| 1. |
- Ntalla, Ioanna, et al.
(författare)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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| 2. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 3. |
- Calais, Fredrik, 1971-
(författare)
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Coronary artery disease and prognosis in relation to cardiovascular risk factors, interventional techniques and systemic atherosclerosis
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To evaluate the prognosis associated with location and severity of coronary and systemic atherosclerosis in patients with coronary artery disease (CAD) in relation to risk factors and interventional techniques.Methods: The thesis comprised six longitudinal studies based on three patient cohorts: The Swedish Coronary Angiography and Angioplasty Registry, the Västmanland Myocardial Infarction Survey, and the Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia study, to evaluate clinical outcome relative to coronary lesion location and severity, extracoronary artery disease (ECAD), intervention techniques, and leisuretime physical inactivity (LTPI).Results: Stent placement in the proximal left anterior descending artery (LAD) was more often associated with restenosis than was stenting in the other coronary arteries. The use of drug-eluting stents in the LAD was associated with a lower risk of restenosis and death compared to baremetal stents. Thrombus aspiration in in the LAD during acute ST elevation myocardial infarction (MI) did not improve clinical outcome, irrespective of adjunct intervention technique. Clinical, but not subclinical, ECAD was associated with poor prognosis in patients with MI. Longitudinal extent of CAD at the time of MI was a predictor of ECAD, and coexistence of extensive CAD and ECAD was associated with particularly poor prognosis following MI. Self-reported LTPI was associated with MI and all-cause mortality independent of ECAD.Conclusions: Drug-eluting stents, but not thrombus aspiration, improved prognosis following percutaneous coronary intervention in the proximal LAD. Self- reported LTPI, clinical ECAD, and systemic atherosclerosis defined groups with poor prognosis after MI.
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| 4. |
- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 5. |
- Grauman, Åsa, 1982-
(författare)
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The publics’ perspective on cardiovascular risk information : Implications for practice
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lay people struggle to understand the implications of cardiovascular risk information. With new advanced testing techniques and the digitalization of personal health information, the communication of cardiovascular risk becomes a challenge. The overall aim of the thesis was to investigate the publics’ perspective of cardiovascular risk information through a multi-method approach, including how individuals perceive risk, factors affecting an underestimation of risk, how cardiovascular risk communication affects individuals’ psychosocial health, and their preferences for risk communication. In study I, research participants’ perceptions about risk information were explored in five focus group interviews. The participants’ (n=31) perceptions about cardiovascular risk were complex, where multifactorial aspects were disregarded. The communication of cardiovascular risk information did not meet the participants’ need for understanding, support, and guidance regarding what to do with this information. Study II was a before-after investigation regarding the impact of cardiovascular risk information on research participants’ health-related quality of life and mental distress. Increased worry and anxiety were observed in individuals referred to hospital because of coronary artery stenosis. Study III was a cross-sectional study, which found that individuals with a very good or excellent self-perceived general health and individuals without a family history of CVD were more likely to underestimate their cardiovascular risk compared to participants with poor or fairly good general health and without a family history. Study IV was a cross-sectional study, investigating the preferences of the Swedish population for communication of cardiovascular risk information from a health checkup using a Discrete Choice Experiment. Besides cost, consultation time was the most important aspect when communicating cardiovascular risk. The findings suggest that cardiovascular risk communication does not reach its fullest potential when it comes to recipients’ perspective of the benefits of CV risk communication. Improvements should aim at increasing the recipients’ personal control and health literacy and furthermore, acknowledge the fact that self-perceived risk is influenced by how a person feels in general and experiences of family history.
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| 6. |
- Lagedal, Rickard, 1981-
(författare)
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Coronary angiography after out-of-hospital cardiac arrest
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Out-of-hospital cardiac arrest (OHCA) is a common cause of death with a survival rate of 10% in Sweden. The chance of survival depends on rapid recognition, high quality cardiopulmonary resuscitation and post-resuscitation care including searching and treating the cause of the arrest. Ischaemic cardiac disease including acute coronary artery occlusions is the most common cause of OHCA. Acute coronary artery lesions can be diagnosed and treated with coronary angiography and subsequent PCI. This thesis analyses various aspects of coronary angiography after OHCA. Paper I+II describes the rational, protocol and the results from the pilot phase (n=117) of a randomized multicentre clinical trial. We compared a strategy of immediate coronary angiography in patients successfully resuscitated after OHCA with a strategy without immediate coronary angiography. We did not reach the stipulated time of 120 minutes from first medical contact to angiography, but our study strategy was feasible. No major unexpected safety issues were reported. The main phase of the study could therefore be started with only minor changes from the pilot phase protocol. In a registry study of 1133 patients (Paper III) coronary angiographic findings were compared with ECG and comorbidities in unconscious patients after OHCA. In patients without ST-elevation, the rate of PCI attempts was higher in patients with ST-depression (47%) and in patients with ECG classified as “other findings” (45%) compared to patients with normal ECG (33%), OR 1.78 (CI 1.13-2.82) and OR 1.65 (CI 1.04-2.61), respectively. When analysing patients without ST-elevation, no difference in PCI rates were found between the comorbidity groups and neither between patients with shockable compared to non-shockable initial ECG rhythm. Paper IV is a registry study (n=3906) analysing the impact of patient income on the probability to receive early coronary angiography after OHCA. When dividing patients into income quarters and adjusting for confounders, increasing income was associated with higher rates of early coronary angiography. Thirty-six percent of patients in the highest income quarter received early angiography compared to fifteen percent in the lowest income quarter, OR 1.64 (1.27-2.11). Adding potential mediators to explain this finding gradually decreased the difference, and the main explanatory factor for this difference was that higher income is associated with higher rates of shockable ECG rhythm. 30-day survival was also higher in the highest income quarter compared to the lowest income group in the fully adjusted analysis, OR 1.51 (CI 1.22-1.89).
