Publications

2023

Sims, Kendra D, Pengxiao Carol Wei, Joanne M Penko, Susan Hennessy, Pamela G Coxson, Nita H Mukand, Brandon K Bellows, et al. (2023) 2023. “Projected Impact of Nonpharmacologic Management of Stage 1 Hypertension Among Lower-Risk US Adults.”. MedRxiv : The Preprint Server for Health Sciences. https://doi.org/10.1101/2023.12.26.23300563.

BACKGROUND: The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines newly classified 31 million US adults as having stage 1 hypertension. The ACC/AHA guidelines recommend behavioral change without pharmacology for the low-risk portion of this group. However, the nationwide reduction in cardiovascular disease (CVD) and associated healthcare expenditures achievable by evidence-based dietary improvements, sustained weight loss, adequate physical activity, and alcohol moderation remain unquantified. We estimated the effect of systolic BP (SBP) control and behavioral changes on 10-year CVD outcomes and costs.

METHODS: We used the CVD Policy Model to simulate CVD events, mortality, and healthcare costs among US adults aged 35-64. We simulated interventions on a target population, identified from the 2015-2018 National Health and Nutrition Examination Survey, with low-risk stage 1 systolic hypertension: defined as untreated SBP 130-139 mmHg and diastolic BP <90 mmHg; no history of CVD, diabetes, or chronic kidney disease; and low 10-year risk of CVD. We used published meta-analyses and trials to estimate the effects of behavior modification on SBP. We assessed the extent to which intermittent healthcare utilization or partial uptake of nonpharmacologic therapy would decrease CVD events prevented.

RESULTS: Controlling SBP to <130 mmHg among the estimated 8.8 million U.S. adults (51% women) in the target population could prevent 26,100 CVD events, avoid 2,900 deaths, and save $1.6 billion in healthcare costs over 10 years. The Dietary Approaches to Stop Hypertension (DASH) diet could prevent 16,000 CVD events among men and 12,000 among women over a decade. Other nonpharmacologic interventions could avert between 3,700 and 19,500 CVD events. However, only 5.5 million (61%) of the target population regularly utilized healthcare where recommended clinician counseling could occur.

CONCLUSIONS: As only two-thirds of U.S. adults with Stage 1 hypertension regularly receive medical care, substantial benefits to cardiovascular health and associated costs may only stem from policies that promote widespread adoption and sustained adherence of nonpharmacologic therapy. Future work should quantify the population-level costs, benefits, and efficacy of improving the food system and local infrastructure on health behavior change.

Simon, Samantha J, Rushad Patell, Jeffrey I Zwicker, Dhruv S Kazi, and Brian L Hollenbeck. (2023) 2023. “Venous Thromboembolism in Total Hip and Total Knee Arthroplasty.”. JAMA Network Open 6 (12): e2345883. https://doi.org/10.1001/jamanetworkopen.2023.45883.

IMPORTANCE: The optimal pharmacologic thromboprophylaxis agent after total hip and total knee arthroplasty is uncertain and consensus is lacking. Quantifying the risk of postoperative venous thromboembolism (VTE) and bleeding and evaluating comparative effectiveness and safety of the thromboprophylaxis strategies can inform care.

OBJECTIVE: To quantify risk factors for postoperative VTE and bleeding and compare patient outcomes among pharmacological thromboprophylaxis agents used after total hip and knee arthroplasty.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from a large health care claims database. Participants included patients in the United States with hip or knee arthroplasty and continuous insurance enrollment 3 months prior to and following their surgical procedure. Patients were excluded if they received anticoagulation before surgery, received no postsurgical pharmacological thromboprophylaxis, or had multiple postsurgery thromboprophylactic agents. In a propensity-matched analysis, patients receiving a direct oral anticoagulant (DOAC) were matched with those receiving aspirin.

EXPOSURES: Aspirin, apixaban, rivaroxaban, enoxaparin, or warfarin.

MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day cumulative incidence of postdischarge VTE. Other outcomes included postdischarge bleeding.

RESULTS: Among 29 264 patients included in the final cohort, 17 040 (58.2%) were female, 27 897 (95.2%) had inpatient admissions with median (IQR) length of stay of 2 (1-2) days, 10 948 (37.4%) underwent total hip arthroplasty, 18 316 (62.6%) underwent total knee arthroplasty; and median (IQR) age was 59 (55-63) years. At 30 days, cumulative incidence of VTE was 1.19% (95% CI, 1.06%-1.32%) and cumulative incidence of bleeding was 3.43% (95% CI, 3.22%-3.64%). In the multivariate analysis, leading risk factors associated with increased VTE risk included prior VTE history (odds ratio [OR], 5.94 [95% CI, 4.29-8.24]), a hereditary hypercoagulable state (OR, 2.64 [95% CI, 1.32-5.28]), knee arthroplasty (OR, 1.65 [95% CI, 1.29-2.10]), and male sex (OR, 1.34 [95% CI, 1.08-1.67]). In a propensity-matched cohort of 7844 DOAC-aspirin pairs, there was no significant difference in the risk of VTE in the first 30 days after the surgical procedure (OR, 1.14 [95% CI, 0.82-1.59]), but postoperative bleeding was more frequent in patients receiving DOACs (OR, 1.36 [95% CI, 1.13-1.62]).

CONCLUSIONS AND RELEVANCE: In this cohort study of patients who underwent total hip or total knee arthroplasty, underlying patient risk factors, but not choice of aspirin or DOAC, were associated with postsurgical VTE. Postoperative bleeding rates were lower in patients prescribed aspirin. These results suggest that thromboprophylaxis strategies should be patient-centric and tailored to individual risk of thrombosis and bleeding.

Liu, Michael, Rahul Aggarwal, ZhaoNian Zheng, Robert W Yeh, Dhruv S Kazi, Karen E Joynt Maddox, and Rishi K Wadhera. (2023) 2023. “Cardiovascular Health of Middle-Aged U.S. Adults by Income Level, 1999 to March 2020 : A Serial Cross-Sectional Study.”. Annals of Internal Medicine 176 (12): 1595-1605. https://doi.org/10.7326/M23-2109.

BACKGROUND: Although cardiovascular mortality has increased among middle-aged U.S. adults since 2011, how the burden of cardiovascular risk factors has changed for this population by income level over the past 2 decades is unknown.

OBJECTIVE: To evaluate trends in the prevalence, treatment, and control of cardiovascular risk factors among low-income and higher-income middle-aged adults and how social determinants contribute to recent associations between income and cardiovascular health.

DESIGN: Serial cross-sectional study.

SETTING: NHANES (National Health and Nutrition Examination Survey), 1999 to March 2020.

PARTICIPANTS: Middle-aged adults (aged 40 to 64 years).

MEASUREMENTS: Age-standardized prevalence of hypertension, diabetes, hyperlipidemia, obesity, and cigarette use; treatment rates for hypertension, diabetes, and hyperlipidemia; and rates of blood pressure, glycemic, and cholesterol control.

RESULTS: The study population included 20 761 middle-aged adults. The prevalence of hypertension, diabetes, and cigarette use was consistently higher among low-income adults between 1999 and March 2020. Low-income adults had an increase in hypertension over the study period (37.2% [95% CI, 33.5% to 40.9%] to 44.7% [CI, 39.8% to 49.5%]) but no changes in diabetes or obesity. In contrast, higher-income adults did not have a change in hypertension but had increases in diabetes (7.8% [CI, 5.0% to 10.6%] to 14.9% [CI, 12.4% to 17.3%]) and obesity (33.0% [CI, 26.7% to 39.4%] to 44.0% [CI, 40.2% to 47.7%]). Cigarette use was high and stagnant among low-income adults (33.2% [CI, 28.4% to 38.0%] to 33.9% [CI, 29.6% to 38.3%]) but decreased among their higher-income counterparts (18.6% [CI, 13.5% to 23.7%] to 11.5% [CI, 8.7% to 14.3%]). Treatment and control rates for hypertension were unchanged in both groups (>80%), whereas diabetes treatment rates improved only among the higher-income group (58.4% [CI, 44.4% to 72.5%] to 77.4% [CI, 67.6% to 87.1%]). Income-based disparities in hypertension, diabetes, and cigarette use persisted in more recent years even after adjustment for insurance coverage, health care access, and food insecurity.

