| 1. |
- Ekerstad, Niklas, et al.
(author)
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Frailty as an instrument for evaluation of elderly patients with non-ST-segment elevation myocardial infarction: A follow-up after more than 5 years
- 2018
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In: European Journal of Preventive Cardiology. - : SAGE PUBLICATIONS LTD. - 2047-4873 .- 2047-4881. ; 25:17, s. 1813-1821
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Journal article (peer-reviewed)abstract
- Background There is a growing body of evidence on the relevance of using frailty measures also in a cardiovascular context. The estimated time to death is crucial in clinical decision-making in cardiology. However, data on the importance of frailty in long-term mortality are very scarce. The aim of the study was to assess the prognostic value of frailty on mortality at long-term follow-up of more than 5 years in patients 75 years or older hospitalised for non-ST-segment elevation myocardial infarction. We hypothesised that frailty is independently associated with long-term mortality. Design This was a prospective, observational study conducted at three centres. Methods and results Frailty was assessed according to the Canadian Study of Health and Aging clinical frailty scale (CFS). Of 307 patients, 149 (48.5%) were considered frail according to the study instrument (degree 5-7 on the scale). The long-term all-cause mortality of more than 5 years (median 6.7 years) was significantly higher among frail patients (128, 85.9%) than non-frail patients (85, 53.8%), (P amp;lt; 0.001). In Cox regression analysis, frailty was independently associated with mortality from the index hospital admission to the end of follow-up (hazard ratio 2.06, 95% confidence interval 1.51-2.81; P amp;lt; 0.001) together with age (P amp;lt; 0.001), ejection fraction (P = 0.012) and Charlson comorbidity index (P = 0.018). Conclusions In elderly non-ST-segment elevation myocardial infarction patients, frailty was independently associated with all-cause mortality at long-term follow-up of more than 6 years. The combined use of frailty and comorbidity may be the ultimate risk prediction concept in the context of cardiovascular patients with complex needs.
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| 2. |
- Ha, Hojin, et al.
(author)
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Age-Related Vascular Changes Affect Turbulence in Aortic Blood Flow
- 2018
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In: Frontiers in Physiology. - : FRONTIERS MEDIA SA. - 1664-042X. ; 9
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Journal article (peer-reviewed)abstract
- Turbulent blood flow is implicated in the pathogenesis of several aortic diseases but the extent and degree of turbulent blood flow in the normal aorta is unknown. We aimed to quantify the extent and degree of turbulece in the normal aorta and to assess whether age impacts the degree of turbulence. 22 young normal males (23.7 +/- 3.0 y.o.) and 20 old normal males (70.9 +/- 3.5 y.o.) were examined using four dimensional flow magnetic resonance imaging (4D Flow MRI) to quantify the turbulent kinetic energy (TKE), a measure of the intensity of turbulence, in the aorta. All healthy subjects developed turbulent flow in the aorta, with total TKE of 3-19 mJ. The overall degree of turbulence in the entire aorta was similar between the groups, although the old subjects had about 73% more total TKE in the ascending aorta compared to the young subjects (young = 3.7 +/- 1.8 mJ, old = 6.4 +/- 2.4 mJ, p amp;lt; 0.001). This increase in ascending aorta TKE in old subjects was associated with age-related dilation of the ascending aorta which increases the volume available for turbulence development. Conversely, age-related dilation of the descending and abdominal aorta decreased the average flow velocity and suppressed the development of turbulence. In conclusion, turbulent blood flow develops in the aorta of normal subjects and is impacted by age-related geometric changes. Non-invasive assessment enables the determination of normal levels of turbulent flow in the aorta which is a prerequisite for understanding the role of turbulence in the pathophysiology of cardiovascular disease.
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| 3. |
- Joshi, Peter K, et al.
(author)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Journal article (peer-reviewed)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 4. |
- Lindenberger, Marcus, et al.
