title: QTc changes after meal intake: sex differences and correlates.
abstract: BACKGROUND
  Detection of food-induced QTc shortening has been proposed as an assay sensitivity in thorough QT/QTc (TQT) studies. Data of a large clinical study were used to investigate the food effects on QTc intervals.
  
  
  METHODS
  Day-time drug-free 12-lead Holter recordings starting around 8:20AM were repeated 4 times in each of 176 female and 176 male healthy subjects aged 32.7±9.1years. The recordings contained 16 episodes during which the subjects were in strict supine position. Heart rate and QTc intervals individually corrected for rate and QT/RR hysteresis were measured during these episodes and averaged over the 4 repeated recordings. In the morning hours, the subjects were fasting. Standardized lunch and dinner were served at around 2:00PM and 7:30PM, respectively. Heart rate and QTc changes induced by lunch and dinner were assessed by calculating the differences of averaged measurements from 2hours before till 2hours after the meals.
  
  
  RESULTS
  In women, lunch and dinner led to statistically significant heart rate accelerations by 11.0±4.0 and 6.8±3.4 beats per minute [bpm], respectively. In men, the corresponding significant heart rate accelerations were by 9.9±3.4 and 4.5±2.6bpm, respectively. On the contrary, the QTc responses to both meals were inconsistent. After lunch, QTc intervals shortened significantly by 2.87±3.46ms and 0.79±3.64ms in women and men, respectively. However, after dinner, QTc intervals prolonged significantly by 4.69±3.66ms and 3.53±2.88ms in women and men, respectively.
  
  
  CONCLUSIONS
  There were systematic changes in individually corrected QTc intervals with QTc shortening after lunch and QTc lengthening after dinner, both in women and men. Because of these divergent diurnal effects, the use of meal-induced QTc changes to prove the assay sensitivity in TQT studies requires further evaluation.
authors.affiliation: Imperial College, London, UK.
authors.forename: Katerina
authors.initials: K
authors.lastname: Hnatkova
authors.affiliation: Global Clinical Pharmacology and Exploratory Development, Astellas Pharma Global Development Inc., Northbrook, IL, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Kowalski
authors.affiliation: Global Clinical Pharmacology and Exploratory Development, Astellas Pharma Global Development Inc., Northbrook, IL, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Keirns
authors.affiliation: Global Clinical Pharmacology and Exploratory Development, Astellas Pharma Europe B.V., Leiden, The Netherlands.
authors.forename: E Marcel
authors.initials: EM
authors.lastname: van Gelderen
authors.affiliation: St. Paul's Cardiac Electrophysiology and Imperial College, London, UK. Electronic address: marek.malik@btinternet.com.
authors.forename: Marek
authors.initials: M
authors.lastname: Malik
mesh_terms: D000328:Adult; D004435:Eating / Q000502:physiology*; D015716:Electrocardiography, Ambulatory / Q000379:methods*; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D019518:Postprandial Period / Q000502:physiology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012727:Sex Characteristics
keywords: Assay sensitivity; Heart rate; Meal intake; QTc interval