Publications

2018

Chen, Shu, Enying Gong, Dhruv S Kazi, Ann B Gates, Rong Bai, Hua Fu, Weixia Peng, et al. (2018) 2018. “Using Mobile Health Intervention to Improve Secondary Prevention of Coronary Heart Diseases in China: Mixed-Methods Feasibility Study.”. JMIR MHealth and UHealth 6 (1): e9. https://doi.org/10.2196/mhealth.7849.
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BACKGROUND: Coronary heart disease (CHD) is the leading cause of cardiovascular mortality worldwide, yet implementation of evidence-based strategies for secondary prevention remains suboptimal.

OBJECTIVE: This study aimed to evaluate the feasibility, specifically the usability and acceptability, and estimate the preliminary effectiveness of a mobile health (mHealth) intervention targeting both physicians and patients to improve adherence to evidence-based medications and lifestyle modifications.

METHODS: We conducted a 12-week pre-post interventional pilot study at two sites in Shanghai and Hainan, China. Physicians used the app designed in this study to prescribe evidence-based medicines and record patient information. Eligible and consenting patients received automatic text messages or voice calls 4 to 5 times per week for 12 weeks on medication adherence and healthy behaviors. Interviews were conducted among 10 physicians and 24 patients at the two sites for their thoughts on medication adherence and feedback on the usability and acceptability. Questions on usability and acceptability were also asked in a patient follow-up survey. With regard to estimating effectiveness, the primary outcome was medication adherence (as estimated by the Morisky Green Levine Scale) at 12 weeks. Secondary outcomes included physical activity, smoking status, fruits and vegetables consumption, and facility visit frequency.

RESULTS: Interview findings and patient survey showed the good usability and acceptability of the intervention. Among 190 patients who completed the intervention, there was a significant increase in medication adherence (odds ratio [OR] 1.80, 95% CI 1.14-2.85). The study also showed decrease of smokers' percentage (-5%, P=.05), increase of daily vegetables consumption frequency (+0.3/day, P=.01), and community health care center visit frequency (+3 in 3 months, P=.04). The following site-specific differences were noted: medication adherence appeared to increase in Hainan (OR 14.68, 95% CI 5.20-41.45) but not in Shanghai (OR 0.61, 95% CI 0.33-1.12).

CONCLUSIONS: Our study demonstrated that the intervention was feasible in both a tertiary care center and an urban community health center in China. Preliminary results from pre-post comparison suggest the possibility that provider and patient-linked mHealth interventions may improve medication adherence and lifestyle modifications among CHD patients, especially in resource-scarce settings. Randomized controlled trials are needed to verify the findings.

Collaborators, GBD 2017 SDG. (2018) 2018. “Measuring Progress from 1990 to 2017 and Projecting Attainment to 2030 of the Health-Related Sustainable Development Goals for 195 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2017.”. Lancet (London, England) 392 (10159): 2091-2138. https://doi.org/10.1016/S0140-6736(18)32281-5.
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BACKGROUND: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of "leaving no one behind", it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990-2017, projected indicators to 2030, and analysed global attainment.

METHODS: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0-100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator.

FINDINGS: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4-67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6-14·0) to a high of 84·9 (83·1-86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030.

INTERPRETATION: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains-curative interventions in the case of NCDs-towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions-or inaction-today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.

FUNDING: Bill & Melinda Gates Foundation.

Collaborators, GBD 2017 Causes of Death. (2018) 2018. “Global, Regional, and National Age-Sex-Specific Mortality for 282 Causes of Death in 195 Countries and Territories, 1980-2017: A Systematic Analysis for the Global Burden of Disease Study 2017.”. Lancet (London, England) 392 (10159): 1736-88. https://doi.org/10.1016/S0140-6736(18)32203-7.
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BACKGROUND: Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017.

METHODS: The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries-Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised.

FINDINGS: At the broadest grouping of causes of death (Level 1), non-communicable diseases (NCDs) comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5-74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 18·6% (17·9-19·6), and injuries 8·0% (7·7-8·2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22·7% (21·5-23·9), representing an additional 7·61 million (7·20-8·01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7·9% (7·0-8·8). The number of deaths for CMNN causes decreased by 22·2% (20·0-24·0) and the death rate by 31·8% (30·1-33·3). Total deaths from injuries increased by 2·3% (0·5-4·0) between 2007 and 2017, and the death rate from injuries decreased by 13·7% (12·2-15·1) to 57·9 deaths (55·9-59·2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000-289 000) globally in 2007 to 352 000 (334 000-363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118·0% (88·8-148·6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36·4% (32·2-40·6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33·6% (31·2-36·1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respiratory infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990-neonatal disorders, lower respiratory infections, and diarrhoeal diseases-were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases.

INTERPRETATION: Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade.

FUNDING: Bill & Melinda Gates Foundation.