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| 7. |
- Lindholm, Daniel, 1982-
(författare)
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Platelet Inhibition, Revascularization, and Risk Prediction in Non-ST-elevation Acute Coronary Syndromes
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiovascular disease is the leading cause of death worldwide and ischemic heart disease is the most common manifestation. Despite improved outcomes during the last decades, patients with acute coronary syndromes (ACS) are still at substantial risk of recurrent ischemic events and mortality.The aims of this thesis were to investigate the effect of the novel antiplatelet agent ticagrelor versus clopidogrel in patients with non-ST-elevation ACS (NSTE-ACS), overall and in relation to initial revascularization, and to explore this effect in relation to cardiac biomarkers. The impact of timing of revascularization in non-ST-elevation myocardial infarction (NSTEMI) was also studied, by assessing risk of mortality and recurrent myocardial infarction in relation to delay of percutaneous coronary intervention (PCI) in a nation-wide cohort. Finally, a novel clinical prediction model based on angiographic findings, biomarkers, and clinical characteristics was developed to estimate risk of ischemic events after performed revascularization.Ticagrelor treatment compared with clopidogrel was associated with a reduction in the composite endpoint of cardiovascular death/myocardial infarction/stroke and mortality alone, without any increase in overall major bleeding, but increased non-CABG-related major bleeding. The effect of ticagrelor over clopidogrel was consistent independent of initial revascularization. Elevated high-sensitivity cardiac troponin-T predicted benefit of ticagrelor over clopidogrel, while no difference between treatments was detected at normal levels. In patients with NSTEMI, PCI treatment within two days after hospital admission was associated with lower risk of all-cause death and recurrent myocardial infarction compared with delayed PCI. The new clinical prediction model included the following variables: prior vascular disease, extent of coronary artery disease, level of N-terminal pro-B-type natriuretic peptide and estimated glomerular filtration rate; and showed good discriminatory ability for the risk prediction of cardiovascular death/myocardial infarction/stroke and cardiovascular death alone.In conclusion, these results show that ticagrelor reduces the risk of recurrent ischemic events and mortality in patients with NSTE-ACS when compared with clopidogrel, and this effect seems independent of performed revascularization. The results also indicate that biomarkers could be used to select patients who would benefit most from more intense platelet inhibition. Furthermore, early PCI in NSTEMI seems to be associated with improved outcome. Finally, the novel clinical prediction model based only on four variables showed good discriminatory ability, which makes it a potentially effective and simple tool for tailored treatment based on individual risk of recurrent events.
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| 8. |
- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 9. |
- Bergström, Göran, 1964, et al.
(författare)
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Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS.
- 2023
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 373, s. 46-54
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Tidskriftsartikel (refereegranskat)abstract
- Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change.We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomography angiography (CCTA) and expressed as segment involvement score (SIS).The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p<0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women.Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.
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| 10. |
- Bixby, H., et al.
(författare)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Tidskriftsartikel (refereegranskat)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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| 11. |
- Broadaway, K Alaine, et al.
(författare)
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Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
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Ingår i: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
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Tidskriftsartikel (refereegranskat)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
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| 12. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 13. |
- Gaziano, Liam, et al.
(författare)
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Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
- 2022
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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| 14. |
- Henriksson, Robin, 1986-
(författare)
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Secondary prevention after acute coronary syndrome : antiplatelet therapy and risk factor control
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: One of the leading causes of death and disability worldwide is cardiovascular disease (CVD), including acute myocardial infarction (AMI). Despite improvements in medical treatment, management, and care over the years and the halving of mortality in recent decades, there is considerable room for improvement. Following myocardial infarction (MI), a patient is at great risk for subsequent infarctions or other related complications. In addition, the risk of ischemic stroke is increased following MI. Secondary prevention after MI is paramount for reducing further complications and consists of lifestyle changes, optimised medical treatment, and risk factor control of blood pressure (BP) and blood lipid levels. Although secondary preventive measures are effective, the proportion of patients reaching set treatment target levels is disappointingly low.Most patients are prescribed dual antiplatelet therapy (DAPT) following MI as part of their secondary preventive treatment. Several articles have been published on treatment efficacy based on comparisons with different kinds of antiplatelet drugs and in different combinations. However, little data specifically address the incidence of ischemic stroke after MI in real-world populations. In addition to antiplatelet