| 8561. |
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| 8562. |
- Dondo, Tatendashe B., et al.
(författare)
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beta-Blockers and Mortality After Acute Myocardial Infarction in Patients Without Heart Failure or Ventricular Dysfunction
- 2017
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 69:22, s. 2710-2720
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if beta-blockers are associated with reduced mortality.OBJECTIVES: The goal of this study was to determine the association between beta-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD).METHODS: This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of beta-blockers and 1-year mortality.RESULTS: Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non-ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received beta-blockers, respectively. For the entire cohort, with> 163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received beta-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without beta-blocker use (average treatment effect [ATE] coefficient: 0.07; 95% confidence interval [CI]: -0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: -0.98 to 1.58; p = 0.637) and non-ST-segment elevation myocardial infarction (ATE coefficient: -0.07; 95% CI: -0.68 to 0.54; p = 0.819).CONCLUSIONS: Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of beta-blockers was not associated with a lower risk of death at any time point up to 1 year.
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| 8563. |
- Dongiovanni, Paola, et al.
(författare)
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Protein phosphatase 1 regulatory subunit 3B gene variation protects against hepatic fat accumulation and fibrosis in individuals at high risk of nonalcoholic fatty liver disease.
- 2018
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Ingår i: Hepatology communications. - : Ovid Technologies (Wolters Kluwer Health). - 2471-254X. ; 2:6, s. 666-675
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Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver damage and has a strong genetic component. The rs4841132 G>A variant, modulating the expression of protein phosphatase 1 regulatory subunit 3B (PPP1R3B), which is involved in glycogen synthesis, has been reported to reduce the risk of NAFLD but at the same time may favor liver disease by facilitating glycogen accumulation. The aim of this study was to assess the impact of rs4841132 on development of histologic steatosis and fibrosis in 1,388 European individuals in a liver biopsy cohort, on NAFLD hepatocellular carcinoma in a cross-sectional Italian cohort (n = 132 cases), and on liver disease at the population level in the United Kingdom Biobank cohort. We investigated the underlying mechanism by examining the impact of the variant on gene expression profiles. In the liver biopsy cohort, the rs4841132 minor A allele was associated with protection against steatosis (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.42-0.95; P = 0.03) and clinically significant fibrosis (OR, 0.35; 95% CI, 0.14-0.87; P = 0.02) and with reduced circulating cholesterol (P = 0.02). This translated into protection against hepatocellular carcinoma development (OR, 0.22; 95% CI, 0.07-0.70; P = 0.01). At the population level, the rs4841132 variation was not associated with nonalcoholic or nonviral diseases of the liver but was associated with lower cholesterol (P = 1.7 × 10-8). In individuals with obesity, the A allele protecting against steatosis was associated with increased PPP1R3B messenger RNA expression and activation of lipid oxidation and with down-regulation of pathways related to lipid metabolism, inflammation, and cell cycle. Conclusion: The rs4841132 A allele is associated with protection against hepatic steatosis and fibrosis in individuals at high risk of NAFLD but not in the general population and against dyslipidemia. The mechanism may be related to modulation of PPP1R3B expression and hepatic lipid metabolism. (Hepatology Communications 2018;2:666-675).
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| 8564. |
- Dongiovanni, Paola, et al.
(författare)
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Statin use and nonalcoholic steatohepatitis in at risk individuals.
- 2015
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Ingår i: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 63:3, s. 705-712
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Tidskriftsartikel (refereegranskat)abstract
- Excess hepatic free cholesterol contributes to the pathogenesis of nonalcoholic steatohepatitis, and statins reduce cholesterol synthesis. Aim of this study was to assess whether statin use is associated with histological liver damage related to steatohepatitis.
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| 8565. |
- Donovan, Killian, et al.
