Effects of interactions between ApoE polymorphisms,alcohol consumption and obesity on age-related trends of blood pressure levels in postmenopausal women: The Bambuì cohort study of aging (1997–2008)

Objectives

To evaluate the effects of interactions between ApoE genotypes, alcohol consumption and obesity on the age-related trends of blood pressure (BP) levels in postmenopausal women.

Study design

A population-based prospective cohort study of all residents in Bambuì, south-eastern Brazil, aged 60 years or older. Repeated BP measurements were obtained in four waves from 851 women who underwent ApoE genotyping at baseline (88.3% of those enrolled), and multi-level random-effects pattern-mixture models were used to evaluate the age-related BP trajectories, while accounting for non-ignorable dropouts/deaths and handling heterogeneities as random parameter variations. The few measurements (2.1%) made during hormone replacement therapy were excluded from the analysis.

Results

Alcohol consumption was associated with high levels of systolic and diastolic BP in an age × genotype-dependent manner only in the non-obese women (BMI < 27 kg/m²). Among those with the ?3/3 genotype, the differences in systolic and diastolic levels between drinkers and non-drinkers estimated at the age of 60 years were respectively 13.7 mmHg (p = 0.022) and 10.7 mmHg (p = 0.002), and disappeared in the older age groups, in which drinking was associated with systolic/diastolic hypertension if the non-obese women were ?4 carriers.

Conclusion

In non-obese postmenopausal women, alcohol consumption is associated with systolic and diastolic hypertension early in those with the ?3/3 ApoE genotype, and late in ?4 carriers. We hypothesize the mediation of androgen hormones and the influence of ApoE genotypes on age at natural menopause. A better understanding of these mechanisms may guide better preventive choices.     

Different diabetogenic response to moderate doses of streptozotocin in pregnant rats, and its long-term consequences in the offspring

Diabetes during pregnancy results in congenital malformations and long-term postnatal diseases. Experimental models are still needed to investigate the mechanism responsible for these alterations. Thus, by the administration of different doses of streptozotocin (STZ) (0, 25, 30, or 35 mg/kg body weight, intravenous) at the onset of pregnancy in rats, the present study sought an appropriate animal model for this pathology. At day 6 of pregnancy, plasma glucose was progressively higher with an increasing STZ dose, and in rats receiving the 35-mg dose, 2 subgroups were detected: some animals had plasma glucose levels above controls but below 200 mg/dL (mildly diabetic, MD), whereas others had levels above 400 mg/dL (severely diabetic, SD). At day 20 of pregnancy, the MD rats had normal glycemia, but after an oral glucose load (2 g/kg body weight), plasma glucose increased more and insulin increased less than in controls. The SD rats maintained their hyperglycemia and had a greatly impaired oral glucose tolerance. At day 20, fetuses of SD dams were fewer, weighed less, and had enhanced plasma glucose and triglycerides and decreased insulin, whereas those from MD dams did not differ from controls. At birth, newborns from MD dams had higher body weight, plasma insulin, and liver triglycerides as well as total body lipid concentrations than controls, and on day 21, remained macrosomic and showed higher plasma glucose and liver triglyceride concentrations. At 70 days of age, offspring of MD dams had impaired oral glucose tolerance but normal plasma insulin change in the case of females, whereas plasma insulin increased less in males. These alterations were manifest more in those offspring from dams that had >50% macrosomic newborns than in those from dams that had <50% macrosomic newborns. In conclusion, whereas our MD rats mimic the changes taking place in gestational diabetic women and show the long-term risk of macrosomia, the SD rats are more similar to uncontrolled diabetics. Thus these two rat models, obtained with moderate amounts of STZ, could be used to study the pathophysiological consequences of these different diabetic conditions.     

Assessment of Platelet REACtivity After Transcatheter Aortic Valve Replacement: The REAC-TAVI Trial

Objectives

The REAC-TAVI (Assessment of platelet REACtivity after Transcatheter Aortic Valve Implantation) trial enrolled patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) pre-treated with aspirin + clopidogrel, aimed to compare the efficacy of clopidogrel and ticagrelor in suppressing high platelet reactivity (HPR) after TAVI.