When the At-Risk Do Not Develop Heart Failure: Understanding Positive Deviance Among Postmenopausal African American and Hispanic Women

BackgroundAfrican American and Hispanic postmenopausal women have the highest risk for heart failure compared with other races, but heart failure prevalence is lower than expected in some national cohorts. It is unknown whether psychosocial factors are associated with lower risk of incident heart failure hospitalization among high-risk postmenopausal minority women.Methods and ResultsUsing the Women's Health Initiative Study, African American and US Hispanic women were classified as high-risk for incident heart failure hospitalization with 1 or more traditional heart failure risk factors and the highest tertile heart failure genetic risk scores. Positive psychosocial factors (optimism, social support, religion) and negative psychosocial factors (living alone, social strain, depressive symptoms) were measured using validated survey instruments at baseline. Adjusted subdistribution hazard ratios of developing heart failure hospitalization were determined with death as a competing risk. Positive deviance indicated not developing incident heart failure hospitalization with 1 or more risk factors and the highest tertile for genetic risk. Among 7986 African American women (mean follow-up of 16 years), 27.0% demonstrated positive deviance. Among high-risk African American women, optimism was associated with modestly reduced risk of heart failure hospitalization (subdistribution hazard ratio 0.94, 95% confidence interval 0.91–0.99), and social strain was associated with modestly increased risk of heart failure hospitalization (subdistribution hazard ratio 1.07, 95% confidence interval 1.02–1.12) in the initial models; however, no psychosocial factors were associated with heart failure hospitalization in fully adjusted analyses. Among 3341 Hispanic women, 25.1% demonstrated positive deviance. Among high-risk Hispanic women, living alone was associated with increased risk of heart failure hospitalization (subdistribution hazard ratio 1.97, 95% confidence interval 1.06–3.63) in unadjusted analyses; however, no psychosocial factors were associated with heart failure hospitalization in fully adjusted analyses.ConclusionsAmong postmenopausal African American and Hispanic women, a significant proportion remained free from heart failure hospitalization despite having the highest genetic risk profile and 1 or more traditional risk factors. No observed psychosocial factors were associated with incident heart failure hospitalization in high-risk African Americans and Hispanics. Additional investigation is needed to understand protective factors among high-risk African American and Hispanic women.     

Continuous subcutaneous insulin infusion: A long-term study

Summary The authors report data obtained from a 3-year study of CSII and humanized insulin (semi-synthetic human insulin) administered to 18 insulin-dependent subjects in the outpatient clinic. The aim of this study was to evaluate the validity of insulin pumps in long-term treatment. Metabolic parameters were significantly improved (p<0.001) in the first month and remained so with only slight alterations throughout treatment. The authors underline some metabolic problems (ketosis) caused by malfunctioning of the insulin pumps, by the difficulties with the infusion sytem or by nodular skin lesions at the infusion site. Only these lesions called for treatment to be discontinued in 4 patients. The highest incidence of nodular skin lesions was seen after one year’s uninterrupted treatment and they seem connected to the duration of treatment rather than to the patients’ negligence (inadequate hygiene, delayed needle substitution). The authors conclude that CSII treatment is valid over short-term periods, whereas it presents drawbacks over long-term administration.     

Carotid artery stenting in the presence of contralateral carotid occlusion: mind the hyperperfusion syndrome!