(författare)
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Fibroblast Growth Factor-23 and Risk of Cardiovascular Diseases A Mendelian Randomization Study
- 2023
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Ingår i: American Society of Nephrology. Clinical Journal. - : Wolters Kluwer. - 1555-9041 .- 1555-905X. ; 18:1, s. 17-27
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Tidskriftsartikel (refereegranskat)abstract
- Background Fibroblast growth factor-23 (FGF-23) is associated with a range of cardiovascular and noncardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding.Methods SCALLOP Consortium data of 19,195 participants were used to generate an FGF-23 genetic score. Data from 337,448 UK Biobank participants were used to estimate associations between higher genetically predicted FGF-23 concentration and the odds of any atherosclerotic cardiovascular disease (n=26,266 events), nonatherosclerotic cardiovascular disease (n=12,652), and noncardiovascular diseases previously linked to FGF-23. Measurements of carotid intima-media thickness and left ventricular mass were available in a subset. Associations with cardiovascular outcomes were also tested in three large case-control consortia: CARDIOGRAMplusC4D (coronary artery disease, n=181,249 cases), MEGASTROKE (stroke, n=34,217), and HERMES (heart failure, n=47,309).Results We identified 34 independent variants for circulating FGF-23, which formed a validated genetic score. There were no associations between genetically predicted FGF-23 and any of the cardiovascular or non cardiovascular outcomes. In UK Biobank, the odds ratio (OR) for any atherosclerotic cardiovascular disease per 1-SD higher genetically predicted logFGF-23 was 1.03 (95% confidence interval [95% CI], 0.98 to 1.08), and for any nonatherosclerotic cardiovascular disease, it was 1.01 (95% CI, 0.94 to 1.09). The ORs in the case-control consortia were 1.00 (95% CI, 0.97 to 1.03) for coronary artery disease, 1.01 (95% CI, 0.95 to 1.07) for stroke, and 1.00 (95% CI, 0.95 to 1.05) for heart failure. In those with imaging, logFGF-23 was not associated with carotid or cardiac abnormalities.Conclusions Genetically predicted FGF-23 levels are not associated with atherosclerotic and nonatherosclerotic cardiovascular diseases, suggesting no important causal link.
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| 8566. |
- Doolub, Gemina, et al.
(författare)
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Impact of Sex on Clinical Outcomes in Patients undergoing Complex Percutaneous Coronary Angioplasty (from the e-ULTIMASTER Study)
- 2023
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Ingår i: American Journal of Cardiology. - : Elsevier. - 0002-9149 .- 1879-1913. ; 186, s. 71-79
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Tidskriftsartikel (refereegranskat)abstract
- Female gender has been shown to be associated with worse clinical outcomes after percutaneous coronary intervention (PCI). However, the impact of gender on the clinical outcomes of complex PCI is still poorly understood. This study examined the differences in patient and coronary lesion characteristics and longer-term clinical outcomes in male and female patients who underwent complex PCI. This was a sub-analysis of the e-ULTIMASTER study, which was a large, multicontinental, prospective, observational study enrolling 37,198 patients who underwent PCI with the Ultimaster stent. Patients who underwent complex PCI were stratified by gender. The primary outcome was target lesion failure at 12 months, defined as the composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target lesion revascularization at 12 months. A total of 13,623 patients underwent complex procedures, of which 35.7% were women. Women were twice as likely as men to be aged ≥80 years (17.6% vs 9%, p <0.0001) and had a higher prevalence of cardiovascular risk factors. Women had fewer lesions treated than men (1.5 ± 0.8 vs 1.6 ± 0.8, p <0.0001) and fewer stents implanted (2.0 ± 1.1 vs 2.1 ± 1.1, p <0.0001). There was no statistically significant difference in clinical outcomes at 12 months between women and men. Event rates were comparable in women and men for target lesion failure (4.7% vs 4.3%, p = 0.30), target vessel failure (5.1% vs 4.9%, p = 0.73), and cardiac death (1.8% vs 1.7%, p = 0.80).In conclusion, our findings suggest no significant differences in clinical outcomes between women and men who underwent complex PCI.
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| 8567. |
- DOria, Mario, et al.
