Hypertension evaluation and management in new young patients: are we doing our female patients a disservice?

PURPOSE: Cardiovascular disease (CVD) is one of the leading causes of death in women, largely underpinned by hypertension. Current guidelines recommend first-line therapy with a RAAS-blocking agent especially in young people. There are well documented sex disparities in CVD outcomes and management. We evaluate the management of patients with newly diagnosed hypertension in a tertiary care clinic to assess male-female differences in investigation and treatment. METHODS: Clinic letters of all new patients under the age of 51 attending the Glasgow Blood Pressure Clinic between January and December 2023 were reviewed. The primary outcomes measured were first-line treatment choices, deviations from guideline-recommended treatment, investigations for secondary hypertension, and documentation of female-specific risk factors and family planning advice. Secondary outcomes included clinical characteristics such as systolic and diastolic blood pressure at referral and at the new patient appointment, age at diagnosis, age at first appointment, and the number of antihypertensive drugs prescribed at referral. RESULTS: One hundred and five (59:46, M:F) new patient encounters were reviewed after sixteen exclusions for non-attendance and inappropriate clinic coding. Choice of first line antihypertensive agent did not vary between sexes with no deviation from guideline-recommended medical therapy. Men, however, had more biochemical investigations conducted for secondary causes across all ages. This was greatest in those under 40 years old. There was suboptimal documentation of female-specific risk factors (obstetric and gynaecological history), contraceptive drug history and family planning with 35%, 20%, and 15.6%, respectively. CONCLUSION: In 2023, women under 51 years of age seen in a tertiary care hypertension clinic received similar first-line treatment to their male peers. However, relevant female-specific histories were suboptimally documented for these patients. Whilst therapeutic approaches in men and women appear to be similar in this clinic, there are opportunities to improve CVD prevention in women, even in a specialised clinic setting.

Hypertension, or persistent high blood pressure, is a condition that can lead to serious cardiovascular diseases such as stroke and heart failure. Evidence has shown that women have cardiovascular disease more than men and it is the leading cause of death in women in Europe. To understand how male and female patients are treated for hypertension, we examined documented consultations and treatments of 105 patients under the age of 51 (46 women and 59 men) at a Glasgow hypertension clinic in 2023. We found that men had more investigations for specific causes of their hypertension across all ages (men = 88%, women = 61%). Recording of reproductive history (35%), contraceptive drug history (20%) and advice on family planning (15.6%) was not as thorough as they could be. Incorrect management of female reproductive history and contraceptive drug history can increase the risk of long-term hypertension complications, so managing this is crucial. A class of drugs commonly used to manage hypertension called RAAS blockers are dangerous to the foetus when pregnant - another factor to consider when managing young women with high blood pressure. Overall, these findings mean that there may be a need for more thorough consideration of women's health factors in hypertension treatment. By paying attention to these areas, we can enhance long-term cardiovascular health for women.

APOE ε4 is associated with decreased synaptic density in cognitively impaired participants.

INTRODUCTION: We aimed to investigate the effect of apolipoprotein E4 (APOE) ε4 on synaptic density in cognitively impaired (CI) participants. METHODS: One hundred ten CI participants underwent amyloid positron emission tomography (PET) with 18F-florbetapir and synaptic density PET with 18F-SynVesT-1. We evaluated the influence of APOE ε4 allele on synaptic density and investigated the effects of ε4 genotype on the associations of synaptic density with Alzheimer's disease (AD) biomarkers. The mediation effects of AD biomarkers on ε4-associated synaptic density loss were analyzed. RESULTS: Compared with non-carriers, APOE ε4 allele carriers exhibited significant synaptic loss in the medial temporal lobe. Amyloid beta (Aß) and tau pathology mediated the effects of APOE ε4 on synaptic density to different extents. The associations between synaptic density and tau pathology were regulated by the APOE ε4 genotype. DISCUSSION: The APOE ε4 allele was associated with decreased synaptic density in CI individuals and may be driven by AD biomarkers.

