Population-average mediation analysis for zero-inflated count outcomes.

Mediation analysis is an increasingly popular statistical method for explaining causal pathways to inform intervention. While methods have increased, there is still a dearth of robust mediation methods for count outcomes with excess zeroes. Current mediation methods addressing this issue are computationally intensive, biased, or challenging to interpret. To overcome these limitations, we propose a new mediation methodology for zero-inflated count outcomes using the marginalized zero-inflated Poisson (MZIP) model and the counterfactual approach to mediation. This novel work gives population-average mediation effects whose variance can be estimated rapidly via delta method. This methodology is extended to cases with exposure-mediator interactions. We apply this novel methodology to explore if diabetes diagnosis can explain BMI differences in healthcare utilization and test model performance via simulations comparing the proposed MZIP method to existing zero-inflated and Poisson methods. We find that our proposed method minimizes bias and computation time compared to alternative approaches while allowing for straight-forward interpretations.

Risk Prediction for Atherosclerotic Cardiovascular Disease With and Without Race Stratification.

Importance: Use of race-specific risk prediction in clinical medicine is being questioned. Yet, the most commonly used prediction tool for atherosclerotic cardiovascular disease (ASCVD)-pooled cohort risk equations (PCEs)-uses race stratification. Objective: To quantify the incremental value of race-specific PCEs and determine whether adding social determinants of health (SDOH) instead of race improves model performance. Design, Setting, and Participants: Included in this analysis were participants from the biracial Reasons for Geographic and Racial Differences in Stroke (REGARDS) prospective cohort study. Participants were aged 45 to 79 years, without ASCVD, and with low-density lipoprotein cholesterol level of 70 to 189 mg/dL or non-high-density lipoprotein cholesterol level of 100 to 219 mg/dL at baseline during the period of 2003 to 2007. Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke. Study data were analyzed from July 2022 to February 2023. Main outcome/measures: Discrimination (C statistic, Net Reclassification Index [NRI]), and calibration (plots, Nam D'Agostino test statistic comparing observed to predicted events) were assessed for the original PCE, then for a set of best-fit, race-stratified equations including the same variables as in the PCE (model C), best-fit equations without race stratification (model D), and best-fit equations without race stratification but including SDOH as covariates (model E). Results: This study included 11 638 participants (mean [SD] age, 61.8 [8.3] years; 6764 female [58.1%]) from the REGARDS cohort. Across all strata (Black female, Black male, White female, and White male participants), C statistics did not change substantively compared with model C (Black female, 0.71; 95% CI, 0.68-0.75; Black male, 0.68; 95% CI, 0.64-0.73; White female, 0.77; 95% CI, 0.74-0.81; White male, 0.68; 95% CI, 0.64-0.71), in model D (Black female, 0.71; 95% CI, 0.67-0.75; Black male, 0.68; 95% CI, 0.63-0.72; White female, 0.76; 95% CI, 0.73-0.80; White male, 0.68; 95% CI, 0.65-0.71), or in model E (Black female, 0.72; 95% CI, 0.68-0.76; Black male, 0.68; 95% CI, 0.64-0.72; White female, 0.77; 95% CI, 0.74-0.80; White male, 0.68; 95% CI, 0.65-0.71). Comparing model D with E using the NRI showed a net percentage decline in the correct assignment to higher risk for male but not female individuals. The Nam D'Agostino test was not significant for all race-sex strata in each model series, indicating good calibration in all groups. Conclusions: Results of this cohort study suggest that PCE performed well overall but had poorer performance in both BM and WM participants compared with female participants regardless of race in the REGARDS cohort. Removal of race or the addition of SDOH did not improve model performance in any subgroup.

Social Determinants of Health and Cardiologist Involvement in the Care of Adults Hospitalized for Heart Failure.

