Publications

Background Heterozygous familial hypercholesterolemia (FH) is a common genetic disorder causing premature cardiovascular disease. Despite this, there is no national screening program in the United States to identify individuals with FH or likely pathogenic FH genetic variants. Methods and Results The clinical characteristics and FH variant status of 49 738 UK Biobank participants were used to develop a regression model to predict the probability of having any FH variants. The regression model and modified Dutch Lipid Clinic Network criteria were applied to 39 790 adult participants (aged ≥20 years) in the National Health and Nutrition Examination Survey to estimate the yield of FH screening programs using Dutch Lipid Clinic Network clinical criteria alone (excluding genetic variant status), genetic testing alone, or combining clinical criteria with genetic testing. The regression model accurately predicted FH variant status in UK Biobank participants (observed prevalence, 0.27%; predicted, 0.26%; area under the receiver-operator characteristic curve, 0.88). In the National Health and Nutrition Examination Survey, the estimated yield per 1000 individuals screened (95% CI) was 3.7 (3.0-4.6) FH cases with the Dutch Lipid Clinic Network clinical criteria alone, 3.8 (2.7-5.1) cases with genetic testing alone, and 6.6 (5.3-8.0) cases by combining clinical criteria with genetic testing. In young adults aged 20 to 39 years, using clinical criteria alone was estimated to yield 1.3 (95% CI, 0.6-2.5) FH cases per 1000 individuals screened, which was estimated to increase to 4.2 (95% CI, 2.6-6.4) FH cases when combining clinical criteria with genetic testing. Conclusions Screening for FH using a combination of clinical criteria with genetic testing may increase identification and the opportunity for early treatment of individuals with FH.

BACKGROUND: The COVID-19 pandemic has disproportionately affected low-income and racial/ethnic minority populations in the United States. However, it is unknown whether hospitalized patients with COVID-19 from socially vulnerable communities experience higher rates of death and/or major adverse cardiovascular events (MACEs). Thus, we evaluated the association between county-level social vulnerability and in-hospital mortality and MACE in a national cohort of hospitalized COVID-19 patients.

METHODS: Our study population included patients with COVID-19 in the American Heart Association COVID-19 Cardiovascular Disease Registry across 107 US hospitals between January 14, 2020 to November 30, 2020. The Social Vulnerability Index (SVI), a composite measure of community vulnerability developed by Centers for Disease Control and Prevention, was used to classify the county-level social vulnerability of patients' place of residence. We fit a hierarchical logistic regression model with hospital-level random intercepts to evaluate the association of SVI with in-hospital mortality and MACE.

RESULTS: Among 16 939 hospitalized COVID-19 patients in the registry, 5065 (29.9%) resided in the most vulnerable communities (highest national quartile of SVI). Compared with those in the lowest quartile of SVI, patients in the highest quartile were younger (age 60.2 versus 62.3 years) and more likely to be Black adults (36.7% versus 12.2%) and Medicaid-insured (31.1% versus 23.0%). After adjustment for demographics (age, sex, race/ethnicity) and insurance status, the highest quartile of SVI (compared with the lowest) was associated with higher likelihood of in-hospital mortality (OR, 1.25 [1.03-1.53]; P=0.03) and MACE (OR, 1.26 [95% CI, 1.05-1.50]; P=0.01). These findings were not attenuated after accounting for clinical comorbidities and acuity of illness on admission.

CONCLUSIONS: Patients hospitalized with COVID-19 residing in more socially vulnerable communities experienced higher rates of in-hospital mortality and MACE, independent of race, ethnicity, and several clinical factors. Clinical and health system strategies are needed to improve health outcomes for socially vulnerable patients.

BACKGROUND: Racial and social disparities exist in outcomes related to cancer and cardiovascular disease (CVD).

OBJECTIVES: The aim of this cross-sectional study was to study the impact of social vulnerability on mortality attributed to comorbid cancer and CVD.

