Life-Threatening Reaction to Lifesaving Medication: Stepwise Approach to Severe Adverse Reactions to PCSK-9 Monoclonal Antibodies.

Typical side effects of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies including influenza-like illness and injection site reactions, are minor and well tolerated. This case, however, highlights a less common but severe reaction, indicating the need for clinicians to understand and manage potential rare side effects noted with biologics.

Lipoprotein Apheresis: Utility, Outcomes, and Implementation in Clinical Practice: A Scientific Statement From the American Heart Association.

Despite the availability of multiple classes of lipoprotein-lowering medications, some high-risk patients have persistent hypercholesterolemia and may require nonpharmacologic therapy. Lipoprotein apheresis (LA) is a valuable but underused adjunctive therapeutic option for low-density lipoprotein cholesterol and lipoprotein(a) lowering, particularly in children and adults with familial hypercholesterolemia. In addition to lipid lowering, LA reduces serum levels of proinflammatory and prothrombotic factors, reduces blood viscosity, increases microvascular myocardial perfusion, and may provide beneficial effects on endothelial function. Multiple observational studies demonstrate strong evidence for improved cardiovascular outcomes with LA; however, use in the United States is limited to a fraction of its Food and Drug Administration-approved indications. In addition, there are limited data regarding LA benefit for refractory focal segmental glomerulosclerosis. In this scientific statement, we review the history of LA, mechanisms of action, cardiovascular and renal outcomes data, indications, and options for treatment.

Traditional and non-traditional cardiovascular risk factor profiles in young patients with coronary artery disease.

Study objective: There is an increasing trend in myocardial infarction (MI) hospitalizations in young individuals. The prevalence of modifiable cardiovascular risk factors is high in this population. This study aims to assess the prevalence of traditional and non-traditional cardiovascular risk factors among young patients with coronary artery disease (CAD) including novel lipid and dietary biomarkers with a focus on potential gender differences. Design: The Young Heart study is a prospective, single-center pilot cohort study. Baseline data included medical history, medications, and lifestyle factors. We also collected blood samples for lipid profile, lipoprotein (a), high-sensitivity C-reactive protein (hsCRP), and trimethylamine N-oxide (TMAO). Participants: A total of 60 patients aged <60 years with CAD (on coronary CT or invasive angiogram) were included in the study. Results: The median age was 51 years and predominantly male (70 %). Baseline assessment revealed a high prevalence of hypertension (76.7 %), hyperlipidemia (91.7 %), and obstructive CAD (88.3 %). 36.7 % had diabetes, 28.3 % had prediabetes, and 38.3 % had prior MI. Uncontrolled risk factors were prevalent, including increased waist circumference (54.6 %), metabolic syndrome (60.0 %), and LDL ≥70 mg/dL (47.5 %), Lp(a) ≥75 nmol/L (47.5 %). Furthermore, 41.7 % had hsCRP ≥2 mg/L, and 28.3 % had suboptimal TMAO levels. 70.0 % of patients were on guideline-directed doses of statins. Conclusion: Young patients with CAD demonstrated a substantial burden of traditional and non-traditional cardiovascular risk factors. The study findings highlight the need for targeted interventions to improve risk factor control and optimize lifestyle behaviors. Further investigation is warranted to assess the impact of these interventions on cardiovascular outcomes.

Coronary Artery Calcium for Risk Stratification Among Persons With Very High HDL Cholesterol.

Background: Compared to normal high-density lipoprotein (HDL) cholesterol values, very high HDL cholesterol is associated with a higher incidence of mortality and atherosclerotic cardiovascular disease (ASCVD). As such, clinical risk stratification among persons with very high HDL cholesterol is challenging. Objectives: Among persons with very high HDL cholesterol, the purpose was to determine the prevalence of coronary artery calcium (CAC) and compare the association between traditional risk factors vs CAC for all-cause mortality and ASCVD. Methods: The primary analysis was completed among 446 participants from the Cedars-Sinai Medical Center of the CAC Consortium with very high HDL cholesterol (≥77 mg/dL in men, ≥97 mg/dL in women). Cox proportional hazards regression assessed the association of CAC and traditional risk factors with all-cause mortality during a median follow-up of 10.7 years. Replication and validation analyses were performed for all-cause mortality among 119 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with very high HDL cholesterol, who also had information on incident ASCVD. Results: The mean age was 57.9 years old, 49% were women, and the median HDL cholesterol was 98 mg/dL. One-half of participants (50%) had prevalent CAC, in whom the median CAC score was 118. Prevalent CAC conferred a 3.6-fold higher risk of all-cause mortality (HR: 3.64; 95% CI: 1.21-11.01), which appeared to be a more robust predictor than individual traditional risk factors beyond age. In the validation sample, prevalent CAC but not individual traditional risk factors were associated with all-cause mortality (HR: 2.39; 95% CI: 1.07-5.34) and a 4.0-fold higher risk of ASCVD (HR: 4.06; 95% CI: 1.11-14.84). Conclusions: Measurement of CAC may facilitate clinical risk assessment among individuals with very high HDL cholesterol.

