Factor VIII and Incident Hypertension in Black and White Adults: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort.

BACKGROUND: Nearly half of all Americans have hypertension, and Black adults experience a disproportionate burden. Hypercoagulability may relate to hypertension risk, and higher levels of factor VIII increase thrombosis risk. Black adults have higher factor VIII and more hypertension than other groups. Whether higher factor VIII associates with incident hypertension is unknown. METHODS: The Biomarkers as Mediators of Racial Disparities in Risk Factors (BioMedioR) study measured certain biomarkers in a sex-race stratified sample of 4,400 REGARDS participants who attended both visits. We included BioMedioR participants, excluding those with prevalent hypertension, missing factor VIII level, or covariates of interest. Modified Poisson regression estimated risk ratios (RR) for incident hypertension by higher log-transformed factor VIII level per SD (SD of log-transformed factor VIII, 0.33). Weighting was applied to take advantage of REGARDS sampling design. RESULTS: Among the 1,814 participants included (55% female, 24% Black race), median follow-up was 9.5 years and 35% (2,146/6,138) developed hypertension. Black participants had a higher median (IQR) factor VIII level (105.6%; 87.1 to 126.9%) than White participants (95.6%; 79.8% to 115.9%; p<0.001). . The age and sex-adjusted Black-White hypertension RR was 1.45 (95% CI 1.28, 1.63). Higher factor VIII was not associated with more hypertension (final model RR 1.01; 95% CI 0.94, 1.07). CONCLUSIONS: In a prospective study of Black and White adults without prevalent hypertension, factor VIII was not associated with greater hypertension risk.

Hepatocyte growth factor and risk of incident stroke in Black and White Americans in the Reasons for Geographic and Racial Differences in Stroke study.

Background: Hepatocyte growth factor (HGF) is a cytokine produced in response to endothelial damage. Higher levels correlate with cardiovascular risk factors, including hypertension and diabetes. Objectives: We hypothesized that HGF is associated with stroke. Methods: The Reasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30,239 Black and White Americans aged ≥45 years from 2003 to 2007. In this case-cohort study, after 5.5 years of follow-up, circulating baseline HGF was measured in 557 participants with incident ischemic stroke and in a cohort random sample of 964 participants. Hazard ratios (HRs) per SD log-transformed HGF and by HGF quintile were calculated using Cox proportional hazards models adjusting for stroke risk factors and other correlates of HGF. Differences by race and sex were tested using interaction terms. Results: Median HGF was 295 (IQR, 209-402) pg/mL. HGF was higher with older age, male sex, prevalent cardiovascular disease, smoking, and warfarin use, but did not differ by race. The adjusted HR of incident ischemic stroke per SD higher baseline HGF (145 pg/mL) was 1.30 (CI, 1.00-1.70), with no difference by sex or race. HGF in the highest (>434 pg/mL) vs lowest quintile (<135 pg/mL) was associated with an adjusted HR of incident stroke of 2.12 (CI, 1.31-3.41). Conclusion: In the REGARDS study, higher HGF was associated with increased risk of incident ischemic stroke in Black and White adults, with a doubling in risk of HGF in the top quintile compared with the lowest quintile after adjusting for other stroke risk factors.

Cytokines, C-Reactive Protein, and Risk of Incident Hypertension in the REGARDS Study.

