| Background:It is well known that high sodium intake is associated with a variety of health outcomes,including hypertension,heart disease,and mortality.Additionally,observational studies have found a positive correlation between sodium intake or urinary sodium and body mass index(BMI).High sodium intake and obesity are common worldwide.Emerging evidence suggests a strong and direct relationship between high sodium intake and obesity.The bidirectional association between obesity and sodium intake suggests that the relationship between the two is a vicious cycle.This is because people with a greater BMI tend to consume more sodium,further increasing their BMI.High sodium intake and obesity are common risk factors for many chronic diseases,and they also have adverse health effects and disease burdens.Left atrium(LA)function is receiving more and more attention,and is regarded as an excellent indicator of upcoming cardiac function changes.Its function can provide key prognostic information and be used for the diagnosis of subclinical diseases.Impaired left atrial function indicates an early diastolic function obstacle.Assessment of LA strain allows for earlier detection of LA dysfunction.Among cardiac function parameters,LA reservior function(LA reservior strain)was the most reliable predictor of HF death or HF hospital admission.However,the mechanism of LA dysfunction is currently unknown.Objective:1.To explore the relationship between 24-hour urinary sodium(a surrogate indicator of sodium intake)and left atrial function assessed by cardiac MRI,while using mediation analysis to investigate whether BMI has a relationship between 24-hour urinary sodium and left atrial function Play a mediator role;2.To evaluate the impact of different degrees of overall obesity and visceral obesity on the left atrial function of participants without structural heart disease.In addition,considering that insulin resistance is closely related to obesity and heart failure,we use mediation analysis to investigate whether the TyG index(an indicator of insulin resistance)plays a role in obesity and subclinical left atrial dysfunction.3.Apply proteomics technology to detect plasma exosomal proteins in two groups of patients with both normal left atrial function and left atrial dysfunction.Screen out proteins with statistically different expression levels for subsequent proteomic functional annotation.logical analysis and protein interaction network analysis provide directions for exploring the mechanism of early left atrial dysfunction and provide reference for finding biomarkers of subclinical left atrial dysfunction.Methods:1.Participants with no history of structural heart disease were recruited.They voluntarily underwent extensive cardiovascular health examinations.Clinical characteristics,laboratory data,24-hour urine,routine echocardiographic measurements,and CMR feature tracking parameters;2.When studying the correlation between sodium intake and left atrial function,according to the dividing line of low sodium,medium sodium and high sodium intake,the selected patients were divided into three groups according to 24-hournary sodium,that is,the low urinary sodium group:Urinary sodium ≤100mmol/24h(sodium intake≤6g/d),moderate urinary sodium group:100mmol/24h<urinary sodium ≤200mmol/24h(6g/d<sodium intake ≤12g/d),high urinary sodium group:sodium>200mmol/24h(sodium intake>12g/d);3.When studying the correlation between obesity and left atrial function,participants were divided into two groups according to body mass index.The obese group was≥25kg/m2,and the non-obese group was 18-24.9kg/m2;4.When conducting proteomics research on patients with left atrial dysfunction,from patients with healthy left atrial function and decreased left atrial function,according to age,height,weight,gender,basic medical history(such as history of hypertension,diabetes history)and other clinical data,and screened out 9 pairs of patients with matching clinical characteristics;5.All participants completed routine echocardiography and cardiac magnetic resonance.After subjects had fasted for at least 8 hours,venous blood was collected and analyzed to determine fasting plasma glucose(FPG),total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),serum creatinine(Scr),BNP and other indicators.Glycated hemoglobin A1c(HbA1c)was analyzed by high performance liquid chromatography.Under the normal diet,empty the bladder from 7:00 on the first day and discard it,start timing at this time,store all the urine excreted for 24 hours until the last urination at 7:00 the next morning;6.Collect venous blood in a vacuum tube without an anticoagulant.Let