| 31. |
- Franklin, Stanley S., et al.
(author)
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The Cardiovascular Risk of White-Coat Hypertension
- 2016
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 68:19, s. 2033-2043
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Journal article (peer-reviewed)abstract
- BACKGROUND The role of white-coat hypertension (WCH) and the white-coat-effect (WCE) in development of cardiovascular disease (CVD) risk remains poorly understood. OBJECTIVES Using data from the population-based, 11-cohort IDACO (International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes), this study compared daytime ambulatory blood pressure monitoring with conventional blood pressure measurements in 653 untreated subjects with WCH and 653 normotensive control subjects. METHODS European Society Hypertension guidelines were used as a 5-stage risk score. Low risk was defined as 0 to 2 risk factors, and high risk was defined as >= 3 to 5 risk factors, diabetes, and/or history of prior CVD events. Age-and cohort-matching was done between 653 untreated subjects with WCH and 653 normotensive control subjects. RESULTS In a stepwise linear regression model, systolic WCE increased by 3.8 mm Hg (95% confidence interval [CI]: 3.1 to 4.6 mm Hg) per 10-year increase in age, and was similar in low-and high-risk subjects with or without prior CVD events. Over a median 10.6-year follow-up, incidence of new CVD events was higher in 159 high-risk subjects with WCH compared with 159 cohort-and age-matched high-risk normotensive subjects (adjusted hazard ratio [HR]: 2.06; 95% CI: 1.10 to 3.84; p = 0.023). The HR was not significant for 494 participants with low-risk WCH and age-matched low-risk normotensive subjects. Subgroup analysis by age showed that an association between WCH and incident CVD events is limited to older (age >= 60 years) high-risk WCH subjects; the adjusted HR was 2.19 (95% CI: 1.09 to 4.37; p = 0.027) in the older high-risk group and 0.88 (95% CI: 0.51 to 1.53; p = 0.66) in the older low-risk group (p for interaction = 0.044). CONCLUSIONS WCE size is related to aging, not to CVD risk. CVD risk in most persons with WCH is comparable to age-and risk-adjusted normotensive control subjects.
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| 32. |
- Frazier-Wood, Alexis C., et al.
(author)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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In: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Journal article (peer-reviewed)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 33. |
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| 34. |
- Ganna, Andrea, et al.
(author)
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Large-scale non-targeted metabolomic profiling in three human population-based studies
- 2016
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In: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 12
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Journal article (peer-reviewed)abstract
- Non-targeted metabolomic profiling is used to simultaneously assess a large part of the metabolome in a biological sample. Here, we describe both the analytical and computational methods used to analyze a large UPLC–Q-TOF MS-based metabolomic profiling effort using plasma and serum samples from participants in three Swedish population-based studies of middle-aged and older human subjects: TwinGene, ULSAM and PIVUS. At present, more than 200 metabolites have been manually annotated in more than 3600 participants using an in-house library of standards and publically available spectral databases. Data available at the metabolights repository include individual raw unprocessed data, processed data, basic demographic variables and spectra of annotated metabolites. Additional phenotypical and genetic data is available upon request to cohort steering committees. These studies represent a unique resource to explore and evaluate how metabolic variability across individuals affects human diseases.
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| 35. |
- Hedman, Åsa K., et al.
