Abstract 14054: Soluble ACE2, Cardiac Biomarkers, Structure, Function and Events: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Aliza Hussain ◽  
Olive Tang ◽  
Wensheng Sun ◽  
Xiaoming Jia ◽  
Elizabeth Selvin ◽  
...  

Introduction: Membrane-bound angiotensin-converting enzyme 2 (ACE2) has been identified to a have prominent role in SARS-COV-2 infection and is an important counter-regulator of renin-angiotensin system. But the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) remains unclear. We sought to identify the association of sACE2 with cardiac biomarkers, structure, function and events in the Atherosclerosis Risk in Communities (ARIC) Study. Methods: sACE2 was measured in a subset of 497 patients from a case-control study of incident heart failure (HF) at visit 5 (2011-2013), mean age 78 (SD 5.4), 53% men and 27% black. We used linear regression to evaluate the associations of sACE2 with cardiac biomarkers (hs-cTnI, hs-cTnT, NT-proBNP) and echocardiographic parameters. We used Cox regression to evaluate associations of sACE2 with risk of HF hospitalization, global CVD events (CHD, ischemic stroke or HF hospitalization) and all-cause death. Results: Over a median follow up of 6.1 (4.6, 6.8) years, 282 global CVD events and 190 all-cause deaths occurred. sACE2 levels were higher in men, blacks, those with prevalent CVD, diabetes and hypertension. Higher sACE2 levels were associated with significantly higher hs-cTnI, hs-cTnT, NT-proBNP levels, greater left ventricular (LV) mass index, impaired diastolic function ( Table ) and increased risk for HF hospitalization (adjusted HR 1.32 per log unit increase, 95% CI 1.10-1.58), global CVD events (HR 1.34, 95% CI 1.13-1.60) and all-cause death (HR 1.26, 95% CI 1.01-1.57). Conclusions: In an elderly biracial cohort, sACE2 was positively associated with biomarkers reflecting myocardial injury and neurohormonal activation, LV mass index, impaired diastolic function, CVD events and all-cause death. Future research is needed to elucidate the significance of sACE2 in development of CVD, not only in patients with SAR—COV2 infection, but the general population

2020 ◽  
Vol 9 (18) ◽  
Author(s):  
Mengyuan Shi ◽  
Lin Y. Chen ◽  
Wobo Bekwelem ◽  
Faye L. Norby ◽  
Elsayed Z. Soliman ◽  
...  

Background Atrial fibrillation (AF) increases the risk of stroke and extracranial systemic embolic events (SEEs), but little is known about the magnitude of the association of AF with SEE. Methods and Results This analysis included 14 941 participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age, 54.2±5.8, 55% women, 74% White) without AF at baseline (1987–1989) followed through 2017. AF was identified from study ECGs, hospital discharges, and death certificates, while SEEs were ascertained from hospital discharges. CHA 2 DS 2 ‐VASc was calculated at the time of AF diagnosis. Cox regression was used to estimate associations of incident AF with SEE risk in the entire cohort, and between CHA 2 DS 2 ‐VASc score and SEE risk in those with AF. Among eligible participants, 3114 participants developed AF and 270 had an SEE (59 events in AF). Incident AF was associated with increased risk of SEE (hazard ratio [HR], 3.58; 95% CI, 2.57–5.00), after adjusting for covariates. The association of incident AF with SEE was stronger in women (HR, 5.26; 95% CI, 3.28–8.44) than in men (HR, 2.68; 95% CI, 1.66–4.32). In those with AF, higher CHA 2 DS 2 ‐VASc score was associated with increased SEE risk (HR per 1‐point increase, 1.24; 95% CI, 1.05–1.47). Conclusions AF is associated with more than a tripling of the risk of SEE, with a stronger association in women than in men. CHA 2 DS 2 ‐VASc is associated with SEE risk in AF patients, highlighting the value of the score to predict adverse outcomes and guide treatment decisions in people with AF.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Michelle C Johansen ◽  
Amil Shah ◽  
Michael Griswold ◽  
Seth Lirette ◽  
Thomas H Mosley ◽  
...  