Importance: Involvement of a cardiologist in the care of adults during a hospitalization for heart failure (HF) is associated with reduced rates of in-hospital mortality and hospital readmission. However, not all patients see a cardiologist when they are hospitalized for HF. Objective: To determine whether social determinants of health (SDOH) are associated with cardiologist involvement in the management of adults hospitalized for HF. Design, Setting, and Participants: This retrospective cohort study used data from the Reasons for Geographic and Racial Difference in Stroke (REGARDS) cohort. Participants included adults who experienced an adjudicated hospitalization for HF between 2009 and 2017 in all 48 contiguous states in the US. Data analysis was performed from November 2022 to January 2023. Exposures: A total of 9 candidate SDOH, aligned with the Healthy People 2030 conceptual model, were examined: Black race, social isolation, social network and/or caregiver availability, educational attainment less than high school, annual household income less than $35 000, living in rural area, living in a zip code with high poverty, living in a Health Professional Shortage Area, and living in a state with poor public health infrastructure. Main Outcomes and Measures: The primary outcome was cardiologist involvement, defined as involvement of a cardiologist as the primary responsible clinician or as a consultant. Bivariate associations between each SDOH and cardiologist involvement were examined using Poisson regression with robust SEs. Results: The study included 1000 participants (median [IQR] age, 77.8 [71.5-84.0] years; 479 women [47.9%]; 414 Black individuals [41.4%]; and 492 of 876 with low income [56.2%]) hospitalized at 549 unique US hospitals. Low annual household income (<$35 000) was the only SDOH with a statistically significant association with cardiologist involvement (relative risk, 0.88; 95% CI, 0.82-0.95). In a multivariable analysis adjusting for age, race, sex, HF characteristics, comorbidities, and hospital characteristics, low income remained inversely associated with cardiologist involvement (relative risk, 0.89; 95% CI, 0.82-0.97). Conclusions and Relevance: This cohort study found that adults with low household income were 11% less likely than adults with higher incomes to have a cardiologist involved in their care during a hospitalization for HF. These findings suggest that socioeconomic status may bias the care provided to patients hospitalized for HF.

Myocardial infarction and physical function: the REasons for Geographic And Racial Differences in Stroke prospective cohort study.

Objective: To examine associations between myocardial infarction (MI) and multiple physical function metrics. Methods: Among participants aged ≥45 years in the REasons for Geographic And Racial Differences in Stroke prospective cohort study, instrumental activities of daily living (IADL), activities of daily living (ADL), gait speed, chair stands, and Short Form-12 physical component summary (PCS) were assessed after approximately 10 years of follow-up. We examined associations between MI and physical function (no MI [n = 9,472], adjudicated MI during follow-up [n = 288, median 4.7 years prior to function assessment], history of MI at baseline [n = 745], history of MI at baseline and adjudicated MI during follow-up [n = 70, median of 6.7 years prior to function assessment]). Models were adjusted for sociodemographic characteristics, health behaviours, depressive symptoms, cognitive impairment, body mass index, diabetes, hypertension, and urinary albumin to creatinine ratio. We examined subgroups defined by age, gender, and race. Results: The average age at baseline was 62 years old, 56% were women, and 35% Black. MI was significantly associated with worse IADL and ADL scores, IADL dependency, chair stands, and PCS, but not ADL dependency or gait speed. For example, compared to participants without MI, IADL scores (possible range 0-14, higher score represents worse function) were greater for participants with MI during follow-up (difference: 0.37 [95% CI 0.16, 0.59]), MI at baseline (0.26 [95% CI 0.12, 0.41]), and MI at baseline and follow-up (0.71 [95% CI 0.15, 1.26]), p < 0.001. Associations tended to be greater in magnitude among participants who were women and particularly Black women. Conclusion: MI was associated with various measures of physical function. These decrements in function associated with MI may be preventable or treatable.

Recurrent Atherosclerotic Cardiovascular Disease Events Potentially Prevented with Guideline-Recommended Cholesterol-Lowering Therapy following Myocardial Infarction.

