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.

Adipokines and incident venous thromboembolism: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Obesity leads to adipocyte hypertrophy and adipokine dysregulation and is an independent risk factor for venous thromboembolism (VTE). However, the association between adipokines and VTE is not well established. OBJECTIVES: To examine whether adipokines are associated with increased risk of incident VTE. METHODS: We studied 1888 participants of the Multi-Ethnic Study of Atherosclerosis cohort who were initially free of VTE and had adipokine (adiponectin, leptin, and resistin) levels measured at either examination 2 or 3 (2002-2004 or 2004-2005, respectively). During follow-ups, VTE was ascertained through hospitalization records and death certificates by using ICD-9 and 10 codes. We used multivariable Cox proportional hazards regression to assess the association between 1 standard deviation (SD) log-transformed increments in adipokines and incident VTE. RESULTS: The mean ± SD age was 64.7 ± 9.6 years, and 49.8% of participants were women. Medians (interquartile range) of adiponectin, leptin, and resistin were 17.3 (11.8-26.2) mcg/mL, 13.5 (5.6-28.2) ng/mL, and 15.0 (11.9-19.0) ng/mL, respectively. There were 78 incident cases of VTE after a median of 9.7 (5.0-12.4) years of follow-up. After adjusting for sociodemographics, smoking, and physical activity, the hazard ratios (95% CIs) per 1 SD increment of adiponectin, leptin, and resistin were 1.14 (0.90-1.44), 1.29 (1.00-1.66), and 1.38 (1.09-1.74), respectively. The association for resistin persisted after further adjustments for body mass index and computed tomography-derived total visceral adipose tissue area. CONCLUSION: Higher resistin levels were independently associated with greater risk of incident VTE. Larger prospective cohort studies are warranted to confirm this association.

Evaluation of an Internal Medicine Transition to Residency Course.

OBJECTIVES: We sought to evaluate the effectiveness of a novel Internal Medicine (IM) transition to residency (TTR) curriculum. METHODS: We performed a paired pre-/postsurvey evaluation of graduating fourth-year medical students' perceived preparedness and medical knowledge after participating in a recently developed IM TTR course. RESULTS: The response rate was 51% (24 of 47). There was a significant improvement in 15 of 17 perceived preparedness items and significant improvement in the medical students' performance on the 8-question medical knowledge test. CONCLUSIONS: The IM TTR curriculum improved medical students' medical knowledge and perceived preparedness for internship on a variety of high-yield clinical topics. The curriculum may be appealing to other institutions that are developing or revamping TTR courses.

Ischemia with No Obstructive Arteries (INOCA): A Review of the Prevalence, Diagnosis and Management.

Ischemia with no obstructive arteries (INOCA) is defined as patients with angiographic evidence of ischemia but no obstructive coronary artery disease (CAD) at coronary angiography. INOCA is estimated to be prevalent is 3-4 million individuals with a female predominance. INOCA is composed of different endotypes including: microvascular dysfunction, vasospasm and a combination of the 2. Diagnosis of INOCA requires either non-invasive or invasive techniques aimed at assessing coronary flow reserve (CFR), Index of Microcirculatory Resistance (IMR) and spasm secondary to acetylcholine injection. Although INOCA is associated with an increased risk of MACE and a decrease in quality of life, less than half of patients are appropriately treated. Treatment of INOCA remains elusive with current therapeutics tailored towards the specific endotype and ongoing clinical trials looking to assess the efficacy of traditional CAD medications.

The Fourth Trimester: a Time for Enhancing Transitions in Cardiovascular Care.

