Apixaban vs Aspirin in Patients With Cancer and Cryptogenic Stroke: A Post Hoc Analysis of the ARCADIA Randomized Clinical Trial.

Importance: Approximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke. Objective: To compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke. Design, Setting, and Participants: Post hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024. Exposures: Oral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined. Main Outcomes and Measures: The primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage. Results: Among 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%]). Conclusions and Relevance: Among participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Relationships of hematocrit concentration with dementia from a multiethnic population-based study.

OBJECTIVE: Red blood cell (RBC) concentration impacts cerebrovascular disease, yet it is unclear whether RBC concentrations relate to dementia risk, particularly in racially/ethnically diverse cohorts. We investigated whether RBC concentrations associate with incident dementia risk in a diverse population of stroke-free individuals and explored whether cerebral small vessel disease (CSVD) mediates this relationship. METHODS: A longitudinal observational analysis was performed using a population-based cohort of stroke-free, older adult participants (>50 years) from the Northern Manhattan Study (NOMAS) enrolled between 2003-2008. Participants received baseline hematocrit testing, MRI neuroimaging, and cognitive assessments at baseline and long-term follow-up. Associations of baseline hematocrit as a categorical variable (low, normal [reference], and high based on laboratory reference levels) with incident dementia were assessed using Cox models adjusting for relevant covariates. Separate analyses investigated whether MRI CSVD mediated these relationships. RESULTS: We studied 1207 NOMAS participants (mean age 71±9 years, 60% female, 66% Hispanic). Mean hematocrit was 41.2% (±3.8) with 16% of participants developing incident dementia. Lower hematocrit associated with increased dementia risk (adjusted hazard ratio 1.81 [1.01-3.23]) after adjusting for age, sex, race/ethnicity, education, APOE status, and comorbidities. High hematocrit was not associated with dementia risk. No interactions by sex or race/ethnicity were seen and baseline CSVD did not mediate relationships between hematocrit and dementia. CONCLUSIONS: Low hematocrit associated with dementia risk in our diverse population cohort. Further work is needed to assess mechanisms behind anemia's relationship with dementia to assess whether this can serve as a trackable, preventable/treatable risk factor for dementia.

International Initiatives of the American Heart Association: Original Concepts, Present Programs, and Future Focus: A Science Advisory From the American Heart Association.

The American Heart Association (AHA), founded in 1924, is anchored in the core belief that scientific research can lead the way to better prevention, treatment, recovery, and ultimately a cure for cardiovascular disease. Historically, the association's involvement in international efforts centered on scientific cooperation. Activities mostly involved AHA leadership presenting at international scientific meetings and leaders from other countries sharing scientific and medical information at AHA meetings. Although the AHA's and American Stroke Association's international efforts have expanded substantially since those early days, global knowledge exchange remains the bedrock of its international endeavors. As the AHA turns 100, we reflect on the successful global efforts in prevention, resuscitation, global advocacy, quality improvement, and health equity that have guided the organization to a place of readiness for "advancing health and hope, for everyone, everywhere." Motivated by the enormous potential for population health gains in an aging world, the AHA is entering its second century with redoubled commitment to improving global cardiovascular and cerebrovascular health for all.

Estimated Pulse-Wave Velocity and Magnetic Resonance Imaging Markers of Cerebral Small-Vessel Disease in the NOMAS.

