Age-dependent differences in diabetes and acute hyperglycemia between men and women with ST-elevation myocardial infarction: a cohort study

BACKGROUND: Both acute hyperglycemia as diabetes results in an impaired prognosis in ST-elevation myocardial infarction (STEMI) patients. It is unknown whether there is a different prevalence of diabetes and acute hyperglycemia in men and women within age-groups. METHODS: Between 2004 and 2010, 4640 consecutive patients (28% women) with STEMI, were referred for primary PCI. Patients were stratified into two age groups, < 65 years (2447 patients) and ≥65 years (2193 patients). Separate analyses were performed in 3901 patients without diabetes. Diabetes was defined as known diabetes or HbA1c ≥6.5 mmol/l at admission. RESULTS: The prevalence of diabetes was comparable between women and men in the younger age group (14% vs 12%, p = 0.52), whereas in the older age group diabetes was more prevalent in women (25% vs 17% p < 0.001). In patients without diabetes, admission glucose was comparable between both genders in younger patients (8.1 ± 2.0 mmol/l vs 8.0 ± 2.2 mmol/l p = 0.36), but in older patients admission glucose was higher in women than in men (8.7 ± 2.1 mmol/l vs 8.4 ± 2.1 mmol/l p = 0.028). After multivariable analyses, the occurrence of increased admission glucose was comparable between men and women in the younger age group (OR 1.1, 95%CI 0.9-1.5), but increased in women in the older age group (OR 1.3, 95% CI 1.1-1.7). Both diabetes and hyperglycemia were associated with a higher one-year mortality in both men and women. CONCLUSIONS: The differences between men and women in hyperglycemia and diabetes in patients with STEMI are age dependent and can only be observed in older patients. This may have implications for medical treatment and should be investigated further

Frequency, Determinants, and Prognostic Effects of Acute Kidney Injury and Red Blood Cell Transfusion in Patients Undergoing Transcatheter Aortic Valve Implantation

Objectives: To determine the frequency and independent predictors of acute kidney injury (AKI) in addition to the prognostic implications of both AKI and periprocedural red blood cell (RBC) transfusions on 30 day and cumulative late mortality in patients undergoing transcatheter aortic valve implantation (TAVI). Background: RBC transfusions have been reported to predict AKI following TAVI. Data on the prognostic implications of both factors, however, are lacking. Methods: 126 consecutive patients underwent TAVI with the Medtronic Core Valve Revalving System. AKI was defined according to the valve academic research consortium definitions as an absolute increase in serum creatinine >= 0.3 mg dL(-1) (>= 26.4 mu mol L(-1)) or a percentage increase >= 50% within 72 hr following TAVI. Results: Five patients on chronic haemodialysis and three intraprocedural deaths were excluded, leading to a final study population of 118 patients. AKI occurred in 19% of the patients necessitating temporary haemodialysis in 2%. Independent predictors of AKI included: previous myocardial infarction (OR: 5.72; 95% CI: 1.64-19.94), periprocedural (<24 hr) RBC transfusions (OR: 1.29; 95% CI: 1.01-1.70), postprocedural (<72 hr) leucocyte count (OR: 1.18; 95% CI: 1.02-1.37), and logistic EuroSCORE (OR: 1.08; 95% CI: 1.01-1.14). In patients with AKI, 30-day mortality was 23% and cumulative late mortality (median: 13 months) was 55%. AKI (OR: 5.47; 95% CI: 1.23-24.21) and postprocedural leucocyte count (OR: 1.20; 95% CI: 1.03-1.38) were independent predictors of 30-day mortality while AKI (HR: 2.79; 95% CI: 1.36-5.71) was the only independent predictor of late mortality. Conclusions: AKI following TAVI occurred in 19% of the patients. RBC transfusion was found to be an independent predictor of AKI, which in turn predicted both 30-day and cumulative late mortality. (C) 2011 Wiley-Liss, Inc

A comparison of patient characteristics and 30-day mortality outcomes after transcatheter aortic valve implantation and surgical aortic valve replacement for the treatment of aortic stenosis: a two-centre study