Estradiol improves behavior in FAD transgenic mice that express APOE3 but not APOE4 after ovariectomy.

Increasing evidence suggests that female individuals have a higher Alzheimer's disease (AD) risk associated with post-menopausal loss of circulating estradiol (E2). However, clinical data are conflicting on whether E2 lowers AD risk. One potential contributing factor is APOE. The greatest genetic risk factor for AD is APOE4, a factor that is pronounced in female individuals post-menopause. Clinical data suggests that APOE impacts the response of AD patients to E2 replacement therapy. However, whether APOE4 prevents, is neutral, or promotes any positive effects of E2 is unclear. Therefore, our goal was to determine whether APOE modulates the impact of E2 on behavior and AD pathology in vivo. To that end, mice that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce Aß42 were ovariectomized at either 4 months (early) or 8 months (late) and treated with vehicle or E2 for 4 months. In E3FAD mice, we found that E2 mitigated the detrimental effect of ovariectomy on memory, with no effect on Aß in the early paradigm and only improved learning in the late paradigm. Although E2 lowered Aß in E4FAD mice in the early paradigm, there was no impact on learning or memory, possibly due to higher Aß pathology compared to E3FAD mice. In the late paradigm, there was no effect on learning/memory and Aß pathology in E4FAD mice. Collectively, these data support the idea that, in the presence of Aß pathology, APOE impacts the response to E2 supplementation post-menopause.

Risk factors for major adverse cardiovascular events in postmenopausal women: UK Biobank prospective cohort study.

BACKGROUND AND AIMS: Cardiovascular risk increases during menopause, so the medical and scientific community should consider women's specific risk factors to prevent cardiovascular disease. This study aims to assess the risk factors for the incidence of major adverse cardiovascular events (MACE) exclusive to postmenopausal women. METHODS: We conducted a prospective cohort study in postmenopausal women aged 40 years and older, who were included in the UK Biobank cohort between 2006 and 2010 and followed to 2021 (12 years). A total of 156,787 women were followed for a median of 12.5 years (nearly 2 million person-years), and MACE risk was assessed using Fine-Gray competing risk models. RESULTS: The cumulative incidence of cardiovascular morbidity and mortality was 1.2% (0.97 cases per 1000 women-years). Not having taken birth control pills, not having children, and early menarche (≤12 years) were independently associated with cardiovascular morbidity and mortality. CONCLUSIONS: Risk factors for cardiovascular disease that are specific to women include early menarche, not having taken oral contraceptives, and reproductive history, and this relationship is independent of classic cardiovascular risk factors.

APOE genotype and sex modulate Alzheimer's disease pathology in aged EFAD transgenic mice.

Increasing evidence supports that age, APOE and sex interact to modulate Alzheimer's disease (AD) risk, however the underlying pathways are unclear. One way that AD risk factors may modulate cognition is by impacting amyloid beta (Aß) accumulation as plaques, and/or neuroinflammation Therefore, the goal of the present study was to evaluate the extent to which age, APOE and sex modulate Aß pathology, neuroinflammation and behavior in vivo. To achieve this goal, we utilized the EFAD mice, which express human APOE3 or APOE4 and have five familial AD mutations (FAD) that result in Aß42 overproduction. We assessed Aß levels, reactive glia and Morris water maze performance in 6-, 10-, 14-, and 18-month-old EFAD mice. Female APOE4 mice had the highest Aß deposition, fibrillar amyloid deposits and neuroinflammation as well as earlier behavior deficits. Interestingly, we found that female APOE3 mice and male APOE4 mice had similar levels of pathology. Collectively our data support that the combination of APOE4 and female sex is the most detrimental combination for AD, and that at older ages, female sex may be equivalent to APOE4 genotype.

Female-specific risk of Alzheimer's disease is associated with tau phosphorylation processes: A transcriptome-wide interaction analysis.