(författare)
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Robustness of Longitudinal Safety and Efficacy After Paclitaxel-Based Endovascular Therapy for Treatment of Femoro-Popliteal Artery Occlusive Disease : An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
- 2024
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Ingår i: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 101, s. 164-178
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Tidskriftsartikel (refereegranskat)abstract
- Background:The aims of this study were: i) to assess fragility indices (FIs) of individual randomized controlled trials (RCTs) that compared paclitaxel-based drug-coated balloons (DCBs) or drug-eluting stents (DESs) versus standard endovascular devices, and ii) to meta-analyze mid-term and long-term safety and efficacy outcomes from available RCT data while also estimating the FI of pooled results.Methods:This systematic review has been registered in the PROSPERO public database (CRD42022304326 http://www.crd.york.ac.uk/PROSPERO). A query of PubMed (Medline), EMBASE (Excerpta Medical Database), Scopus, and CENTRAL (Cochrane Central Register of Controlled Trials) databases was performed to identify eligible RCTs. Rates of primary patency (PP) and target lesion revascularization (TLR) were assessed as efficacy outcomes, while lower limb amputation (LLA) consisting of major amputation that is. below or above the knee and all-cause mortality were estimated as safety outcomes. All outcomes were pooled with a random effects model to account for any clinical and study design heterogeneity. The analyses were performed by dividing the RCTs according to their maximal follow-up length (mid-term was defined as results up to 2-3 years, while long-term was defined as results up to 4-5 years). For each individual outcome, the FI and reverse fragility index (RFI) were calculated according to whether the outcome results were statistically significant or not, respectively. The fragility quotient (FQ) and reverse fragility quotient (RFQ), which are the FI or RFI divided by the sample size, were also calculated.Results:A total of 2,337 patients were included in the systematic review and meta -analysis. There were 2 RCTs examining DES devices and 14 RCTs evaluating different DCBs. For efficacy outcomes, there was evidence that paclitaxel-based endovascular therapy increased the PP rate and reduced the TLR rate at mid-term, with a calculated pooled risk ratio (RR) of 1.66 for patency (95% CI, 1.55-1.86; P < 0.001), with a corresponding number needed -totreat (NNT) of 3 patients (95% CI, 2.9-3.8) and RR of 0.44 for TLR (95% CI, 0.35-0.54; P = 0.027), respectively. Similarly, there was evidence that paclitaxel-based endovascular therapy both increased PP and decreased TLR rates at long-term, with calculated pooled RR values of 1.73 (95% CI, 1.12-2.61; P = 0.004) and 0.53 (95% CI, 0.45-0.62; P = 0.82), respectively. For safety outcomes, there was evidence that paclitaxel-based endovascular therapy increased all -cause mortality at mid-term, with a calculated pooled RR of 2.05 (95% CI, 1.21-3.24). However, there was no difference between treatment arms in LLA at mid-term (95% CI, 0.1-2.7; P = 0.68). Similarly, neither all -cause mortality nor LLA at long-term differed between treatment arms, with a calculated pooled RR of 0.66, 1.02 (95% CI, 0.31-3.42) and 1.02 (95% CI, 0.305.21; P = 0.22), respectively. The pooled estimates of PP at mid-term were robust (FI = 28 and FQ = 1.9%) as were pooled rates of TLR (FI = 18 and FQ = 0.9%). However, when safety outcomes were analyzed, the robustness of the meta -analysis decreased significantly. In fact, the relationship between the use of paclitaxel-coated devices and all -cause mortality at mid-term showed very low robustness (FI = 4 and FQ = 0.2%). At 5 years, only the benefit of paclitaxel-based devices to reduce TLR remained robust, with an FI of 32 and an FQ of 3.1%.Conclusions:The data supporting clinical efficacy endpoints of RCTs that examined paclitaxelbased devices in the treatment of femoral-popliteal arterial occlusive disease were robust; however, the pooled safety endpoints were highly fragile and prone to bias due to loss of patient follow-up in the original studies. These findings should be considered in the ongoing debate concerning the safety of paclitaxel-based devices.
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| 8568. |
- Dorkhan, Mozhgan, et al.
(författare)
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A review of pioglitazone HCL and glimepiride in the treatment of type 2 diabetes.
- 2007
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Ingår i: Vascular Health and Risk Management. - 1178-2048. ; 3:5, s. 721-731
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Forskningsöversikt (refereegranskat)abstract
- Type 2 diabetes (T2D) is a progressive disorder with a consistent and steady increase in glycosylated hemoglobin (HbA1c) over time associated with enhanced risk of micro- and macrovascular complications and a substantial reduction in life expectancy. There are three major pathophysiologic abnormalities associated with T2D: impaired insulin secretion, excessive hepatic glucose output, and insulin resistance in skeletal muscle, liver, and adipose tissue. These defects have been treated in clinical praxis by use of oral insulin secretagogues (sulfonylureas/ glinides) or insulin, biguanides, and thiazolidinediones (TZDs) respectively. Pioglitazone HCL is an insulin sensitizer in the TZD family and glimepiride is an insulin secretagogue in the SU family. This article reviews mechanisms of action and clinical data behind the use of these two commonly used oral hypoglycemic agents with documented efficacy and good safety profile of once-daily administration, alone or in combination with insulin or metformin, in the management of T2D in terms of glycemic and non-glycemic effects, tolerability and side effects, and impact on vascular health.
