Cardiac effects of prolonged exercise

Detta är en avhandling från Stockholm : Karolinska Institutet, Department of Medicine

Sammanfattning: Long-distance running is growing in popularity. While moderate exercise unquestionably gives major health benefits, the effects of extreme physical exhaustion on cardiac function have been studied less. It has previously been observed that elevated cardiac biomarkers may be observed after exercise, the significance of which is not known. We aimed to study the cardiac impact of the 30-km endurance race Lidingöloppet using biomarkers N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) and troponin T (TnT) and characterised cardiac function by echocardiography and vectorcardiographic measures of ventricular repolarisation. In study I, 22 healthy senior runners that participated twice in the Lidingöloppet race (in 2003 and 2006) were studied using cardiac biomarkers (TnT, NT-proBNP) at baseline and after the race. Echocardiography was performed at baseline. TnT increased reproducibly in a subset of participants. NT-proBNP increased in all subjects and individuals reached similar levels at the two races. Both biomarkers were associated with larger left atrium and NT-proBNP was associated with greater LV mass suggesting a link to cardiac filling pressures. In study II, a group of 15 runners were studied longitudinally from baseline before the race, immediately post-race, on the next day and on day six. Vectorcardiography was used to determine measures of ventricular repolarisation and echocardiography was performed to examine cardiac functional changes. The race led to QT-interval prolongation mainly due to an increased Tpeak-to-Tend interval, as well as an enlarged Tarea which was sustained during the next 6 days. Runners with higher baseline NT-proBNP developed greater attenuation of myocardial velocities and a larger increase in Tarea. Functional fatigue of the heart thus occurs in parallel with altered ventricular repolarisation. In study III, predictors of biomarker release were analysed at baseline and after the race in 185 runners aged an average of 61 years. In multivariable regression, independent predictors of large biomarker release were established. NT-proBNP release was predicted by (1) a higher level present at baseline, (2) a larger increase in creatinine, (3) higher age and (4) longer race duration. Elevation of TnT was predicted by (1) higher age, (2) a larger increase in creatinine and (3) fewer previous race participations. In 15 cases (8.1%), NT-proBNP was already elevated at baseline. Clinical work-up showed that 4 of these runners (2.2% of whole study population) harboured serious cardiovascular disease of whom one suffered sudden cardiac death within a few months after the race. In study IV, 23 experienced runners (median 11 previous race participations) were age-matched against 20 beginners (never raced previously in Lidingöloppet). Tissue Doppler imaging was used to analyse intra-left ventricular mechanical synchrony by computing the standard deviation of time-to-peak myocardial systolic velocity across 12 myocardial segments (Ts-SD). Furthermore, the I/D polymorphism of the Angiotensin-Converting Enzyme (ACE) gene was analysed. Post-race, beginners had higher levels of TnT in association with greater dyssynchrony. In multivariable analysis, post-race dyssynchrony was predicted by (1) lack of race experience, (2) more copies of the ACE D allele and (3) lower peak longitudinal systolic velocity. In study V, 31 experienced participants were age-matched against 35 beginners and studied before and after Lidingöloppet. Blood tests drawn included NT-proBNP, TnT and C-reactive protein (CRP). Genetic analysis of ACE I/D status was also performed. Despite similar levels at baseline, post-race levels of all biomarkers were higher in beginners. Homozygous carriers of the D allele exhibited a larger release of NT-proBNP despite non-significant differences between allele groups at baseline, showing that genetic factors are important for the release of NT-proBNP in runners. In conclusion, this study of predominantly senior long distance runners shows that prolonged exercise causes significant immediate and short-term effects on different aspects of cardiac function including biomarkers, myocardial velocities, ventricular repolarisation and intra-ventricular synchrony. Biomarkers rise especially in runners with less experience of endurance events. Levels of NT-proBNP are influenced by genetic factors and rise in the presence of cardiac dysfunction. Future studies need to address the potential clinical impact of these findings.

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