METHODS: The Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database (2015-2019) was used to obtain county-level mortality data attributed to cancer, CVD, and comorbid cancer and CVD. County-level social vulnerability index (SVI) data (2014-2018) were obtained from the CDC's Agency for Toxic Substances and Disease Registry. SVI percentiles were generated for each county and aggregated to form SVI quartiles. Age-adjusted mortality rates (AAMRs) were estimated and compared across SVI quartiles to assess the impact of social vulnerability on mortality related to cancer, CVD, and comorbid cancer and CVD.

RESULTS: The AAMR for comorbid cancer and CVD was 47.75 (95% CI: 47.66-47.85) per 100,000 person-years, with higher mortality in counties with greater social vulnerability. AAMRs for cancer and CVD were also significantly greater in counties with the highest SVIs. However, the proportional increase in mortality between the highest and lowest SVI counties was greater for comorbid cancer and CVD than for either cancer or CVD alone. Adults <45 years of age, women, Asian and Pacific Islanders, and Hispanics had the highest relative increase in comorbid cancer and CVD mortality between the fourth and first SVI quartiles, without significant urban-rural differences.

CONCLUSIONS: Comorbid cancer and CVD mortality increased in counties with higher social vulnerability. Improved education, resource allocation, and targeted public health interventions are needed to address inequities in cardio-oncology.

Background The AHA Registry (American Heart Association COVID-19 Cardiovascular Disease Registry) captures detailed information on hospitalized patients with COVID-19. The registry, however, does not capture information on social determinants of health or long-term outcomes. Here we describe the linkage of the AHA Registry with external data sources, including fee-for-service (FFS) Medicare claims, to fill these gaps and assess the representativeness of linked registry patients to the broader Medicare FFS population hospitalized with COVID-19. Methods and Results We linked AHA Registry records of adults ≥65 years from March 2020 to September 2021 with Medicare FFS claims using a deterministic linkage algorithm and with the American Hospital Association Annual Survey, Rural Urban Commuting Area codes, and the Social Vulnerability Index using hospital and geographic identifiers. We compared linked individuals with unlinked FFS beneficiaries hospitalized with COVID-19 to assess the representativeness of the AHA Registry. A total of 10 010 (47.0%) records in the AHA Registry were successfully linked to FFS Medicare claims. Linked and unlinked FFS beneficiaries were similar with respect to mean age (78.1 versus 77.9, absolute standardized difference [ASD] 0.03); female sex (48.3% versus 50.2%, ASD 0.04); Black race (15.1% versus 12.0%, ASD 0.09); dual-eligibility status (26.1% versus 23.2%, ASD 0.07); and comorbidity burden. Linked patients were more likely to live in the northeastern United States (35.7% versus 18.2%, ASD 0.40) and urban/metropolitan areas (83.9% versus 76.8%, ASD 0.18). There were also differences in hospital-level characteristics between cohorts. However, in-hospital outcomes were similar (mortality, 23.3% versus 20.1%, ASD 0.08; home discharge, 45.5% versus 50.7%, ASD 0.10; skilled nursing facility discharge, 24.4% versus 22.2%, ASD 0.05). Conclusions Linkage of the AHA Registry with external data sources such as Medicare FFS claims creates a unique and generalizable resource to evaluate long-term health outcomes after COVID-19 hospitalization.

AIMS: Prediction of mitral (MR) and tricuspid (TR) regurgitation progression on transthoracic echocardiography (TTE) is needed to personalize valvular surveillance intervals and prognostication.

METHODS AND RESULTS: Structured TTE report data at Beth Israel Deaconess Medical Center, 26 January 2000-31 December 2017, were used to determine time to progression (≥1+ increase in severity). TTE predictors of progression were used to create a progression score, externally validated at Massachusetts General Hospital, 1 January 2002-31 December 2019. In the derivation sample (MR, N = 34 933; TR, N = 27 526), only 5379 (15.4%) individuals with MR and 3630 (13.2%) with TR had progression during a median interquartile range) 9.0 (4.1-13.4) years of follow-up. Despite wide inter-individual variability in progression rates, a score based solely on demographics and TTE variables identified individuals with a five- to six-fold higher rate of MR/TR progression over 10 years (high- vs. low-score tertile, rate of progression; MR 20.1% vs. 3.3%; TR 21.2% vs. 4.4%). Compared to those in the lowest score tertile, those in the highest tertile of progression had a four-fold increased risk of mortality. On external validation, the score demonstrated similar performance to other algorithms commonly in use.