it stand at room temperature for 1 hour.Centrifuge at 2,000g for 10 minutes,and take the supernatant as serum.Aliquoted and stored in a refrigerator below-80℃ until use.Then,label free quantification(LFQ)proteomics technology was used to detect the plasma exosomal proteins of the two groups of patients with healthy left atrial function and left atrial dysfunction.Results:Part 1:1.Participants with higher 24-hour urine sodium had higher rates of hypertension and obesity prevalence;2.Both LA reservoir function and LA conduit function decreased significantly with the increase in 24-hour urine sodium;3.Correlation analyses found pairwise associations between 24-hour urinary sodium,BMI,and LA function(LA reserve function,LA conduit function),and mediation analysis showed that BMI mediated sodium intake(assessed with 24-hour urinary sodium)and left atrial function.Part 2:1.Obese study participants had higher levels of insulin resistance,epicardial fat volume,and prevalence of metabolic syndrome;2.Compared with non-obese patients,all LA functional parameters(LA reservoir,LA conduit,LA booster strain and strain rate)were significantly reduced in obese group participants;3.Correlation analysis showed that there was a pairwise correlation between BMI,TyG index(representing insulin resistance),and left atrial function(left atrial strain),and mediation analysis showed that TyG index mediated the correlation between BMI and LA function;4.TyG index can be used as a predictor of LA dysfunction,and the appropriate cut-off point of TyG index is 9.33.Part 3:1.According to the protein expression ratio of the left atrial function group/left atrial function group,differential expression analysis was carried out.The two groups took1.2 times the protein expression difference as the threshold,and a total of 643 quantifiable proteins were identified by mass spectrometry analysis.Relatively,compared to the healthy left atrial function group,in the left atrial dysfunction group,33 proteins were up-regulated(log2>0.263),and 15 proteins were down-regulated(log2<-0.263);2.Go analysis showed that in intracellular localization,the number of proteins located in exocrine tissues was the largest,indicating that the effect of exocrine enrichment was satisfactory.In terms of biological processes,it is shown that most of the differential proteins are involved in a variety of metabolic processes.These processes involve glycolysis,bicarbonate transport,lipid metabolism,gluconeogenesis and so on.It is suggested that metabolic abnormalities such as glucose and lipid metabolism play an active role in left atrial dysfunction.3.KEGG analysis of differential proteins showed that most of the differential proteins were involved in a variety of metabolic processes.These processes include nitrogen metabolism,glycolysis and gluconeogenesis,amino acid biosynthesis,carbon metabolism,the glucagon signaling pathway and so on.It is worth noting that the amount of proteins enriched by the glycolysis and gluconeogenesis pathway is the largest and the difference is the most significant.In addition,the enrichment multiple is the highest.4.Protein-protein interaction network analysis showed that proteins related to blood lipid metabolism,such as APOB,APOH and LPA,suggested that lipid metabolism may play a key role in left atrial dysfunction.Conclusions:1.Higher BMI and impaired left atrial function are related.BMI seems to explain the significant indirect effect between 24-hour urinary sodium and poor left atrial function;2.High EAT levels may also contribute to the risk stratification of early cardiac insufficiency,emphasizing the importance of visceral obesity(visceral fat)in addition to overall obesity;3.Compared to visceral obesity,overall obesity(represented by BMI)is the main risk factor for subclinical left atrial function impairment;4.The underlying mechanism between the TyG index calculated with triglycerides and blood glucose(represented by insulin resistance)and subclinical LA dysfunction provides valuable information,and the use of the TyG index may help in the early identification of high-risk individuals for HF;5.There are differentially expressed exosomal proteins in the serum of patients with left atrial dysfunction and healthy left atrial function;the biological processes involved in these differentially expressed proteins may be related to the occurrence and development of early left atrial dysfunction;6.Pathways such as glycolysis,lipid metabolism,insulin resistance,oxidative stress,cardiac calcium-contraction coupling,and activation of the RAAS system may be involved in early left atrial dysfunction. |
PDF Full Text Request