LIMITATION: Sample size limitations could preclude detection of small changes in treatment and control rates.

CONCLUSION: Over 2 decades in the United States, hypertension increased in low-income middle-aged adults, whereas diabetes and obesity increased in their higher-income counterparts. Income-based disparities in hypertension, diabetes, and smoking persisted even after adjustment for other social determinants of health.

PRIMARY FUNDING SOURCE: National Institutes of Health.

Iyengar, Varun, Rushad Patell, Siyang Ren, Sirui Ma, Amanda Pinson, Amelia Barnett, Pavania Elavalakanar, Dhruv S Kazi, Donna Neuberg, and Jeffrey I Zwicker. (2023) 2023. “Influence of Thrombocytopenia on Bleeding and Vascular Events in Atrial Fibrillation.”. Blood Advances 7 (24): 7516-24. https://doi.org/10.1182/bloodadvances.2023011235.

Whether thrombocytopenia substantively increases the risk of hemorrhage associated with anticoagulation in patients with atrial fibrillation (AF) is not established. The purpose of this study was to compare rates of bleeding in patients with AF and thrombocytopenia (platelet count < 100 000/μL) to patients with AF and normal platelet counts (>150 000/μL). We performed a propensity score-matched, retrospective cohort study of adults (n = 1070) with a new diagnosis of AF who received a prescription for an oral anticoagulant between 2015 and 2020. The thrombocytopenia cohort was defined as having at least 2 platelet counts <100 000/μL on separate days in the period spanning the 12 weeks preceding the initiation of anticoagulation to 6 weeks after the initiation of anticoagulation. The primary end point was the 1-year cumulative incidence of major bleeding; secondary end points included clinically relevant bleeding, arterial and venous thrombotic events, and all-cause mortality. Patients with AF and thrombocytopenia experienced a higher 1-year cumulative incidence of major bleeding (13.3% vs 5.7%; P < .0001) and clinically relevant bleeding (24.5% vs 16.7%; P = .005) than the controls. Thrombocytopenia was identified as an independent risk factor for major bleeding (hazard ratio, 2.20; confidence interval, 1.36-3.58; P = .001), with increasing risk based on the severity of thrombocytopenia. The cumulative incidence of arterial thrombosis at 1 year was 3.6% in the group with thrombocytopenia and 1.5% in controls (Gray test, P = .08). These findings suggest that baseline platelet counts are an important biomarker for hemorrhagic outcomes in AF and that the degree of thrombocytopenia is an important factor in determining the level of risk.

Chung, Mabel, Zaid I Almarzooq, Jiaman Xu, Yang Song, Suzanne J Baron, Dhruv S Kazi, and Robert W Yeh. (2023) 2023. “Days at Home After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients.”. Circulation. Cardiovascular Quality and Outcomes 16 (12): e010034. https://doi.org/10.1161/CIRCOUTCOMES.123.010034.

BACKGROUND: Days at home (DAH) represents an important patient-oriented outcome that quantifies time spent at home after a medical event; however, this outcome has not been fully evaluated for low-surgical-risk patients undergoing transcatheter aortic valve replacement (TAVR). We sought to compare 1- and 2-year DAH (DAH365 and DAH730) among low-risk patients participating in a randomized trial of TAVR with a self-expanding bioprosthesis versus surgical aortic valve replacement (SAVR).