BACKGROUND: Hypertension is a highly prevalent cardiovascular disease risk factor that may be related to inflammation. Whether adverse levels of specific inflammatory cytokines relate to hypertension is unknown. The present study sought to determine whether higher levels of IL (interleukin)-1ß, IL-6, TNF (tumor necrosis factor)-α, IFN (interferon)-γ, IL-17A, and CRP (C-reactive protein) are associated with a greater risk of incident hypertension. METHODS: The REGARDS study (Reasons for Geographic and Racial Difference in Stroke) is a prospective cohort study that recruited 30 239 community-dwelling Black and White adults from the contiguous United States in 2003 to 2007 (visit 1), with follow-up 9 years later in 2013 to 2016 (visit 2). We included participants without prevalent hypertension who attended follow-up 9 years later and had available laboratory measures and covariates of interest. Poisson regression estimated the risk ratio of incident hypertension by level of inflammatory biomarkers. RESULTS: Among 1866 included participants (mean [SD] aged of 62 [8] years, 25% Black participants, 55% women), 36% developed hypertension. In fully adjusted models comparing the third to first tertile of each biomarker, there was a greater risk of incident hypertension for higher IL-1ß among White (1.24 [95% CI, 1.01-1.53]) but not Black participants (1.01 [95% CI, 0.83-1.23]) and higher TNF-α (1.20 [95% CI, 1.02-1.41]) and IFN-γ (1.22 [95% CI, 1.04-1.42]) among all participants. There was no increased risk with IL-6, IL-17A, or CRP. CONCLUSIONS: Higher levels of IL-1ß, TNF-α, and IFN-γ, representing distinct inflammatory pathways, are elevated in advance of hypertension development. Whether modifying these cytokines will reduce incident hypertension is unknown.

Development and validation of a risk model for hospital-acquired venous thrombosis: the Medical Inpatients Thrombosis and Hemostasis study.

BACKGROUND: Regulatory organizations recommend assessing hospital-acquired (HA) venous thromboembolism (VTE) risk for medical inpatients. OBJECTIVES: To develop and validate a risk assessment model (RAM) for HA-VTE in medical inpatients using objective and assessable risk factors knowable at admission. METHODS: The development cohort included people admitted to medical services at the University of Vermont Medical Center (Burlington, Vermont) between 2010 and 2019, and the validation cohorts included people admitted to Hennepin County Medical Center (Minneapolis, Minnesota), University of Michigan Medical Center (Ann Arbor, Michigan), and Harris Health Systems (Houston, Texas). Individuals with VTE at admission, aged <18 years, and admitted for <1 midnight were excluded. We used a Bayesian penalized regression technique to select candidate HA-VTE risk factors for final inclusion in the RAM. RESULTS: The development cohort included 60 633 admissions and 227 HA-VTE, and the validation cohorts included 111 269 admissions and 651 HA-VTE. Seven HA-VTE risk factors with t statistics ≥1.5 were included in the RAM: history of VTE, low hemoglobin level, elevated creatinine level, active cancer, hyponatremia, increased red cell distribution width, and malnutrition. The areas under the receiver operating characteristic curve and calibration slope were 0.72 and 1.10, respectively. The areas under the receiver operating characteristic curve and calibration slope were 0.70 and 0.93 at Hennepin County Medical Center, 0.70 and 0.87 at the University of Michigan Medical Center, and 0.71 and 1.00 at Harris Health Systems, respectively. The RAM performed well stratified by age, sex, and race. CONCLUSION: We developed and validated a RAM for HA-VTE in medical inpatients. By quantifying risk, clinicians can determine the potential benefits of measures to reduce HA-VTE.

Lipoprotein(a) and risk of cognitive impairment in Black and White Americans: the Reasons for Geographic and Racial Differences in Stroke cohort.

Background: Cognitive impairment has a substantial vascular etiology. Higher lipoprotein(a) [Lp(a)] is associated with cardiovascular disease risk, but its association with cognitive function is uncertain. We hypothesized that Lp(a) is a risk factor for cognitive impairment, a relationship that would be modified by race and sex. Objectives: To study the association of Lp(a) with cognitive impairment in a biracial cohort. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study recruited 30,239 Black and White Americans aged >45 years from 2003 to 2007. After 3.4 years, among participants with normal baseline cognition, baseline Lp(a) was measured in 434 cases of incident cognitive impairment and 557 controls. Cognitive impairment was defined as scores below the sixth percentile based on age, sex, race, and education norms on 2 or 3 components of a 3-test battery administered every 2 years. Results: Median Lp(a) was higher in Black than in White individuals. Among Black participants, the adjusted odds ratio (OR) of cognitive impairment per SD higher increment Lp(a) was 1.39 (95% CI: 1.05, 1.84). The OR in White participants was 1.03 (95% CI: 0.87, 1.21; P for race difference = .03). The relationship of Lp(a) with cognitive trajectory differed by sex and race. Elevated Lp(a) was associated with worse baseline memory in Black men and a steeper trajectory of verbal fluency decline in Black men than in White men and women. Conclusion: Higher Lp(a) was associated with increased risk of cognitive impairment in Black but not White individuals. Future studies should evaluate the biological and social mechanisms through which race and Lp(a) interact to increase risk of cognitive impairment.