(author)
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Cardiovascular biomarkers and echocardiographic findings at rest and during graded hypovolemic stress in women with recurrent vasovagal syncope
- 2019
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In: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1045-3873 .- 1540-8167. ; 30:12, s. 2936-2943
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Journal article (peer-reviewed)abstract
- Introduction: Vasovagal reflex is the most common type of syncope but its etiology is not fully elucidated. Venous return and cardiac output are key in hemodynamic control. The aim of the study was to assess cardiovascular biomarkers and echocardiographic measures at rest and during hypovolemia in women with and without a history of vasovagal syncope. Methods: Fourteen women (aged 18-30) suffering from recurrent vasovagal syncope and 15 age-matched healthy women were included. Graded lower body negative pressure (LBNP) was used to create central hypovolemic stress until signs of presyncope occurred. Echocardiography was applied at rest and throughout LBNP. Cardiovascular biomarkers: copeptin, mid-regional proadrenomedullin, mid-regional pro-ANP, C-terminal proendothelin-1, and plasma norepinephrine were measured both at rest and throughout graded hypovolemia to presyncope. Results: Women prone to vasovagal syncope presented with a narrower right ventricle (RV) (29 ± 1 vs 32 ± 1 mm, P <.05), smaller left atrium (36 ± 2 vs 47 ± 3 cm3, P <.01) and lower cardiac output at rest (3.1 ± 0.2 vs 3.7 ± 0.2 L/min, P <.05) and during graded hypovolemia (P <.05). Copeptin was elevated at rest (4.3 ± 0.8 vs 2.5 ± 0.2 pmol/L, P <.05) and increased more in women with vasovagal syncope during progression of LBNP (P <.01). At rest, lower C-terminal proendothelin-1 (35 ± 5 vs 46 ± 2 pmol/L, P <.05) and higher norepinephrine levels (1.1 ± 0.1 vs 0.8 ± 0.1 nmol/L, P <.01) were seen in women with vasovagal syncope. Conclusion: Women prone to vasovagal syncope demonstrate reduced cardiac preload, lower cardiac output, as well as increased release of vasopressin in rest and during hypovolemic challenge. The results emphasize the importance of venous return and cardiac output in the pathogenesis of vasovagal syncope.
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| 5. |
- Lindenberger, Marcus
(author)
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Reduced Venous Compliance in Young Women with Type 1 Diabetes - Further Aggravated by Prolonged Elevated Levels of HbA1c
- 2016
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In: Frontiers in Endocrinology. - : FRONTIERS MEDIA SA. - 1664-2392. ; 7:126
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Journal article (peer-reviewed)abstract
- Background: Young patients with diabetes present with reduced compensatory responses to hypovolemic stress. Less compliant veins could be a contributing factor, since roughly two-thirds of the blood volume resides in the venous system as a blood reservoir, adjusting proper venous inflow to the heart. The aim of this study was to measure venous compliance and lower limb blood pooling during hypovolemic stress, and to correlate them to indices of diabetes severity and glucose control. Methods: Fifteen young women with type 1 diabetes (DW) and 18 healthy age-matched women (C) were subjected to lower body negative pressure (LBNP) (11-44 mmHg), creating hypovolemic stress. Lower limb blood pooling was measured with strain gage technique and venous compliance calculated as the relationship between Delta V/Delta P. Results: DW presented with reduced blood pooling (e.g., blood pooling during LBNP of 44 mmHg, DW, 1.69 +/- 0.10; C, 2.10 +/- 0.08 (ml/100 ml), and P = 0.003). Calculated venous compliance was also reduced in DW (e.g., compliance at 20 mmHg, DW, 0.046 +/- 0.003; C, 0.059 +/- 0.002 (ml/100 ml/mmHg), and P = 0.002). A progressive reduction in both venous compliance (P amp;lt; 0.007) and blood pooling (P amp;lt; 0.005) was seen with increasing level of HbA(1c), and furthermore, less strongly associated with presence of microvascular disease (signs of retinopathy). Conclusion: Women with type 1 diabetes present with both reduced venous compliance and blood pooling. The reductions were particularly present in patients with long-standing poor glycemic control.
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| 6. |
- Lindenberger, Marcus, et al.
(author)
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Slower lower limb blood pooling in young women with orthostatic intolerance.