treatment, secondary prevention comprises risk factor control of hypertension and hyperlipidaemia. Given the low proportion of patients reaching set target levels for BP and blood lipids, new strategies are needed.Aims: The aim of this dissertation is partly to elucidate if the rapid change in preferred DAPT in Sweden, from clopidogrel to ticagrelor in addition to aspirin, affected the incidence of ischemic stroke in patients suffering AMI (paper I) and in patients suffering AMI who have a history of ischemic stroke (paper II).The second part of the dissertation aims to investigate the feasibility and implementation of a randomised controlled trial of a nurse-led telephone-based secondary preventive program, and to assess the proportion of patients who can be included in an unselected acute coronary syndrome (ACS) population (paper III). Furthermore, the aim of the trial was to assess the long term results regarding systolic BP (SBP), diastolic BP (DBP), and low-density lipoprotein cholesterol (LDL-C) after 36 months of intervention and follow-up compared to a control group receiving usual care (paper IV).Methods: Papers I and II examined the impact of a change in the antiplatelet regimen following MI in regard to ischemic stroke occurrence. Data were obtained from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (i.e., RIKS-HIA). The register was combined with the National Patient Register (NPR) and the Cause of Death Register (CDR) in order to obtain data on stroke occurrence. Patients with AMI and treated with either clopidogrel or ticagrelor were assigned to one of two cohorts, each covering a 2- year time period, with the initial prescription of ticagrelor (20 Dec 2011) used as a cutoff point. Patients in the early cohort (n=23,447) were treated exclusively with clopidogrel, whereas those in the later cohort (n=24,227) were treated with either clopidogrel (47.9%) or ticagrelor (52.1%). In paper II, the same methodology was used, but with a study sample restricted to AMI patients with a history of ischemic stroke. In paper II, there were 1633 patients in the early cohort and 1642 in the late cohort. In the late cohort, 66.3% patients were treated with clopidogrel and 33.7% with ticagrelor. Kaplan–Meier analysis was used to assess the risk of ischemic stroke over time, with multivariable Cox regression analysis used to identify predictors of ischemic stroke. Nurse-based Age independent Intervention to Limit Evolution of Disease (Papers III and IV were based on the NAILED)-ACS trial. The NAILED-ACS trial was an open randomised controlled trial of whether a nurse-led telephone-based follow-up and medical titration after MI or unstable angina achieved lower levels of BP and LDL-C than usual care. In paper III, patients admitted for ACS during January 2010 and December 2013 were evaluated for participation. Factors predicting participation and non- participation were assessed using logistic regression. Mortality rates after one year among included and excluded patients and patients declining participation were assessed using Kaplan–Meier analysis. For paper IV, all patients admitted with ACS at Östersund Hospital between January 2010 and December 2014 were screened for inclusion based on their ability to participate in a telephone- based follow-up. Participants were randomised into two parallel groups, an intervention group and a control group receiving usual care. BP and LDL-C were measured at 1, 12, 24, and 36 months. The baseline consisted of randomised patients who completed the one-month follow-up. The intervention group received counselling and medical titration to attain treatment targets (BP <140/<90 mmHg and LDL-C <2.5/<1.8 mmol/L). Adjusted means stratified by sex and type of ACS were calculated for SBP and DBP and LDL-C. The proportion of patients who achieved treatment target levels at the end of the study was also assessed.Results: Among the general AMI population treated with either clopidogrel or ticagrelor, the incidence of ischemic stroke after one year was 2.8% in the early cohort vs. 2.4% in the late cohort (p=0.001) (paper I). The study population in paper II, in which all patients had a history of previous ischemic stroke, was overall older and had a higher prevalence of comorbidities than the population in paper I. In paper II, incidence of ischemic stroke in the early cohort was 12.1% vs. 8.6% in the late cohort (p<0.01). Corresponding incidence of intracranial bleeding for the population in paper II was a non-significant 1.2% vs 1.5%.In the feasibility study of the NAILED-ACS trial (paper III), 907 patients were assessed for inclusion. Among these, 72.9% could be included (n=661), 146 patients (16.1%) were excluded, and 100 patients declined participation (11 %). Reasons for exclusion were mainly participation in another trial, dementia, inability to use a telephone, and advanced disease. Examples of predictors of both exclusion and declining participation were older age, lower functional status, and lower education. Non-participating patients had significantly higher mortality rates at one year compared to participating patients.Paper IV presents the final results of the NAILED-ACS risk factor trial in which a total of 962 patients were randomised and completed the one-month follow- up. Of this group, 797 were available for analysis after 36 months. Compared to the control group, in the intervention group, mean SBP was 4.1 mmHg lower, mean DBP was 2.9 mmHg lower, and mean LDL-C was 0.28 mmol/L lower (p<0.001 for all). The proportions of patients reaching treatment target goals for SBP, DBP, and LDL-C were significantly higher in the intervention group. In regard to SBP, 77.6% of intervention patients achieved treatment target levels, compared to 62.9% in the control group. Corresponding numbers for DBP were 90.9% vs. 80.8% and for LDL-C, they were 65.6% vs. 53.1%Conclusion: The incidence of ischemic stroke was significantly lower in a cohort of AMI patients following a change in preferred treatment from clopidogrel to ticagrelor (paper I). In AMI patients with a history of ischemic stroke (paper II), the incidence rate of ischemic stroke was significantly lower in the late cohort compared to the early cohort, and overall incidence rates were markedly higher than in paper I.The NAILED-ACS trial was shown to be both feasible (paper III) and successful, with a higher proportion of patients reaching treatment target levels in the intervention group, and significantly lower mean values for SBP, DBP, and LDL- C (paper IV).