BACKGROUND: Pulse-wave velocity is a measure of arterial stiffness and a risk factor for cardiovascular disease. Recently, an estimated pulse-wave velocity (ePWV) was introduced that was predictive of increased risk of cardiovascular disease. Our objective was to determine whether ePWV was associated with cerebral small-vessel disease on magnetic resonance imaging. METHODS AND RESULTS: We included 1257 participants from the NOMAS (Northern Manhattan Study). The ePWV values were calculated using a nonlinear function of age and mean arterial blood pressure. The association between ePWV and white matter hyperintensity volume was assessed. Modification by race and ethnicity was evaluated. Associations between ePWV and other cerebral small-vessel disease markers, covert brain infarcts, cerebral microbleeds, and enlarged perivascular spaces, were explored as secondary outcomes. Mean±SD age of the cohort was 64±8 years; 61% were women; 18% self-identified as non-Hispanic Black, 67% as Hispanic, and 15% as non-Hispanic White individuals. Mean±SD ePWV was 11±2 m/s in the total NOMAS population and was similar across race and ethnic groups. The ePWV was significantly associated with white matter hyperintensity volume (ß=0.23 [95% CI, 0.20-0.26]) after adjustment. Race and ethnicity modified the association between ePWV and white matter hyperintensity volume, with stronger associations in Hispanic and non-Hispanic Black individuals. Significant associations were found between ePWV and covert brain infarcts, cerebral microbleeds, and perivascular spaces after adjustment. CONCLUSIONS: The ePWV function may provide a vascular mechanism for deleterious cerebrovascular outcomes in individuals with cerebral small-vessel disease and is particularly apparent in the racial and ethnic minorities represented in the NOMAS cohort.

Evidence of varicella zoster virus (VZV) reactivation in children with arterial ischemic stroke: Results of the VIPS II Study.

Background: Varicella zoster virus (VZV) has been associated with focal cerebral arteriopathy (FCA) and arterial ischemic stroke (AIS) in childhood. The Vascular effects of Infection in Pediatric Stroke (VIPS) II study aimed to examine this relationship in the modern era when most children in North America and Australia receive VZV vaccination with live, attenuated virus. Methods: This 22-center prospective cohort study enrolled 205 children (28 days-18 years) with AIS (2017-2022), collected baseline [hyperacute (≤72 hours; n=194) and acute (4-6 days; n=181)] and convalescent (1-6 weeks; n=74) serum samples. Sites enrolled 95 stroke-free controls with single serum samples. A virology research laboratory measured VZV IgM and IgG titers by an in-house enzyme-linked immunosorbent assay (ELISA). Baseline IgG seropositivity indicated prior exposure (vaccination/infection) and elevated IgM titers indicated recent reactivation. Results: Median (IQR) age was 11.6 (5.5-15.6) years for cases and 11.8 (6.8-15.3) years for controls. Baseline serologies indicated prior VZV exposure in 198 cases (97%) and all controls. Parents of cases reported VZV vaccination in 160 (78%) and remote chicken pox in three (1.4%). Twenty cases (9.8%) and three controls (3.1%) had serologic evidence of recent VZV reactivation (p=0.06); all had remote VZV exposure (vaccination in 19 cases and all controls) and all were asymptomatic. Recent VZV reactivation was seen in similar proportions in arteriopathic, cardioembolic, and idiopathic stroke. Of 32 cases of FCA, 4 (12.5%) had recent VZV reactivation, versus no cases of arterial dissection (n=10) or moyamoya (n=16). Conclusions: Serologic evidence of recent VZV reactivation (≈1-6 weeks prior to stroke) was present in one in 10 cases of childhood AIS, including those without arteriopathy. Clinically silent VZV reactivation may be a childhood stroke trigger despite widespread vaccination. These cases could represent waning immunity with reactivation of either vaccine virus or wild-type virus after an unrecognized secondary VZV infection.

Forecasting the Burden of Cardiovascular Disease and Stroke in the United States Through 2050-Prevalence of Risk Factors and Disease: A Presidential Advisory From the American Heart Association.