- 2015
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In: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 100:1, s. 2-11
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Journal article (peer-reviewed)abstract
- NEW FINDINGS: What is the central question of this study? Orthostatic stress is mostly caused by venous blood pooling in the lower limbs. Venous distension elicits sympathetic responses, and increased distension speed enhances the cardiovascular response. We examine whether lower limb blood pooling rate during lower body negative pressure is linked to orthostatic intolerance. What is the main finding and its importance? A similar amount of blood was pooled in the lower limb, but at a slower rate in women who developed signs of orthostatic intolerance. The difference in blood pooling rate increased with orthostatic stress and was most prominent at a presyncope-inducing level of lower body negative pressure. The findings have implications for the pathophysiology as well as treatment of orthostatic intolerance. Vasovagal syncope is common in young women, but its aetiology remains elusive. Orthostatic stress-induced lower limb blood pooling is linked with central hypovolaemia and baroreceptor unloading. Venous distension in the arm elicits a sympathetic response, which is enhanced with more rapid distension. Our aim was to study both the amount and the speed of lower limb pooling during orthostatic stress and its effects on compensatory mechanisms to maintain cardiovascular homeostasis in women with orthostatic intolerance. Twenty-seven healthy women, aged 20-27 years, were subjected to a lower body negative pressure (LBNP) of 11-44 mmHg. Five women developed symptoms of vasovagal syncope (orthostatic intolerant) and were compared with the remaining women, who tolerated LBNP well (orthostatic tolerant). Lower limb blood pooling, blood flow and compensatory mobilization of venous capacitance blood were measured. Lower body negative pressure induced equal lower limb blood pooling in both groups, but at a slower rate in orthostatic intolerant women (e.g. time to 50% of total blood pooling, orthostatic intolerant 44 ± 7 s and orthostatic tolerant 26 ± 2 s; P < 0.001). At presyncope-inducing LBNP, the mobilization of venous capacitance blood was both reduced (P < 0.05) and much slower in orthostatic intolerant women (P = 0.0007). Orthostatic intolerant women elicited blunted arterial vasoconstriction at low-grade LBNP, activating only cardiopulmonary baroreceptors, while orthostatic tolerant women responded with apparent vasoconstriction (P < 0.0001). In conclusion, slower lower limb blood pooling could contribute to orthostatic intolerance in women. Mobilization of venous capacitance blood from the peripheral to the central circulation was both slower and decreased; furthermore, reduced cardiopulmonary baroreceptor sensitivity was found in women who developed orthostatic intolerance. Further studies including women who experience syncope in daily life are needed.
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| 7. |
- Skoog, Johan, et al.
(author)
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Calf venous compliance measured by venous occlusion plethysmography : methodological aspects.
- 2015
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In: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 115:2, s. 245-56
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Journal article (peer-reviewed)abstract
- PURPOSE: Calf venous compliance (C calf) is commonly evaluated with venous occlusion plethysmography (VOP) during a standard cuff deflation protocol. However, the technique relies on two not previously validated assumptions concerning thigh cuff pressure (P cuff) transmission and the impact of net fluid filtration (F filt) on C calf. The aim was to validate VOP in the lower limb and to develop a model to correct for F filt during VOP.METHODS: Strain-gauge technique was used to study calf volume changes in 15 women and 10 age-matched men. A thigh cuff was inflated to 60 mmHg for 4 and 8 min with a subsequent decrease of 1 mmHg s(-1). Intravenous pressure (P iv) was measured simultaneously. C calf was determined with the commonly used equation [Compliance = β 1 + 2β 2 × P cuff] describing the pressure-compliance relationship. A model was developed to identify and correct for F filt.RESULTS: Transmission of P cuff to P iv was 100 %. The decrease in P cuff correlated well with P iv reduction (r = 0.99, P < 0.001). Overall, our model showed that C calf was underestimated when F filt was not accounted for (all P < 0.01). F filt was higher in women (P < 0.01) and showed a more pronounced effect on C calf compared to men (P < 0.05). The impact of F filt was similar during 4- and 8-min VOP.CONCLUSIONS: P cuff is an adequate substitute for P iv in the lower limb. F filt is associated with an underestimation of C calf and differences in the effect of F filt during VOP can be accounted for with the correction model. Thus, our model seems to be a valuable tool in future studies of venous wall function.
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| 8. |
- Skoog, Johan
(author)
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Cardiovascular regulation in women with vasovagal syncope : With special reference to the venous system
- 2016
-
Doctoral thesis (other academic/artistic)abstract
- Although vasovagal syncope (VVS) is a common clinical condition the mechanisms behind VVS remain elusive. Upright posture is the major trigger of VVS and lower limb blood pooling affecting cardiac output has been proposed as a major determinant. The overall aim of this thesis was twofold. First, to develop new methodology for calculating limb venous compliance. Second, to study lower limb venous volume load and cardiovascular responses during hypovolemic circulatory stress caused by lower body negative pressure (LBNP) in healthy women and women with VVS, emphasizing compensatory mechanisms to maintain central blood volume.Net fluid filtration was associated with an underestimation ofvenous compliance. This could be accounted for with a correctionmodel. Further, a new venous wall model made it possible to adopt thevenous pressure-volume curve through the entire pressure range andthus provide a valid characterization of venous compliance.Calf blood pooling was similar between the groups and was not associated with tolerance to hypovolemic circulatory stress. Venous compliance was reduced at low venous pressures in VVS and correlated with decreased tolerance to circulatory stress. VVS women displayed attenuated sympathetic vasoconstrictor responses during graded circulatory stress, and mobilization of arm capacitance blood as well as capillary fluid absorption from extra- to intravascular space were reduced. Accordingly, more pronounced reductions in cardiac output were found in VVS. Thus, reduced compensatory mechanisms to maintain cardiac output could contribute to the pathogenesis oforthostatic VVS.In healthy women, rapid pooling in the lower limb was associated with higher tolerance to circulatory stress and more efficient cardiovascular responses, in part due to speed-dependent baroreflex-mediated sympathetic activation. In VVS however, rapid lower limb blood pooling was associated with lower tolerance and deficient cardiovascular responses. No speed-dependent baroreflexmediated sympathetic activation was found in VVS, indicating welldefined differences in cardiovascular regulation already in the initial responses to orthostatic stress.