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| 15. |
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| 16. |
- Nilsson, Konrad, 1992-
(författare)
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Clinical Outcomes of Transcatheter Aortic Valve Implantation (TAVI)
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aortic stenosis (AS) is the most common valvular heart disease and most prevalent in the elderly. In the latest decades, a new method for replacement of the aortic valve: transcatheter aortic valve implantation (TAVI) has been introduced. This has enabled treatment of patients who were earlier not candidates for surgery, and has also led to a shift towards TAVI from open surgery for many patients with symptomatic AS. The aims of this thesis were to examine clinical outcomes after TAVI since its implementation in Sweden.In Study I we analysed the burden of disease after TAVI with focus on causes of hospitalisation, hospitalisation patterns and predictors of repeated hospitalisation. We identified that hospitalisations are common and from various indications. Heart failure was the most prevalent diagnosis and efforts should be made to reduce the burden of heart failure hospitalisations.In Study II we performed an external validation of an existing prediction model of risk for short-term hospitalisations after TAVI. The model underperformed in a Swedish setting and it is therefore not recommended for clinical use in its current state. The findings highlight the challenges of developing reliable models that are valid after transportation into a new setting.In Study III we investigated regional differences in availability to TAVI in Sweden with focus on regional procedure rates, short-term mortality and waiting times. The findings indicated no major regional differences. Hence, despite that Sweden is a geographically large and sparsely populated country the current system with a few specialised TAVI centres seems sufficient for providing national coverage of TAVI procedures.In Study IV we examined the need for and indications for coronary interventions after TAVI. We concluded that most patients do not need interventions after TAVI and in case an intervention is needed, the outcome is in a majority of cases successful, even though the success rates are lower than in patients without prior aortic valve replacement. The most common indication for intervention was non-ST elevation acute myocardial infarction and only a minority of patients underwent angiography at the time of a myocardial infarction post TAVI.
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| 17. |
- Tödt, Tim, 1964-
(författare)
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Strategies to improve outcome in patients with ST elevation myocardial infarction treated with primary PCI
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: ST elevation myocardial infarction (STEMI) caused by a ruptured atherosclerotic plaque with overlying thrombosis leads to ischemia and progressively to the death of the myocardial cells supplied by the affected coronary artery. Rapid reperfusion with primary Percutaneous Coronary Intervention (PCI) in an experienced centre is the preferred therapy for these patients. The aim of the research program on which this thesis is based was to study the effect of antiplatelet therapy with abciximab on coronary patency when administered early to an unselected cohort of patients with STEMI intended for primary PCI, to study the impact of health care delay time on infarct size measured with contrast enhanced Magnetic Resonance Imaging (ceMRI), and to evaluate if time delays could be reduced through reorganisation of logistics and personal feedback to staff involved in the care of STEMI patients. Finally measures of wall motion on cine MRI were evaluated to elucidate if functional measurements of the left ventricular wall could detect scar tissue visualised on ceMRI in a post-acute phase of primary PCI.Material and results: In paper I we report on a study of all consecutive patients who sustained a STEMI in 2005 in the county of Östergötland and who were to be treated with primary PCI. Abciximab given as pretreatment before (n=133) or at the cath-lab after a diagnostic angiography (n=109) was associated with a patent Infarct Related Artery (IRA), i.e. Thrombolysis in Myocardial Infarction (TIMI) flow 2-3, in 45.9% of patients in the early group versus 20.2% in the cath-lab group, p=0.0001. There were no statistically significant differences in bleeding or mortality rate during the initial hospital stay, nor were there any significant differences between the groups during one-year follow up regarding a Major Adverse Cardiac Event (MACE).Paper II is based on an examination of 30 patients in a stable clinical condition with ceMRI 4-8 weeks after they had been treated with primary PCI because of STEMI. Patients were selected on the presence of extensive myocardial scar in the anteroseptal segments (n=17) or no scar visible at all in this area or in any other part of the myocardium (n=13). The purpose of the study was to evaluate the ability of a new feature tracking software to measure functional parameters of the heart. The left ventricular wall was divided into 18 segments and myocardial contraction was measured with velocity, displacement and strain in the longitudinal and radial direction. The software calculated a mean value for the 18 segments for each parameter. Receiver-operatorcharacteristics curves (ROC) were constructed. The best area-under-curve (AUC) was for radial strain where a cut-off value of 38.8% had 80% sensitivity and 86% specificity to detect segments with scar>50%.The impact of health care delay was examined in paper III based on a study in which 89 STEMI patients treated with primary PCI had their infarct size measured with ceMRI in the post-acute phase. Time from First Medical Contact (FMC) to a patent artery correlated weakly with infarct size, r=0.27, p=0.01. However, multivariable analysis showed the LAD as the Infarct Related Artery (IRA), active smoking and occlusion of the IRA at the time of the diagnostic angiogram were correlated with infarct size and that time from FMC to patent artery was not so correlated.Finally, in the study leading to paper IV, extensive measurements on time delays were performed on 67 consecutive patients with STEMI treated with primary PCI. Through collaboration with different stakeholders in the treatment of STEMI in the catchment area the following types of targeted refining of logistics were done; 1. Ambulance staff prioritise ECG recording, 2. Central evaluation of ECG in all patients with suspected STEMI, and 3. PCI team is ready to accept the patient when two out of three members are on site. Moreover, personal feedback on time delays for each STEMI patient was given to all staff involved in the treatment of the patient. Thereafter, all the time delays for a similar group of consecutive STEMI patients (n=89) were analysed and compared with the delays for the former group. Improvements seen in the post-intervention group were a reduction in time from ECG to cath-lab arrival by 11 minutes, p=0.02 and a non-significant decrease of FMC to a patent artery by six minutes. The main part of this improvement could probably be ascribed to the decision to see to it that an attending cardiologist was present 24/7 and to central evaluation of ECG.Conclusion: Abciximab given as pre-treatment to patients with STEMI intended for primary PCI was associated with a patent artery in 46% of patients. Moreover, we demonstrated a relationship between health care delay time and infarct size. This delay time could be reduced by a reorganisation of logistics and personal feedback on time delays. Finally, feature tracking analysis of cine MR images could detect segments with extensive myocardial scar in anterior infarction with 80% sensitivity and 86% specificity.
