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

BACKGROUND: 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 HLA-DQ2 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. METHODS: The Illumina InfiniumMethylation450 Beadchip array (HM450) was used to compare DNA methylation profiles in saliva, in CD and non-CD affected individuals. CD individuals who had been diagnosed at least 2 years previously; were on a GFD; and who were currently asymptomatic; were compared to age and sex-matched non-CD affected healthy controls. Bisulphite pyrosequencing was used to validate regions found to be differentially methylated. These regions were also validated in a second larger cohort of CD and non-CD affected individuals. RESULTS: Methylation differences within the HLA region at HLA-DQB1 were identified on HM450 but could not be confirmed with pyrosequencing. Significant methylation differences near the SLC17A3 gene were confirmed on pyrosequencing in the initial pilot cohort. Interestingly pyrosequencing sequencing of these same sites within a second cohort of CD and non-CD affected controls produced significant methylation differences in the opposite direction. CONCLUSION: Altered DNA methylation profiles appear to be present in saliva in CD individuals. Further work to confirm whether these differences are truly associated with CD is needed.

Comparing DNA methylation profiles in saliva and intestinal mucosa.

BACKGROUND: Altered epigenetic profiles are a feature of intestinal diseases, including ulcerative colitis and Crohn's disease. DNA methylation studies in these diseases have utilised intestinal mucosal tissue or blood which can be difficult to collect, particularly for large-scale research studies. Saliva is an attractive alternative for epigenetic studies as it is easy to collect and provides high quality methylation profiles. The aim of the study was to determine the utility of saliva as an alternative for DNA methylation studies of intestinal disorders. RESULTS: DNA methylation in saliva and intestinal mucosa samples were compared in individuals (n = 10) undergoing endoscopies using the Illumina Infinium Methylation 450 K Beadchip array. We found that DNA methylation was correlated between tissue types within an individual (Pearson correlation co-efficient r = 0.92 to 0.95, p < 0.001). Of the 48,541 probes (approximately 11% of CpG sites) that were differentially methylated between saliva and intestinal mucosa (adjusted p < 0.001, |Δß| ≥ 20%), these mapped to genes involved in tissue-specific pathways, including the apelin signalling and oxytocin pathways which are important in gastrointestinal cytoprotection and motility. CONCLUSIONS: This study suggests that saliva has the potential to be used as an alternate DNA source to invasive intestinal mucosa for DNA methylation research into intestinal conditions.

Interrogating the Relationship Between Schizotypy, the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism, and Neuronal Oscillatory Activity.

The COMT Val158Met polymorphism affects the availability of synaptic dopamine in the prefrontal cortex and has been widely studied as a genetic risk factor for psychosis. Schizotypy is associated with an increased risk of psychosis, with some studies implicating similar neurobiological mechanisms to schizophrenia. The present study sought to interrogate the link between the COMT Val158Met polymorphism and schizotypy using electroencephalogram (EEG) to identify neurophysiological mechanisms underpinning psychosis risk. Neurotypical (N = 91) adults were genotyped for the COMT Val158Met polymorphism, completed the Schizotypal Personality Questionnaire (SPQ), and had eyes open resting-state EEG recorded for 4 min. SPQ suspiciousness subscale scores were higher for individuals homozygous for Val/Val and Met/Met versus Val/Met genotypes. Delta, theta, alpha-2, beta-1, and beta-2 amplitudes were lower for Val/Val than Met/Met individuals. Lower theta amplitudes were correlated with higher total SPQ scores (P = 0.050), and multiple regression revealed that higher delta, and lower theta and beta-2 amplitudes (but not COMT genotype) best predicted total SPQ scores (P = 0.014). This study demonstrates the importance of COMT genotype in determining trait suspiciousness and EEG oscillatory activity. It also highlights relationships between dopaminergic alterations, EEG and schizotypy that are dissimilar to those observed in schizophrenia.

Increased salt sensitivity in offspring of pregnancies complicated by experimental preeclampsia.