(author)
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DNA methylation patterns associated with oxidative stress in an ageing population
- 2016
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In: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 9
-
Journal article (peer-reviewed)abstract
- Background: Oxidative stress has been related to type 2 diabetes (T2D) and cardiovascular disease (CVD), the leading global cause of death. Contributions of environmental factors such as oxidative stress on complex traits and disease may be partly mediated through changes in epigenetic marks (e.g. DNA methylation). Studies relating differential methylation with intermediate phenotypes and disease endpoints may be useful in identifying additional candidate genes and mechanisms involved in disease. Methods: To investigate the role of epigenetic variation in oxidative stress marker levels and subsequent development of CVD and T2D, we performed analyses of genome-wide DNA methylation in blood, ten markers of oxidative stress (total glutathione [TGSH], reduced glutathione [GSH], oxidised glutathione [GSSG], GSSG to GSH ratio, homocysteine [HCY], oxidised low-density lipoprotein (oxLDL), antibodies against oxLDL [OLAB], conjugated dienes [CD], baseline conjugated dienes [BCD]-LDL and total antioxidant capacity [TAOC]) and incident disease in up to 966 age-matched individuals. Results: In total, we found 66 cytosine-guanine (CpG) sites associated with one or more oxidative stress markers (false discovery rate [FDR] <0.05). These sites were enriched in regulatory regions of the genome. Genes annotated to CpG sites showed enrichment in annotation clusters relating to phospho-metabolism and proteins with pleckstrin domains. We investigated the contribution of oxidative stress-associated CpGs to development of cardiometabolic disease. Methylation variation at CpGs in the 3'-UTR of HIST1H4D (cg08170869; histone cluster 1, H4d) and in the body of DVL1 (cg03465880; dishevelled-1) were associated with incident T2D events during 10 years of follow-up (all permutation p-values < 0.01), indicating a role of epigenetic regulation in oxidative stress processes leading to development or progression of diabetes. Methylation QTL (meQTL) analysis showed significant associations with genetic sequence variants in cis at 28 (42%) of oxidative stress phenotype-associated sites (FDR < 0.05). Integrating cis-meQTLs with genotype-phenotype associations indicated that genetic effects on oxidative stress phenotype at one locus (cg07547695; BCL2L11) may be mediated through DNA methylation. Conclusions: In conclusion, we report novel associations of DNA methylation with oxidative stress, some of which also show evidence of a relation with T2D incidence.
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| 36. |
- Helmersson, Johanna, et al.
(author)
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Reference values for 34 frequently used laboratory tests in 80-year-old men and women
- 2016
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In: Maturitas. - : Elsevier BV. - 0378-5122 .- 1873-4111. ; 92, s. 97-101
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Reference values are usually based on blood samples from healthy individuals in the age range 20-50 years. Most patients seeking health care are older than this reference population. Many reference intervals are age dependent and there is thus a need to have appropriate reference intervals also for elderly individuals.METHODS: We analyzed a group of frequently used laboratory tests in an 80-year-old population (n=531, 266 females and 265 males). The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines on the statistical treatment of reference values.RESULTS: Reference values are reported for serum alanine transaminase (ALT), albumin, alkaline phosphatase, pancreatic amylase, apolipoprotein A1, apolipoprotein B, apolipoprotein B/apolipoprotein A1 ratio, aspartate aminotransferase (AST), AST/ALT ratio, bilirubin, calcium, calprotectin, cholesterol, HDL-cholesterol, creatinine kinase (CK), creatinine, creatinine estimated GFR, C-reactive protein, cystatin C, cystatin C estimated GFR, gamma-glutamyltransferase (GGT), iron, iron saturation, lactate dehydrogenase (LDH), magnesium, phosphate, transferrin, triglycerides, urate, urea, zinc, hemoglobin, platelet count and white blood cell count. The upper reference limit for creatinine and urea was significantly increased while the lower limit for iron and albumin was decreased in this elderly population in comparison with the population in the Nordic Reference Interval Project (NORIP).CONCLUSIONS: Reference values calculated from the whole population and a subpopulation without cardiovascular disease showed strong concordance. Several of the reference interval limits were outside the 90% confidence interval of NORIP.
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| 37. |
- Helmersson-Karlqvist, Johanna, et al.