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| 18. |
- Williamson, Alice, et al.
(författare)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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| 19. |
- Åkerblom, Axel, 1977-
(författare)
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Biomarkers of Renal Function in Acute Coronary Syndromes
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis aimed to investigate cystatin C and creatinine-based estimates of glomerular filtration rate (eGFR), both at admission and during follow-up, on the combined endpoint of cardiovascular death and myocardial infarction in patients with acute coronary syndrome (ACS). We also evaluated two cystatin C assays and assessed genetic determinants of cystatin C concentrations.We used the PLATelet inhibition and Patient Outcomes study, where all types of ACS patients (n=18624) were randomized to ticagrelor or clopidogrel treatment. Multivariable Cox regression models, including clinical variables and biomarkers (troponin and NT-proBNP), and c-statistics were calculated.Cystatin C and the creatinine-based CKD-EPI equation exhibited similar significant prognostic impact on the combined endpoint, with Area Under Curves (AUC) 0.6923 and 0.6941, respectively. Follow-up samples of renal biomarkers did not improve risk prediction.Patients randomized to ticagrelor treatment were associated with a non-sustained larger increase in renal markers at discharge, but neither the change nor the difference between the randomized groups affected cardiovascular risk.Two different cystatin C assays exhibited good correlation 0.86 (95% confidence interval 0.85-0.86), however moderate level of agreement. Risk prediction with a combination of creatinine and cystatin C did not outperform the creatinine-based CKD-EPI equation, AUC: 0.6913 and 0.6924, respectively (n=13050).The genetic polymorphism rs6048952 independently affected the cystatin C concentration with mean levels of 0.85mg/L, 0.80mg/L and 0.73mg/L for the A/A, A/G, and G/G genotypes, respectively.The genetic polymorphism did not affect outcome overall, however in the non-ST-elevation ACS subgroup a signal that genetic polymorphism may be associated with cardiovascular death was observed (p=0.002).In conclusion: cystatin C or eGFR, irrespective of equation or assay, are important cardiovascular risk factors in ACS patients. Nonetheless, the incremental value of adding any renal variable, to a multivariable risk model, is small. Further research on the impact of cystatin C genetic polymorphism is warranted.
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| 20. |
- Östgren, Carl Johan, et al.
(författare)
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Prevalence of atherosclerosis in individuals with prediabetes and diabetes compared to normoglycaemic individuals-a Swedish population-based study.
- 2023
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Ingår i: Cardiovascular diabetology. - : BioMed Central (BMC). - 1475-2840. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased atherosclerotic burden in the coronary and carotid arteries. This study will estimate the cross-sectional prevalence of atherosclerosis in the coronary and carotid arteries in individuals with prediabetes and diabetes, compared with normoglycaemic individuals in a large population-based cohort.The 30,154 study participants, 50-64years, were categorized according to their fasting glycaemic status or self-reported data as normoglycaemic, prediabetes, and previously undetected or known diabetes. Prevalence of affected coronary artery segments, severity of stenosis and coronary artery calcium score (CACS) were determined by coronary computed tomography angiography. Total atherosclerotic burden was assessed in the 11 clinically most relevant segments using the Segment Involvement Score and as the presence of any coronary atherosclerosis. The presence of atherosclerotic plaque in the carotid arteries was determined by ultrasound examination.Study participants with prediabetes (n=4804, 16.0%) or diabetes (n=2282, 7.6%) had greater coronary artery plaque burden, more coronary stenosis and higher CACS than normoglycaemic participants (all, p<0.01). Among male participants with diabetes 35.3% had CACS≥100 compared to 16.1% among normoglycaemic participants. For women, the corresponding figures were 8.9% vs 6.1%. The prevalence of atherosclerosis in the coronary arteries was higher in participants with previously undetected diabetes than prediabetes, but lower than in patients with known diabetes. The prevalence of any plaque in the carotid arteries was higher in participants with prediabetes or diabetes than in normoglycaemic participants.In this large population-based cohort of currently asymptomatic people, the atherosclerotic burden in the coronary and carotid arteries increased with increasing degree of dysglycaemia. The finding that the atherosclerotic burden in the coronary arteries in the undetected diabetes category was midway between the prediabetes category and patients with known diabetes may have implications for screening strategies and tailored prevention interventions for people with dysglycaemia in the future.
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| 21. |
- Andersen, Kasper, 1974-, et al.
