1. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(author)
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Home Blood Pressure Compared With Office Blood Pressure in Relation to Dysglycemia
- 2022
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In: American Journal of Hypertension. - Oxford, United Kingdom : Oxford University Press. - 0895-7061 .- 1941-7225. ; 35:9, s. 810-819
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Journal article (peer-reviewed)abstract
- Background: Masked hypertension is more common in individuals with type 2 diabetes than in individuals with normoglycemia. We aimed to explore if there is a discrepancy between office blood pressure (office BP) and home blood pressure monitoring (HBPM) in relation to HbA1c as well as glycemic status in 5,029 middle-aged individuals.Methods: HBPM was measured in a subsample of 5,029 participants in The Swedish CardioPulmonary BioImage Study (SCAPIS), a population-based cohort of 50–64 years old participants. Both office BP and HBPM were obtained after 5 minutes’ rest using the semiautomatic Omron M10-IT oscillometric device. White coat effect was calculated by subtracting systolic HBPM from systolic office BP. Participants were classified according to glycemic status: Normoglycemia, prediabetes, or diabetes based on fasting glucose, HbA1c value, and self-reported diabetes diagnosis.Results: Of the included 5,025 participants, 947 (18.8%) had sustained hypertension, 907 (18.0%) reported taking antihypertensive treatment, and 370 (7.4%) had diabetes mellitus. Both systolic office BP and HBPM increased according to worsened glycemic status (P for trend 0.002 and 0.002, respectively). Masked hypertension was more prevalent in participants with dysglycemia compared with normoglycemia (P = 0.036). The systolic white coat effect was reversely associated with HbA1c (P = 0.012).Conclusions: The systolic white coat effect was reversely associated with HbA1c, and the prevalence of masked hypertension increased with dysglycemia.
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2. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(author)
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Masked hypertension in a middle-aged population and its relation to manifestations of vascular disease
- 2023
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In: Journal of Hypertension. - : Wolters Kluwer. - 0263-6352 .- 1473-5598. ; 41:7, s. 1084-1091
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Journal article (peer-reviewed)abstract
- Background: Masked hypertension is associated with cardiovascular disease (CVD). However, previous large studies have not used the same device to measure office and home blood pressure (BP) and adhered to current home BP measurement recommendations of the European Society of Hypertension. We aimed to characterize masked hypertension and explore its relation to manifestations of CVD.Methods: A randomly selected cohort of 5057 participants aged 50–64 years from the Swedish CardioPulmonary BioImage Study (SCAPIS) was evaluated with office and home BP using the semi-automatic Omron M10-IT oscillometric device. Additional analyses included pulse wave velocity (PWV) and coronary artery calcium score (CACS).Results: Of participants, 4122 did not have current antihypertensive treatment, and were thus included in our analyses. Of these, 2634 (63.9%) had sustained normotension, and 172 (4.2%) had masked hypertension. Participants with masked hypertension vs. sustained normotension were more often men (66.9 vs. 46.2%, P < 0.001). Those with masked hypertension had higher mean PWV [9.3 (95% confidence interval, 95% CI 9.1–9.5) vs. 8.3 (95% CI 8.2–8.4) m/s, P < 0.001] and odds ratio for CACS at least 100 [1.65 (95% CI 1.02–2.68), P = 0.040]. These associations were similar in a posthoc analysis of masked hypertension and sustained normotension, matched for age, sex and systolic office BP.Conclusion: Masked hypertension was associated with markers of CVD. This suggests that home BP is a better predictor of risk, even when the recordings are performed with the same measurement device, in a population-based setting with randomized recruitment.
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3. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(author)
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Smoking and cardiovascular disease in patients with type 2 diabetes: a prospective observational study
- 2023
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In: Journal of Cardiovascular Disease. - : Wolters Kluwer. - 2330-4596 .- 2330-460X. ; 24:11, s. 802-807
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Journal article (peer-reviewed)abstract
- BackgroundCigarette smoking is a major risk factor for cardiovascular disease. In type 2 diabetes mellitus (T2D), medications such as antihypertensives and statins can reduce the increased cardiovascular risk. The aim of this study was to evaluate the impact of cigarette smoking on major adverse cardiovascular event (MACE) and all-cause mortality in patients with T2D in a relatively well treated Swedish cohort.MethodsSeven hundred and sixty-one patients with T2D aged 55–66 years were followed in the prospective observational CArdiovascular Risk factors in patients with DIabetes – a Prospective study in Primary care (CARDIPP) study. Baseline data included blood samples of markers of dysglycemia and inflammation, blood pressure as well as questionnaire responses regarding cigarette smoking. Participants were followed for incidence of MACE and all-cause mortality.ResultsOf the included 663 participants, the mean age was 60.6 (SD 3.1) years and 423 (63.8%) were men. Levels of C-reactive protein and vitamin D, as well as the proportion of participants treated with antihypertensives, acetylic salicylic acid, statins, and diabetes medications, were similar between smokers and nonsmokers. Median follow-up time was 11.9 (Q1–Q3 10.8–12.7) years. Cigarette smoking was associated with all-cause mortality [hazard ratio 2.24 (95% confidence interval, 95% CI 1.40–3.56), P < 0.001], but not MACE [hazard ratio 1.30 (95% CI 0.77–2.18), P = 0.328].ConclusionIn patients with T2D, cigarette smoking was not associated with an increased risk of MACE. This raises the question of whether cardioprotective drugs in individuals with T2D to some degree mitigate the cardiovascular harm of smoking, even though they do not affect other dire consequences of smoking.
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4. |
- Carlsson, Axel C, et al.
(author)
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Growth differentiation factor 15 (GDF-15) is a potential biomarker of both diabetic kidney disease and future cardiovascular events in cohorts of individuals with type 2 diabetes : a proteomics approach
- 2020
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In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 25:1, s. 37-43
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Journal article (peer-reviewed)abstract
- Background: Diabetic kidney disease (DKD) is a leading risk factor for end-stage renal disease and is one of the most important risk factors for cardiovascular disease in patients with diabetes. It is possible that novel markers portraying the pathophysiological underpinning processes may be useful.Aim: To investigate the associations between 80 circulating proteins, measured by a proximity extension assay, and prevalent DKD and major adverse cardiovascular events (MACE) in type 2 diabetes.Methods: We randomly divided individuals with type 2 diabetes from three cohorts into a two-thirds discovery and one-third replication set (total n = 813, of whom 231 had DKD defined by estimated glomerular filtration rate <60 mg/mL/1.73 m2 and/or urinary albumin-creatinine ratio ≥3 g/mol). Proteins associated with DKD were also assessed as predictors for incident major adverse cardiovascular events (MACE) in persons with DKD at baseline.Results: Four proteins were positively associated with DKD in models adjusted for age, sex, cardiovascular risk factors, glucose control, and diabetes medication: kidney injury molecule-1 (KIM-1, odds ratio [OR] per standard deviation increment, 1.65, 95% confidence interval [CI] 1.27-2.14); growth differentiation factor 15 (GDF-15, OR 1.40, 95% CI 1.16-1.69); myoglobin (OR 1.57, 95% CI 1.30-1.91), and matrix metalloproteinase 10 (MMP-10, OR 1.43, 95% CI 1.17-1.74). In patients with DKD, GDF-15 was significantly associated with increased risk of MACE after adjustments for baseline age, sex, microalbuminuria, and kidney function and (59 MACE events during 7 years follow-up, hazard ratio per standard deviation increase 1.43 [95% CI 1.03-1.98]) but not after further adjustments for cardiovascular risk factors.Conclusion: Our proteomics approach confirms and extends previous associations of higher circulating levels of GDF-15 with both micro- and macrovascular disease in patients with type 2 diabetes. Our data encourage additional studies evaluating the clinical utility of our findings.
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5. |
- Claesson, Ing-Marie, 1953-, et al.
(author)
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Weight gain restriction for obese pregnant women : A case-control intervention study
- 2008
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In: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 115:1, s. 44-50
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Journal article (peer-reviewed)abstract
- Objective: To minimise obese women's total weight gain during pregnancy to less than 7 kg and to investigate the delivery and neonatal outcome. Design: A prospective case-control intervention study. Setting: Antenatal care clinics in the southeast region of Sweden. Population: One hundred fifty-five pregnant women in an index group and one hundred ninety-three women in a control group. Methods: An intervention programme with weekly motivational talks and aqua aerobic classes for obese pregnant women. Main outcome measures: Weight gain in kilograms, delivery and neonatal outcome. Results: The index group had a significantly lower weight gain during pregnancy compared with the control group (P < 0.001). The women in the index group weighed less at the postnatal check-up compared with the weight registered in early pregnancy (P < 0.001). The percentage of women in the index group who gained less than 7 kg was greater than that of women in the control group who gained less than 7 kg (P = 0.003). The percentage of nulliparous women in this group was greater than that in the control group (P = 0.018). In addition, the women in the index group had a significantly lower body mass index at the postnatal check-up, compared with the control group (P < 0.001). There were no differences between the index group and the control group regarding birthweight, gestational age and mode of delivery. Conclusion: The intervention programme was effective in controlling weight gain during pregnancy and did not affect delivery or neonatal outcome.
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6. |
- Davidson, Lee Ti, et al.
(author)
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Copeptin and asymptomatic arterial disorder in patients with type 2 diabetes, a cross-sectional study
- 2024
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Conference paper (other academic/artistic)abstract
- Background: Individuals with diabetes are at higher risk for developing arterial disorders. The toe-brachial index (TBI) is associated with peripheral vascular disease, and aortic pulse-wave velocity (aPWV) is currently the gold standard for assessing arterial stiffness. High concentrations of plasma arginine vasopressin (AVP) preferentially stimulate V1a receptors, which affect the vascular bed and may contribute to cardiovascular (CV) complications. Copeptin, a more stable peptide of AVP, is co-secreted from the pituitary gland in equimolar amounts to AVP upon hemodynamic, osmotic, and other stress-related stimuli. Elevated levels of copeptin are potentially linked to vascular dysfunction.Objective: To analyze the association of copeptin to TBI and aPWV as a marker of arterial disorder in patients with type 2 diabetes mellitus (T2D).Methods: A cross-sectional analysis was conducted on 681 patients from the epidemiological study CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes – a Prospective Study in Primary Care; ClinicalTrials.gov identifier NCT01049737) with data on copeptin, TBI, and aPWV. The relationship between the conventional cardiovascular risk factors and copeptin with TBI and aPWV were examined, respectively. Pearson correlation analysis and linear regression analyses were used.Results: Copeptin correlated to TBI (r=-0.086, P=0.027) and aPWV (r=0.143, P<0,001). Copeptin was also negatively associated with TBI (β=-0.093, P=0.027) and aPWV (β=0.121, P=0.004) independently of age, sex, diabetes duration, BMI, smoking, previous cardiovascular diseases, HbA1c, HDL cholesterol, and estimated glomerular filtration rate.Conclusion: Copeptin is independently associated with TBI and aPWV. Copeptin may play an important role in the development of arterial disorders. Measuring copeptin levels may be a simpler method and more efficient way to identify individuals at risk for arterial disorders compared to current methods such as TBI and aPWV.