Purpose of Review: The "fourth trimester" concept, defined as the first 12 weeks after delivery (and beyond), is a critical window of time for clinicians to intervene to optimize women's cardiovascular health after pregnancy. A timely and comprehensive postpartum cardiovascular assessment should be performed in all women following delivery in order to (1) follow up medical conditions present prior to conception, (2) evaluate symptoms and signs of common postpartum complications, and (3) identify risk factors and prevent future adverse cardiovascular outcomes. In this review, we aim to discuss major maternal cardiovascular risk factors such as hypertensive disorders of pregnancy, gestational diabetes mellitus, postpartum weight retention, and postpartum depression, as well as lactation as a potential protective risk modifying factor. Additionally, we will review effectiveness of outpatient interventions to enhance transitions in cardiovascular care during the fourth trimester. Recent Findings: A seamless hand-off from obstetric to primary care, and potentially cardiology, is needed for early detection and management of hypertension, weight, glycemic control, stress and mood, and long-term cardiovascular risk. Additionally, the use of telemedicine, blood pressure self-monitoring, remote activity monitoring, and behavioral health coaches are potentially feasible modalities to augment clinic-based care for cardiovascular risk factors and weight management, but additional studies are needed to study their long-term effectiveness. Summary: Development of a comprehensive postpartum care plan with careful consideration of each patient's risk profile and access to resources is critical to improve maternal morbidity and mortality, reduce health disparities, and achieve long-term cardiovascular health for women. Supporting postpartum well-being of women during this transition period requires a multidisciplinary approach, especially primary care engagement, and planning should start before delivery.

Recent Updates in Hypertriglyceridemia Management for Cardiovascular Disease Prevention.

PURPOSE OF REVIEW: Mounting evidence continues to support the causal role of triglyceride-rich lipoproteins (TRL) in the development of atherosclerotic cardiovascular disease (ASCVD). Substantial residual ASCVD risk remains among high-risk patients who have elevated triglycerides despite reduction in low-density lipoprotein cholesterol (LDL-C) with statin therapy. Ongoing research efforts have focused on evaluating triglyceride-lowering therapies among patients with hypertriglyceridemia. RECENT FINDINGS: The REDUCE-IT trial showed that the addition of icosapent ethyl, a highly purified form of eicosapentaenoic acid (EPA), can reduce vascular events among statin-treated individuals with elevated triglycerides who have either clinical ASCVD or diabetes plus another risk factor. Although additional evidence for EPA has emerged from other trials, conflicting results have been reported by subsequent trials that tested different omega-3 fatty acid formulations. Randomized clinical trials have not demonstrated incremental ASCVD benefit of fibrates on background of statin therapy, but fibrates are used to help prevent pancreatitis in patients with severe hypertriglyceridemia. Selective inhibitors of apolipoprotein C-III (apoC3) and angiopoietin-like protein 3 (ANGPTL3), proteins that are involved in metabolism of TRLs by regulating lipoprotein lipase, have been tested in selected patient populations and showed significant reduction in triglyceride and LDL-C levels. Statin therapy continues to be the cornerstone of pharmacologic reduction of cardiovascular risk. High-dose EPA in the form of icosapent ethyl has been demonstrated to have cardiovascular benefit on top of statins in persons with elevated triglycerides at high ASCVD risk. Ongoing clinical trials are evaluating novel selective therapies such as apoC3 and ANGPTL3 inhibitors.