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| 8569. |
- dos Remedios, C. G., et al.
(författare)
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The Sydney Heart Bank : improving translational research while eliminating or reducing the use of animal models of human heart disease
- 2017
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Ingår i: Biophysical Reviews. - : Springer Nature. - 1867-2450 .- 1867-2469. ; 9:4, s. 431-441
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Tidskriftsartikel (refereegranskat)abstract
- The Sydney Heart Bank (SHB) is one of the largest human heart tissue banks in existence. Its mission is to provide high-quality human heart tissue for research into the molecular basis of human heart failure by working collaboratively with experts in this field. We argue that, by comparing tissues from failing human hearts with age-matched non-failing healthy donor hearts, the results will be more relevant than research using animal models, particularly if their physiology is very different from humans. Tissue from heart surgery must generally be used soon after collection or it significantly deteriorates. Freezing is an option but it raises concerns that freezing causes substantial damage at the cellular and molecular level. The SHB contains failing samples from heart transplant patients and others who provided informed consent for the use of their tissue for research. All samples are cryopreserved in liquid nitrogen within 40 min of their removal from the patient, and in less than 5–10 min in the case of coronary arteries and left ventricle samples. To date, the SHB has collected tissue from about 450 failing hearts (>15,000 samples) from patients with a wide range of etiologies as well as increasing numbers of cardiomyectomy samples from patients with hypertrophic cardiomyopathy. The Bank also has hearts from over 120 healthy organ donors whose hearts, for a variety of reasons (mainly tissue-type incompatibility with waiting heart transplant recipients), could not be used for transplantation. Donor hearts were collected by the St Vincent’s Hospital Heart and Lung transplantation team from local hospitals or within a 4-h jet flight from Sydney. They were flushed with chilled cardioplegic solution and transported to Sydney where they were quickly cryopreserved in small samples. Failing and/or donor samples have been used by more than 60 research teams around the world, and have resulted in more than 100 research papers. The tissues most commonly requested are from donor left ventricles, but right ventricles, atria, interventricular system, and coronary arteries vessels have also been reported. All tissues are stored for long-term use in liquid N or vapor (170–180 °C), and are shipped under nitrogen vapor to avoid degradation of sensitive molecules such as RNAs and giant proteins. We present evidence that the availability of these human heart samples has contributed to a reduction in the use of animal models of human heart failure.
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| 8570. |
- Dotevall, Annika, 1957, et al.
(författare)
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Considerable disturbances of cardiovascular risk factors in women with diabetes and myocardial infarction
- 2005
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Ingår i: J Diabetes Complications. - : Elsevier BV. - 1056-8727. ; 19:1, s. 26-34
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate to which extent differences in cardiovascular risk factors explain the increased risk of myocardial infarction (MI) and complication rate in women with diabetes mellitus (DM). DESIGN: Case-control study. SUBJECTS: We compared women with diabetes and previous MI (n=29), diabetes but no MI (n=46), prior MI but no diabetes (n=64), and healthy controls (n=125). MEASUREMENTS: Smoking habits, physical activity, blood pressure (BP), body mass index (BMI), waist/hip ratio (WHR), serum lipids, plasma fibrinogen, and serum sex hormones. RESULTS: Despite the fact that diabetic women had similar BMI, those with a past MI, compared to diabetic women without MI, had significantly higher WHR (mean, 95% CI) [0.89 (0.87, 0.92) vs. 0.84 (0.81, 0.86) mmol/l, P=.001] and very high S-triglycerides [3.03 (2.23, 3.83) vs. 1.69, (1.39, 1.99) mmol/l, P=.001] and low HDL-cholesterol [1.09 (0.94, 1.24) vs. 1.56 (1.41, 1.71) mmol/l, P<.001], indicating pronounced metabolic disturbances. Women with MI but no diabetes had intermediate values for WHR, triglycerides, and HDL-cholesterol. Furthermore, women with diabetes and MI had significantly higher p-fibrinogen, were smokers, and lived a more sedentary life than the other women. Over half of all women with prior MI were on lipid-lowering therapy and tended to have nonsignificantly lower S-cholesterol than women without MI. CONCLUSIONS: Women with diabetes who have manifested an MI carry a very substantial cardiovascular risk factor burden, which probably explain their increased morbidity and mortality. In order to improve prognosis, studies targeted at investigating treatment modalities for these abnormalities are needed.
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