| 1. |
- Carlsson, Axel C., et al.
(författare)
-
Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes
- 2016
-
Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease.METHODS: The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used.RESULTS: Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32-1.93, p < 0.001 and OR 1.54, 95 % CI 1.21-1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29-2.174, p < 0.001 and HR 1.47, 95 % CI 1.13-1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality.CONCLUSIONS/INTERPRETATIONS: Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.
|
|
| 2. |
- Vos, T., et al.
(författare)
-
Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016
- 2017
-
Ingår i: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1211-1259
-
Tidskriftsartikel (refereegranskat)abstract
- Background As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. Methods We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57.6 million (95% uncertainty interval [UI] 40.8-75.9 million [7.2%, 6.0-8.3]), 45.1 million (29.0-62.8 million [5.6%, 4.0-7.2]), 36.3 million (25.3-50.9 million [4.5%, 3.8-5.3]), 34.7 million (23.0-49.6 million [4.3%, 3.5-5.2]), and 34.1 million (23.5-46.0 million [4.2%, 3.2-5.3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2.7% (95% UI 2.3-3.1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10.4% (95% UI 9.0-11.8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228). Interpretation The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-todate information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
|
|
| 3. |
- Hay, S. I., et al.
(författare)
-
Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016 : A systematic analysis for the Global Burden of Disease Study 2016
- 2017
-
Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1260-1344
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). Methods: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE difered from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. Findings: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs ofset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the fve lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. Interpretation: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs ofset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention eforts, and development assistance for health, including fnancial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. © The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
|
|
| 4. |
- Larsson, Anders, et al.
(författare)
-
Validation of a Novel Point-of-Care Testing Device Designed for Assessment of NT-pro BNP
- 2023
-
Ingår i: Journal of Family Medicine and Primary Care Open access. - : Gavin Publishers. - 2688-7460. ; 7:2
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Our main objective was to compare Point-Of-Care Technology (POCT) to central laboratory immunochemistry testing, to assess N-terminal pro B-type Natriuretic Peptide (NT-proBNP) in ambulatory patients. A second objective was to use POCT to analyze NT-proBNP in a cohort of healthy blood donors to define reference values. Methods: Blood samples were obtained from 102 outpatients and 133 blood donors, respectively. Samples analyzed using a point-of-care instrument [NT-proBNPLumiraDx (LumiraDx, Solna, Sweden)] were compared to a commercial electrochemiluminescence immunoassay method [(NTproBNPRoche) on the Cobas Pro analyzer (Roche Diagnostics, Mannheim, Germany)]. The study was ethically approved (01–367) and complied with the Declaration of Helsinki. Values are given as Median and Interquartile Range (IQR). Results: There was a distinct correlation between the two assays for assessing the circulating levels of NT-proBNP in outpatients (R² = 0.9546). NT-proBNPLumiraDx ranged between 50–3966 ng/L [Median: 276 (IQR: 679)] whereas NT-proBNPRoche ranged between 50–3820 ng/L; (Median: 268 (IQR: 628)]. NT-proBNPLumiraDx was 3% higher than NT-proBNPRoche (p<0.05). NT-proBNPLumiraDx levels were not affected by age in our cohort of blood donors. Conclusion: In cases where short turnaround-times for assessment of NT-proBNP are desirable, the LumiraDx instrument can safely be used as an analytical option.
|
|
| 5. |
- Ricci, Fabrizio, et al.
(författare)
-
Orthostatic hypotension is associated with higher levels of circulating endostatin
- 2024
-
Ingår i: European Heart Journal Open. - 2752-4191.
-
Tidskriftsartikel (refereegranskat)abstract
- AimsThe pathophysiology of orthostatic hypotension (OH), a common clinical condition, associated with adverse outcomes, is incompletely understood. We examined the relationship between OH and circulating endostatin, an endogenous angiogenesis inhibitor with antitumor effects proposed to be involved in blood pressure (BP) regulation.MethodsWe compared endostatin levels in 146 patients with OH and 150 controls. A commercial chemiluminescence sandwich immunoassay was used to measure circulating levels of endostatin. Linear and multivariate logistic regressions were conducted to test the association between endostatin and OH.ResultsEndostatin levels were significantly higher in OH patients (59,024 ± 2513 pg/mL) versus controls (44,090 ± 1978 pg/mL, p<0.001). A positive linear correlation existed between endostatin and the magnitude of systolic BP decline upon standing (p<0.001). Using multivariate analysis, endostatin was associated with OH (adjusted odds ratio per 10% increase of endostatin in the whole study population = 1.264, 95%CI 1.141-1.402), regardless of age, sex, prevalent cancer, and cardiovascular disease, as well as traditional cardiovascular risk factors.ConclusionCirculating endostatin is elevated in patients with orthostatic hypotension and may serve as a potential clinical marker of increased cardiovascular risk in patients with orthostatic hypotension. Our findings call for external validation. Further research is warranted to clarify the underlying pathophysiological mechanisms.
