Study On Cardiovascular Disease For Salt-sensitive Groups And Chronic Kidney Disease Patients

Part?: Urinary metabolites associated with blood pressure on a low-or high-sodium dietHypertension is one of the most common lifestyle diseases today.It is also an independent risk factor for myocardial infarction,heart failure,cerebrovascular disease,and chronic kidney disease.And it significantly increases the mortality of these related complication.In most patients there is no known cause for hypertension.Interactions among numerous genetic and environmental factors underlie blood pressure(BP)regulation.High-dietary sodium intake is one of the most important environmental risk factors for elevated BP.There is also much evidence from epidemiological,clinical medicine,genetic,and animal studies that dietary salt(sodium chloride)plays an important role in regulating BP.Individual blood pressure responds differently to dietary sodium intake,a phenomenon known as salt sensitivity difference.The increase in blood pressure drivenby a salt load is characteristic of salt-sensitive hypertension,a condition affecting more than two thirds of individuals with essential hypertension who are older than 60 years.Salt sensitivity of BP has been associated with an increased risk of hypertension,cardiovascular disease,and premature death.Cardiovascular risk increases even in normotensive subjects if their blood pressure is sensitive to salt,suggesting it is important to also identify the presence of sodium sensitivity even in normotensive subjects.At present,with more and more salt-sensitive hypertensives patients,it is very important to seek measures to reduce salt-sensitive hypertension,particularly in high-risk individuals.However,the molecular mechanisms underlying salt-sensitivehypertension remains unknow now.At present,in addition to the renin-angiotensin system,vascular smooth muscle,and endothelial system,the relationship between hypertension and metabolomics has also received increasing attention.Recently,animal studies have shown that abnormalities in cellular metabolism could promote the development of salt-sensitive hypertension.Dahl salt-sensitive(Dahl/Slat Sensitive,Dahl/SS)rat is a widely used salt-sensitive hypertension research model.As it lacks fumarase,an enzyme in the tricarboxylic acid cycle,It promotes the development of hypertension.However,whether the salt intake in the diet affects human blood pressure and the extensive changes in the intermediates of cellular metabolism,and whether they are related,is still unknown.The goal of the present study was to utilize urine samples from the DASH-Sodium trial 2 and a targeted metabolomic approach to identify associations of urinary metabolites with blood pressure phenotypes on low-or high-sodium intake.Significant associations were identified for several metabolites including metabolites previously not known to influence blood pressure.A proof-of-principle experiment performed in SS rats demonstrated a previously unknown effect of one of the identified metabolites on salt-induced hypertension.Methods: We examined the levels of metabolites in urinary samples of 103 participants in the Dietary Approaches to Stop Hypertension(DASH)-Sodium trial 2 after nearly 30 days on a defined diet containing high sodium(targeting 150 mmol sodium intake per day)or low sodium(50 mmol per day).Targeted chromatography/mass spectrometry analysis was performed in 24 h urine samples for amino metabolites and metabolites related to the tricarboxylic acid cycle.The effect of an identified metabolite on blood pressure was examined in Dahl salt-sensitive rats.Results: 1.Demographic and clinical characteristics of the study participantsOf the 51 salt-sensitive participants,18 were men and 40 were blacks.Average systolic blood pressure(SBP)was 123 ± 8 mm Hg on the low-sodium intake and 140 ± 6 mm Hg on the high-sodium intake.Average diastolic blood pressure(DBP)was 78 ± 9mm Hg and 87 ± 6 mm Hg on the two levels of sodium intake,respectively.Of the 52 salt-insensitive participants,25 were men and 22 were blacks.The means and standard deviations of their blood pressures were nearly identical between low and high-sodium intakes(123 ± 7 mm Hg and 80 ± 5mm Hg,respectively,for SBP and DBP).2.Using urinary metabolites to predict the classification of study participants as salt-sensitive and salt-insensitive The area under the curve(AUC)for the receiver operating characteristic(ROC)curve was 0.64 ± 0.08 when levels of all metabolites on low-or high-sodium intake were used,indicating a modest ability of the urinary levels of the metabolites analyzed to classify blood pressure salt-sensitivity.Adding the urinary metabolites to race,age and sex improved the prediction performance(AUC,0.80 ± 0.01).Adding SBP and DBP on the high-sodium diet,as expected,improved the performance even more(AUC,0.91 ± 0.01).3.Urinary metabolites associated with SBP on low-or high-sodium intake GLMM analysis of the metabolites nominated by the randomforest analysis confirmed