Stroke is the third cause of death in western countries and its complications lead to significant socio-economic problems related to the prolonged hospitalization and rehabilitation of patients with neurological lesions. Severe atherosclerotic lesions of the carotid artery are the main cause of stroke and transient ischemic attacks. Their incidence may reach 5-7% per year in patients with carotid artery stenosis > 70% with or without symptoms. Time-honored carotid endarterectomy is still regarded as the gold standard therapy for primary and secondary prevention of stroke. However, surgery is not free of complications and the rate of perioperative stroke ranges from 5.1 to 14.3%. A group of patients at a particularly high risk of stroke during surgical endarterectomy is represented by patients with significant carotid stenosis in the presence of an occluded contralateral artery. Indeed, carotid cross-clamping during operative surgery in the absence of an adequate collateral flow may result in a critical flow reduction during the operation and therefore increases the risk of periprocedural strokes. In the North American Symptomatic Carotid Endarterectomy (NASCET) trial, the overall risk of stroke was 5.1%, whereas it increased up to 14.3% in patients with an occluded contralateral carotid artery. Recently, carotid stenting has been increasingly used as an endovascular technique for carotid revascularization, especially after the introduction of neuroprotection devices which improved the safety of the procedure. Therefore, it may be an attractive alternative to carotid endarterectomy, especially when the surgical risk is too high. We describe the immediate and late outcomes of 3 patients treated with carotid artery stenting in the presence of contralateral carotid occlusion.     

Neuroendocrine response to the serotonin agonist M-chlorophenylpiperazine in women with menstrual status migrainosus

To assess the neuroendocrine correlates of menstrual status migrainosus (MSM) and menstrual migraine (MM), we evaluated the prolactin (PRL) and cortisol responses to the direct central serotoninergic (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) administered orally (0.5 mg/kg) during the follicular (FP: +6, +8) and luteal phases (LP: -4, -6) of the same menstrual cycle. Ten women with MSM (migraine attacks occurring within 2 days of the onset of menstrual bleeding but lasting more than 72 h) and 9 women with MM (migraine occurring within 2 days of the onset of menstrual bleeding with a typical duration of attacks) were studied. Six healthy women served as controls. Blood samples were taken at times -30, 0 and every 30 min over 4 h. Statistical analysis was performed using MANOVA followed by Duncan's post hoc comparisons. We found that the PRL response to the m-CPP test was significantly blunted in MSM compared with MM and controls in both phases of the menstrual cycle (F = 4.6; p < 0.001). Indeed, the PRL area under the curve (AUC) after m-CPP was higher in both MM and controls compared with MSM (F = 12.7; p < 0.001). The m-CPP-induced cortisol response was absent in MSM compared with MM and controls in both FP and LP (F = 4.1; p < 0.001). On the other hand, the pattern of the plasma cortisol response to m-CPP was similar in MM and controls throughout the menstrual cycle. In addition, the basal plasma cortisol levels were significantly higher in MSM compared with controls (p < 0.001) and MM (p < 0.001) during FP, but not in LP, and progressively decreased over time. Thus, no significant effect of the menstrual cycle phase and diagnosis on the cortisol AUC was found, while a significant diagnosis effect (F = 25.6; p < 0.001) on %delta(max) plasma cortisol levels was evident and consistent with the lack of cortisol response to m-CPP in MSM during the FP and LP compared with MM and controls. A derangement in central 5-HT control of pituitary PRL, and even more so in cortisol release, is present in women with MSM, but not with MM, regardless of the phase of the menstrual cycle, suggesting the involvement of some 5-HT(1) and 5-HT(2) receptor subtypes in the occurrence of extremely severe migraine attacks triggered by menstruation.     

Cerebral vein thrombosis in patients with Philadelphia‐negative myeloproliferative neoplasms An European Leukemia Net study

