Showing papers by "Tomi Laitinen published in 2016"
Janina S. Ried, Janina M. Jeff1, Audrey Y. Chu2, Jennifer L. Bragg-Gresham3 +327 more•Institutions (76)
TL;DR: In this paper, the authors examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits, and identified six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AVPC3, and ARL15 and ANP32 for Avpc4.
Abstract: Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
65 citations
TL;DR: Prediction of adulthood hypertension and high-risk intima-media was compared between one observation of abnormal blood pressure in childhood/youth and multiple observations by improved Pearson correlation coefficients and area under the receiver operating curve.
Abstract: Hypertension may be predicted from childhood risk factors. Repeated observations of abnormal blood pressure in childhood may enhance prediction of hypertension and subclinical atherosclerosis in adulthood compared with a single observation. Participants (1927, 54% women) from the Cardiovascular Risk in Young Finns Study had systolic and diastolic blood pressure measurements performed when aged 3 to 24 years. Childhood/youth abnormal blood pressure was defined as above 90th or 95th percentile. After a 21- to 31-year follow-up, at the age of 30 to 45 years, hypertension (>140/90 mm Hg or antihypertensive medication) prevalence was found to be 19%. Carotid intima-media thickness was examined, and high-risk intima-media was defined as intima-media thickness >90th percentile or carotid plaques. Prediction of adulthood hypertension and high-risk intima-media was compared between one observation of abnormal blood pressure in childhood/youth and multiple observations by improved Pearson correlation coefficients and area under the receiver operating curve. When compared with a single measurement, 2 childhood/youth observations improved the correlation for adult systolic (r=0.44 versus 0.35, P 0.05). A higher number of childhood/youth observations of abnormal blood pressure did not enhance prediction of adult high-risk intima-media thickness. Compared with a single measurement, the prediction of adult hypertension was enhanced by 2 observations of abnormal blood pressure in childhood/youth.
61 citations
TL;DR: Poor CRF was independently associated with increased arterial stiffness and impaired arterial dilation capacity among children and was associated with high body fat percentage when CRF, unstructured PA, and BF% were in the same model.
Abstract: Associations of cardiorespiratory fitness (CRF), physical activity (PA), sedentary behavior, and body fat percentage (BF%) with arterial stiffness and dilation capacity were investigated in 160 prepubertal children (83 girls) 6-8 years of age We assessed CRF (watts/lean mass) by maximal cycle ergometer exercise test, total PA, structured exercise, unstructured PA, commuting to and from school, recess PA and total and screen-based sedentary behavior by questionnaire, BF% using dual-energy X-ray absorptiometry, and arterial stiffness and dilation capacity using pulse contour analysis Data were adjusted for sex and age Poorer CRF (standardized regression coefficient β = -0297, P < 0001), lower unstructured PA (β = -0162, P = 0042), and higher BF% (β = 0176, P = 0044) were related to higher arterial stiffness When CRF, unstructured PA, and BF% were in the same model, only CRF was associated with arterial stiffness (β = -0246, P = 0006) Poorer CRF was also related to lower arterial dilation capacity (β = 0316, P < 0001) Children with low CRF (< median) and high BF% (≥ median; P = 0002), low CRF and low unstructured PA (< median; P = 0006) or children with low unstructured PA and high BF% (P = 0005) had higher arterial stiffness than children in the opposite halves of these variables Poor CRF was independently associated with increased arterial stiffness and impaired arterial dilation capacity among children
55 citations
TL;DR: Prediction of adult fatty liver was enhanced by taking into account genetic variants in PNPLA3 and TM6SF2 genes, suggesting that a multifactorial approach with both lifestyle and genetic factors included would improve early identification of children with a high risk ofAdult fatty liver.
49 citations
TL;DR: Lower SES in childhood may be associated with an increased risk for MetS, IFG, and type 2 diabetes in adulthood, and special attention could be paid to children of low SES families to decrease the prevalence of MetS in adulthood.