Preeclampsia is a hypertensive disorder of pregnancy known to increase the risk of cardiovascular disease in mothers and offspring. Offspring exposed to a suboptimal intrauterine environment may experience altered fetal programming and subsequent long-term cardiovascular changes. This study investigated changes in the vascular response in offspring from experimental preeclampsia (EPE) induced by uterine artery ligation, in the absence of fetal growth restriction, compared to normal baboon pregnancies (controls), following a high salt diet challenge. After 1 week of standard diet (containing <1% salt), animals were fed a high salt diet (6%) for 2 weeks. Systolic and diastolic blood pressure (SBP, DBP), aldosterone, renin and creatinine clearance were evaluated in EPE (n = 6, 50% male) and control (n = 6, 50% male) offspring. A repeated measures analysis was performed, and P < 0.05 was considered significant. At baseline, there were no differences between the groups in any parameter (EPE, mean age and weight 3.2 ± 1.2 years, 6.8 ± 1.0 kg, respectively; Control, 2.9 ± 0.8 years, 7.1 ± 1.5 kg). After salt loading the EPE group had significantly higher SBP (92 ± 5 mm Hg) compared to the control group (83 ± 4 mm Hg, P = 0.03). Aldosterone concentration was higher in the EPE group despite the same salt excretion and no difference in renal function. Salt sensitivity may differ in offspring from hypertensive pregnancies due to fetal programming. This could have long-term consequences for cardiovascular health of EPE offspring and further research is required to determine the exact pathological mechanisms.

Does Telomere Shortening Precede the Onset of Hypertension in Spontaneously Hypertensive Mice?

Telomere length is widely considered as a marker of biological aging. Clinical studies have reported associations between reduced telomere length and hypertension. The aim of this study was to compare telomere length in hypertensive and normotensive mice at pre-disease and established disease time points to determine whether telomere length differs between the strains before and after the onset of disease. Genomic DNA was extracted from kidney and heart tissues of 4-, 12-, and 20-week-old male hypertensive (BPH/2J) and normotensive (BPN/3J) mice. Relative telomere length (T/S) was measured using quantitative PCR. Age was inversely correlated with telomere length in both strains. In 4-week-old pre-hypertensive animals, no difference in T/S was observed between BPH/2J and BPN/3J animals in kidney or heart tissue (kidney p = 0.14, heart p = 0.06). Once the animals had established disease, at 12 and 20 weeks, BPH/2J mice had significantly shorter telomeres when compared to their age-matched controls in both kidney (12 weeks p < 0.001 and 20 weeks p = 0.004) and heart tissues (12 weeks p < 0.001 and 20 weeks p < 0.001). This is the first study to show that differences in telomere lengths between BPH/2J and BPN/3J mice occur after the development of hypertension and do not cause hypertension in the BPH/2J mice.

A Cross-Sectional Study of Ageing and Cardiovascular Function over the Baboon Lifespan.

BACKGROUND: Ageing is associated with changes at the molecular and cellular level that can alter cardiovascular function and ultimately lead to disease. The baboon is an ideal model for studying ageing due to the similarities in genetic, anatomical, physiological and biochemical characteristics with humans. The aim of this cross-sectional study was to investigate the changes in cardiovascular profile of baboons over the course of their lifespan. METHODS: Data were collected from 109 healthy baboons (Papio hamadryas) at the Australian National Baboon Colony. A linear regression model, adjusting for sex, was used to analyse the association between age and markers of ageing with P < 0.01 considered significant. RESULTS: Male (n = 49, 1.5-28.5 years) and female (n = 60, 1.8-24.6 years) baboons were included in the study. Age was significantly correlated with systolic (R2 = 0.23, P < 0.001) and diastolic blood pressure (R2 = 0.44, P < 0.001), with blood pressure increasing with age. Age was also highly correlated with core augmentation index (R2 = 0.17, P < 0.001) and core pulse pressure (R2 = 0.30, P < 0.001). Creatinine and urea were significantly higher in older animals compared to young animals (P < 0.001 for both). Older animals (>12 years) had significantly shorter telomeres when compared to younger (<3 years) baboons (P = 0.001). CONCLUSION: This study is the first to demonstrate that cardiovascular function alters with age in the baboon. This research identifies similarities within cardiovascular parameters between humans and baboon even though the length of life differs between the two species.

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.

DNA methylation profiles in preeclampsia and healthy control placentas.

