Dataset Information

Heart Rate Performance Curve Is Dependent on Age, Sex, and Performance.

ABSTRACT: Introduction: The Heart Rate Performance Curve (HRPC) is neither linear nor uniform and related to ß1-adrenoceptor sensitivity. As aging and exercise influence ß1-adrenoceptors we suggested age, sex and performance effects on the HRPC. Aim of the study was to examine the effects of aging on the deflection of the HRPC in maximal incremental cycle ergometer exercise (CE) in a large cohort of healthy subjects. Methods: Heart rate (HR) data of 2,980 men (51 ± 15 years) and 1,944 women (52 ± 14 years) were classified into age groups (?20 up to >80 years). We analyzed age and performance (Plow 25%-quartile and Phigh 75%-quartile of age predicted power) effects on HRmax and on the degree (k) and the type (regular downward deflection k > 0.1, linear -0.1 ? k ? 0.1 and atypical upward deflection k < -0.1) of the HRPC. Results: k-values decreased significantly with age in men and women and were significantly higher in women. Atypical HRPC's increased by a linear trend from ?20 to 70 years (m) respectively 80 years (w) from 10 to 43% (m) and 9 to 30% (w). HRmax of all age groups was lower in Plow and overall number of atypical HRPC's was 21% (m) and 16% (w) higher compared to Phigh. Conclusion: Aging increased the number of atypical HRPC's with upward deflection in CE tests, which influences exercise intensity prescription especially when using fixed percentages of HRmax. Changes in HRPC's were affected by sex and performance, where women generally and subjects with higher performance presented less atypical HRPC's even at older age.

SUBMITTER: Birnbaumer P

PROVIDER: S-EPMC7144539 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Heart Rate Performance Curve Is Dependent on Age, Sex, and Performance.

Birnbaumer Philipp P Traninger Heimo H Borenich Andrea A Falgenhauer Markus M Modre-Osprian Robert R Harpf Hanns H Hofmann Peter P

Frontiers in public health 20200402

<b>Introduction:</b> The Heart Rate Performance Curve (HRPC) is neither linear nor uniform and related to ß1-adrenoceptor sensitivity. As aging and exercise influence ß1-adrenoceptors we suggested age, sex and performance effects on the HRPC. Aim of the study was to examine the effects of aging on the deflection of the HRPC in maximal incremental cycle ergometer exercise (CE) in a large cohort of healthy subjects. <b>Methods:</b> Heart rate (HR) data of 2,980 men (51 ± 15 years) and 1,944 women ...[more]

PMID: 32300582

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Project description:BackgroundThere are two main reasons for drug withdrawals at the various levels of the development path - hepatic and cardiac toxicity. The latter one is mainly connected with the proarrhythmic potency and according to the present practice is supposed to be recognized at the pre-clinical (in vitro and animal in vivo) or clinical level (human in vivo studies). There are, although, some limitations to all the above mentioned methods which have led to novel in vitro - in vivo extrapolation methods being introduced. With the use of in silico implemented mathematical and statistical modelling it is possible to translate the in vitro findings into the human in vivo situation at the population level. Human physiology is influenced by many parameters and one of them which needs to be properly accounted for is a heart rate which follows the circadian rhythm. We described such phenomenon statistically which enabled the improved assessment of the drug proarrhythmic potency.MethodsA publicly available data set describing the circadian changes of the heart rate of 18 healthy subjects, 5 males (average age 36, range 26-45) and 13 females (average age 34, range 20-50) was used for the heart rate model development. External validation was done with the use of a clinical research database containing heart rate measurements derived from 67 healthy subjects, 34 males and 33 females (average age 33, range 17-72). The developed heart rate model was then incorporated into the ToxComp platform to simulate the impact of circadian variation in the heart rate on QTc interval. The usability of the combined models was assessed with moxifloxacin (MOXI) as a model drug.ResultsThe developed heart rate model fitted well, both to the training data set (RMSE = 128 ms and MAPE = 12.3%) and the validation data set (RMSE = 165 ms and MAPE = 17.1%). Simulations performed at the population level proved that the combination of the IVIVE platform and the population variability description allows for the precise prediction of the circadian variation of drugs proarrhythmic effect.ConclusionsIt can be concluded that a flexible and practically useful model describing the heart rate circadian variation has been developed and its performance was verified.

Project description:The incidence of life-threatening ventricular arrhythmias, the most common cause of sudden cardiac death (SCD), depends largely on the arrhythmic substrate that develops in the myocardium during the aging process. There is a large deficit of comparative studies on the development of this substrate in both sexes, with a particular paucity of studies in females. To identify the substrates of arrhythmia, fibrosis, cardiomyocyte hypertrophy, mitochondrial density, oxidative stress, antioxidant defense and intracellular Ca2+ signaling in isolated cardiomyocytes were measured in the hearts of 3- and 24-month-old female and male rats. Arrhythmia susceptibility was assessed in ex vivo perfused hearts after exposure to isoproterenol (ISO) and hydrogen peroxide (H2O2). The number of ventricular premature beats (PVBs), ventricular tachycardia (VT) and ventricular fibrillation (VF) episodes, as well as intrinsic heart rate, QRS and QT duration, were measured in ECG signals recorded from the surfaces of the beating hearts. After ISO administration, VT/VFs were formed only in the hearts of males, mainly older ones. In contrast, H2O2 led to VT/VF formation in the hearts of rats of both sexes but much more frequently in older males. We identified several components of the arrhythmia substrate that develop in the myocardium during the aging process, including high spontaneous ryanodine receptor activity in cardiomyocytes, fibrosis of varying severity in different layers of the myocardium (nonheterogenic fibrosis), and high levels of oxidative stress as measured by nitrated tyrosine levels. All of these elements appeared at a much greater intensity in male individuals during the aging process. On the other hand, in aging females, antioxidant defense at the level of H2O2 detoxification, measured as glutathione peroxidase expression, was weaker than that in males of the same age. We showed that sex has a significant effect on the development of an arrhythmic substrate during aging. This substrate determines the incidence of life-threatening ventricular arrhythmias in the presence of additional stimuli with proarrhythmic potential, such as catecholamine stimulation or oxidative stress, which are constant elements in the pathomechanism of most cardiovascular diseases.

Dataset Information

Heart Rate Performance Curve Is Dependent on Age, Sex, and Performance.

Publications

Heart Rate Performance Curve Is Dependent on Age, Sex, and Performance.

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