| 1. |
- Arefalk, Gabriel, et al.
(author)
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Smokeless tobacco (snus) and risk of heart failure : results from two Swedish cohorts
- 2012
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In: European Journal of Cardiovascular Prevention & Rehabilitation. - : Sage Publications. - 1741-8267 .- 1741-8275 .- 2047-4873 .- 2047-4881. ; 19:5, s. 1120-1127
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Journal article (peer-reviewed)abstract
- Background: Oral moist snuff (snus) is discussed as a safer alternative to smoking, and its use is increasing. Based on its documented effect on blood pressure, we hypothesized that use of snus increases the risk of heart failure.Design: Two independent Swedish prospective cohorts; the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based sample of 1076 elderly men, and the Construction Workers Cohort (CWC), a sample of 118,425 never-smoking male construction workers. Methods: Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure.Results: In ULSAM, 95 men were hospitalized for heart failure, during a median follow up of 8.9 years. In a model adjusted for established risk factors including past and present smoking exposure, current snus use was associated with a higher risk of heart failure [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.22] relative to non-use. Snus use was particularly associated with risk of non-ischaemic heart failure (HR 2.55, 95% CI 1.12-5.82). In CWC, 545 men were hospitalized for heart failure, during a median follow up of 18 years. In multivariable-adjusted models, current snus use was moderately associated with a higher risk of heart failure (HR 1.28, 95% CI 1.00-1.64) and non-ischaemic heart failure (HR 1.28, 95% CI 0.97-1.68) relative to never tobacco use.Conclusion: Data from two independent cohorts suggest that use of snus may be associated with a higher risk of heart failure.
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| 2. |
- Fall, Tove, 1979-, et al.
(author)
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Relations of circulating vitamin D concentrations with left ventricular geometry and function
- 2012
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 14:9, s. 985-991
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Journal article (peer-reviewed)abstract
- Vitamin D deficiency has been associated with risk of overt cardiovascular disease (CVD), but associations with subclinical disease are not well characterized. Hence, we examined associations of circulating vitamin D concentrations and left ventricular (LV) geometry and function by echocardiography at baseline and after 5 years in a community-based study. In the PIVUS study, we measured serum 25-dihydroxyvitamin-D (25-OH D) at age 70 and performed echocardiography including LV mass, wall thickness, end-diastolic diameter, end-systolic diameter (LVESD), left atrial diameter, fractional shortening, ejection fraction, isovolumic relaxation time, and E/A ratio at both age 70 and 75. We included 870 participants (52 women) without prior myocardial infarctions, heart failure, or prevalent valvular disease. After adjusting for potential confounders, 25-OH D at baseline was found to be significantly associated with LVESD, fractional shortening, and ejection fraction (, 0.42 mm, P 0.03; , 0.70, P 0.03; and , 0.91 P 0.01, respectively), per 1 SD increase in 25-OH D (SD 20 nmol/L) at baseline. In longitudinal analyses, vitamin D levels at baseline were not significantly associated with change in LV geometry and function after 5 years. In our community-based study among the elderly, we found higher circulating vitamin D concentrations to be associated cross-sectionally with better LV systolic function and smaller LVESD at baseline. The association persisted after adjusting for several potential confounders, including cardiovascular risk factors and calcium, phosphate, and parathyroid hormone levels. Randomized clinical trials are needed to establish firmly or refute a causal relationship between vitamin D levels and changes in LV geometry and function.
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| 3. |
- Fall, Tove, 1979-, et al.
(author)
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The role of obesity-related genetic loci in insulin sensitivity
- 2012
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In: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 29:7, s. E62-E66
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Journal article (peer-reviewed)abstract
- Aims Despite rapid advancements and many new diabetes susceptibility loci found in the past few years, few genetic variants associated with insulin sensitivity have been described, potentially attributable to the lack of larger cohorts examined with gold standard methods for insulin sensitivity assessment. There is a strong link between obesity and insulin sensitivity, and we hypothesized that known obesity susceptibility loci may act via effects on insulin sensitivity. Methods A cohort of 71-year-old men without diabetes (Uppsala Longitudinal Study of Adult Men) underwent a euglycaemichyperinsulinaemic clamp and genotyping for genetic variants representing 32 loci recently reported to be associated with BMI (n = 926). The effect of these loci on the insulin sensitivity index (M/I ratio) was examined using linear regression. An in silico replication was performed in publically available data for the three top single-nucleotide polymorphisms from the Meta-Analyses of Glucose and Insulin-related traits Consortium analyses of homeostasis model assessment of insulin resistance (n = 37 037). Results Three loci (SH2B1, MTCH2 and NEGR1) were associated with decreased insulin sensitivity at a nominal significance (P = 0.05) after adjustment for BMI, but did not hold for multiple comparison correction. SH2B1 rs7359397 was also associated with homeostasis model assessment of insulin resistance in the Meta-Analyses of Glucose and Insulin-related traits Consortium data set (P = 3.9 x 10(3)). Conclusions Our study supports earlier reports of SH2B1 to be of importance in insulin sensitivity and, in addition, suggests potential roles of NEGR1 and MTCH2.