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7. |
- Davidson, Lee Ti, et al.
(author)
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Plasma copeptin and markers of arterial disorder in patients with type 2 diabetes, a cross-sectional study
- 2024
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In: Cardiovascular Diabetology. - : Springer. - 1475-2840. ; 23:1
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Journal article (peer-reviewed)abstract
- Objectives There is currently limited understanding of the relationship between copeptin, the midregional portion of proadrenomedullin (MRproADM) and the midregional fragment of the N-terminal of proatrial natriuretic peptide (MRproANP), and arterial disorders. Toe brachial index (TBI) and aortic pulse wave velocity (aPWV) are established parameters for detecting arterial disorders. This study evaluated whether copeptin, MRproADM, and MRproANP were associated with TBI and aPWV in patients with type 2 diabetes with no history of cardiovascular disease (CVD).Methods In the CARDIPP study, a cross-sectional analysis of 519 patients with type 2 diabetes aged 55–65 years with no history of CVD at baseline, had complete data on copeptin, MRproADM, MRproANP, TBI, and aPWV was performed. Linear regression analysis was used to investigate the associations between conventional CVD risk factors, copeptin, MRproADM, MRproANP, TBI, and aPWV.Results Copeptin was associated with TBI (β–0.0020, CI–0.0035– (–0.0005), p = 0.010) and aPWV (β 0.023, CI 0.002–0.044, p = 0.035). These associations were independent of age, sex, diabetes duration, mean 24-hour ambulatory systolic blood pressure, glycated hemoglobin A1c, total cholesterol, estimated glomerular filtration rate, body mass index, and active smoking.Conclusions Plasma copeptin may be a helpful surrogate for identifying individuals at higher risk for arterial disorders.
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8. |
- Fryk, Emanuel, et al.
(author)
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Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patients
- 2016
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In: Metabolism-Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 65:7, s. 998-1006
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Journal article (peer-reviewed)abstract
- Objective. To identify a potential therapeutic target for type 2 diabetes by comparing the subcutaneous interstitial fluid from type 2 diabetes patients and healthy men. Methods. Proteomics was performed on the interstitial fluid of subcutaneous adipose tissue obtained by microdialysis from 7 type 2 diabetes patients and 8 healthy participants. 851 proteins were detected, of which 36 (including galectin-1) showed significantly altered expression in type 2 diabetes. We also measured galectin-1 expression in: (1) adipocytes isolated from adipose tissue biopsies from these participants; (2) subcutaneous adipose tissue of 24 obese participants before, during and after 16 weeks on a very low calorie diet (VLCD); and (3) adipocytes isolated from 6 healthy young participants after 4 weeks on a diet and lifestyle intervention to promote weight gain. We also determined the effect of galectin-1 on glucose uptake in human adipose tissue. Results. Galectin-1 protein levels were elevated in subcutaneous dialysates from type 2 diabetes compared with healthy controls (p < 0.05). In agreement, galectin-1 mRNA expression was increased in adipocytes from the type 2 diabetes patients (p < 0.05). Furthermore, galectin-1 mRNA expression was decreased in adipose tissue after VLCD (p < 0.05) and increased by overfeeding (p < 0.05). Co-incubation of isolated human adipocytes with galectin-1 reduced glucose uptake (p < 0.05) but this was independent of the insulin signal. Conclusion. Proteomics of the interstitial fluid in subcutaneous adipose tissue in vivo identified a novel adipokine, galectin-1, with a potential role in the pathophysiology of type 2 diabetes. (C) 2016 Elsevier Inc. All rights reserved.
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9. |
- Lystedt, Erika, 1978-, et al.
(author)
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Subcutaneous adipocytes from obese hyperinsulinemic women with polycystic ovary syndrome exhibit normal insulin sensitivity but reduced maximal insulin responsiveness
- 2005
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In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 153:6, s. 831-835
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Journal article (peer-reviewed)abstract
- Background: Polycystic ovary syndrome (PCOS) has a high prevalence in women and is often associated with insulin resistance and hence with aspects of the so-called metabolic syndrome.Methods: Ten women diagnosed with PCOS were consecutively included (aged 21-39 years, average 30.2 +/- 1.9 years: body mass index 28.4-42.5 kg/m(2), average 37.5 +/- 1.7 kg/m(2) (mean +/- S.E.)). Adipocytes were isolated from the subcutaneous fat and, after overnight incubation to recover from insulin resistance due to the surgical cell isolation procedures, they were analyzed for insulin sensitivity.Results: The patients with PCOS exhibited marked clinical hyperinsulinemia with 3.6-fold higher blood levels of C-peptide than a healthy lean control group (1.7 +/- 0.2 and 0.5 +/- 0.02 nmol/l respectively, P < 0.0001). The patients with PCOS also exhibited 2.4-fold higher concentrations of serum triacylglycerol (2.1 +/- 0.3 and 0.9 +/- 0.06 mmol/l respectively, P < 0.0001), but only slightly elevated blood pressure (118 +/- 12/76 +/- 6 and 113 +/- 7/72 +/- 6 mmHg respectively, P = 0.055/0.046). However, insulin sensitivity for stimulation of glucose transport in the isolated adipocytes was indistinguishable from a non-PCOS, non-diabetic control group, while the maximal insulin effect on glucose uptake was significantly lower (2.2 +/- 0.2- and 3.8 +/- 0.8-fold respectively, P = 0.02).Conclusions: Subcutaneous adipocytes from patients with PCOS do not display reduced insulin sensitivity. The findings show that the insulin resistance of PCOS is qualitatively different from that of type 2 diabetes.
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10. |
- Nowak, Christoph, et al.
(author)
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Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes
- 2018
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In: Diabetologia. - : SPRINGER. - 0012-186X .- 1432-0428. ; 61:8, s. 1748-1757
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Journal article (peer-reviewed)abstract
- Aims/hypothesis Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. Methods We combined data from six prospective epidemiological studies of 30-77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularised Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. Results Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (+/- SD) of 6.4 +/- 2.3 years. We replicated associations (< 5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)-12, IL-27 subunit alpha (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. Conclusions/interpretation We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardiovascular event.
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11. |
- Sandberg, Klas, 1961-
(author)
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Effects of exercise in different phases after stroke
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Background: Stroke is a complex disease that can vary in severity. After a stroke, patients often have long-term disabilities that require major rehabilitation efforts. Evaluation of treatment and methods are important for development of effective rehabilitation after stroke. Various forms of physiotherapy interventions have been tested in different phases after stroke, but there are still questions about timing and forms of exercise. In this work, aerobic exercise with an ergometer cycle and an in-bed cycle were used as models for intervention in subacute and acute phase after stroke. Exercise has been evaluated both after discharge from hospital and in hospital care. Aim: The overall aim of the dissertation was to study the effects of exercise in different phases after stroke of varying severity.Method: Two studies were performed in Swedish stroke units during 2013- 2018. Both studies were randomized controlled trials focusing on the effects of exercise in different phases after stroke. Study A included 56 patients with mild stroke from one hospital. Patients were discharged from the hospital and enrolled to intervention in median 22.5 days after stroke onset. All patients received usual care in a stroke unit according to national guidelines, and the intervention group received additionally aerobic exercise for 1 hour 2 times per week for 12 weeks post-discharge. The session included 2x8 minutes of intense aerobic exercise on an ergometer cycle. In study A, the effects of exercise were evaluated by aerobic exercise, walking distance and hemodynamic responses and compared to usual care.Study B included 52 patients in the acute phase of moderate to severe stroke from two hospitals. Patients were enrolled to intervention 2 days after onset, and all patients received usual care. In addition to usual care, one group received in-bed cycle exercise 20 minutes daily, 5 days per week for 3 weeks. In study B, the effects of exercise were evaluated by walking distance and hemodynamic responses and compared to usual care.Results: Study A showed that intensive aerobic exercise twice weekly for 12 weeks during the subacute phase of mild stroke improved the patient’s aerobic capacity and walking distance after the intervention period. The study also showed that exaggerated blood pressure reactions associated with exercise were common in the subacute phase but not significantly affected by participation in a 12-week exercise period.Study B showed that the addition of in-bed cycle exercise in the acute phase after more severe stroke was not superior to usual care with regards to walking distance after 3 months. From baseline to post-intervention, systolic blood pressure decreased significantly to a similar extent in both groups, but the exercise group seemed to normalize their blood pressure response to exercise to a greater extent than patients in the control group.Conclusion: For patients with mild symptoms, aerobic exercise initiated 3 weeks after stroke onset was beneficial for aerobic capacity and walking distance. In the acute phase after stroke, starting two days after onset, 3 weeks 4 of in-bed cycle exercise was not superior to usual care with regards to walking distance after 3 months. Exercise-related exaggerated blood pressure reactions were common in the subacute phase but not affected by participation in a 12- week exercise period. An effect of the in-bed cycle exercise in the acute phase after stroke seemed to be that patients randomized to the intervention normalized their blood pressure reaction in connection with exercise.
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12. |
- Ström, Edvin, 1992-, et al.
(author)
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Dissatisfaction with teeth in type 2 diabetes is associated with increased risk of cardiovascular disease
- 2022
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In: Diabetes Epidemiology and Management. - : Elsevier. - 2666-9706. ; 8
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Journal article (peer-reviewed)abstract
- Background and aimPoor dental health status has been linked to increased risk of cardiovascular events in type 2 diabetes (T2D). Less is known about self-perceived dental health and cardiovascular risk. Our aim with this study was to investigate this association.MethodsRecruitment of T2D patients took place between 2005 and 2008 in Swedish primary care. Teeth satisfaction was assessed by questionnaire at baseline. The major adverse cardiovascular events (MACE) in this study were hospitalization due to myocardial infarction, stroke or cardiovascular death. Cox regression models were used.ResultsOut of 761 participants 601 had complete data. Ninety-two MACEs occurred (median follow-up time: 11.6 years). Those satisfied with their teeth (n = 458) had 61 events (1.2 events per 100 person-years), while those dissatisfied with teeth (n = 143) had 31 events (2.2 events per 100 person-years). Dissatisfaction with teeth was associated with an increased risk of MACE independent of age, sex and levels of CRP (HR 1.85, 95% CI 1.20 – 2.86).ConclusionsIn patients with T2D, dissatisfaction with teeth was associated with increased risk of MACE and may be considered as a marker of risk.