Yeh, Robert W, Linda R Valsdottir, Michael W Yeh, Changyu Shen, Daniel B Kramer, Jordan B Strom, Eric A Secemsky, et al. (2018) 2018. “Parachute Use to Prevent Death and Major Trauma When Jumping from Aircraft: Randomized Controlled Trial.”. BMJ (Clinical Research Ed.) 363: k5094. https://doi.org/10.1136/bmj.k5094.
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OBJECTIVE: To determine if using a parachute prevents death or major traumatic injury when jumping from an aircraft.

DESIGN: Randomized controlled trial.

SETTING: Private or commercial aircraft between September 2017 and August 2018.

PARTICIPANTS: 92 aircraft passengers aged 18 and over were screened for participation. 23 agreed to be enrolled and were randomized.

INTERVENTION: Jumping from an aircraft (airplane or helicopter) with a parachute versus an empty backpack (unblinded).

MAIN OUTCOME MEASURES: Composite of death or major traumatic injury (defined by an Injury Severity Score over 15) upon impact with the ground measured immediately after landing.

RESULTS: Parachute use did not significantly reduce death or major injury (0% for parachute v 0% for control; P>0.9). This finding was consistent across multiple subgroups. Compared with individuals screened but not enrolled, participants included in the study were on aircraft at significantly lower altitude (mean of 0.6 m for participants v mean of 9146 m for non-participants; P<0.001) and lower velocity (mean of 0 km/h v mean of 800 km/h; P<0.001).

CONCLUSIONS: Parachute use did not reduce death or major traumatic injury when jumping from aircraft in the first randomized evaluation of this intervention. However, the trial was only able to enroll participants on small stationary aircraft on the ground, suggesting cautious extrapolation to high altitude jumps. When beliefs regarding the effectiveness of an intervention exist in the community, randomized trials might selectively enroll individuals with a lower perceived likelihood of benefit, thus diminishing the applicability of the results to clinical practice.

Marafino, Ben J, Miran Park, Jason M Davies, Robert Thombley, Harold S Luft, David C Sing, Dhruv S Kazi, et al. (2018) 2018. “Validation of Prediction Models for Critical Care Outcomes Using Natural Language Processing of Electronic Health Record Data.”. JAMA Network Open 1 (8): e185097. https://doi.org/10.1001/jamanetworkopen.2018.5097.
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IMPORTANCE: Accurate prediction of outcomes among patients in intensive care units (ICUs) is important for clinical research and monitoring care quality. Most existing prediction models do not take full advantage of the electronic health record, using only the single worst value of laboratory tests and vital signs and largely ignoring information present in free-text notes. Whether capturing more of the available data and applying machine learning and natural language processing (NLP) can improve and automate the prediction of outcomes among patients in the ICU remains unknown.

OBJECTIVES: To evaluate the change in power for a mortality prediction model among patients in the ICU achieved by incorporating measures of clinical trajectory together with NLP of clinical text and to assess the generalizability of this approach.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 101 196 patients with a first-time admission to the ICU and a length of stay of at least 4 hours. Twenty ICUs at 2 academic medical centers (University of California, San Francisco [UCSF], and Beth Israel Deaconess Medical Center [BIDMC], Boston, Massachusetts) and 1 community hospital (Mills-Peninsula Medical Center [MPMC], Burlingame, California) contributed data from January 1, 2001, through June 1, 2017. Data were analyzed from July 1, 2017, through August 1, 2018.

MAIN OUTCOMES AND MEASURES: In-hospital mortality and model discrimination as assessed by the area under the receiver operating characteristic curve (AUC) and model calibration as assessed by the modified Hosmer-Lemeshow statistic.

RESULTS: Among 101 196 patients included in the analysis, 51.3% (n = 51 899) were male, with a mean (SD) age of 61.3 (17.1) years; their in-hospital mortality rate was 10.4% (n = 10 505). A baseline model using only the highest and lowest observed values for each laboratory test result or vital sign achieved a cross-validated AUC of 0.831 (95% CI, 0.830-0.832). In contrast, that model augmented with measures of clinical trajectory achieved an AUC of 0.899 (95% CI, 0.896-0.902; P < .001 for AUC difference). Further augmenting this model with NLP-derived terms associated with mortality further increased the AUC to 0.922 (95% CI, 0.916-0.924; P < .001). These NLP-derived terms were associated with improved model performance even when applied across sites (AUC difference for UCSF: 0.077 to 0.021; AUC difference for MPMC: 0.071 to 0.051; AUC difference for BIDMC: 0.035 to 0.043; P < .001) when augmenting with NLP at each site.

CONCLUSIONS AND RELEVANCE: Intensive care unit mortality prediction models incorporating measures of clinical trajectory and NLP-derived terms yielded excellent predictive performance and generalized well in this sample of hospitals. The role of these automated algorithms, particularly those using unstructured data from notes and other sources, in clinical research and quality improvement seems to merit additional investigation.

