Comparison of DNA methylation profiles from saliva in Coeliac disease and non-coeliac disease individuals

Coeliac disease (CD) is a autoimmune disease characterised by mucosal inflammation in the small intestine in response to dietary gluten. Genetic factors play a key role with CD individuals carrying either the HLADQ2 or HLA-DQ8 haplotype, however these haplotypes are present in half the general population making them necessary but insufficient to cause CD. Epigenetic modifications, including DNA methylation that can change in response to environmental exposure could help to explain how interactions between genes and environmental factors combine to trigger disease development. Identifying changes in DNA methylation profiles in individuals with CD could help discover novel genomic regions involved in the onset and development of CD

Menopausal hormone therapy is associated with having high blood pressure in postmenopausal women : observational cohort study

Background: The relationship between menopausal hormone therapy (MHT) and cardiovascular risk remains controversial, with a number of studies advocating the use of MHT in reducing risk of cardiovascular diseases, while others have shown it to increase risk. The aim of this study was to determine the association between menopausal hormone therapy and high blood pressure. Methods and Findings: A total of 43,405 postmenopausal women were included in the study. Baseline data for these women were sourced from the 45 and Up Study, Australia, a large scale study of healthy ageing. These women reported being postmenopausal, having an intact uterus, and had not been diagnosed with high blood pressure prior to menopause. Odds ratios for the association between MHT use and having high blood pressure were estimated using logistic regression, stratified by age (<56 years, 56-61 years, 62-70 years and over 71 years) and adjusted for demographic and lifestyle factors. MHT use was associated with higher odds of having high blood pressure: past menopausal hormone therapy use: <56 years (adjusted odds ratio 1.59, 99% confidence interval 1.15 to 2.20); 56-61 years (1.58, 1.31 to 1.90); 62-70 years (1.26, 1.10 to 1.44). Increased duration of hormone use was associated with higher odds of having high blood pressure, with the effect of hormone therapy use diminishing with increasing age. Conclusions: Menopausal hormone therapy use is associated with significantly higher odds of having high blood pressure, and the odds increase with increased duration of use. High blood pressure should be conveyed as a health risk for people considering MHT use

Magnetic resonance imaging detects placental hypoxia and acidosis in mouse models of perturbed pregnancies

Endothelial dysfunction as a result of dysregulation of anti-angiogenic molecules secreted by the placenta leads to the maternal hypertensive response characteristic of the pregnancy complication of preeclampsia. Structural abnormalities in the placenta have been proposed to result in altered placental perfusion, placental oxidative stress, cellular damage and inflammation and the release of anti-angiogenic compounds into the maternal circulation. The exact link between these factors is unclear. Here we show, using Magnetic Resonance Imaging as a tool to examine placental changes in mouse models of perturbed pregnancies, that T2 contrast between distinct regions of the placenta is abolished at complete loss of blood flow. Alterations in T2 (spin-spin or transverse) relaxation times are explained as a consequence of hypoxia and acidosis within the tissue. Similar changes are observed in perturbed pregnancies, indicating that acidosis as well as hypoxia may be a feature of pregnancy complications such as preeclampsia and may play a prominent role in the signalling pathways that lead to the increased secretion of anti-angiogenic compounds

Genetic discoveries in hypertension : steps on the road to therapeutic translation

Genes and environmental factors contribute to an individual's risk of hypertension. Recent advances in DNA sequencing technology have enabled the discovery of new causative genes in inherited forms of hypertension, identifying novel pathways for blood pressure control. Meta-analyses of genome-wide association studies have also identified regions of the genome that are significantly associated with blood pressure control, and these regions may be involved in an individual's response to antihypertensive medication. This article reviews the latest gene discoveries in inherited forms of hypertension, recent meta-analyses of genome-wide association studies, genetic determinants of antihypertensive therapy response, and development of genetic risk scores

Past oral contraceptive use and self-reported high blood pressure in postmenopausal women