Abstract: OBJECTIVE We prospectively examined whether family socioeconomic status (SES) in childhood is associated with metabolic syndrome (MetS), impaired fasting glucose (IFG), or type 2 diabetes in adulthood. RESEARCH DESIGN AND METHODS The sample comprised 2,250 participants from the longitudinal Cardiovascular Risk in Young Finns Study cohort. Participants were 3–18 years old at baseline (mean age 10.6 years), and they were followed for 31 years. SES was characterized as reported annual income of the family and classified on an 8-point scale. RESULTS For each 1-unit increase in family SES in childhood, the risk for adult MetS decreased (risk ratio [95% confidence interval] 0.94 [0.90–0.98]; P = 0.003) when adjusted for age, sex, childhood cardiometabolic risk factors (lipids, systolic blood pressure, insulin, and BMI), childhood physical activity, and fruit and vegetable consumption. The association remained after adjustment for participants’ own SES in adulthood (0.95 [0.91–0.99]; P = 0.005). A similar association was seen between childhood SES and the risk of having either adult IFG or type 2 diabetes (0.96 [0.92–0.99]; P = 0.01, age and sex adjusted). This association became nonsignificant after adjustment for childhood risk factors (P = 0.08). Of the individual components of MetS, lower SES in childhood predicted large waist circumference (0.96 [0.93–0.99]; P = 0.003) and a high triglycerides concentration (0.96 [0.92–1.00]; P = 0.04) after adjustment for the aforementioned risk factors. CONCLUSIONS Lower SES in childhood may be associated with an increased risk for MetS, IFG, and type 2 diabetes in adulthood. Special attention could be paid to children of low SES families to decrease the prevalence of MetS in adulthood.
47 citations
TL;DR: In this paper, the authors examined the utility of continuous metabolic syndrome (cMetS) scores vs a dichotomous MetS definition in youth to predict adult type 2 diabetes mellitus (T2DM) and carotid intima-media thickness (IMT).
42 citations
TL;DR: Reducing childhood infections, especially in socioeconomic disadvantaged children, may reduce the cardiometabolic disease burden in adults, and this findings suggest childhood infection may contribute to social gradients observed in adult cardiometric disease risk factors.
Abstract: BACKGROUND AND OBJECTIVES: Socioeconomic disadvantage throughout the life course is associated with increased risk of cardiometabolic diseases, but traditional risk factors do not fully account for the social gradient. We investigated the interactions between low socioeconomic status (SES) and infection in childhood and adverse cardiometabolic parameters in adulthood. METHODS: Participants from the Cardiovascular Risk in Young Finns Study, a cohort well phenotyped for childhood and adulthood cardiometabolic risk factors and socioeconomic parameters, were linked to lifetime hospitalization data from birth onward available from the Finnish National Hospital Registry. In those with complete data, we investigated relationships between infection-related hospitalization in childhood, SES, and childhood and adult cardiometabolic parameters. RESULTS: The study cohort consisted of 1015 participants (age range 3–18 years at baseline and 30–45 years at follow-up). In adults who were raised in below-median income families, childhood infection-related hospitalizations (at age 0–5 years) were significantly associated with higher adult BMI (β ± SE comparing those with 0 vs ≥1 hospitalizations 2.4 ± 0.8 kg/m 2 , P = .008), waist circumference (7.4 ± 2.3 cm, P = .004), and reduced brachial flow–mediated dilatation (−2.7 ± 0.9%, P = .002). No equivalent associations were observed in participants from higher-SES families. CONCLUSIONS: Infection was associated with worse cardiovascular risk factor profiles only in those from lower-SES families. Childhood infection may contribute to social gradients observed in adult cardiometabolic disease risk factors. These findings suggest reducing childhood infections, especially in socioeconomic disadvantaged children, may reduce the cardiometabolic disease burden in adults.
42 citations
TL;DR: An independent association between childhood psychosocial well-being and reduced coronary artery calcification in adulthood is observed and may represent a potentially modifiable risk determinant.