2017

Kazi, Dhruv S, Joanne Penko, Pamela G Coxson, Andrew E Moran, Daniel A Ollendorf, Jeffrey A Tice, and Kirsten Bibbins-Domingo. (2017) 2017. “Updated Cost-Effectiveness Analysis of PCSK9 Inhibitors Based on the Results of the FOURIER Trial.”. JAMA 318 (8): 748-50. https://doi.org/10.1001/jama.2017.9924.
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This study uses the results of the FOURIER trial to assess the current cost-effectiveness of PCSK9 inhibitors over the lifetime analytic horizon for patients with atherosclerotic cardiovascular disease in the United States.

  • Aggarwal, Rahul, Kirsten Bibbins-Domingo, Robert W Yeh, Yang Song, Nicholas Chiu, Rishi K Wadhera, Changyu Shen, and Dhruv S Kazi. (2022) 2022. “Diabetes Screening by Race and Ethnicity in the United States: Equivalent Body Mass Index and Age Thresholds.”. Annals of Internal Medicine 175 (6): 765-73. https://doi.org/10.7326/M20-8079.
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    BACKGROUND: Racial/ethnic minority populations in the United States have increased rates of diabetes compared with White populations. The 2021 guidelines from the U.S. Preventive Services Task Force recommend diabetes screening for adults aged 35 to 70 years with a body mass index (BMI) of 25 kg/m2 or greater.

    OBJECTIVE: To determine the BMI threshold for diabetes screening in major racial/ethnic minority populations with benefits and harms equivalent to those of the current diabetes screening threshold in White adults.

    DESIGN: Cross-sectional study.

    SETTING: NHANES (National Health and Nutrition Examination Survey), 2011 to 2018.

    PARTICIPANTS: Nonpregnant U.S. adults aged 18 to 70 years (n = 19 335).

    MEASUREMENTS: A logistic regression model was used to estimate diabetes prevalence at various BMIs for White, Asian, Black, and Hispanic Americans. For each racial/ethnic minority group, the equivalent BMI threshold was defined as the BMI at which the prevalence of diabetes in 35-year-old persons in that group is equal to that in 35-year-old White adults at a BMI of 25 kg/m2. Ranges were estimated to account for the uncertainty in prevalence estimates for White and racial/ethnic minority populations.

    RESULTS: Among adults aged 35 years with a BMI of 25 kg/m2, the prevalence of diabetes in Asian Americans (3.8% [95% CI, 2.8% to 5.1%]), Black Americans (3.5% [CI, 2.7% to 4.7%]), and Hispanic Americans (3.0% [CI, 2.1% to 4.2%]) was significantly higher than that in White Americans (1.4% [CI, 1.0% to 2.0%]). Compared with a BMI threshold of 25 kg/m2 in White Americans, the equivalent BMI thresholds for diabetes prevalence were 20 kg/m2 (range, <18.5 to 23 kg/m2) for Asian Americans, less than 18.5 kg/m2 (range, <18.5 to 23 kg/m2) for Black Americans, and 18.5 kg/m2 (range, <18.5 to 24 kg/m2) for Hispanic Americans.

    LIMITATION: Sample size limitations precluded assessment of heterogeneity within racial/ethnic groups.

    CONCLUSION: Among U.S. adults aged 35 years or older, offering diabetes screening to Black Americans and Hispanic Americans with a BMI of 18.5 kg/m2 or greater and Asian Americans with a BMI of 20 kg/m2 or greater would be equivalent to screening White adults with a BMI of 25 kg/m2 or greater. Using screening thresholds specific to race/ethnicity has the potential to reduce disparities in diabetes diagnosis.

    PRIMARY FUNDING SOURCE: Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology.

  • Almarzooq, Zaid I, Dhruv S Kazi, Yun Wang, Mabel Chung, Wei Tian, Jordan B Strom, Suzanne J Baron, and Robert W Yeh. (2022) 2022. “Outcomes of Stroke Events During Transcatheter Aortic Valve Implantation.”. EuroIntervention : Journal of EuroPCR in Collaboration With the Working Group on Interventional Cardiology of the European Society of Cardiology 18 (4): e335-e344. https://doi.org/10.4244/EIJ-D-21-00951.
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    BACKGROUND: Despite improvements in the safety of transcatheter aortic valve implantation (TAVI),  4% of patients experience a procedure-related stroke. Understanding long-term health and healthcare implications of these events may motivate the development and adoption of preventative strategies.  Aims: We aimed to assess the association of TAVI-related ischaemic stroke with subsequent clinical outcomes and healthcare utilisation.

    METHODS: We used Medicare fee-for-service claims to identify patients who underwent their first TAVI between January 2012 and December 2017. Previously used ICD-9-CM and ICD-10-CM codes were used to identify TAVI-related ischaemic stroke. Among those with and without TAVI-related ischaemic stroke, we compared the risk of a composite endpoint that included all-cause mortality, acute myocardial infarction, and subsequent stroke using inverse probability treatment weighted Cox regression. We also performed a difference-in-difference analysis to compare 1-year Medicare expenditures and days spent at home during the first year after TAVI.