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| 9. |
- Skoog, Johan, 1977-, et al.
(author)
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Reduced compensatory responses to maintain central blood volume during hypovolemic stress in women with vasovagal syncope
- 2017
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In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : AMER PHYSIOLOGICAL SOC. - 0363-6119 .- 1522-1490. ; 312:1, s. R55-R61
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Journal article (peer-reviewed)abstract
- Although vasovagal syncope (VVS) is a common clinical condition, the underlying pathophysiology is not fully understood. A decrease in cardiac output has recently been suggested as a factor in orthostatic VVS. The aim was to investigate compensatory mechanisms to maintain central blood volume and venous return during hypovolemic stress in women with VVS. Fourteen VVS women (25.7 +/- 5.0 yr) and 15 matched controls (22.8 +/- 3.2 yr) were investigated. Single-step and graded lower body negative pressure (LBNP) to presyncope were used to create hypovolemic stress. Peripheral mobilization of venous blood from the arm (capacitance response and net capillary fluid absorption) and lower limb blood pooling (calf capacitance response) were evaluated using a volumetric technique. Cardiovascular responses and plasma norepinephrine (P-NE) were measured. Resting P-NE was elevated in VVS women (P amp;lt; 0.01). Despite a similar hypovolemic stimulus, the increase in P-NE was blunted (P amp;lt; 0.01) and the maximal percent increase in total peripheral resistance was reduced (P amp;lt; 0.05) during graded LBNP in VVS women. The arm capacitance response was slower (P amp;lt; 0.05) and reduced in VVS women at higher levels of LBNP (P amp;lt; 0.05). Capillary fluid absorption from extra-to intravascular space was reduced by similar to 40% in VVS women (P amp;lt; 0.05). Accordingly, the reduction in cardiac output was more pronounced (P amp;lt; 0.05). In conclusion, in VVS women, mobilization of peripheral venous blood and net fluid absorption from tissue to blood during hypovolemic stress were decreased partly as a result of an attenuated vasoconstrictor response. This may seriously impede maintenance of cardiac output during hypovolemic stress and could contribute to the pathogenesis of VVS.
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| 10. |
- Skoog, Johan, et al.
(author)
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Reduced venous compliance: an important determinant for orthostatic intolerance in women with vasovagal syncope
- 2016
-
In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : AMER PHYSIOLOGICAL SOC. - 0363-6119 .- 1522-1490. ; 310:3, s. R253-R261
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Journal article (peer-reviewed)abstract
- The influence of lower limb venous compliance on orthostatic vasovagal syncope (VVS) is uncertain. The most widespread technique to calculate venous compliance uses a nonphysiological quadratic regression equation. Our aim was therefore to construct a physiologically derived venous wall model (VWM) for calculation of calf venous compliance and to determine the effect of venous compliance on tolerance to maximal lower body negative pressure (LBNP). Venous occlusion plethysmography was used to study calf volume changes in 15 women with VVS (25.5 +/- 1.3 yr of age) and 15 controls (22.8 +/- 0.8 yr of age). The fit of the VWM and the regression equation to the experimentally induced pressure-volume curve was examined. Venous compliance was calculated as the derivative of the modeled pressure-volume relationship. Graded LBNP to presyncope was used to determine the LBNP tolerance index (LTI). The VWM displayed a better fit to the experimentally induced pressure-volume curve (P < 0.0001). Calf blood pooling was similar in the groups and was not correlated to the LTI (r = 0.204, P = 0.30). Venous compliance was significantly reduced at low venous pressures in women with VVS (P = 0.042) and correlated to the LTI (r = 0.459, P = 0.014) in the low pressure range. No correlation was found between venous compliance at high venous pressures and the LTI. In conclusion, the new VWM accurately adopted the curvilinear pressure-volume curve, providing a valid characterization of venous compliance. Reduced venous compliance at low venous pressures may adversely affect mobilization of peripheral venous blood to the central circulation during hypovolemic circulatory stress in women with VVS.
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