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13. |
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14. |
- Vavruch, Camilla
(author)
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Leptin and the Intersection of Cardiovascular Disease, Metabolism, and Adipose Tissue
- 2023
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Doctoral thesis (other academic/artistic)abstract
- According to the World Health Organization, cardiovascular disease (CVD) is a group of disorders of the heart and blood vessels, and it is the leading cause of death worldwide. The risk factors for CVD are divided into two major classes: non-modifiable (age, gender, family history) and modifiable (including tobacco use, type 2 diabetes mellitus (T2DM), physical inactivity, unhealthy diet, abdominal obesity, high cholesterol, dyslipidemia, and stress). Because CVD is a major cause of mortality and morbidity, new and clinically useful biomarkers of cardiovascular risk are of essence. Since obesity is a risk factor for CVD, new ways to achieve weight loss are also important. In this thesis, the focus is on leptin, a metabolic hormone with a pivotal function in the balance of appetite and satiety, and inducing weight loss. The adipose tissue releases leptin, with plasma levels of leptin reflecting the total adipose mass. Since it is related to both fat mass and cardiovascular risk, and is pro-inflammatory, it has been studied as a potential link between obesity, inflammation, hypertension, and vascular function. In paper I, we aimed to see if repeated cold exposure increased metabolic rate and/or brown adipose tissue (BAT) volume in humans. Out of 28 recruited participants, we allocated 16 to expose themselves to cold for one hour every day for six weeks, while 12 were controls, instructed to avoid cold exposure. Through magnetic resonance imaging, we found that supra-clavicular BAT volume had increased in an on-treatment analysis of the cold exposure group. In paper II, we used baseline data from 720 participants in “Cardiovascular Risk factors In Patients with Diabetes—a Prospective study in Primary care” (CARDIPP), all of whom had T2DM and were 55-66 years old at recruitment. We followed patients for incidence of ischemic heart disease (IHD) mortality and morbidity for 4-7 years, using the national Swedish Cause of Death and Hospitalization Registries. Our study showed that serum leptin levels related positively to the hazard ratio in both men and women, and predicted IHD independently of age, HbA1c, BMI, systolic blood pressure, and LDL/HDL-cholesterol ratio. This supports the use of serum leptin in patients with T2DM to add independent prognostic information in terms of IHD. When adding pulse wave velocity (PWV) and intima-media thickness to the model as markers of arterial stiffness, the finding of increased risk of IHD related to leptin levels remained statistically significant in men, but not in women. In paper III, we aimed to discover novel associations between leptin and circulating proteins, to possibly link leptin with the development of CVD in patients with T2DM. Using proximity extension assay, we investigated associations between 88 plasma proteins in the CARDIPP population. We replicated the associations passing the significance threshold in patients with T2DM in an independent cohort and found that adipocyte fatty acid binding protein (A-FABP) was significantly associated with leptin in both cohorts, more so in men than women. A-FABP can be found in white adipocytes and macrophages, and some studies have identified it as a circulating biomarker for metabolic syndrome, T2DM, and cardiovascular events. Finally, in paper IV, we analyzed data from 1 658 men and 1 678 women aged 50 to 65 when included in “The Swedish CardioPulmonary bioImage Study” (SCAPIS), focusing on leptin and its possible correlation with PWV. In bivariate correlations, we found log transformed leptin, and inflammatory markers IL-6, IL-18, and CRP, were all correlated in both men and women. In a multivariable linear regression, log transformed leptin correlated positively with PWV, independently of home blood pressure, smoking, non-HDL, BMI, T2DM, and IL-6, IL-18, and CRP. This suggests it may be possible to use leptin as a marker for PWV and arterial stiffness.In conclusion, this thesis provides new insights into leptin and its potential associations with other circulating proteins, and its connection to cardiovascular disease and inflammation, both in patients with T2DM and in healthy subjects. It also provides more insight into brown adipose tissue.
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15. |
- Vergara, Marta, 1976-
(author)
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Impact of different interventions on cardiovascular risk factors
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Obesity and related complications such as diabetes mellitus type 2 (T2DM) and cardiovascular events, are a growing major health problem worldwide. Achieving a negative energy balance by increasing physical activity in combination with reduced caloric intake, is the most common approach in weight reduction strategies, something that is difficult to maintain in the long term. Other possible strategy to increase energy expenditure could be enhancing resting metabolic rate (RMR) by increasing energy consumption in muscle tissue.Regular exercise is often recommended as part of the treatment and prevention of cardiovascular disease (CVD) and it is expected to ameliorate risk factors associated with the metabolic syndrome, such as glucose and insulin metabolism, lipid profile and blood pressure. However, extreme exercise performance seems to have potential unbeneficial effects on inflammation, oxidation, and cardiac health. We intended to study the impact of a more common way of exercise in different cardiovascular risk factors and how natural antioxidants, protein supplementation or hypercaloric diet could influence the results. In patients with already established T2DM, it is important to find new and easy to manage markers for CVD, as it is the main cause of morbidity and mortality in this patient group. Even if quality of life (QoL) is strongly related to CVD in patients with T2DM, it is still not incorporated in routinary clinical assessments.Paper I: Resistance training (RT) performed by healthy men for three months, increased lean body-mass and RMR. The increase of RMR was dependent on both an increase in muscle mass and a higher RMR per kg of muscle tissue. Even if it was equally efficient to combine training with whey protein supplementation or with increased energy intake, hyperalimentation with an extra intake of a fast-food resulted in an impaired cardiovascular profile, with reduced insulin sensitivity and higher ApoB levels. Thus, regularly performed RT could be helpful in the treatment of obesity by increasing RMR.Paper II: Regularly running 5 km for 4 weeks resulted in a positive outcome, leading to lower insulin and triglyceride levels, higher HDL cholesterol, and a tendency to lower inflammation when compared with a period of minimal physical activity. However, Troponin-T, marker of myocardial injury, was detectable after a 5 km race at maximal speed in almost half of the races. Consuming blueberries showed a cardioprotective effect, blunting troponin-T release and improving the lipid profile. Less positive was the increase of fasting glucose in consumers of blueberries, which could be an indirect effect of concomitant diet. Paper III: Running 5 km at maximal speed may not be as advantageous for cardiovascular health as expected, at least when looking at the acute effects of a single race in healthy young individuals. A relative short race seemed to reduce insulin sensitivity and despite increased insulin levels, glucose was higher directly after the race compared with a resting day. Indeed, we found elevated cortisol and Troponin-T levels after the races, which suggests that running a distance that is common among recreational runners, may not be fully advantageous for cardiovascular health when performed in a strenuous way.Paper IV: We investigated if selected questions regarding the domains "general mental health and well-being" and "vitality", from QoL measurement instrument SF-36, could predict cardiovascular events and death in patients with T2DM in primary care. These two questions: "During the last 4 weeks, did you feel full of pep?" and "During the last 4 weeks, did you have a lot of energy?" were shown to be markers for major adverse cardiovascular events (MACE) independently of traditional vascular risk factors as well as arterial stiffness.
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16. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(author)
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A low dose of daily licorice intake affects renin, aldosterone, and home blood pressure in a randomized crossover trial
- 2024
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In: American Journal of Clinical Nutrition. - : ELSEVIER SCIENCE INC. - 0002-9165 .- 1938-3207. ; 119:3, s. 682-691
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Journal article (peer-reviewed)abstract
- BackgroundLicorice, through the effects of glycyrrhizic acid (GA), raises blood pressure (BP). The World Health Organization has suggested that 100 mg GA/d would be unlikely to cause adverse effects, but of 13 previously published studies none have been randomized and controlled and independently quantified the GA content.ObjectiveOur aim was to analyze the effects on home BP of a daily licorice intake containing 100 mg GA.MethodsHealthy volunteers were randomly assigned to start with either licorice or a control product in a nonblinded, 2 × 2 crossover study. Home BP was measured daily, and blood samples were collected at the end of each 2-wk period.ResultsThere were 28 participants and no dropouts. The median age was 24.0 y (interquartile range 22.8–27.0 y). During the licorice compared with control intake period, the systolic home BP increased [mean difference: 3.1 mm Hg (95% confidence interval [CI]: 0.8, 5.4 mm Hg) compared with −0.3 mm Hg (95% CI: −1.8, 1.3 mm Hg); P = 0.018] and renin and aldosterone were suppressed [mean change: −30.0% (95% CI: −56.7%, −3.3%) compared with 15.8% (95% CI: −12.8%, 44.4%); P = 0.003; and −45.1% (95% CI: −61.5%, −28.7%) compared with 8.2% (95% CI: −14.7%, 31.1%); P <0.001, respectively]. In the quartile of participants with the most pronounced suppression of renin and aldosterone, N-terminal prohormone of brain natriuretic peptide concentration increased during the licorice compared with control period [mean change: 204.1% (95% CI: −11.6%, 419.7%) compared with 72.4% (95% CI: −52.2%, 197.1%); P = 0.016].ConclusionsWe found licorice to be more potent than previously known, with significant increases in BP, after a daily intake of only 100 mg GA. Thus, the safe limit of intake of this substance might need to be reconsidered.
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17. |
- af Geijerstam, Peder, Doktorand, 1983-
(author)
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Home Blood Pressure in Health and Disease
- 2024
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Doctoral thesis (other academic/artistic)abstract
- Hypertension is the most common preventable cause of premature all-cause mortality, primarily from cardiovascular disease (CVD). Individuals with dysglycemia, including prediabetes and diabetes, are at increased risk. Licorice intake raises blood pressure (BP) through the effects of glycyrrhizic acid (GA), but the true limit of safe intake is uncertain. Home BP has several benefits over BP measured at a clinic, including a higher predictive value for CVD. By combining office and home BP, it is possible to diagnose masked hypertension (MH), in which home but not office BP is elevated, and white coat hypertension (WCH), in which office but not home BP is elevated. The aim of this thesis was to advance our knowledge on home BP in relation to dysglycemia, markers of CVD, and licorice intake. The first 3 papers used data from the Linköping cohort of the prospective Swedish CArdioPulmonary bioImage Study (SCAPIS). Study IV was a randomized controlled cross-over study. Data was obtained from questionnaires, blood samples and office and home BP measurements. In studies I-III, pulse wave velocity (PWV), coronary artery calcium score (CACS), and carotid artery plaques as markers of CVD were also included. In Study I, we examined 5025 men and women aged 50-64 years old for the relation between dysglycemia and home BP. Both the systolic office and home BP measurements were positively as-sociated with dysglycemia. Participants with dysglycemia vs normoglycemia more often had MH. The findings were in line with previous research and strengthened the association between dysglycemia and MH. In Study II, we examined the associations between MH and markers of CVD in 4122 individuals without BP-lowering treatment. Of participants, 4.2% had MH, and these were more often men and had higher BMI than those with normotension. Participants with MH also had higher odds for CACS ≥100, an as-sociation which has previously been suggested as a trend.In Study III, we examined the relation between soluble P-se-lectin (sP-selectin) as a measure of thrombotic activity, plasma high-sensitivity C-reactive protein (hsCRP) as a measure of inflammation, and home BP in 4548 participants. Both markers were higher in each hypertension phenotype compared with sustained normotension. The quartile of participants with the highest sP-se-lectin values had higher odds for CACS ≥100 and carotid artery plaques. The association between sP-selectin and sustained hyper-tension was novel and not affected by adjustments for hsCRP. In Study IV, 28 healthy participants aged 18-30 years old were evaluated for the effects of a daily intake of licorice containing 100 mg of GA compared with a control product for 2 weeks. During the licorice intake period, the systolic home BP increased with 3.1 mmHg, and the suppression of serum aldosterone and plasma renin levels indicated that this was due to the licorice intake. In conclusion, this thesis further strengthens the idea that both home and office BP measurements have values beyond that of the other, and that home BP may be most valuable in individuals with dysglycemia and obesity, and in men. Finally, licorice may be more potent than previously known, suggesting the need for increased awareness.