Advances in targeting LDL cholesterol: PCSK9 inhibitors and beyond.

There is a direct relationship between the duration and level of exposure to low density lipoprotein cholesterol (LDL-C) levels over one's lifespan and cardiovascular events. Early treatment to lower elevated LDL-C is crucial for better outcomes with multiple therapies currently available to reduce atherogenic lipoproteins. Statins remain the foundation of LDL-C lowering therapy as one of the most cost-effective drugs to reduce atherosclerotic events (ASCVD) and mortality. Nonetheless, LDL-driven goal attainment remains suboptimal globally, highlighting a considerable need for non-statin therapies to address residual risk related to statin intolerance, non-adherence, and inherited lipoprotein disorders. LDL-C lowering interventions beyond statins include ezetimibe, PCSK9 monoclonal antibodies, inclisiran and bempedoic acid with specific guideline recommendations as to when to consider each. For patients with homozygous familial hypercholesterolemia requiring more advanced therapy, lomitapide and evinacumab are available, providing mechanisms that are not LDL receptor dependent. Lipoprotein apheresis remains an effective option for clinical familial hypercholesterolemia as well as elevated lipoprotein (a). There are investigational therapies being explored to add to our current armamentarium including CETP inhibitors, a third-generation PCSK9 inhibitor (small recombinant fusion protein oral PCSK9 inhibitor) and gene editing which aims to directly restore or disrupt genes of interest at the DNA level. This article is a brief review of the pharmacotherapy options beyond statins for lowering LDL-C and their impact on ASCVD risk reduction. Our primary aim is to guide physicians on the role these therapies play in achieving appropriate LDL-C goals, with an algorithm of when to consider each based on efficacy, safety and outcomes.

Dyslipidemia management in women of reproductive potential: An expert clinical consensus from the national lipid association.

Cardiovascular disease (CVD) is the leading cause of death among women and its incidence has been increasing recently, particularly among younger women. Across major professional society guidelines, dyslipidemia management remains a central tenet for atherosclerotic CVD prevention for both women and men. Despite this, women, particularly young women, who are candidates for statin therapy are less likely to be treated and less likely to achieve their recommended therapeutic objectives for low-density lipoprotein cholesterol (LDL-C) levels. Elevated LDL-C and triglycerides are the two most common dyslipidemias that should be addressed during pregnancy due to the increased risk for adverse pregnancy outcomes, such as preeclampsia, gestational diabetes mellitus, and pre-term delivery, as well as pancreatitis in the presence of severe hypertriglyceridemia. In this National Lipid Association Expert Clinical Consensus, we review the roles of nutrition, physical activity, and pharmacotherapy as strategies to address elevated levels of LDL-C and/or triglycerides among women of reproductive age. We include a special focus on points to consider during the shared decision-making discussion regarding pharmacotherapy for dyslipidemia during preconception planning, pregnancy, and lactation.

Statin utilization and cardiovascular outcomes in a real-world primary prevention cohort of older adults.

Background: Statins are a cost-effective therapy for prevention of atherosclerotic cardiovascular disease (ASCVD). Guidelines on statins for primary prevention are unclear for older adults (>75 years). Objective: Investigate statin utility in older adults without ASCVD events, by risk stratifying in a large healthcare network. Methods: We included 8,114 older adults, without CAD, PVD or ischemic stroke. Statin utilization based on ACC/AHA 10-year ASCVD risk calculation, was evaluated in intermediate (7.5%-19.9%) and high-risk patients (≥ 20%); and categorized using low and 'moderate or high' intensity statins with a follow up period of ∼7 years. Cox regression models were used to calculate hazard ratios for incident ASCVD and mortality across risk categories stratified by statin utilization. Data was adjusted for competing risk using Elixhauser Comorbidity Index. Results: Compared with those on moderate or high intensity statins, high-risk older patients not on any statin had a significantly increased risk of MI [HR 1.51 (1.17-1.95); p<0.01], stroke [HR 1.47 (1.14-1.90); p<0.01] and all-cause mortality [HR 1.37 (1.19-1.58); p<0.001] in models adjusted for Elixhauser Comorbidity Index. When comparing the no statin group versus the moderate or high intensity statin group in the intermediate risk cohort, although a trend for increased risk was seen, it did not meet statistical significance thresholds for MI, stroke or all-cause mortality. Conclusion: Lack of statin use was associated with increased cardiovascular events and mortality in high-risk older adults. Given the benefits appreciated, statin use may need to be strongly considered for primary ASCVD prevention among high-risk older adults. Future studies will assess the risk-benefit ratio of statin intervention in older adults.