METHODS: Using Medicare-linked data from the Evolut Low Risk trial, we identified 619 patients: 606 (322 TAVR/284 SAVR) and 593 (312 TAVR/281 SAVR) were analyzed at 1 and 2 years, respectively. DAH was calculated as days alive and spent outside a hospital, inpatient rehabilitation, skilled nursing facility, long-term acute care hospital, emergency department, or observation stay. Mean DAH was compared using the t test.

RESULTS: The mean (SD) age and female sex were 74.7 (5.1) and 74.3 (4.9) years and 34.6% (115/332) and 30.3% (87/287) in TAVR and SAVR, respectively. Postprocedural discharge to rehabilitation occurred in ≤3.0% (≤10/332) in TAVR and 4.5% (13/287) in SAVR. The mean DAH365 was comparable in TAVR versus SAVR (352.2±45.4 versus 347.8±39.0; difference in days, 4.5 [95% CI, 2.3-11.2]; P=0.20). DAH730 was also comparable in TAVR versus SAVR (701.6±106.0 versus 699.6±94.5; difference in days, 2.0 [-14.1 to 18.2]; P=0.81). Secondary outcomes DAH30 and DAH90 were higher in TAVR (DAH30, 26.0±3.6 versus 20.7±6.4; difference in days, 5.3 [4.5-6.2]; P<0.001; DAH90, 85.1±8.3 versus 78.7±13.6; difference in days, 6.4 [4.6-8.2]; P<0.001).

CONCLUSIONS: In the Evolut Low Risk trial linked to Medicare, low-risk patients undergoing TAVR spend a similar number of days at home at 1 and 2 years compared with SAVR. Days spent at home at 30 and 90 days were higher in TAVR. In contrast to higher-risk patients studied in prior work, there is no clear advantage of TAVR versus SAVR for DAH in the first 2 years after AVR in low-surgical-risk patients.

Sims, Kendra D, Pengxiao Carol Wei, Joanne M Penko, Susan Hennessy, Pamela G Coxson, Nita H Mukand, Brandon K Bellows, et al. (2023) 2023. “Projected Impact of Nonpharmacologic Management of Stage 1 Hypertension Among Lower-Risk US Adults.”. MedRxiv : The Preprint Server for Health Sciences. https://doi.org/10.1101/2023.12.26.23300563.

BACKGROUND: The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines newly classified 31 million US adults as having stage 1 hypertension. The ACC/AHA guidelines recommend behavioral change without pharmacology for the low-risk portion of this group. However, the nationwide reduction in cardiovascular disease (CVD) and associated healthcare expenditures achievable by evidence-based dietary improvements, sustained weight loss, adequate physical activity, and alcohol moderation remain unquantified. We estimated the effect of systolic BP (SBP) control and behavioral changes on 10-year CVD outcomes and costs.

METHODS: We used the CVD Policy Model to simulate CVD events, mortality, and healthcare costs among US adults aged 35-64. We simulated interventions on a target population, identified from the 2015-2018 National Health and Nutrition Examination Survey, with low-risk stage 1 systolic hypertension: defined as untreated SBP 130-139 mmHg and diastolic BP <90 mmHg; no history of CVD, diabetes, or chronic kidney disease; and low 10-year risk of CVD. We used published meta-analyses and trials to estimate the effects of behavior modification on SBP. We assessed the extent to which intermittent healthcare utilization or partial uptake of nonpharmacologic therapy would decrease CVD events prevented.

RESULTS: Controlling SBP to <130 mmHg among the estimated 8.8 million U.S. adults (51% women) in the target population could prevent 26,100 CVD events, avoid 2,900 deaths, and save $1.6 billion in healthcare costs over 10 years. The Dietary Approaches to Stop Hypertension (DASH) diet could prevent 16,000 CVD events among men and 12,000 among women over a decade. Other nonpharmacologic interventions could avert between 3,700 and 19,500 CVD events. However, only 5.5 million (61%) of the target population regularly utilized healthcare where recommended clinician counseling could occur.