(författare)
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Long-Distance Skiing and Incidence of Hypertension : A Cohort Study of 206,889 Participants in a Long-Distance Cross-Country Skiing Event
- 2020
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Ingår i: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. ; 141:9, s. 743-750
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypertension is the leading risk factor for death worldwide and high levels of physical activity is associated with lower incidence of hypertension. The associations of excessive levels of exercise and incidence of hypertension is less known. We aim to compare the incidence of hypertension among 206,889 participants in a long-distance cross-country skiing event and 505,542 persons randomly sampled from the general population (matched to the skiers on age sex and place of residence). Methods: Skiers best performance (in per cent of winning time) and number of completed races during the study period were associated to incidence of hypertension after participation in Vasaloppet. Hypertension was defined as prescription of blood pressure-lowering drugs as obtained from the national drug registry. Models were adjusted for sex, age, education and income (total effect). Results: During a median time-of-risk of 8.3 years skiers had lower incidence of hypertension compared to non-skiers (HR 0.59; 95% confidence interval [CI] 0.58-0.60). Among the skiers, better performance (in % of winning time) in Vasaloppet was strongly associated with lower incidence of hypertension (Fastest fifth: HR 0.41; 95% CI 0.39-0.42. Slowest fifth: 0.78 CI 0.75-0.81). The association was near linear and did not differ between sexes. Among the skiers, a weaker association of number of completed races during the study period with incidence of hypertension (1 race: HR 0.63; 95% CI 0.62-0.65.>5 races: HR 0.51; 95% CI 0.50-0.53). A sub-analysis of 10,804 participants including adjustment for lifestyle factors showed similar results. Conclusions: Participation in a long-distance skiing event was associated with 41% lower incidence of hypertension over the next 8 years, compared to non-participation; and the better the performance, the lower the incidence of hypertension. This adds to the list of beneficial effects of intensive training, as hypertension is the leading risk factor of premature death globally.
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| 22. |
- Grimfjärd, Per, 1975-
(författare)
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Invasive treatment of coronary artery disease : Aspects on antithrombotic and percutaneous treatment options
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The outcome after percutaneous coronary intervention (PCI) has improved considerably thanks to more effective antithrombotic treatment strategies and improved coronary stents. Stent thrombosis (ST) is a rare complication to PCI associated with considerable mortality and morbidity.The general aim of this thesis was to add real-world evidence for antithrombotic and technical strategies in invasive treatment of coronary artery disease. Five observational studies were performed on a large, unselected, real-world population undergoing PCI. All studies were based on data from the national registry SWEDEHEART.In 31,258 patients undergoing PCI for ST-elevation myocardial infarction (STEMI), the rate of definite early ST was low (0.84%, n=265) but ST was associated with very high mortality (21%, n=51) at one year.Among 20,600 patients with STEMI, we compared the outcomes for those treated with heparin and those treated with bivalirudin during PCI. Rates of ST were low and similar with heparin and bivalirudin but all-cause mortality at 30 days and one year was significantly higher with heparin. We found no differences in rates of major bleeding, re-infarction and stroke.A novel bioresorbable scaffold (Absorb), used in patients undergoing PCI for all indications, was associated with a four- to eightfold higher adjusted rate of definite ST over two years, compared with conventional modern drug-eluting stents (DES). One in four ST events occurred later than one year after PCI. Rates of in-stent restenosis were comparable with Absorb and DES. Suboptimal implantation technique and non-adherence to antiplatelet therapy guidelines was common among patients with bioresorbable scaffold thrombosis.The novel parenteral and potent platelet inhibitor cangrelor was used nearly exclusively in STEMI (n=899), in early presenters with high-risk, often with cardiac arrest (18%) but was associated with low ST rates and no major bleeding events.In an unselected population of 65,000 patients undergoing PCI for all indications, the Xience permanent polymer everolimus eluting stent (n=36,600) appears to be safe and effective with low event rates of ST and in-stent restenosis. Compared with a control group of other modern DES (n=167,000) including a high proportion of thinner struts and absorbable polymers, Xience exhibits similar results in all important endpoints.All studies of this thesis provided important real-world evidence on antithrombotic and technical treatment strategies in invasive management of coronary artery disease.
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| 23. |
- James, Stefan
(författare)
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Coagulation, Inflammation and Myocardial Dysfunction in Unstable Coronary Artery Disease and the Influence of Glycoprotein IIb/IIIa Inhibition and Low Molecular Weight Heparin