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18. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(author)
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Liten mängd lakrits ökar hemblodtrycket
- 2024
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In: Vaskulär Medicin. - Ballingslöv : Svensk förening för hypertoni, stroke och vaskulär medicin. - 2000-3188. ; 40:1, s. -24
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Journal article (pop. science, debate, etc.)
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19. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(author)
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P-selectin and C-reactive protein in relation to home blood pressure and coronary calcification: a SCAPIS substudy
- 2024
-
In: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 42:7, s. 1226-1234
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Journal article (peer-reviewed)abstract
- Background: Soluble P-selectin (sP-selectin) and high-sensitivity C-reactive protein (hsCRP) have previously been associated with hypertension, but the relation with out-of-office blood pressure (BP) and coronary artery calcification score is unknown. We aimed to examine the relationship between sP-selectin, hsCRP and home BP, as well as coronary artery calcification score and carotid artery plaques.Methods: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), 5057 randomly selected participants were evaluated with office and home BP using the semi-automatic Omron M10-IT device. For this cross-sectional study, participants with sP-selectin <4 standard deviations above mean and hsCRP <5 mg/l, representing low-grade inflammation, were included. Using generalized linear models, these inflammatory markers were evaluated in relation to BP classifications, as well as coronary artery calcification score and carotid artery plaques.Results: Of participants, 4548 were included in the analyses. The median age was 57.2 (53.4–61.2) years, and 775 (17.0%) reported taking medication for hypertension. Participants in the highest quartile of sP-selectin [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.40–1.98, P < 0.001] and hsCRP [OR 2.25, (95% CI 1.89–2.60), P < 0.001] were more likely to have sustained hypertension. Participants in the highest quartile of hsCRP were also more likely to have masked hypertension, OR (95% CI) 2.31 (1.72–3.10), P < 0.001 and carotid artery plaques, OR (95% CI) 1.21 (1.05–1.38), P = 0.007.Conclusion: Increased sP-selectin and hsCRP were independently associated with sustained hypertension. These findings indicate an association between hypertension and platelet activity, as expressed by sP-selectin.
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20. |
- Anfelter, P, et al.
(author)
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The effect of percutaneous dilatation of renal arterial stenosis on captopril renography in hypertension
- 2005
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In: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 14:6, s. 359-365
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Journal article (peer-reviewed)abstract
- Background. The clinical effects of percutaneous transluminal renal artery angioplasty (PTRA) in patients with renal vascular stenosis and hypertension is controversial. Methods. We consecutively recruited all 23 patients referred for evaluation of renovascular hypertension that eventually underwent unilateral PTRA, to be investigated with captopril MAG3 renography (CR), both before and after the endovascular procedure. Data were evaluated on an intention-to-treat basis. Results. We found that the relative MAG3 clearance of the stenotic kidney increased (from 29.9 ± 14% to 35.1 ± 14%, p=0.01) and that the creatinine levels fell following the intervention (from 110 ± 19 to 99 ± 17 μmol/l, p=0.0003). Blood pressure levels were also lowered (from 173 ± 32/93 ± 17 to 158 ± 31/86 ± 15 mmHg, p<0.006) while the mean number of anti-hypertensive drugs was unchanged following PTRA (2.9 ± 1.4 before and 2.8 ± 1.3 drugs after the intervention, respectively, p-0.6). Conclusion. This prospective trial showed statistically significant improvements of individual kidney function as measured by CR and blood pressure in subjects with suspected renovascular hypertension treated with PTRA. Although the endovascular procedure was found to be safe, the magniture of the absolute improvements was rather modest. © 2005 Taylor & Francis.
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21. |
- Barmano, Neshro, et al.
(author)
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Predictors of improvement in arrhythmia-specific symptoms and health-related quality of life after catheter ablation of atrial fibrillation
- 2018
-
In: Clinical Cardiology. - : John Wiley & Sons. - 0160-9289 .- 1932-8737. ; 42:2, s. 247-255
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Journal article (peer-reviewed)abstract
- Background: The primary goal of radiofrequency ablation (RFA) of atrial fibrillation (AF) is to improve symptoms and health-related quality of life (HRQoL). However, most studies have focused on predictors of AF recurrence rather than on predictors of improvement in symptoms and HRQoL.Hypothesis: We sought to explore predictors of improvement in arrhythmia-specific symptoms and HRQoL after RFA of AF, and to evaluate the effects on symptoms, HRQoL, anxiety, and depression. Methods: We studied 192 patients undergoing their first RFA of AF. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), arrhythmia-specific questionnaire in tachycardia and arrhythmia (ASTA), and hospital anxiety and depression scale (HADS) questionnaires were filled out at baseline, at 4 months, and at a 1-year follow-up.Results: All questionnaire scale scores improved significantly over time. In the ASTA symptom scale score, female gender and > 10 AF episodes the month before RFA were significant positive predictors of improvement, while diabetes and AF recurrence within 12 months after RFA were significant negative predictors (R2 = 0.18; P < 0.001). In the ASTA HRQoL scale score, the presence of heart failure and > 10 AF episodes the month before RFA were significant positive predictors of improvement, while diabetes, maximum left atrial volume and AF recurrence were significant negative predictors (R2 = 0.20; P < 0.001).Conclusion: Left atrial volume, gender, diabetes, heart failure, the frequency of AF attacks prior to RFA, and recurrence of AF after RFA were significant factors affecting improvement in symptoms and HRQoL after RFA of AF. Future studies are warranted to confirm these findings.
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22. |
- Barmano, Neshro, 1980-
(author)
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Structured management, Symptoms, Health-related Quality of Life and Alcohol in Patients with Atrial Fibrillation
- 2019
-
Doctoral thesis (other academic/artistic)abstract
- Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting at least 2.9 % of the Swedish population. Although AF is associated with increased risk of ischaemic stroke, there have been many reports on the underuse of oral anticoagulants (OAC) and non-adherence to guidelines in other areas as well. AF is also associated with disabling symptoms and decreased health-related quality of life (HRQoL), but some patients are asymptomatic. The reasons for the great variation of symptoms remain unclear. Furthermore, although research on AF has increased, studies have mainly focused on treatment, while studies on risk factors, such as alcohol consumption, have only recently gained attention.The aim of this thesis was to investigate whether structured care of patients with AF could improve guideline adherence and HRQoL compared to standard care, and to determine which factors affect symptoms and HRQoL prior to treatment with radiofrequency catheter ablation (RFA), as well as improvement after RFA. Furthermore, we aimed to examine the associations of alcohol consumption with cardiac biomarkers, the size of the left atrium (LA), and re-ablation.This thesis is based on two studies. In the ‘Structured Management and Coaching – Patients with Atrial Fibrillation’ (SMaC-PAF) study, 176 patients were recruited to the intervention group, receiving a structured follow-up programme, and 146 patients were recruited to the control group, receiving standard care. The two groups were compared in regard to adherence to guidelines and patient-reported outcome measures (PROMs) assessing symptoms and HRQoL.In the ‘Symptom burden, Metabolic profile, Ultrasound findings, Rhythm, neurohormonal activation, haemodynamics and health-related quality of life in patients with atrial Fibrillation’ (SMURF) study, 192 patients referred for their first RFA of AF were included. PROMs questionnaires were filled out, echocardiography was performed, and cardiac biomarkers were analysed. Alcohol consumption was assessed through interview and through analysis of ethyl glucuronide in hair (hEtG). AF recurrence and re-ablation within 12 months were examined.In the first study, after one year, 94% (n=112) and 74% (n=87) of patients with indication for OAC in the intervention and the control groups, respectively, actually received treatment with OAC (p <0.01). Both groups improved in anxiety and HRQoL scores over the year, but in the intervention group, arrhythmia-specific symptoms were less frequently experienced and the SF-36 scores were more similar to the norm population.In the second study, the most important predictors of arrhythmia-related symptoms and HRQoL prior to RFA were anxiety, depression and low-grade inflammation, while frequent AF attacks prior to RFA, freedom from AF recurrence after RFA, female gender, no enlarged LA, absence of diabetes, and the presence of heart failure were significant predictors of improvement in symptoms and HRQoL after RFA. Men with hEtG ≥7 pg/mg had higher levels of cardiac biomarkers, larger LA volumes and a higher re-ablation rate than men with hEtG <7 pg/mg, while no such findings were present in women.In conclusion, structured management was superior to standard care in patients with AF, emphasising the importance of structured care, adjusted to local requirements, in order to improve the care and well-being of patients with AF. Although the reasons for the great variety of symptoms in patients with AF still are not yet fully understood, it seems that psychological factors and inflammation play a role, and that improvement in symptoms and HRQoL after RFA is influenced by gender, diabetes, heart failure, LA size and the frequency of attacks before, as well as freedom from AF after, RFA. Finally, alcohol consumption corresponding to hEtG ≥7 pg/mg was associated with higher levels of cardiac biomarkers, larger LA size and a higher rate of re-ablation in men, implying that men with an hEtG-value ≥7 pg/mg have a higher risk for LA remodelling that could potentially lead to a deterioration of the AF situation.
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23. |
- Barmano, Neshro, 1980-, et al.