Higher Leptin Levels Are Associated with Coronary Artery Calcium Progression: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Adipokines play a role in cardiometabolic pathways. Coronary artery calcium (CAC) progression prognosticates cardiovascular disease (CVD) risk. However, the association of adipokines with CAC progression is not well established. We examined the association of adipokines with CAC progression in a multi-ethnic cohort free of CVD at baseline. METHODS: We included 1,904 randomly-selected adults enrolled in the Multi-Ethnic Study of Atherosclerosis who had both adipokine levels [leptin, resistin, adiponectin] and CAC by CT measured at either exam 2 (2002-2004) or exam 3 (2004-2005). CAC was previously measured at exam 1 (2000-2002) and a subset (n=566) had CAC measured at exam 5 (2010-2012). We used logistic regression to examine odds of CAC progression between exam 1 and 2/3 (defined as >0 Agatston units of change/year). We used linear mixed effect models to examine CAC progression from exam 2/3 to 5. RESULTS: At exam 2/3, the mean age was 65(10) yrs; 50% women. In models adjusted for sociodemographic factors and BMI, the highest tertile of leptin, compared to lowest, was associated with an increased odds of CAC progression over the preceding 2.6yrs [OR 1.60 (95% CI: 1.10-2.33)]. In models further adjusted for visceral fat and CVD risk factors, the highest tertile of leptin was statistically significantly associated with a 4% (1-7%) greater CAC progression over an average of 7yrs. No associations were seen for resistin and adiponectin. CONCLUSIONS: Higher leptin levels were independently, but modestly, associated with CAC progression. Atherosclerosis progression may be one mechanism through which leptin confers increased CVD risk.

Medical Student Attitudes on Explicit Informed Consent for Pelvic Exams Under Anesthesia.

OBJECTIVE: To obtain an overview of medical student attitudes on the need for explicit consent for pelvic exams under anesthesia performed for educational purposes DESIGN: From February to October 2020, 201 medical students at a single medical school in the United States participated in a cross-sectional survey after completion of the obstetrics and gynecology clerkship. Outcome measures included endorsement of need for explicit informed consent for educational pelvic exams under anesthesia, and knowledge of informed consent processes for such exams. SETTING: University of Pittsburgh School of Medicine PARTICIPANTS: Third- and fourth-year medical students RESULTS: Overall, 75% of medical students endorsed a need for explicit informed consent for educational pelvic exams under anesthesia, which extended to prostate, rectal, and breast exams under anesthesia. Additionally, 45% and 77% of these participants indicated that consent for educational pelvic exams under anesthesia should take the form of a separate signature line on the surgical consent form and/or a verbal form, respectively. Only 40% of students correctly identified institutional policy for obtaining informed consent for educational pelvic exams under anesthesia. Rotation with the oncologic surgical service (p = 0.02) and correct identification of institutional informed consent policies (p = 0.002) were associated with decreased perceptions of the importance of explicit informed consent for educational pelvic exams under anesthesia. CONCLUSIONS: Medical students at the institution studied largely support explicit informed consent for educational pelvic and other sensitive exams under anesthesia, but a knowledge gap on institutional informed consent policy exists. Medical students support increased transparency and bodily autonomy. Due to the agreement of patients and medical students and the ethical rationale for this position, it may be appropriate for physicians and institutions to consider new processes of obtaining explicit informed consent for pelvic exams under anesthesia by medical students.

Associations between endogenous sex hormone levels and adipokine levels in the Multi-Ethnic Study of Atherosclerosis.

Background: Differences in sex hormone levels contribute to differences in cardiovascular disease (CVD) risk. Adipokines play a role in cardiometabolic pathways and have differing associations with CVD. Adipokine levels differ by sex; however, the association between sex hormone profiles and adipokines is not well established. We hypothesized that a more androgenic sex hormone profile would be associated with higher leptin and resistin and lower adiponectin levels among postmenopausal women, with the opposite associations in men. Methods: We performed an analysis of 1,811 adults in the Multi-Ethnic Study of Atherosclerosis who had both sex hormones and adipokines measured an average of 2.6 years apart. Sex hormones [Testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG), and dehydroepiandrosterone (DHEA)] were measured at exam 1; free T was estimated. Serum adipokines (leptin, resistin, adiponectin) were measured at exams 2 or 3. We used multivariable linear regression to examine the cross-sectional associations between sex hormones and adipokines. Results: The mean (SD) age was 63 (10) years, 48% were women; 59% non-White participants. For leptin, after adjusting for demographics only, higher free T and lower SHBG, were associated with higher leptin in women; this association was attenuated after further covariate adjustment. However in men, higher free T and lower SHBG were associated with greater leptin levels in fully adjusted models. For adiponectin, lower free T and higher SHBG were associated with greater adiponectin in both women and men after adjustment for CVD risk factors. For resistin, no significant association was found women, but an inverse association with total T and bioT was seen in men. Conclusion: Overall, these results further suggest a more androgenic sex profile (higher free T and lower SHBG) is associated with a less favorable adipokine pattern. These findings may provide mechanistic insight into the interplay between sex hormones, adipokines, and CVD risk.