Abstract: Importance There is increasing evidence supporting the importance of psychosocial factors in the pathophysiology of atherosclerotic disease. They have been shown to be associated with the population attributable risk for myocardial infarction. Objective To determine if a score of favorable childhood psychosocial factors would be associated with decreased coronary artery calcification in adulthood. Design, Setting, and Participants The analyses were performed in 2015 using data gathered in 1980 and 2008 within the longitudinal Cardiovascular Risk in Young Finns Study. The data source consisted of 311 individuals who had psychosocial factors measured at ages 12 years to 18 years and coronary artery calcification measured 28 years later in adulthood. The summary measure of psychosocial factors in childhood comprised measures of socioeconomic factors, emotional factors, parental health behaviors, stressful events, self-regulation of the child, and social adjustment of the child. Main Outcomes and Measures Coronary artery calcification at ages 40 years to 46 years. Results Of the 311 participants, 48.2% were men. Of the participants, 55 (17.7%) had some calcium observed in their coronary arteries. A 1-SD increase in a favorable summary score of childhood psychological factors was associated with an adulthood coronary artery calcification probability of 0.85 (95% CI, 0.76-0.95) ( P = .006). This inverse relationship remained significant after adjustment for age, sex, and conventional childhood risk factors (0.85; 95% CI, 0.74-0.97; P = .02) or for age, sex, adulthood conventional cardiovascular risk factors, socioeconomic status, social support, and depressive symptoms (0.83; 95% CI, 0.71-0.97; P = .02). Conclusions and Relevance In this longitudinal study, we observed an independent association between childhood psychosocial well-being and reduced coronary artery calcification in adulthood. A positive childhood psychosocial environment may decrease cardiovascular risk in adulthood and may represent a potentially modifiable risk determinant.
35 citations
TL;DR: The associations between sex, age, education, and cognitive performance are already apparent in young adulthood or middle age, and principal component analyses, categorical and standardized classifications are useful tools to analyze CANTAB cognitive data.
Abstract: Objective Age, education, and sex associate with cognitive performance. We investigated associations between age, sex, education, and cognitive performance in young or middle-aged adults and evaluated data reduction methods to optimally capture cognitive performance in our population-based data. Method This study is part of the Cardiovascular Risk in Young Finns Study. The 3,596 randomly selected subjects (aged 3-18 years in 1980) have been followed up for 30 years. In 2011, a computer-based cognitive testing battery (the Cambridge Neuropsychological Test Automated Battery [CANTAB]) was used to assess several cognitive domains. Principal component analysis, categorical and standardized classifications were applied to the cognitive data. Results Among 34- to 49-year-old participants, cognitive performance declined with age, while education associated with better cognitive functions in several cognitive domains. Men had higher performance on all cognitive domains except visual or episodic memory, in which women outperformed men. The results were similar regardless of the data reduction method used. Conclusions The associations between sex, age, education, and cognitive performance are already apparent in young adulthood or middle age. Principal component analyses, categorical and standardized classifications are useful tools to analyze CANTAB cognitive data. (PsycINFO Database Record
28 citations
01 Jan 2016
27 citations
TL;DR: After an initial increase in parasympathetic regulation, continuous fingolimod dosing shifts cardiac autonomic regulation towards sympathetic predominance, especially in men.
Abstract: Background:Fingolimod modulates sphingosine-1-phosphate receptors that are also found in cardiovascular tissue.Objective:To investigate the effects of fingolimod on cardiac autonomic regulation pro...
TL;DR: This study tested the previously published motion tracking algorithm and validated the method against applanation tonometry measurements, finding it to be applicable to longitudinal wall motion of carotid artery.
Abstract: Summary
Background
Longitudinal wall motion of carotid artery is a useful but challenging parameter to measure. In this study, we tested our previously published motion tracking algorithm and validated our method against applanation tonometry measurements.