PURPOSE: Many adults with atherosclerotic cardiovascular disease (ASCVD) who are recommended to take a statin, ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) by the 2018 American Heart Association/American College of Cardiology cholesterol guideline do not receive these medications. We estimated the percentage of recurrent ASCVD events potentially prevented with guideline-recommended cholesterol-lowering therapy following a myocardial infarction (MI) hospitalization. METHODS: We conducted simulations using data from US adults with government health insurance through Medicare or commercial health insurance in the MarketScan database. We used data from patients with an MI hospitalization in 2018-2019 to estimate the percentage receiving guideline-recommended therapy. We used data from patients with an MI hospitalization in 2013-2016 to estimate the 3-year cumulative incidence of recurrent ASCVD events (i.e., MI, coronary revascularization or ischemic stroke). The low-density lipoprotein cholesterol (LDL-C) reduction with guideline-recommended therapy was derived from trials of statins, ezetimibe and PCSK9i, and the associated ASCVD risk reduction was estimated from a meta-analysis by the Cholesterol-Lowering Treatment Trialists Collaboration. RESULTS: Among 279,395 patients with an MI hospitalization in 2018-2019 (mean age 75 years, mean LDL-C 92 mg/dL), 27.3% were receiving guideline-recommended cholesterol-lowering therapy. With current cholesterol-lowering therapy use, 25.3% (95%CI: 25.2%-25.4%) of patients had an ASCVD event over 3 years. If all patients were to receive guideline-recommended therapy, 19.8% (95%CI: 19.5%-19.9%) were estimated to have an ASCVD event over 3 years, representing a 21.6% (95%CI: 20.5%-23.6%) relative risk reduction. CONCLUSION: Implementation of guideline-recommended cholesterol-lowering therapy could prevent a substantial percentage of recurrent ASCVD events.

Social Determinants of Health and Cardiologist Involvement in the Care of Adults Hospitalized for Heart Failure.

Introduction: The involvement of a cardiologist in the care of adults during a hospitalization for heart failure (HF) is associated with reduced rates of in-hospital mortality and hospital readmission. However, not all patients see a cardiologist when they are hospitalized for HF. Since reasons for this are not entirely clear, we sought to determine whether social determinants of health (SDOH) are associated with cardiologist involvement in the management of adults hospitalized for HF. We hypothesized that SDOH would be inversely associated with cardiologist involvement in the care of adults hospitalized for HF. Methods: We included adult participants from the national REasons for Geographic And Racial Difference in Stroke (REGARDS) cohort, who experienced an adjudicated hospitalization for HF between 2009 and 2017. We excluded participants who were hospitalized at institutions that lacked cardiology services (n=246). We examined nine candidate SDOH, which align with the Healthy People 2030 conceptual model: Black race, social isolation (0-1 visits from a family or friend in the past month), social network/caregiver availability (having someone to care for them if ill), educational attainment < high school, annual household income < $35,000, living in rural areas, living in a zip code with high poverty, living in a Health Professional Shortage Area, and residing in a state with poor public health infrastructure. The primary outcome was cardiologist involvement, a binary variable which was defined as involvement of a cardiologist as the primary responsible clinician or as a consultant, collected via chart review. We examined associations between each SDOH and cardiologist involvement using Poisson regression with robust standard errors. Candidate SDOH with statistically significant associations (p<0.10) were retained for multivariable analysis. Potential confounders/covariates for the multivariable analysis included age, race, sex, HF characteristics, comorbidities, and hospital characteristics. Results: We examined 876 participants hospitalized at 549 unique US hospitals. The median age was 77.5 years (IQR 71.0-83.7), 45.9% were female, 41.4% were Black, and 56.2% had low income. Low household income (<$35,000/year) was the only SDOH that had a statistically significant association with cardiologist involvement in a bivariate analysis (RR: 0.88 [95% CI: 0.82-0.95]). After adjusting for potential confounders, low income remained inversely associated (RR: 0.89 [95% CI: 0.82-0.97]). Conclusions: Adults with low household income were 11% less likely to have a cardiologist involved in their care during a hospitalization for HF. This suggests that socioeconomic status may implicitly bias the care provided to patients hospitalized for HF.

