Gender-affirming or cross-sex hormone therapy is integral to the management of transgender individuals yet our appreciation of the effects of such hormones on cardiovascular health is limited. Insights into vascular pathophysiology and outcomes in transgender people receiving sex steroids could be fundamental in providing better care for this population through the management of cardiovascular risk and more broadly advance our understanding of the role of sex and gender in vascular health and disease. In addition, there is a need to understand how gender-affirming hormone therapy impacts cardiovascular disease risk and events as transgender individuals age. This review explores the available evidence on the associations between gender-affirming hormones and cardiovascular events such as coronary artery disease, stroke, hypertension, thrombosis, lipid abnormalities, and diabetes mellitus. Current research about vascular outcomes in adults receiving hormonal therapy is limited by the absence of large cohort studies, lack of appropriate control populations, and inadequate data acquisition from gender identity services. Existing epidemiological data suggest that the use of estrogens in transgender females confers an increased risk of myocardial infarction and ischemic stroke. Conversely, transgender males receiving testosterone lack any consistent or convincing evidence of increased risk of cardiovascular or cerebrovascular disease. Further studies are required to confirm whether such risk exists and the mechanisms by which they occur.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. There is robust evidence of heterogeneity in underlying mechanism, manifestation, prognosis, and response to treatment of CVD between male and female patients. Gender, which refers to the socially constructed roles, behaviours, expressions, and identities of individuals, is an important determinant of CV health, and its consideration might help in attaining a broader understanding of the observed sex differences in CVD. Established risk factors such as hypertension, dyslipidemia, diabetes mellitus, obesity, and smoking R ESUM ELes maladies cardiovasculaires (MCV) sont la principale cause de morbidit e et de mortalit e à l' echelle mondiale. Des donn ees robustes t emoignent de l'h et erog en eit e entre hommes et femmes concernant le m ecanisme sous-jacent, la manifestation, le pronostic et la r eponse au traitement de MCV. Le genre, qui renvoie à une construction sociale des rôles, des comportements, de l'expression et de l'identit e individuelle, est un d eterminant important de la sant e cardiovasculaire (CV), et sa prise en compte pourrait aider à mieux comprendre les diff erences observ ees entre les sexes à l' egard des MCV. Il est bienCardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. 1 Despite growing awareness of the role of sex and gender in the management of CVD, female patients continue to experience delays in diagnosis and treatment, 2,3 are referred to and participate less in cardiac rehabilitation, 4 are not sufficiently represented in clinical trials, 5 and as a consequence may often suffer worse outcomes.In the medical literature, the terms "sex" and "gender" are sometimes interchangeably used, generating confusion. Sex refers to the biological characteristics of an individual as determined by chromosomal complement and sex hormones. The impact of these biological factors on CV risk are well established. [6][7][8][9] For example, low levels of estrogen in younger females are associated with an increased risk of CVD, 10,11 and declining estrogen levels after menopause, in addition to advancing age, are associated with unfavourable lipid profiles, 12 blood pressure (BP) elevation, and increased CV risk. 13 Moreover, pregnancy-related complications, such as gestational diabetes and preeclampsia, may alter this risk, as well as endocrine disorders, such as polycystic ovarian syndrome, which may promote CVD. 14,15 Beyond sex, gender derives from the social, cultural, and behavioural factors that may modulate health. 16,17 Gender is a multidimensional concept that incorporates identity (ie, an inner sense of masculinity, femininity, or gender nonconformity), role (ie, societal and environmental expectations), relationships (ie, interpersonal interactions and dynamics), and institutionalised gender (ie, distribution of power in political, educational, social institutions in society). 18 Gender may significantly influence health-related behaviours and interact with CV risk factors....

Purpose of Review To review recent data on sex differences in the prevalence, outcomes and management of hypertension. Recent Findings Although hypertension is overall more common in males, females experience a much sharper incline in blood pressure from the third decade of life and consequently the prevalence of hypertension accelerates comparatively with age. Mechanisms responsible for these blood pressure trajectories may include the sustained vascular influence of hypertensive disorders of pregnancy, interactions between the renin–angiotensin–aldosterone system and sex hormones or even psychosocial gendered factors such as socioeconomic deprivation. Moreover, the impact of hypertension is not uniform and females are at higher risk of developing a multitude of adverse cardiovascular outcomes at lower blood pressure thresholds. Summary Blood pressure is a sexually dimorphic trait and although significant differences exist in the prevalence, pathophysiology and outcomes of hypertension in males and females, limited data exist to support sex-specific blood pressure targets.

AimsMetformin is renally excreted and has been associated with the development of lactic acidosis. Although current advice is to omit metformin during illnesses that may increase the risk of acute kidney injury (AKI), the evidence supporting this is lacking. We investigated the relationship between AKI, lactate concentrations and the risk of lactic acidosis in those exposed to metformin.Materials and MethodsWe undertook a population‐based case‐control study of lactic acidosis in 1746 participants with Type 2 diabetes and 846 individuals without diabetes with clinically measured lactates with and without AKI between 1994 and 2014. AKI was stratified by severity according to “Kidney Disease: Improving Global Outcomes” guidelines. Mixed‐effects logistic and linear regression were used to analyse lactic acidosis risk and lactate concentrations, respectively.ResultsEighty‐two cases of lactic acidosis were identified. In Type 2 diabetes, those treated with metformin had a greater incidence of lactic acidosis [45.7 per 100 000 patient years; 95% confidence interval (CI) 35.9‐58.3] compared to those not exposed to this drug (11.8 per 100 000 patient years; 95% CI 4.9‐28.5). Lactate concentrations were 0.34 mmol/L higher in the metformin‐exposed cohort (P < .001). The risk of lactic acidosis was higher in metformin users [odds ratio (OR) 2.3; P = .002] and increased with AKI severity (stage 1: OR 3.0, P = .002; stage 2: OR 9.4, P < .001; stage 3: OR 16.1, P < .001).ConclusionsA clear association was found between metformin, lactate accumulation and the development of lactic acidosis. This relationship is strongest in those with AKI. These results provide robust evidence to support current recommendations to omit metformin in any illness that may precipitate AKI.