Methods and Results
We measured the two-dimensional carotid artery wall motion from 19 healthy subjects and, as a reference, performed applanation tonometry measurements in parallel with the ultrasound study. The results show that peak velocities (R = −0·484; P 0·05). The amplitudes of the longitudinal motion, between intima and adventitia, are related more to the physical size of the subject, as they correlated significantly with the height (R = 0·597; P<0·01) and weight (R = 0·562; P<0·05) of the subject as well as the cross-sectional dimension of the measured artery (R = 0·611; P<0·01). Furthermore, two new indices have been introduced, Polydeg and RAlength, with which to study the shape of the longitudinal motion curve; both parameters displayed significant correlation with arterial stiffness, for example augmentation index (R = 0·468; P<0·05 and R = 0·609; P<0·01, respectively).
Conclusions
The new longitudinal motion parameters presented here displayed clear potential to be used as novel stiffness indices.
TL;DR: A comprehensive set of reference limits of cardiac function and dimensions in a group of young and middle‐aged Finnish men and women produced by the recommendations of European Society of Echocardiography and American Society of Cardiology are reported.
Abstract: Background
Population and sex-specific reference limits produced with modern ultrasound equipment are needed for accurate clinical echocardiography diagnostics. We report a comprehensive set of reference limits of cardiac function and dimensions in a group of young and middle-aged Finnish men and women produced by the recommendations of European Society of Echocardiography and American Society of Cardiology.
Methods and Results
Cardiac structure and function was studied in a standardized comprehensive echocardiographic examination in 1,079 healthy volunteers without cardiovascular diseases or major known risk factors participating in the population-based Young Finns study (444 men and 635 women, age range 34 and 49 years). We present sex-specific reference values for echocardiographic parameters reflecting cardiac structure (ventricular and atrial dimensions and volumes, left ventricular wall thickness and mass, aortic root) and function. From the 86 measured parameters, only 7 were not statistically significantly different between sexes.
Conclusion
The Young Finns study provides echocardiographic reference ranges for cardiac structure and function quantification that can be utilized to enhance the accuracy or echocardiography diagnostics. The results emphasize the need for sex-specific assessment for most echocardiographic parameters.
TL;DR: Long-time risk factor exposure to higher LDL-C, total cholesterol and Apo-B levels already starting in adolescence and higher SBP levels in adulthood is associated with CAC at middle-age.
TL;DR: The children born LGA remained taller and heavier than those born AGA or SGA in mid-childhood, and they had a higher body mass index and body fat percentage than the SGA-born children.
Abstract: Background: Both large and small birth sizes are associated with an increased risk of developing cardiovascular and metabolic problems later in life. We studied w
TL;DR: The second principal component of the longitudinal motion may be a useful parameter reflecting vascular health and reveal the characteristic features of wall motion and their relation to known arterial stiffness indices.
Abstract: The longitudinal motion of the carotid wall during a heart cycle has a multiphasic waveform. Recent studies have examined the amplitude of this motion. Instead of amplitude measurements, we focus on making a detailed characterization of the motion waveform. Two-minute carotid ultrasound videos were obtained for 19 healthy volunteers, and a speckle tracking algorithm was used to measure the motion of the carotid wall. Principal component analysis revealed the characteristic features of wall motion and their relation to known arterial stiffness indices. By estimating two principal components, we could account for more than 92% of the variation in the motion graphs. The first principal component derived from the longitudinal motion curves was significantly correlated to pulse pressure, indicating that the main dominant base waveform of the longitudinal motion was related to blood pressure. The second principal component derived from the longitudinal motion curves had multiple significant correlations to known stiffness indices, indicating that the stronger biphasic structure of the motion curve, especially on the adventitia layer, was associated with higher distensibility and compliance, as well as reduced carotid artery stiffness. According to this study, the second principal component of the longitudinal motion may be a useful parameter reflecting vascular health.
