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- Aagaard, Philip
(författare)
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Cardiovascular assessment in middle-aged male long distance runners
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Endurance events such as long distance running races are increasing in popularity and convey multiple health benefits. However, such exercise forms also represent a major challenge to human cardiovascular physiology and are associated with a momentarily increased risk for adverse cardiac events. Using the world’s largest cross-country running race Lidingöloppet as a model of endurance events, this thesis aims to: 1) investigate male and female participation and performance trends 2) detail the cardiovascular findings of a comprehensive cardiovascular preparticipation evaluation in novice male race participants aged 45 years and older 3) study the impact of race participation on cardiac autonomic tone and 4) assess features of cardiovascular function and vectorcardiography (VCG), and their response to endurance exercise in individuals with early repolarisation (ER). Study I: Participation and performance trends were investigated in >120,000 runners partaking in the Lidingöloppet between 1993 and 2007. In a subgroup of 249 middle-aged males, the association between the cardiac biomarker NT-proBNP and runtime was also studied. Participation increased over the study period, particularly in females and older males, while participants’ fitness deteriorated, as measured by an average increase in runtime of 21 ± 31 min. Longer runtimes were independently associated with higher levels of NT-proBNP. Study II: A preparticipation cardiovascular exam was performed in 153 middle-aged male first-time Lidingöloppet race participants. Runners were assessed by medical history and physical exam, 12-lead ECG, echocardiography, and blood tests. 9 % of runners required further diagnostic work-up and 2 % were discouraged from race participation due to cardiac abnormalities that could increase their risk of exercise- related cardiac events. Study III: Heart rate (HR) and heart rate variability (HRV) was continuously measured from 48 hours before until 96 hours after a Lidingöloppet 30km race. Compared to pre-race values, HR was elevated during the night after the race while HRV remained depressed for 64 [51 - 96] hours after the race. A reduced HR recovery and a greater fall in HRV post race were associated with higher levels of high-sensitivity troponin T (hsTnT). Study IV: The prevalence and associated cardiac features of ER, characterized by ST-segment elevation (STE) and/or J-waves, was investigated in 153 middle-aged males registered for first-time participation in the Lidingöloppet 10, 15 or 30km race. ER was present in 40 % and generally associated with features of better cardiovascular fitness. The cardiovascular effects of participating in the 30km race (n= 94) were also assessed after the race; runners with J-waves, but not with STE alone, showed changes of repolarisation parameters usually considered unfavourable (e.g. prolonged T peak-to-end (Tpe) and QTc). Conclusion: This thesis demonstrated that increased participation in a long distance running event (Lidingöloppet) was paralleled by deteriorating runtimes. In middle-aged men, longer runtimes were associated with higher levels of NT-proBNP. These findings may raise concern regarding the fitness and cardiovascular health of some of today’s race participants. A comprehensive preparticipation evaluation identified 9 % of first- time runners needing additional work-up and 2% who were ultimately discouraged from participating, suggesting that such a protocol is useful to identify individuals requiring further testing prior to vigorous exercise. After the race there was a prolonged depression of HRV. The magnitude and duration of HRV depression correlated with higher levels of hsTnT, suggesting that the degree of troponin (Tn) increase after strenuous exercise may reflect the level of exercise-induced cardiovascular stress. ER was generally associated with a benign cardiovascular profile, although subjects with J-waves showed post-race changes in some parameters of ventricular repolarisation that are usually associated with increased arrhythmia propensity. More research into the mechanisms and potential preventive measures of adverse exercise related effects on cardiac function is warranted.
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| 2. |
- Aagaard, Philip, et al.
(författare)
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Early Repolarization in Middle-Age Runners-Cardiovascular Characteristics.