Clinical Significance of Supraventricular Tachycardia During Pregnancy in Healthy Women.

BACKGROUND: Supraventricular tachycardias (SVT) are the most frequently encountered arrhythmias in pregnancy with unclear clinical significance. OBJECTIVES: This study sought to report the prevalence, describe the management, and explore the association between SVT and adverse obstetric outcomes. METHODS: Cohort study of primiparous and multiparous women without history of Cesarean section (CS), and with structurally normal hearts admitted in labor. The study group consisted of women with at least 1 SVT episode during pregnancy, and the control group was randomly selected in a 4:1 ratio. RESULTS: Of 141,769 women meeting the inclusion criteria, SVT diagnosis was confirmed in 122. A total of 76 (age 33.2 ± 4.8 years) had at least 1 symptomatic and documented episode during pregnancy. In women with a known SVT diagnosis before pregnancy, medical therapy was not associated with a lower risk of SVT recurrence (OR: 1.07; 95% CI: 0.41-2.80). However, catheter ablation before pregnancy was associated with significantly lower risk of SVT recurrence (OR: 0.09; 95% CI: 0.04-0.23). Women with SVT during pregnancy had higher incidence of CS (39.5% vs 27.0%; P = 0.03), and preterm labor (PTL) (30.3% vs 8.6%; P < 0.001). Adjusting for age and parity, SVT during pregnancy was an independent predictor of CS (OR: 1.80; 95% CI: 1.03-3.10), particularly planned CS (OR: 2.89; 95% CI: 1.06-7.89) and PTL (OR: 4.37; 95% CI: 2.30-8.31). CONCLUSIONS: SVT during pregnancy is associated with increased risk for CS and PTL in healthy women. History of SVT should be sought as early as preconception counseling, and a multidisciplinary approach is warranted for both prevention and management of SVT occurrence.

Patterns of Statin Therapy Use and Associated Outcomes in Older Veterans Across Kidney Function.

BACKGROUND: Despite significant morbidity and mortality related to atherosclerotic cardiovascular disease, to date, most major clinical trials studying the effects of statin therapy have excluded older adults. The objective of this analysis was to evaluate the effect of initiating statin therapy on incident dementia and mortality among individuals 75 years of age or older across the complete spectrum of kidney function. METHODS: We conducted a retrospective cohort study of 640,191 VA health system patients who turned 75 years of age between 2000 and 2018. Patients on statin therapy received the medication for an average of 6.3 years (standard deviation 4.6 years). The primary outcome of interest included incident dementia diagnosis during the study period. The secondary outcome was all-cause mortality. Cox proportional hazard analysis was used to evaluate the adjusted association of statin initiation with these outcomes. RESULTS: There was a higher rate of incident dementia in the No Statin group (4.7%) vs the Statin group (3.2%). Additionally, we observed a 22% all-cause mortality benefit associated with statin therapy. We did not observe a treatment effect with respect to primary or secondary outcomes across varying levels of kidney function. CONCLUSION: This large cohort study did not reveal an association between the initiation of statin therapy and incident dementia. A survival benefit was seen in statin users compared with nonusers. Prospective studies in more diverse populations including older adults will be needed to verify these findings.

Clinical, Sociodemographic, and Neighborhood Characteristics Associated with Adverse Pregnancy Outcomes.

