| 1. |
- 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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| 2. |
- 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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| 3. |
- Lind, Lars, et al.
(författare)
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Plasma Protein Profile of Carotid Artery Atherosclerosis and Atherosclerotic Outcomes : Meta-Analyses and Mendelian Randomization Analyses
- 2021
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1079-5642 .- 1524-4636. ; 41:5, s. 1777-1788
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To identify causal pathophysiological mechanisms for atherosclerosis and incident cardiovascular events using protein measurements.APPROACH AND RESULTS: Carotid artery atherosclerosis was assessed by ultrasound, and 86 cardiovascular-related proteins were measured using the Olink CVD-I panel in 7 Swedish prospective studies (11 754 individuals). The proteins were analyzed in relation to intima-media thickness in the common carotid artery (IMT-CCA), plaque occurrence, and incident cardiovascular events (composite end point of myocardial infarction or ischemic stroke) using a discovery/replication approach in different studies. After adjustments for traditional cardiovascular risk factors, 11 proteins remained significantly associated with IMT-CCA in the replication stage, whereas 9 proteins were replicated for plaque occurrence and 17 proteins for incident cardiovascular events. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and MMP (matrix metalloproteinase)-12 were associated with both IMT-CCA and incident events, but the overlap was considerably larger between plaque occurrence and incident events, including MMP-12, TIM-1 (T-cell immunoglobulin and mucin domain 1), GDF (growth/differentiation factor)-15, IL (interleukin)-6, U-PAR (urokinase plasminogen activator surface receptor), LOX-1 (lectin-like oxidized LDL [low-density lipoprotein] receptor 1), and TRAIL-R2 (TNF [tumor necrosis factor]-related apoptosis-inducing ligand receptor 2). Only MMP-12 was associated with IMT-CCA, plaque, and incident events with a positive and concordant direction of effect. However, a 2-sample Mendelian randomization analysis suggested that increased MMP-12 may be protective against ischemic stroke (P=5.5x10(-7)), which is in the opposite direction of the observational analyses.CONCLUSIONS: The present meta-analysis discovered several proteins related to carotid atherosclerosis that partly differed in their association with IMT-CCA, plaque, and incident atherosclerotic disease. Mendelian randomization analysis for the top finding, MMP-12, suggests that the increased levels of MMP-12 could be a consequence of atherosclerotic burden rather than the opposite chain of events.
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| 6. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Weight gain and blood pressure
- 2020
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 38:3, s. 387-394
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Although the causality of the obesity—hypertension association is established, the potential for prevention is not. We hypothesized that weight gain between early adulthood and mid-life is associated with higher mid-life blood pressure.METHODS: We investigated the hypothesis using a large contemporaneous population-based mid-life cohort of men and women aged 50-64 years. Recalled body weight at age 20 years was self-reported, and mid-life body weight and office blood pressures were measured in accordance with a detailed protocol.RESULTS: On average, men had gained 14.9 (95% CI 14.6-15.2) kg of weight, and women 14.6 (95% CI 14.4-14.9) kg, between age 20 years and the mid-life examination, corresponding to 0.40 (95% CI 0.39-0.41) kg/year for men and women. Both weight at age 20 years and weight at the mid-life examination were associated with mid-life blood pressures. On average, a 10 kg weight increase between age 20 years and mid-life was associated with 2.2 (95% CI 0.9-3.5) mmHg higher systolic and 1.7 (95% CI 0.9-2.5) mmHg higher diastolic mid-life blood pressure in men, and 3.2 (2.5-4.0) mmHg higher systolic and 2.4 (1.9-2.9) mmHg higher diastolic mid-life blood pressure in women. Mid-life weight was more closely associated than weight at age 20 years with mid-life blood pressure. For a given mid-life weight, blood pressure was higher in persons with higher weight gain from age 20 years.CONCLUSION: In sum, weight gain between early adulthood and mid-life was associated with higher mid-life blood pressure. The magnitude of the association indicates a potentially great public health impact of strategies to prevent weight gain throughout adulthood.