BACKGROUND: Cardiovascular disease and stroke are common and costly, and their prevalence is rising. Forecasts on the prevalence of risk factors and clinical events are crucial. METHODS: Using the 2015 to March 2020 National Health and Nutrition Examination Survey and 2015 to 2019 Medical Expenditure Panel Survey, we estimated trends in prevalence for cardiovascular risk factors based on adverse levels of Life's Essential 8 and clinical cardiovascular disease and stroke. We projected through 2050, overall and by age and race and ethnicity, accounting for changes in disease prevalence and demographics. RESULTS: We estimate that among adults, prevalence of hypertension will increase from 51.2% in 2020 to 61.0% in 2050. Diabetes (16.3% to 26.8%) and obesity (43.1% to 60.6%) will increase, whereas hypercholesterolemia will decline (45.8% to 24.0%). The prevalences of poor diet, inadequate physical activity, and smoking are estimated to improve over time, whereas inadequate sleep will worsen. Prevalences of coronary disease (7.8% to 9.2%), heart failure (2.7% to 3.8%), stroke (3.9% to 6.4%), atrial fibrillation (1.7% to 2.4%), and total cardiovascular disease (11.3% to 15.0%) will rise. Clinical CVD will affect 45 million adults, and CVD including hypertension will affect more than 184 million adults by 2050 (>61%). Similar trends are projected in children. Most adverse trends are projected to be worse among people identifying as American Indian/Alaska Native or multiracial, Black, or Hispanic. CONCLUSIONS: The prevalence of many cardiovascular risk factors and most established diseases will increase over the next 30 years. Clinical and public health interventions are needed to effectively manage, stem, and even reverse these adverse trends.

Forecasting the Economic Burden of Cardiovascular Disease and Stroke in the United States Through 2050: A Presidential Advisory From the American Heart Association.

BACKGROUND: Quantifying the economic burden of cardiovascular disease and stroke over the coming decades may inform policy, health system, and community-level interventions for prevention and treatment. METHODS: We used nationally representative health, economic, and demographic data to project health care costs attributable to key cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia) and conditions (coronary heart disease, stroke, heart failure, atrial fibrillation) through 2050. The human capital approach was used to estimate productivity losses from morbidity and premature mortality due to cardiovascular conditions. RESULTS: One in 3 US adults received care for a cardiovascular risk factor or condition in 2020. Annual inflation-adjusted (2022 US dollars) health care costs of cardiovascular risk factors are projected to triple between 2020 and 2050, from $400 billion to $1344 billion. For cardiovascular conditions, annual health care costs are projected to almost quadruple, from $393 billion to $1490 billion, and productivity losses are projected to increase by 54%, from $234 billion to $361 billion. Stroke is projected to account for the largest absolute increase in costs. Large relative increases among the Asian American population (497%) and Hispanic American population (489%) reflect the projected increases in the size of these populations. CONCLUSIONS: The economic burden of cardiovascular risk factors and overt cardiovascular disease in the United States is projected to increase substantially in the coming decades. Development and deployment of cost-effective programs and policies to promote cardiovascular health are urgently needed to rein in costs and to equitably enhance population health.

Ischemic Stroke with Comorbid Cancer Has Specific miRNA-mRNA Networks in Blood That Vary by Ischemic Stroke Mechanism.

OBJECTIVE: Approximately half of ischemic strokes (IS) in cancer patients are cryptogenic, with many presumed cardioembolic. We evaluated whether there were specific miRNA and mRNA transcriptome architectures in peripheral blood of IS patients with and without comorbid cancer, and between cardioembolic versus noncardioembolic IS etiologies in comorbid cancer. METHODS: We studied patients with cancer and IS (CS; n = 42), stroke only (SO; n = 41), and cancer only (n = 28), and vascular risk factor-matched controls (n = 30). mRNA-Seq and miRNA-Seq data, analyzed with linear regression models, identified differentially expressed genes in CS versus SO and in cardioembolic versus noncardioembolic CS, and miRNA-mRNA regulatory pairs. Network-level analyses identified stroke etiology-specific responses in CS. RESULTS: A total of 2,085 mRNAs and 31 miRNAs were differentially expressed between CS and SO. In CS, 122 and 35 miRNA-mRNA regulatory pairs, and 5 and 3 coexpressed gene modules, were associated with cardioembolic and noncardioembolic CS, respectively. Complement, growth factor, and immune/inflammatory pathways showed differences between IS etiologies in CS. A 15-gene biomarker panel assembled from a derivation cohort (n = 50) correctly classified 81% of CS and 71% of SO participants in a validation cohort (n = 33). Another 15-gene panel correctly identified etiologies for 13 of 13 CS-cardioembolic and 11 of 11 CS-noncardioembolic participants upon cross-validation; 11 of 16 CS-cryptogenic participants were predicted cardioembolic. INTERPRETATION: We discovered unique mRNA and miRNA transcriptome architecture in CS and SO, and in CS with different IS etiologies. Cardioembolic and noncardioembolic etiologies in CS showed unique coexpression networks and potential master regulators. These may help distinguish CS from SO and identify IS etiology in cryptogenic CS patients. ANN NEUROL 2024;96:565-581.