AIMS: It is unclear whether transcatheter aortic valve implantation (TAVI) addresses an unmet clinical need for those currently rejected for surgical aortic valve replacement (SAVR) and whether there is a subgroup of high-risk patients benefiting more from TAVI compared to SAVR. In this two-centre, prospective cohort study, we compared baseline characteristics and 30-day mortality between TAVI and SAVR in consecutive patients undergoing invasive treatment for aortic stenosis. METHODS AND RESULTS: We pre-specified different adjustment methods to examine the effect of TAVI as compared with SAVR on overall 30-day mortality: crude univariable logistic regression analysis, multivariable analysis adjusted for baseline characteristics, analysis adjusted for propensity scores, propensity score matched analysis, and weighted analysis using the inverse probability of treatment (IPT) as weights. A total of 1,122 patients were included in the study: 114 undergoing TAVI and 1,008 patients undergoing SAVR. The crude mortality rate was greater in the TAVI group (9.6% vs. 2.3%) yielding an odds ratio [OR] of 4.57 (95%-CI 2.17-9.65). Compared to patients undergoing SAVR, patients with TAVI were older, more likely to be in NYHA class III and IV, and had a considerably higher logistic EuroSCORE and more comorbid conditions. Adjusted OR depended on the method used to control for confounding and ranged from 0.60 (0.11-3.36) to 7.57 (0.91-63.0). We examined the distribution of propensity scores and found scores to overlap sufficiently only in a narrow range. In patients with sufficient overlap of propensity scores, adjusted OR ranged from 0.35 (0.04-2.72) to 3.17 (0.31 to 31.9). In patients with insufficient overlap, we consistently found increased odds of death associated with TAVI compared with SAVR irrespective of the method used to control confounding, with adjusted OR ranging from 5.88 (0.67-51.8) to 25.7 (0.88-750). Approximately one third of patients undergoing TAVI were found to be potentially eligible for a randomised comparison of TAVI versus SAVR. CONCLUSIONS: Both measured and unmeasured confounding limit the conclusions that can be drawn from observational comparisons of TAVI versus SAVR. Our study indicates that TAVI could be associated with either substantial benefits or harms. Randomised comparisons of TAVI versus SAVR are warranted

A comparison of patient characteristics and 30-day mortality outcomes after transcatheter aortic valve implantation and surgical aortic valve replacement for the treatment of aortic stenosis: A two-centre study

Aims: It is unclear whether transcatheter aortic valve implantation (TAVI) addresses an unmet clinical need for those currently rejected for surgical aortic valve replacement (SAVR) and whether there is a subgroup of high-risk patients benefiting more from TAVI compared to SAVR. In this two-centre, prospective cohort study, we compared baseline characteristics and 30-day mortality between TAVI and SAVR in consecutive patients undergoing invasive treatment for aortic stenosis. Methods and results: We pre-specified different adjustment methods to examine the effect of TAVI as compared with SAVR on overall 30-day mortality: crude univariable logistic regression analysis, multivariable analysis adjusted for baseline characteristics, analysis adjusted for propensity scores, propensity score matched analysis, and weighted analysis using the inverse probability of treatment (IPT) as weights. A total of 1,122 patients were included in the study: 114 undergoing TAVI and 1,008 patients undergoing SAVR. The crude mortality rate was greater in the TAVI group (9.6% vs. 2.3%) yielding an odds ratio [OR] of 4.57 (95%-CI 2.17-9.65). Compared to patients undergoing SAVR, patients with TAVI were older, more likely to be in NYHA class III and IV, and had a considerably higher logistic EuroSCORE and more comorbid conditions. Adjusted OR depended on the method used to control for confounding and ranged from 0.60 (0.11-3.36) to 7.57 (0.91-63.0). We examined the distribution of propensity scores and found scores to overlap sufficiently only in a narrow range. In patients with sufficient overlap of propensity scores, adjusted OR ranged from 0.35 (0.04-2.72) to 3.17 (0.31 to 31.9). In patients with insufficient overlap, we consistently found increased odds of death associated with TAVI compared with SAVR irrespective of the method used to control confounding, with adjusted OR ranging from 5.88 (0.67-51.8) to 25.7 (0.88-750). Approximately one third of patients undergoing TAVI were found to be potentially eligible for a randomised comparison of TAVI versus SAVR. Conclusions: Both measured and unmeasured confounding limit the conclusions that can be drawn from observational comparisons of TAVI versus SAVR. Our study indicates that TAVI could be associated with either substantial benefits or harms. Randomised comparisons of TAVI versus SAVR are warranted

Mutations in 2 distinct genetic pathways result in cerebral cavernous malformations in mice

Cerebral cavernous malformations (CCMs) are a common type of vascular malformation in the brain that are a major cause of hemorrhagic stroke. This condition has been independently linked to 3 separate genes: Krev1 interaction trapped (KRIT1), Cerebral cavernous malformation 2 (CCM2), and Programmed cell death 10 (PDCD10). Despite the commonality in disease pathology caused by mutations in these 3 genes, we found that the loss of Pdcd10 results in significantly different developmental, cell biological, and signaling phenotypes from those seen in the absence of Ccm2 and Krit1. PDCD10 bound to germinal center kinase III (GCKIII) family members, a subset of serine-threonine kinases, and facilitated lumen formation by endothelial cells both in vivo and in vitro. These findings suggest that CCM may be a common tissue manifestation of distinct mechanistic pathways. Nevertheless, loss of heterozygosity (LOH) for either Pdcd10 or Ccm2 resulted in CCMs in mice. The murine phenotype induced by loss of either protein reproduced all of the key clinical features observed in human patients with CCM, as determined by direct comparison with genotype-specific human surgical specimens. These results suggest that CCM may be more effectively treated by directing therapies based on the underlying genetic mutation rather than treating the condition as a single clinical entity