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| 4. |
- Ganna, Andrea, 1985-, et al.
(author)
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Risk prediction measures for case-cohort and nested case-control designs : an application to cardiovascular disease.
- 2012
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 175:7, s. 715-724
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Journal article (peer-reviewed)abstract
- Case-cohort and nested case-control designs are often used to select an appropriate subsample of individuals from prospective cohort studies. Despite the great attention that has been given to the calculation of association estimators, no formal methods have been described for estimating risk prediction measures from these 2 sampling designs. Using real data from the Swedish Twin Registry (2004-2009), the authors sampled unstratified and stratified (matched) case-cohort and nested case-control subsamples and compared them with the full cohort (as "gold standard"). The real biomarker (high density lipoprotein cholesterol) and simulated biomarkers (BIO1 and BIO2) were studied in terms of association with cardiovascular disease, individual risk of cardiovascular disease at 3 years, and main prediction metrics. Overall, stratification improved efficiency, with stratified case-cohort designs being comparable to matched nested case-control designs. Individual risks and prediction measures calculated by using case-cohort and nested case-control designs after appropriate reweighting could be assessed with good efficiency, except for the finely matched nested case-control design, where matching variables could not be included in the individual risk estimation. In conclusion, the authors have shown that case-cohort and nested case-control designs can be used in settings where the research aim is to evaluate the prediction ability of new markers and that matching strategies for nested case-control designs may lead to biased prediction measures.
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| 5. |
- Ghani Zadegan, Farrokh, et al.
(author)
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Access Time Analysis for IEEE P1687
- 2012
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In: IEEE Transactions on Computers. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9340 .- 1557-9956. ; 61:10, s. 1459-1472
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Journal article (peer-reviewed)abstract
- The IEEE P1687 (IJTAG) standard proposal aims at providing a standardized interface between the IEEE Standard 1149.1 test access port (TAP) and on-chip embedded test, debug and monitoring logic (instruments), such as scan chains and temperature sensors. A key feature in P1687 is to include Segment Insertion Bits (SIBs) in the scan path to allow flexibility both in designing the instrument access network and in scheduling the access to instruments. This paper presents algorithms to compute the overall access time (OAT) for a given P1687 network. The algorithms are based on analysis for flat and hierarchical network architectures, considering two access schedules, i.e., concurrent schedule and sequential schedule. In the analysis, two types of overhead are identified, i.e., network configuration data overhead and JTAG protocol overhead. The algorithms are implemented and employed in a parametric analysis and in experiments on realistic industrial designs.
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| 6. |
- Ghani Zadegan, Farrokh, et al.
(author)
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Reusing and Retargeting On-Chip Instrument Access Procedures in IEEE P1687
- 2012
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In: IEEE Design & Test of Computers. - : IEEE. - 0740-7475 .- 1558-1918. ; 29:2, s. 79-88
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Journal article (peer-reviewed)abstract
- Modern chips may contain a large number of embedded test, debugging, configuration, and monitoring features, called instruments. An instrument and its instrument access procedures may be pre-developed and reused, and each instrument—in different chips and through the life-time of a chip—may be accessed in different ways, which requires retargeting. To address reuse and retargeting of instrument access procedures, IEEE P1678 specifies a hardware architecture, a hardware description language, and an access procedure description language. In this paper, we investigate how P1687 facilitates instrument access procedure reuse and retargeting.
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| 7. |
- Hong, Mun-Gwan, et al.
