| 1. |
- Connolly, Stuart J., et al.
(författare)
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Dabigatran versus warfarin in patients with atrial fibrillation
- 2009
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 361:12, s. 1139-1151
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor. METHODS: In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran--110 mg or 150 mg twice daily--or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism. RESULTS: Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P=0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150 mg of dabigatran (P=0.051). CONCLUSIONS: In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. (ClinicalTrials.gov number, NCT00262600.)
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| 2. |
- Dutoit, Andrea P, et al.
(författare)
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Cardiac baroreflex sensitivity is not correlated to sympathetic baroreflex sensitivity within healthy, young humans.
- 2010
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Ingår i: Hypertension. - 1524-4563. ; 56:6, s. 1118-1123
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the relationship between the cardiac and sympathetic baroreflex sensitivities within healthy, young humans. The sensitivities of the cardiac and sympathetic baroreflexes were compared in 53 normotensive individuals (28 men and 25 women; age: 24.0 ± 0.9 years; body mass index: 24.0 ± 0.3 cm/kg², mean ± SEM). Heart rate, arterial blood pressure, and peroneal muscle sympathetic nerve activity were recorded under resting conditions (heart rate: 58 ± 1 bpm; systolic blood pressure: 126 ± 2 mm Hg; diastolic blood pressure: 72 ± 1 mm Hg; mean arterial blood pressure: 89 ± 1 mm Hg; muscle sympathetic nerve activity: 18 ± 1 bursts per min) and during rapid changes in blood pressure induced by sequential boluses of nitroprusside and phenylephrine. Cardiac and sympathetic baroreflex sensitivities were analyzed using the slopes of the linear portions of the muscle sympathetic nerve activity-diastolic blood pressure and R-R interval-systolic blood pressure relationships, respectively. When individual cardiac baroreflex sensitivity was compared with sympathetic baroreflex sensitivity, no correlation (R-R interval: r = -0.13; heart rate: r = 0.21) was observed when studied as a group. Analysis by sex unveiled a correlation in women between the cardiac and sympathetic baroreflex sensitivities (R-R interval: r = -0.54; P = 0.01; no correlation with hazard ratio: r = 0.29). No relationship was found in men (R-R interval: r = 0.17; heart rate: r = 0.12). These results indicate that, although both cardiac and sympathetic efferents function in baroreflex control of arterial pressure, there is no correlation in their sensitivities within healthy normotensive humans. However, sex-stratified data indicate that sex-based differential correlations might exist.
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| 3. |
- Fiuza-Luces, Carmen, et al.
(författare)
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Exercise benefits in cardiovascular disease : beyond attenuation of traditional risk factors
- 2018
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Ingår i: Nature Reviews Cardiology. - : Springer Science and Business Media LLC. - 1759-5002 .- 1759-5010. ; 15:12, s. 731-743
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Tidskriftsartikel (refereegranskat)abstract
- Despite strong scientific evidence supporting the benefits of regular exercise for the prevention and management of cardiovascular disease (CVD), physical inactivity is highly prevalent worldwide. In addition to merely changing well-known risk factors for systemic CVD, regular exercise can also improve cardiovascular health through non-traditional mechanisms. Understanding the pathways through which exercise influences different physiological systems is important and might yield new therapeutic strategies to target pathophysiological mechanisms in CVD. This Review includes a critical discussion of how regular exercise can have antiatherogenic effects in the vasculature, improve autonomic balance (thereby reducing the risk of malignant arrhythmias), and induce cardioprotection against ischaemia–reperfusion injury, independent of effects on traditional CVD risk factors. This Review also describes how exercise promotes a healthy anti-inflammatory milieu (largely through the release of muscle-derived myokines), stimulates myocardial regeneration, and ameliorates age-related loss of muscle mass and strength, a frequently overlooked non-traditional CVD risk factor. Finally, we discuss how the benefits of exercise might also occur via promotion of a healthy gut microbiota. We argue, therefore, that a holistic view of all body systems is necessary and useful when analysing the role of exercise in cardiovascular health.
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| 4. |
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| 5. |
- Hart, Emma C, et al.
(författare)
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Baroreflex control of muscle sympathetic nerve activity: a nonpharmacological measure of baroreflex sensitivity.
- 2010
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Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 298:3
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Tidskriftsartikel (refereegranskat)abstract
- The sensitivity of baroreflex control of sympathetic nerve activity (SNA) represents the responsiveness of SNA to changes in blood pressure. In a slightly different analysis, the baroreflex threshold measures the probability of whether a sympathetic burst will occur at a given diastolic blood pressure. We hypothesized that baroreflex threshold analysis could be used to estimate the sensitivity of the sympathetic baroreflex measured by the pharmacological modified Oxford test. We compared four measures of sympathetic baroreflex sensitivity in 25 young healthy participants: the "gold standard" modified Oxford analysis (nitroprusside and phenylephrine), nonbinned spontaneous baroreflex analysis, binned spontaneous baroreflex analysis, and threshold analysis. The latter three were performed during a quiet baseline period before pharmacological intervention. The modified Oxford baroreflex sensitivity was significantly related to the threshold slope (r = 0.71, P < 0.05) but not to the binned (1 mmHg bins) and the nonbinned spontaneous baroreflex sensitivity (r = 0.22 and 0.36, respectively, P > 0.05), which included burst area. The threshold analysis was also performed during the modified Oxford manipulation. Interestingly, we found that the threshold analysis results were not altered by the vasoactive drugs infused for the modified Oxford. We conclude that the noninvasive threshold analysis technique can be used as an indicator of muscle SNA baroreflex sensitivity as assessed by the modified Oxford technique. Furthermore, the modified Oxford method does not appear to alter the properties of the baroreflex.