To investigate the characteristics and clinical course of cerebral vein thrombosis (CVT) in patients with myeloproliferative neoplasms (MPN) we compared 48 patients with MPN and CVT (group MPN‐CVT) to 87 with MPN and other venous thrombosis (group MPN‐VT) and 178 with MPN and no thrombosis (group MPN‐NoT) matched by sex, age at diagnosis of MPN (±5 years) and type of MPN. The study population was identified among 5,500 patients with MPN, from January 1982 to June 2013. Thrombophilia abnormalities were significantly more prevalent in the MPN‐CVT and MPN‐VT than in MPN‐NoT group (P = 0.015), as well as the JAK2 V617F mutation in patients with essential thrombocythemia (P = 0.059). Compared to MPN‐VT, MPN‐CVT patients had a higher rate of recurrent thrombosis (42% vs. 25%, P = 0.049) despite a shorter median follow‐up period (6.1 vs. 10.3 years, P = 0.019), a higher long‐term antithrombotic (94% vs. 84%, P = 0.099) and a similar cytoreductive treatment (79% vs. 70%, P = 0.311). The incidence of recurrent thrombosis was double in MPN‐CVT than in MPN‐VT group (8.8% and 4.2% patient‐years, P = 0.022), and CVT and unprovoked event were the only predictive variables in a multivariate model including also sex, blood count, thrombophilia, cytoreductive, and antithrombotic treatment (HR 1.97, 95%CI 1.05–3.72 and 2.09, 1.09–4.00, respectively). Am. J. Hematol. 89:E200–E205, 2014. © 2014 Wiley Periodicals, Inc.     

Second cancers in MPN: Survival analysis from an international study

One out of ten patients with Philadelphia-negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of MPN-specific therapies. Data were therefore extracted from an international nested case-control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person-years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1-6.9) deaths for every 100 PYs. A “poor prognosis” SC (stomach, esophagus, liver, pancreas, lung, ovary, head-and-neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the cause of death in 65% of them (MR 11.0/100 PYs). In contrast, patients with a “non-poor prognosis” SC (NPPSC) incurred a MR of 4.6/100 PYs: 31% of the deaths were attributed to SC and 15% to MPN evolution. At multivariable analysis, death after SC diagnosis was independently predicted (HR and 95% CI) by patient age greater than 70 years (2.68; 1.88-3.81), the SC prognostic group (2.57; 1.86-3.55), SC relapse (1.53; 10.6-2.21), MPN evolution (2.72; 1.84-4.02), anemia at SC diagnosis (2.32; 1.49-3.59), exposure to hydroxyurea (1.89; 1.26-2.85) and to ruxolitinib (3.63; 1.97-6.71). Aspirin was protective for patients with a NPPSC (0.60; 0.38-0.95). In conclusion, SC is a relevant cause of death competing with MPN evolution. Prospective data are awaited to confirm the role of cytoreductive and anti-platelet drugs in modulating patient survival after the occurrence of a SC.     

Timing of clamping and factors associated with iron stores in full-term newborns

OBJECTIVE

To analyze the impact of timing of clamping and obstetric, biological and socioeconomic factors on the iron stores of full-term newborns.

METHODS

Cross-sectional study between October 2011 and July 2012 in which hematological parameters were evaluated for newborns in Viçosa, MG, Southeastern Brazil. It involved collecting 7 mL of umbilical cord blood from 144 full-term not underweight newborns. The parameters investigated were complete blood count, serum iron, ferritin and C-reactive protein. The time of umbilical cord clamping was measured using a digital timer without interfering in the procedures of childbirth. The birth data were collected from Live Birth Certificates and other information was obtained from the mother through a questionnaire applied in the first month postpartum. Analysis of multiple linear regression was then used to estimate the influence of biological, obstetrics and socioeconomic factors on the ferritin levels at birth.

RESULTS

The median ferritin was 130.3 µg/L (n = 129, minimum = 16.4; maximum = 420.5 µg/L), the mean serum iron was 137.9 μg/dL (n = 144, SD = 39.29) and mean hemoglobin was 14.7 g/dL (n = 144, SD = 1.47). The median time of cord clamping was 36 seconds, ranging between 7 and 100. The bivariate analysis detected an association between ferritin levels and color of the child, timing clamping of 60 seconds, type of delivery, the presence of gestational diabetes and per capita family income. In multivariate analysis, the variables per capita income, number of antenatal visits and length at birth accounted for 22.0% of variation in ferritin levels.

CONCLUSIONS

Iron stores at birth were influenced by biological, obstetric and social characteristics. Tackling anemia should involve creating policies aimed at reducing social inequalities, improving the quality of antenatal care, as well as implementing a criterion of delayed clamping of the umbilical cord within the guidelines of labor.