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  • 1
    Online Resource
    Online Resource
    COVID-19-Associated Cardiovascular Complications
    MDPI AG ; 2021
    In:  Diseases Vol. 9, No. 3 ( 2021-06-29), p. 47-
    Details
    In: Diseases, MDPI AG, Vol. 9, No. 3 ( 2021-06-29), p. 47-
    Abstract: Coronavirus disease 2019 (COVID-19) has been reported to cause cardiovascular complications such as myocardial injury, thromboembolic events, arrhythmia, and heart failure. Multiple mechanisms—some overlapping, notably the role of inflammation and IL-6—potentially underlie these complications. The reported cardiac injury may be a result of direct viral invasion of cardiomyocytes with consequent unopposed effects of angiotensin II, increased metabolic demand, immune activation, or microvascular dysfunction. Thromboembolic events have been widely reported in both the venous and arterial systems that have attracted intense interest in the underlying mechanisms. These could potentially be due to endothelial dysfunction secondary to direct viral invasion or inflammation. Additionally, thromboembolic events may also be a consequence of an attempt by the immune system to contain the infection through immunothrombosis and neutrophil extracellular traps. Cardiac arrhythmias have also been reported with a wide range of implicated contributory factors, ranging from direct viral myocardial injury, as well as other factors, including at-risk individuals with underlying inherited arrhythmia syndromes. Heart failure may also occur as a progression from cardiac injury, precipitation secondary to the initiation or withdrawal of certain drugs, or the accumulation of des-Arg9-bradykinin (DABK) with excessive induction of pro-inflammatory G protein coupled receptor B1 (BK1). The presenting cardiovascular symptoms include chest pain, dyspnoea, and palpitations. There is currently intense interest in vaccine-induced thrombosis and in the treatment of Long COVID since many patients who have survived COVID-19 describe persisting health problems. This review will summarise the proposed physiological mechanisms of COVID-19-associated cardiovascular complications.
    Type of Medium: Online Resource
    ISSN: 2079-9721
    URL: Article
    DOI: 10.3390/diseases9030047
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720869-2
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  • 2
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    Effect of hypoglycaemia on measures of myocardial blood flow and myocardial injury in adults with and without type 1 diabetes: A prospective, randomised, open‐label, blinded endpoint, cross‐over study
    Wiley ; 2021
    In:  Endocrinology, Diabetes & Metabolism Vol. 4, No. 3 ( 2021-07)
    Details
    In: Endocrinology, Diabetes & Metabolism, Wiley, Vol. 4, No. 3 ( 2021-07)
    Abstract: This study examined the effect of experimentally‐induced hypoglycaemia on measures of myocardial blood flow and myocardial injury in adults with, and without, type 1 diabetes. Methods In a prospective, randomised, open‐label, blinded, endpoint cross‐over study, 17 young adults with type 1 diabetes with no cardiovascular risk factors, and 10 healthy non‐diabetic volunteers, underwent hyperinsulinaemic‐euglycaemic (blood glucose 4.5–5.5 mmol/L) and hypoglycaemic (2.2–2.5 mmol/L) clamps. Myocardial blood flow was assessed using transthoracic echocardiography Doppler coronary flow reserve (CFR) and myocardial injury using plasma high‐sensitivity cardiac troponin I (hs‐cTnI) concentration. Results During hypoglycaemia, coronary flow reserve trended non‐significantly lower in those with type 1 diabetes than in the non‐diabetic participants (3.54 ± 0.47 vs. 3.89 ± 0.89). A generalised linear mixed‐model analysis examined diabetes status and euglycaemia or hypoglycaemia as factors affecting CFR. No statistically significant difference in CFR was observed for diabetes status ( p  = .23) or between euglycaemia and hypoglycaemia ( p  = .31). No changes in hs‐cTnI occurred during hypoglycaemia or in the recovery period ( p  = .86). Conclusions A small change in CFR was not statistically significant in this study, implying hypoglycaemia may require more than coronary vasomotor dysfunction to cause harm. Further larger studies are required to investigate this putative problem.