Associations of adipokine levels with the prevalence and extent of valvular and thoracic aortic calcification: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Extra-coronary calcification (ECC) is a marker of atherosclerosis and independently associated with cardiovascular disease (CVD). Adipokines may mediate the effect of obesity on atherosclerosis. However, the relationship of adipokines with ECC is not well-established. We examined the associations of leptin, resistin and adiponectin with ECC in a diverse community-based cohort. METHODS: We performed a cross-sectional analysis of 1897 adults without clinical CVD in the MESA cohort. Serum adipokine levels and non-contrast cardiac CT scans were obtained at Exam 2 or 3 (randomly assigned). ECC was quantified by Agatston score and included calcification of the mitral annulus (MAC), aortic valve (AVC), ascending thoracic aorta (ATAC) and descending thoracic aorta (DTAC). We used multivariable regression to evaluate the associations between leptin, resistin and adiponectin [per 1 SD ln(adipokine] with ECC prevalence (score >0) and extent [ln(score+1)]. RESULTS: The mean age of participants was 65 ± 10 years; 49% women. After adjusting for demographic factors, adiponectin was inversely associated with AVC prevalence and extent; leptin positively associated with MAC prevalence and extent; and resistin positively associated with ATAC prevalence and extent and DTAC extent. After adjustment for BMI and other CVD risk factors, adiponectin remained inversely associated with AVC prevalence, and resistin remained associated with greater ATAC prevalence and extent. Leptin was not associated with measures of ECC after full adjustment. No adipokine was associated with MAC after full adjustment. CONCLUSIONS: We identified significant associations between select adipokines and specific markers of ECC. Adipokines may play a role in the development of systemic atherosclerosis.

Reducing disparities in adverse pregnancy outcomes in the United States.

There is growing evidence that rural and racial disparities and social determinants of health (SDOH) impact adverse pregnancy outcomes (APOs) and overall maternal mortality in the United States. These APOs, such as preeclampsia, preterm birth, and intrauterine growth restriction, are in-turn associated with increased risk of future cardiovascular disease (CVD) later in life. Importantly, SDOH such as socioeconomic disadvantages, poor health literacy, transportation barriers, lack of access to adequate health care, food insecurity, and psychosocial stressors have cascading effects on APOs and downstream cardiovascular health. These SDOH are also deeply intertwined with and compounded by existing racial and rural disparities. Pregnancy thus provides a unique opportunity to identify at-risk women from a social determinants perspective, and provide early interventions to optimize long-term CVD and mitigate cardiovascular health disparities. Addressing the challenges posed by these disparities requires a multi-pronged approach and involves national, regional, and individual level solutions. Eliminating disparities will necessitate a nationwide obligation to ensure health care equity via enhanced health insurance coverage, resource investment, and public and clinician accountability.

A Survey of Internal Medicine Interns Regarding the Most Useful Topics to Include in an Internal Medicine Track of a "Get Ready for Residency Boot Camp" Course.

In the last decade, boot camp residency preparatory courses for fourth-year medical students have become increasingly popular in medical schools across the USA; however, the curricular content of these courses varies widely. The authors surveyed internal medicine interns at a large academic medical center regarding clinical and non-clinical topics that would be useful for an internal medicine residency preparatory curriculum. The response rate was 79% (64/81). A rational approach to antibiotics (42%) and electrolyte management (41%) were the most frequent clinical topics and cross-cover (69%) was the most frequent non-clinical topic selected by interns.