CONCLUSIONS: As only two-thirds of U.S. adults with Stage 1 hypertension regularly receive medical care, substantial benefits to cardiovascular health and associated costs may only stem from policies that promote widespread adoption and sustained adherence of nonpharmacologic therapy. Future work should quantify the population-level costs, benefits, and efficacy of improving the food system and local infrastructure on health behavior change.

2022

Loccoh, Eméfah C, Karen E Joynt Maddox, Yun Wang, Dhruv S Kazi, Robert W Yeh, and Rishi K Wadhera. (2022) 2022. “Rural-Urban Disparities in Outcomes of Myocardial Infarction, Heart Failure, and Stroke in the United States.”. Journal of the American College of Cardiology 79 (3): 267-79. https://doi.org/10.1016/j.jacc.2021.10.045.

BACKGROUND: U.S. policy efforts have focused on reducing rural-urban health inequities. However, it is unclear whether gaps in care and outcomes remain among older adults with acute cardiovascular conditions.

OBJECTIVES: This study aims to evaluate rural-urban differences in procedural care and mortality for acute myocardial infarction (AMI), heart failure (HF), and ischemic stroke.

METHODS: This is a retrospective cross-sectional study of Medicare fee-for-service beneficiaries aged ≥65 years with acute cardiovascular conditions from 2016 to 2018. Cox proportional hazards models with random hospital intercepts were fit to examine the association of presenting to a rural (vs urban) hospital and 30- and 90-day patient-level mortality.

RESULTS: There were 2,182,903 Medicare patients hospitalized with AMI, HF, or ischemic stroke from 2016 to 2018. Patients with AMI were less likely to undergo cardiac catherization (49.7% vs 63.6%, P < 0.001), percutaneous coronary intervention (42.1% vs 45.7%, P < 0.001) or coronary artery bypass graft (9.0% vs 10.2%, P < 0.001) within 30 days at rural versus urban hospitals. Thrombolysis rates (3.1% vs 10.1%, P < 0.001) and endovascular therapy (1.8% vs 3.6%, P < 0.001) for ischemic stroke were lower at rural hospitals. After adjustment for demographics and clinical comorbidities, the 30-day mortality HR was significantly higher among patients presenting to rural hospitals for AMI (HR: 1.10, 95% CI: 1.08 to 1.12), HF (HR: 1.15; 95% CI: 1.13 to 1.16), and ischemic stroke (HR: 1.20; 95% CI: 1.18 to 1.22), with similar patterns at 90 days. These differences were most pronounced for the subset of critical access hospitals that serve remote, rural areas.

CONCLUSIONS: Clinical, public health, and policy efforts are needed to improve rural-urban gaps in care and outcomes for acute cardiovascular conditions.

Chung, Mabel, Kamil F Faridi, Dhruv S Kazi, Zaid I Almarzooq, Yang Song, Suzanne J Baron, and Robert W Yeh. (2022) 2022. “Days at Home After Transcatheter Vs Surgical Aortic Valve Replacement in Intermediate-Risk Patients.”. JAMA Cardiology 7 (1): 110-12. https://doi.org/10.1001/jamacardio.2021.4036.

This comparative effectiveness research study uses Medicare claims data to examine the total number of days at home among intermediate-risk patients recovering from transcatheter aortic valve replacement (TAVR) vs patients recovering from surgical aortic valve replacement (SAVR).

Howell, Benjamin A, Lisa B Puglisi, Jenerius Aminawung, Kirsten Bibbins- Domingo, Johanna Elumn, Colleen Gallagher, Nadine Horton, et al. (2022) 2022. “A Prospective Cohort Study Examining Exposure to Incarceration and Cardiovascular Disease (Justice-Involved Individuals Cardiovascular Disease Epidemiology - JUSTICE Study): A Protocol Paper.”. BMC Public Health 22 (1): 331. https://doi.org/10.1186/s12889-022-12688-x.

