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- Aavik, Einari, et al.
(författare)
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Global DNA methylation analysis of human atherosclerotic plaques reveals extensive genomic hypomethylation and reactivation at imprinted locus 14q32 involving induction of a miRNA cluster
- 2015
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 36:16, s. 993-U23
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Tidskriftsartikel (refereegranskat)abstract
- Aims Genetics can explain just above 10% of the observed heritability in cardiovascular diseases. Epigenetics is about to provide some further explanations, but the information needed for that is in the accumulation phase. Genome-wide DNA methylation analysis has revealed thousands of genes, which are epigenetically differentially regulated in atherosclerotic plaques. Our results point to an additional level of complexity that needs to be integrated into the aetiology of atherogenesis.We conducted a genome-wide analysis to identify differentially methylated genes in atherosclerotic lesions. Methods DNA methylation at promoters, exons and introns was identified by massive parallel sequencing. Gene expression was analysed by microarrays, qPCR, immunohistochemistry and western blots. Results Globally, hypomethylation of chromosomal DNA predominates in atherosclerotic plaques and two-thirds of genes showing over 2.5-fold differential in DNA methylation are up-regulated in comparison to healthy mammary arteries. The imprinted chromatin locus 14q32 was identified for the first time as an extensively hypomethylated area in atherosclerosis with highly induced expression of miR127, -136, -410, -431, -432, -433 and capillary formation-associated gene RTL1. The top 100 list of hypomethylated promoters exhibited over 1000-fold enrichment for miRNAs, many of which mapped to locus 14q32. Unexpectedly, also gene body hypermethylation was found to correlate with stimulated mRNA expression. Conclusion Significant changes in genomic methylation were identified in atherosclerotic lesions. The most prominent gene cluster activated via hypomethylation was detected at imprinted chromosomal locus 14q32 with several clustered miRNAs that were up-regulated. These results suggest that epigenetic changes are involved in atherogenesis and may offer new potential therapeutic targets for vascular diseases.
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| 2. |
- Abdul-Rahim, A. H., et al.
(författare)
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Risk of stroke in chronic heart failure patients with preserved ejection fraction, but without atrial fibrillation: analysis of the CHARM-Preserved and I-Preserve trials
- 2017
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:10, s. 742-750
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Tidskriftsartikel (refereegranskat)abstract
- Aims The incidence and predictors of stroke in patients with heart failure and preserved ejection fraction (HF-PEF), but without atrial fibrillation (AF), are unknown. We described the incidence of stroke in HF-PEF patients with and without AF and predictors of stroke in those without AF. Methods and results We pooled data from the CHARM-Preserved and I-Preserve trials. Using Cox regression, we derived a model for stroke in patients without AF in this cohort and compared its performance with a published model in heart failure patients with reduced ejection fraction (HF-REF)-predictive variables: age, body mass index, New York Heart Association class, history of stroke, and insulin-treated diabetes. The two stroke models were compared and Kaplan-Meier curves for stroke estimated. The risk model was validated in a third HF-PEF trial. Of the 6701 patients, 4676 did not have AF. Stroke occurred in 124 (6.1%) with AF and in 171 (3.7%) without AF (rates 1.80 and 1.00 per 100 patient-years, respectively). There was no difference in performance of the stroke model derived in the HF-PEF cohort and the published HF-REF model (c-index 0.71, 95% confidence interval 0.57-0.84 vs. 0.73, 0.59-0.85, respectively) as the predictive variables overlapped. The model performed well in the validation cohort (0.86, 0.62-0.99). The rate of stroke in patients in the upper third of risk approximated to that in patients with AF (1.60 and 1.80 per 100 patient-years, respectively). Conclusions A small number of clinical variables identify a subset of patients with HF-PEF, but without AF, at elevated risk of stroke.
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| 7. |
- Abrahamsson, Putte, 1965, et al.
(författare)
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Impact of hospitalization for acute coronary events on subsequent mortality in patients with chronic heart failure
- 2009
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Ingår i: Eur Heart J. - 1522-9645. ; 30:3, s. 338-45
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: We explored the impact of having a hospital admission for an acute coronary syndrome (ACS) on the subsequent prognosis among patients with chronic heart failure (CHF). METHODS AND RESULTS: A total of 7599 patients with CHF, New York Heart Association Classes II-IV, were randomly assigned to candesartan or placebo. We assessed the risk of death after a first ACS using time-updated Cox proportional hazard models adjusted for baseline predictors. During a mean follow-up of 3.3 years, 1174 patients experienced at least one ACS. Myocardial infarction (MI) was the first ACS in 442 subjects and unstable angina (UA) in 732. After these events, 219 (49.5%) and 167 (22.8%) patients died during follow-up. The early risk of death was more pronounced after MI: 30.2% died within 30 days compared with 3.6% after UA. After an ACS event, the risk of death declined steadily over time, although 18 months after an MI the risk was still twice that of patients without an ACS. CONCLUSION: Patients with CHF, who develop an ACS, have markedly increased subsequent mortality, particularly in the early phase after an MI.
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| 8. |
- Aburawi, Elhadi, et al.
(författare)
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Relation of aortic root dilatation and age in Marfan's syndrome
- 2007
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 28:3, s. 376-379
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Tidskriftsartikel (refereegranskat)abstract
- Aims The main aim of this study was to describe the age at which pathological aortic root dilation occurs in patients with Marfan's syndrome (MFS). Methods and results A total of 160 patients with MFS attending a regional cardiac centre were reviewed retrospectively. Dilation of the ascending aorta was diagnosed by comparing the maximum aortic sinus measurement with control data from the literature. We employed a Kaplan-Meier survival curve to estimate the age at which dilatation occurs. The mean age of the total group at presentation was 15.5 years (range 1.5-40 years). Skeletal abnormalities were present in 95%. Eye involvement was found in 18%. In the 115/160 patients with an abnormal aortic root, 78/115 (68%) developed aortic root dilatation before 19 years of age. From the Kaplan-Meier curve, it can be estimated that about 35% of the patients have aortic root dilatation already at the age of 5 years and 70% before the age of 20 years, and at least 80% by 40 years. There were 31 patients with normal aortic root when first seen but 24/31 (77%) developed aortic root dilatation before the age of 19 years and 7/31 (22.6%) after 19 years of age. Of those (seven patients) who developed new pathological aortic root dilatation after age 19 years, the age range was between 21 and 40 years with a mean of 27 years. Overall, 13 patients (8%) had surgery for aortic root replacement. Conclusion Aortic root dilatation develops early in MFS and was present in 35% by the age of 5 years and 68% by 19 years. Even though new aortic root dilation is relatively rare, it is not possible to safely discharge patients with MFS as about one-third of the patients in our series who developed new pathological aortic root dilation did so after the age of 19 years.
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