Epidemiologic Features of Recovery From SARS-CoV-2 Infection.

Importance: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden. Objective: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days. Design, Setting, and Participants: For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection. Exposure: Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires. Main Outcomes and Measures: Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days. Results: Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections. Conclusions and Relevance: In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.

Associations Between Stroke Type, Ischemic Stroke Subtypes, and Post-Stroke Cognitive Trajectories.

Background: It is unclear how post-stroke cognitive trajectories differ by stroke type and ischemic stroke subtype. We studied associations between stroke types (ischemic, hemorrhagic), ischemic stroke subtypes (cardioembolic, large artery atherosclerotic, lacunar/small vessel, cryptogenic/other determined etiology), and post-stroke cognitive decline. Methods: This pooled cohort analysis from four US cohort studies (1971-2019) identified 1,143 dementia-free individuals with acute stroke during follow-up: 1,061 (92.8%) ischemic, 82 (7.2%) hemorrhagic, 49.9% female, 30.8% Black. Median age at stroke was 74.1 (IQR, 68.6, 79.3) years. Outcomes were change in global cognition (primary) and changes in executive function and memory (secondary). Outcomes were standardized as T-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Median follow-up for the primary outcome was 6.0 (IQR, 3.2, 9.2) years. Linear mixed-effects models estimated changes in cognition after stroke. Results: On average, the initial post-stroke global cognition score was 50.78 points (95% CI, 49.52, 52.03) in ischemic stroke survivors and did not differ in hemorrhagic stroke survivors (difference, -0.17 points [95% CI, -1.64, 1.30]; P=0.82) after adjusting for demographics and pre-stroke cognition. On average, ischemic stroke survivors showed declines in global cognition, executive function, and memory. Post-stroke declines in global cognition, executive function, and memory did not differ between hemorrhagic and ischemic stroke survivors. 955 ischemic strokes had subtypes: 200 (20.9%) cardioembolic, 77 (8.1%) large artery atherosclerotic, 207 (21.7%) lacunar/small vessel, 471 (49.3%) cryptogenic/other determined etiology. On average, small vessel stroke survivors showed declines in global cognition and memory, but not executive function. Initial post-stroke cognitive scores and cognitive declines did not differ between small vessel survivors and survivors of other ischemic stroke subtypes. Post-stroke vascular risk factor levels did not attenuate associations. Conclusion: Stroke survivors had cognitive decline in multiple domains. Declines did not differ by stroke type or ischemic stroke subtype.

Cumulative Systolic Blood Pressure and Incident Stroke Type Variation by Race and Ethnicity.