    RESULTS:  Among 129,628 primary TAVI patients, 5,549 (4.3%) had a procedure-related stroke. These patients were more likely to be female and have had prior stroke, peripheral vascular disease, ischaemic heart disease, or renal failure. After adjustment, TAVI-related ischaemic stroke was associated with a higher risk of the 1-year composite outcome (HR 1.67, 95% CI: 1.56-1.78), higher 1-year Medicare expenditures (difference $9,245 [standard error 790], p<0.001), and fewer days at home during the first year (difference 16 days [standard error 1], p<0.001).

    CONCLUSIONS: Among Medicare beneficiaries undergoing TAVI, procedure-related ischaemic stroke was associated with worse outcomes, increased Medicare expenditures, and less time spent at home. Procedure-related ischaemic stroke during TAVI remains a critically important and potentially preventable source of patient mortality, morbidity and healthcare utilisation.

  • Bellows, Brandon K, Amit Khera V, Yiyi Zhang, Natalia Ruiz-Negrón, Henry M Stoddard, John B Wong, Dhruv S Kazi, Sarah D de Ferranti, and Andrew E Moran. (2022) 2022. “Estimated Yield of Screening for Heterozygous Familial Hypercholesterolemia With and Without Genetic Testing in US Adults.”. Journal of the American Heart Association 11 (11): e025192. https://doi.org/10.1161/JAHA.121.025192.
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    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.

  • Islam, Shabatun J, Gargya Malla, Robert W Yeh, Arshed A Quyyumi, Dhruv S Kazi, Wei Tian, Yang Song, et al. (2022) 2022. “County-Level Social Vulnerability Is Associated With In-Hospital Death and Major Adverse Cardiovascular Events in Patients Hospitalized With COVID-19: An Analysis of the American Heart Association COVID-19 Cardiovascular Disease Registry.”. Circulation. Cardiovascular Quality and Outcomes 15 (8): e008612. https://doi.org/10.1161/CIRCOUTCOMES.121.008612.
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    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.

  • Ganatra, Sarju, Sourbha S Dani, Ashish Kumar, Safi U Khan, Rishi Wadhera, Tomas G Neilan, Paaladinesh Thavendiranathan, et al. (2022) 2022. “Impact of Social Vulnerability on Comorbid Cancer and Cardiovascular Disease Mortality in the United States.”. JACC. CardioOncology 4 (3): 326-37. https://doi.org/10.1016/j.jaccao.2022.06.005.
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    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.

  • Oseran, Andrew S, Tianyu Sun, Rishi K Wadhera, Issa J Dahabreh, James A de Lemos, Sandeep R Das, Christine Rutan, Aarti H Asnani, Robert W Yeh, and Dhruv S Kazi. (2022) 2022. “Enriching the American Heart Association COVID-19 Cardiovascular Disease Registry Through Linkage With External Data Sources: Rationale and Design.”. Journal of the American Heart Association 11 (18): e7743. https://doi.org/10.1161/JAHA.122.027094.
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    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.

  • Riley, Elise D, Dhruv S Kazi, Phillip O Coffin, Eric Vittinghoff, Amanda N Wade, Tommaso C Bulfone, Kara L Lynch, Zahra Atai, and Alan H B Wu. (2022) 2022. “Impact of Multiple Substance Use on Circulating ST2, a Biomarker of Adverse Cardiac Remodelling, in Women.”. Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals 27 (8): 802-8. https://doi.org/10.1080/1354750X.2022.2129451.
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    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.

  • Strom, Jordan B, Yuansong Zhao, Changyu Shen, Jason H Wasfy, Jiaman Xu, Evin Yucel, Varsha Tanguturi, et al. (2022) 2022. “Development and Validation of an Echocardiographic Algorithm to Predict Long-Term Mitral and Tricuspid Regurgitation Progression.”. European Heart Journal. Cardiovascular Imaging 23 (12): 1606-16. https://doi.org/10.1093/ehjci/jeab254.
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    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.

  • Chung, Mabel, Neel M Butala, Kamil F Faridi, Zaid I Almarzooq, Dingning Liu, Jiaman Xu, Yang Song, et al. (2023) 2023. “Days at Home After Transcatheter or Surgical Aortic Valve Replacement in High-Risk Patients.”. American Heart Journal 255: 125-36. https://doi.org/10.1016/j.ahj.2022.10.080.
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    BACKGROUND: Days at home (DAH) quantifies time spent at home after a medical event but has not been fully evaluated for TAVR. We sought to compare 1- and 5-year DAH (DAH365, DAH1825) among high-risk patients participating in a randomized trial of transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis versus surgical aortic valve replacement (SAVR).