TL;DR: A transfer function analysis with 20 healthy subjects is presented to derive how the energy from the blood pressure moves the innermost arterial wall longitudinally and how the kinetic energy is then transferred to the outer most arterial layer.
Abstract: The longitudinal motion of the carotid wall is a potential new measure of arterial stiffness. Despite the over decade long research on the subject, the driving force and the specific longitudinal kinetics of the carotid wall has remained unclear. In this study, a transfer function analysis with 20 healthy subjects is presented to derive how the energy from the blood pressure moves the innermost arterial wall longitudinally and how the kinetic energy is then transferred to the outermost arterial layer. The power spectrums display that the main kinetic energy of the longitudinal motion is on band 0-3 Hz with a peak on the 1.1 Hz frequency. There is a large variation among the individuals, how the energy from the blood pressure transfers into the longitudinal motion of the arterial wall since the main direction of the longitudinal motion varies individually and because early arterial stiffening potentially has an effect on the time characteristics of the energy transfer. The energy transfer from the innermost to the outermost wall layer is more straightforward: on average, a 17 % of the longitudinal amplitude is lost and an 18.9 ms delay is visible on the 1.0 Hz frequency.
TL;DR: Higher IMT was found in eastern Finns than in western Finns and participants who migrated east-to-west had a lower IMT and a better cardiometabolic risk profile than those who stayed in the east.
Abstract: Background: Coronary heart disease mortality has been internationally high in eastern Finland. The excessive mortality risk in Eastern compared with western Finns is explained by differences in cardiometabolic risk profile. Current risk profile differences and association with migration have not been reported. We examined the association of place of residence (east–west) and specifically migration with cardiometabolic risk markers and carotid intima–media thickness (IMT). Methods: The study population included 2204 participants with data available from childhood/youth in 1980 and follow-up examination in 2007. Results: Participants residing in eastern Finland in adulthood had 0.022±0.004mm higher IMT than Western participants. Those who migrated east-to-west had lower IMT than those staying in the east (0.027±0.006mm, p<0.0001) while no difference to those continuously living in the west was found. Those who moved east-to-west had a lower body mass index (25.3±4.3 kg/m2 vs. 26.2±4.5kg/m2, p=0.01), waist c...
TL;DR: Cardiac autonomic regulation (pNN50>10%) at baseline can be used to predict the magnitude of HR decrease after the first dose of fingolimod.
Abstract: Background Fingolimod is an immunomodulator with a disease modifying effect on relapsing-remitting multiple sclerosis (RRMS). A heart rate (HR) decrease shortly after fingolimod initiation, however, requires a clinical vigilance. The aim of this study was to prospectively investigate whether cardiac autonomic regulation can predict the magnitude of HR decrease after fingolimod initiation. Methods Twenty-five patients with RRMS underwent ambulatory 24-h electrocardiogram recording to assess HR variability 20±16 days before fingolimod initiation (baseline) and repeated at the day of fingolimod initiation to assess the magnitude of HR decrease. The percentage of normal RR-intervals with duration more than 50 ms different from the previous normal RR-interval (pNN50) was calculated (among the other HR variability parameters) to assess cardiac autonomic regulation. The maximal HR decrease (ΔHR) after the first dose of fingolimod was assessed in absolute units (beats/min) and in percentage (%). Results The maximal ΔHR was −20±11 beats/min (−23±12%) on the average. pNN50 calculated at baseline correlated with ΔHR% (r=−0.657, p Conclusions Cardiac autonomic regulation (pNN50>10%) at baseline can be used to predict the magnitude of HR decrease after the first dose of fingolimod. Trial registration ClinicalTrials.gov (NCT01704183).
TL;DR: It is indicated that phase analysis results may be less reproducible in patients with high BMI, whereas global longitudinal strain in echocardiography seems to be less critical for a patient’s BMI.
