Sex-specific differences in cardiovascular risk factors and implications for cardiovascular disease prevention in women.

Cardiovascular disease (CVD) is the leading cause of mortality for women globally. Sex differences exist in the relative risks conferred by traditional CVD risk factors, including diabetes, hypertension, obesity, and smoking. Additionally, there are female-specific risk factors, including age of menarche and menopause, polycystic ovary syndrome, infertility and the use of assisted reproductive technology, spontaneous pregnancy loss, parity, and adverse pregnancy outcomes, as well as female-predominant conditions such as autoimmune diseases, migraines, and depression, that enhance women's cardiovascular risk across the lifespan. Along with measurement of traditional risk factors, these female-specific factors should also be ascertained as a part of cardiovascular risk assessment to allow for a more comprehensive overview of the risk for developing cardiometabolic disorders and CVD. When present, these factors can identify women at elevated cardiovascular risk, who may benefit from more intensive preventive interventions, including lifestyle changes and/or pharmacotherapy such as statins. This review describes sex differences in traditional risk factors and female-specific/female-predominant risk factors for CVD and examines the role of coronary artery calcium scores and certain biomarkers that can help further risk stratify patients and guide preventive recommendations.

Assessment and Prediction of Cardiovascular Contributions to Severe Maternal Morbidity.

Severe maternal morbidity (SMM) refers to any unexpected outcome directly related to pregnancy and childbirth that results in both short-term delivery complications and long-term consequences to a women's health. This affects about 60,000 women annually in the United States. Cardiovascular contributions to SMM including cardiac arrest, arrhythmia, and acute myocardial infarction are on the rise, probably driven by changing demographics of the pregnant population including more women of extreme maternal age and an increased prevalence of cardiometabolic and structural heart disease. The utilization of SMM prediction tools and risk scores specific to cardiovascular disease in pregnancy has helped with risk stratification. Furthermore, health system data monitoring and reporting to identify and assess etiologies of cardiovascular complications has led to improvement in outcomes and greater standardization of care for mothers with cardiovascular disease. Improving cardiovascular disease-related SMM relies on a multipronged approach comprised of patient-level identification of risk factors, individualized review of SMM cases, and validation of risk stratification tools and system-wide improvements in quality of care. In this article, we review the epidemiology and cardiac causes of SMM, we provide a framework of risk prediction clinical tools, and we highlight need for organization of care to improve outcomes.

Temporal trends of arrhythmias at delivery hospitalizations in the United States: Analysis from the National Inpatient Sample, 2009-2019.

Background: Cardiac arrhythmias are associated with increased maternal morbidity. There are limited data on trends of arrhythmias among women hospitalized for delivery. Materials and methods: We used the National Inpatient Sample (NIS) database to identify delivery hospitalizations for individuals aged 18-49 years between 2009 to 2019 and utilized coding data from the 9th and 10th editions of the International Classification of Diseases to identify supraventricular tachycardias (SVT), atrial fibrillation (AF), atrial flutter, ventricular tachycardia (VT), and ventricular fibrillation (VF). Arrhythmia trends were analyzed by age, race-ethnicity, hospital setting, and hospital geographic regions. Multivariable logistic regression was used to evaluate the association of demographic, clinical, and socioeconomic characteristics with arrhythmias. Results: Among 41,576,442 delivery hospitalizations, the most common arrhythmia was SVT (53%), followed by AF (31%) and VT (13%). The prevalence of arrhythmia among delivery hospitalizations increased between 2009 and 2019. Age > 35 years and Black race were associated with a higher arrhythmia burden. Factors associated with an increased risk of arrhythmias included valvular disease (OR: 12.77; 95% C1:1.98-13.61), heart failure (OR:7.13; 95% CI: 6.49-7.83), prior myocardial infarction (OR: 5.41, 95% CI: 4.01-7.30), peripheral vascular disease (OR: 3.19, 95% CI: 2.51-4.06), hypertension (OR: 2.18; 95% CI: 2.07-2.28), and obesity (OR 1.69; 95% CI: 1.63-1.76). Delivery hospitalizations complicated by arrhythmias compared with those with no arrhythmias had a higher proportion of all-cause in-hospital mortality (0.95% vs. 0.01%), cardiogenic shock (0.48% vs. 0.00%), preeclampsia (6.96% vs. 3.58%), and preterm labor (2.95% vs. 2.41%) (all p < 0.0001). Conclusion: Pregnant individuals with age > 35 years, obesity, hypertension, valvular heart disease, or severe pulmonary disease are more likely to have an arrhythmia history or an arrhythmia during a delivery hospitalization. Delivery hospitalizations with a history of arrhythmia are more likely to be complicated by all-cause in-hospital mortality, cardiovascular, and adverse pregnancy outcomes (APOs). These data highlight the increased risk associated with pregnancies among individuals with arrhythmias.

