| Objective:Aging is a complex network-like systemic change affected by multi-factors interaction,and heart aging is no exception.Age-related changes in the expression and function of various ion channels,receptors,enzymes and signaling pathways play a key role in the pathophysiological basis of the aged heart,increasing the susceptibility of aging myocardium to external pressure,and lead to the increase of the incidence and prevalence of cardiovascular diseases in the elderly.Cardiac dysfunction is very common in the elderly population,and about 21%of them show asymptomatic diastolic dysfunction.The mechanism of cardiac diastolic dysfunction is different from that in systolic dysfunction.Some studies have reported that electrical repolarization abnormalities are associated with declining diastolic function,suggesting that diastolic electromechanical coupling represents a unifier linking diastolic dysfunction,calcium handling,and repolarization abnormalities with the development of symptomatic heart failure.However,there are few studies on the relationship between ventricular repolarization stability and cardiac diastolic function in healthy population.The purpose of this study is to assess the correlation between ventricular repolarization stability and cardiac diastolic function in healthy population from both cross-sectional and longitudinal perspectives,to explore the predictive value of ventricular repolarization variables in the changes of cardiac diastolic function,and to provide a theory for improving ventricular repolarization stability as a potential treatment for heart failure in the future.Methods:1 Study population:This was a community-based cross-sectional study in which all subjects were randomly selected from 15 different Shenyang communities between September 2007 and June 2008.Registration requirements for the subjects were as follows:junior middle school education or higher;≥30 years;no self-reported history of disease(heart,brain,lung,kidney,liver disease,hypertension,diabetes,hyperthyroidism,tumor,rheumatoid disease,and chronic infection);no medication use(including estrogen treatment,steroid use,and other drugs);good health(including normal visual and auditory function,emotionally stable,able to handle family and social relationships,able to adapt to the environment,and capable of learning and committing skills to memory);capable of caring for themselves and complete daily living activities without difficulty or the need for help;and of sound mind and able to provide self-reported data and sign informed consent.After excluding persons with abnormal physical examination or laboratory results,414 healthy subjects(186 men and 228 women)were included in the study.In 2011,414 healthy subjects who were selected in 2008 made an appointment for a longitudinal follow-up visit.Following a three-year follow-up,13 subjects were excluded by incompletion and 7 subjects were excluded due to end point events.The end point includes cardiovascular composite endpoint event,myocardial infarction,congestive heart failure,stroke,kidney failure or death.Finally,270 subjects(119 women and 115 men aged 34–84 years)were confirmed as participants.This study was approved by the Ethics Committee of China Medical University,and all study subjects signed written informed consent.2 Study methods2.1 Clinical measurements and laboratory testsThe participants underwent a clinical examination and completed a detailed questionnaire at the time of enrollment.Before being examined,the subjects rested for 10-15 minutes in a temperature-controlled environment.Physical parameters,including height and weight,were measured with a digital scale while the participants were wearing light clothing and were not wearing shoes,on a digital scale.Blood pressure was measured using a manual stethoscope and a sphygmomanometer with an adjustable cuff.Two measurements were performed 2 min apart,and the average of the two measurements was calculated.Body mass index(BMI)was calculated as mass in kilograms divided by height in meters squared,and body surface area(BSA)was calculated according to the following formula:BSA(m~2)=0.0061×height(cm)+0.0128×weight(kg)-0.1529.Blood samples were collected from the subjects between 8:00 and 9:00 am after the subjects had fasted for at least 10 hours overnight.Blood biochemical parameters were assayed on-site at the medical laboratory of the study center.2.2 ElectrocardiographyAll subjects underwent a 12-lead ECG,which was recorded at a paper speed of 25mm/sec and a voltage of 10 mm/mV by a standard ECG system.For ECG analysis,we performed manual measurements of the values with a digital caliper using a computer program.The QT interval was measured between the QRS onset and the end of T wave,and the Tpe interval was measured from the peak of the T wave to the end of the T wave.The QT interval and the Tpe interval were corrected separately for heart rate using the Bazett formula.We also calculated