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| 7. |
- Vikström, Anna, et al.
(författare)
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Coding of procedures documented by general practitioners in Swedish primary care - an explorative study using two procedure coding systems.
- 2012
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Ingår i: BMC family practice. - : Springer Science and Business Media LLC. - 1471-2296. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Procedures documented by general practitioners in primary care have not been studied in relation to procedure coding systems. We aimed to describe procedures documented by Swedish general practitioners in electronic patient records and to compare them to the Swedish Classification of Health Interventions (KVA) and SNOMED CT. METHODS: Procedures in 200 record entries were identified, coded, assessed in relation to two procedure coding systems and analysed. RESULTS: 417 procedures found in the 200 electronic patient record entries were coded with 36 different Classification of Health Interventions categories and 148 different SNOMED CT concepts. 22.8% of the procedures could not be coded with any Classification of Health Interventions category and 4.3% could not be coded with any SNOMED CT concept. 206 procedure-concept/category pairs were assessed as a complete match in SNOMED CT compared to 10 in the Classification of Health Interventions. CONCLUSIONS: Procedures documented by general practitioners were present in nearly all electronic patient record entries. Almost all procedures could be coded using SNOMED-CT. Classification of Health Interventions covered the procedures to a lesser extent and with a much lower degree of concordance. SNOMED CT is a more flexible terminology system that can be used for different purposes for procedure coding in primary care.
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| 8. |
- Waldenström, Jesper, 1985, et al.
(författare)
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Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naive patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-alpha (pegIFN-alpha), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-alpha, or (iii) standard-of-care (SOC) ribavirin dosing concurrent with pegIFN-alpha. Four weeks of ribavirin mono-therapy resulted in a mean 0.46 log(10) IU/mL HCV RNA reduction differentially regulated across IL28B genotypes (0.89 vs. 0.21 log(10) IU/mL for CC and CT/TT respectively; P = 0.006), increased likelihood of undetectable HCV RNA week 4 after initiating pegIFN-alpha and thus shortened treatment duration (P < 0.05), and decreased median IP-10 concentration from 550 to 345 pg/mL (P < 0.001). Both experimental strategies impacted on ribavirin concentrations, and high levels were achieved after one week of double dosing. However, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an antiviral effect differently regulated across IL28B genotypes.
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| 9. |
- Wang, Chao, 1986-, et al.
(författare)
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S100A9-Driven Amyloid-Neuroinflammatory Cascade in Traumatic Brain Injury as a Precursor State for Alzheimer's Disease
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Pro-inflammatory and amyloidogenic S100A9 protein is an important contributor to Alzheimer's disease (AD) pathology. Traumatic brain injury (TBI) is viewed as a precursor state for AD. Here we have shown that S100A9-driven amyloid-neuroinflammatory cascade was initiated in TBI and may serve as a mechanistic link between TBI and AD. By analyzing the TBI and AD human brain tissues, we demonstrated that in post-TBI tissues S100A9, produced by neurons and microglia, becomes drastically abundant compared to A beta and contributes to both precursor-plaque formation and intracellular amyloid oligomerization. Conditions implicated in TBI, such as elevated S100A9 concentration, acidification and fever, provide strong positive feedback for S100A9 nucleation-dependent amyloid formation and delay in its proteinase clearance. Consequently, both intracellular and extracellular S100A9 oligomerization correlated with TBI secondary neuronal loss. Common morphology of TBI and AD plaques indicated their similar initiation around multiple aggregation centers. Importantly, in AD and TBI we found S100A9 plaques without A beta. S100A9 and A beta plaque pathology was significantly advanced in AD cases with TBI history at earlier age, signifying TBI as a risk factor. These new findings highlight the detrimental consequences of prolonged post-TBI neuroinflammation, which can sustain S100A9-driven amyloid-neurodegenerative cascade as a specific mechanism leading to AD development.
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