Ten things to know about ten cardiovascular disease risk factors - 2022.

The American Society for Preventive Cardiology (ASPC) "Ten things to know about ten cardiovascular disease risk factors - 2022" is a summary document regarding cardiovascular disease (CVD) risk factors. This 2022 update provides summary tables of ten things to know about 10 CVD risk factors and builds upon the foundation of prior annual versions of "Ten things to know about ten cardiovascular disease risk factors" published since 2020. This 2022 version provides the perspective of ASPC members and includes updated sentinel references (i.e., applicable guidelines and select reviews) for each CVD risk factor section. The ten CVD risk factors include unhealthful dietary intake, physical inactivity, dyslipidemia, pre-diabetes/diabetes, high blood pressure, obesity, considerations of select populations (older age, race/ethnicity, and sex differences), thrombosis (with smoking as a potential contributor to thrombosis), kidney dysfunction and genetics/familial hypercholesterolemia. Other CVD risk factors may be relevant, beyond the CVD risk factors discussed here. However, it is the intent of the ASPC "Ten things to know about ten cardiovascular disease risk factors - 2022" to provide a tabular overview of things to know about ten of the most common CVD risk factors applicable to preventive cardiology and provide ready access to applicable guidelines and sentinel reviews.

Cardio-Obstetrics: the Next Frontier in Cardiovascular Disease Prevention.

PURPOSE OF REVIEW: Internationally, cardiovascular disease (CVD) is the leading cause of death in women. With risk factors for CVD continuing to rise, early identification and management of chronic diseases such as hypertension, diabetes, and obstructive sleep apnea is necessary for prevention. Pregnancy is a natural stress test for women with risk factors who may be predisposed to CVD and offers a unique opportunity to not only recognize disease but also implement effective and long-lasting strategies for prevention. RECENT FINDINGS: Prevention begins before pregnancy, as preconception screening, counseling, and optimization of chronic diseases can improve maternal and fetal outcomes. Throughout pregnancy, women should maintain close follow-up, continued reevaluation of risk factors, with counseling when necessary. Continued healthcare engagement during the "fourth trimester," 3 months following delivery, allows clinicians to continue monitoring the evolution of chronic diseases, encourage ongoing lifestyle counseling, and connect women with primary care and appropriate specialists if needed. Unfortunately, this postpartum period represents a major care gap, as a significant proportion of most women do not attend their scheduled visits. Social determinants of health including decreased access to care and economic instability lead to increased risk factors throughout pregnancy but particularly play a role in poor compliance with postpartum follow-up. The use of telemedicine clinics and remote monitoring may prove to be effective interventions, bridging the gap between physicians and patients and improving follow-up for at-risk women. While many clinicians are beginning to understand the impact of CVD on women, screening and prevention strategies are not often implemented until much later in life. Pregnancy creates an opportunity to begin engaging women in cardiovascular protective strategies before the development of the disease.