(author)
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The association between alcohol consumption, cardiac biomarkers, left atrial size and re-ablation in patients with atrial fibrillation referred for catheter ablation
- 2019
-
In: PLOS ONE. - San Francisco, CA, United States : Public Library of Science. - 1932-6203. ; 14:4
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Journal article (peer-reviewed)abstract
- BackgroundInformation on alcohol consumption in patients undergoing radiofrequency ablation (RFA) of atrial fibrillation (AF) is often limited by the reliance on self-reports. The aim of this study was to describe the long-term alcohol consumption, measured as ethyl glucuronide in hair (hEtG), in patients undergoing RFA due to AF, and to examine potential associations with cardiac biomarkers, left atrial size and re-ablation within one year after the initial RFA.MethodsThe amount of hEtG was measured in patients referred for RFA, and a cut-off of 7 pg/mg was used. N-terminal pro B-type natriuretic peptide (NT-proBNP) and the mid-regional fragment of pro atrial natriuretic peptide (MR-proANP) were examined and maximum left atrium volume index (LAVI) was measured. The number of re-ablations was examined up to one year after the initial RFA. Analyses were stratified by gender, and adjusted for age, systolic blood pressure, body mass index, presence of heart failure and heart rhythm for analyses regarding NT-proBNP, MR-proANP and LAVI and heart rhythm being replaced by type of AF for analyses regarding re-ablation.ResultsIn total, 192 patients were included in the study. Median (25th– 75th percentile) NT-proBNP in men with hEtG ≥ 7 vs. < 7 pg/mg was 250 (96–695) vs. 130 (49–346) pg/ml (p = 0.010), and in women it was 230 (125–480) vs. 230 (125–910) pg/ml (p = 0.810). Median MR-proANP in men with hEtG ≥ 7 vs. < 7 pg/mg was 142 (100–224) vs. 117 (83–179) pmol/l (p = 0.120) and in women it was 139 (112–206) vs. 153 (93–249) pmol/l (p = 0.965). The median of maximum LAVI was 30.1 (26.7–33.9) vs. 25.8 (21.4–32.0) ml/m2 (p = 0.017) in men, and 25.0 (18.9–29.6) vs. 25.7 (21.7–34.6) ml/m2 (p = 0.438) in women, with hEtG ≥ 7 vs. < 7 pg/ml, respectively. Adjusted analyses showed similar results, except for MR-proANP turning out significant in men with hEtG ≥ 7 vs. < 7 pg/mg (p = 0.047). The odds ratio of having a re-ablation was 3.5 (95% CI 1.3–9.6, p = 0.017) in men with hEtG ≥ 7 vs. < 7 pg/mg, while there was no significant difference in women.ConclusionsIn male patients with AF and hEtG ≥ 7 pg/mg, NT-proBNP and MR-proANP were higher, LA volumes larger, and there was a higher rate of re-ablations, as compared to men with hEtG < 7 pg/mg. This implies that men with an alcohol consumption corresponding to an hEtG-value ≥ 7, have a higher risk for LA remodelling that could potentially lead to a deterioration of the AF situation.
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24. |
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25. |
- Blomstrand, Peter, et al.
(author)
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Overweight and obesity impair left ventricular systolic function as measured by left ventricular ejection fraction and global longitudinal strain
- 2018
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In: Cardiovascular Diabetology. - : BioMed Central. - 1475-2840. ; 17:1
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Journal article (peer-reviewed)abstract
- AimsObesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons.MethodsWe prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight < 25 kg/m2, overweight 25–29 kg/m2, and obesity ≥ 30 kg/m2). Echocardiography was performed at the beginning of the study and after 4-years in the patient group.ResultsUnivariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/é (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. − 18.6% (2.3%) for normal weight patients, 53% (8%) vs. − 17.5% (2.3%) for overweight, and 49% (9%) vs. − 16.2% (3.0%) for obese (p < 0.05 vs. p < 0.05). Corresponding results in the control group were 58% (6%) vs. − 22.3% (3.0%), 55% (7%) vs. − 20.8% (3.1%) and 54% (8%) − 19.6% (4.0%) (p < 0.05 vs. p < 0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by − 1.0 (9.0) % (n = 187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n = 179) (p < 0.05).ConclusionOverweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons.
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26. |
- Bojestig, M, et al.
(author)
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The renin-angiotensin-aldosterone system is suppressed in adults with Type 1 diabetes
- 2000
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In: jraas. Journal of the renin-angiotensin-aldosterone system. - 1470-3203 .- 1752-8976. ; 1:4, s. 353-356
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Journal article (peer-reviewed)abstract
- Poor glycaemic control and high blood pressure are two important risk factors for the development of retinopathy and nephropathy in Type 1 diabetes. The renin-angiotensin-aldosterone system (RAAS) may be involved in this process, since treatment with angiotensin-converting enzyme (ACE) inhibitors postpones the development of these complications. We investigated whether plasma renin activity (PRA), plasma angiotensin II (Ang II) and atrial natriuretic peptide (ANP) differed in Type 1 diabetic patients compared with healthy controls. We recruited 80 patients with Type 1 diabetes of more than 10 years' duration and 75 age-matched controls. We found that PRA and Ang II concentrations were significantly lower in patients than in the controls. The levels of ANP, on the other hand, were higher in patients than in controls. PRA correlated negatively to the mean value of HbA1c during the previous five years. PRA and Ang II were significantly lower in patients with mean HbA1c. >8.4% compared with those with mean HbA1c 7.2%. In summary, we found patients with Type 1 diabetes to have RAAS suppression and increased ANP levels, suggesting a state of fluid retention.
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27. |
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28. |
- Davidson, Lee Ti, et al.
(author)
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Association of physiological stress markers at the emergency department to readmission and death within 90 days: a prospective observational study
- 2023
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In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 128:1
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Journal article (peer-reviewed)abstract
- Background: Predicting the risk of readmission or death in patients at the emergency department (ED) is essential in identifying patients who would benefit the most from interventions. We aimed to explore the prognostic value of mid-regional proadrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin, and high-sensitivity troponin T (hs-TnT) to identify patients with a higher risk of readmission and death among patients presenting with chest pain (CP) and/or shortness of breath (SOB) in the ED.Methods: This single-center prospective observational study included non-critically ill adult patients with a chief complaint of CP and/or SOB who visited the ED at Linköping University Hospital. Baseline data and blood samples were collected, and patients were followed up for 90 days after inclusion. The primary outcome was a composite of readmission and/or death from non-traumatic causes within 90 days of inclusion. Binary logistic regression was used and receiver operating characteristics (ROC) curves were constructed to determine the prognostic performance for predicting readmission and/or death within 90 days.Results: A total of 313 patients were included and 64 (20.4%) met the primary endpoint. MR-proADM > 0.75 pmol/L (odds ratio [OR]: 2.361 [95% confidence interval [CI]: 1.031 – 5.407], P = 0.042) and multimorbidity (OR: 2.647 [95% CI: 1.282 – 5.469], P = 0.009) were significantly associated with readmission and/or death within 90 days. MR-proADM increased predictive value in the ROC analysis to age, sex, and multimorbidity (P = 0.006).Conclusions: In non-critically ill patients with CP and/or SOB in the ED, MR-proADM and multimorbidity may be helpful for the prediction of the risk of readmission and/or death within 90 days.
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29. |
- Ekman, Bertil, et al.
(author)
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A dose titration model for recombinant GH substitution aiming at normal plasma concentrations of IGF-I in hypopituitary adults
- 2002
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In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 147:1, s. 49-57
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate a dose titration model for recombinant human GH substitution in adult patients with GH deficiency, aiming at normal plasma levels of IGF-I.DESIGN AND METHODS: Eighteen patients participated and a start dose of 0.17 mg GH/day was used except by two men who started with 0.33 mg/day. To demonstrate a clear GH effect the patients were first titrated, with steps of 0.17 mg GH/day every 6-8 weeks, to IGF-I levels in the upper range of age-adjusted reference values. The GH dose was then reduced 1 dose step and kept for a further 6 months. For comparison we investigated 17 healthy control subjects.RESULTS: Plasma IGF-I was increased after 2 weeks on the start dose and did not increase further for up to 8 weeks. Women had significantly lower GH sensitivity than men measured as net increment of IGF-I on the start dose of GH. GH sensitivity was not changed by age. The plasma IGF-I levels increased from 76.3+/-47.0 (s.d.) to 237+/-97 microg/l at the end of the study (P<0.001), and similar IGF-I levels were obtained in both sexes. The maintenance median GH dose was 0.33 mg/day in males and 0.83 mg/day in females (P=0.017). The GH dose correlated negatively with age in both sexes. Body weight, very low density triglycerides, lipoprotein(a) (Lp(a)), and fasting insulin increased, whereas insulin sensitivity index (QUICKI) decreased significantly. In comparison with the controls, the patients had lower fasting blood glucose, fasting insulin and Lp(a) levels at baseline, but these differences disappeared after GH substitution. The two groups had equal insulin sensitivity (QUICKI), but 2 h oral glucose tolerance test values of blood glucose and insulin were significantly higher in the patients at the end of the study.CONCLUSIONS: In conclusion our data suggest that the starting dose of GH substitution and the dose titration steps should be individualised according to GH sensitivity (gender) and the IGF-I level aimed for (age). The reduced insulin sensitivity induced by GH substitution could be viewed as a normalisation if compared with control subjects.
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30. |
- Ekman, Bertil, et al.
(author)
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Circulating IGF-I concentrations are low and not correlated to glycaemic control in adults with type 1 diabetes
- 2000
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In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 143:4, s. 505-510
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To study plasma concentrations of insulin-like growth factor-I (IGF-I) in adults with type 1 diabetes (IDDM) in comparison with a reference population, and the influence of glycaemic control, dose of insulin, and sex on the concentration of circulating IGF-I in IDDM.DESIGN AND METHODS: Patients with type 1 diabetes were recruited consecutively from our outpatient diabetes unit. In all, 79 men and 55 women aged 20-60 years with a disease duration >/=6 years (range 6-51 years) took part in the study. A reference population of 80 men and 83 women aged 20-60 years was randomly obtained from the population registry. IGF-I was measured with radioimmunoassay after acid-ethanol extraction.RESULTS: Mean +/- s. d. values of IGF-I were lower in patients with diabetes (146+/-66 microg/l) than in controls (238+/-83 microg/l, P<0.001). Those with diabetes had lower IGF-I concentrations in all age groups and the differences were highly significant in all decades except in women aged 50-59 years. IGF-I was negatively correlated with age in patients and controls. No correlation was found between IGF-I and glycaemic control measured as haemoglobin A(1c) (HbA(1c)) in the patients. IGF-I was positively associated with the dose of insulin/kg body weight in male patients independently of age, HbA(1c) and body mass index (P<0.03), but not in female patients (P=0.14).CONCLUSIONS: Our data show that IGF-I concentrations are low in adult patients with type 1 diabetes with a disease duration >/=6 years, independently of glycaemic control. This suggests that subcutaneous insulin substitution is inadequate to normalize circulating IGF-I concentrations in patients without endogenous insulin secretion.