Background: Cardiovascular risk is increased by a history of adverse pregnancy outcomes (APOs). Efforts to understand and prevent these adverse outcomes may improve both fetal and birthing persons' outcomes in the peripartum period, and over the patient's lifetime. This study aims to assess the association of clinical, sociodemographic, and economic neighbor-hood factors with preterm birth (PTB) and APOs (the composite of stillbirth, small for gestation age, and low birthweight). Materials and Methods: This is a cross-sectional study using the electronic medical records of deliveries from seven Northwell Health hospitals between January 1, 2018 and July 31, 2020. There were 62,787 deliveries reviewed in this study. Deliveries that were not the first for the patient during the study period and multiple gestational pregnancies were excluded. Patients with incomplete data on outcome were also excluded. Main outcomes were PTB and composite APOs. Measures included history of PTB, hypertension, diabetes, body mass index, race/ethnicity, age, preferred language, marital status, parity, health insurance, and median income, percent unemployment, and mean household size by zip code. Results: Of the 62,787 deliveries, 43.3% were from white, Non-Hispanic, and Non-Latino patients. There were 4,552 (7.2%) PTBs and 8,634 (13.8%) APOs. Patients enrolled in public insurance had higher odds of PTB (odds ratio [OR] 1.15, 95% CI 1.06-1.24) and APOs (OR 1.19, 95% CI 1.12-1.25). There was a statistically significant association of both PTB (p = 0.037) and APOs (p = 0.005) when comparing patients that live in a zip code with a median income over 100k to those with an income <100k. In addition, living in a zip code within the second quintile of unemployment was associated with lower odds of APOs (OR 0.92, 95% CI 0.84-0.99). Conclusions: Numerous sociodemographic and clinical factors are associated with both PTB and APOs. Tailored programs addressing these disparities may improve outcomes in pregnant persons.

A system approach to improving guideline-directed therapy for cardio-renal-metabolic conditions: The "beyond diabetes" initiative.

Objective: Despite demonstrating improvements in cardiovascular disease, kidney disease, and survival outcomes, guideline-directed antihyperglycemic medications such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like-peptide-1 receptor agonists (GLP1-RA), are underutilized. Many obstacles constrain their use including lack of systematic provider and patient education, concern for medication side effects, and patient affordability. Methods: We designed a multimodality, systems-based approach to address these challenges with the goal of increasing medication utilization across the largest healthcare system in New York State. This multispecialty collaborative included provider and patient education, an electronic health record-enabled platform to identify eligible patients, and access to pharmacists for medication guidance and addressing insurance coverage barriers. Surveys were administered following grand rounds lectures and knowledge-based questionnaires were given before and after case-based sessions for housestaff, with results analyzed using a two-sided Student's t-test. Rates of first prescriptions of SGLT2i/GLP1-RA in combined and individual analyses were compared between the pre- and post-education periods (6 months prior to 3/31/2021 and 6 months post 8/19/2021), and the change in prescriptions per 100 eligible-visits was assessed using the incidence density approach. Results: Among grand rounds participants, 69.3% of respondents said they would make changes to their clinical practice. Knowledge increased by 14.7% (p-value <0.001) among housestaff following case-based sessions. An increase in SGLT2i/GLP1-RA prescribing was noted for eligible patients among internal medicine, cardiology, nephrology, and endocrinology providers, from 11.9 per 100 eligible visits in the pre-education period to 14.8 in the post-education period (absolute increase 2.9 [24.4%], incidence risk ratio 1.24 [95% CI 1.18-1.31]; p-value <0.001). Increases in prescribing rates were also seen among individual medical specialties. Conclusions: Our "Beyond Diabetes" initiative showed an improvement in provider knowledge-base and was associated with a modest, but statistically significant increase in the use of SGLT2i and GLP1-RA throughout our healthcare system.

JCL Roundtable: Lipidology and Women's Health.

In this JCL Roundtable, we bring together three experts to discuss women's cardiovascular health throughout the lifespan, viewed from the standpoint of clinical lipidology. Overall, heart disease leads to one out of every 3 deaths of American women, but unfortunately patient awareness of cardiovascular risk actually has declined since 2009. Younger women are not exempt, since their risk can be increased by smoking, birth control, adverse lifestyle and diet, and genetic disorders. Age at menarche can influence lifetime risk. Polycystic ovary syndrome, noted in 5-13% of women of reproductive age, has been linked to increased cardiovascular risk, partly through atherogenic dyslipidemia. Oral contraception has improved greatly since its introduction, but remains a risk for venous thromboembolism and stroke, particularly in smokers. Fetal nutritional and metabolic requirements in pregnancy impose high vascular demand on the placenta and lead to escalating maternal triglycerides and cholesterol especially in the 3rd trimester. Triglycerides may require special management. Adverse pregnancy outcomes associated with placental dysfunction signal subsequent increased risk for maternal atherosclerotic disease. Early menopause has long been recognized as a risk enhancing factor for atherosclerosis with pathophysiology remaining unclear. The menopause transition represents a period when cardiovascular risk for women increases rapidly and approaches that of men. Current studies are evaluating hormonal changes and even clonal hematopoiesis as potential causes. At the same time, lifestyle habits and routine chronic conditions such as hypertension and obesity/diabetes/metabolic syndrome play a large role and need attention.

Transgender Cardiovascular Health: Practical Management for the Clinician.