Personalizing Direct Oral Anticoagulant Therapy for a Diverse Population: Role of Race, Kidney Function, Drug Interactions, and Pharmacogenetics.

Oral anticoagulants (OACs) are commonly used to reduce the risk of venous thromboembolism and the risk of stroke in patients with atrial fibrillation. Endorsed by the American Heart Association, American College of Cardiology, and the European Society of Cardiology, direct oral anticoagulants (DOACs) have displaced warfarin as the OAC of choice for both conditions, due to improved safety profiles, fewer drug-drug and drug-diet interactions, and lack of monitoring requirements. Despite their widespread use and improved safety over warfarin, DOAC-related bleeding remains a major concern for patients. DOACs have stable pharmacokinetics and pharmacodynamics; however, variability in DOAC response is common and may be attributed to numerous factors, including patient-specific factors, concomitant medications, comorbid conditions, and genetics. Although DOAC randomized controlled trials included patients of varying ages and levels of kidney function, they failed to include patients of diverse ancestries. Additionally, current evidence to support DOAC pharmacogenetic associations have primarily been derived from European and Asian individuals. Given differences in genotype frequencies and disease burden among patients of different biogeographic groups, future research must engage diverse populations to assess and quantify the impact of predictors on DOAC response. Current under-representation of patients from diverse racial groups does not allow for proper generalization of the influence of clinical and genetic factors in relation to DOAC variability. Herein, we discuss factors affecting DOAC response, such as age, sex, weight, kidney function, drug interactions, and pharmacogenetics, while offering a new perspective on the need for further research including frequently excluded groups.

The Projected Impact of Population-Wide Achievement of LDL Cholesterol <70 mg/dL on the Number of Recurrent Events Among US Adults with ASCVD.

PURPOSE: Adults with atherosclerotic cardiovascular disease (ASCVD) are recommended high-intensity statins, with those at very high risk for recurrent events recommended adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor if their low-density lipoprotein cholesterol (LDL-C) is ≥70 mg/dL. We estimated the number of recurrent ASCVD events potentially averted if all adults in the United States (US) ≥45 years of age with ASCVD achieved an LDL-C <70 mg/dL. METHODS: The number of US adults with ASCVD and LDL-C ≥70 mg/dL was estimated from the National Health and Nutrition Examination Survey 2009-2016 (n = 596). The 10-year cumulative incidence of recurrent ASCVD events was estimated from the REasons for Geographic And Racial Differences in Stroke study (n = 5390), weighted to the US population by age, race, and sex. The ASCVD risk reduction by achieving an LDL-C <70 mg/dL was estimated from meta-analyses of lipid-lowering treatment trials. RESULTS: Overall, 14.7 (95% CI, 13.7-15.8) million US adults had ASCVD, of whom 11.6 (95% CI, 10.6-12.5) million had LDL-C ≥70 mg/dL. The 10-year cumulative incidence of ASCVD events was 24.3% (95% CI, 23.2-25.6%). We projected that 2.823 (95% CI, 2.543-3.091) million ASCVD events would occur over 10 years among US adults with ASCVD and LDL-C ≥70 mg/dL. Overall, 0.634 (95% CI, 0.542-0.737) million ASCVD events could potentially be averted if all US adults with ASCVD achieved and maintained LDL-C <70 mg/dL. CONCLUSION: A substantial number of recurrent ASCVD events could be averted over 10 years if all US adults with ASCVD achieved, and maintained, an LDL-C <70 mg/dL.

Lipid-Lowering Therapy Use and Intensification Among United States Veterans Following Myocardial Infarction or Coronary Revascularization Between 2015 and 2019.