(author)
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Genome-wide and gene-based association implicates FRMD6 in Alzheimer disease
- 2012
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In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 33:3, s. 521-529
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) that allow for allelic heterogeneity may facilitate the discovery of novel genes not detectable by models that require replication of a single variant site. One strategy to accomplish this is to focus on genes rather than markers as units of association, and so potentially capture a spectrum of causal alleles that differ across populations. Here, we conducted a GWAS of Alzheimer disease (AD) in 2,586 Swedes and performed gene-based meta-analysis with three additional studies from France, Canada, and the United States, in total encompassing 4,259 cases and 8,284 controls. Implementing a newly designed gene-based algorithm, we identified two loci apart from the region around APOE that achieved study-wide significance in combined samples, the strongest finding being for FRMD6 on chromosome 14q (P = 2.6 × 10(-14)) and a weaker signal for NARS2 that is immediately adjacent to GAB2 on chromosome 11q (P = 7.8 × 10(-9)). Ontology-based pathway analyses revealed significant enrichment of genes involved in glycosylation. Results suggest that gene-based approaches that accommodate allelic heterogeneity in GWAS can provide a complementary avenue for gene discovery and may help to explain a portion of the missing heritability not detectable with single nucleotide polymorphisms (SNPs) derived from marker-specific meta-analysis.
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| 8. |
- Ingelsson, Erik, 1975-, et al.
(author)
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Nationwide cohort study of the leukotriene receptor antagonist montelukast and incident or recurrent cardiovascular disease
- 2012
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 129:3, s. 702-707.e2
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Journal article (peer-reviewed)abstract
- BACKGROUND: The leukotriene pathway has been associated with an increased cardiovascular risk. However, the effects of the antileukotriene treatment used in asthmatic patients on cardiovascular outcomes have remained largely unexplored.OBJECTIVE: We sought to examine a potential protective role of the leukotriene receptor antagonist montelukast on future risk of incident and recurrent myocardial infarction and ischemic stroke.METHODS: A nationwide population-based cohort of approximately 7 million persons integrating data from the Prescribed Drug, Patient, Cause of Death, Income, Educational, and Emigration Registers was followed from July 1, 2005, to December 31, 2008. Analyses were performed in the whole population after exclusion of subjects with a prior cardiovascular diagnosis (incident events; sample size, n = 6,910,923 for myocardial infarction and n = 6,932,578 for stroke) and in subjects with a prior diagnosis (recurrent events; n = 153,937 and n = 132,291 for stroke and myocardial infarction, respectively).RESULTS: Cox proportional hazard ratios (HRs) did not reveal an association of montelukast use with incident events. In contrast to these findings, montelukast use was associated with a lower risk for recurrent stroke (HR, 0.62; 95% CI, 0.38-0.99) accounting for age, sex, education level, and yearly income. Adjusting the latter finding also for respiratory and cardiovascular medications and diagnoses revealed similar point estimates (HR, 0.62; 95% CI, 0.39-1.0). Post hoc analyses revealed a significant association of montelukast use with a lower risk for recurrent myocardial infarction in male subjects (HR, 0.65; 95% CI, 0.43-0.99).CONCLUSION: These data provide a first indication for a potential role of the antiasthma drug montelukast for secondary prevention of cardiovascular disease.
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| 9. |
- Jobs, Elisabeth, et al.
(author)
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Serum cathepsin S is associated with decreased insulin sensitivity and the development of diabetes type 2 in a community-based cohort of elderly men
- 2012
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In: Diabetes Care. - : American diabetes association. - 0149-5992 .- 1935-5548. ; 36:1, s. 163-165
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Journal article (peer-reviewed)abstract
- OBJECTIVE. To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes.RESEARCH DESIGN AND METHODS. Serum cathepsin S, insulin sensitivity (euglycaemic-hyperinsulinaemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up.RESULTS. After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase -0.09 [95% CI -0.14 to -0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08-2.01], P = 0.01).CONCLUSIONS. Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.
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| 10. |
- Kaptoge, S., et al.
(author)
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C-Reactive Protein, Fibrinogen, and Cardiovascular Disease Prediction
- 2012
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 367:14, s. 1310-1320
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Journal article (peer-reviewed)abstract
- Background There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. Methods We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. Results The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P < 0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of "low" (< 10%), " intermediate" (10% to < 20%), and "high" (>= 20%) (P < 0.02 for both comparisons). We estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of >= 20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. Conclusions In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.)
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