Gender Specificities in Risk Stratification After Myocardial Infarction

Objective: Although gender specificities of various risk factors have been well documented, risk stratification after myocardial infarction has never been compared in women and men. Methods: The power of left ventricular ejection fraction, heart rate variability, and mean RR interval computed from 24-hour Holter recordings, was compared in women and men for the prediction of cardiac mortality after an acute myocardial infarction. The study population consisted of 456 patients (108 women, 348 men) aged 50–75 years. Results: During a follow-up of 3 years, there were 41 cardiac deaths (13 women vs 28 men, P = NS). The positive predictive accuracy of left ventricular ejection fraction, heart rate variability, and mean RR interval at all sensitivity levels was higher in women than in men. For a 40% sensitivity, positive predictive accuracy of left ventricular ejection fraction was 46% in women and 16% in men (P < 0.05), positive predictive accuracy of mean RR interval was 90% in women and 28% in men (P < 0.05), and positive predictive accuracy of heart rate variability was 61% in women and 43% in men (P = NS). Mean RR interval had the highest positive predictive accuracy for cardiac mortality in women, but its superiority over heart rate variability was not statistically significant. In men, heart rate variability was the strongest predictor of mortality that was significantly more powerful than mean RR interval and left ventricular ejection fraction (P < 0.05). Conclusion: Increased 24-hour mean heart rate is the strongest predictor of cardiac mortality in women in whom it performs significantly better than in men. While in men, heart rate variability is a significantly better predictor of postinfarction cardiac mortality than 24-hour mean heart rate, this is not the case in women.     

Changes in myocardial electrical impedance in human heart graft rejection

BACKGROUND: Monitoring of post-transplant heart rejection is currently based on endomyocardial biopsy analysis. This study aimed to assess the effects of heart graft rejection on myocardial electrical impedance. METHODS AND RESULTS: Twenty-nine cardiac transplant patients and 9 controls underwent measurement of myocardial electrical impedance using a specifically designed amplifying system. The module and phase angle of myocardial impedance were measured. Histopathological rejection grading was performed according to ISHLT classification. Fifty impedance tests were performed in transplanted patients. Myocardial impedance (Z) was higher in controls than in transplanted patients (p<0.001) and followed a progressive decline at increasing current frequencies (p<0.001). Likewise, the phase angle of impedance in controls ranged from positive values at low frequencies to negative values at higher frequencies (from 2.5+/-0.9 degrees at 10 kHz to -3.8+/-2.1 degrees at 300 kHz, p<0.001). Rejection was associated with a significant decrease in myocardial impedance (Z) (15+/-6.6 Omega in grade 0, 13+/-6.0 Omega in grade 1A, and 3.3+/-0.9 Omega in grade 3A at 10 kHz, p<0.003). CONCLUSIONS: Mild degrees of cardiac graft rejection are associated with significant changes in myocardial electrical impedance in transplant patients. Further clinical investigation is warranted to assess the potential of cardiac impedance to detect heart graft rejection.     

Urokinase-type plasminogen activator regulates neurodegeneration and neurogenesis but not vascular changes in the mouse hippocampus after status epilepticus

Expression of urokinase-type plasminogen activator (uPA) is increased after brain injury, suggesting that, like in cancer tissue, uPA plays roles in brain remodeling. Here we injured brain with intrahippocampal kainic acid (KA) injection in adult Wt and uPA?/? mice. At 20 days post-injury, uPA?/? mice had more severe loss of contralateral pyramidal (p < 0.05) and hilar neurons (p < 0.05) than Wt mice. The number of doublecortin (DCX)-positive newly born neurons was also reduced in uPA?/? mice as compared to Wt (p < 0.01). No difference was observed in granule cell dispersion or distribution of DCX-positive neurons in the dentate gyrus. uPA deficiency did not affect the total length of hippocampal blood vessels or vessel density. No differences were observed in the severity of status epilepticus or consequent epilepsy between the genotypes. These data indicate that uPA deficiency can unfavorably modulate both delayed neurodegeneration and neurogenesis but has little effect on post-injury neuronal migration and vascular density. Our results favor the idea that elevated uPA during the post-injury phase is neuroprotective.     

Analysis of Three Functional Polymorphisms in Relation to Osteoporosis Phenotypes: Replication in a Spanish Cohort

Osteoporosis is a complex disease involving many putative genetic factors. Association analysis of functional SNPs in candidate genes is an important tool for their identification. However, this approach is affected by limited power, population stratification, and other drawbacks that lead to discordant results. Replication in independent cohorts is essential. We performed association analyses of three functional polymorphisms previously associated with bone phenotypes—namely, Ala222Val in MTHFR, Ile1062Val in LRP6, and −13910C>T in LCT—in a cohort of 944 postmenopausal Spanish women, all of them with lumbar spine (LS) bone mineral density (BMD) data and most with femoral neck (FN) BMD and fracture data. We found significant differences between genotypes only for the MTHFR polymorphism and vertebral factures, with an OR of 2.27 (95% CI 1.17–4.38) for the TT vs. CC/CT genotypes, P = 0.018. We present genotype and allele frequency data for LCT −13910C>T for a Spanish population, where the T allele (conferring lactase persistence) has a frequency of 38.6%. Genotype frequencies were consistent with observed clines in Europe and with the prevalence of lactase nonpersistence. The LCT −13910C>T polymorphism was significantly associated with height and weight, such that T allele carriers were 0.88 cm taller (95% CI 0.08–1.59 cm, P = 0.032, adjusted by age) than CC individuals and TT homozygotes were 1.91 kg heavier than CC/CT individuals (95% CI 0.11–3.71 kg, P = 0.038, adjusted by age). In conclusion, no significant association was observed between the studied polymorphisms and LS BMD or FN BMD in postmenopausal Spanish women, and only MTHFR Ala222Val was associated with vertebral fractures.     

Early Fluid Resuscitation

Solid evidence exists that fluid therapy must be started as a first-line treatment in all patients with septic shock as soon as hypotension is detected, with the goal of rapidly restoring tissue perfusion. Crystalloids or colloids can be used for initial fluid therapy, and albumin should be reserved for patients with patent or supposed hypoalbuminemia. Once fluid administration is started, its effect must be carefully monitored. In the early stages, appropriate monitoring should ensure that fluid resuscitation actually increases cardiac preload, mean arterial pressure, and tissue oxygenation. In later stages, monitoring should help to avoid fluid overload. For this purpose, the end-point of fluid therapy should not be the static values of preload indicators, but rather the disappearance of indicators of preload responsiveness. Finally, the risk of fluid overload must always be kept in mind, especially in case of lung injury.