|
|
| 6. |
- Pettersson-Pablo, Paul, 1986-
(författare)
-
Biomarkers of vascular function and structure in young healthy adults
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerosis is a disease affecting the blood vessels in the body. Its pathophysiologic mechanisms involve infiltration of the vessel walls by fatty matter and immune cells. This process is slow, starting in childhood but typically not manifesting as symptomatic disease until late adulthood (after 60 years of age). The identification of younger individuals with a high risk for early intervention has a higher potential of preventing morbidity and mortality.In this thesis, part of the Lifestyle, Biomarkers and Atherosclerosis study (LBA), the earliest stages of vascular dysfunction have been examined in a population of young, healthy, non-smoking subjects. Vascularfunction and structure measurements predict a future risk of cardiovascular disease (CVD). The measurements were analyzed in relation to clinical chemistry analyses of various biomarkers in serum and plasma that have been associated with inflammation or cardiovascular risk. A secondary aim was to examine estrogen containing contraceptive use and its relation to the CVD biomarkers.In Paper I and Paper II of the thesis, the association between inflammatory biomarkers, body fat percentage and vascular function and structure measurements was examined in multivariable linear regression models. A higher body fat percentage predicted an increased serum concentration of C-reactive protein (CRP) and orosomucoid. In Paper II, a higher body fat percentage and a higher CRP were associated with a more unfavorable vascular function and structure.In Paper III and Paper IV, we employed two multiplex proteomics panels to analyze inflammatory proteins and proteins previously implicated in CVD. In multivariable linear regression models, proteins implicated in hemostasis, inflammatory signaling and chemoattraction correlated with different vascular function and structure measurements. InPaper IV, insulin-like growth factor-binding protein 1 (IGFBP1) and IGFBP2 were independently predictive of an increased vascular stiffness.In conclusion, even in young, healthy individuals, altered concentrations of serum biomarkers can be detected in subjects with increased body fat and unfavorable vascular function and structure.
|
|
| 7. |
|
|
| 8. |
- Olsson, Erik, 1967-, et al.
(författare)
-
The effect of group-based cognitive behavioral therapy on inflammatory biomarkers in patients with coronary disease : results from the SUPRIM-trial
- 2018
-
Ingår i: Upsala Journal of Medical Sciences, Supplement. - : Uppsala Medical Society. - 0300-9726 .- 0300-9734 .- 2000-1967. ; 123:3, s. 167-173
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The Secondary Prevention in Uppsala Primary Healthcare Project (SUPRIM) is a prospective randomized controlled trial of a group-based cognitive behavioral therapy (CBT) stress management program for coronary heart disease (CHD) patients. The intervention reduced the risk of fatal or non-fatal first recurrent cardiovascular (CV) events. The aim of the present study was to analyze if the positive effects of the CBT program on clinical outcomes could have been mediated by changes in biomarkers for inflammation.Methods: Altogether 362 patients with CHD were randomly assigned to intervention or usual care. The inflammatory biomarkers (VCAM-1, TNF-R1, TNF-R2, PTX3, and hs-CRP) were serially assessed at five time points every six months from study start until 24 months later, and analyzed with linear mixed models.Results: Baseline levels of the inflammatory markers were near normal, indicating a stable phase. The group-based CBT stress management program did not significantly affect the levels of inflammatory biomarkers in patients with CHD. Three out of five (VCAM-1, TNF-R2, and PTX3) inflammatory biomarkers showed a slight increase over time in both study groups, and all were positively associated with age.Conclusion: Group-based CBT stress management did not affect biomarkers for inflammation in patients with CHD. It is therefore unlikely that inflammatory processes including these biomarkers were mediating the effect the CBT program had on the reduction in CV events. The close to normal baseline levels of the biomarkers and the lack of elevated psychological distress symptoms indicate a possible floor effect which may have influenced the results.Keywords: Biomarkers, CBT, CHD, inflammation, stress management
|
|
