease: A Systematic Review , 2019, Front. Physiol..

[3]  T. Nestares,et al.  Oxidative stress, DNA stability and evoked inflammatory signaling in young celiac patients consuming a gluten-free diet , 2019, European Journal of Nutrition.

[4]  D. Sanders,et al.  European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders , 2019, United European gastroenterology journal.

[5]  P. Hegyi,et al.  Haemorheological and haemostatic alterations in coeliac disease and inflammatory bowel disease in comparison with non-coeliac, non-IBD subjects (HERMES): a case–control study protocol , 2019, BMJ Open.

[6]  Carrie Brown,et al.  Are Gluten-Free Diets More Nutritious? An Evaluation of Self-Selected and Recommended Gluten-Free and Gluten-Containing Dietary Patterns , 2018, Nutrients.

[7]  S. Mrakic-Sposta,et al.  Oxidative stress as a biomarker for monitoring treated celiac disease , 2018, Clinical and Translational Gastroenterology.

[8]  P. H. Green,et al.  Global Prevalence of Celiac Disease: Systematic Review and Meta‐analysis , 2018, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[9]  N. Talley,et al.  Effect of the gluten‐free diet on cardiovascular risk factors in patients with coeliac disease: A systematic review , 2018, Journal of gastroenterology and hepatology.

[10]  R. Fallaize,et al.  An investigation into the nutritional composition and cost of gluten‐free versus regular food products in the UK , 2018, Journal of human nutrition and dietetics : the official journal of the British Dietetic Association.

[11]  T. Alempijevic,et al.  Deep Venous Thrombosis and Bilateral Pulmonary Embolism Revealing Silent Celiac Disease: Case Report and Review of the Literature , 2017, Case reports in gastrointestinal medicine.

[12]  P. Hegyi,et al.  Younger age at diagnosis predisposes to mucosal recovery in celiac disease on a gluten-free diet: A meta-analysis , 2017, PloS one.

[13]  J. Muchova,et al.  Acute dark chocolate ingestion is beneficial for hemodynamics via enhancement of erythrocyte deformability in healthy humans. , 2017, Nutrition research.

[14]  M. Woodward,et al.  Plasma and blood viscosity in the prediction of cardiovascular disease and mortality in the Scottish Heart Health Extended Cohort Study , 2017, European journal of preventive cardiology.

[15]  I. Comino,et al.  Biomarkers to Monitor Gluten-Free Diet Compliance in Celiac Patients , 2017, Nutrients.

[16]  V. Polzonetti,et al.  Gluten free diet and nutrient deficiencies: A review. , 2016, Clinical nutrition.

[17]  J. Radošinská,et al.  The role of red blood cell deformability and Na,K-ATPase function in selected risk factors of cardiovascular diseases in humans: focus on hypertension, diabetes mellitus and hypercholesterolemia. , 2016, Physiological research.

[18]  M. Blank,et al.  Hypercoagulability in celiac disease--an update. , 2014, Autoimmunity reviews.

[19]  M. Bustamante,et al.  Nutritional Differences Between a Gluten-free Diet and a Diet Containing Equivalent Products with Gluten , 2014, Plant Foods for Human Nutrition.

[20]  A. Rubio‐Tapia,et al.  ACG Clinical Guidelines: Diagnosis and Management of Celiac Disease , 2013, The American Journal of Gastroenterology.

[21]  G. Eslick,et al.  Meta‐analysis: coeliac disease and the risk of all‐cause mortality, any malignancy and lymphoid malignancy , 2012, Alimentary pharmacology & therapeutics.

[22]  M. Akarsu,et al.  Erythrocyte Deformability and Oxidative Stress in Inflammatory Bowel Disease , 2012, Digestive Diseases and Sciences.

[23]  K. Giersiepen,et al.  European Society for Pediatric Gastroenterology, Hepatology, and Nutrition Guidelines for the Diagnosis of Coeliac Disease , 2012, Journal of pediatric gastroenterology and nutrition.

[24]  M. Santos,et al.  Hemorheological parameters are related to subclinical atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis patients. , 2011, Atherosclerosis.

[25]  R. Abbate,et al.  Role of hemodynamic shear stress in cardiovascular disease. , 2011, Atherosclerosis.

[26]  C. Popa,et al.  Deficiencies of Proteins C, S and Antithrombin and Activated Protein C Resistance–Their Involvement in the Occurrence of Arterial Thromboses , 2010, Journal of medicine and life.

[27]  Y. Arbel,et al.  Increased strength of erythrocyte aggregates in blood of patients with inflammatory bowel disease , 2009, Inflammatory bowel diseases.