Background: Studies have reported current hormonal contraceptive use is associated with adverse cardiovascular outcomes, including high blood pressure. The aim of this study was to determine the association between past hormonal contraception use and high blood pressure in Australian postmenopausal women. Methods: Women were recruited from the 45 and Up Study, an observational cross-sectional study, conducted from February 2006 to December 2009, NSW Australia. All of the variables used in this study were derived from self-reported data. These women reported being postmenopausal, having an intact uterus, and had given birth to one or more children. Odds ratios and 99% confidence intervals for the association between past hormonal contraceptive use and current treatment for high blood pressure, stratified by current age (<58 yrs, 58–66 yrs, and ≥67 yrs) were estimated using logistic regression, adjusted for income, country of origin, BMI, smoking, alcohol, exercise, family history of high blood pressure, menopausal hormone therapy use, number of children, whether they breastfed, and age of menopause. Results: A total of 34,289 women were included in the study. No association between past hormonal contraception use and odds of having high blood pressure were seen in any of the age groups (<58 yrs: odds ratio (OR) 1.1, 99% confidence interval (CI) 0.8 to 1.5, p = 0.36; 58–66 yrs: OR 0.9, 99% CI 0.7 to 1.1, p = 0.11; and ≥67 yrs: OR 0.9, 99% CI 0.8 to 1.0. p = 0.06). In women with a history of hormonal contraception use, no association between duration of hormonal contraception use and high blood pressure was observed. Conclusions: Past hormonal contraception use and duration of use is not associated with high blood pressure in postmenopausal women

Menopausal hormone therapy : examining cardiovascular and clinical impacts of treatment

Postmenopausal women have reduced levels of female sex hormones and this may play a significant role in the onset of cardiovascular disease. Menopausal hormone therapy (MHT), which is primarily prescribed for the treatment of perimenopausal symptoms, has been associated with risk of coronary heart disease, hypertension and stroke in women. This review will summarize the outcomes of observational studies and randomized clinical trials that have investigated the influence of MHT use on the cardiovascular system. In addition, it will explore how the timing of MHT prescription relative to menopause, dosage and route of administration may alter the impact of MHT on cardiovascular health

Psychosocial impact of specialized cardiac genetic clinics for hypertrophic cardiomyopathy

PURPOSE: The diagnosis of hypertrophic cardiomyopathy, an autosomal dominant chronic heart disease, can have significant implications, including increased risk of sudden death, exercise limitations, and risk of transmission to offspring. This study sought to describe the psychosocial factors associated with attending a specialty cardiac genetic clinic, and to determine whether these may be predictors of comorbid anxiety and depression in this population. METHODS: Questionnaires were sent to 184 individuals attending the Royal Prince Alfred Hospital Hypertrophic Cardiomyopathy Clinic. Questionnaires were anonymous and comprised demographics, the Hospital Anxiety and Depression Scale, Patient Experience Scales, and Patient Satisfaction Scales. RESULTS: Completed questionnaires were returned by 109 participants (59.2% response rate), of which 76.9% had a diagnosis of hypertrophic cardiomyopathy, while 23.1% were at-risk relatives attending for clinical screening. Patient satisfaction scores were generally high to very high across all groups, though only 24% of HCM patients showed good adjustment to hypertrophic cardiomyopathy and 10% had low worry about hypertrophic cardiomyopathy scores. Within the disease group, logistic regression analysis adjusting for age, gender, and education revealed adjustment to hypertrophic cardiomyopathy and worry about hypertrophic cardiomyopathy scores to be significantly associated with anxiety, while adjustment scores and location of patient follow-up (i.e., Hypertrophic Cardiomyopathy clinic or another cardiologist) to be significantly associated with depression scores. CONCLUSION: HCM patients who attend specialized cardiac genetic clinics are better adjusted and worry less, than those who do not attend. An integrated approach, including a genetic counselor, is important in the management of HCM families

