GLP-1 Receptor Agonists and Cardiovascular Disease: What Do Clinicians Need to Know?

PURPOSE OF REVIEW: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are gaining importance due to their effects on cardiovascular parameters. This review discusses the findings of dedicated cardiovascular outcome trials of GLP-1RAs and summarizes their utility to help clinicians understand their role in cardiovascular disease. RECENT FINDINGS: Patients with diabetes mellitus are at an increased risk of cardiovascular disease. Cardiovascular outcome trials have shown GLP-1RAs decrease the primary composite outcome of the first occurrence of major adverse cardiovascular events (MACE) in patients with diabetes. Additionally, select GLP-1RAs have also shown improved cardiovascular outcomes in patients without diabetes who are either overweight (BMI ≥ 27), or obese (BMI ≥ 30). There have also been encouraging results in patients with heart failure with preserved ejection fraction. There is increasing evidence showing GLP-1RAs are beneficial across the cardiometabolic spectrum of disease. Implementation of these therapeutics into clinical practice is important to improve cardiovascular risk.

Sustainable Approach to Justice, Equity, Diversity, and Inclusion Through Better Quality Measurement.

The US health care industry has broadly adopted performance and quality measures that are extracted from electronic health records and connected to payment incentives that hope to improve declining life expectancy and health status and reduce costs. While the development of a quality measurement infrastructure based on electronic health record data was an important first step in addressing US health outcomes, these metrics, reflecting the average performance across diverse populations, do not adequately adjust for population demographic differences, social determinants of health, or ecosystem vulnerability. Like society as a whole, health care must confront the powerful impact that social determinants of health, race, ethnicity, and other demographic variations have on key health care performance indicators and quality metrics. Tools that are currently available to capture and report the health status of Americans lack the granularity, complexity, and standardization needed to improve health and address disparities at the local level. In this article, we discuss the current and future state of electronic clinical quality measures through a lens of equity.

Relationship between body mass index and cardiometabolic health in a multi-ethnic population: A project baseline health study.

Objective: Obesity is associated with a higher risk of cardiovascular disease. Understanding the associations between comprehensive health parameters and body mass index (BMI) may lead to targeted prevention efforts. Methods: Project Baseline Health Study (PBHS) participants were divided into six BMI categories: underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), class I obesity (30-34.9 kg/m2), class II obesity (35-39.9 kg/m2), and class III obesity (BMI ≥40 kg/m2). Demographic, cardiometabolic, mental health, and physical health parameters were compared across BMI categories, and multivariable logistic regression models were fit to evaluate associations. Results: A total of 2,493 PBHS participants were evaluated. The mean age was 50±17.2 years; 55 % were female, 12 % Hispanic, 16 % Black, and 10 % Asian. The average BMI was 28.4 kg/m2±6.9. The distribution of BMI by age group was comparable to the 2017-2018 National Health and Nutrition Examination Survey (NHANES) dataset. The obesity categories had higher proportions of participants with CAC scores >0, hypertension, diabetes, lower HDL-C, lower vitamin D, higher triglycerides, higher hsCRP, lower mean step counts, higher mean PHQ-9 scores, and higher mean GAD-7 scores. Conclusion: We identified associations of cardiometabolic and mental health characteristics with BMI, thereby providing a deeper understanding of cardiovascular health across BMI.

Generalizability of an EHR-network dataset to the United States for cardiovascular disease conditions: Comparison of Cerner real world data with the national inpatient sample.