Impact of preexisting autoimmune disease on myelodysplastic syndromes outcomes: a population analysis.

Preexisting autoimmune disease affects between 10% and 30% of patients with myelodysplastic syndromes (MDS). Studies comparing outcomes in patients with MDS with and without autoimmune disease show discordant results. Using the Surveillance, Epidemiology, and End Results Medicare database, we conducted a population analysis to define the impact of autoimmunity on MDS outcomes. Cases were ascertained between 2007 and 2017 and claim algorithms used to identify autoimmune disease, demographic characteristics, comorbidity scores, MDS histology, transfusion burden, treatment with hypomethylating agents, and hematopoietic stem cell transplantation. Cox regression models estimated the impact on survival, and competing-risk regression models defined the effect on leukemic transformation. We analyzed 15 277 patients with MDS, including 2442 (16%) with preexisting autoimmune disease. The epidemiologic profile was distinctive in cases with preexisting autoimmunity, who were younger, were predominantly female, and had higher transfusion burden without difference in MDS histologic distribution. Autoimmune disease was associated with 11% decreased risk of death (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.85-0.94; P < .001). The effect on risk of leukemic transformation differed based on MDS histology. In low-risk MDS histologies, autoimmunity was associated with a 1.9-fold increased risk of leukemia (HR, 1.87; 95% CI, 1.17-2.99; P = .008), whereas no significant effect was seen in other groups. These results suggest that autoimmune disease affects survival in MDS and is associated with decreased mortality. The survival effect was evident in low-risk histologies despite higher risk of progression to leukemia. This could represent inflammation-driven hematopoiesis, simultaneously favoring less aggressive phenotypes and clonal expansion, which warrants further investigation.

Alpha globin gene copy number and incident ischemic stroke risk among Black Americans.

Introduction: People with African ancestry have greater stroke risk and greater heritability of stroke risk than people of other ancestries. Given the importance of nitric oxide (NO) in stroke, and recent evidence that alpha globin restricts nitric oxide release from vascular endothelial cells, we hypothesized that alpha globin gene (HBA) deletion would be associated with reduced risk of incident ischemic stroke. Methods: We evaluated 8,947 participants self-reporting African ancestry in the national, prospective Reasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Incident ischemic stroke was defined as non-hemorrhagic stroke with focal neurological deficit lasting ≥ 24 hours confirmed by the medical record or focal or non-focal neurological deficit with positive imaging confirmed with medical records. Genomic DNA was analyzed using droplet digital PCR to determine HBA copy number. Multivariable Cox proportional hazards regression was used to estimate the hazard ratio (HR) of HBA copy number on time to first ischemic stroke. Results: Four-hundred seventy-nine (5.3%) participants had an incident ischemic stroke over a median (IQR) of 11.0 (5.7, 14.0) years' follow-up. HBA copy number ranged from 2 to 6: 368 (4%) -α/-α, 2,480 (28%) -α/αα, 6,014 (67%) αα/αα, 83 (1%) ααα/αα and 2 (<1%) ααα/ααα. The adjusted HR of ischemic stroke with HBA copy number was 1.04; 95%CI 0.89, 1.21; p = 0.66. Conclusions: Although a reduction in HBA copy number is expected to increase endothelial nitric oxide signaling in the human vascular endothelium, HBA copy number was not associated with incident ischemic stroke in this large cohort of Black Americans.

Venous thromboembolism mortality and trends in older US adults, 2011-2019.