- 2014
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Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 46:7, s. 1285-1292
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study aimed to assess the prevalence and patterns of early repolarization (ER) in middle-age long-distance runners, its relation to cardiac structure and function, and its response to strenuous physical activity. Methods: Male first-time cross-country race participants >45 yr were assessed pre-and postrace by medical history and physical examination, 12-lead ECG, vectorcardiography, blood tests, and echocardiography. ER was defined either as ST elevation or J wave and categorized according to localization and morphology. Results: One hundred and fifty-one subjects (50 +/- 5 yr) were evaluated before the race, and 47 subjects were evaluated after the race. Altogether, 67 subjects (44%) had ER. Subjects with versus without ER had a lower resting HR (56 +/- 8 vs 69 +/- 9 bpm, P = 0.02), lower body mass index (24 +/- 2 vs 25 +/- 3 kg.m(-2), P < 0.001), higher training volume (3.0 +/- 2.6 vs 2.1 +/- 2.7 h.wk(-1), P = 0.03), and faster 30-km running times (194 +/- 28 vs 208 +/- 31 min, P = 0.01). Vectorcardiography parameters in subjects with ER showed more repolarization heterogeneity: vector gradient (QRS-T-area) (120 +/- 25 vs 92 +/- 29 mu Vs, P < 0.001), T-area (105 +/- 18 vs 73 +/- 23 mu Vs, P < 0.001), and T-amplitude (0.63 +/- 0.13 vs 0.53 +/- 0.16 mm, P < 0.001); these parameters were inversely related to HR (r = -0.37 to -0.48, P < 0.001). ER disappeared in 15 (75%) of 20 subjects after the race. Conclusions: ER is a common finding in middle-age male runners. This ECG pattern, regardless of morphology and localization, is associated with normal cardiac examinations including noninvasive electrophysiology, features of better physical conditioning, and disappears after strenuous exercise in most cases. These findings support that ER should be regarded as a common and training-related finding also in middle-age physically active men.
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| 3. |
- Ikram, M. Arfan, et al.
(författare)
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Common variants at 6q22 and 17q21 are associated with intracranial volume
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 539-544
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Tidskriftsartikel (refereegranskat)abstract
- During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
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| 4. |
- Sahlén, Anders, et al.
(författare)
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Altered ventriculo-arterial coupling during exercise in athletes releasing biomarkers after endurance running
- 2012
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 112:12, s. 4069-4079
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Tidskriftsartikel (refereegranskat)abstract
- Exercise can lead to release of biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), a poorly understood phenomenon proposed to especially occur with highintensity exercise in less trained subjects. We hypothesised that haemodynamic perturbations during exercise are larger in athletes with cTnT release, and studied athletes with detectable cTnT levels after an endurance event (HIGH; n = 16; 46 ± 9 years) against matched controls whose levels were undetectable (LOW; n = 11; 44 ± 7 years). Echocardiography was performed at rest and at peak supine bicycle exercise stress. Left ventricular (LV) end-systolic elastance (ELV a load-independent measure of LV contractility), effective arterial elastance (EA a lumped index of arterial load) and end-systolic meridional wall stress were calculated from cardiac dimensions and brachial blood pressure. Efficiency of cardiac work was judged from the ventriculo-arterial coupling ratio (EA/ELV: optimal range 0.5-1.0). While subgroups had similar values at rest, we found ventriculo-arterial mismatch during exercise in HIGH subjects (0.47 (0.39-0.58) vs. LOW: 0.73 (0.62-0.83); p<0.01] due to unopposed increase in ELV (p<0.05). In LOW subjects, a greater increase occurred in EA during exercise (+81 ± 67 % vs. HIGH: +39 ± 32 %; p = 0.02) which contributed to a maintained coupling ratio. Subjects with higher baseline NT-proBNP had greater systolic wall stress during exercise (R2 = 0.39; p<0.01) despite no correlation at rest (p = ns). In conclusion, athletes with exercise-induced biomarker release exhibit ventriculo-arterial mismatch during exercise, suggesting non-optimal cardiac work may contribute to this phenomenon.
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| 5. |
- Taal, H. Rob, et al.
(författare)
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Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
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