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hjärt-kärl sjukdom är den vanligaste dödsorsaken i västvärlden. Samtidigt som antalet patienter med hjärtinfarkt har minskat, har antalet patienter med instabil kranskärlsjukdom d.v.s. svår kärlkramp ökat påtagligt. Diagnosen är nu den vanligaste orsaken till vård på hjärtinfarktavdelningar i Sverige. Modern behandling av instabil kranskärlssjukdom består av en kombination av läkemedel för att minska blodproppsbildning och avlasta hjärtarbetet samt, i de flesta fall, s.k. ballongvidning eller operation av hjärtats kranskärl. Trots stora behandlingsframsteg är risken för hjärtinfarkt och död hög, såväl på kort som lång sikt. Det finns därför ett stort behov av ytterligare förbättrad behandling utan att samtidigt erhålla oacceptabelt hög risk för allvarliga biverkningar. För att erbjuda en effektiv behandling till patienter med hög risk och samtidigt undvika dyr och potentiellt riskfylld behandling till patienter med låg risk behövs också bättre instrument för tidig riskbedömning. Syftet med avhandlingen var att undersöka en stor grupp patienter med instabil kranskärlssjukdom avseende säkerhet och effektivitet av en behandlingskombination av två moderna blodproppshämmande läkemedel, dalteparin och abciximab (ca 1000 patienter). Syftet var också att studera hur denna behandling påverkar system för inflammation och koagulation (ca 400 patienter). Dessutom ville vi värdera hur blodnivåer av markörer för inflammation, hjärtmuskelskada och nedsatt hjärtfunktion kan förutsäga risken för framtida komplikationer (ca 7000 patienter). Tillägg av abciximab till dalteparin minskade inte risken för dödsfall eller hjärtinfarkt inom trettio dagar. Däremot ökade antalet blödningskomplikationer. Totala antalet blödningar var emellertid relativt lågt och behandlingen syntes vara lika säker som kombinationen av abciximab och det internationellt mycket använda blodproppshämmande medlet heparin. Trots den kraftfulla behandlingskombinationen skedde en samtidig aktivering av system för såväl inflammation som koagulation. Detta kan vara en orsak till den observerade avsaknaden av behandlingseffekt av abciximab. Att hindra denna aktivering skulle samtidigt kunna innebära möjligheter för nya behandlingsstrategier. Förhöjda nivåer av markörer för hjärtmuskelskada (troponin T), inflammation (CRP), nedsatt hjärtfunktion (proBNP) eller nedsatt njurfunktion (kreatininclearance) ökade risken för dödlig utgång både på kort och lång sikt, oberoende av andra riskfaktorer. En kombination av två av dessa markörer gav den högsta risken för dödlig utgång. Således dog endast 0.3 % av patienter med låga nivåer av proBNP och normal njurfunktion inom ett år, jämfört med 25.7 % av patienter med höga nivåer av proBNP och nedsatt njurfunktion. Förhöjda nivåer av troponin T eller nedsatt kreatininclearance (men inte av CRP eller proBNP) ökade dessutom risken för hjärtinfarkt. Resultaten i avhandlingsarbetet har givit kliniskt tillämpbar kunskap om hur kärlkrampspatienter med hög respektive låg risk kan selekteras tidigt efter inkomst till sjukhus och ny kunskap om behandlingseffekt av abciximab och dalteparin. Resultaten har redovisats på internationella kongresser och i högt rankade medicinska tidskrifter och har citerats i europeiska och amerikanska ”guidelines” för behandling av instabil kranskärlssjukdom.
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| 24. |
- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 25. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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Adaptation of the Charlson Comorbidity Index for Register-Based Research in Sweden
- 2021
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Ingår i: Clinical Epidemiology. - : Dove Medical Press Ltd.. - 1179-1349. ; 13, s. 21-41
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Comorbidity indices are often used to measure comorbidities in register-based research. We aimed to adapt the Charlson comorbidity index (CCI) to a Swedish setting.Methods: Four versions of the CCI were compared and evaluated by disease-specific experts.Results: We created a cohesive coding system for CCI to 1) harmonize the content between different international classification of disease codes (ICD-7,8,9,10), 2) delete incorrect codes, 3) enhance the distinction between mild, moderate or severe disease (and between diabetes with and without end-organ damage), 4) minimize duplication of codes, and 5) briefly explain the meaning of individual codes in writing.Conclusion: This work may provide an integrated and efficient coding algorithm for CCI to be used in medical register-based research in Sweden.
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| 26. |
- Mostafavi, Seyed Samie, et al.
(författare)
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ExPECA : An Experimental Platform for Trustworthy Edge Computing Applications
- 2023
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Ingår i: 2023 IEEE/ACM SYMPOSIUM ON EDGE COMPUTING, SEC 2023. - : Association for Computing Machinery (ACM). ; , s. 294-299
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Konferensbidrag (refereegranskat)abstract
- This paper presents ExPECA, an edge computing and wireless communication research testbed designed to tackle two pressing challenges: comprehensive end-to-end experimentation and high levels of experimental reproducibility. Leveraging OpenStack-based Chameleon Infrastructure (CHI) framework for its proven flexibility and ease of operation, ExPECA is located in a unique, isolated underground facility, providing a highly controlled setting for wireless experiments. The testbed is engineered to facilitate integrated studies of both communication and computation, offering a diverse array of Software-Defined Radios (SDR) and Commercial Off-The-Shelf (COTS) wireless and wired links, as well as containerized computational environments. We exemplify the experimental possibilities of the testbed using OpenRTiST, a latency-sensitive, bandwidthintensive application, and analyze its performance. Lastly, we highlight an array of research domains and experimental setups that stand to gain from ExPECA's features, including closed-loop applications and time-sensitive networking.
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| 27. |
- Svedberg, Niclas, et al.