Background: Heart failure (HF) is a disease that impacts many organs, but the effect on the brain remains poorly understood. To explore associations with subclinical disease, in the Atherosclerosis Risk in Communities (ARIC) study, we evaluated the relationship between cardiac dysfunction on echocardiography and vascular lesions on brain MRI. Methods: A cross-sectional analysis between subclinical cardiac and brain markers was performed using echo and brain MRI data from the 5 th visit of the ARIC study (n=1974), a community-based biracial cohort study. LV structure was assessed using wall thickness (mm) and mass index (g/m 2 ), while diastolic function was assessed as LA volume index (g/m2). MRI was evaluated for presence/size/location/number of infarcts and white matter hyperintensities (WMH). Demographic and vascular risk factors (including hypertension) were considered as covariates in statistical models. Results: In adjusted models, worse LV structure was significantly associated with the presence of WMH as well as infarction. WMH was 0.66 cm 3 greater (95%CI [0.11, 1.21]) for every 1 mm increase in wall thickness, and 0.65 cm 3 greater (95%CI [0.27, 1.03]) for every 10g/m 2 increase in LV mass index. Odds of infarction increased (OR 1.11, 95%CI [1.02, 1.21]), per 1 mm thicker LV wall increase as well as with larger LV mass (per 10 g/m 2 ) (OR 1.08, 95%CI [1.02, 1.14]). The rate of accumulating additional cortical infarcts was increased by 2.4% (95%CI 1.01, 1.04) per ml/m 2 increase in LA volume index, a marker of LV diastolic function. The rate of accumulation of lacunar infarcts was increased by 1.5% per ml/m2 increase in LA volume index (95% CI [1.00, 1.03]). No significant interactions were detected by race. Conclusions: Among participants in a large cohort study, subclinical changes in markers of LV structure were associated with increased odds of infarction and volume of WMH even when controlling for hypertension. Our findings could suggest that the brain represents another end-organ at risk among patients with even early stages of heart failure.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Aliza Hussain ◽  
VIJAY NAMBI ◽  
Elizabeth Selvin ◽  
Wensheng Sun ◽  
Kunihiro Matsushita ◽  
...  

Introduction: Cardiovascular disease (CVD) is the most common cause of death in nonalcoholic steatohepatitis (NASH). While these conditions share many cardio-metabolic risk factors including metabolic syndrome, diabetes and dyslipidemia, limited data exist on whether NASH is independently and prospectively associated with incident CVD beyond traditional risk factors. Fibrosis-4 (FIB-4) index is a scoring system based on platelet count, age, AST and ALT, shown to be comparable to magnetic resolution elastography for predicting advanced fibrosis in biopsy-proven NASH. We sought to evaluate the association of elevated FIB-4 with global CVD events and CVD mortality in the Atherosclerosis Risk in Communities (ARIC) Study Methods: We studied 5531 individuals, mean age of 76 (SD 5.2) years, 58% female, 22% black, at ARIC visit 5 (2011-2013). FIB-4 was categorized as low risk of advanced fibrosis for score <1.45, intermediate for 1.45-3.25 and high for >3.25. Cox regression was used to estimate the association of FIB-4 with time to first global CVD event (CHD, ischemic stroke or heart failure hospitalization) and CVD mortality adjusted for pooled cohort equation risk factors. Results: Over a median follow up of 6.2 (5.3-6.8) years, there were 1108 global CVD events and 457 CVD deaths. In adjusted models, compared to participants with low FIB-4 (<1.45), those with elevated FIB-4 >3.25, had significantly increased risk for global CVD events (HR 1.58, 95% CI 1.23-2.02) and CVD mortality (HR 1.70, 95% CI 1.16-2.50). Conclusions: In a large prospective cohort, presence of advanced liver fibrosis, as assessed by elevated FIB-4 index >3.25, was associated with increased risk for CVD events and CVD mortality, beyond traditional CVD risk factors. Future clinical trials of candidate medications under study for NASH should examine whether effective NASH treatment will impact CV outcomes.


2020 ◽  
Vol 22 (3) ◽  
pp. 357-368
Author(s):  
Angela Ruban ◽  
Natalie Daya ◽  
Andrea L.C. Schneider ◽  
Rebecca Gottesman ◽  
Elizabeth Selvin ◽  
...  