significant associations with SBP at the level of FDR<0.05 for ?????,cystine,citrulline,homocysteine,and lysine but not cis-aconitic acid.The associations were significant regardless of whether demographic factors identified.4.Urinary metabolites associated with DBP on low-or high-sodium intakeGLMM analysis of these metabolites confirmed significant associations with DBP at the level of FDR<0.05 for cystine but not the other metabolites.The associations were significant regardless of whether demographic factors identified.5.BAIBA attenuates salt-induced increases of blood pressure in SS rats BAIBA could attenuate salt-induced increases of blood pressure in SS rats.Conclusion: BAIBA,cystine,citrulline,homocysteine and lysine,these five metabolite intermediates play an important role in the new mechanism of blood pressure regulation,which could be developed as markers or therapeutic targets for salt-sensitive hypertension.Part?: Estimated glomerular filtration rate decline detection using left ventricular hypertrophy in patients with type 2 diabetes mellitusDiabetes Mellitus(DM)is becoming one of the uninfectious diseases that do harm to the public health.In both developed and developing countries,the number of DM patients is increasing year by year.The prevalence of diabetes has increased in an accelerated rate in our country.DM patients can experience chronic damage and dysfunction in many organs,such as the heart,the kidneys,blood vessels,nerves,and eyes.The chronic complications caused by diabetes have had a serious impact on patients' lives and quality of life,and have caused a serious economic burden on the entire society.The heart and kidney are of utmost importance for the maintenance of cardiovascular homeostasis.Hemodynamic changes in either organ may affect hemodynamics of the other organ.Dysfunction or disease of one organ may initiate,accentuate,or precipitate dysfunction or disease state in the other organ,often leading to a vicious cycle.Maintenance of intravascular volume and hemodynamic homeostasis depends on a set of complex and delicate interactions between the heart and kidney.Hemodynamic changes are more severe in DM patients.Therefore,the interaction between the heart and the kidney is stronger in DM patients.However,the relationship between the renal damage and the cardiac remodeling in clinical data is unclear in Type 2 Diabetes Mellitus(T2DM)patients.And it is unknown whether cardiac remodeling can be used to assess renal damage in T2 DM patients.It is important to solve these issues for T2 DM patients' treatment.Methods: We retrospectively analyze the relationship between renal damage and cardiac remodeling in clinical data.We chose 265 patients with T2 DM,who were diagnosed between 2011 and 2015 and followed for ?3 months.The patients were followed every 3 months for at least 3 months until study endpoint or deadline.The deadline for the study was June 30,2016,and the composite endpoint was an end-stage renal disease(ESRD)or a 50% reduction in the evaluated GFR.Two-dimensional echocardiography(TDE)is well recognized as a non-invasive technique to study cardiac structure and function.In this study,parameters of cardiac remodeling including left atrial diameter(LAD),left ventricular diameter at the end of diastole(LVDd),interventricular septum(IVS)thickness and left ventricular posterior wall(LVPW)thickness were determined using TDE.LAD>34 mm was defined as left atrial(LA)enlargement.LVDd>54 mm was defined as left ventricular(LV)enlargement.IVS and LVPW thickness>11 mm was defined as IVS and LVPW thickening.Results: 1.In this study,265 T2 DM patients were enrolled,including 166 males(62.6%),with a male-to-female ratio of 1.67:1,mean age of 58.08±12.37 years,and known diabetes duration of 33.54±63.81 months.2.The patients were divided into groups with normal cardiac structures and abnormal cardiac structures based on their LAD,LVDd,IVS thickness,and LVPW thickness.Compared to patients with normal cardiac structures,patients with abnormal cardiac structures were older,had diabetes for a longer duration,and had a higher prevalence of a history of hypertension.Additionally,patients with abnormal cardiac structures had higher BMI,systolic BP,and Scr,BUN,24-h total urinary protein,24-h urinary albumin,TC,LDL levels,EF value and lower hemoglobin,e GFR,albumin,and HDL than did patients with normal cardiac structures(P<0.05).However,sex,diastolic BP,SUA,fasting blood glucose,Hb A1 c,TG,total calcium,phosphate and potassium were not significantly different between the two groups(P>0.05).3.The levels of Scr,24-h urinary albumin and 24-h urinary protein increased gradually with the number of abnormalities.However,the e GFR decreased with increasing number of abnormalities.In the Cox regression model,after adjusting age,body mass index(BMI),history of hypertension,duration of diabetes,the Estimated Glomerular Filtration Rate(e GFR),24-h Urinary protein,or using of angiotensin-converting enzyme inhibitors(ACEI)and(or)angiotensin receptor