Cardiovascular disease prevention in women - the current state in 2023.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality for women globally. The purpose of this review is to provide an updated overview of CVD prevention in women, focusing on what is currently understood about female-specific or female-predominant CVD risk factors and the importance of tailored strategies for risk assessment and medical interventions. RECENT FINDINGS: Recent studies have demonstrated the need to account for risk factors specific to women in current risk assessment models for CVD, including early menarche, polycystic ovary syndrome, adverse pregnancy outcomes, early menopause, and chronic inflammatory conditions. Incorporation of these findings has led to advancements in sex-specific guidelines, diagnostic tools, and treatment approaches that have led to improvement in the precision of CVD prevention strategies. At-risk women benefit similarly to lipid-lowering and other preventive therapies as men but are less likely to be treated. SUMMARY: CVD prevention in women has made substantial progress over the past decade, marked by increasing awareness among clinicians, improved understanding of sex-specific risk-enhancing factors, and incorporation of sex-specific guidelines for management. However, there remain knowledge gaps that warrant ongoing efforts to optimize CVD prevention strategies in women, which will ultimately lead to improved cardiovascular health outcomes.

Preventing Adverse Cardiovascular Outcomes in Pregnancy Complicated by Obesity.

Purpose of review: Obesity is a chronic disease that is becoming increasingly prevalent, and more individuals of reproductive age have obesity prior to becoming pregnant. Obesity in pregnancy is associated with short- and long-term adverse consequences for both the birthing person and their offspring which have been associated with increased long-term cardiovascular morbidity and mortality. The goal of this review is to discuss what is currently understood about the relationship between maternal obesity and adverse pregnancy outcomes (APOs), the association between APOs and future cardiovascular disease (CVD) risk, and what evidence-based interventions can be implemented to prevent adverse outcomes in this population. Recent findings: Maternal obesity has been associated with an increased risk of APOs such as gestational diabetes, hypertensive disorders of pregnancy, and preterm birth as well as an increased risk of future CVD, such as metabolic syndrome, chronic hypertension, coronary heart disease, and stroke. The impact of maternal obesity also extends beyond the pregnant individual to the offspring, increasing the risk of fetal, neonatal, and infant mortality, as well as of congenital malformations, prematurity, and long-term health problems such as insulin resistance and childhood obesity. Prevention guidelines are incorporating the increased risk of adverse outcomes from maternal obesity into formalized risk assessments to guide both prenatal and postpartum care. It is becoming evident that a multidisciplinary cardio-obstetrics team is an important part of providing comprehensive care for pregnant individuals with obesity and other cardiovascular risk factors, including preexisting CVD and a history of prior APOs. There remains a need for further studies to better understand the mechanisms underlying the relationship between maternal obesity and APOs, as well as the racial and ethnic disparities that have been noted in the prevalence of APOs and associated CVD risk and mortality. Summary: There is increasing awareness that obesity in pregnancy is associated with various short- and long-term adverse maternal and offspring outcomes. There are multiple screening and prevention strategies that may be implemented before, during, and after pregnancy to prevent these adverse outcomes.

Outcomes of autogenous fistulas and prosthetic grafts for hemodialysis access in diabetic and nondiabetic patients.

BACKGROUND: This study evaluated the effect of diabetes on outcomes of autogenous fistulas and prosthetic grafts for hemodialysis access in a large population-based cohort of patients. METHODS: A retrospective cohort study was conducted of all patients who initiated hemodialysis in the United States Renal Database System (2007-2014). The χ2 test, Student t-test, Kaplan-Meier analysis, log-rank test, and multivariable logistic and Cox regression analyses were employed to evaluate maturation, interventions, patency, infection, and mortality. RESULTS: The study of 381,622 patients comprised 303,307 (79.5%) autogenous fistulas and 78,315 (20.5%) prosthetic grafts placed in 231,134 (60.6%) diabetic patients and 150,488 (39.4%) nondiabetic patients. There was decrease in maturation for diabetics compared to nondiabetics who received autogenous fistulas (adjusted hazard ratio [aHR], 0.86; 95% confidence interval [CI], 0.83-0.88; P < .001) and prosthetic grafts (aHR, 0.88; 95% CI, 0.83-0.93; P < .001). Comparing diabetics vs nondiabetics, primary patency at 5 years was 19.4% vs 23.5% (P < .001) for autogenous fistulas and 9.1% vs 11.2% (P < .001) for prosthetic grafts. Primary assisted patency at 5 years was 35.2% vs 38.7% (P < .001) for autogenous fistulas and 17.2% vs 19.2% (P = .015) for prosthetic grafts. Secondary patency at 5 years was 44.8% vs 48.6% (P < .001) for autogenous fistulas and 34.1% vs 36.8% (P = .002) for prosthetic grafts. There was 5% decrease in primary patency (aHR, 0.95; 95% CI, 0.94-0.96; P < .001) for diabetics compared to nondiabetics who received autogenous fistulas. There was no difference in primary assisted and secondary patency for autogenous fistulas as well as primary, primary assisted, and secondary patency for prosthetic grafts in comparing diabetic to nondiabetic patients. There was also no significant difference in severe prosthetic graft infection between the groups (aHR, 0.99; 95% CI, 0.92-1.08; P = .90). There was a 19% increase in patient mortality for diabetic relative to nondiabetic autogenous fistula recipients (aHR, 1.19; 95% CI, 1.17-1.20; P < .001) and 12% increase for prosthetic graft recipients (aHR, 1.12; 95% CI, 1.10-1.15; P < .001). CONCLUSIONS: In this population-based cohort of hemodialysis patients, diabetes mellitus was associated with a decrease in patient survival, access maturation, and primary fistula patency. In contrast, there was no association between diabetes and prosthetic graft patency and severe prosthetic graft infection warranting excision.

