| 1. |
- Hagstrom, Emil, et al.
(författare)
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IMPACT OF BODY WEIGHT AT AGE 20 AND WEIGHT GAIN DURING ADULTHOOD ON MIDLIFE CORONARY ARTERY CALCIUM IN 15,000 MEN AND WOMEN : AN INTERIM ANALYSIS OF THE SWEDISH CARDIOPULMONARY BIOIMAGE STUDY
- 2019
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 73:9, s. 1692-1692
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundElevated body weight in adolescence is strongly associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, or to weight gain with subsequent high adult weight is not known. Using data from the Swedish CArdioPulmonary bioImage Study (SCAPIS), we investigated the association between weight at age 20, weight gain to midlife and coronary artery calcium score (CACS) at midlife.MethodsIn the first 15,810 participants in SCAPIS (mean age 58 years, 52% women), data on CACS at midlife, self-reported body weight at age 20 and weight at examination in SCAPIS were recorded.ResultsCACS in midlife was significantly higher with increasing weight at age 20 (p<0.001 for both sexes), and then increased with weight gain until midlife at all levels of body weight at age 20 after adjusting for age, height, smoking, alcohol intake, education level, exercise levels and LDL cholesterol. However, the association with weight gain was only significant in men (p = 0.047), not in women (p=0.474). No significant interaction was seen between weight at age 20 and midlife weight with CACS. The effect of weight at age 20 on CACS was significantly more marked in men than in women, as was the effect of weight gain (p<0.001 for both interactions).ConclusionWeight at age 20 and weight gain to midlife were both related to CACS, but much more markedly so in men than in women, indicating a generally larger effect of both early adult weight and further weight gain until midlife on CACS in men, compared to women.
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| 2. |
- Hasvold, Pal, et al.
(författare)
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Association Between Paradoxical HDL Cholesterol Decrease and Risk of Major Adverse Cardiovascular Events in Patients Initiated on Statin Treatment in a Primary Care Setting
- 2016
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Ingår i: Clinical drug investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 36:3, s. 225-233
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Statin-induced changes in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are unrelated. Many patients initiated on statins experience a paradoxical decrease in HDL-C. The aim of this study was to evaluate the association between a decrease in HDL-C and risk of major adverse cardiovascular events (MACE). Methods Data from 15,357 primary care patients initiated on statins during 2004-2009 were linked with data from mandatory national hospital, drug-dispensing, and cause-of-death registers, and were grouped according to HDL-C change: decreased >= 0.1 mmol/L, unchanged +/- 0.1 or >= 0.1 mmol/L increased. To evaluate the association between decrease in HDL-C and risk of MACE, a sample of propensity score-matched patients from the decreased and unchanged groups was created, using the latter group as reference. MACE was defined as myocardial infarction, unstable angina pectoris, ischaemic stroke, or cardiovascular mortality. Cox proportional hazards models were used to estimate relative risks. Results HDL-C decreased in 20 %, was unchanged in 58%, and increased in 22 % of patients initiated on statin treatment (96 % treated with simvastatin). The propensity score-matched sample comprised 5950 patients with mean baseline HDL-C and LDL-C of 1.69 and 4.53 mmol/L, respectively. HDL-C decrease was associated with 56 % higher MACE risk (hazard ratio 1.56; 95 % confidence interval 1.12-2.16; p < 0.01) compared with the unchanged HDL-C group. Conclusions Paradoxical statin-induced reduction in HDL-C was relatively common and was associated with increased risk of MACE.
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| 3. |
- Huang, Biying, et al.
(författare)
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Effects of cigarette smoking on cardiovascular-related protein profiles in two community-based cohort studies
- 2016
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 254, s. 52-58
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Cardiovascular diseases account for the largest fraction of smoking-induced deaths. Studies of smoking in relation to cardiovascular-related protein markers can provide novel insights into the biological effects of smoking. We investigated the associations between cigarette smoking and 80 protein markers known to be related to cardiovascular diseases in two community-based cohorts, the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 969, 50% women, all aged 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 717, all men aged 77 years). Methods: Smoking status was self-reported and defined as current smoker, former smoker or never-smoker. Levels of the 80 proteins were measured using the proximity extension assay, a novel PCR-based proteomics technique. Results: We found 30 proteins to be significantly associated with current cigarette smoking in PIVUS (FDR<5%); and ten were replicated in ULSAM (p<0.05). Matrix metalloproteinase-12 (MMP-12), growth/differentiation factor 15 (GDF-15), urokinase plasminogen activator surface receptor (uPAR), TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), lectin-like oxidized LDL receptor 1 (LOX-1), hepatocyte growth factor (HGF), matrix metalloproteinase-10 (MMP-10) and matrix metalloproteinase-1 (MMP-1) were positively associated, while endothelial cell-specific molecule 1 (ESM-1) and interleukin-27 subunit alpha (IL27-A) showed inverse associations. All of them remained significant in a subset of individuals without manifest cardiovascular disease. Conclusions: The findings of the present study suggest that cigarette smoking may interfere with several essential parts of the atherosclerosis process, as evidenced by associations with protein markers representing endothelial dysfunction, inflammation, neointimal formation, foam cell formation and plaque instability. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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| 4. |
- Larsson, David, 1986, et al.