    Type of Medium: Online Resource
    ISSN: 2398-9238 , 2398-9238
    URL: Issue
    URL: Article
    DOI: 10.1002/edm2.v4.3
    DOI: 10.1002/edm2.258
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2934368-9
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  • 3
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    Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
    Springer Science and Business Media LLC ; 2020
    In:  Nature Communications Vol. 11, No. 1 ( 2020-01-09)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-01-09)
    Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development ( MYOZ1 , SYNPO2L ), protein homoeostasis ( BAG3 ), and cellular senescence ( CDKN1A ). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-019-13690-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2553671-0
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  • 4
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    Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Circulation: Genomic and Precision Medicine Vol. 12, No. 4 ( 2019-04)
    Details
    In: Circulation: Genomic and Precision Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 12, No. 4 ( 2019-04)
    Abstract: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. Methods: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD. Results: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99–1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18–1.22; P for interaction 〈 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04–1.09). Conclusions: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
    Type of Medium: Online Resource
    ISSN: 2574-8300
    URL: Article
    DOI: 10.1161/CIRCGEN.119.002471
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2927603-2
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  • 5
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    Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Circulation: Genomic and Precision Medicine Vol. 12, No. 4 ( 2019-04)
    Details
    In: Circulation: Genomic and Precision Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 12, No. 4 ( 2019-04)
    Abstract: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. Methods: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. Results: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%–100%), mostly male (44%–91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14–1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13–1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35–1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. Conclusions: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
    Type of Medium: Online Resource
    ISSN: 2574-8300
    URL: Article
    DOI: 10.1161/CIRCGEN.119.002470
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2927603-2
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  • 6
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    The genomics of heart failure: design and rationale of the HERMES consortium
    Wiley ; 2021
    In:  ESC Heart Failure Vol. 8, No. 6 ( 2021-12), p. 5531-5541
    Details
    In: ESC Heart Failure, Wiley, Vol. 8, No. 6 ( 2021-12), p. 5531-5541
    Abstract: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome‐wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow‐up following heart failure diagnosis ranged from 2 to 116 months. Forty‐nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low‐frequency variants (allele frequency 0.01–0.05) at P   〈  5 × 10 −8 under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
    Type of Medium: Online Resource
    ISSN: 2055-5822 , 2055-5822
    URL: Issue
    URL: Article
    DOI: 10.1002/ehf2.v8.6
    DOI: 10.1002/ehf2.13517
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2814355-3
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  • 7
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    Impact of Selection Bias on Estimation of Subsequent Event Risk
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Circulation: Cardiovascular Genetics Vol. 10, No. 5 ( 2017-10)
    Details
    In: Circulation: Cardiovascular Genetics, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 5 ( 2017-10)
    Abstract: Studies of recurrent or subsequent disease events may be susceptible to bias caused by selection of subjects who both experience and survive the primary indexing event. Currently, the magnitude of any selection bias, particularly for subsequent time-to-event analysis in genetic association studies, is unknown. Methods and Results— We used empirically inspired simulation studies to explore the impact of selection bias on the marginal hazard ratio for risk of subsequent events among those with established coronary heart disease. The extent of selection bias was determined by the magnitudes of genetic and nongenetic effects on the indexing (first) coronary heart disease event. Unless the genetic hazard ratio was unrealistically large ( 〉 1.6 per allele) and assuming the sum of all nongenetic hazard ratios was 〈 10, bias was usually 〈 10% (downward toward the null). Despite the low bias, the probability that a confidence interval included the true effect decreased (undercoverage) with increasing sample size because of increasing precision. Importantly, false-positive rates were not affected by selection bias. Conclusions— In most empirical settings, selection bias is expected to have a limited impact on genetic effect estimates of subsequent event risk. Nevertheless, because of undercoverage increasing with sample size, most confidence intervals will be over precise (not wide enough). When there is no effect modification by history of coronary heart disease, the false-positive rates of association tests will be close to nominal.