Dopamine Signaling in the Suprachiasmatic Nucleus Enables Weight Gain Associated with Hedonic Feeding.

The widespread availability of energy-dense, rewarding foods is correlated with the increased incidence of obesity across the globe. Overeating during mealtimes and unscheduled snacking disrupts timed metabolic processes, which further contribute to weight gain. The neuronal mechanism by which the consumption of energy-dense food restructures the timing of feeding is poorly understood. Here, we demonstrate that dopaminergic signaling within the suprachiasmatic nucleus (SCN), the central circadian pacemaker, disrupts the timing of feeding, resulting in overconsumption of food. D1 dopamine receptor (Drd1)-null mice are resistant to diet-induced obesity, metabolic disease, and circadian disruption associated with energy-dense diets. Conversely, genetic rescue of Drd1 expression within the SCN restores diet-induced overconsumption, weight gain, and obesogenic symptoms. Access to rewarding food increases SCN dopamine turnover, and elevated Drd1-signaling decreases SCN neuronal activity, which we posit disinhibits downstream orexigenic responses. These findings define a connection between the reward and circadian pathways in the regulation of pathological calorie consumption.

Endoscopic endonasal versus transcranial approach to resection of olfactory groove meningiomas: a systematic review.

Despite the increasing utility of the endoscopic endonasal approach (EEA) for management of anterior skull base (ASB) pathologies, the optimal treatment strategy for olfactory groove meningiomas (OGM) remains unclear. This project sought to systematically compare outcomes of EEA management with conventional transcranial approach (TCA) for the treatment of OGMs. A systematic review was performed to identify studies that compared outcomes following EEA and TCA for OGMs. Data extracted from each study included gross total resection (GTR), incidence of cerebrospinal fluid (CSF) leaks, and post-operative complications including anosmia. The results of the search yielded 5 studies which met the criteria for inclusion and analysis. All studies compared TCA (n = 922) with EEA (n = 141) outcomes for OGMs. Overall, the rate of gross total resection (GTR) was lower among the endoscopic group (70.9%) relative to the transcranial group (91.5%). The rate of post-operative CSF leak was 6.3% vs. 25.5% for the transcranial and endoscopic groups, respectively. Post-operative anosmia was higher for patients undergoing EEA (95.9%) compared with patients in the transcranial group (37.4%). In this analysis, EEA was associated with a lower rate of GTR and higher incidences of CSF leaks and post-operative anosmia. However, with increasing surgeon familiarity of the endoscopic anatomy and technique for managing ASB pathologies, a nuanced approach may be used to minimize patient morbidity and widen the spectrum of skull base surgery.

Direct Midbrain Dopamine Input to the Suprachiasmatic Nucleus Accelerates Circadian Entrainment.

Dopamine (DA) neurotransmission controls behaviors important for survival, including voluntary movement, reward processing, and detection of salient events, such as food or mate availability. Dopaminergic tone also influences circadian physiology and behavior. Although the evolutionary significance of this input is appreciated, its precise neurophysiological architecture remains unknown. Here, we identify a novel, direct connection between the DA neurons of the ventral tegmental area (VTA) and the suprachiasmatic nucleus (SCN). We demonstrate that D1 dopamine receptor (Drd1) signaling within the SCN is necessary for properly timed resynchronization of activity rhythms to phase-shifted light:dark cycles and that elevation of DA tone through selective activation of VTA DA neurons accelerates photoentrainment. Our findings demonstrate a previously unappreciated role for direct DA input to the master circadian clock and highlight the importance of an evolutionarily significant relationship between the circadian system and the neuromodulatory circuits that govern motivational behaviors.

Genetically targeted magnetic control of the nervous system.

Optogenetic and chemogenetic actuators are critical for deconstructing the neural correlates of behavior. However, these tools have several limitations, including invasive modes of stimulation or slow on/off kinetics. We have overcome these disadvantages by synthesizing a single-component, magnetically sensitive actuator, "Magneto," comprising the cation channel TRPV4 fused to the paramagnetic protein ferritin. We validated noninvasive magnetic control over neuronal activity by demonstrating remote stimulation of cells using in vitro calcium imaging assays, electrophysiological recordings in brain slices, in vivo electrophysiological recordings in the brains of freely moving mice, and behavioral outputs in zebrafish and mice. As proof of concept, we used Magneto to delineate a causal role of striatal dopamine receptor 1 neurons in mediating reward behavior in mice. Together our results present Magneto as an actuator capable of remotely controlling circuits associated with complex animal behaviors.