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31. |
- Ekman, Bertil, et al.
(author)
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Individualized growth hormone substitution with normalized IGF-I levels does not stimulate the renin–angiotensin–aldosterone system
- 2002
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In: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 57:4, s. 473-479
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Journal article (peer-reviewed)abstract
- objective To study the effects of individualized recombinant GH substitution, aiming at normal circulating IGF-I levels, in GH-deficient adults on blood pressure, the renin–angiotensin–aldosterone system (RAAS), natriuretic peptides and urine free cortisol.study design Open study with control group. The patients were titrated in dose steps of 0·17 mg GH/day every 6–8 weeks until an IGF-I level around the mean + 1 SD was attained (Tmax). After another month the dose was reduced by 0·17 mg (minimum dose 0·17 mg/day) to produce IGF-I levels at or slightly below the age-related mean (Tend), and this maintenance dose was held constant for 6 months.subjects Eighteen patients (11 males and seven females) with GH deficiency participated. For comparison we also prospectively evaluated 17 matched control subjects.measurements Blood pressure and heart rate, circulating levels of IGF-I, plasma renin activity (PRA), immunoreactive active renin (IRR), angiotensin II, aldosterone, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and 24-h urine aldosterone and urine free cortisol levels.results Blood pressure was unchanged by GH substitution but heart rate increased significantly (P < 0·03). PRA was elevated on the highest GH dose (Tmax) compared to baseline (P < 0·01), but returned to baseline and levels of controls at Tend. Four patients developed transient oedema and tended to have higher PRA levels than the rest of the subjects (P = 0·09). The circulating levels of IRR, angiotensin II, aldosterone, BNP and 24-h urine aldosterone and urine free cortisol levels were unchanged by GH substitution, and did not differ from the levels in the control subjects. Baseline ANP levels in the patients were lower than in the controls (P < 0·01), but increased after GH substitution (P < 0·01) to levels found in with the controls.conclusions We found no major changes of the variables in the circulating renin–angiotensin–aldosterone system and a normalization of atrial natriuretic peptide when an individualized dose of GH was titrated to near-normal IGF-I levels.
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32. |
- Engvall, Jan, 1953-, et al.
(author)
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Daytime ambulatory blood pressure correlates strongly with the echocardiographic diameter of aortic coarctation
- 2001
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In: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 35:5, s. 335-339
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Journal article (peer-reviewed)abstract
- Objective.-To relate the echocardiographic aortic arch-diameter to ambulatory and clinic blood pressure (BP) in patients with aortic coarctation. Design.-Eighteen adult patients (50% men) were recruited from the coarctation registry of the Linkoping Heart Centre. Biplane-trans-oesophageal echocardiography (TEE) was performed with Acuson XP 128/10, ambulatory BP was recorded with Spacelab models 90202/90205. Results.-Systolic clinic and ambulatory BP levels were higher in patients than in the 36 controls (clinic BP: 146 ▒ 25 mmHg vs 119 ▒ 10 mmHg, p = 0.0009, ambulatory BP: 140 ▒ 18 mmHg vs 124 ▒ 11 mmHg, p = 0.009). The differences in diastolic BP levels were less obvious (clinic BP: 87 ▒ 16 mmHg vs 76 ▒ 8 mmHg, p = 0.02, ambulatory BP: 84 ▒ 13 mmHg vs 77 ▒ 9 mmHg, p = 0.052). Daytime ambulatory BP was more strongly related than clinic BP to the coarctation diameter (AD) (systolic BP r = -0.73, p = 0.0006 and r = -0.61, p = 0.007, respectively). In surgically corrected patients (n = 14) only the correlations between ambulatory systolic daytime (r = -0.61, p = 0.02) and night-time (r = -0.58, p = 0.03) BP to AD was statistically significant. Conclusion.-Ambulatory BP correlates strongly with aortic coarctation measured by TEE and would thus be the preferred technique for evaluating BP in this patient category.
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33. |
- Forssell, Claes, et al.
(author)
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A Pilot Study of Perioperative External Circumferential Cryoablation of Human Renal Arteries for Sympathetic Denervation
- 2020
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In: Vascular specialist international. - Seongnam, Korea, Republic of : Korean Society for Vascular Surgery. - 2288-7970 .- 2288-7989. ; 36:3, s. 151-157
-
Journal article (peer-reviewed)abstract
- Cryoablation, which induces cellular death without extensive tissue damage, has been extensively used to denervate the myocardium. However, periadventitial external circumferential application of cryotherapy to denervate the renal artery sympathetic nerves has, to our knowledge, never been tested in humans. The main aim of this study was to examine the safety and potential effects of cryotherapy on ambulatory blood pressure levels and other outcomes that are indirectly related to sympathetic tone, including pulse-wave velocity, central pulse pressure, and glucose levels.
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34. |
- Fridell, Sara, et al.
(author)
-
A randomised study in young subjects of the effects of eating extra fruit or nuts on periodontal inflammation
- 2018
-
In: BDJ Open. - : Nature Publishing Group. - 2056-807X. ; 3
-
Journal article (peer-reviewed)abstract
- Objectives/Aims:Fruit is often advocated as a healthy source of nutrients and vitamins. However, the high contents of sugars in many fruits could potentially counteract positive effects on the teeth.Materials and methods:We recruited 30 healthy non-obese participants who were randomised to either supplement their diet with extra fruits or nuts, each at +7 kcal/kg body weight/day, for 2 months.Results:Fructose intake increased from 9.1±6.0 to 25.6±9.6 g/day, P<0.0001, in the fruit group and was reduced from 12.4±5.7 to 6.5±5.3 g/day, P=0.007, in the nut group. Serum-vitamin C increased in both groups (fruit: P=0.017; nuts: P=0.009). α-Tocopherol/cholesterol ratio increased in the fruit group (P=0.0033) while β-carotene/cholesterol decreased in the nut group (P<0.0001). The amount of subjects with probing pocket depths ⩾4 mm in the fruit group was reduced (P=0.045) according to blinded examinations, and the difference in the changes in probing pockets ⩾4 mm was also statistically significant between the food groups (P=0.010).Conclusion:A large increase of fruit intake, compared with nuts, had a favourable effect on periodontal status in some respects, despite the high sugar contents. To search for potential protective micronutrients in fruit that protect the teeth could be an aim for further research.
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35. |
- Hallberg, Pär, et al.
(author)
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Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy
- 2003
-
In: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261 .- 1471-2261. ; 18:3, s. 11-
-
Journal article (peer-reviewed)abstract
- BackgroundAdipocyte-derived leucine aminopeptidase (ALAP) is a recently identified member of the M1 family of zinc-metallopeptidases and is thought to play a role in blood pressure control through inactivation of angiotensin II and/or generation of bradykinin. The enzyme seems to be particularly abundant in the heart. Recently, the Arg528-encoding allele of the ALAP gene was shown to be associated with essential hypertension.MethodsWe evaluated the influence of this polymorphism on the change in left ventricular mass index in 90 patients with essential hypertension and echocardiographically diagnosed left ventricular hypertrophy, randomised in a double-blind study to receive treatment with either the angiotensin II type I receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol for 48 weeks. Genyotyping was performed using minisequencing.ResultsAfter adjustment for potential covariates (blood pressure and left ventricular mass index at baseline, blood pressure change, age, sex, dose and added antihypertensive treatment), there was a marked difference between the Arg/Arg and Lys/Arg genotypes in patients treated with irbesartan; those with the Arg/Arg genotype responded on average with an almost two-fold greater regression of left ventricular mass index than patients with the Lys/Arg genotype (-30.1 g/m2 [3.6] vs -16.7 [4.5], p = 0.03).ConclusionsThe ALAP genotype seems to determine the degree of regression of left ventricular hypertrophy during antihypertensive treatment with the angiotensin II type I receptor antagonist irbesartan in patients with essential hypertension and left ventricular hypertrophy. This is the first report of a role for ALAP/aminopeptidases in left ventricular mass regulation, and suggests a new potential target for antihypertensive drugs.
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36. |
- Hallberg, Pär, et al.
(author)
-
B2 bradykinin receptor (B2BKR) polymorphism and change in left ventricular mass in response to antihypertensive treatment : results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial
- 2003
-
In: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 21:3, s. 621-4
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Hypertension is associated with a number of adverse morphologic and functional changes in the cardiovascular system, including left ventricular (LV) hypertrophy. Studies have demonstrated that bradykinin, through the B2 bradykinin receptor (B2BKR), mediates important cardiovascular effects that may protect against LV hypertrophy. Recently, a +9/-9 exon 1 polymorphism of the B2BKR was shown to be strongly associated with LV growth response among normotensive males undergoing physical training. We aimed to clarify whether the processes found in exercise-induced LV growth in normotensive people also occur in pathological LV hypertrophy. DESIGN AND METHODS: We determined the B2BKR genotype of 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, included in a double-blind study to receive treatment for 48 weeks with either the angiotensin II type 1 (AT1) receptor antagonist irbesartan or the beta1-adrenoceptor antagonist atenolol. RESULTS: B2BKR +9/+9 genotypes responded poorly in LV mass regression, independent of blood pressure reduction or treatment, as compared to the other genotypes (adjusted mean change in LV mass index = -10.0 +/- 4.6 versus -21.6 +/- 2.2 g/m2, P = 0.03). CONCLUSIONS: Our results suggest an impact of the B2BKR polymorphism on LV mass regression during antihypertensive treatment.
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37. |
- Hallberg, Pär, et al.
(author)
-
Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment : results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA)
- 2004
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In: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 27:5, s. 287-290
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Studies suggest that endothelin-1 contributes to the pathogenesis of hypertension. A G5665T gene polymorphism of preproendothelin-1 has been shown to be associated with higher blood pressure in overweight patients. No study has yet determined the effect of this polymorphism on the change in blood pressure during antihypertensive treatment.HYPOTHESIS:This study aimed to determine this effect in hypertensive patients with left ventricular (LV) hypertrophy during antihypertensive treatment with either irbesartan or atenolol.METHODS: We determined the preproendothelin-1 genotype using minisequencing in 102 patients with essential hypertension and LV hypertrophy verified by echocardiography, randomized in a double-blind fashion to treatment with either the AT1-receptor antagonist irbesartan or the beta1-adrenoceptor antagonist atenolol.RESULTS:The change in systolic blood pressure (SBP) after 12 weeks of treatment was related to the preproendothelin-1 genotype in men; after adjustment for potential covariates (age, blood pressure, and LV mass index at study entry, dose of irbesartan/atenolol, and type of treatment), those carrying the T-allele responded on average with a more than two-fold greater reduction than those with the G/G genotype (-21.9 mmHg [13.9] vs. -8.9 [2.3], p = 0.007). No significant differences in blood pressure change between G/G and carriers of the T-allele were seen among women.CONCLUSIONS:Our finding suggests a gender-specific relationship between the G5665T preproendothelin-1 polymorphism and change in SBP in response to antihypertensive treatment with irbesartan or atenolol, suggesting the endothelin pathway to be a common mechanism included in the hypertensive action of the drugs.