Abstract: AIM Cardiac resynchronization therapy (CRT) is a treatment for patients with end-stage heart failure. However, two-thirds of the patients are nonresponders. Evaluation of left ventricular mechanical dyssynchrony may help in finding patients who will benefit from CRT. Dyssynchrony can be evaluated by the phase analysis method in myocardial perfusion imaging (MPI) or with cardiac ultrasound. The aim of this study was to investigate the reproducibility of phase analysis parameters in MPI and echocardiographic parameters in the evaluation of left ventricular mechanical dyssynchrony. In particular, the influence of BMI on reproducibility was studied. METHODS AND RESULTS Twenty-one patients underwent an ECG-gated MPI scan. Acquisition was repeated after the rest image. The patients were also studied twice with transthoracic echocardiography. Of MPI phase analysis parameters bandwidth, histogram SD and entropy% were highly reproducible in the pooled population: Cronbach's α 0.927-0.967 and intraclass correlation (ICC) 0.868-0.967, (P<0.001 for all). However, the reproducibility of bandwidth and SD was poorer in patients with BMI≥29 kg/m group (α 0.203 and -0.055; ICC 0.106 and -0.027, NS for both) than in those with BMI<29 kg/m (α 0.984 and 0.980; ICC 0.968 and 0.961, P<0.001 for both). In contrast, BMI had no obvious influence on the reproducibility of global longitudinal strain in echocardiography. CONCLUSION Parameters reflecting mechanical dyssynchrony were found to be well reproducible. However, this study indicates that phase analysis results may be less reproducible in patients with high BMI, whereas global longitudinal strain in echocardiography seems to be less critical for a patient's BMI.
TL;DR: In this paper, a comparison of parameters from maximal cycle ergometer exercise tests that were done first without respiratory gas analysis and thereafter with it in 38 prepubertal and healthy children (20 girls, 18 boys).
Abstract: It is important to distinguish true and clinically relevant changes and methodological noise from measure to measure. In the clinical practice, maximal cycle ergometer tests are typically performed first without respiratory gas analysis and thereafter, if needed, with respiratory gas analysis. Therefore, we report a comparison of parameters from maximal cycle ergometer exercise tests that were done first without respiratory gas analysis and thereafter with it in 38 prepubertal and healthy children (20 girls, 18 boys). The Bland-Altman method was used to assess agreement in maximal workload (WMAX), heart rate (HR), and systolic blood pressure (SBP) between rest and maximum. Girls achieved higher WMAX in the exercise tests with respiratory gas analysis compared with exercise tests without respiratory gas analysis (p = 0.016), whereas WMAX was similar in the tests among boys. Maximal HR (proportional offset, -1%; coefficients of variation, 3.3%) and highest SBP (proportional offset, 3%; coefficients of variation, 10.6%) were similar in the tests among children. Precision and agreement for HR improved and precision for SBP worsened with increasing exercise intensity. Heteroscedasticity was not observed for WMAX, HR, or SBP. We conclude that maximal cycle ergometer tests without and with respiratory gas analysis can be used consecutively because measurement of respiratory gases did not impair performance or have a significant effect on the maximality of the exercise tests. Our results suggest that similar references can be used for children who accept or refuse using a mask during a maximal exercise test.
01 Jan 2016
TL;DR: It is concluded that maximal cycle ergometer tests without and with respiratory gas analysis can be used consecutively because measurement of respiratory gases did not impair performance or have a significant effect on the maximality of the exercise tests.
Abstract: It is important to distinguish true and clinically relevant changes and methodological noise from measure to measure. In the clinical practice, maximal cycle ergometer tests are typically performed first without respiratory gas analysis and thereafter, if needed, with respiratory gas analysis. Therefore, we report a comparison of parameters from maximal cycle ergometer exercise tests that were done first without respiratory gas analysis and thereafter with it in 38 prepubertal and healthy children (20 girls, 18 boys). The Bland-Altman method was used to assess agreement in maximal workload (WMAX), heart rate (HR), and systolic blood pressure (SBP) between rest and maximum. Girls achieved higher WMAX in the exercise tests with respiratory gas analysis compared with exercise tests without respiratory gas analysis (p = 0.016), whereas WMAX was similar in the tests among boys. Maximal HR (proportional offset, -1%; coefficients of variation, 3.3%) and highest SBP (proportional offset, 3%; coefficients of variation, 10.6%) were similar in the tests among children. Precision and agreement for HR improved and precision for SBP worsened with increasing exercise intensity. Heteroscedasticity was not observed for WMAX, HR, or SBP. We conclude that maximal cycle ergometer tests without and with respiratory gas analysis can be used consecutively because measurement of respiratory gases did not impair performance or have a significant effect on the maximality of the exercise tests. Our results suggest that similar references can be used for children who accept or refuse using a mask during a maximal exercise test.