the Tpe/QT ratio and Tpe/QTc ratio.All measurements were performed in lead V5.In cases in which lead V5 could not be used for analysis,leads V4 and V6(in that order)were utilized.ECG measurements were performed by a single trained reader who was blinded to the echocardiographic results.2.3 EchocardiographyAll subjects underwent a complete M-mode,two-dimensional and pulsed-wave(PW)Doppler echocardiographic examination,and all echocardiographic measurements were performed according to published guidelines.PW Doppler was performed in the apical4-chamber view to obtain data pertaining to mitral inflow velocities and time intervals.The primary measurements performed during this procedure included measurements of mitral early diastolic inflow velocity(E),late diastolic inflow velocity(A),the E/A ratio,and E-wave deceleration time(DT).We used the apical four-chamber views to measure left atrial anterior-posterior diameter(LA-AP-D),left atrial medial-lateral diameter(LA-ML-D)and left atrial superior-inferior diameter(LA-SI-D).The left atrial volume(LAV)was computed by the equation 4π/3(LA-SI-D/2)(LA-AP-D/2)(LA-ML-D/2),according to the ellipsoid model,and the left atrial volume index(LAVI)was calculated as LAV in milliliters divided by BSA in meters squared.According to American Society of Echocardiography guidelines,in this study,E/A<0.75 was considered to be reduced diastolic function.2.4 Statistical analysisThe Kolmogorov-Smirnov test was used for normal distribution analysis.Normally distributed data were expressed as mean±standard deviation(SD),and the differences in these variables among groups were examined using a one-way analysis of variance(ANOVA).Least-significant Difference(LSD)analysis or Dunnett’s T3 analyses were used for comparisons between pairs of groups according to the homogeneity of variance test.Simple correlation analyses were performed by calculating Pearson’s coefficients for the relationships between two variables.Multiple regression analyses were used to adjust for possible confounding variables.Categorical data are expressed as numbers,and the differences in these variables among groups were examined using Chi-square test and Fisher probabilities.Binary logistic regression was reformed to investigate the associations between abnormal diastolic function and levels of QTc interval.P-values<0.05 were considered to indicate statistical significance.All statistical analyses were performed using SPSS 17.0 statistical software.Results:In this cross-sectional study,we found electromechanical coupling variables were significantly different among the three age groups,and they also were significantly different between the sexes.Ventricular repolarizations variables were associated with cardiac diastolic function parameters in healthy people.The binary logistic regression analyses performed using reduced diastolic function as the dependent variable and the longer QTc interval as the independent variables shows that,in men,compared to the subjects with normal QTc interval,the odds ratios in subjects with longer QTc interval was 2.567(95%CI,1.227-5.370,P=0.012)after adjustment for all other variables.In the longitudinal study,we found that baseline ventricular repolarizations variables were significantly different among the four groups based on cardiac diastolic function.Baseline levels of QTc interval was significantly correlated with cardiac diastolic function.The multiple logistic regression analysis shows that,compared to the individuals with normal baseline QTc interval,the individuals with longer baseline QTc interval seemed to have higher risk of deteriorate and impaired diastolic function with the odds of 1.946(95%CI 0.921-4.098,p=0.081)and 1.919(95%CI 0.935-3.953,p=0.076)separately.Conclusions:This cross-sectional study reveals that even in healthy people,ventricular repolarization variables are linearly associated with cardiac diastolic function parameters and the associations are different between the sexes.A prolonged QTc interval is associated with a decline in cardiac diastolic function.We also note an independent linear association between the QTc interval and echocardiographic diastolic function parameters in males.Furthermore,longer QTc interval tend to have increased risk of diastolic dysfunction in men.In this longitudinal study,our results confirm that there is interaction of ventricular repolarization variables and various cardiac diastolic function.Baseline levels of QTc interval was significantly correlated with cardiac diastolic function.Longer baseline QTc interval tend to have a higher risk of deteriorate and impared diastolic function.Measurement of the QTc interval can provide information valuable for predicting cardiac diastolic function in healthy people.Identifying a pharmacological intervention to restore repolarization to a more normal state may be a novel target for the therapy of diastolic dysfunction. |
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