BACKGROUND: Electronic Health Record (EHR) data from health systems are increasingly being combined for clinical research purposes. Yet, it remains unclear whether these large EHR data sources provide a representative assessment of national disease prevalence and treatment. To evaluate this, we compared Cerner RealWorldData (CRWD), a large EHR data source, to those seen in the National Inpatient Sample (NIS) for 3 cardiovascular conditions (myocardial infarction (MI), congestive heart failure (CHF), and stroke. METHODS: Adult patients (age ≥18 years) hospitalized with MI, CHF, and stroke were identified in both CRWD (86 health systems) and the NIS (4,782 hospitals). Patient demographics, comorbidities, procedures, outcomes (length of stay and in-hospital mortality) and hospital type (teaching or nonteaching) were compared between NIS and CRWD patients. RESULTS: Of 86 health systems participating in CRWD, 33 were excluded for potential data quality issues which accounted for about 11% of hospitalizations in the dataset, leaving 53 for inclusion in analysis which accounted for about 89% of hospitalizations in the dataset. Between January 1, 2017 and December 31, 2018, 116,956 MI, 188,107 CHF, and 93,968 stroke hospitalizations were identified in CRWD vs 2,245,300 MI, 4,310,745 CHF, and 1,333,480 stroke hospitalizations in the NIS. Patient demographics were similar among patients in CWRD and the NIS for all 3 cardiovascular groups except for ethnicity, with underrepresentation of Hispanic individuals in CRWD vs the NIS. Patients hospitalized in CRWD had a slightly higher proportion of coded co-morbidities compared with NIS hospitalizations due to a longer potential look-back period. For patients with MI, hospital mortality, length of stay, coronary artery bypass graft (CABG) rates, and percutaneous coronary intervention (PCI) rates were similar between CRWD and NIS. Additionally, there was similar in hospital mortality and length of stay for those with CHF and stroke hospitalizations between CRWD and NIS. CONCLUSIONS: On aggregate, characteristics of hospitalizations for MI, CHF, and stroke using EHR data from one nationwide EHR-derived database, CRWD, appears similar to characteristics of hospitalizations in the nationally representative NIS. Important limitations of CRWD include lack of geographic representativeness, under-representation of Hispanic adults, and the need to exclude health systems for missing data.

Uptake of non-statin lipid-lowering therapies for secondary prevention in community practice.

Nearly two-thirds of individuals with atherosclerotic cardiovascular disease (ASCVD) do not reach target low-density lipoprotein cholesterol despite statin therapy. Three novel lipid-lowering therapies have proven to further reduce ASCVD beyond statins, including: ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), and icosapent ethyl. This study evaluated the use of these three agents in 728,423 individuals with ASCVD from 89 US health systems from 01/2018 through 03/2021 using the electronic health record. As of 2021, only 6.0% of ASCVD patients were on ezetimibe, 1.6% were on a PCSK9i, and 1.3% on icosapent ethyl, with utilization only marginally increasing over the study period. Addressing the underutilization of non-statin lipid-lowering therapy for secondary prevention is a critical step in improving the treatment gap of patients with residual risk of ASCVD.

Call to action: Understanding the differences in the use of SGLT-2 inhibitors and GLP-1 receptor agonists.

Cardiovascular disease remains one of the most prominent global health problems and has been demonstrated to disproportionally affect certain communities. Despite an increasing collective effort to improve health inequalities, a multitude of disparities continue to affect cardiovascular outcomes. Among the most prominent disparities within cardiovascular disease prevention are with the use and distribution of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. Several landmark trials have demonstrated the efficacy of these novel agents, not only in cardiovascular disease prevention among those with diabetes, but also in heart failure and chronic kidney disease. However, the use of these agents remains limited by disparities in certain racial/ethnic, sex, and socioeconomic groups. This review works to highlight and understand these differences on the use and prescribing patterns of pivotal agents in cardiovascular disease prevention, SGLT-2 inhibitors and GLP-1 agonists. Our aim is to enrich understanding and to inspire efforts to end disparities in cardiovascular morbidity and mortality due to race, sex and income inequality.

Bending the Cardiovascular Event Curve by Evaluating the Potential Impact of Achieving Low-Density Lipoprotein Cholesterol Goal Across a Large Health System Among Secondary Prevention Patients.

Guidelines recommend aggressive low-density lipoprotein cholesterol (LDL-C) lowering in patients with atherosclerotic cardiovascular disease (ASCVD). However, the recommended threshold of LDL-C ≤70 mg/dL is often not achieved. We used data from the Duke University Health System electronic health record to characterize patterns of lipid levels and lipid management in patients with ASCVD to estimate the number of clinical events that could be prevented by achieving LDL-C ≤70 mg/dL . A multivariable logistic regression model was developed to predict the 1-year composite of all-cause mortality, myocardial infarction, stroke, or coronary revascularization and was validated through bootstrapping. The number needed to treat to prevent an event was then determined. Among 56,230 patients with ASCVD, the median (quartile 1, quartile 3) age was 68.6 years (59.9, 76.2), 47% were women, and 27% were non-Hispanic Black. LDL-C was >70 mg/dL in 39,566 of patients (70%); these patients were more frequently female (51% vs 36%), non-Hispanic Black (28% vs 23%), and less frequently on statin therapy (67% vs 91%) than those with LDL-C ≤70 mg/dL . A predictive model with reasonable discrimination (c-index 0.77, 95% confidence interval 0.760 to 0.77) and calibration (slope 0.99) determined that if the overall population achieved an LDL-C ≤70 mg/dL, 734 clinical events (455 myocardial infarctions, 186 strokes, and 93 coronary revascularizations) could be prevented in a year. Achieving LDL-C ≤70 mg/dL in patients with ASCVD across a health system could prevent significant clinical events within a single year. In conclusion, this study quantifies the potential benefit of a system-wide effort to achieve guideline-based LDL-C goals.