BACKGROUND: Understanding how statins, ezetimibe, and PCSK9i (proprotein convertase subtilisin/kexin type 9 serine protease inhibitors) are prescribed after a myocardial infarction (MI) or elective coronary revascularization may improve lipid-lowering therapy (LLT) intensification and reduce recurrent atherosclerotic cardiovascular disease events. We described the use and intensification of LLT among US veterans who had a MI or elective coronary revascularization between July 24, 2015, and December 9, 2019, within 12 months of hospital discharge. METHODS: LLT intensification was defined as increasing statin dose, or initiating a statin, ezetimibe, or a PCSK9i, overall and among those with an LDL-C (low-density lipoprotein cholesterol) ≥70 or 100 mg/dL. Poisson regression was used to determine patient characteristics associated with a greater likelihood of LLT intensification following hospitalization for MI or elective coronary revascularization. RESULTS: Among 81 372 index events (mean age, 69.0 years, 2.3% female, mean LDL-C 89.6 mg/dL, 33.8% with LDL-C <70 mg/dL), 39.7% were not taking any LLT, and 22.0%, 37.2%, and 0.6% were taking a low-moderate intensity statin, a high-intensity statin, and ezetimibe, respectively, before MI/coronary revascularization during the study period. Within 14 days, 3 months, and 12 months posthospitalization, 33.3%, 41.9%, and 47.3%, respectively, of veterans received LLT intensification. LLT intensification was most common among veterans taking no LLT (82.5%, n=26 637) before MI/coronary revascularization. Higher baseline LDL-C, having a lipid test, and attending a cardiology visit were each associated with a greater likelihood of LLT intensification, while age ≥75 versus <65 years was associated with a lower likelihood of LLT intensification within 12 months posthospitalization. CONCLUSIONS: Less than half of veterans received LLT intensification in the year after MI or coronary revascularization suggesting a missed opportunity to reduce atherosclerotic cardiovascular disease risk.

Establishing Care Post Discharge Following a Heart Failure Hospitalization in an Uninsured Heart Failure Population.

Multidisciplinary interprofessional outpatient care improves mortality for patients with heart failure (HF) but is underutilized. We sought to identify factors associated with not establishing outpatient care among uninsured individuals with HF. We included uninsured individuals referred to an interprofessional clinic after a hospitalization with HF from 2016 to 2019. The primary outcome was establishing care, defined as presenting to clinic within 7 days of discharge from the hospital. We constructed multivariable adjusted logistic regression models to identify predictors of establishing care. A total of 698 uninsured individuals were referred, of whom 583 (84%) established care. Mean age was 49.5 ± 11 years, 15% were rural-dwelling, 59% were black, and 31% were female. Black participants who were rural-dwelling (adusted odds ratio [aOR] 0.07, 95% confidence interval [CI] 0.03 to 0.17) or reported alcohol use (aOR 0.32, 95% CI 0.16 to 0.64) had lower odds of establishing care. White participants who were rural-dwelling (aOR 2.63, 95% CI 1.17 to 5.90) had higher odds of establishing care. Uninsured black individuals with HF who live in rural communities or who are active alcohol users represent a group that is at high risk of not establishing outpatient follow-up after a hospitalization with HF. Efforts to reduce this disparity are warranted to improve health outcomes in this population.

Lipoprotein(a) and the Risk for Coronary Heart Disease and Ischemic Stroke Events Among Black and White Adults With Cardiovascular Disease.

Background It is unclear whether lipoprotein(a) is associated with coronary heart disease (CHD) and ischemic stroke events in White and Black adults with atherosclerotic cardiovascular disease (ASCVD). Methods and Results We conducted a case-cohort analysis, including Black and White REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants ≥45 years of age with prevalent ASCVD (ie, CHD or stroke) at baseline between 2003 and 2007. Baseline lipoprotein(a) molar concentration was measured in participants with ASCVD who experienced a CHD event by December 2017 (n=1166) or an ischemic stroke by September 2019 (n=492) and in a random subcohort of participants with prevalent ASCVD (n=1948). The hazard ratio (HR) for CHD events per 1 SD (1.5 units) higher log-transformed lipoprotein(a) was 1.26 (95% CI, 1.02-1.56) among Black participants and 1.16 (95% CI, 1.02-1.31) among White participants (P value comparing HRs, 0.485). The HR for CHD events per 1 SD higher log-lipoprotein(a) within subgroups with hs-CRP (high-sensitivity C-reactive protein) ≥2 and <2 mg/L was 1.31 (95% CI, 0.99-1.73) and 1.23 (95% CI, 0.85-1.80), respectively (P value comparing HRs, 0.836), among Black participants, and 1.07 (95% CI, 0.91-1.27) and 1.36 (95% CI, 1.10-1.70), respectively (P value comparing HRs, 0.088), among White participants. There was no evidence that the association between lipoprotein(a) and CHD events differed by statin use. There was no evidence of an association between lipoprotein(a) and ischemic stroke events among Black or White participants. Conclusions Higher lipoprotein(a) levels were associated with an increased risk for CHD events in Black and White adults with ASCVD.