blockers(ARB),the IVS thickness,and LVPW thickness were associated with the composite endpoint(IVS thickness: hazard ratio [HR],1.328;95% confidence interval [95% CI],1.095 to 1.611;P=0.004;LVPW thickness: HR,1.277;95% CI,1.052 to 1.551;P=0.014;).The number of LAD,LVDd,IVS thickness and LVPW thickness abnormalities was positivelyassociated with an increased HR of the composite endpoint.After adjusting age,body mass index(BMI),history of hypertension,duration of diabetes,the Estimated Glomerular Filtration Rate(e GFR),24-h Urinary protein,or using of angiotensin-converting enzyme inhibitors(ACEI)and(or)angiotensin receptor blockers(ARB),the risk of renal damage in patients with T2 DM was higher(HR,6.234;95% CI,1.306 to 29.748;P=0.022;)in the group with the highest number of abnormal echocardiographic parameters,than in the group with no abnormal echocardiographic parameters.4.The area under the curve(AUC)for LAD was 0.609(95% CI,0.522 to 0.696;P=0.015),which was significantly lower than the AUC for IVS thickness(0.702;95% CI,0.617 to 0.786;P=0.000).However,the AUC for LVPW thickness was higher than that for IVS thickness(0.723;95% CI,0.642 to 0.805;P=0.000).Moreover,the AUC for LVDd was 0.573(95% CI,0.485 to 0.660;P=0.104),which was not statistically significant.Therefore,LVPW thickness was superior to the other three parameters as represented by the higher AUC values generated according to the sensitivity and specificity.The optimal cut-off values for LAD,IVS thickness,and LVPW thickness for predicting renal damage were 37.5 mm,11.5 mm and 10.5 mm,respectively.Conclusion: Echocardiographic parameters are strongly correlated with renal damage in patients with T2 DM.Moreover,the severity of cardiac remodeling is closely associated with renal damage in patients with T2 DM.Therefore,the recognition of cardiac structural alterations in patients with T2 DM may evaluate renal damage at an early stage.Part ?: The association between serum i PTH and left ventricular hypertrophy in peritoneal dialysis patientsIn the recent decade,the prevalence of chronic kidney disease(CKD)has continued to grow in the world.The CKD has become one of the common diseases in China.Cardiovascular disease(CVD)is one of the major complications of CKD patients and one of the main causes of death.About 50% of CKD patients die of CVD and its complications in the advanced stage.Peritoneal dialysis(PD)patients have a higher risk of developing cardiovascular disease.This may be related to high blood pressure,high blood pressure fluctuations,high blood lipids,atherosclerosis,chronic inflammationand and other factors.In the cardiovascular events of dialysis patients,left ventricular hypertrophy(LVH)and functional impairment are most common.It is an independent risk factor for predicting cardiovascular mortality.Secondary hyperparathyroidism(SHPT)is a common complication of CKD.Within a certain range,lowering blood PTH,serum calcium,and blood phosphorus levels can significantly reduce cardiovascular complications and mortality in patients with SHPT.The USA Early Kidney Assessment Program(KEEP)has shown that i PTH is an independent risk factor for cardiovascular events in CKD patients.However,in patients with peritoneal dialysis,there are few studies in the effects of i PTH on left ventricular hypertrophyfor PD patients.This study investigates the association between the i PTH and left ventricular hypertrophy(LVH).And To explore the incidence and affecting factors of LVH in PD patients in single dialysis center.Methods:Clinical data of 122 peritoneal dialysis patients admitted from January 2006 to August 2013 in Shenzheng 2nd people's hospital were collected and retrospectively analyzed.Correlational analysis between LVH and EF,IVST,LVMI.Regression analysis between LVH and gender,age,hypertension,diabetes,i PTH,serum CRP levels,serum uric acid concentration,BNP,homocysteine concentration,KT/V,peritoneal dialysis duration were conducted.Results: 1.LVH was found in 74(60.7%)cases of the analysis group which included 41males(55.4%)and 33 females(44.6%).38 patients with LVH were found aged over 60(51.4%),only 36 cases with LVH were less than 60 years old(48.6%).The average age of patients with LVH is 56.20±14.57 years.The average age of patients with no LVH is 54.17±15.21 years.But the difference was not statistically significant(P=0.230).2.Significantly negative correlation was revealed between i PTH level and EF(r=-0.260,P=0.004),while positive correlation revealed between i PTH level and IVST(r=0.557,P=0.001),LVMI(r=0.298,P=0.020)in patients.3.Multivariate unconditional logistic regression analysis showed that hypertension(P=0.013),diabetes(P=0.015),i PTH(P=0.035)were independent risk factors for LVH in peritoneal dialysis patients.Conclusion: The incidence of LVH in our peritoneal dialysis patients was 60.7%.Hypertension,diabetes,i PTH were independent risk factors for LVH in peritoneal dialysis patients.Increased serum i PTH in peritoneal dialysis patients contributes to cardiovascular complications.