Venous thromboembolism (VTE) affects 1.2 million people per year in the United States. With several clinical changes in diagnosis and treatment approaches in the past decade, we evaluated contemporary post-VTE mortality risk profiles and trends. Incident VTE cases were identified from the 2011-2019 Medicare 20% Sample, which is representative of nearly all Americans aged 65 and older. The social deprivation index was linked from public data; race/ethnicity and sex were self-reported. The all-cause mortality risk 30 days and 1 year after incident VTE was calculated in demographic subgroups and by prevalent cancer diagnosis status using model-based standardization. Risks for major cancer types, risk differences by age, sex, race/ethnicity, and socio-economic status (SES), and trends over time are also reported. The all-cause mortality risk among older US adults following incident VTE was 3.1% (95% CI 3.0-3.2) at 30 days and 19.6% (95% CI 19.2-20.1) at 1 year. For cancer-related VTE events, the age-sex-race-standardized risk was 6.0% at 30 days and 34.7% at 1 year. The standardized 30-day and 1-year risks were higher among non-White beneficiaries and among those with low SES. One-year mortality risk decreased 0.28 percentage points per year (95% CI 0.16-0.40) on average across the study period, with no trend observed for 30-day mortality risk. In sum, all-cause mortality risk following incident VTE has decreased slightly in the last decade, but racial and socio-economic disparities persist. Understanding patterns of mortality among demographic subgroups and in cancer-associated events is important for targeting efforts to improve VTE management.

Development of a computable phenotype using electronic health records for venous thromboembolism in medical inpatients: the Medical Inpatient Thrombosis and Hemostasis study.

Background: Accurate and efficient methods to identify venous thromboembolism (VTE) events in hospitalized people are needed to support large-scale studies. Validated computable phenotypes using a specific combination of discrete, searchable elements in electronic health records to identify VTE and distinguish between hospital-acquired (HA)-VTE and present-on-admission (POA)-VTE would greatly facilitate the study of VTE, obviating the need for chart review. Objectives: To develop and validate computable phenotypes for POA- and HA-VTE in adults hospitalized for medical reasons. Methods: The population included admissions to medical services from 2010 to 2019 at an academic medical center. POA-VTE was defined as VTE diagnosed within 24 hours of admission, and HA-VTE as VTE identified more than 24 hours after admission. Using discharge diagnosis codes, present-on-admission flags, imaging procedures, and medication administration records, we iteratively developed computable phenotypes for POA-VTE and HA-VTE. We assessed the performance of the phenotypes using manual chart review and survey methodology. Results: Among 62,468 admissions, 2693 had any VTE diagnosis code. Using survey methodology, 230 records were reviewed to validate the computable phenotypes. Based on the computable phenotypes, the incidence of POA-VTE was 29.4 per 1000 admissions and that of HA-VTE was 3.6 per 1000 admissions. The POA-VTE computable phenotype had positive predictive value and sensitivity of 88.8% (95% CI, 79.8%-94.0%) and 99.1% (95% CI, 94.0%- 99.8%), respectively. Corresponding values for the HA-VTE computable phenotype were 84.2% (95% CI, 60.8%-94.8%) and 72.3% (95% CI, 40.9%-90.8%). Conclusion: We developed computable phenotypes for HA-VTE and POA-VTE with adequate positive predictive value and sensitivity. This phenotype can be used in electronic health record data-based research.

Nonalcoholic fatty liver disease and cognitive impairment: A prospective cohort study.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is prevalent and may affect cognitive function. We studied associations of NAFLD with risk of cognitive impairment. Secondarily we evaluated liver biomarkers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), their ratio, and gamma-glutamyl transpeptidase). METHODS: In a prospective cohort study, the REasons for Geographic and Racial Differences in Stroke, among 30,239 black and white adults aged ≥45,495 cases of incident cognitive impairment were identified over 3.4 years follow up. Cognitive impairment was identified as new impairment in two of three cognitive tests administered every two years during follow up; word list learning and recall, and verbal fluency. 587 controls were selected from an age, race, sex-stratified sample of the cohort. The fatty liver index was used to define baseline NAFLD. Liver biomarkers were measured using baseline blood samples. RESULTS: NAFLD at baseline was associated with a 2.01-fold increased risk of incident cognitive impairment in a minimally adjusted model (95% CI 1.42, 2.85). The association was largest in those aged 45-65 (p interaction by age = 0.03), with the risk 2.95-fold increased (95% CI 1.05, 8.34) adjusting for cardiovascular, stroke and metabolic risk factors. Liver biomarkers were not associated with cognitive impairment, except AST/ALT >2, with an adjusted OR 1.86 (95% CI 0.81, 4.25) that did not differ by age. CONCLUSIONS: A laboratory-based estimate of NAFLD was associated with development of cognitive impairment, particularly in mid-life, with a tripling in risk. Given its high prevalence, NAFLD may be a major reversible determinant of cognitive health.