Social Determinants of Health and 30-Day Readmissions Among Adults Hospitalized for Heart Failure in the REGARDS Study.

BACKGROUND: It is not known which social determinants of health (SDOH) impact 30-day readmission after a heart failure (HF) hospitalization among older adults. We examined the association of 9 individual SDOH with 30-day readmission after an HF hospitalization. METHODS AND RESULTS: Using the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), we included Medicare beneficiaries who were discharged alive after an HF hospitalization between 2003 and 2014. We assessed 9 SDOH based on the Healthy People 2030 Framework: race, education, income, social isolation, social network, residential poverty, Health Professional Shortage Area, rural residence, and state public health infrastructure. The primary outcome was 30-day all-cause readmission. For each SDOH, we calculated incidence per 1000 person-years and multivariable-adjusted hazard ratios of readmission. Among 690 participants, the median age was 76 years at hospitalization (interquartile range, 71-82), 44.3% were women, 35.5% were Black, 23.5% had low educational attainment, 63.0% had low income, 21.0% had zip code-level poverty, 43.5% resided in Health Professional Shortage Areas, 39.3% lived in states with poor public health infrastructure, 13.1% were socially isolated, 13.3% had poor social networks, and 10.2% lived in rural areas. The 30-day readmission rate was 22.4%. In an unadjusted analysis, only Health Professional Shortage Area was significantly associated with 30-day readmission; in a fully adjusted analysis, none of the 9 SDOH were individually associated with 30-day readmission. CONCLUSIONS: In this modestly sized national cohort, although prevalent, none of the SDOH were associated with 30-day readmission after an HF hospitalization. Policies or interventions that only target individual SDOH to reduce readmissions after HF hospitalizations may not be sufficient to prevent readmission among older adults.

Estimated number and percentage of US adults with atherosclerotic cardiovascular disease recommended add-on lipid-lowering therapy by the 2018 AHA/ACC multi-society cholesterol guideline.

Study objective: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline recommends a maximally-tolerated statin with add-on lipid-lowering therapy, ezetimibe and/or proprotein convertase subtilisin/kexin type 9 (PCSK9) for adults with very-high atherosclerotic cardiovascular disease (ASCVD) risk to achieve a low-density lipoprotein cholesterol (LDL-C) <70 mg/dL. We estimated the percentage of US adults with ASCVD recommended, by the 2018 AHA/ACC cholesterol guideline, and receiving add-on lipid-lowering therapy. Design setting and participants: Cross-sectional study including 805 participants from the US National Health and Nutrition Examination Survey (NHANES) 2013-2020 data. NHANES sampling weights were used to obtain estimates for the US adult population. Main measures: Very-high ASCVD risk was defined as either: ≥2 ASCVD events, or one ASCVD event with ≥2 high-risk conditions. Being recommended add-on lipid-lowering therapy was defined as having very-high ASCVD risk and LDL-C ≥ 70 mg/dL, or LDL-C < 70 mg/dL while taking ezetimibe or a PCSK9 inhibitor. Results: An estimated 18.7 (95%CI, 16.0-21.4) million US adults had ASCVD, of whom 81.6 % (95%CI, 76.7 %-86.4 %) had very-high ASCVD risk, and 60.1 % (95%CI, 54.5 %-65.7 %) had very-high ASCVD risk and LDL-C ≥ 70 mg/dL. Overall, 61.4 % (95%CI, 55.8 %-66.9 %) were recommended add-on lipid-lowering therapy and 3.2 % (95 % CI, 1.2 %-5.3 %) were taking it. Smokers, adults with diabetes, hypertension and chronic kidney disease were more likely, while those taking atorvastatin or rosuvastatin were less likely, to be recommended add-on lipid-lowering therapy. Conclusion: The majority of US adults with ASCVD are recommended add-on lipid-lowering therapy by the 2018 AHA/ACC cholesterol guideline but few are receiving it.

