Association Between Hypertension And Impairment Of Intestinal Barrier Function

Background and Aim: As the increasing aging of the population,hypertension has become a global public health problem.In China,the prevalence of hypertension is about 37.2%,which is significantly higher than global prevalence.Hypertension doesn't cause obvious symptoms at early stage.However,its complications often cause high morbidity and mortality.Increasing evidence showed a link between hypertension and intestinal tract,and revealed the existence of “gutheart” axis and “gut-kidney” axis.Basic research revealed that hypertensive animal model showed a series of pathophysiological changes in gut,such as abnormal vascular structure,intestinal sympathetic nerve over-activation and dysbiosis of intestinal microbiota.Moreover,some studies showed that hypertensive rats showed obvious intestinal barrier injuries,and these injuries could be alleviated after controlling the blood pressure by antihypertensive medications,which suggested that hypertension can cause intestinal barrier injuries.However,the association between hypertension and intestinal barrier injuries mainly focus on experimental research.To the best of our knowledge,there is no clinical research to investigate the association between hypertension and intestinal barrier injuries.Therefore,this study was performed to explore the association between hypertension and intestinal barrier injuries using the clinical data,to provide more sufficient clinical evidence for the “gut-heart” axis,and to find a new strategy for the prevention and treatment of hypertension related intestinal barrier injuries.Materials and Methods: Inclusion criteria: inpatients who were tested for intestinal barrier function from January 1,2017 to December 31,2017,in Department of Gastroenterology of the First Affiliated Hospital of Guangdong Pharmaceutical University.Exclusion criteria:(1)previous diagnosis of carcinoma;(2)serious heart,lung,liver and kidney diseases(except hypertensive complications);(3)non-steroidal anti-inflammatory drug use in the previous month;(4)primary intestinal diseases,such as Crohn's disease,ulcerative colitis,and intestinal obstruction;(5)history of digestive tract surgery;(6)bacterial infection(except Helicobacter pylori);(7)secondary hypertension caused by renal parenchymal,adrenal,renovascular or thyroid disease;(8)incomplete medication data.General data(gender,age,height,weight,smoking status,alcohol use),medical history(hypertension history,diabetes history and liver disease history),auxiliary examination(intestinal barrier function,Helicobacter pylori infection and blood lipid concentration)were recorded.Patients were divided into hypertension group and non-hypertension group according to whether they had hypertension or not.The baseline data of the two groups were analyzed.Chisquare test was used to compare the abnormal rates of intestinal barrier function indexes(diamine oxidase,D-lactate,lipopolysaccharide)between the two groups.Chi-square test was also used to analyze the abnormal rate of intestinal barrier function in hypertensive patients with different cardiovascular risk stratification,different duration of hypertension,different blood pressure control status,different hypertensive complications or not,and using different number of antihypertensive drugs.For adjustment of potential confounders and to determine the risk factors for elevated intestinal barrier function markers,logistic regression analyses with a backward stepwise approach were used.Results: 1.The incidence of elevated diamine oxidase and lipopolysaccharide in patients with hypertension were significantly higher than those in patients without hypertension(28.30% vs.18.73%,P = 0.044;22.64% vs.11.16%,P = 0.005).Logistic regression showed that hypertension was a risk factor for elevated diamine oxidase and lipopolysaccharide(OR = 1.71,95% CI: 1.01-2.91,P = 0.046;OR = 2.64,95% CI: 1.42-4.92,P = 0.002).2.There were no significant differences in the prevalence of elevated intestinal barrier function markers among different hypertension risk stratification groups.3.The prevalence of elevated diamine oxidase in patients with hypertension for ?20 years was significantly higher than in those with hypertension for 20 years (53.85% vs.23.19%,P = 0.040).Logistic regression adjusted for confounding factors showed that duration ? 20 years was a risk factor for elevated diamine oxidase(OR = 5.92,95% CI: 1.22-28.78,P = 0.028).4.There was no significant difference in the prevalence of elevated intestinal barrier function markers between patients with poor or good control of systolic or diastolic blood pressure.However,after adjustment for confounding factors,logistic regression showed that poor control of diastolic blood pressure was a risk factor for elevated diamine oxidase(OR = 8.93,95% CI: 1.65-48.35,P = 0.011).5.There was no significant difference in the prevalence of elevated intestinal barrier function markers between patients with and without various complications.However,after adjustment for confounding factors,logistic regression showed that hypertensive cardiac complications and renal complications were high risk factors for elevated diamine oxidase elevation(OR = 12.00,95% CI: 1.39-103.44,P = 0.024;OR = 8.01,95% CI: 1.17-54.69,P = 0.034).6.There was no significant difference in the prevalence of elevated intestinal barrier function markers among patients who used different number of antihypertensive medications.However,after adjustment for confounding factors,the logistic regression analyses showed that use of multiple antihypertensive medication was associated with a significantly increased risk of elevated diamine oxidase(OR = 3.61,95% CI: 1.36–9.58,P = 0.010)and elevated D-lactate(OR = 3.24,95% CI: 1.31–7.98,P = 0.011).Conclusions: The incidence of impairment of intestinal barrier function in patients with hypertension is higher than that in patients without hypertension.Hypertensive patients showed a higher incidence of intestinal mucosa impairment and lipopolysaccharide translocation.Therefore,when hypertensive patients,especially those with long duration,poor blood pressure control,hypertensive heart or kidney complications,and those who need to use a variety of antihypertensive medications,have gastrointestinal symptoms such as occult abdominal pain,diarrhea and malabsorption,the possibility of hypertensive related impairment of intestinal barrier function should be considered,and the digestive endoscopy and intestinal barrier function examination should be performed as soon as possible.