| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 3. |
- 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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| 4. |
- Bergström, Göran, 1964, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 5. |
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| 6. |
- Lind, Lars, et al.
(författare)
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Obesity is associated with coronary artery stenosis independently of metabolic risk factors : the population-based SCAPIS study
- 2022
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 362, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Previous studies reported divergent results on whether metabolically healthy obesity is associated with increased coronary artery calcium and carotid plaques. We investigated this in a cross-sectional fashion in a large, well-defined, middle-aged population using coronary CT angiography (CCTA) and carotid ultrasound. Methods: In the SCAPIS study (50–65 years, 51% female), CCTA and carotid artery ultrasound were performed in 23,674 individuals without clinical atherosclerotic disease. These subjects were divided into six groups according to BMI (normal weight, overweight, obese) and the presence of metabolic syndrome (MetS) according to the NCEP consensus criteria. Results: The severity of coronary artery stenosis was increased in individuals with obesity without MetS compared to normal-weight individuals without MetS (OR 1.47, 95%CI 1.34–1.62; p < 0.0001), even after adjusting for non-HDL-cholesterol and several lifestyle factors. Such difference was not observed for the presence of carotid artery plaques (OR 0.94, 95%CI 0.87–1.02; p = 0.11). Obese or overweight individuals without any MetS criteria (except the waist criterion) showed significantly more pronounced stenosis in the coronary arteries as compared to the normal-weight individuals, while one criterion was needed to show increased plaque prevalence in the carotid arteries. High blood pressure was the most important single criterion for increased atherosclerosis in this respect. Conclusions: Individuals with obesity without MetS showed increased severity of coronary artery stenosis, but no increased occurrence of carotid artery plaques compared to normal-weight individuals without MetS, further emphasizing that obesity is not a benign condition even in the absence of MetS.
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| 7. |
- Malinovschi, Andrei, 1978-, et al.
(författare)
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Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry
- 2023
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 208:4, s. 461-471
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Post-bronchodilator (BD) spirometry is used for diagnosis of chronic obstructive pulmonary disease (COPD). However, pre-BD reference values are used for spirometry interpretation.OBJECTIVES: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or post-BD reference values generated within the Swedish CArdioPulmonary bioImage Study (SCAPIS) when interpreting post-BD spirometry in a general population.METHODS: SCAPIS reference values for post-BD and pre-BD spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or post-BD reference values, with respiratory burden in the SCAPIS general population (28,851 individuals).MEASUREMENTS AND MAIN RESULTS: Bronchodilation resulted in higher predicted median and lower limit of normal (LLN) for FEV1/FVC ratio. The prevalence of post-BD FEV1/FVC < pre-bronchodilator LLN was 4.8% and that of post-BD FEV1/FVC < post-bronchodilator LLN was 9.9% for the general population. An additional 5.1% was identified as having an abnormal post-BD FEV1/FVC ratio and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%, p<0.001) and self-reported physician-diagnosed COPD (2.8% vs. 0.5%, p<0.001) than subjects with post-BD FEV1/FVC ratio > LLN for both pre- and post-bronchodilation).CONCLUSIONS: Pre- and post-bronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of post-bronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using post-bronchodilator reference values when interpreting post-bronchodilator spirometry might enable identification of individuals with mild disease and be clinically relevant.
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| 8. |
- Persson, Frederik, et al.
(författare)
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Different patterns of second-line treatment in type 2 diabetes after metformin monotherapy in Denmark, Finland, Norway and Sweden (D360 Nordic) : A multinational observational study.
- 2018
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Ingår i: Endocrinology, diabetes & metabolism. - : Wiley. - 2398-9238. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The understanding of second-line use of glucose-lowering drugs (GLDs) in the general population with type 2 diabetes (T2D) treatment is important as recent results have shown cardiovascular benefits with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). Our aim was to describe second-line GLD treatment patterns in four Nordic countries.Methods: All T2D patients treated with GLD between 2006 and 2015 were identified in prescribed drug registries in Denmark, Finland, Norway and Sweden, and linked with National Patient and Cause of Death Registries. Second-line treatment was defined as a prescription of a second GLD class following ≥6 months of metformin monotherapy. Index was the date of first dispense of the second-line drug.Results: A rapid uptake of newer GLDs (GLP-1RA, DPP-4i and SGLT-2i) over the 10-year observation period was seen in Denmark, Finland and Norway, while slower in Sweden. In 2015, 33,880 (3.1%) of 1,078,692 T2D patients initiated second-line treatment, and newer GLDs were more commonly used in Finland (92%), Norway (71%) and Denmark (70%) vs Sweden (44%). In 2015, the use of older GLDs (insulin and sulphonylureas) was 7-fold greater in Sweden compared to Finland (49% vs 7%), and 1.6-fold greater compared with Denmark and Norway (49% vs 30% and 29%, respectively).Conclusions: Despite comparable demography and healthcare systems in four neighbouring countries, surprisingly large differences in second-line use of newer GLDs were found. With recent evidence of potential cardiovascular benefits with newer GLDs, such differences may have an important impact on cardiovascular outcomes.
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| 9. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Are there lost opportunities in chronic kidney disease? A region-wide cohort study
- 2024
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Identify the windows of opportunity for the diagnosis of chronic kidney disease (CKD) and the prevention of its adverse outcomes and quantify the potential population gains of such prevention.DESIGN AND SETTING: Observational, population-wide study of residents in the Stockholm and Skåne regions of Sweden between 1 January 2015 and 31 December 2020.PARTICIPANTS: All patients who did not yet have a diagnosis of CKD in healthcare but had CKD according to laboratory measurements of CKD biomarkers available in electronic health records.OUTCOME MEASURES: We assessed the proportions of the patient population that received a subsequent diagnosis of CKD in healthcare, that used guideline-directed pharmacological therapy (statins, renin-angiotensin aldosterone system inhibitors (RAASi) and/or sodium-glucose cotransporter-2 inhibitors (SGLT2i)) and that experienced adverse outcomes (all-cause mortality, cardiovascular mortality or major adverse cardiovascular events (MACE)). The potential to prevent adverse outcomes in CKD was assessed using simulations of guideline-directed pharmacological therapy in untreated subsets of the study population.RESULTS: We identified 99 382 patients with undiagnosed CKD during the study period. Only 33% of those received a subsequent diagnosis of CKD in healthcare after 5 years. The proportion that used statins or RAASi was of similar size to the proportion that didn't, regardless of how advanced their CKD was. The use of SGLT2i was negligible. In simulations of optimal treatment, 22% of the 21 870 deaths, 27% of the 14 310 cardiovascular deaths and 39% of the 22 224 MACE could have been avoided if every patient who did not use an indicated medication for their laboratory-confirmed CKD was treated with guideline-directed pharmacological therapy for CKD.CONCLUSIONS: While we noted underdiagnosis and undertreatment of CKD in this large contemporary population, we also identified a substantial realisable potential to improve CKD outcomes and reduce its burden by treating patients early with guideline-directed pharmacological therapy.
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| 10. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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