(författare)
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Long-Term Incidence of Atrial Fibrillation and Stroke Among Cross-Country Skiers Cohort Study of Endurance-Trained Male and Female Athletes
- 2019
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 140:11, s. 910-920
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies have revealed a higher incidence of atrial fibrillation among well-trained athletes. We aim to investigate associations of endurance training with incidence of atrial fibrillation and stroke and to establish potential sex differences of such associations in a cohort of endurance trained athletes. Methods: All Swedish skiers (208 654) completing 1 or more races in the 30 to 90 km cross-country skiing event Vasaloppet (1989-2011) and a matched sample (n=527 448) of nonskiers were followed until first event of atrial fibrillation or stroke. Cox regression was used to investigate associations of number of completed races and finishing time with incidence of atrial fibrillation and stroke. Results: Female skiers in Vasaloppet had a lower incidence of atrial fibrillation than did female nonskiers (hazard ratio [HR], 0.55; 95% CI, 0.48-0.64), independent of finishing time and number of races. Male skiers had a similar incidence to that of nonskiers (HR, 0.98; 95% CI, 0.93-1.03). Skiers with the highest number of races or fastest finishing times had the highest incidence. Skiers of either sex had a lower incidence of stroke than did nonskiers (HR, 0.64; 95% CI, 0.60-0.67), independent of the number of races and finishing time. Skiers with atrial fibrillation had higher incidence of stroke than did skiers and nonskiers without atrial fibrillation (men: HR, 2.28; 95% CI, 1.93-2.70; women: HR, 3.51; 95% CI, 2.17-5.68; skiers with atrial fibrillation vs. skiers without atrial fibrillation). After diagnosis of atrial fibrillation, skiers with atrial fibrillation had a lower incidence of stroke (HR, 0.73; 95% CI, 0.50-0.91) and lower mortality compared with nonskiers with atrial fibrillation (HR, 0.57; 95% CI, 0.49-0.65). Conclusions: Female skiers in Vasaloppet had lower incidence of atrial fibrillation and stroke. Male skiers had similar incidence of atrial fibrillation and lower risk of stroke. Men with higher number of races and faster finishing times had the highest incidence of atrial fibrillation. After diagnosis of atrial fibrillation, skiers had lower incidence of stroke and death than did nonskiers with atrial fibrillation. This indicates that although on an individual level atrial fibrillation in well-trained individuals is associated with higher incidence of stroke, on population level, risk of stroke is low and that exercise should not be avoided.
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| 28. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 29. |
- Varenhorst, Christoph, 1977-
(författare)
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Platelet Inhibition in Coronary Artery Disease – Mechanisms and Clinical Importance : Studies with Focus on P2Y12 Inhibition
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite the currently recommended dual antiplatelet treatment (DAT) with aspirin and P2Y12 inhibition in patients with coronary artery disease (CAD) there is a risk of adverse clinical outcome. Pharmacodynamic (PD) poor response to clopidogrel occurs in ~ 30% of clopidogrel-treated patients and is associated with an increased risk of recurrent thrombotic events. The aims of this thesis were to compare the PD and pharmacokinetic effects of clopidogrel 600 mg loading dose (LD)/ 75 mg standard maintenance dose (MD) with the novel P2Y12 inhibitor prasugrel 60 mg LD/10 mg MD, in 110 patients with CAD. The mechanisms behind clopidogrel poor response were investigated by assessing the pharmacodynamics after adding clopidogrel active metabolite (AM) and genotyping for variation in CYP-genes involved in thienopyridine metabolism. In another study, we compared the on-clopidogrel platelet reactivity of patients with stent thrombosis (ST) (n=48) or myocardial infarction (MI) (n=30) while on DAT and their matched controls (n=50 + 28). Prasugrel achieved a faster and greater P2Y12-mediated platelet inhibition than clopidogrel measured with light transmission aggregometry, VASP and VerifyNow® P2Y12. Prasugrel’s greater platelet inhibition was associated with higher exposure of AM. The addition of clopidogrel AM led to maximal platelet inhibition in all subjects, suggesting that prasugrel’s greater antiplatelet effect was related to more efficient AM generation compared to that of clopidogrel. Lower levels of AM as well as less platelet inhibition were seen in clopidogrel-treated patients with reduced-metabolizer genotype CYP2C19 compared to those with normal genotype. Patients with ST while on DAT showed higher on-clopidogrel platelet reactivity compared to matched stented controls. Patients with spontaneous MI after stenting did not. In conclusion, these results showed a high rate PD poor response to a high bolus dose of clopidogrel because of a partly genetically caused lower generation of AM which could be overcome by prasugrel treatment. In patients after coronary stenting, clopidogrel poor response was related to ST but not to spontaneous MI, illustrating difficulties in optimizing treatment with clopidogrel based on platelet function or genetic testing in individual patients.
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| 30. |
- Zhao, Tianyu, et al.
(författare)
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Impact of long-term exposure to ambient ozone on lung function over a course of 20 years (The ECRHS study) : a prospective cohort study in adults
- 2023
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 34
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: While the adverse effects of short-term ambient ozone exposure on lung function are well-documented, the impact of long-term exposure remains poorly understood, especially in adults.METHODS: We aimed to investigate the association between long-term ozone exposure and lung function decline. The 3014 participants were drawn from 17 centers across eight countries, all of which were from the European Community Respiratory Health Survey (ECRHS). Spirometry was conducted to measure pre-bronchodilation forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at approximately 35, 44, and 55 years of age. We assigned annual mean values of daily maximum running 8-h average ozone concentrations to individual residential addresses. Adjustments were made for PM2.5, NO2, and greenness. To capture the ozone-related change in spirometric parameters, our linear mixed effects regression models included an interaction term between long-term ozone exposure and age.FINDINGS: Mean ambient ozone concentrations were approximately 65 μg/m³. A one interquartile range increase of 7 μg/m³ in ozone was associated with a faster decline in FEV1 of -2.08 mL/year (95% confidence interval: -2.79, -1.36) and in FVC of -2.86 mL/year (-3.73, -1.99) mL/year over the study period. Associations were robust after adjusting for PM2.5, NO2, and greenness. The associations were more pronounced in residents of northern Europe and individuals who were older at baseline. No consistent associations were detected with the FEV1/FVC ratio.INTERPRETATION: Long-term exposure to elevated ambient ozone concentrations was associated with a faster decline of spirometric lung function among middle-aged European adults over a 20-year period.
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