Emerging role of positron emission tomography (PET) imaging in cardiac surgery.

Historically, structural and anatomical imaging has been the mainstay in the diagnosis and management of cardiovascular diseases. In recent years there has been a shift toward increased use of functional imaging studies, including positron emission tomography (PET). PET is a noninvasive nuclear medicine-imaging technique that uses radiotracers to generate images of a radionucleotide distribution by detecting the physiologic substrates that emit positron radionuclides. This article will focus on the applications of PET imaging for the cardiac surgeon and highlight the collaborative nature of using PET imaging for the management of complex heart disease. We present cases that demonstrate the value of using PET imaging in the diagnosis of coronary artery disease and management of complex endocarditis, and in targeted cardiovascular therapies.

Trends in Oral Anticoagulant Use Among 436 864 Patients With Atrial Fibrillation in Community Practice, 2011 to 2020.

Background Among patients with nonvalvular atrial fibrillation (AF) and an elevated stroke risk, guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention. Changes in DOAC use over the past decade have not been well described. Methods and Results We evaluated trends in use of DOACs and warfarin from 2011 to 2020 among adults with AF and a CHA2DS2-VASc score ≥2 based on electronic health record data from 88 health systems in the United States contributing to Cerner Real World Data. The use of DOACs and warfarin was described over time, by age, sex, race, and ethnicity, and at the health-system level. We identified 436 864 patients with AF at risk for stroke (median age, 78 years; 52.1% men). From 2011 to 2020, overall anticoagulation rates increased from 56.3% to 64.7%, as DOAC use increased steadily (from 4.7% to 47.9%), while warfarin use declined (from 52.4% to 17.7%). DOAC uptake was similar across age, sex, and race and ethnicity groups but varied by health system. In 2020, the median health-system-level proportion of patients with AF on a DOAC was 49% (interquartile range, 40%-54%). Conclusions Over the past decade, anticoagulation rates for patients with AF have increased modestly as DOACs largely replaced warfarin, though significant gaps remain: One in 3 high-risk patients with AF is not on any anticoagulant. While DOAC adoption was generally consistent across major demographic groups, use between health systems remained highly variable, suggesting that provider and system factors influence DOAC uptake use more than patient-level factors.

Eradicating Atherosclerosis: Should We Start Statins at Younger Ages and at Lower LDL-Cs.

PURPOSE OF REVIEW: Given the increasing burden of cardiovascular disease, we review the literature for earlier initiation of statin therapy at younger ages and lower low-density lipoprotein cholesterol (LDL-C) levels, with the goal of preventing the development of atherosclerosis prior to clinical events. RECENT FINDINGS: There is a rising prevalence of dyslipidemia among younger adults. Although guidelines offer recommendations for adults over 40, there is little guidance for the management of younger adults with moderately elevated LDL-C levels. Earlier and more aggressive statin use may slow progression, or even halt atherosclerosis, and may likewise be beneficial and cost-effective on a population level. Further research is needed to define the exact age and LDL-C level at which to start statin therapy. Until then, more detailed risk stratification with lab testing and imaging should be used to identify younger adults at the highest risk.

Lipid-Lowering Therapy in Women of Childbearing Age: a Review and Stepwise Clinical Approach.

PURPOSE OF REVIEW: Women are less often recognized to have cardiovascular disease (CVD) risk and are underrepresented in randomized trials of lipid-lowering therapy. Here, we summarize non-pharmacologic and pharmacologic strategies for lipid-lowering in women of childbearing age, lipid changes during pregnancy and lactation, discuss sex-specific outcomes in currently available literature, and discuss future areas of research. RECENT FINDINGS: While lifestyle interventions form the backbone of CVD prevention, some women of reproductive age have an indication for pharmacologic lipid-lowering. Sex-based evidence is limited but suggests that both statin and non-statin lipid-lowering agents are beneficial regardless of sex, especially at high cardiovascular risk. Pharmacologic lipid-lowering therapies, both during the pregnancy period and during lactation, have historically been and continue to be limited by safety concerns. This oftentimes limits lipid-lowering options in women of childbearing age. In this review, we summarize lipid-lowering strategies in women of childbearing age and the impact of therapies during pregnancy and lactation. The limited sex-specific data regarding efficacy, adverse events, and cardiovascular outcomes underscore the need for a greater representation of women in randomized controlled trials. More data on lipid-lowering teratogenicity are needed, and through increased clinician awareness and reporting to incidental exposure registries, more data can be harvested.