Importance: Stroke risk varies by systolic blood pressure (SBP), race, and ethnicity. The association between cumulative mean SBP and incident stroke type is unclear, and whether this association differs by race and ethnicity remains unknown. Objective: To examine the association between cumulative mean SBP and first incident stroke among 3 major stroke types-ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH)-and explore how these associations vary by race and ethnicity. Design, Setting, and Participants: Individual participant data from 6 US longitudinal cohorts (January 1, 1971, to December 31, 2019) were pooled. The analysis was performed from January 1, 2022, to January 2, 2024. The median follow-up was 21.6 (IQR, 13.6-31.8) years. Exposure: Time-dependent cumulative mean SBP. Main Outcomes and Measures: The primary outcome was time from baseline visit to first incident stroke. Secondary outcomes consisted of time to first incident IS, ICH, and SAH. Results: Among 40 016 participants, 38 167 who were 18 years or older at baseline with no history of stroke and at least 1 SBP measurement before the first incident stroke were included in the analysis. Of these, 54.0% were women; 25.0% were Black, 8.9% were Hispanic of any race, and 66.2% were White. The mean (SD) age at baseline was 53.4 (17.0) years and the mean (SD) SBP at baseline was 136.9 (20.4) mm Hg. A 10-mm Hg higher cumulative mean SBP was associated with a higher risk of overall stroke (hazard ratio [HR], 1.20 [95% CI, 1.18-1.23]), IS (HR, 1.20 [95% CI, 1.17-1.22]), and ICH (HR, 1.31 [95% CI, 1.25-1.38]) but not SAH (HR, 1.13 [95% CI, 0.99-1.29]; P = .06). Compared with White participants, Black participants had a higher risk of IS (HR, 1.20 [95% CI, 1.09-1.33]) and ICH (HR, 1.67 [95% CI, 1.30-2.13]) and Hispanic participants of any race had a higher risk of SAH (HR, 3.81 [95% CI, 1.29-11.22]). There was no consistent evidence that race and ethnicity modified the association of cumulative mean SBP with first incident stroke and stroke type. Conclusions and Relevance: The findings of this cohort study suggest that cumulative mean SBP was associated with incident stroke type, but the associations did not differ by race and ethnicity. Culturally informed stroke prevention programs should address modifiable risk factors such as SBP along with social determinants of health and structural inequities in society.

Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.

BACKGROUND AND OBJECTIVES: Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT. METHODS: Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the "RoPE-Ox" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium). To estimate stroke recurrence risk, observed outcomes were calculated for patients older than 60 years in the age-inclusive observational databases (n = 549). To estimate the reduction in the rate of recurrent stroke associated with PFO closure vs medical therapy based on the RoPE score and the presence of high-risk PFO features, a Cox proportional hazards regression model was developed on the RCT data in the SCOPE database (n = 3,740). These estimates were used to calculate sample sizes required for a future RCT. RESULTS: Five-year risk of stroke recurrence using Kaplan-Meier estimates was 13.7 (95% CI 10.5-17.9) overall, 14.9% (95% CI 10.2-21.6) in those with high-risk PFO features. Predicted relative reduction in the event rate with PFO closure was 12.9% overall, 48.8% in those with a high-risk PFO feature. Using these estimates, enrolling all older patients with cryptogenic stroke and PFO would require much larger samples than those used for prior PFO closure trials, but selectively enrolling patients with high-risk PFO features would require totals of 630 patients for 90% power and 471 patients for 80% power, with an average of 5 years of follow-up. DISCUSSION: Based on our projections, anticipated effect sizes in older patients with high-risk features make a trial in these subjects feasible. With lengthening life expectancy in almost all regions of the world, the utility of PFO closure in older adults is increasingly important to explore.

Development and validation of the Michigan Chronic Disease Simulation Model (MICROSIM).

Strategies to prevent or delay Alzheimer's disease and related dementias (AD/ADRD) are urgently needed, and blood pressure (BP) management is a promising strategy. Yet the effects of different BP control strategies across the life course on AD/ADRD are unknown. Randomized trials may be infeasible due to prolonged follow-up and large sample sizes. Simulation analysis is a practical approach to estimating these effects using the best available existing data. However, existing simulation frameworks cannot estimate the effects of BP control on both dementia and cardiovascular disease. This manuscript describes the design principles, implementation details, and population-level validation of a novel population-health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP-COG) study of the effect of BP levels over the life course on dementia and cardiovascular disease. MICROSIM is an agent-based Monte Carlo simulation designed using computer programming best practices. MICROSIM estimates annual vascular risk factor levels and transition probabilities in all-cause dementia, stroke, myocardial infarction, and mortality in a nationally representative sample of US adults 18+ using the National Health and Nutrition Examination Survey (NHANES). MICROSIM models changes in risk factors over time, cognition and dementia using changes from a pooled dataset of individual participant data from 6 US prospective cardiovascular cohort studies. Cardiovascular risks were estimated using a widely used risk model and BP treatment effects were derived from meta-analyses of randomized trials. MICROSIM is an extensible, open-source framework designed to estimate the population-level impact of different BP management strategies and reproduces US population-level estimates of BP and other vascular risk factors levels, their change over time, and incident all-cause dementia, stroke, myocardial infarction, and mortality.