The levels of tau phosphorylation differ between sexes in Alzheimer's disease (AD). Transcriptome-wide associations of sex by disease interaction could indicate whether specific genes underlie sex differences in tau pathology; however, no such study has been reported yet. We report the first analysis of the effect of the interaction between disease status and sex on differential gene expression, meta-analyzing transcriptomic data from the 3 largest publicly available case-control studies (N = 785) in the brain to date. A total of 128 genes, significantly associated with sex-AD interactions, were enriched in phosphoproteins (false discovery rate (FDR) = 0.001). High and consistent associations were found for the overexpressions of NCL (FDR = 0.002), whose phosphorylated protein generates an epitope against neurofibrillary tangles and KIF2A (FDR = 0.005), a microtubule-associated motor protein gene. Transcriptome-wide interaction analyses suggest sex-modulated tau phosphorylation, at sites like Thr231, Ser199, or Ser202 that could increase the risk of women to AD and indicate sex-specific strategies for intervention and prevention.

Caracterización clínica-epidemiológica de pacientes menores o iguales a 40 años con cáncer de mama / Clinical-epidemiological characterization of patients under or equal to 40 years old with breast cancer

El cáncer de mama se encuentra dentro de los tres primeros cánceres diagnosticados en las mujeres a nivel mundial. En las mujeres menores de 40 años ocupa el primer puesto de incidencia. Alrededor de 146 000 nuevos casos son diagnosticados en mujeres menores de 40 años a nivel global. Objetivo. Identificar las características epidemiológicas y clínicas de las pacientes con edad menor o igual a 40 años con diagnóstico de cáncer de mama en un hospital de tercer nivel especializado en la atención de la mujer. Metodología. Estudio transversal descriptivo. Se recolectó información de 60 expedientes de pacientes con diagnóstico de cáncer de mama con edad menor o igual de 40 años diagnosticados entre enero 2019 y diciembre 2020. Resultados. El mayor número de casos se encontró en las mujeres entre 39 y 40 años (18,3 %, cada uno). El 60 % era del área urbana; el 80 % de las pacientes tenía una paridad entre uno a cuatro hijos; el 40 % de se encontraba con sobrepeso y el 58 % no tenía antecedentes familiares de cáncer de mama. El estadio clínico más frecuente fue IIIA. El diagnóstico histopatológico más común fue carcinoma de mama invasivo de tipo no especial (91,6 %), pobremente diferenciado, con receptores para estrógeno y progesterona positivos. Conclusión. Las mujeres con edad menor o igual a 40 años, con cáncer de mama, son pacientes procedentes del área urbana, con sobrepeso, con uno a cuatro hijos y sin antecedentes familiares de cáncer de mama; con presentación clínica inicial en etapas localmente avanzadas, con diagnóstico de carcinoma de mama invasivo de tipo no especial, pobremente diferenciado y receptores para estrógeno y progesterona positivos

Breast Breast cancer is among the first three cancers diagnosed in women worldwide. In women younger than 40 years old it occupies the first place in incidence. About 146 000 new cases are diagnosed globally in women under 40 years old. Objective. To identify the epidemiological and clinical characteristics of patients under or equal to 40 years old, diagnosed with breast cancer in a tertiary hospital specialized in women's care. Methodology. Descriptive cross-sectional study. Information was collected from 60 clinical records of patients diagnosed with breast cancer with an age less than or equal to 40 years old, between January 2019 and December 2020. Results. The highest number of cases was found in women between 39 and 40 years old (18.3 % each). Sixty percent were from the urban area; 80 % of the patients had parity between one and four children; 40 % were overweight and 58 % had no family history of breast cancer. The most frequent clinical stage was IIIA. The most common histopathological diagnosis was invasive breast carcinoma of non-special type (91.6 %), poorly differentiated with positive estrogen and progesterone receptors. Conclusion. Women aged less than or equal to 40 years old, with breast cancer, are patients from urban areas, overweight, with one to four children and no family history of breast cancer, with initial clinical presentation in locally advanced stages, with a diagnosis of invasive breast carcinoma of non-special type, poorly differentiated and positive estrogen and progesterone receptors