Bleeding risk in patients with multiple myeloma treated for venous thromboembolism: a MarketScan analysis.

Background: Multiple myeloma (MM) is associated with high risk of venous thromboembolism (VTE). Thromboprophylaxis is thoroughly studied in MM. Contrarily, studies assessing the risk of bleeding in people with MM on anticoagulation are lacking. Objectives: To determine the rate of serious bleeding in patients with MM receiving anticoagulation for VTE and the clinical factors associated with bleeding risk. Methods: Using the MarketScan commercial database, we identified 1298 people with MM treated with anticoagulation for incident VTE events between 2011 and 2019. Hospitalized bleeding was identified using the Cunningham algorithm. Rates of bleeding were calculated and Cox regression identified risk factors for bleeding. Results: Bleeding occurred in 51 (3.9%) cases during median follow-up of 1.13 years. Rate of bleeding among patients with MM on anticoagulation was 24.0 per 1000 person-years. In adjusted regression, factors associated with increased bleeding included age (HR, 1.31 per 10-year increase; 95% CI, 1.03-1.65), Charlson comorbidity index (HR, 1.29 per SD increase; 95% CI, 1.02-1.58), use of antiplatelet agents (HR, 2.4; 95% CI, 1.03-5.68), diabetes (HR, 1.85; 95% CI, 1.06-3.26), and renal disease (HR, 1.80; 95% CI, 1.05-3.16). Cumulative incidence of bleeding was 4.7%, 3.2%, and 3.4% for warfarin, low molecular weight heparin, and direct oral anticoagulants, respectively. Conclusion: In this real-world analysis, the rate of bleeding in people with MM on anticoagulation was comparable to those in other subsets of cancer-related VTE. Bleeding rate was lower with low molecular weight heparin and direct oral anticoagulants than warfarin. Higher comorbidity index, diabetes, antiplatelet agent use, and renal disease were risk factors for serious bleeding.

Autoimmune disease and risk of postpartum venous thromboembolism.

Background: The risk of pregnancy-related mortality in the United States has nearly doubled since 1990, with venous thromboembolism (VTE) accounting for approximately 10% of these deaths. Objectives: The objective of this study was to assess whether preexisting autoimmune disease is a risk factor for postpartum VTE. Methods: Using the MarketScan Commercial and Medicare Supplemental administrative databases, a retrospective cohort study analyzed whether postpartum persons with autoimmune disease had a higher risk of postpartum VTE incidence than postpartum persons without autoimmune disease. Using International Classification of Diseases codes, we identified 757,303 individuals of childbearing age who had a valid delivery date with at least 12 weeks of follow-up. Results: Individuals were, on average, 30.7 years old (SD, 5.4), and 3.7% (N = 27,997 of 757,303) of them had evidence of preexisting autoimmune disease. In covariate-adjusted models, postpartum persons with preexisting autoimmune disease had higher rates of postpartum VTE than postpartum persons without autoimmune disease (hazard ratio [HR], 1.33; 95% CI, 1.07-1.64). When analyzed by individual autoimmune disease, those with systemic lupus erythematosus (HR, 2.49; 95% CI, 1.47-4.21) and Crohn's disease (HR, 2.49; 95% CI, 1.34-4.64) were at an elevated risk of postpartum VTE compared with those without autoimmune disease. Conclusion: Autoimmune disease was associated with a higher rate of postpartum VTE, with evidence that the association was most pronounced among individuals with systemic lupus erythematosus and Crohn's disease. These findings suggest that postpartum persons of childbearing age with autoimmune disease may require more monitoring and prophylactic care after delivery to prevent potentially fatal VTE events.