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38. |
- Hallberg, Pär, et al.
(author)
-
The CYP2C9 genotype predicts the blood pressure response to irbesartan : results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial
- 2002
-
In: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 20:10, s. 2089-2093
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The cytochrome P450 CYP2C9 enzyme (CYP2C9) metabolizes many clinically important drugs, for example, phenytoin, warfarin and the angiotensin II type 1 (AT(1)) receptor antagonists, losartan and irbesartan. Single nucleotide polymorphisms in the CYP2C9 gene result in the expression of three important variants, CYP2C9*1(wild-type), CYP2C9*2 and CYP2C9*3, the last two exhibiting reduced catalytic activity compared with the wild-type. The CYP2C9 genotype is known to determine sensitivity to and dose requirements for both warfarin and phenytoin, and also the rate of metabolism of losartan. However, its influence on clinical response to treatment with the AT(1) receptor antagonist, irbesartan, has not been investigated. OBJECTIVE: To determine whether the CYP2C9genotype influences the blood pressure-decreasing response to antihypertensive treatment with irbesartan. DESIGN AND METHODS: One hundred and two patients with essential hypertension and left ventricular hypertrophy were allocated randomly to groups to receive double-blind treatment with either irbesartan (n = 49) or the beta(1)-adrenergic receptor blocker, atenolol ( n= 53). Blood pressure was measured before and after 12 weeks of treatment. genotyping was performed using solid-phase minisequencing. RESULTS: The diastolic blood pressure (DBP) response differed in relation to the CYP2C9 genotype in patients given irbesartan: the reduction in patients with genotype CYP2C9*1/CYP2C9*1 (n = 33) was 7.5% and that with CYP2C9*1/CYP2C9*2 (n = 12) was 14.4% ( P= 0.036). A similar trend was seen for systolic blood pressure. In contrast, no relation was seen between the CYP2C9 genotype and blood pressure response to atenolol, a drug not metabolized via CYP2C9. CONCLUSIONS: The CYP2C9 genotype seems to predict the DBP response to irbesartan, but not to atenolol, in patients with essential hypertension.
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39. |
- Hallberg, Pär, et al.
(author)
-
Transforming growth factor beta1 genotype and change in left ventricular mass during antihypertensive treatment : results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA)
- 2004
-
In: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 27:3, s. 169-73
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Angiotensin II, via the angiotensin II type 1 (AT1) receptor, may mediate myocardial fibrosis and myocyte hypertrophy seen in hypertensive left ventricular (LV) hypertrophy through production of transforming growth factor beta1 (TGF-beta1); AT1-receptor antagonists reverse these changes. The TGF-beta1 G + 915C polymorphism is associated with interindividual variation in TGF-beta1 production. No study has yet determined the impact of this polymorphism on the response to antihypertensive treatment. HYPOTHESIS: We aimed to determine whether the TGF-beta1 G + 915C polymorphism was related to change in LV mass during antihypertensive treatment with either an AT1-receptor antagonists or a beta1-adrenoceptor blocker. The polymorphism was hypothesized to have an impact mainly on the irbesartan group. METHODS: We determined the association between the TGF-beta1 genotype and regression of LV mass in 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, randomized in a double-blind study to receive treatment for 48 weeks with either the AT1-receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol. RESULTS: Irbesartan-treated patients who were carriers of the C-allele, which is associated with low expression of TGF-beta1, responded with a markedly greater decrease in LV mass index (LVMI) than subjects with the G/G genotype (adjusted mean change in LVMI -44.7 g/m2 vs. -22.2 g/m2, p = 0.007), independent of blood pressure reduction. No association between genotype and change in LVMI was observed in the atenolol group. CONCLUSIONS: The TGF-beta1 G + 915C polymorphism is related to the change in LVMI in response to antihypertensive treatment with the AT1-receptor antagonist irbesartan.
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40. |
-
Hypertoni och Metabola Syndromet
- 2008. - 1
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Editorial collection (other academic/artistic)abstract
- Boken ger en modern syn på diagnostik och behandling av metabola syndromets olika komponenter, med beskrivning av bakomliggande mekanismer. Boken är skriven av författare som samtidigt är både forskare och läkare, och vänder sig till personer som är verksamma inom allmänmedicin och internmedicins olika grenar, kardiologi, endokrinologi, diabetologi och geriatrik. Den vänder sig även till AT- och ST-läkare samt till studenter på främst läkarlinjen.
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41. |
- Johansson, Martina AK, 1984-, et al.
(author)
-
Overview of The Current Progress of Facultative Anaerobic Bacteria in Cancer Biotherapy with TNF-α as Main Mechanism of Action
- 2024
-
Other publication (other academic/artistic)abstract
- This review article focuses on the use of infectious bacteria as delivery tool for tumour necrosis factor α (TNF-α), a well-studied cytokine, in the context of immunotherapy for cancer treatment. The tumour targeting properties of certain bacteria strains has been known for decades as well as the tumour catabolizing effect of TNF-α. The combination of these two have been studied in murine models for various types of cancer with promising results. Research in this fascinating field is unfortunately uncommon, thus the number of high-quality articles is limited. Search was done via Google Scholar in combination with PubMed, to increase the coverage and find peer-reviewed, original, and primary research articles.Key findings show that attenuated or genetically modified species of bacteria have fewer side effects and can be effective in delivering cytokines to tumour sites. TNF-α is produced by macrophages/monocytes during acute inflammation or infection, thus can be triggered by infectious bacteria which in turn induce apoptosis. The cytotoxic effect of the bacteria can be enhanced with localized irradiation. Promising results have been shown in bladder, breast, colon, glial, lung, ovarian, pancreatic, prostate, and renal cancer cells.The need for better, safer, and more effective cancer treatment is apparent as traditional chemotherapy and radiation can cause a lot of harm for the patient, and not necessarily prolong the lifespan. The success-rate for these treatments vary greatly depending on the type of cancer, but for tumours that cannot be surgically removed the outcome is generally quite poor. A drawback of chemotherapy is that tumours can grow resistant to the treatment while healthy cells continue to be exposed, increasing the risk of severe side effects. Different types of biological therapies are a modern and possibly safer approach, even though immunotherapy comes with substantial risks. Using the innate immune system to fight tumour cells is not always safe, because uncontrolled and excessive release of pro-inflammatory signalling molecules can result in multisystem organ failure and death. This phenomenon is called cytokine release syndrome (cytokine storm) and is one of the major risks of immunotherapy. However, tailored biological therapies have proven their effectiveness for a wide range of cancer types, and the next step in this evolution is to genetically engineer both delivery systems and mechanisms of action. This approach can be combined with the traditional radiation and chemotherapy for increased effectiveness, even if biological therapies as a stand-alone treatment, can be a goal for the future.
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42. |
- Jonasson, Hanna, et al.
(author)
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Skin microvascular endothelial dysfunction is associated with type 2 diabetes independently of microalbuminuria and arterial stiffness
- 2017
-
In: Diabetes & Vascular Disease Research. - : SAGE PUBLICATIONS LTD. - 1479-1641 .- 1752-8984. ; 14:4, s. 363-371
-
Journal article (peer-reviewed)abstract
- Skin and kidney microvascular functions may be affected independently in diabetes mellitus. We investigated skin microcirculatory function in 79 subjects with diabetes type 2, where 41 had microalbuminuria and 38 not, and in 41 age-matched controls. The oxygen saturation, fraction of red blood cells and speed-resolved microcirculatory perfusion (% red blood cells x mm/s) divided into three speed regions: 0-1, 1-10 and above 10 mm/s, were assessed during baseline and after local heating of the foot with a new device integrating diffuse reflectance spectroscopy and laser Doppler flowmetry. Arterial stiffness was assessed as carotid-femoral pulse wave velocity. Subjects with diabetes and microalbuminuria had significantly higher carotid-femoral pulse wave velocity compared to subjects without microalbuminuria and to controls. The perfusion for speeds 0-1 mm/s and red blood cell tissue fraction were reduced in subjects with diabetes at baseline and after heating, independent of microalbuminuria. These parameters were correlated to HbA1c. In conclusion, the reduced nutritive perfusion and red blood cell tissue fraction in type 2 diabetes were related to long-term glucose control but independent of microvascular changes in the kidneys and large-vessel stiffness. This may be due to different pathogenic pathways in the development of nephropathy, large-vessel stiffness and cutaneous microvascular impairment.
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43. |
- Karlsson, J, et al.
(author)
-
Beta1-adrenergic receptor gene polymorphisms and response to beta1-adrenergic receptor blockade in patients with essential hypertension
- 2004
-
In: Clinical Cardiology. - 0160-9289 .- 1932-8737. ; 27:6 SUPPL. 3, s. 347-350
-
Journal article (peer-reviewed)abstract
- Background: Studies suggest that the Ser49Gly and Arg389Gly polymorphisms in the β1-adrenergic receptor might be of functional importance for the cardiovascular system. Both have been associated with altered receptor activity in vitro, and with hypertension and cardiac failure in vivo. Hypothesis: The aim of this study was to test whether these polymorphisms were associated with the change in heart rate or blood pressure in patients with essential hypertension and left ventricular (LV) hypertrophy treated with the β1-adrenergic receptor blocker atenolol. Methods: Blood pressure and heart rate were measured in 101 hypertensive patients with echocardiographically verified LV hypertrophy, randomized in a double-blind study to treatment with either the β1-adrenergic receptor blocker atenolol or the angiotensin II type I receptor antagonist irbesartan. Changes in blood pressure and heart rate were evaluated after 12 weeks. Beta1-adrenergic receptor genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism. Results: We found no significant associations between the changes in the measured variables and either of the two polymorphisms. However, carriers of the 49Gly allele showed a tendency toward a greater reduction in heart rate compared with patients with the Ser/Ser49 genotype (p = 0.06). Conclusions: The Ser49Gly and Arg389Gly β1-adrenergic receptor polymorphisms do not seem to exert a major effect on the changes in heart rate and blood pressure during 12 weeks of treatment with atenolol in patients with essential hypertension and LV hypertrophy.
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44. |
- Karlsson, Margareta, 1942-, et al.