    Type of Medium: Online Resource
    ISSN: 1942-325X , 1942-3268
    URL: Article
    DOI: 10.1161/CIRCGENETICS.116.001616
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2927603-2
    detail.hit.zdb_id: 2457085-0
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  • 8
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    The effects and costs of home-based rehabilitation for heart failure with reduced ejection fraction: The REACH-HF multicentre randomized controlled trial
    Oxford University Press (OUP) ; 2019
    In:  European Journal of Preventive Cardiology Vol. 26, No. 3 ( 2019-02), p. 262-272
    Details
    In: European Journal of Preventive Cardiology, Oxford University Press (OUP), Vol. 26, No. 3 ( 2019-02), p. 262-272
    Abstract: Cardiac rehabilitation improves health-related quality of life (HRQoL) and reduces hospitalizations in patients with heart failure, but international uptake of cardiac rehabilitation for heart failure remains low. Design and methods The aim of this multicentre randomized trial was to compare the REACH-HF (Rehabilitation EnAblement in CHronicHeart Failure) intervention, a facilitated self-care and home-based cardiac rehabilitation programme to usual care for adults with heart failure with reduced ejection fraction (HFrEF). The study primary hypothesis was that the addition of the REACH-HF intervention to usual care would improve disease-specific HRQoL (Minnesota Living with Heart Failure questionnaire (MLHFQ)) at 12 months compared with usual care alone. Results The study recruited 216 participants, predominantly men (78%), with an average age of 70 years and mean left ventricular ejection fraction of 34%. Overall, 185 (86%) participants provided data for the primary outcome. At 12 months, there was a significant and clinically meaningful between-group difference in the MLHFQ score of –5.7 points (95% confidence interval –10.6 to –0.7) in favour of the REACH-HF intervention group ( p = 0.025). With the exception of patient self-care ( p  〈  0.001) there was no significant difference in other secondary outcomes, including clinical events ( p  〉  0.05) at follow-up compared with usual care. The mean cost of the REACH-HF intervention was £418 per participant. Conclusions The novel REACH-HF home-based facilitated intervention for HFrEF was clinically superior in disease-specific HRQoL at 12 months and offers an affordable alternative to traditional centre-based programmes to address current low cardiac rehabilitation uptake rates for heart failure.
    Type of Medium: Online Resource
    ISSN: 2047-4873 , 2047-4881
    URL: Article
    DOI: 10.1177/2047487318806358
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2646239-4
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  • 9
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    The cost effectiveness of REACH-HF and home-based cardiac rehabilitation compared with the usual medical care for heart failure with reduced ejection fraction: A decision model-based analysis
    Oxford University Press (OUP) ; 2019
    In:  European Journal of Preventive Cardiology Vol. 26, No. 12 ( 2019-08), p. 1252-1261
    Details
    In: European Journal of Preventive Cardiology, Oxford University Press (OUP), Vol. 26, No. 12 ( 2019-08), p. 1252-1261
    Abstract: The REACH-HF (Rehabilitation EnAblement in CHronic Heart Failure) trial found that the REACH-HF home-based cardiac rehabilitation intervention resulted in a clinically meaningful improvement in disease-specific health-related quality of life in patients with reduced ejection fraction heart failure (HFrEF). The aims of this study were to assess the long-term cost-effectiveness of the addition of REACH-HF intervention or home-based cardiac rehabilitation to usual care compared with usual care alone in patients with HFrEF. Design and methods A Markov model was developed using a patient lifetime horizon and integrating evidence from the REACH-HF trial, a systematic review/meta-analysis of randomised trials, estimates of mortality and hospital admission and UK costs at 2015/2016 prices. Taking a UK National Health and Personal Social Services perspective we report the incremental cost per quality-adjusted life-year (QALY) gained, assessing uncertainty using probabilistic and deterministic sensitivity analyses. Results In base case analysis, the REACH-HF intervention was associated with per patient mean QALY gain of 0.23 and an increased mean cost of £400 compared with usual care, resulting in a cost per QALY gained of £1720. Probabilistic sensitivity analysis indicated a 78% probability that REACH-HF is cost effective versus usual care at a threshold of £20,000 per QALY gained. Results were similar for home-based cardiac rehabilitation versus usual care. Sensitivity analyses indicate the findings to be robust to changes in model assumptions and parameters. Conclusions Our cost-utility analyses indicate that the addition of the REACH-HF intervention and home-based cardiac rehabilitation programmes are likely to be cost-effective treatment options versus usual care alone in patients with HFrEF.
    Type of Medium: Online Resource
    ISSN: 2047-4873 , 2047-4881
    URL: Article
    DOI: 10.1177/2047487319833507
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2646239-4
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  • 10
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    Serial changes in blood pressure, renal function, endothelin and lipoprotein (a) during the first 9 days of cyclosporin therapy in males
    Ovid Technologies (Wolters Kluwer Health) ; 1995
    In:  Journal of Hypertension Vol. 13, No. 6 ( 1995-06), p. 667-673
    Details
    In: Journal of Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 13, No. 6 ( 1995-06), p. 667-673
    Type of Medium: Online Resource
    ISSN: 0263-6352
    URL: Article
    DOI: 10.1097/00004872-199506000-00014
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1995
    detail.hit.zdb_id: 2017684-3
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