Alpha globin gene copy number and incident ischemic stroke risk among Black Americans.

Introduction: People with African ancestry have greater stroke risk and greater heritability of stroke risk than people of other ancestries. Given the importance of nitric oxide (NO) in stroke, and recent evidence that alpha globin restricts nitric oxide release from vascular endothelial cells, we hypothesized that alpha globin gene ( HBA) deletion would be associated with reduced risk of incident ischemic stroke. Methods: We evaluated 8,947 participants self-reporting African ancestry in the national, prospective Reasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Incident ischemic stroke was defined as non-hemorrhagic stroke with focal neurological deficit lasting ≥ 24 hours confirmed by the medical record or focal or non-focal neurological deficit with positive imaging confirmed with medical records. Genomic DNA was analyzed using droplet digital PCR to determine HBA copy number. Multivariable Cox proportional hazards regression was used to estimate the hazard ratio (HR) of HBA copy number on time to first ischemic stroke. Results: Four-hundred seventy-nine (5.3%) participants had an incident ischemic stroke over a median (IQR) of 11.0 (5.7, 14.0) years' follow-up. HBA copy number ranged from 2 to 6: 368 (4%) -α/-α, 2,480 (28%) -α/αα, 6,014 (67%) αα/αα, 83 (1%) ααα/αα and 2 (<1%) ααα/ααα. The adjusted HR of ischemic stroke with HBA copy number was 1.04; 95%CI 0.89, 1.21; p = 0.66. Conclusions: Although a reduction in HBA copy number is expected to increase endothelial nitric oxide signaling in the human vascular endothelium, HBA copy number was not associated with incident ischemic stroke in this large cohort of Black Americans.

A multilevel framework to investigate cardiovascular health disparities among South Asian immigrants in the United States.

PURPOSE: Prior studies of cardiovascular health (CVH) disparities among immigrants of South Asian origin in the United States have examined South Asians as one homogenous group, focused primarily on Indian-origin immigrants, and examined risk at the individual level. METHODS: We present current knowledge and evidence gaps about CVH in the three largest South Asian-origin populations in the United States-Bangladeshi, Indian, and Pakistani-and draw on socioecological and lifecourse frameworks to propose a conceptual framework for investigating multilevel risk and protective factors of CVH across these groups. RESULTS: The central hypothesis is that CVH disparities among South Asian populations exist due to differences in structural and social determinants, including lived experiences like discrimination, and that acculturation strategies and resilience resources (e.g., neighborhood environment, education, religiosity, social support) ameliorate stressors to act as health protective factors. RESULTS: Conclusions: Our framework advances conceptualization of the heterogeneity and drivers of cardiovascular disparities in diverse South Asian-origin populations. We present specific recommendations to inform the design of future epidemiologic studies on South Asian immigrant health and the development of multilevel interventions to reduce CVH disparities and promote well-being.

D-dimer and the risk of hypertension: The REasons for Geographic And Racial Differences in Stroke Cohort Study.

Background: Reasons for increased risk of hypertension in Black compared with White people are only partly understood. D-dimer, a thrombo-inflammatory marker higher in Black individuals, is also higher in people with hypertension. However, the impact of D-dimer on racial disparities in risk of incident hypertension has not been studied. Objectives: To assess whether D-dimer is associated with the risk of incident hypertension, whether the association between D-dimer and the risk of incident hypertension differs by race, and whether the biology reflected by D-dimer explains racial disparities in the risk of incident hypertension. Methods: This study included 1867 participants in the REasons for Geographic And Racial Differences in Stroke cohort study without baseline hypertension and with a second visit 9.4 years after baseline. Risk ratios of incident hypertension by baseline D-dimer level were estimated, a D-dimer-by-race interaction was tested, and the mediating effect of D-dimer (which represents underlying biological processes) on the association of race and hypertension risk was assessed. Results: The risk of incident hypertension was 47% higher in persons in the top quartile than in those in the bottom quartile of D-dimer (risk ratio [RR]: 1.47; 95% CI: 1.23-1.76). The association was partly attenuated after adjusting for sociodemographic and adiposity-related risk factors (RR: 1.22; 95% CI: 1.02-1.47). The association of D-dimer and hypertension did not differ by race, and D-dimer did not attenuate the racial difference in the risk of incident hypertension. Conclusion: D-dimer concentration reflects pathophysiology related to the development of hypertension. Specific mechanisms require further study and may involve adiposity.