(author)
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Urinary KIM-1, but not urinary cystatin C, should be corrected for urinary creatinine
- 2016
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In: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 49:15, s. 1164-1166
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The interest for tubular damage markers such as urinary cystatin C (U-CystC) and kidney injury molecule-1 (U-KIM-1) grows, especially for the diagnosis of acute kidney injury. The trend to measure proteins in spot urine samples instead of 24-h urine collections calls for adjustment of urine dilution with urinary creatinine (UCr). However, it is not known whether UCr adjustment provides a more true value of basal U-CystC and U-KIM-1 levels than absolute values.DESIGN & METHODS: This study examines the rationale for UCr correction for U-CystC and U-KIM-1 by exploring the linear relations between U-CystC and U-KIM-1 and UCr, respectively, and the biological day to day variation of absolute concentrations and UCr adjusted values of the two biomarkers.RESULTS: Both U-CystC and U-KIM-1 concentrations correlated positively with UCr (R=0.37, P<0.001 and R=0.62, P<0.001, respectively) in 378 participants in a community cohort, which indicated a rationale for adjustment with UCr. However, U-CystC/Cr ratio associated negatively with UCr (R=- 0.31, P<0.001), which could indicate a certain amount of 'over-adjustment'. Morning urine collected for 10 consecutive days from 13 healthy volunteers showed a biological day to day variation of 82% for U-CystC, 75% for U-cystC/Cr ratio, 70% for U-KIM-1 and 46% for U-KIM-1/Cr ratio.CONCLUSIONS: This study supports the use of U-KIM-1/Cr ratio in clinical population studies. Data supporting the use of U-CysC/U-Cr ratio were less convincing and the possible confounding of UCr has to be acknowledged in clinical settings.
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| 38. |
- Huang, Biying, et al.
(author)
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Effects of cigarette smoking on cardiovascular-related protein profiles in two community-based cohort studies
- 2016
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In: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 254, s. 52-58
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Journal article (peer-reviewed)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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| 39. |
- Jansson, Kristofer, et al.
(author)
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Amplifier Design Using Vertical InAs Nanowire MOSFETs
- 2016
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In: IEEE Transactions on Electron Devices. - 0018-9383. ; 63:6, s. 2353-2359
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Journal article (peer-reviewed)abstract
- In this paper, an amplifier design using ballistic vertical InAs nanowire (NW) transistors is investigated, focusing on a basic common-source amplifier. The maximum power gain at 90 GHz is evaluated for different NW transistor architectures together with the power dissipation. The linearity of the amplifier is evaluated by estimating the IIP3 and 1-dB compression points. Furthermore, the impact of the parasitic capacitances and resistances is quantified and it is demonstrated that the gain may be increased by a cascode design. It is concluded that a power gain exceeding 20 dB at 90 GHz may be achieved by a common-source amplifier based on an InAs NW transistor architecture. A power consumption below 1 mW is possible, while still maintaining a high power gain. Furthermore, IIP3 exceeding 10 dBm is predicted. The combination of these qualities makes the NW transistor architecture an attractive prospect for low-power amplifiers at millimeter wave frequencies.
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| 40. |
- Jansson, Kristofer, et al.
(author)
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Ballistic modeling of InAs nanowire transistors
- 2016
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In: Solid-State Electronics. - : Elsevier BV. - 0038-1101. ; 115, s. 47-53
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Journal article (peer-reviewed)abstract
- In this work, the intrinsic performance of InAs nanowire transistors is evaluated in the ballistic limit. A self-consistent Schrodinger-Poisson solver is utilized in the cylindrical geometry, while accounting for conduction band non-parabolicity. The transistor characteristics are derived from simulations of ballistic transport within the nanowire. Using this approach, the performance is calculated for a continuous range of nanowire diameters and the transport properties are mapped. A transconductance exceeding 4 S/mm is predicted at a gate overdrive of 0.5 V and it is shown that the performance is improved with scaling. Furthermore, the influence from including self-consistency and non-parabolicity in the band structure simulations is quantified. It is demonstrated that the effective mass approximation underestimates the transistor performance due to the highly non-parabolic conduction band in InAs. Neglecting self-consistency severely overestimates the device performance, especially for thick nanowires. The error introduced by both of these approximations gets increasingly worse under high bias conditions. (C) 2015 Elsevier Ltd. All rights reserved.
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