Preeclampsia is a hypertensive disorder of pregnancy that affects 3-5% of all pregnancies. There is evidence to suggest that epigenetic mechanisms, such as DNA methylation, play a role in placental development and function. This study compared DNA methylation profiles of placentas from preeclampsia-affected pregnancies with placentas from healthy pregnancies to identify gene-specific changes in DNA methylation that may contribute to the development of preeclampsia. The methylation status of eight placental biopsies taken from preeclampsia-affected and 16 healthy pregnancies was analyzed using the Illumina Infinium Methylation 450 BeadChip array. Bisulfite pyrosequencing was used to confirm regions found to be differentially methylated between preeclampsia and healthy placentas. A total of 303 differentially methylated regions, 214 hypermethylated and 89 hypomethylated, between preeclampsia cases and controls were identified, after adjusting for gestational age (adjusted P < 0.05). Functional annotation found cell adhesion, wingless type MMTV Integration Site family member 2 (Wnt) signaling pathway, and regulation of transcription were significantly enriched in these gene regions. Hypermethylation of WNT2, sperm equatorial segment protein (SPESP1), NADPH oxidase 5 (NOX5), and activated leukocyte cell adhesion molecule (ALCAM) in preeclampsia placentas was confirmed with pyrosequencing. This study found differences in methylation in gene regions involved in cell signaling (WNT2), fertilization and implantation (SPESP1), reactive oxygen species signaling (NOX5), and cell adhesion (ALCAM). These results build on recently published studies that have reported significant differences in DNA methylation in preeclampsia placentas.

Evaluation of an antenatal acupuncture intervention as an adjunct therapy for antenatal depression (AcuAnteDep): study protocol for a pragmatic randomised controlled trial.

BACKGROUND: Depressed pregnant women face difficulty navigating a course between the potentially serious consequences of leaving depression untreated and significant limitations associated with conventional therapies, such as foetal toxicity and teratogenicity. Preliminary evidence is suggestive that acupuncture may provide a safe and effective alternative treatment option for antenatal depression; however, additional research is required. The purpose of this study is to further investigate this treatment possibility, with an additional examination of a potential biomechanistic acupuncture effect. METHODS/DESIGN: In this pragmatic randomised controlled trial, we will compare individually tailored, flexible antenatal depression-oriented acupuncture with equivalent attention progressive muscle relaxation and routine antenatal depression hospital care. Eligible women at 24 weeks of gestation with Edinburgh Postnatal Depression Scale scores of 13 or more will be recruited from 2 antenatal clinics in South Western Sydney, Australia. The recruitment goal of 96 is powered to demonstrate a significant difference in Edinburgh Postnatal Depression Scale score severity between acupuncture and usual care, with intervention groups receiving weekly 1-h treatments for 8 weeks from 24 to 31 weeks of gestation. Mental health and quality-of-life assessments will occur at study commencement, intervention weeks 4 and 8 and 6 weeks post-natally via the collection of completed Edinburgh Postnatal Depression Scale scores, Depression, Stress and Anxiety Scale scores and World Health Organisation Quality of Life Scale scores. Adjustment to mothering will also be evaluated at 6 weeks post-natally using the Being a Mother Scale. A putative biomechanistic effect of acupuncture on the oxytocinergic system will additionally be examined by comparing baseline salivary hormone levels with those measured at intervention weeks 4 and 8, as well as leucocyte oxytocin receptor expression at baseline and intervention week 8. DISCUSSION: Ethical approval was received in February 2015, and recruitment is underway and expected to be completed in July 2016. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000250538, Registered on 19 March 2015.

Neuroprotection of Neuro2a cells and the cytokine suppressive and anti-inflammatory mode of action of resveratrol in activated RAW264.7 macrophages and C8-B4 microglia.

Chronic inflammation is a hallmark of neurodegenerative disease and cytotoxic levels of nitric oxide (NO) and pro-inflammatory cytokines can initiate neuronal death pathways. A range of cellular assays were used to assess the anti-inflammatory and neuroprotective action of resveratrol using murine microglial (C8-B4), macrophage (RAW264.7) and neuronal-like (Neuro2a) cell lines. We examined the release of NO by Griess assay and used a Bioplex array to measure a panel of pro- and anti-inflammatory cytokines and chemokines, in response to the inflammatory stimuli lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Resveratrol was a potent inhibitor of NO and cytokine release in activated macrophages and microglia. The activity of resveratrol increased marginally in potency with longer pre-incubation times in cell culture that was not due to cytotoxicity. Using an NO donor we show that resveratrol can protect Neuro2a cells from cytotoxic concentrations of NO. The protective effect of resveratrol from pro-inflammatory signalling in RAW264.7 cells was confirmed in co-culture experiments leading to increased survival of Neuro2a cells. Together our data are indicative of the potential neuroprotective effect of resveratrol during nitrosative stress and neuroinflammation.