Cardiovascular disease in women : the significance of hypertension and gestational diabetes during pregnancy

Purpose of review: Cardiovascular disease (CVD) remains the major killer of women around the globe. Complications during pregnancy, including hypertensive disorders of pregnancy and gestational diabetes mellitus, are now recognized as risk factors for future CVD. Recent findings: Studies of diverse populations demonstrate the links between these complications of pregnancy and a woman's future risk of CVD including atherosclerosis, hypertension, stroke, coronary artery disease, and heart failure. Markers that persist in these women following pregnancy continue to be identified and include microalbuminuria, proteinuria, elevated homocysteine levels, C-reactive protein, and salt sensitivity. Efforts are now being placed on establishing specialized clinics to monitor women beyond pregnancy to help reduce the burden of future disease. Summary: Pregnancy offers a unique window through which women at risk of future CVD may be identified. Clinicians have an opportunity to implement health monitoring, lifestyle modifications, and other interventions during this period, and beyond, that will help reduce the burden of CVD. Research should continue to focus on identifying and understanding the mechanisms that lead to future CVD in these women; deciphering whether pregnancy unmasks an existing predisposition to disease, compounds the risk of future disease, or is the direct cause of future disease

Association between a woman's age at first birth and high blood pressure

The aim of this article is to determine whether the age of a woman at first birth is associated with treatment for high blood pressure (HBP) later in life. Baseline data for 62,914 women were sourced from the ‘‘45 and Up Study,’’ an observational cohort study of healthy aging in Australia. These women had given first birth between the ages of 18 and 45 years. Odds ratios and 95% confidence intervals for the association between age that a woman gave first birth and treatment for HBP were estimated using logistic regression. Data were stratified by current age (<60 and ≥60 years) and adjusted for demographic and lifestyle factors. There was a significant association between age at first birth and present day HBP. Older age at first birth was associated with a lower likelihood of HBP in women aged 25 to <35 years and 35 to 45 years at first birth (in women currently<60 years) and 35 to 45 years at first birth (in women currently _60 years of age), compared with women aged 18 to <25 years at first birth, adjusting for demographic and lifestyle factors. Women who were older when they gave first birth had lower odds of treatment for HBP compared with women who were younger when they gave birth to their first child. The contribution of a woman’s pregnancy history, including her age at first birth, should be discussed with a patient when assessing her risk of HBP

Development of a risk score for extraintestinal manifestations of coeliac disease

The aim of this study was to identify indicators of coeliac disease (CD) in an Australian cohort, beyond the known gastrointestinal symptoms. Individuals were recruited from the general population and at the 2014 Gluten Free Expo in Sydney and in Melbourne, Australia. Data on their current health status including medical history, diagnosis for CD, and family history were collected. Multivariable logistic regression was used to identify independent predictors of CD. A weighted risk score system was then generated for the independent predictors, and a risk score was calculated for each individual. A total of 301 individuals were included in the study. We found an association between CD and having a family history of CD (odds ratio [OR] 7.6, 95%confidence interval [CI] 3.7–15.6), an autoimmune disorder (OR 2.1, 95%CI 1.1–4.1), anemia (OR 5.8, 95%CI 2.8–11.9), lactose intolerance (OR 4.5, 95%CI 1.2–17.7), and depression (OR 4.8, 95%CI 1.9–11.6). Risk score analysis found individuals in the medium (OR 4.8, 95%CI 2.5 to 9.3) and high-risk (OR 36.6, 95%CI 16.4 to 81.6) groups were significantly more likely to report having CD compared with those in the low-risk group. This study identifies a set of factors more commonly observed in individuals with CD, beyond the traditional gastrointestinal complaints. These include a family history of CD, the presence of another autoimmune disorder, anemia, lactose intolerance, and depression. A risk score was developed (Coeliac Risk COMPARE) which scores individuals based on the presence or absence of these additional symptoms and provides an additional screening tool when assessing whether the patient requires follow-up testing for CD