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

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

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

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

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

A hypertension gene : are we there yet?

Cardiovascular diseases are the leading cause of death worldwide. Essential hypertension is a major risk factor for the development of other cardiovascular diseases and is caused by a combination of environmental and genetic factors, with up to 50% of blood pressure variance currently attributed to an individual's genetic makeup. By studying genes that cause monogenic forms of hypertension and pathways relevant to blood pressure control, a number of polymorphisms have been identified that increase an individual's risk of developing high blood pressure. We report on candidate gene association studies and genome-wide association studies that have been performed to date in the field of hypertension research. It is becoming clear that for the majority of people there is no single gene polymorphism that causes hypertension, but rather a number of common genetic variants, each having a small effect. Using pharmacogenomics to personalize the treatment of hypertension holds promise for achieving and sustaining normotensive pressures quickly, while minimizing the risk of adverse reactions and unwanted side-effects. This will decrease the risk of stroke and myocardial infarction in individuals and lead to a reduced burden of disease upon society as a whole

Postmortem molecular analysis of KCNQ1 and SCN5A genes in sudden unexplained death in young Australians

The cause of sudden death in young people remains unknown in up to 50% of postmortem cases. Mutations in the ion channel genes are known to cause primary arrhythmogenic disorders such as long QT and Brugada syndromes, which can present with sudden cardiac death and a negative autopsy. In this study, 59 sudden unexplained deaths occurring in Australians aged ≤ 35 years with a negative autopsy, from 1994-2002, were studied. Genomic DNA was extracted from paraffin-embedded tissues. Genetic analysis of the KCNQ1 and SCN5A genes was performed using denaturing high-performance liquid chromatography and direct DNA sequencing. Nine DNA sequence variants were identified in the KCNQ1 gene and 9 sequence variants were identified in the SCN5A gene. In total, 23 out of 59 cases were found to have at least one DNA variant in KCNQ1 or SCN5A, of which one, H558R in the SCN5A gene, caused an amino acid substitution. None of the DNA variants were determined to be disease causing as they were also identified in control populations. In conclusion, no disease-causing mutations were found in the KCNQ1 or SCN5A genes in this cohort. A more selective screening approach, including only individuals with a clinical or family history of arrhythmogenic disorders, may yield greater success in identifying disease-causing mutations in cohorts of young individuals who have died suddenly

Parent of origin influences the cardiac expression of vascular endothelial growth factor (Vegfa)

Background: Vascular endothelial growth factor A (VEGFA) is a major regulator of both physiological and pathological angiogenesis. Associations between polymorphisms in VEGFA and complex disease have been inconsistent. The parent from whom the allele was inherited may account for these inconsistencies. This study examined the parent of origin effect on the expression of murine Vegfa. Methods: Two homozygous, inbred mouse strains A/J (AJ) and 129x1/SvJ (129) were crossed to produce reciprocal AJ129 and 129AJ offspring, respectively. RNA was extracted from cardiac tissue of 6 week old male (n = 8) and female (n = 8) parental, and male and female F1 offspring mice (AJ129 n = 8 and 129AJ n = 8). Vegfa and Hif1a expression levels were measured by qPCR and compared between the F1 offspring from the reciprocal crosses. Results: We found significant differences in the expression of Vegfa in F1 offspring (AJ129 and 129AJ mice) of the reciprocal crosses between AJ and 129 mice. Offspring of male AJ mice had significantly higher expression of Vegfa than offspring of male 129 mice (p = 0.006). This difference in expression was not the result of preferential allele expression (allelic imbalance). Expression of Hif1a, a transcriptional regulator of Vegfa expression, was also higher in F1 offspring of an AJ father (p = 0.004).Conclusion: Differences in Vegfa and Hif1a gene expression are likely the result of an upstream angiogenic regulator gene that is influenced by the parent of origin. These results highlight the importance of including inheritance information, such as parent of origin, when undertaking allelic association studies

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