(författare)
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Cardiovascular risk factor assessment in late-onset seizures: A study protocol to assess the value of structured intervention
- 2024
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Ingår i: EPILEPSIA OPEN. - 2470-9239. ; 9:4, s. 1611-1617
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveA growing body of evidence suggests patients with late-onset seizures are at an increased risk of stroke, but the potential for reducing cardiovascular morbidity through risk factor screening and management is unknown. We aim to determine whether individuals with new-onset unprovoked seizures after middle age should undergo vascular risk assessment. The long follow-up needed to assess stroke risk and the known benefit of vascular risk factor modification make a standard RCT logistically and ethically challenging. Instead, we propose and have developed a protocol for a cluster project assessing the effect of vascular risk factor screening in an intervention trial as well as a cohort study.MethodsParticipating neurology clinics will implement standard cardiovascular risk factor assessment into the routine evaluation for individuals aged >= 50 years attending their first specialized consultation after an unprovoked seizure, excluding those with progressive brain disease. The project has two interlinked components: a prospective single group trial, in which risk factor assessment is performed and subsequent management is followed for one year; and a register-based cohort study examining the long-term effects of the intervention on a system level by comparing patients attending initial consultations in the 2 years after start of the study, with patients seen in the four preceding years at the same clinics.AnalysisThe primary outcome of the intervention trial is the proportion of patients receiving subsequent pharmacological treatment. The primary outcome of the cohort study is the incidence of acute stroke in the Swedish Stroke Register.Ethics and DisseminationSwedish Ethical Review Authority approval (which is valid for 2 years only) will be sought when funding is obtained. The results will be disseminated through peer-reviewed scientific publications.Registration DetailsThe study will be registered at .Plain Language SummaryA first seizure in a middle-aged or older person indicates a higher risk of stroke. It is not known whether investigating and treating blood pressure, blood cholesterol, or similar risk factors after a first seizure is an effective way to prevent stroke. A traditional clinical study would need too many patients and it would be unethical not to treat the control group. We have designed a study in which participating neurology departments change their practice to test and treat vascular risk factors. Patients are then compared to historic controls using registered data.
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| 5. |
- Nowak, Christoph, et al.
(författare)
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Metabolite profiles during an oral glucose tolerance test reveal new associations with clamp-measured insulin sensitivity
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Impaired insulin sensitivity (IS) is a major risk factor for cardiovascular disease and type 2 diabetes. Metabolomic profiling during an oral glucose tolerance test (OGTT) can reveal early pathogenic alterations in healthy individuals. Our aim was to identify IS biomarkers and gain new pathophysiologic insights by applying untargeted metabolomics to repeated OGTT plasma samples in association with a hyperinsulinemic-euglycemic clamp assessment. We studied 192 metabolites identified by non-targeted liquid chromatography/mass spectrometry in plasma samples taken at 0, 30, and 120 min during an OGTT in 470 non-diabetic 71-yr-old men. Insulin sensitivity was associated with 35 metabolites at one or more time points in multivariable-adjusted linear regression. The trajectories of nine metabolites during the OGTT were related to IS, six of which (oleic and palmitoleic acid, decanoyl- and dodecanoylcarnitine, deoxycholate-glycine and hexose) showed no associations with IS in the baseline fasting state. The strongest effects were detected for medium-chain acylcarnitines, which increased between 30-120 min in insulin-resistant individuals compared to those with normal IS. In this large community sample, we identified novel associations between clamp-measured IS and metabolite profiles that became apparent only after an oral glucose challenge. Associations of differential medium-chain acylcarnitine and monounsaturated fatty acid trajectories with IS provide new insights into the pathogenesis of insulin resistance.
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| 6. |
- Schlosser, P, et al.
(författare)
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Meta-analyses identify DNA methylation associated with kidney function and damage
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7174-
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.
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| 7. |
- Sundelöf, Johan, 1974-
(författare)
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Amyloid β-protein, Cystatin C and Cathepsin B as Biomarkers of Alzheimer's Disease
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is suggested that Alzheimer’s disease (AD) is caused by an imbalance between production, degradation and clearance of the amyloid-β (Aβ) protein. This imbalance leads to aggregation of Aβ and tau proteins and neurodegeneration in the brain. Today there is increasing evidence that the balance between the protease cathepsin B and the protease inhibitor cystatin C affects the tendency for Aβ to aggregate. The primary aim of this thesis was to investigate Aβ, cystatin C and cathepsin B levels in blood and cerebro-spinal fluid (CSF) in relation to the risk of AD.Studies I & II were based on the re-examinations of participants, at ages 70 and 77, in the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based prospective study initiated in 1970 (participants then being 50 years of age). In ULSAM, low plasma Aβ1-40 (Study I) and low serum cystatin C levels (Study II) were associated with a higher risk of AD. Studies III & IV were based on a cross-sectional sample of people with AD, mild cognitive impairment and healthy controls, recruited at three Swedish Memory Disorder units: Uppsala University Hospital, Uppsala, Skåne University Hospital, Malmö, and Karolinska University Hospital, Huddinge, Stockholm. In Study III, CSF cystatin C levels were positively correlated with both Aβ1-42 and tau levels. In Study IV, individuals with AD had higher mean plasma cathepsin B levels than healthy controls.In conclusion, low plasma Aβ1-40 and low serum cystatin C levels may precede clinically manifest AD in elderly men, cystatin C levels are positively correlated with Aβ1-42 and tau levels in CSF, and mean plasma cathepsin B levels are higher in people with AD compared to healthy controls. In addition to Aβ1-42 and tau levels in CSF, Aβ1-40, cystatin C and cathepsin B levels in blood may reflect the risk of AD.