Network characteristics of a referral system for patients with hypertension in Western Kenya: results from the Strengthening Referral Networks for Management of Hypertension Across the Health System (STRENGTHS) study.

BACKGROUND: Health system approaches to improve hypertension control require an effective referral network. A national referral strategy exists in Kenya; however, a number of barriers to referral completion persist. This paper is a baseline assessment of a hypertension referral network for a cluster-randomized trial to improve hypertension control and reduce cardiovascular disease risk. METHODS: We used sociometric network analysis to understand the relationships between providers within a network of nine geographic clusters in western Kenya, including primary, secondary, and tertiary care facilities. We conducted a survey which asked providers to nominate individuals and facilities to which they refer patients with controlled and uncontrolled hypertension. Degree centrality measures were used to identify providers in prominent positions, while mixed-effect regression models were used to determine provider characteristics related to the likelihood of receiving referrals. We calculated core-periphery correlation scores (CP) for each cluster (ideal CP score = 1.0). RESULTS: We surveyed 152 providers (physicians, nurses, medical officers, and clinical officers), range 10-36 per cluster. Median number of hypertensive patients seen per month was 40 (range 1-600). While 97% of providers reported referring patients up to a more specialized health facility, only 55% reported referring down to lower level facilities. Individuals were more likely to receive a referral if they had higher level of training, worked at a higher level facility, were male, or had more job experience. CP scores for provider networks range from 0.335 to 0.693, while the CP scores for the facility networks range from 0.707 to 0.949. CONCLUSIONS: This analysis highlights several points of weakness in this referral network including cluster variability, poor provider linkages, and the lack of down referrals. Facility networks were stronger than provider networks. These shortcomings represent opportunities to focus interventions to improve referral networks for hypertension. TRIAL REGISTRATION: Trial Registered on ClinicalTrials.gov NCT03543787 , June 1, 2018.

Secondary Prevention of Cardiovascular Disease in Women: Closing the Gap.

Cardiovascular disease (CVD) remains the leading cause of death in women globally. Younger women (<55 years of age) who experience MI are less likely to receive guideline-directed medical therapy (GDMT), have a greater likelihood of readmission and have higher rates of mortality than similarly aged men. Women have been under-represented in CVD clinical trials, which limits the generalisability of results into practice. Available evidence indicates that women derive a similar benefit as men from secondary prevention pharmacological therapies, such as statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, icosapent ethyl, antiplatelet therapy, sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists. Women are less likely to be enrolled in cardiac rehabilitation programs than men. Mitigating risk and improving outcomes is dependent on proper identification of CVD in women, using appropriate GDMT and continuing to promote lifestyle modifications. Future research directed at advancing our understanding of CVD in women will allow us to further develop and tailor CVD guidelines appropriate by sex and to close the gap between diagnoses, treatment and mortality.

Human-centered implementation research: a new approach to develop and evaluate implementation strategies for strengthening referral networks for hypertension in western Kenya.

BACKGROUND: Human-centered design (HCD) is an increasingly recognized approach for engaging stakeholders and developing contextually appropriate health interventions. As a component of the ongoing STRENGTHS study (Strengthening Referral Networks for Management of Hypertension Across the Health System), we report on the process and outcomes of utilizing HCD to develop the implementation strategy prior to a cluster-randomized controlled trial. METHODS: We organized a design team of 15 local stakeholders to participate in an HCD process to develop implementation strategies. We tested prototypes for acceptability, appropriateness, and feasibility through focus group discussions (FGDs) with various community stakeholder groups and a pilot study among patients with hypertension. FGD transcripts underwent content analysis, and pilot study data were analyzed for referral completion and reported barriers to referral. Based on this community feedback, the design team iteratively updated the implementation strategy. During each round of updates, the design team reflected on their experience through FGDs and a Likert-scale survey. RESULTS: The design team developed an implementation strategy consisting of a combined peer navigator and a health information technology (HIT) package. Overall, community participants felt that the strategy was acceptable, appropriate, and feasible. During the pilot study, 93% of referrals were completed. FGD participants felt that the implementation strategy facilitated referral completion through active peer engagement; enhanced communication between clinicians, patients, and health administrators; and integrated referral data into clinical records. Challenges included referral barriers that were not directly addressed by the strategy (e.g. transportation costs) and implementation of the HIT package across multiple health record systems. The design team reflected that all members contributed significantly to the design process, but emphasized the need for more transparency in how input from study investigators was incorporated into design team discussions. CONCLUSIONS: The adaptive process of co-creation, prototyping, community feedback, and iterative redesign aligned our implementation strategy with community stakeholder priorities. We propose a new framework of human-centered implementation research that promotes collaboration between community stakeholders, study investigators, and the design team to develop, implement, and evaluate HCD products for implementation research. Our experience provides a feasible and replicable approach for implementation research in other settings. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02501746 , registration date: July 17, 2015.