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.

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.

Identification of genes with altered expression in male and female Schlager hypertensive mice.

BACKGROUND: Numerous studies have shown sex differences in the onset and severity of hypertension. Despite these sex-differences the majority of animal studies are carried out in males. This study investigated expression changes in both male and female hypertensive mouse kidneys to identify common mechanisms that may be involved in the development of hypertension. METHODS: The Schlager hypertensive mouse model (BPH/2J) and its normotensive control (BPN/3J) were used in this study. Radiotelemetry was performed on 12 to 13 week old BPH/2J and BPN/3J male and female animals. Affymetrix GeneChip Mouse Gene 1.0 ST Arrays were performed in kidney tissue from 12 week old BPH/2J and BPN/3J male and female mice (n = 6/group). Genes that were differentially expressed in both male and female datasets were validated using qPCR. RESULTS: Systolic arterial pressure and heart rate was significantly higher in BPH/2J mice compared with BPN/3J mice in both males and females. Microarray analysis identified 153 differentially expressed genes that were common between males and females (70 upregulated and 83 downregulated). We validated 15 genes by qPCR. Genes involved in sympathetic activity (Hdc, Cndp2), vascular ageing (Edn3), and telomere maintenance (Mcm6) were identified as being differentially expressed between BPH/2J and BPN/3J comparisons. Many of these genes also exhibited expression differences between males and females within a strain. CONCLUSIONS: This study utilised data from both male and female animals to identify a number of genes that may be involved in the development of hypertension. We show that female data can be used to refine candidate genes and pathways, as well as highlight potential mechanisms to explain the differences in prevalence and severity of disease between men and women.

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.

Comparison of indirect and direct blood pressure measurements in baboons during ketamine anaesthesia.

BACKGROUND: The aim of this study was to assess agreement between different methods of blood pressure measurement in anaesthetised baboons. METHODS: Systolic and diastolic blood pressure (SBP and DBP) were measured in anaesthetised baboons using intra-arterial radiotelemetry, automated oscillometry and mercury sphygmomanometry. Correlation between the different methods was assessed. RESULTS: The correlation between intra-arterial radiotelemetry and automated oscillometry was 0.9 (P < 0.001) for SBP and 0.9 (P < 0.001) for DBP. Between-method differences were -4.4 ± 7.2 mm Hg for SBP and -3.4 ± 7.1 mm Hg for DBP. For automated oscillometry vs. mercury sphygmomanometry, correlation was 0.4 for both SBP (P < 0.001) and DBP (P < 0.001). Between-method differences were 7.9 ± 12.7 mm Hg for SBP and 7.3 ± 12.6 mm Hg for DBP. CONCLUSIONS: Our study demonstrates that automated oscillometry may be an appropriate alternative to telemetry for measuring blood pressure in anaesthetised baboons.

Variability in mRNA expression of fms-like tyrosine kinase-1 variants in normal and preeclamptic placenta.

BACKGROUND: Preeclampsia is a complication of pregnancy characterised by gestational hypertension and proteinuria and is a leading cause of morbidity and mortality in both mothers and infants. Certain anti-angiogenic factors have long been implicated in the pathogenesis of preeclampsia and the placental expression of factors such as soluble fms-like tyrosine kinase-1 (sFLT-1) are often reported in studies of normal and diseased placentae. Despite evidence showing significant differences in placental gene expression by collection site, many studies fail to provide sufficient details on sample selection and collection. FINDINGS: With ourselves and others investigating and reporting on the expression of FLT-1 variants and other genes in the placenta of normotensive and preeclamptic patients, we felt it prudent to examine the variation in expression of FLT-1 variants across human placenta. We examined the differential expression of FLT-1 variants in samples obtained from 12 sites on normal and preeclamptic placentae and found expression to be highly variable between sites. We therefore developed an algorithim to calculate the mean expression for any number of these sites collected and in any combination. The coefficient of variation for all combinations of sites was then used to determine the minimum number of sites required to reduce coefficient of variation to below an acceptable 10%. We found that 10 and 11 sites had to be sampled in the normal and preeclamptic placentae respectively to ensure a representative expression pattern for all FLT-1 variants for an individual placenta. CONCLUSIONS: These findings demonstrate significant variation in expression levels of several commonly investigated genes across sites in both normal and preeclamptic placenta. This highlights both the importance of adequate sampling of human placenta for expression studies and the effective communication of sample selection and collection methods, for data interpretation and to ensure the reproducibility and reliability of results and conclusions drawn.