Derivation and Validation of a Clinical Risk Assessment Model for Cancer-Associated Thrombosis in Two Unique US Health Care Systems.

PURPOSE: Venous thromboembolism (VTE), especially pulmonary embolism (PE) and lower extremity deep vein thrombosis (LE-DVT), is a serious and potentially preventable complication for patients with cancer undergoing systemic therapy. METHODS: Using retrospective data from patients diagnosed with incident cancer from 2011-2020, we derived a parsimonious risk assessment model (RAM) using least absolute shrinkage and selection operator regression from the Harris Health System (HHS, n = 9,769) and externally validated it using the Veterans Affairs (VA) health care system (n = 79,517). Bootstrapped c statistics and calibration curves were used to assess external model discrimination and fit. Dichotomized risk strata using integer scores were created and compared against the Khorana score (KS). RESULTS: Incident VTE and PE/LE-DVT at 6 months occurred in 590 (6.2%) and 437 (4.6%) patients in HHS and 4,027 (5.1%) and 3,331 (4.2%) patients in the VA health care system. Assessed at the time of systemic therapy initiation, the new RAM included components of the KS with the modified cancer subtype, cancer staging, systemic therapy class, history of VTE, history of paralysis/immobility, recent hospitalization, and Asian/Pacific Islander race. The c statistic was 0.71 in HHS and 0.68 in the VA health care system (compared with 0.65 and 0.60, respectively, for KS). Furthermore, the new RAM appropriately reclassified 28% of patients and increased the proportion of VTEs in the high-risk group from 37% to 68% in the validation data set. CONCLUSION: The novel RAM stratified patients with cancer into a high-risk group with 8%-10% cumulative incidence of VTE and 7% PE/LE-DVT at 6 months (v 3% and 2%, respectively, in the low-risk group). The model had improved performance over the original KS and doubled the number of VTE events in the high-risk stratum. We encourage additional external validation from prospective studies.[Media: see text].

The relative risk of bleeding after medical hospitalization: the medical inpatient thrombosis and hemorrhage study.

BACKGROUND: Clinically relevant bleeding risk in discharged medical patients is underestimated and leads to rehospitalization, morbidity, and mortality. Studies assessing this risk are lacking. OBJECTIVE: The aim of this study was to develop and validate a computable phenotype for clinically relevant bleeding using electronic health record (EHR) data and quantify the relative and absolute risks of this bleeding after medical hospitalization. METHODS: We conducted an observational cohort study of people receiving their primary care at sites affiliated with an academic medical center in northwest Vermont, United States. We developed a computable phenotype using EHR data (diagnosis codes, procedure codes, laboratory, and transfusion data) and validated it by manual chart review. Cox proportional hazard models with hospitalization modeled as a time-varying covariate were used to estimate clinically relevant bleeding risk. RESULTS: The computable phenotype had a positive predictive value of 80% and a negative predictive value of 99%. The bleeding rate in individuals with no medical hospitalizations in the past 3 months was 2.9 per 1000 person-years versus 98.9 per 1000 person-years in those who were discharged in the past 3 months. This translates into a hazard ratio (95% CI) of clinically relevant bleeding of 22.9 (18.9, 27.7), 13.0 (10.0, 16.9), and 6.8 (4.7, 9.8) over the first, second, and third months after discharge, respectively. CONCLUSION: We developed and validated a computable phenotype for clinically relevant bleeding and determined its relative and absolute risk in the 3 months after medical hospitalization discharge. The high rates of bleeding observed underscore the clinical importance of capturing and further studying bleeding after medical discharge.