    METHODS: We linked data from the U.S. CoreValve High Risk Trial to Medicare Fee-for-Service claims in 456 patients with 450 (234 TAVR/216 SAVR) and 427 (222 TAVR/205 SAVR) analyzed at 1 and 5 years. DAH was calculated as the number of days alive and spent outside of a hospital, skilled nursing facility, rehabilitation, long-term acute care hospital, emergency department, or observation stay.

    RESULTS: Mean DAH365 was higher in patients who underwent TAVR compared with SAVR (295.1 ± 106.9 vs 267.8 ± 122.3, difference in days 27.2 [95% CI 6.0, 48.5], P = .01). Compared with SAVR, TAVR patients had a shorter index length of stay (LOS) (7.4 ± 4.5 vs 12.5 ± 9.0, difference in days -5.1 [-6.5, -3.8], P < .001). The largest contributions to decreased DAH365 were mortality days and total facility days after discharge from the index hospitalization (mortality days-TAVR: 34.7 ± 93.1 vs SAVR: 48.0 ± 108.8, difference in days -13.3 [95% CI -32.1, 5.5], P = .17; total facility days-TAVR: 27.9 ± 47.4 vs SAVR: 36.7 ± 48.9, difference in days -8.8 [95% CI -17.8, 0.1], P = .05). Mean DAH1825 was numerically but not statistically significantly higher in TAVR (TAVR: 1154.2 ± 659.0 vs SAVR: 1067.6 ± 697.3, difference in days 86.6 [95% CI -42.3, 215.6], P = .19). Landmark analysis showed no difference in DAH from years 1 to 5 (TAVR: 1040.4 ± 477.5 vs SAVR: 1022.9 ± 489.3, P = .74).

    CONCLUSIONS: In the U.S. CoreValve High Risk Trial linked to Medicare, high-risk patients undergoing TAVR spend an average of 27 additional DAH compared with SAVR in the first year after the procedure due to a shorter index LOS and the additive effect of fewer but nonsignificantly different mortality and total facility days after discharge from the index hospitalization compared with SAVR. After the first year, both groups spend a similar number of DAH. These results describe the postprocedural course of high-risk patients from a patient-centered perspective, which may guide expectations regarding longitudinal health care needs and inform shared decision-making.

  • Varghese, Merilyn S, Alexis L Beatty, Yang Song, Jiaman Xu, Laurence S Sperling, Gregg C Fonarow, Steven J Keteyian, et al. (2022) 2022. “Cardiac Rehabilitation and the COVID-19 Pandemic: Persistent Declines in Cardiac Rehabilitation Participation and Access Among US Medicare Beneficiaries.”. Circulation. Cardiovascular Quality and Outcomes 15 (12): e009618. https://doi.org/10.1161/CIRCOUTCOMES.122.009618.
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    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.

  • Tsao, Connie W, Aaron W Aday, Zaid I Almarzooq, Cheryl A M Anderson, Pankaj Arora, Christy L Avery, Carissa M Baker-Smith, et al. (2023) 2023. “Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association.”. Circulation 147 (8): e93-e621. https://doi.org/10.1161/CIR.0000000000001123.
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    BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).

    METHODS: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2023 Statistical Update is the product of a full year's worth of effort in 2022 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. The American Heart Association strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional COVID-19 (coronavirus disease 2019) publications, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains.

    RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics.

    CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

  • Narasimmaraj, Prihatha R, Andrew Oseran, Archana Tale, Jiaman Xu, Utibe R Essien, Dhruv S Kazi, Robert W Yeh, and Rishi K Wadhera. (2023) 2023. “Out-of-Pocket Drug Costs for Medicare Beneficiaries With Cardiovascular Risk Factors Under the Inflation Reduction Act.”. Journal of the American College of Cardiology 81 (15): 1491-1501. https://doi.org/10.1016/j.jacc.2023.02.002.
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    BACKGROUND: High out-of-pocket prescription drug costs contribute to financial toxicity, medication nonadherence, and adverse cardiovascular (CV) outcomes. Policymakers recently passed the Inflation Reduction Act, which will cap Medicare out-of-pocket drug costs at $2,000/year and expand full low-income subsidies (LIS). It is unclear how these provisions will affect Medicare beneficiaries with CV risk factors and/or conditions.

    OBJECTIVES: The authors sought to characterize the population of Medicare beneficiaries with CV risk factors/conditions experiencing out-of-pocket prescription drug costs >$2,000/year and estimate their potential savings under the Inflation Reduction Act's spending cap; identify sociodemographic characteristics associated with out-of-pocket costs >$2,000/year; and characterize beneficiaries newly eligible for LIS under the Inflation Reduction Act.

    METHODS: This was a cross-sectional study of Medicare beneficiaries aged ≥65 years with ≥1 CV risk factor/condition from 2016 to 2019.

