Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

     

Physical activity combined with massage improves bone mineralization in premature infants: a randomized trial.

BACKGROUND: Osteopenia of prematurity is a known source for morbidity in preterm infants. Premature infants have shown favorable outcomes in response to massage and physical activity. Whether such intervention can stimulate bone formation or decrease bone resorption is yet to be determined. OBJECTIVE: To test the hypothesis that massage combined with physical activity can stimulate bone formation and ameliorate bone resorption in premature infants. DESIGN/METHODS: A prospective double-blinded randomized trial was conducted at the Neonatal Intensive Care Unit of Ain Shams University in Cairo, Egypt. Thirty preterm infants (28 to 35 weeks' gestation) were randomly assigned to either control group (Group I, n=15) or intervention group (Group II, n=15). Infants in the intervention group received a daily protocol of combined massage and physical activity. Serum type I collagen C-terminal propeptide (PICP) and urinary pyridinoline crosslinks of collagen (Pyd) were used as indices for bone formation and resorption, respectively. PICP and Pyd were measured at enrollment and at discharge for all subjects. t-Test, ANOVA and linear regression analysis were used for statistical analyses. RESULTS: There was no difference between groups I and II in gestational age (32.1+/-1.8 vs 31.5+/-1.4 weeks) or birth weight (1.429+/-0.148 vs 1.467+/-0.132 g). In the control group, serum PICP decreased over time from 82.3+/-8.5 to 68.78+/-14.6 (p<0.01), while urinary Pyd increased from 447.7+/-282.8 to 744.9+/-373.6 (p<0.01) indicating decreased bone formation and increased bone resorption, respectively. In the intervention group, serum PICP increased over time from 62.5+/-13.8 to 73.84+/-12.9 (p<0.01). Urinary Pyd also increased over time from 445.7+/-266.5 to 716.8+/-301.8 (p<0.01). In a linear regression model including gestational age and intervention, serum PICP increased significantly in the intervention group (regression coefficient 18.8+/-4.6, p=0.0001) while urinary Pyd did not differ between groups (regression coefficient=5.6+/-114.3, p=0.961). CONCLUSIONS: A combined massage and physical activity protocol improved bone formation (PICP) but did not affect bone resorption (Pyd). Pyd increased over time in both groups, possibly due to continuous bone resorption and Ca mobilization.     

Activation of central GABAB receptors offsets the cyclosporine counteraction of endotoxic cardiovascular outcomes in conscious rats

We have previously shown that cyclosporine (CSA) counteracts cardiovascular manifestations induced by endotoxemia (lipopolysaccharide, LPS) such as hypotension and cardiac autonomic dysfunction in conscious rats. In this study, we investigated whether the facilitation of central γ‐amino butyric acid (GABA) neurotransmission blunts these favorable influences of CSA. The LPS‐CSA interaction was determined in the absence and presence of drugs that activate GABA_A or GABA_B receptors or elevate synaptic GABA levels in the central nervous system. The consequent i.v. administration of CSA (10 mg/kg) blunted the LPS‐evoked hypotension, tachycardia, and reductions in time‐ and frequency‐domain indices of heart rate variability (measures of cardiac autonomic control) evoked by LPS (10 mg/kg i.v.). The ability of CSA to reverse the LPS effects disappeared in rats treated intracisternally (i.c.) with baclofen (selective GABA_B agonist, 2 μg/rat) but not muscimol (selective GABA_A agonist, 1 μg/rat), indicating a preferential compromising action for central GABA_B receptors on the advantageous effects of CSA. Moreover, the improvement by CSA of LPS‐evoked cardiovascular derangements was also eliminated after concurrent i.c. administration of vigabatrin (GABA transaminase inhibitor, 200 μg/rat) or tiagabine (GABA reuptake inhibitor, 100 μg/rat). These results demonstrate that the activation of central GABA_B receptors either directly via baclofen or indirectly following interventions that boost GABA levels in central synapses counterbalances the rectifying action of CSA on endotoxemia.     

Characteristics of Women Lost to Follow-Up in Cardiovascular Community Health Interventions: Findings from the Sister to Sister Campaign

Community-based interventions (CBI) have been targeted as a potential means of tackling cardiovascular disease in women. However, there have been mixed results in terms of their impact on health, with at least some of this being attributed to high attrition rates. This study explores factors that may be contributing to the low retention of women in cardiovascular CBIs. In 2009, Sister to Sister, a national organization that sponsors community health fairs, provided free cardiovascular health screenings for a total of 9,443 women nationwide. All participants were invited to enroll in a 1 year, survey-based observational study to assess the effectiveness of these community health screenings. Of these 9,443 women, 5.9 % actively participated in the follow-up study. Participants were more likely to have health insurance (75.5 vs. 65.3 %, p < 0.001), have an annual income above 75,000 dollars (26.7 vs. 19.7 %, p < 0.001), and identify themselves as white (50.0 vs. 31.5 %, p < 0.001). They were also more likely to have hypertension (32.1 vs. 27.4 %, p = 0.018) and metabolic syndrome (35.7 vs. 20.4 %, p < 0.001). Our results suggest that white, affluent women with health insurance and cardiovascular risk factors are more likely to engage in CBIs that require longitudinal assessment. This study gives insight into the demographics, socioeconomic status, and cardiovascular comorbidities of women who participate in cardiovascular CBIs. The results may prove to be useful in understanding the biopsychosocial barriers to participation in CBIs in order to develop more effective interventions in the future.