CONCLUSION: Four-fifths of individuals had no progression of MR or TR over two decades. Despite wide interindividual variability in progression rates, a score, based solely on TTE parameters, identified individuals with a five- to six-fold higher rate of MR/TR progression. Compared to the lowest tertile, individuals in the highest score tertile had a four-fold increased risk of mortality. Prediction of long-term MR/TR progression is not only feasible but prognostically important.

CONTEXT: Cardiovascular disease (CVD) and heart failure (HF) are major causes of mortality in low-income populations and differ by sex. Risk assessment that incorporates cardiac biomarkers is common. However, research evaluating the utility of biomarkers rarely includes controlled substances, which may influence biomarker levels and thus influence CVD risk assessment.

MATERIALS AND METHODS: We identified the effects of multiple substances on soluble "suppression of tumorigenicity 2" (sST2), a biomarker of adverse cardiac remodelling, in 245 low-income women. Adjusting for CVD risk factors, we examined associations between substance use and sST2 over six monthly visits.

RESULTS: Median age was 53 years and 74% of participants were ethnic minority women. An sST2 level > 35 ng/mL (suggesting cardiac remodelling) during ≥1 study visit was observed in 44% of participants. In adjusted analysis, higher sST2 levels were significantly and positively associated with the presence of cocaine (Adjusted Linear Effect [ALE]:1.10; 95% CI:1.03-1.19), alcohol (ALE:1.10; 95% CI:1.04-1.17), heroin (ALE:1.25; 95% CI:1.10-1.43), and the interaction between heroin and fentanyl use.

CONCLUSION: Results suggest that the use of multiple substances influences the level of sST2, a biomarker often used to evaluate cardiovascular risk. Incorporating substance use alongside cardiac biomarkers may improve CVD risk assessment in vulnerable women.

BACKGROUND: The impact of the COVID-19 pandemic on participation in and availability of cardiac rehabilitation (CR) is unknown.

METHODS: Among eligible Medicare fee-for-service beneficiaries, we evaluated, by month, the number of CR sessions attended per 100 000 beneficiaries, individuals eligible to initiate CR, and centers offering in-person CR between January 2019 and December 2021. We compared these outcomes between 2 periods: December 1, 2019 through February 28, 2020 (period 1, before declaration of the pandemic-related national emergency) and October 1, 2021 through December 31, 2021 (period 2, the latest period for which data are currently available).

RESULTS: In period 1, Medicare beneficiaries participated in (mean±SD) 895±84 CR sessions per 100 000 beneficiaries each month. After the national emergency was declared, CR participation sharply declined to 56 CR sessions per 100 000 beneficiaries in April 2020. CR participation recovered gradually through December 2021 but remained lower than prepandemic levels (period 2: 698±29 CR sessions per month per 100 000 beneficiaries, P=0.02). Declines in CR participation were most marked among dual Medicare and Medicaid enrollees and patients residing in rural areas or socially vulnerable communities. There was no statistically significant change in CR eligibility between the 2 periods. Compared with 2618±5 CR centers in period 1, there were 2464±7 in period 2 (P<0.01). Compared with CR centers that survived the pandemic, 220 CR centers that closed were more likely to be affiliated with public hospitals, located in rural areas, and serve the most socially vulnerable communities.

CONCLUSIONS: The COVID-19 pandemic was associated with a persistent decline in CR participation and the closure of CR centers, which disproportionately affected rural and low-income patients and the most socially vulnerable communities. Innovation in CR financing and delivery is urgently needed to equitably enhance CR participation among Medicare beneficiaries.