    RESULTS: An annual estimated 34,056,335 ± 855,653 Medicare beneficiaries (mean ± SE) had ≥1 CV risk factor/condition, of whom 1,020,484 ± 77,055 experienced out-of-pocket drug costs >$2,000/year. The likelihood of experiencing out-of-pocket drug costs >$2,000/year was lower among adults ≥75 years vs 65 to 74 years (adjusted OR: 0.67; 95% CI: 0.49-0.93) and for low-income vs higher-income adults. Among beneficiaries currently spending >$2,000/year, estimated median out-of-pocket drug savings would be $855/year and total annual savings $1,723,031,307 ± $91,150,609 under the Inflation Reduction Act. An estimated 1,289,861 beneficiaries would also become newly eligible for LIS.

    CONCLUSIONS: More than 1 million older adults with CV risk factors and/or conditions spend >$2,000/year out-of-pocket on prescription drugs and will likely benefit from the Inflation Reduction Act's cap, with estimated total out-of-pocket savings of $1.7 billion/year, while another 1.3 million will also become newly eligible for LIS.

  • Cohen, Laura P, Nicolas Isaza, Inmaculada Hernandez, Gregory D Lewis, Jennifer E Ho, Gregg C Fonarow, Dhruv S Kazi, and Brandon K Bellows. (2023) 2023. “Cost-Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors for the Treatment of Heart Failure With Preserved Ejection Fraction.”. JAMA Cardiology 8 (5): 419-28. https://doi.org/10.1001/jamacardio.2023.0077.
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    IMPORTANCE: Adding a sodium-glucose cotransporter-2 inhibitor (SGLT2-I) to standard-of-care treatment in patients with heart failure with preserved ejection fraction (HFpEF) reduces the risk of a composite outcome of worsening heart failure or cardiovascular mortality, but the cost-effectiveness in US patients with HFpEF is uncertain.

    OBJECTIVE: To evaluate the lifetime cost-effectiveness of standard therapy plus an SGLT2-I compared with standard therapy in individuals with HFpEF.

    DESIGN, SETTING, AND PARTICIPANTS: In this economic evaluation conducted from September 8, 2021, to December 12, 2022, a state-transition Markov model simulated monthly health outcomes and direct medical costs. Input parameters including hospitalization rates, mortality rates, costs, and utilities were extracted from HFpEF trials, published literature, and publicly available data sets. The base-case annual cost of SGLT2-I was $4506. A simulated cohort with similar characteristics as participants of the Empagliflozin in Heart Failure With a Preserved Ejection Fraction (EMPEROR-Preserved) and Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction (DELIVER) trials was used.

    EXPOSURES: Standard of care plus SGLT2-I vs standard of care.

    MAIN OUTCOMES AND MEASURES: The model simulated hospitalizations, urgent care visits, and cardiovascular and noncardiovascular death. Future medical costs and benefits were discounted by 3% per year. Main outcomes were quality-adjusted life-years (QALYs), direct medical costs (2022 US dollars), and incremental cost-effectiveness ratio (ICER) of SGLT2-I therapy from a US health care sector perspective. The ICER of SGLT2-I therapy was evaluated according to the American College of Cardiology/American Heart Association value framework (high value: <$50 000; intermediate value: $50 000 to <$150 000; and low value: ≥$150 000).

    RESULTS: The simulated cohort had a mean (SD) age of 71.7 (9.5) years and 6828 of 12 251 participants (55.7%) were male. Standard of care plus SGLT2-I increased quality-adjusted survival by 0.19 QALYs at an increased cost of $26 300 compared with standard of care. The resulting ICER was $141 200 per QALY gained, with 59.1% of 1000 probabilistic iterations indicating intermediate value and 40.9% indicating low value. The ICER was most sensitive to SGLT2-I costs and effect of SGLT2-I therapy on cardiovascular death (eg, increasing to $373 400 per QALY gained if SGLT2-I therapy was assumed to have no effect on mortality).

    CONCLUSIONS AND RELEVANCE: Results of this economic evaluation suggest that at 2022 drug prices, adding an SGLT2-I to standard of care was of intermediate or low economic value compared with standard of care in US adults with HFpEF. Efforts to expand access to SGLT2-I for individuals with HFpEF should be coupled with efforts to lower the cost of SGLT2-I therapy.

  • Suen, Leslie W, Eric Vittinghoff, Alan H B Wu, Akshay Ravi, Phillip O Coffin, Priscilla Hsue, Kara L Lynch, Dhruv S Kazi, and Elise D Riley. (2023) 2023. “Multiple Substance Use and Blood Pressure in Women Experiencing Homelessness.”. Addictive Behaviors Reports 17: 100483. https://doi.org/10.1016/j.abrep.2023.100483.
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    BACKGROUND: Substance use increases risk of cardiovascular events, particularly among women with additional risk factors like housing instability. While multiple substance use is common among unstably housed individuals, relationships between multiple substance use and cardiovascular risk factors like blood pressure are not well characterized.