Characteristics of patients with diabetes and a history of myocardial infarction initiating PCSK9 and SGLT2 inhibitors.

Study objective: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk for atherosclerotic cardiovascular disease (ASCVD) events in patients with diabetes and ASCVD. We assessed factors associated with initiating either medication among patients with diabetes and a prior myocardial infarction (MI). Setting/participants: US adults ≥19 years old with private health insurance (MarketScan) or government health insurance (Medicare) who had diabetes and a prior MI and initiated a PCSK9i or an SGLT2i in 2017 or 2018. Main outcome measures: PCSK9i or SGLT2i initiation was identified using pharmacy claims. Results: Overall, 8102 patients initiated a PCSK9i (n = 1501; 18.5%) or an SGLT2i (n = 6601; 81.5%). Patients with 2 and ≥3 versus 1 prior MI (risk ratio [RR]: 1.32 [95%CI: 1.17-1.48] and 1.68 [1.41-2.01], respectively), prior coronary revascularization (1.47 [1.31-1.64]), prior stroke (1.28 [1.06-1.56]), history of peripheral artery disease (1.27 [1.14-1.41]), receiving cardiologist care (1.51 [1.36-1.67]) or taking ezetimibe (2.57 [2.35-2.82]) were more likely to initiate a PCSK9i versus an SGLT2i. Patients with a history of short-term (RR 1.07 [95%CI 1.05-1.09]) or long-term (1.07 [1.04-1.09]) diabetes complications, and taking a low/moderate- and high-intensity statin dosage (1.61 [1.51-1.70] and 1.68 [1.58-1.77], respectively) were more likely to initiate an SGLT2i versus a PCSK9i. Among patients who initiated a PCSK9i, 2.9% subsequently initiated an SGLT2i; 0.8% who initiated an SGLT2i subsequently initiated a PCSK9i. Conclusion: The decision to initiate PCSK9i or SGLT2i is explained by having very high cardiovascular disease risk for those initiating PCSK9i and diabetes complications for those initiating SGLT2i.

Million Hearts Cardiac Rehabilitation Think Tank: Accelerating New Care Models.

This article describes the October 2020 proceedings of the Million Hearts Cardiac Rehabilitation Think Tank: Accelerating New Care Models, convened with representatives from professional organizations, cardiac rehabilitation (CR) programs, academic institutions, federal agencies, payers, and patient representative groups. As CR delivery evolves, terminology is evolving to reflect not where activities occur (eg, center, home) but how CR is delivered: in-person synchronous, synchronous with real-time audiovisual communication (virtual), or asynchronous (remote). Patients and CR staff may interact through ≥1 delivery modes. Though new models may change how CR is delivered and who can access CR, new models should not change what is delivered-a multidisciplinary program addressing CR core components. During the coronavirus disease 2019 (COVID-19) public health emergency, Medicare issued waivers to allow virtual CR; it is unclear whether these waivers will become permanent policy post-public health emergency. Given CR underuse and disparities in delivery, new models must equitably address patient and health system contributors to disparities. Strategies for implementing new CR care models address safety, exercise prescription, monitoring, and education. The available evidence supports the efficacy and safety of new CR care models. Still, additional research should study diverse populations, impact on patient-centered outcomes, effect on long-term outcomes and health care utilization, and implementation in diverse settings. CR is evolving to include in-person synchronous, virtual, and remote modes of delivery; there is significant enthusiasm for implementing new care models and learning how new care models can broaden access to CR, improve patient outcomes, and address health inequities.