Effect of Population-Level Blood Pressure Treatment Strategies on Cardiovascular and Cognitive Outcomes.

BACKGROUND: The large and increasing number of adults living with dementia is a pressing societal priority, which may be partially mitigated through improved population-level blood pressure (BP) control. We explored how tighter population-level BP control affects the incidence of atherosclerotic cardiovascular disease (ASCVD) events and dementia. METHODS: Using an open-source ASCVD and dementia simulation analysis platform, the Michigan Chronic Disease Simulation Model, we evaluated how optimal implementation of 2 BP treatments based on the Eighth Joint National Committee recommendations and SPRINT (Systolic Blood Pressure Intervention Trial) protocol would influence population-level ASCVD events, global cognitive performance, and all-cause dementia. We simulated 3 populations (usual care, Eighth Joint National Committee based, SPRINT based) using nationally representative data to annually update risk factors and assign ASCVD events, global cognitive performance scores, and dementia, applying different BP treatments in each population. We tabulated total ASCVD events, global cognitive performance, all-cause dementia, optimal brain health, and years lived in each state per population. RESULTS: Optimal implementation of SPRINT-based BP treatment strategy, compared with usual care, reduced ASCVD events in the United States by ≈77 000 per year and produced 0.4 more years of stroke- or myocardial infarction-free survival when averaged across all Americans. Population-level gains in years lived free of ASCVD events were greater for SPRINT-based than Eighth Joint National Committee-based treatment. Survival and years spent with optimal brain health improved with optimal SPRINT-based BP treatment implementation versus usual care: the average patient with hypertension lived 0.19 additional years and 0.3 additional years in optimal brain health. SPRINT-based BP treatment increased the number of years lived without dementia (by an average of 0.13 years/person with hypertension), but increased the total number of individuals with dementia, mainly through more adults surviving to advanced ages. CONCLUSIONS: Tighter BP control likely benefits most individuals but is unlikely to reduce dementia prevalence and might even increase the number of older adults living with dementia.

Racial-Ethnic disparities in stroke prevalence among patients with heart failure.

Racial-ethnic disparities exist in the prevalence and outcomes of heart failure (HF) and are presumed to be related to differences in cardiovascular risk factor burden and control. There is little data on stroke disparities among patients with HF or the factors responsible. We hypothesized disparities in stroke prevalence exist among patients with HF in a manner not fully explained by burden of cardiovascular disease. We analyzed data from the National Health and Nutrition Examination Survey (1999-2014). Cardiovascular profiles were compared by race/ethnicity. Using survey-weighted models, effect modification of the relationship between HF and stroke by race/ethnicity was examined adjusting for cardiovascular profiles. Of 40,437 participants, 2.5 % had HF. The HF cohort had a greater proportion of White and Black participants (77 % vs 74 % and 15 % vs 12 %, respectively) and fewer participants of Hispanic ethnicity (8 % vs 14 %). Stroke was 8 times more prevalent in HF (19.6 % vs 2.3 %, <0.001). Among individuals with HF, race-ethnic differences were identified in the prevalence and mean values of vascular risk factors but were largely driven by higher rates in Black participants. There was significant interaction between HF and race/ethnicity; HF increased the odds of stroke over 7-fold in participants of Hispanic ethnicity (aOR: 7.84; 95 % CI: 4.11-15.0) but to a lesser extent in Black and White participants (Black aOR: 2.49; 95 % CI: 1.72-3.60; White aOR: 3.36; 95 % CI: 2.57-4.40). People of Hispanic ethnicity with HF have a disproportionately higher risk of stroke in a manner not fully explained by differences in vascular risk profiles.