    METHODS: We conducted a cohort study between 2016 and 2019 to examine associations between multiple substance use and blood pressure in women experiencing homelessness and unstable housing. Participants completed six monthly visits including vital sign assessment, interview, and blood draw to assess toxicology-confirmed substance use (e.g., cocaine, alcohol, opioids) and cardiovascular health. We used linear mixed models to evaluate the outcomes of systolic and diastolic blood pressure (SBP; DBP).

    RESULTS: Mean age was 51.6 years; 74 % were women of color. Prevalence of any substance use was 85 %; 63 % of participants used at least two substances at baseline. Adjusting for race, body mass index and cholesterol, cocaine was the only substance significantly associated with SBP (4.71 mmHg higher; 95 % CI 1.68, 7.74) and DBP (2.83 mmHg higher; 95 % CI 0.72, 4.94). Further analysis found no differences in SBP or DBP between those with concurrent use of other stimulants, depressants, or both with cocaine, compared to those who used cocaine only.

    CONCLUSIONS: Cocaine was the only substance associated with higher SBP and DBP, even after accounting for simultaneous use of other substances. Along with interventions to address cocaine use, stimulant use screening during cardiovascular risk assessment and intensive blood pressure management may improve cardiovascular outcomes among women experiencing housing instability.

  • Kazi, Dhruv S, Colette DeJong, Randi Chen, Rishi K Wadhera, and Chien-Wen Tseng. (2023) 2023. “The Inflation Reduction Act and Out-of-Pocket Drug Costs for Medicare Beneficiaries With Cardiovascular Disease.”. Journal of the American College of Cardiology 81 (21): 2103-11. https://doi.org/10.1016/j.jacc.2023.03.414.
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    BACKGROUND: High out-of-pocket costs can impede access to guideline-directed cardiovascular drugs. The 2022 Inflation Reduction Act (IRA) will eliminate catastrophic coinsurance and cap annual out-of-pocket costs for Medicare Part D patients by 2025.

    OBJECTIVES: This study sought to estimate the IRA's impact on out-of-pocket costs for Part D beneficiaries with cardiovascular disease.

    METHODS: The investigators chose 4 cardiovascular conditions that frequently require high-cost guideline-recommended drugs: severe hypercholesterolemia; heart failure with reduced ejection fraction (HFrEF); HFrEF with atrial fibrillation (AF); and cardiac transthyretin amyloidosis. This study included 4,137 Part D plans nationwide and compared projected annual out-of-pocket drug costs for each condition in 2022 (baseline), 2023 (rollout), 2024 (5% catastrophic coinsurance eliminated), and 2025 ($2,000 cap on out-of-pocket costs).

    RESULTS: In 2022, mean projected annual out-of-pocket costs were $1,629 for severe hypercholesterolemia, $2,758 for HFrEF, $3,259 for HFrEF with AF, and $14,978 for amyloidosis. In 2023, the initial IRA rollout will not significantly change out-of-pocket costs for the 4 conditions. In 2024, elimination of 5% catastrophic coinsurance will lower out-of-pocket costs for the 2 costliest conditions: HFrEF with AF ($2,855, 12% reduction) and amyloidosis ($3,468, 77% reduction). By 2025, the $2,000 cap will lower out-of-pocket costs for all 4 conditions to $1,491 for hypercholesterolemia (8% reduction), $1,954 for HFrEF (29% reduction), $2,000 for HFrEF with AF (39% reduction), and $2,000 for cardiac transthyretin amyloidosis (87% reduction).

    CONCLUSIONS: The IRA will reduce Medicare beneficiaries' out-of-pocket drug costs for the selected cardiovascular conditions by 8% to 87%. Future studies should assess the IRA's impact on adherence to guideline-directed cardiovascular therapies and health outcomes.

  • Oseran, Andrew S, Yang Song, Jiaman Xu, Issa J Dahabreh, Rishi K Wadhera, James A de Lemos, Sandeep R Das, Tianyu Sun, Robert W Yeh, and Dhruv S Kazi. (2023) 2023. “Long Term Risk of Death and Readmission After Hospital Admission With Covid-19 Among Older Adults: Retrospective Cohort Study.”. BMJ (Clinical Research Ed.) 382: e076222. https://doi.org/10.1136/bmj-2023-076222.
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    OBJECTIVES: To characterize the long term risk of death and hospital readmission after an index admission with covid-19 among Medicare fee-for-service beneficiaries, and to compare these outcomes with historical control patients admitted to hospital with influenza.

    DESIGN: Retrospective cohort study.

    SETTING: United States.

    PARTICIPANTS: 883 394 Medicare fee-for-service beneficiaries age ≥65 years discharged alive after an index hospital admission with covid-19 between 1 March 2020 and 31 August 2022, compared with 56 409 historical controls discharged alive after a hospital admission with influenza between 1 March 2018 and 31 August 2019. Weighting methods were used to account for differences in observed characteristics.