[28]  Achim Zeileis,et al.  BMC Bioinformatics BioMed Central Methodology article Conditional variable importance for random forests , 2008 .

[29]  S. Pocock,et al.  Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and Elaboration , 2007, PLoS medicine.

[30]  G. Corazza,et al.  Hyposplenism: A comprehensive review. Part I: Basic concepts and causes , 2007, Hematology.

[31]  A. Tall,et al.  Change in lipid profile in celiac disease: beneficial effect of gluten-free diet. , 2006, The American journal of medicine.

[32]  A. Mika,et al.  Red Blood Cell Deformability in Patients With Claudication After Pain-free Treadmill Training , 2006, Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine.

[33]  G. Corazza,et al.  Splenic hypofunction and the spectrum of autoimmune and malignant complications in celiac disease. , 2006, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[34]  M. Bardella,et al.  Damaging effects of gliadin on three-dimensional cell culture model. , 2005, World journal of gastroenterology.

[35]  I. Shapira,et al.  Inflammation-Related Erythrocyte Aggregation in Patients with Inflammatory Bowel Disease , 2005, Digestive Diseases and Sciences.

[36]  J. Czopf,et al.  Short-Term Effect of Low-Dose Atorvastatin on Haemorrheological Parameters, Platelet Aggregation and Endothelial Function in Patients with Cerebrovascular Disease and Hyperlipidaemia , 2004, CNS drugs.

[37]  R. Hubbard,et al.  Seroprevalence, correlates, and characteristics of undetected coeliac disease in England , 2003, Gut.

[38]  G. Cloutier,et al.  Contribution of Acute-Phase Proteins and Cardiovascular Risk Factors to Erythrocyte Aggregation in Normolipidemic and Hyperlipidemic Individuals , 1998, Thrombosis and Haemostasis.

[39]  J. Yoshikawa,et al.  Improvement of erythrocyte deformability by cholesterol-lowering therapy with pravastatin in hypercholesterolemic patients. , 1997, Metabolism: clinical and experimental.

[40]  D. Genser,et al.  Changes in blood rheology caused by Crohn's disease , 1996, European journal of gastroenterology & hepatology.

[41]  A. Jones,et al.  Laboratory markers of colonoscopic activity in ulcerative colitis and Crohn's colitis. , 1995, Scandinavian journal of gastroenterology.

[42]  H. Yoshida,et al.  Platelet‐Activating Factor Acetylhydrolase in Red Cell Membranes: Does Decreased Activity Impair Erythrocyte Deformability in Ischemic Stroke Patients? , 1993, Stroke.

[43]  A. Axon,et al.  Plasma viscosity in inflammatory bowel disease. , 1992, Journal of clinical pathology.

[44]  M. Meurer,et al.  Blood rheology in lupus erythematosus. , 1991, Annals of the rheumatic diseases.

[45]  J. Svedlund,et al.  GSRS—A clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease , 1988, Digestive Diseases and Sciences.

[46]  F E Preston,et al.  The effects of dietary omega-3 polyunsaturated fatty acids on erythrocyte membrane phospholipids, erythrocyte deformability and blood viscosity in healthy volunteers. , 1985, Atherosclerosis.

[47]  E. Serin,et al.  Plasma viscosity: a potential predictor of both medical treatment response and clinical stage of ulcerative colitis. , 2016, Annali italiani di chirurgia.

[48]  H. Meiselman,et al.  The role of hemorheological factors in cardiovascular medicine. , 2014, Clinical hemorheology and microcirculation.

[49]  O. Baskurt,et al.  Erythrocyte aggregation: basic aspects and clinical importance. , 2013, Clinical hemorheology and microcirculation.

[50]  B. Sumegi,et al.  Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease. , 2012, Clinical hemorheology and microcirculation.

[51]  O. Baskurt,et al.  New guidelines for hemorheological laboratory techniques. , 2009, Clinical hemorheology and microcirculation.

[52]  M. Rasia,et al.  Erythrocyte aggregation in rheumatoid arthritis: Cell and plasma factor's role. , 2009, Clinical hemorheology and microcirculation.

[53]  T. Grodzicki,et al.  Left ventricular geometry and rheological properties of erythrocytes in patients at cardiovascular disease risk. , 2009, Clinical hemorheology and microcirculation.

[54]  M. Penco,et al.  Modifications of whole blood filterability during acute myocardial infarction. , 2000, Clinical hemorheology and microcirculation.

[55]  W. Koenig,et al.  Hemorheology, Thrombogenesis, and Atherosclerosis , 1993, Seminars in thrombosis and hemostasis.

[56]  H. Schmid-schönbein.  Microrheology of erythrocytes, blood viscosity, and the distribution of blood flow in the microcirculation. , 1976, International review of physiology.