PURPOSE OF REVIEW: Transgender individuals represent a growing part of our population with current trends indicating that clinicians will be treating more transgender patients in both the inpatient and outpatient setting. Current cardiovascular guidelines lack recommendations for transgender care secondary to limited data in this population. As we await future guideline recommendations, we provide a comprehensive review of the literature and practical management strategies related to transgender cardiovascular health. RECENT FINDINGS: Transgender individuals are at higher risk for some cardiovascular diseases compared to their cisgender counterparts. Gender-affirming hormone therapy, concomitant health conditions, lifestyle habits, access to services, and quality of care all contribute to this finding. While it is likely both safe and appropriate to apply current CVD guidelines to the care of transgender men and women, clinicians should consider additional factors in risk assessment and address unique aspects of care at every visit.

Comparison of American and European Guidelines for Primary Prevention of Cardiovascular Disease: JACC Guideline Comparison.

This review compares the primary prevention recommendations of the recent 2021 European Society of Cardiology (ESC) and 2019 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines on cardiovascular disease (CVD) prevention. Although the 2019 ACC/AHA guideline represents its inaugural version, the ESC guideline is an update to its 2016 statement. Both guidelines address prevention using a holistic approach and agree on the importance of lifestyle optimization and intensified risk factor management. Cardiovascular (CV) risk assessment tools differ, reflecting the unique populations being screened as well as philosophical differences to their approach. Conventional risk factors are used to estimate CV risk, but each guideline acknowledges the role of risk modifiers to refine risk calculation. The ESC guideline recognizes the importance of nonclassical risk factors, including environmental issues, that impact CV health at the population level and calls for legislative action at the local, regional, and national levels.

The effects of gender-affirming hormone therapy on cardiovascular and skeletal health: A literature review.

Approximately 1.5 million people in the United States currently identify as transgender. The use of gender affirming hormone therapy is integral to routine clinical care of transgender individuals, yet our understanding of the effects of this therapy is limited. There are reasons to believe that gender affirming hormone therapy may have important effects on cardiovascular risk and bone health in transgender individuals. The purpose of this review article is to summarize the evidence for the cardiovascular effects (including coronary artery disease, hypertension and stroke) as well as the effects on bone metabolism associated with gender affirming hormone therapy in both transgender men and transgender women.

Challenges in Optimizing Lipid Management in Women.

While there are physiologic differences in lipid metabolism in men and women, pharmacologic therapy is very effective in both with similar management strategies recommended in the current guidelines for the management of dyslipidemia. Despite similar guidelines for treatment, studies have shown that women have worse control of dyslipidemia than their male counterparts. This may stem from multiple contributing factors including underestimation of cardiovascular disease risk in women, decreased prescription and utilization of lipid-lowering therapies, decreased medication adherence, and higher risk of statin intolerance, all of which may contribute to lower attainment of lipid targets. Furthermore, heart disease is the leading cause of mortality in women, with heart disease noted an average of 7-10 years later than in men. This has historically led to the misperception that women are protected from heart disease and can be treated less aggressively. In fact, traditional risk factors for atherosclerotic cardiovascular disease often impact risk in women to a greater extent than they do in men. Unique risk factors such as pregnancy-related disorders also contribute to the level of risk and therefore warrant consideration in risk stratification. This review summarizes the efficacy of contemporary lipid-lowering therapies in women versus men and discusses the challenges that arise with lipid management in women along with potential ways to tackle these obstacles.

Leveraging clinical decision support tools to improve guideline-directed medical therapy in patients with atherosclerotic cardiovascular disease at hospital discharge.

BACKGROUND: Guidelines recommend moderate to high-intensity statins and antithrombotic agents in patients with atherosclerotic cardiovascular disease (ASCVD). However, guideline-directed medical therapy (GDMT) remains suboptimal. METHODS: In this quality initiative, best practice alerts (BPA) in the electronic health record (EHR) were utilized to alert providers to prescribe to GDMT upon hospital discharge in ASCVD patients. Rates of GDMT were compared for 5 months pre- and post-BPA implementation. Multivariable regression was used to identify predictors of GDMT. RESULTS: In 5985 pre- and 5568 post-BPA patients, the average age was 69.1 ± 12.8 years and 58.5% were male. There was a 4.0% increase in statin use from 67.3% to 71.3% and a 3.1% increase in antithrombotic use from 75.3% to 78.4% in the post-BPA cohort. CONCLUSIONS: This simple EHR-based initiative was associated with a modest increase in ASCVD patients being discharged on GDMT. Leveraging clinical decision support tools provides an opportunity to influence provider behavior and improve care for ASCVD patients, and warrants further investigation.