Cardiometabolic Comorbidities in Cancer Survivors: JACC: CardioOncology State-of-the-Art Review.

There are nearly 17 million cancer survivors in the United States, including those who are currently receiving cancer therapy with curative intent and expected to be long-term survivors, as well as those with chronic cancers such as metastatic disease or chronic lymphocytic leukemia, who will receive cancer therapy for many years. Current clinical practice guidelines focus on lifestyle interventions, such as exercise and healthy eating habits, but generally do not address management strategies for clinicians or strategies to increase adherence to medications. We discuss 3 cardiometabolic comorbidities among cancer survivors and present the prevalence of comorbidities prior to a cancer diagnosis, treatment of comorbidities during cancer therapy, and management considerations of comorbidities in long-term cancer survivors or those on chronic cancer therapy. Approaches to support medication adherence and potential methods to enhance a team approach to optimize care of the individual with cancer across the continuum of disease are discussed.

Trends of blood pressure control in the U.S. during the COVID-19 pandemic.

IMPORTANCE: COVID-19 altered lifestyles and disrupted routine health care. Whether blood pressure (BP) control worsened during COVID-19 is unknown. OBJECTIVE: To understand whether home BP control worsened during COVID-19 across the United States (US) . DESIGN, SETTING, AND PARTICIPANTS: A population-based analysis of home BP data from 72,706 participants enrolled in a digital health hypertension control program. Data was compared before (January 2019 to March 2020) and during (April 2020 to August 2020) COVID-19. MAIN OUTCOMES AND MEASURES: Monthly mean home BP readings, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were quantified before and during the pandemic. Multivariable adjustments were made for age, sex, race, region, and months enrolled. Home BP readings were also classified based on monthly averages and highest home BP readings into risk groups: Stage 2 HTN: BP> = 135 or DBP> = 85; Uncontrolled HTN: SBP> = 145 or DBP> = 95; or Severely uncontrolled HTN: SBP> = 160 or DBP> = 100). RESULTS: Overall, 72,706 participants were enrolled in a digital health hypertension program between 1/1/2019 and 8/31/2020. Compared with participants pre-COVID-19 (n = 33,440), those during COVID-19 (n = 39,266) were of similar age (mean 53.0 ± 10.7 years vs 53.3 ± 10.8 years); sex (46% vs 50.6% female) and race (29.1% vs 34.2% non-white). Relative to pre-Covid (Apr-Aug 2019) the mean monthly number of home BP readings rose during COVID-19 (Apr-Aug, 2020), from 7.3 to 9.3 per month (P < .001). During COVID-19, participants had higher monthly adjusted mean SBP (131.6 mmHg vs. 127.5 mmHg, P < .001); DBP (80.2 mmHg vs. 79.2 mmHg, P < .001); and MAP (97.4 mmHg vs. 95.3 mmHg; P < .001). Relative to the pre-pandemic period, during COVID-19 the proportion of participants with a mean monthly BP classified as uncontrolled or severely uncontrolled hypertension also rose, 15% vs 19% and 4% vs 5%, respectively CONCLUSIONS AND RELEVANCE: Based on home BP readings, mean monthly BP rose modestly after COVID-19, despite increased utilization of home monitoring. Further studies are needed to examine the longitudinal effects of the pandemic on cardiovascular disease risk factors, the impact of these on long-term population health.

Low-touch, team-based care for co-morbidity management in cancer patients: the ONE TEAM randomized controlled trial.