Changes in retinal microvascular caliber precede the clinical onset of preeclampsia.

Preeclampsia is a leading cause of maternal morbidity and mortality. The degree of maternal cardiovascular dysfunction that precedes the onset of preeclampsia is largely unknown. This prospective cohort study aimed to characterize differences in vivo in retinal microvascular caliber and blood pressure throughout pregnancy in relation to preeclampsia development. Women were recruited from Royal Prince Alfred Hospital, Sydney, Australia, of which 92 women were included in the study. Retinal images and blood pressures were collected at 13, 19, 29, and 38 weeks of gestation. Retinal vessels were analyzed as the central retinal arteriolar equivalent corrected for mean arterial blood pressure and the central retinal venular equivalent corrected for mean arterial blood pressure, using generalized linear models adjusted for age and body mass index. The preeclampsia group were significantly older (P=0.002) and had a significantly higher mean body mass index (P=0.005). The central retinal arteriolar equivalent corrected for mean arterial blood pressure was significantly reduced at 13 (P=0.03), 19 (P=0.007), and 38 (P=0.03) weeks of gestation in the preeclampsia group. The central retinal venular equivalent corrected for mean arterial blood pressure was also significantly lower at 13 (P=0.04) and 19 (P=0.001) weeks of gestation in the women who progressed to preeclampsia. This study directly documents increased peripheral resistance in vivo, observed as the combination of constricted retinal arterioles or venules and elevated blood pressure, in women who later developed preeclampsia. This difference preceded the clinical signs of preeclampsia.

High blood pressure during pregnancy is associated with future cardiovascular disease: an observational cohort study.

OBJECTIVES: The study aimed to determine if having a hypertensive disorder of pregnancy (HDP) is a risk factor for future cardiovascular disease (CVD), independent of age and body mass index (BMI). DESIGN: Data were sourced from the baseline questionnaire of the 45 and Up Study, Australia, an observational cohort study. SETTING: Participants were randomly selected from the Australian Medicare Database within New South Wales. PARTICIPANTS: A total of 84 619 women were eligible for this study, of which 71 819 were included. These women had given birth between the ages of 18 and 45 years, had an intact uterus and ovaries, and had not been diagnosed with high blood pressure prior to their first pregnancy. RESULTS: HDP was associated with higher odds of having high blood pressure (<58 years: adjusted OR 3.79, 99% CI 3.38 to 4.24; p<0.001 and ≥58 years: 2.83, 2.58 to 3.12; p<0.001) and stroke (<58 years: 1.69, 1.02 to 2.82; p=0.008 and ≥58 years: 1.46, 1.13 to 1.88; p<0.001) in later life. Women with HDP had a younger age of onset of high blood pressure (45.6 vs 54.8 years, p<0.001) and stroke (58 vs 62.5 years, p<0.001). Women who had HDP and whose present day BMI was <25 had significantly higher odds of having high blood pressure, compared with women who were normotensive during pregnancy (<58 years: 4.55, 3.63 to 5.71; p<0.001 and ≥58 years, 2.94, 2.49 to 3.47; p<0.001). Women who had HDP and a present day BMI≥25 had significantly increased odds of high blood pressure (<58 years: 12.48, 10.63 to 14.66; p<0.001 and ≥58 years, 5.16, 4.54 to 5.86; p<0.001), compared with healthy weight women with a normotensive pregnancy. CONCLUSIONS: HDP is an independent risk factor for future CVD, and this risk is further exacerbated by the presence of overweight or obesity in later life.

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.