Background and Purpose Liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma-glutamyl transpeptidase [GGT]) are glutamate-regulatory enzymes, and higher glutamate levels correlated with worse prognosis of patients with neurotrauma. However, less is known about the association between liver enzymes and incidence of stroke. We evaluated the association between serum levels of AST, ALT, and GGT and incidence of stroke in the Atherosclerosis Risk in Communities (ARIC) study cohort from 1990 to 1992 through December 31, 2016.Methods We included 12,588 ARIC participants without prevalent stroke and with data on liver enzymes ALT, AST, and GGT at baseline. We used multivariable Cox regression models to examine the associations between liver enzymes levels at baseline and stroke risk (overall, ischemic stroke, and intracerebral hemorrhage [ICH]) through December 31, 2016, adjusting for potential confounders.Results During a median follow-up time of 24.2 years, we observed 1,012 incident strokes (922ischemic strokes and 90 ICH). In age, sex, and race-center adjusted models, the hazard ratios (HRs; 95% confidence intervals [CIs]) for the highest compared to lowest GGT quartile were 1.94 (95% CI, 1.64 to 2.30) for all incident stroke and 2.01 (95% CI, 1.68 to 2.41) for ischemic stroke, with the results supporting a dose-response association (P for linear trend <0.001). Levels of AST were associated with increased risk of ICH, but the association was significant only when comparing the third quartile with the lowest quartile (adjusted HR, 1.82; 95% CI, 1.06 to 3.13).Conclusions Elevated levels of GGT (within normal levels), independent of liver disease, are associated with higher risk of incident stroke overall and ischemic stroke, but not ICH.


Heart ◽  
2017 ◽  
Vol 104 (5) ◽  
pp. 423-429 ◽  
Author(s):  
Brittany M Bogle ◽  
Nona Sotoodehnia ◽  
Anna M Kucharska-Newton ◽  
Wayne D Rosamond

ObjectiveVital exhaustion (VE), a construct defined as lack of energy, increased fatigue and irritability, and feelings of demoralisation, has been associated with cardiovascular events. We sought to examine the relation between VE and sudden cardiac death (SCD) in the Atherosclerosis Risk in Communities (ARIC) Study.MethodsThe ARIC Study is a predominately biracial cohort of men and women, aged 45–64 at baseline, initiated in 1987 through random sampling in four US communities. VE was measured using the Maastricht questionnaire between 1990 and 1992 among 13 923 individuals. Cox proportional hazards models were used to examine the hazard of out-of-hospital SCD across tertiles of VE scores.ResultsThrough 2012, 457 SCD cases, defined as a sudden pulseless condition presumed due to a ventricular tachyarrhythmia in a previously stable individual, were identified in ARIC by physician record review. Adjusting for age, sex and race/centre, participants in the highest VE tertile had an increased risk of SCD (HR 1.48, 95% CI 1.17 to 1.87), but these findings did not remain significant after adjustment for established cardiovascular disease risk factors (HR 0.94, 95% CI 0.73 to 1.20).ConclusionsAmong participants of the ARIC study, VE was not associated with an increased risk for SCD after adjustment for cardiovascular risk factors.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Zhibin Li ◽  
Kristian Wachtell ◽  
Sverre E. Kjeldsen ◽  
Stevo Julius ◽  
Michael H. Olsen ◽  
...  

Background : Whether aortic regurgitation (AI) is associated with higher cardiovascular (CV) morbidity and mortality in hypertension with electrocardiographic (ECG) left ventricular hypertrophy (LVH) is unknown. Methods : Hypertensive patients with ECG-LVH were randomized to losartan- or atenolol-based treatment and followed for 4.8 years in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. In the LIFE echo substudy, echocardiograms were used to detect AI. Baseline clinical, echocardiographic variables and cardiovascular endpoints data were used in current analyses. Results: The presence of AI was detected in 132 participants (68 women; 68.4 ± 7.3 years). AI was associated with older age (p < 0.001) but not gender. After adjustment for age, AI was associated with significantly increased LV mass indexed by body surface area (BSA) and height 2.7 (both p < 0.005), echocardiographic eccentric LVH (p < 0.05) but not concentric left ventricular (LV) geometry (p < 0.05). After adjusting for significant confounders including history of CV disease, Framingham risk score, randomized antihypertensive therapy, LV eccentric geometry, LV mass indexed by BSA and height 2.7 , multivariate Cox regression analyses showed that AI was independently associated with 2.83-fold more CV death (95% confidence interval [CI] 1.12 to 7.13), 2.24-fold more all-cause mortality (95% CI 1.17 to 4.28) (both p < 0.05). Conclusion : In hypertensive patients with ECG-LVH, AI independently identifies patients at increased risk of CV and all-course mortality.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Aaron R Folsom ◽  
Vijay Nambi ◽  
Elizabeth J Bell ◽  
Oludamilola W Oluleye ◽  
Rebecca F Gottesman ◽  
...  