(author)
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Colocalization of insulin receptor and insulin receptor substrate-1 to caveolae in primary human adipocytes
- 2004
-
In: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 271:12, s. 2471-2479
-
Journal article (peer-reviewed)abstract
- Caveolae are plasma membrane invaginations with several functions, one of which appears to be to organize receptor mediated signalling. Here we report that in primary human subcutaneous adipocytes the insulin receptor was localized to caveolae by electron microscopy/immunogold detection and by isolating caveolae from plasma membranes. Part of insulin receptor substrate 1 (IRS1), the immediate downstream signal mediator, was colocalized with the insulin receptor in the plasma membrane and caveolae, as demonstrated by immunofluorescence microscopy, immunogold electron microscopy, and immunogold electron microscopy of transfected recombinant HA-IRS1. In contrast, rat epididymal adipocytes lacked IRS1 at the plasma membrane. Depletion of cholesterol from the cells using β-cyclodextrin blocked insulin stimulation of glucose uptake, insulin inhibition of perilipin phosphorylation in response to isoproterenol, and insulin stimulation of protein kinase B and Map-kinases extracellular signal-related kinase (ERK)1/2 phosphorylation. Insulin-stimulated phosphorylation of the insulin receptor and IRS1 was not affected, indicating that caveolae integrity is required downstream of IRS1. In conclusion we show that insulin receptor and IRS1 are both caveolar proteins and that caveolae are required for both metabolic and mitogenic control in human adipocytes. Our results establish caveolae as foci of insulin action and stress the importance of examining human cells in addition to animal cells and cell lines.
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45. |
- Kentson, Magnus
(author)
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Fatigue and Peripheral Muscle Dysfunction: Studies on Vitamin D Status, Muscle Metabolism and Systemic Inflammation in Patients with COPD : Aspects of COPD severity beyond FEV1 and exacerbations
- 2022
-
Doctoral thesis (other academic/artistic)abstract
- BackgroundThe severity of Chronic Obstructive Pulmonary Disease (COPD) is usually described in terms of forced expiratory volume in one second (FEV1) and number of exacerbations. However, COPD is a complex disease with different ways of expression, involving pulmonary symptoms, extra pulmonal manifestations and comorbidities, which altogether affect the patient by contributing to reduced functional capacity, increased shortness of breath, reduced health-related quality of life and increased mortality. Systemic inflammation is common in COPD and can potentially constitute a link between the lungs and other organs. The aim of this thesis was to broaden the aspects of COPD severity beyond FEV1 and exacerbations by studying fatigue, the role of vitamin D, nutritional factors, systemic inflammation and peripheral muscle function in patients with COPD. Methods and ResultsIn paper I, we included 101 patients with COPD, and 34 control subjects. Assessment of experience of fatigue, functional limitation due to fatigue, and the relationships to physiological, psychological and situational variables and quality of life (QoL) were evaluated. We found that experience of fatigue was highly prevalent (72% versus 56% in control subjects) and a troublesome symptom in COPD. Patients with COPD and fatigue had lower lung function, shorter walking distance, more dyspnoea, anxiety and depressive symptoms and poorer health status compared to patients without fatigue (all p < 0.01). Several contributing factors were identified to experience of fatigue and functional limitations of fatigue with dyspnoea, depressive symptoms and insomnia as the most prominent factors. No clear association with systemic inflammation was found. Paper II evaluated vitamin D status in 66 patients with advanced COPD (28 with long-term oxygen therapy (LTOT)) and 47 control subjects. 25-hydroxyvitamin 25(OH)D were deter-mined in early fall in a short period of seven weeks. Questionnaires about COPD symptoms, general health, lifestyle, dietary habits and QoL were answered. Lung function tests and blood sampling including systemic inflammatory markers, carotenoids and protein carbonylation (PC) were assessed. The peak annual 25(OH)D of COPD patients was significantly lower than in the control subjects, but there was no significant difference between COPD patients with and without LTOT. Among vitamin D-deficient COPD patients, 25(OH)D correlated positively with lung function, blood oxygenation, food portion size, Mediterranean Diet Score and Ultra-violet Score and negatively with dyspnoea and DOSE-index, a composite index for COPD se-verity. Ongoing vitamin D supplementation was the single most important intervention to maintain 25(OH)D levels <50 nmol/L. In paper III, we evaluated in the same cohort as paper II oxidative damage and levels of carotenoids. Patients with COPD (±LTOT) did not demonstrate increased oxidative damage. Com-pared with the control group, levels of several carotenoids were significantly lower in COPD, and the diet contained significantly less fruit and vegetables. Lycopene correlated positively with saturation and lutein correlated positively with some inflammatory markers but negatively with IL-6, an important marker for systemic inflammation. The study highlights the importance of dietary factors in COPD. In paper IV, 32 patients with COPD answered questionnaires, and were subjected to lung function tests and blood analysis including systemic inflammatory markers. Magnetic resonance imaging (MRI) for analysis of whole-body and thigh muscle composition was performed. Bioenergetics in the resting thigh muscle, (PCr/Pi ratio), were analysed using 31phosphorus magnetic resonance spectroscopy (31P-MRS). We found that adverse muscle composition was common in the COPD group. Clinical characteristics reflecting COPD severity were all associated with a raise of the PCr/Pi ratio in the thigh muscle. Increased MFIa correlated positively to systemic inflammatory markers, negative to physical activity and PCr/Pi ratio. We compared the COPD group with a virtual control group from UK Biobank (n= 3200). ConclusionsSevere COPD is much more than airway obstruction and exacerbations. The presence of fatigue is associated, as well as vitamin D status and nutritional factors, with important clinical out-comes reflecting COPD severity. Adverse muscle composition is common in COPD and there seems to be a link between systemic inflammation, muscle fat infiltration and bioenergetics.
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46. |
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47. |
- Kurland, Lisa, 1960-, et al.
(author)
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Polymorphisms in the angiotensinogen and angiotensin II type 1 receptor gene are related to change in left ventricular mass during antihypertensive treatment : results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial
- 2002
-
In: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 20:4, s. 657-663
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Our aim was to determine if gene polymorphisms in the renin-angiotensin-aldosterone system (RAAS) were related to the degree of change in left ventricular hypertrophy (LVH) during antihypertensive treatment. METHODS AND RESULTS: Patients with essential hypertension and echocardiographically diagnosed LVH were included in a double-blind study to receive treatment with either the angiotensin II type 1 receptor (AT1-receptor) antagonist irbesartan (n = 41), or the beta-1 adrenergic receptor blocker atenolol (n = 43) as monotherapy for 3 months. The angiotensinogen T174M and M235T, the angiotensin-converting enzyme I/D, the AT1-receptor A1166C and the aldosterone synthase (CYP11B2) -344 C/T polymorphisms were analysed and related to the change in left ventricular mass (LVM). Patients with the angiotensinogen 174 TM genotype treated with irbesartan responded with the greatest reduction in LVM (-23 +/- 31SD g/m2 for TM and +0.5 +/- 18 g/m2 for TT, P = 0.005), independent of blood pressure reduction. Both the angiotensinogen 235 T-allele (P = 0.02) and the AT1-receptor 1166 AC genotype responded with the greatest reduction in LVM when treated with irbesartan (-0.1 +/- 19 g/m2 for AA and -18 +/- 30 g/m2 for AC, P = 0.02), independent of blood pressure reduction. These polymorphisms were not associated with the change in LVM during treatment with atenolol. DISCUSSION: The angiotensinogen T174M and M235T and the AT1-receptor A1166C polymorphisms were related to the change in LVH during antihypertensive treatment with an AT1-receptor antagonist; of these angiotensinogen T174M was the most powerful. This highlights the role of the RAAS for left ventricular hypertrophy and the potential of pharmacogenetics as a tool for guidance of antihypertensive therapy.
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48. |
- Liljedahl, Ulrika, et al.
(author)
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A microarray minisequencing system for pharmacogenetic profiling of antihypertensive drug response
- 2003
-
In: Pharmacogenetics. - : Ovid Technologies (Wolters Kluwer Health). - 0960-314X .- 1473-561X. ; 13:1, s. 7-17
-
Journal article (peer-reviewed)abstract
- We aimed to develop a microarray genotyping system for multiplex analysis of a panel of single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in blood pressure regulation, and to apply this system in a pilot study demonstrating its feasibility in the pharmacogenetics of hypertension. A panel of 74 SNPs in 25 genes involved in blood pressure regulation was selected from the SNP databases, and genotyped in DNA samples of 97 hypertensive patients. The patients had been randomized to double-blind treatment with either the angiotensin II type 1 receptor blocker irbesartan or the beta 1-adrenergic receptor blocker atenolol. Genotyping was performed using a microarray based DNA polymerase assisted 'minisequencing' single nucleotide primer extension assay with fluorescence detection. The observed genotypes were related to the blood pressure reduction using stepwise multiple regression analysis. The allele frequencies of the selected SNPs were determined in the Swedish population. The established microarray-based genotyping system was validated and allowed unequivocal multiplex genotyping of the panel of 74 SNPs in every patient. Almost 7200 SNP genotypes were generated in the study. Profiles of four or five SNP-genotypes that may be useful as predictors of blood pressure reduction after antihypertensive treatment were identified. Our results highlight the potential of microarray-based technology for SNP genotyping in pharmacogenetics.
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49. |
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50. |
- Löfgren, U B, et al.
(author)
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Diabetes control in Swedish community dwelling elderly : More often tight than poor
- 2004
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 255:1, s. 96-101
-
Journal article (peer-reviewed)abstract
- Objective. To determine glycaemic control in elderly patients with diabetes living in community dwelling. Design. Descriptive, cross-sectional and open. Prospective with regard to blood glucose. Setting. Community-dwelling in-patients. Subjects. From a total number of 351 patients in seven Swedish centres of community dwelling we identified and recruited all 45 patients with diabetes receiving treatment with insulin, and/or oral medication. Main outcome measures. Blood glucose was measured fasting, 2 h after breakfast, in the evening and at night, for three consecutive days. Results. Mean HbA1c was 5.9 ± 1.1% (range 3.6-8.6%). The patients were split in three HbA1c-groups for analysis: lower- (3.6-5.3%), middle-(5.4-6.3%) and higher-tertile (6.4-8.6%). The groups where similar with regard to age, time in community dwelling, ability to eat and move around independently, but body mass index was lower in the lower tertile (P < 0.003 and P < 0.04, compared with middle- and higher-tertiles). We recorded 14 episodes with blood glucose ≤4.0 mmol L-1 in eight patients. Blood glucose ≤4.0 mmol L-1 was mostly recorded during night (n = 8) or in the morning (n = 3). Conclusions. Swedish patients with diabetes in community dwelling are over- rather than undertreated and have low HbA1c levels. Despite very regular eating habits and near total compliance with medication, hypoglycaemias are frequent and possibly linked to malnutrition.
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