Race/ethnic and sex differences in the initiation of non-statin lipid-lowering medication following myocardial infarction.

BACKGROUND: Adults with atherosclerotic cardiovascular disease (ASCVD) at very high-risk for recurrent events who have low-density lipoprotein cholesterol ≥ 70 mg/dL despite maximally-tolerated statin therapy are recommended to initiate ezetimibe or a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. OBJECTIVE: Compare the initiation of ezetimibe and a PCSK9 inhibitor after a myocardial infarction (MI) among very high-risk ASCVD patients by race/ethnicity and sex. METHODS: We analyzed data from 374,786 adults ≥ 66 years of age with Medicare fee-for-service coverage who had an MI between July 1, 2015 and December 31, 2018, were not taking ezetimibe or a PCSK9 inhibitor, and had very high-risk ASCVD defined by the 2018 American Heart Association/American College of Cardiology multi-society cholesterol guideline. Pharmacy claims through December 31, 2018 were used to determine ezetimibe and PCSK9 inhibitor initiation. RESULTS: Overall, 6980 (1.9%) beneficiaries initiated ezetimibe, and 1433 (0.4%) initiated a PCSK9 inhibitor. Adjusted hazard ratios (aHR) for ezetimibe initiation among non-Hispanic Black, Hispanic, and Asian versus non-Hispanic White beneficiaries were 0.77 (95% confidence interval [95%CI]: 0.70-0.86), 0.92 (95%CI: 0.76-1.11) and 0.73 (95%CI: 0.59-0.89), respectively. Compared to non-Hispanic White beneficiaries, the aHRs for PCSK9 inhibitor initiation were 0.63 (95%CI: 0.48-0.81) among non-Hispanic Black, 0.70 (95%CI: 0.43-1.13) among Hispanic, and 0.93 (95%CI: 0.62-1.39) among Asian beneficiaries. The aHRs for ezetimibe and PCSK9 inhibitor initiation comparing women to men were 1.11 (95%CI: 1.06-1.17) and 1.13 (95%CI: 1.01-1.25), respectively. CONCLUSION: There are race/ethnic and sex disparities in the initiation of ezetimibe and a PCSK9 inhibitor following MI among very high-risk ASCVD patients.

Mediterranean Diet Score, Dietary Patterns, and Risk of Sudden Cardiac Death in the REGARDS Study.

Background Sudden cardiac death (SCD) is a common cause of death in the United States. Few previous studies have investigated the associations of diet scores and dietary patterns with risk of SCD. We investigated the associations of the Mediterranean diet score and various dietary patterns with risk of SCD in participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study cohort. Methods and Results Diet was assessed with a food frequency questionnaire administered at baseline in REGARDS. The Mediterranean diet score was derived based on the consumption of specific food groups considered beneficial or detrimental components of that diet. Dietary patterns were derived previously using factor analysis, and adherence to each pattern was scored. SCD events were ascertained through regular contacts. Cox proportional hazards regression was used to examine the risk of SCD events associated with the Mediterranean diet score and adherence to each of the 5 dietary patterns overall and stratifying on history of coronary heart disease at baseline. The analytic sample included 21 069 participants with a mean 9.8±3.8 years of follow-up. The Mediterranean diet score showed a trend toward an inverse association with risk of SCD after multivariable adjustment (hazard ratio [HR] comparing highest with lowest group, 0.74; 95% CI, 0.55-1.01; Ptrend=0.07). There was a trend toward a positive association of the Southern dietary pattern with risk of SCD (HR comparing highest with lowest quartile of adherence, 1.46; 95% CI, 1.02-2.10; Ptrend=0.06). Conclusions In REGARDS participants, we identified trends toward an inverse association of the Mediterranean diet score and a positive association of adherence to the Southern dietary pattern with risk of SCD.