BACKGROUND: People who have been incarcerated have high rates of cardiovascular risk factors, such as hypertension and smoking, and cardiovascular disease (CVD) is a leading cause of hospitalizations and mortality in this population. Despite this, little is known regarding what pathways mediate the association between incarceration exposure and increased rates of CVD morbidity and especially what incarceration specific factors are associated with this risk. The objective of this study is to better understand CVD risk in people exposed to incarceration and the pathways by which accumulate cardiovascular risk over time.

METHODS AND ANALYSIS: The Justice-Involved Individuals Cardiovascular Disease Epidemiology (JUSTICE) study is a prospective cohort study of individuals released from incarceration with known cardiovascular risk factors. We are recruiting 500 individuals within three months after release from jail/prison. At baseline we are assessing traditional risk factors for CVD, including diet, exercise, and smoking, and exposure to incarceration-related policies, psychosocial stress, and self-efficacy. Cardiovascular risk factors are measured at baseline through point of care testing. We are following these individuals for the 12 months following the index release from incarceration with re-evaluation of psychosocial factors and clinical risk factors every 6 months. Using these data, we will estimate the direct and indirect latent effects of incarceration on cardiovascular risk factors and the paths via which these effects are mediated. We will also model the anticipated 10-year burden of CVD incidence, health care use, and mortality associated with incarceration.

DISCUSSION: Our study will identify factors associated with CVD risk factor control among people released from incarceration. Our measurement of incarceration-related exposures, psychosocial factors, and clinical measures of cardiovascular risk will allow for identification of unique targets for intervention to modify CVD risk in this vulnerable population.

Diamond, Jamie E, Susan McIlvaine, Serge Korjian, Patrick Cruden, Tenzin Dechen, Gail Piatkowski, Dhruv S Kazi, and Michael Gavin. (2022) 2022. “Patterns of Recovery in Cardiovascular Care After the COVID-19 Pandemic Surge.”. The American Journal of the Medical Sciences 363 (4): 305-10. https://doi.org/10.1016/j.amjms.2021.09.005.

BACKGROUND: Cardiovascular disease remains the number one cause of death globally. Patients with cardiovascular disease are at risk of poor outcomes from deferral of healthcare during the coronavirus disease 2019 (COVID-19) pandemic. Little is known about recovery of cardiovascular hospitalizations or procedural volume following the COVID-19 surges. We sought to examine the cardiovascular diagnoses requiring healthcare utilization surrounding the first and second COVID-19 waves and characterize trends in return to pre-pandemic levels at a tertiary care center in Massachusetts.

MATERIALS AND METHODS: Using electronic health records and administrative claims data, we performed a retrospective analysis of patients undergoing cardiovascular procedures and admitted to inpatient cardiology services throughout the first two COVID surges. ICD-10 codes were used to categorize admissions.

RESULTS: Patients who presented for care during the initial COVID-19 surge were younger, had higher comorbidity burden, and longer length-of-stay compared with pre- and post-surge. Marked declines in admissions in the first wave (to 29% of pre-surge levels) followed eventually by complete recovery were noted across all cardiac diagnoses, with smaller declines seen in the second wave. Cardiac procedural volume declined significantly during the initial surge but quickly rebounded post-surge, eventually eclipsing pre-COVID volume.

CONCLUSIONS: There was a gradual but initially incomplete recovery to pre-surge levels of hospitalizations and procedures during the reopening phase, which eventually rebounded to meet or exceed pre-COVID-19 levels. To the extent that this reflects deferred or foregone essential care, it may adversely affect long-term cardiovascular outcomes. These results should inform planning for cardiovascular care delivery during future pandemic surges.