BACKGROUND: As treatments for cancer have improved, more people are surviving cancer. However, compared to people without a history of cancer, cancer survivors are more likely to die of cardiovascular disease (CVD). Increased risk for CVD-related mortality among cancer survivors is partially due to lack of medication adherence and problems that exist in care coordination between cancer specialists, primary care physicians, and cardiologists. METHODS/DESIGN: The Onco-primary care networking to support TEAM-based care (ONE TEAM) study is an 18-month cluster-randomized controlled trial with clustering at the primary care clinic level. ONE TEAM compares the provision of the iGuide intervention to patients and primary care providers versus an education-only control. For phase 1, at the patient level, the intervention includes video vignettes and a live webinar; provider-level interventions include electronic health records-based communication and case-based webinars. Participants will be enrolled from across North Carolina one of their first visits with a cancer specialist (e.g., surgeon, radiation or medical oncologist). We use a sequential multiple assignment randomized trial (SMART) design. Outcomes (measured at the patient level) will include Healthcare Effectiveness Data and Information Set (HEDIS) quality measures of management of three CVD comorbidities using laboratory testing (glycated hemoglobin [A1c], lipid profile) and blood pressure measurements; (2) medication adherence assessed pharmacy refill data using Proportion of Days Covered (PDC); and (3) patient-provider communication (Patient-Centered Communication in Cancer Care, PCC-Ca-36). Primary care clinics in the intervention arm will be considered non-responders if 90% or more of their participating patients do not meet the modified HEDIS quality metrics at the 6-month measurement, assessed once the first enrollee from each practice reaches the 12-month mark. Non-responders will be re-randomized to either continue to receive the iGuide 1 intervention, or to receive the iGuide 2 intervention, which includes tailored videos for participants and specialist consults with primary care providers. DISCUSSION: As the population of cancer survivors grows, ONE TEAM will contribute to closing the CVD outcomes gap among cancer survivors by optimizing and integrating cancer care and primary care teams. ONE TEAM is designed so that it will be possible for others to emulate and implement at scale. TRIAL REGISTRATION: This study (NCT04258813) was registered in clinicaltrals.gov on February 6, 2020.

The Impact of Physical Activity on Pericarditis.

PURPOSE OF REVIEW: To discuss the possible harmful effects and pathophysiology of exercise in cases of pericarditis, explore the role of multi-modality imaging to help guide exercise recommendations, and compare U.S. with European guideline recommendations on the safe resumption of physical activity following resolution of pericarditis. RECENT FINDINGS: Despite multiple postulated mechanisms by which exercise may be harmful during active inflammation of the myocardium or pericardium, the exact pathophysiology remains largely unknown. The inclusion of multi-modality cardiac imaging may play a role in further elucidating the relationship of exercise with outcomes in pericarditis. More recently, the prevalence of COVID-19 cardiac involvement in athletes prior to returning to play appears lower than previously reported; however, current recommendations are consistent with those for other etiologies of pericarditis. Further research is certainly needed to better understand the relationship between physical activity and pericarditis, the pathophysiology, and the prognostic role of multimodality imaging.

Association of Serum Lipoprotein (a) Levels and Coronary Atheroma Volume by Intravascular Ultrasound.

Background Lp(a) (lipoprotein (a)) is a risk factor for cardiovascular events, but the mechanism of increased risk is uncertain. This study evaluated the relationship between Lp(a) and coronary atheroma volume by intravascular ultrasound. Methods and Results This was a post hoc analysis of 6 randomized trials of coronary atheroma by intravascular ultrasound. The population was stratified into high (≥60 mg/dL) and low (<60 mg/dL) baseline serum Lp(a). The primary outcome was baseline coronary percent atheroma volume. A mixed model adjusted for baseline low density lipoprotein, ApoB (apoliporotein B100), non-high density lipoprotein, sex, age, race, history of myocardial infarction, statin use, and intravascular ultrasound study was used to provide estimates of baseline plaque burden. Of 3943 patients, 17.3% (683) had Lp(a) ≥ 60 mg/dL and 82.7% (3260) had Lp(a) < 60 mg/dL. At baseline, uncorrected low density lipoprotein level (107.7 ± 32.0 versus 99.1 ± 31.5) and statin therapy (99.0% versus 97.0%) were higher in patients with high Lp(a) levels, but low density lipoprotein corrected for Lp(a) was lower (80.6 ± 32.0 versus 94.0 ± 31.4) in patients with high Lp(a) levels. Percent atheroma volume was significantly higher in the high Lp(a) group in unadjusted (38.2% [32.8, 43.6] versus 37.1% [31.4, 43.1], P=0.01) and risk-adjusted analyses (38.7%±0.5 versus 37.5%±0.5, P<0.001). There was a significant association of increasing risk-adjusted percent atheroma volume across quintiles of Lp(a) (Lp(a) quintiles 1-5; 37.3 ± 0.5%, 37.2 ± 0.5%, 37.3 ± 0.5%, 38.0 ± 0.5%, 38.5 ± 0.5%, P=0.002). Conclusions Elevated Lp(a) is independently associated with increased percent atheroma volume. Further work is needed to clarify the relationship of Lp(a)-lowering treatment with cardiovascular outcomes.