COVID and Cardiovascular Disease: What We Know in 2021.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) has been the cause of significant global morbidity and mortality. Here, we review the literature to date of the short-term and long-term consequences of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection on the heart. RECENT FINDINGS: Early case reports described a spectrum of cardiovascular manifestations of COVID-19, including myocarditis, stress cardiomyopathy, myocardial infarction, and arrhythmia. However, in most cases, myocardial injury in COVID-19 appears to be predominantly mediated by the severity of critical illness rather than direct injury to myocardium from viral particles. While cardiac magnetic resonance imaging remains a powerful tool for diagnosing acute myocarditis, it should be used judiciously in light of low baseline prevalence of myocarditis. Guiding an athletic patient through return to play (RTP) after COVID-19 infection is a challenging process. More recent data show RTP has been a safe endeavor using a screening protocol. "Long COVID" or post-acute sequelae of SARS-CoV-2 infection has also been described. The reported symptoms span a large breadth of cardiopulmonary and neurologic complaints including fatigue, palpitations, chest pain, breathlessness, brain fog, and dysautonomia including postural tachycardia syndrome (POTS). Management of POTS/dysautonomia primarily centers on education, exercise, and salt and fluid repletion. Our understanding of the impact of COVID-19 on the cardiovascular system is constantly evolving. As we enter a new age of survivorship, additional research is needed to catalogue the burden of persistent cardiopulmonary symptoms. Research is also needed to learn how acute management may alter the likelihood and prevalence of this chronic syndrome.

The Duke Hotspotting Initiative: Providing Meaningful Clinical Experiences and Improving Clinical Readiness for First-Year Medical Students.

PROBLEM: Many medical schools now incorporate meaningful clinical experiences for first-year medical students (MS1s). However, these clinical placements often fail to teach components of the physician experience, including health care logistics, cost-conscious care, longitudinal patient care, and interaction with an interprofessional team. The Duke Hotspotting Initiative (DHSI) is a student-led elective longitudinal experience for MS1s to serve as a patient's health care liaison to encourage proactive health management and efficient use of resources. APPROACH: DHSI is a combined didactic-clinical experience at Duke University School of Medicine. Students complete a didactic curriculum to develop relevant skills and maintain weekly contact with a patient in Durham, North Carolina, for the duration of the academic year. In their meetings with patients, students help them set and monitor health goals, identify and address barriers to health resources, and efficiently access primary care. Across 2 academic years (2017-2018 and 2018-2019), 54 MS1s were surveyed electronically before and after their participation in DHSI. They were asked about their comfort navigating various patient management scenarios, using communication tools, and assuming clinical responsibilities. OUTCOMES: DHSI offers MS1s a unique immersive opportunity to gain experience applying the clinical skills they will need in their future careers. Based on comparisons of responses from the 48 students (89%) who completed the pre-DHSI survey and 40 students (74%) who completed the post-DHSI survey, there was a significant increase in comfort with communication and patient advising, managing common chronic diseases, using interview skills, and assuming clinical responsibilities. NEXT STEPS: DHSI continues to expand in both size and scope, with the goal of incorporating team members from other health professions training programs at multiple institutions. Future analysis will investigate the longer-term impact of the program on students' professional development, objective changes in clinical skills, and outcomes for patients involved with DHSI.