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| 6. |
- Hart, Emma C, et al.
(författare)
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Hysteresis in the sympathetic baroreflex: role of baseline nerve activity.
- 2011
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Ingår i: The Journal of physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 589:Pt 13, s. 3395-404
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Tidskriftsartikel (refereegranskat)abstract
- Sympathetic baroreflex sensitivity (BRS) is greater during decreasing compared to increasing diastolic blood pressure (DBP) in young men and women. In older men and women there is no difference in sympathetic BRS to increasing and decreasing DBP. We investigated whether the sensitivity of the central nervous system to increasing and decreasing DBP is dependent upon baseline muscle sympathetic nerve activity (MSNA). We hypothesised that the difference in sympathetic BRS between falling and rising segments of DBP would be positively related to baseline MSNA in 30 young men, 21 young women, 14 older men and 14 postmenopausal women. MSNA was measured using peroneal microneurography and BRS was measured using the spontaneous baroreflex threshold technique. On average, sympathetic BRS was greater during decreasing compared to increasing DBP in young men (P <0.05) and women (P <0.05). In older men and women, mean sympathetic BRS was similar in response to increasing and decreasing DBP. The difference (delta) between the falling and rising BRS correlated with baseline MSNA in young (r =0.58, P <0.05) and older men (r =0.66, P <0.05) and postmenopausal women (r =0.74, P <0.05). Thus, all men, and older women, with higher BRS to falling DBP had lower baseline MSNA. This relationship was not observed in young women (r =0.14, P >0.05). In summary, baseline MSNA plays a role in determining sympathetic BRS to falling and rising DBP in young and older men and postmenopausal women, but not in young women. This relationship is consistent with a decreased potential for sympathoexcitation in people with higher resting MSNA. Furthermore, the lack of relationship in young women suggests important contributions of sex hormones to differential responses of MSNA to falling and rising pressures.
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| 7. |
- Hart, Emma C., et al.
(författare)
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Sex, ageing and resting blood pressure: Gaining insights from the integrated balance of neural and haemodynamic factors
- 2012
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Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 590, s. 2069-2079
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Tidskriftsartikel (refereegranskat)abstract
- Young women tend to have lower blood pressure, and less risk of hypertension, compared to young men. As people age, both blood pressure and the risk of hypertension increase in both sexes; this occurs most strikingly in women after menopause. However, the mechanisms for these influences of sex and age remain incompletely understood. In this review we are specifically interested in the interaction between neural (sympathetic nerve activity; SNA) and haemodynamic factors (cardiac output, blood pressure and vascular resistance) and how these change with sex and age. While peripheral vascular SNA can vary 7- to 10-fold among normotensive young men and women, it is reproducible in a given individual. Surprisingly, higher levels of SNA are not associated with higher blood pressures in these groups. In young men, high SNA is associated with higher total peripheral vascular resistance (TPR), and appears to be balanced by lower cardiac output and less peripheral vascular responsiveness to adrenergic stimulation. Young women do not exhibit the SNA-TPR relationship. Recent evidence suggests that β-adrenergic vasodilatation offsets the vasoconstrictor effects of α-adrenergic vasoconstriction in young women, which may contribute to the generally lower blood pressures in this group. Sympathetic nerve activity increases with age, and in groups over 40, levels of SNA are more tightly linked to levels of blood pressure. The potentially protective β-adrenergic effect seen in young women appears to be lost after menopause and probably contributes to the increased blood pressure and increased risk of hypertension seen in older women. © 2012 The Authors. The Journal of Physiology. © 2012 The Physiological Society.
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| 8. |
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| 9. |
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| 10. |
- Wehrwein, Erica A, et al.
(författare)
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Blood pressure regulation in humans: calculation of an "error signal" in control of sympathetic nerve activity.
- 2010
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Ingår i: Hypertension. - 1524-4563. ; 55:2, s. 264-9
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Tidskriftsartikel (refereegranskat)abstract
- Within an individual, diastolic blood pressure (DBP) is negatively related to sympathetic burst incidence, such that lower pressure is associated with high burst incidence. Our goal was to explore the use of a calculation of a DBP "error signal" in the control of muscle sympathetic nerve activity in men and women. Baseline muscle sympathetic nerve activity was measured in healthy young men (n=22) and women (n=28). Women had significantly lower muscle sympathetic nerve activity than men (29+/-3 versus 43+/-2 bursts per 100 heartbeats; P<0.05). For each individual, the DBP at which there is a 50% likelihood of a muscle sympathetic nerve activity burst, the "T50" value, was calculated. Mean DBP was subtracted from the T50 blood pressure as an approximate error signal for burst activation. Error signal was negative in both sexes, indicating that DBP in both sexes was higher than the DBP value associated with a 50% burst likelihood. However, average error signal was significantly larger in women (-4+/-2 mm Hg) than in men (-1+/-0 mm Hg; P<0.05 versus women). We conclude that women operate at a mean DBP greater than their T50 compared with men, and this may be a contributing factor to low basal muscle sympathetic nerve activity in women. The relationship between error signal and burst incidence may provide important insight into the control of muscle sympathetic nerve activity across sexes and in various populations.
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