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| 8. |
- Sundelöf, Johan, et al.
(författare)
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Cystatin C Levels are Positively Correlated with both Aβ42 and Tau Levels in Cerebrospinal Fluid in Persons with Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls
- 2010
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 21:2, s. 471-478
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Tidskriftsartikel (refereegranskat)abstract
- Cystatin C is suggested to be involved in neurodegeneration and the development of Alzheimer's disease (AD) by binding to soluble amyloid-beta (Abeta) peptides. Studies of cystatin C levels in cerebrospinal fluid (CSF) in relation to risk of AD are conflicting and relations between cystatin C, Abeta42, and tau levels in CSF in AD, mild cognitive impairment (MCI), and healthy controls are unknown. The objective of this study was to investigate cystatin C, Abeta42, and tau levels in CSF in AD, MCI, and controls. As a secondary aim, the relationships between cystatin C, Abeta42, and tau levels across disease groups were investigated. Cystatin C, Abeta42, total tau, and phosphorylated tau levels in CSF were analyzed by turbidimetry (cystatin C) and xMAP Luminex technology (Abeta and tau) in persons with AD (n=101), MCI (n=84), and healthy control subjects (n=28). Mean cystatin C levels were similar in cases of AD (5.6 mumol/L +/- 1.7), MCI (5.4 mumol/L +/- 1.48), and controls (5.6 mumol/L +/- 1.6). However, CSF cystatin C levels were strongly and positively correlated with total tau and phosphorylated tau levels (r=0.61-0.81, p< 0.0001) and Abeta42 (r=0.35-0.65, p< 0.001) independent of age, gender, and APOE genotype. Mean CSF cystatin C levels did not differ between patients with AD and MCI and healthy controls. Interestingly, cystatin C levels were positively correlated with both tau and Abeta42 levels in CSF independent of age, gender, and APOE genotype.
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| 9. |
- Söderberg, Stefan, et al.
(författare)
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MEASURES OF WAIST AND HIP MODIFY SEX-SPECIFIC ASSOCIATIONS BETWEEN BODY MASS INDEX AND PREVALENCE OF CORONARY ARTERY CALCIFICATION IN OPPOSITE DIRECTIONS
- 2019
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 73:9, s. 13-13
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Obesity is associated with increased risk of cardiovascular disease. However, there is still a debate whether accumulation of fat in certain depots modifies this risk. Using data from the CArdioPulmonary bioImage Study (SCAPIS), we investigated if anthropometric measurements of obesity (waist and hip) modifies the risk of coronary artery calcification. Methods: In the first 15,810 participants in SCAPIS (mean age 58 years, 52% women), data on coronary artery calcification score (CACS) and anthropometry were recorded and traditional cardiovascular risk factors were measured. Body mass index (BMI) was categorized as; <25, 25-30, 30-35 and >35 kg/m2 , quartiles of waist and hip circumferences were constructed within each BMI category and compared using the lowest quartile as reference. Results were adjusted for site, age, smoking and diabetes status. Results: Obesity (BMI >30 kg/m2 ) was found in 21.9% of men and in 20.5% of women. In both sexes the odds ratio (OR) for CACS >0 increased with increasing BMI categories: comparing <25 and >35 kg/m2 , OR = 2.1 (95% CI: 1.6-2.7) for men and OR = 1.4 (1.2-1.8) for women. In addition, increasing quartiles of waist significantly increased the prevalence of CACS >0 for men [p = 0.05; OR = 1.2 (1.0-1.4) for highest quartile] and women [p = 0.005; OR = 1.3 (1.1-1.5)] while increasing quartiles of hip significantly decreased the prevalence for men [p = 0.005; OR = 0.8 (0.6-0.9)] and women [p = 0.04; OR = 0.8 (0.7-0.9)]. Data on education level and physical activity did not affect the model. Conclusion: Increased BMI is associated with increased prevalence of coronary artery calcification and the distribution of fat modifies this risk. Our results suggest that gluteofemoral adipose tissue (hip) counteracts the negative effects associated with BMI and abdominal adipose tissue (waist).
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| 10. |
- Tin, A, et al.
(författare)
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Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7173-
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E–7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.
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