Strategies for Effective Stakeholder Engagement in Strengthening Referral Networks for Management of Hypertension Across Health Systems in Kenya.

BACKGROUND: Ineffective referral networks in low- and middle-income countries hinders access to evidence-based therapies by hypertensive patients, leading to high cardiovascular mortality and morbidity. The STRENGTHS (Strengthening Referral Networks for Management of Hypertension Across Health Systems) study evaluates strategies to improve referral processes utilizing the International Association of Public Participation framework to engage stakeholders. OBJECTIVES: This study sought to identify and engage key stakeholders involved in referral of patients in the Ministry of Health, western Kenya. METHODS: Key stakeholders involved in policy formulation, provision, or consumption of public health care service were mapped out and contacted by phone, letters, and emissaries to schedule meetings, explain research objectives, and obtain feedback. RESULTS: Key stakeholders identified were the Ministry of Health, the Academic Model Providing Access to Healthcare, health professionals, communities and their leadership, and patients. Engaging them resulted in permission to contact research in their areas of jurisdiction and enabled collaboration in updating care protocols with emphasis on timely and appropriate referrals. CONCLUSIONS: Early stakeholder identification and engagement using the International Association of Public Participation model eased explanation of research objectives, building consensus, and shaping the interventions to improve the referral process.

Application of Statistically Based Experimental Designs to Optimize Cellulase Production and Identification of Gene.

A natural bacterial strain identified as Bacillus amyloliquefaciens MBAA3 using 16S rDNA partial genome sequencing has been studied for optimization of cellulase production. Statistical screening of media components for production of cellulase by B. amyloliquefaciens MBAA3 was carried out by Plackett-Burman design. Plackett-Burman design showed CMC, MgSO4 and pH as significant components influencing the cellulase production from the media components screened by Plackett-Burman fractional factorial design. The optimum concentrations of these significant parameters were determined employing the response surface central composite design, involving three factors and five levels was adopted to acquire the best medium for the production of cellulase enzyme revealed concentration of CMC (1.84 g), MgSO4 (0.275 g), and pH (8.5) in media for highest enzyme production. Response surface counter plots revealed that middle level of MgSO4 and middle level of CMC, higher level of CMC and lower level of pH and higher level of MgSO4 with lower level of pH increase the production of cellulase. After optimization cellulase activity increased by 6.81 fold. Presence of cellulase gene in MBAA3 was conformed by the amplification of genomic DNA of MBAA3. A PCR product of cellulase gene of 1500 bp was successfully amplified. The amplified gene was conformed by sequencing the amplified product and sequence was deposited in the gene bank under the accession number KF929416. Response surface graph showing interaction effects between concentration of a CMC and MgSO4. b pH and CMC. c MgSO4 and pH.

Role of allelochemicals in plant growth promoting rhizobacteria for biocontrol of phytopathogens.

Soil borne fungal diseases pose serious constraints on agro-productivity. Biological control is non-hazardous strategy to control plant pathogens and improve crop productivity. PGPR (plant growth promoting rhizobacteria) have long been used as plant disease control agents. PGPR produced a wide range of secondary compounds that may act as signals--that is, allelochemicals that include metabolites, siderophores, antibiotics, volatile metabolites, enzymes and others. Their mode of action and molecular mechanisms provide a great awareness for their application for crop disease management. The present review highlights the role of PGPR strains, specifically referring to allelochemicals produced and molecular mechanisms. Further research to fine tune combinations of allelochemicals, plant-microbe-pathogen interaction will ultimately lead to better disease control.