Abstract: The fingertip skin temperature (FST) reflects skin blood flow, and FST measurement has been suggested for the investigation of vascular responses. As a limitation, the multifactorial nature and the seasonal variation in measured values have been earlier described in adults but not in children. In the present study, we identify the modifiers of FST in a population sample of Finnish children. FST was measured in children (age range 8–11 years, n = 432) with infrared thermometer, and its possible determinants including the subjects’ physical characteristics and seasonal variables, such as daylight time and outdoor temperature, were identified. In univariate regression models, FST was dependent on the sex, age and anthropometric characteristics of the children with the higher body fat content-related variables and a lower surface area-to-mass ratio as strongest single modifiers of FST. There was interaction between sex and puberty with FST. In addition, FST was directly related to daylight time and outdoor temperature although the children had stayed inside for at least 2 h before the measurements. The FST values were lowest in the winter and highest in the summer. In multivariate regression model, main determinants of FST were a higher body fat percentage (standardized regression coefficient β = 0.472; p < 0.001), male sex (β = 0.291; p < 0.001) and longer daylight time (0.226; p < 0.001). Altogether, complex effects of body composition and sex with the confounding effect of seasonal variation may complicate the use of FST as a tool to study the vascular function in children.
TL;DR: It is suggested that physiological relation between the circadian pattern of RR‐interval and overall HRV as well as parasympathetic cardiac regulation becomes uncoupled during fingolimod treatment.
Abstract: Fingolimod is an oral sphingosine‐1‐phospate (S1P) receptor modulator for the treatment of relapsing‐remitting multiple sclerosis (RRMS). In addition to therapeutic effects on lymphoid and neural tissue, fingolimod influences cardiovascular system by specific S1P‐receptor modulation. The effects of S1P‐receptor modulation on the endogenous circadian pattern of cardiac autonomic regulation (CAR), however, are not known. We examined the effects of fingolimod on the circadian pattern of CAR. Ambulatory 24‐h ECG recordings were undertaken in 27 RRMS patients before fingolimod (baseline), at the day of fingolimod initiation (1D) and after 3 months of fingolimod treatment (3M). The mean time between two consecutive R‐peaks (RR‐interval) and mean values for measures of heart rate variability (HRV) in time‐ and frequency domain were calculated from ECG recording at daytime and nighttime. The mean night:day‐ratio of RR‐interval was 1.23 ± 0.12 at baseline, decreased temporarily at 1D (1.16 ± 0.12; P 0.01) and was higher at 3M (1.32 ± 0.11; P 0.001) than at baseline. The night:day‐ratio of HRV parameters reflecting parasympathetic cardiac regulation (pNN50, rMSSD, HFnu) decreased at 1D but recovered back to baseline at 3M ( P 0.05 for all). On the other hand, the night:day‐ratio of TP, a parameter reflecting overall HRV gradually decreased and was lower at 3M than at baseline ( P 0.05). Our findings suggest that physiological relation between the circadian pattern of RR‐interval and overall HRV as well as parasympathetic cardiac regulation becomes uncoupled during fingolimod treatment. In addition, fingolimod shifts the circadian equilibrium of CAR toward greater daytime dominance of overall HRV. Accordingly, S1P‐receptor modulation influences circadian pattern of CAR.