| 1. |
- Clough, Rachel E, et al.
(författare)
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Endovascular treatment of acute aortic syndrome
- 2011
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Ingår i: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 54:6, s. 1580-1587
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The term acute aortic syndrome (AAS) encompasses a range of conditions that have a risk of imminent aortic rupture and where delays in treatment result in increased mortality. Endovascular treatment offers an attractive alternative to open surgery but little is known about the durability of the repair and the factors that predict mortality. METHODS: Prospective data were collected for a cohort of 110 consecutive patients with endovascular treatment for AAS. Patient and procedural characteristics were related to short- and midterm outcome using multivariate logistic regression analysis. RESULTS: There were 75 men and 35 women with a median age of 68 (range 57-76) years. The pathologies treated were acute dissection (35), symptomatic aneurysm (32), infected aneurysm (18), transection (12), chronic dissection (9), penetrating ulcer (3), and intramural hematoma (1). Thirty-day mortality was 12.7% and this was associated with hypotension (odds ratio [OR], 5.25), use of general anesthetic (OR, 5.23), long procedure duration (OR, 2.03), and increasing age (OR, 1.07). The causes of death were aortic rupture (4), myocardial infarction (4), stroke (3), and multisystem organ failure (3). The stroke and paraplegia rates were 7.3% and 6.4%, respectively. The 1-year survival was 81% and the 5-year survival 63%. Secondary procedures were required in 13 (11.8%) patients. Factors associated with death at 1 year were presence of an aortic fistula (OR, 9.78), perioperative stroke (OR, 5.87), and use of general anesthetic (OR, 3.76); and at 5 years were aortic fistula (OR, 12.31) and increasing age (OR, 1.06). CONCLUSIONS: Acute aortic syndrome carries significant early and late mortality. Emergency endovascular repair offers a minimally invasive treatment option associated with acceptable short and midterm results. Continued surveillance is important as secondary procedures and aortic-related deaths continue to occur throughout the follow-up period.
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| 2. |
- Schmidt, Amand F., et al.
(författare)
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PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study
- 2017
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Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:2, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.
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| 3. |
- Schmidt, Amand F., et al.
(författare)
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Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
- 2019
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Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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