    MAIN OUTCOME MEASURES: All cause death within 180 days of discharge. Secondary outcomes included first all cause readmission and a composite of death or readmission within 180 days.

    RESULTS: The covid-19 cohort compared with the influenza cohort was younger (77.9 v 78.9 years, standardized mean difference -0.12) and had a lower proportion of women (51.7% v 57.3%, -0.11). Both groups had a similar proportion of black beneficiaries (10.3% v 8.1%, 0.07) and beneficiaries with dual Medicaid-Medicare eligibility status (20.1% v 19.2%; 0.02). The covid-19 cohort had a lower comorbidity burden, including atrial fibrillation (24.3% v 29.5%, -0.12), heart failure (43.4% v 49.9%, -0.13), and chronic obstructive pulmonary disease (39.2% v 52.9%, -0.27). After weighting, the covid-19 cohort had a higher risk (ie, cumulative incidence) of all cause death at 30 days (10.9% v 3.9%; standardized risk difference 7.0%, 95% confidence interval 6.8% to 7.2%), 90 days (15.5% v 7.1%; 8.4%, 8.2% to 8.7%), and 180 days (19.1% v 10.5%; 8.6%, 8.3% to 8.9%) compared with the influenza cohort. The covid-19 cohort also experienced a higher risk of hospital readmission at 30 days (16.0% v 11.2%; 4.9%, 4.6% to 5.1%) and 90 days (24.1% v 21.3%; 2.8%, 2.5% to 3.2%) but a similar risk at 180 days (30.6% v 30.6%;-0.1%, -0.5% to 0.3%). Over the study period, the 30 day risk of death for patients discharged after a covid-19 admission decreased from 17.9% to 7.2%.

    CONCLUSIONS: Medicare beneficiaries who were discharged alive after a covid-19 hospital admission had a higher post-discharge risk of death compared with historical influenza controls; this difference, however, was concentrated in the early post-discharge period. The risk of death for patients discharged after a covid-19 related hospital admission substantially declined over the course of the pandemic.

  • Virani, Salim S, Kristin Newby, Suzanne Arnold V, Vera Bittner, LaPrincess C Brewer, Susan Halli Demeter, Dave L Dixon, et al. (2023) 2023. “2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.”. Circulation 148 (9): e9-e119. https://doi.org/10.1161/CIR.0000000000001168.
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    AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease."

    METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

    STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

  • Members, Writing Committee, Salim S Virani, Kristin Newby, Suzanne Arnold V, Vera Bittner, LaPrincess C Brewer, Susan Halli Demeter, et al. (2023) 2023. “2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.”. Journal of the American College of Cardiology 82 (9): 833-955. https://doi.org/10.1016/j.jacc.2023.04.003.
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    AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease."

    METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

    STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

  • Ravi, Akshay, Eric Vittinghoff, Alan H B Wu, Leslie W Suen, Phillip O Coffin, Priscilla Hsue, Kara L Lynch, Sithu Win, Dhruv S Kazi, and Elise D Riley. (2023) 2023. “Cocaine Use Is Associated With Increased LVMI in Unstably Housed Women With Polysubstance Use.”. Substance Abuse 44 (4): 323-29. https://doi.org/10.1177/08897077231199572.
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    BACKGROUND: While substance use is known to influence cardiovascular health, most prior studies only consider one substance at a time. We examined associations between the concurrent use of multiple substances and left ventricular mass index (LVMI) in unhoused and unstably housed women.

    METHODS: Between 2016 and 2019, we conducted a cohort study of unstably housed women in which measurements included an interview, serum/urine collection, vital sign assessment, and a single transthoracic echocardiogram at baseline. We evaluated independent associations between 39 separate substances confirmed through toxicology and echocardiography-confirmed LVMI.

    RESULTS: The study included 194 participants with a median age of 53.5 years and a high proportion of women of color (72.6%). Toxicology-confirmed substance use included: 69.1% nicotine, 56.2% cocaine, 28.9% methamphetamines, 28.9% alcohol, 23.2% opioid analgesics, and 9.8% opioids with catecholaminergic effects. In adjusted analysis, cocaine was independently associated with higher LVMI (Adjusted linear effect: 18%; 95% CI 9.9, 26.6). Associations with other substances did not reach levels of significance and did not significantly interact with cocaine.

    CONCLUSION: In a population of vulnerable women where the use of multiple substances is common, cocaine stands out as having particularly detrimental influences on cardiac structure. Blood pressure did not attenuate the association appreciably, suggesting direct effects of cocaine on LVMI. Routinely evaluating stimulant use as a chronic risk factor during risk assessment and preventive clinical care planning may reduce end organ damage, particularly in highly vulnerable women.