Increased levels of plasma troponins and natriuretic peptides in the general population are associated with increased future risk of cardiovascular disease, but only limited information exists on these biomarkers and stroke occurrence. In a prospective epidemiological study, the Atherosclerosis Risk in Communities (ARIC) Study, we tested the hypothesis that high-sensitivity troponin T (TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are associated positively with incidence of stroke. We measured plasma high-sensitivity TnT and NT-proBNP in 10,902 men or women initially free of stroke and followed them for a mean of 11.3 years for stroke occurrence (n=507). Analyses were performed using proportional hazards modeling. Both biomarkers were associated positively with total stroke, nonlacunar ischemic, and especially, cardioembolic stroke, but not with lacunar or hemorrhagic stroke. After adjustment for other stroke risk factors, the hazard ratio (95% CI) per one SD greater increment of natural log-transformed TnT was 1.23 (1.13, 1.35) for total stroke, 1.27 (1.15, 1.40) for total ischemic stroke, and 1.36 (1.14, 1.62) for cardioembolic stroke. Likewise, the hazard ratio per one SD greater natural log-transformed NT-proBNP, was 1.37 (1.26, 1.49) for total stroke, 1.39 (1.27, 1.53) for total ischemic stroke, and 1.95 (1.67, 2.28) for cardioembolic stroke. The hazard ratios for jointly high values of TnT (≥0.013 ug/L) and NT-proBNP (≥155.2 pg/mL), versus neither biomarker high, were 2.70 (1.92, 3.79) for total stroke and 6.26 (3.40, 11.5) for cardioembolic stroke, and somewhat stronger for NT-proBNP than TnT. Strikingly, approximately 58% of cardioembolic strokes occurred in the highest quintile of pre-stroke NT-proBNP (versus 3% occurring in the lowest quintile), and 32% of cardioembolic strokes occurred in participants who had both NT-proBNP in the highest quintile and were known by ARIC to have atrial fibrillation sometime before their cardioembolic stroke occurrence. In conclusion, in the general population, elevated plasma TnT and NT-proBNP concentrations are associated with increased risk of cardioembolic and other nonlacunar ischemic strokes.


Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Brittany M Bogle ◽  
Wayne D Rosamond ◽  
Aaron R Folsom ◽  
Paul Sorlie ◽  
Elsayed Z Soliman ◽  
...  

Background: Accurate community surveillance of cardiovascular disease requires hospital record abstraction, which is typically a manual process. The costly and time-intensive nature of manual abstraction precludes its use on a regional or national scale in the US. Whether an efficient system can accurately reproduce traditional community surveillance methods by processing electronic health records (EHRs) has not been established. Objective: We sought to develop and test an EHR-based system to reproduce abstraction and classification procedures for acute myocardial infarction (MI) as defined by the Atherosclerosis Risk in Communities (ARIC) Study. Methods: Records from hospitalizations in 2014 within ARIC community surveillance areas were sampled using a broad set of ICD discharge codes likely to harbor MI. These records were manually abstracted by ARIC study personnel and used to classify MI according to ARIC protocols. We requested EHRs in a unified data structure for the same hospitalizations at 6 hospitals and built programs to convert free text and structured data into the ARIC criteria elements necessary for MI classification. Per ARIC protocol, MI was classified based on cardiac biomarkers, cardiac pain, and Minnesota-coded electrocardiogram abnormalities. We compared MI classified from manually abstracted data to (1) EHR-based classification and (2) final ICD-9 coded discharge diagnoses (410-414). Results: These preliminary results are based on hospitalizations from 1 hospital. Of 684 hospitalizations, 355 qualified for full manual abstraction; 83 (23%) of these were classified as definite MI and 78 (22%) as probable MI. Our EHR-based abstraction is sensitive (>75%) and highly specific (>83%) in classifying ARIC-defined definite MI and definite or probable MI (Table). Conclusions: Our results support the potential of a process to extract comprehensive sets of data elements from EHR from different hospitals, with completeness and accuracy sufficient for a standardized definition of hospitalized MI.


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