Liver Enzymes and Risk of Stroke: The Atherosclerosis Risk in Communities (ARIC) Study

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.

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Abstract 79: Troponin T, NT-proBNP, and Incidence of Stroke: The Atherosclerosis Risk in Communities (ARIC) Study

Stroke ◽

10.1161/str.44.suppl_1.a79 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Aaron R Folsom ◽

Vijay Nambi ◽

Elizabeth J Bell ◽

Oludamilola W Oluleye ◽

Rebecca F Gottesman ◽

...

Keyword(s):

Ischemic Stroke ◽

General Population ◽

Troponin T ◽

High Sensitivity ◽

Hazard Ratio ◽

Cardioembolic Stroke ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Aric Study

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.

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Association of Atrial Fibrillation With Incidence of Extracranial Systemic Embolic Events: The ARIC Study

Journal of the American Heart Association ◽

10.1161/jaha.120.016724 ◽

2020 ◽

Vol 9 (18) ◽

Author(s):

Mengyuan Shi ◽

Lin Y. Chen ◽

Wobo Bekwelem ◽

Faye L. Norby ◽

Elsayed Z. Soliman ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cox Regression ◽

Adverse Outcomes ◽

Hospital Discharges ◽

Atherosclerosis Risk In Communities ◽

Entire Cohort ◽

Point Increase ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Aric Study

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.

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Abstract 14043: Association of Non-Alcoholic Steatohepatitis Assessed by Fib-4 Index and Risk of Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽

10.1161/circ.142.suppl_3.14043 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Aliza Hussain ◽

VIJAY NAMBI ◽

Elizabeth Selvin ◽

Wensheng Sun ◽

Kunihiro Matsushita ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Cox Regression ◽

Advanced Fibrosis ◽

Cvd Risk ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Aric Study ◽

Cvd Mortality

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.

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Abstract WP193: Gum Disease and Ischemic Stroke Risk in the Atherosclerosis Risk in Communities (ARIC) Study

Stroke ◽

10.1161/str.48.suppl_1.wp193 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Souvik Sen ◽

Lauren D Giamberardino ◽

Kevin Moss ◽

Wayne Rosamond ◽

Steven Offenbacher

Keyword(s):

Ischemic Stroke ◽

Latent Class ◽

Sudden Onset ◽

Atherosclerosis Risk In Communities ◽

Entire Cohort ◽

Stroke Subtypes ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Record Review ◽

Aric Study

Introduction: Gum, or periodontal disease (PD) is a risk factor for cardiovascular disease. We assessed the graded association of PD levels with incident ischemic stroke as well as the etiological stroke subtypes in the Atherosclerosis Risk in Communities (ARIC) study. Methods: PD was assessed by full-mouth periodontal measurements from 6 sites per tooth, in subjects without prior stroke and categorized into periodontal profile class (PPC). A Latent Class Analysis was used to identify 7 distinct PPCs using the entire cohort that included tooth level periodontal measurements and tooth loss. Stroke diagnoses were based on computer derived diagnosis medical record review and imaging confirmation. Classification required evidence of sudden onset of neurological deficit(s) lasting ≥24 hours. Strokes were classified according to etiology as thrombotic, lacunar, and cardioembolic subtypes. Results: At the fourth ARIC visit (1996-1998), a cohort of 6711 subjects (mean age±SD=62.3±5.6, 55% female, 81% white and 19% African-American) were assessed for PD. A total of 299 incident ischemic strokes (47% thrombotic, 26% cardioembolic and 20% lacunar) occurred over a 15-year period. The seven levels of PPC showed a graded association with incident ischemic stroke as noted in the figure. Participants with mild PD (adjusted HR 1.9 95% CI 1.2-3.0), moderate PD group (adjusted HR 2.1 95% CI 1.2-3.5) and severe PD (adjusted HR 2.2 95% CI 1.3-3.8) had an increased risk of incident ischemic stroke, compared with participants without PD after adjustment for confounders (age, race, gender, BMI, hypertension, diabetes, LDL cholesterol, smoking and education). There were class specific associations noted between PD with cardioembolic and thrombotic stroke subtypes. Conclusions: A graded association was noted between incident ischemic stroke and increasing levels of PPC. Further, we report class specific associations between PD with cardioembolic and thrombotic stroke subtypes.

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

Circulation ◽

10.1161/circ.142.suppl_3.14054 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Aliza Hussain ◽

Olive Tang ◽

Wensheng Sun ◽

Xiaoming Jia ◽

Elizabeth Selvin ◽

...

Keyword(s):

Structure Function ◽

Diastolic Function ◽

Cox Regression ◽

Left Ventricular ◽

Cardiac Biomarkers ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Lv Mass ◽

Atherosclerosis Risk ◽

Aric Study

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

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Vital exhaustion and sudden cardiac death in the Atherosclerosis Risk in Communities Study

Heart ◽

10.1136/heartjnl-2017-311825 ◽

2017 ◽

Vol 104 (5) ◽

pp. 423-429 ◽

Cited By ~ 2

Author(s):

Brittany M Bogle ◽

Nona Sotoodehnia ◽

Anna M Kucharska-Newton ◽

Wayne D Rosamond

Keyword(s):

Risk Factors ◽

Sudden Cardiac Death ◽

Cardiac Death ◽

Disease Risk ◽

Ventricular Tachyarrhythmia ◽

Atherosclerosis Risk In Communities ◽

Vital Exhaustion ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Aric Study

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.

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Abstract MP44: Biomarker Measures of Fish-Derived Omega-3 Fatty Acids and J-Point Elevation in the Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽

10.1161/circ.127.suppl_12.amp44 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Noelle N Gronroos ◽

Pamela J Schreiner ◽

Elsayed Z Soliman ◽

Lisa Harnack ◽

Richard F MacLehose ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Linear Trend ◽

Antiarrhythmic Agents ◽

Omega 3 ◽

Class Iii ◽

Atherosclerosis Risk In Communities ◽

Surface Ecg ◽

Atherosclerosis Risk ◽

Aric Study

Background: Higher intake of fish-derived omega-3 polyunsaturated fatty acids (PUFAs) has been associated with lower incidence of Sudden Cardiac Death (SCD), but the exact mechanisms underlying this association are unconfirmed. Early ventricular repolarization characterized by an elevation of the QRS-ST junction (J-Point) in the surface ECG has been associated with idiopathic ventricular fibrillation, the most common cause of SCD. We aimed to study the association of fish-derived PUFAs in plasma with the prevalence of J-Point elevation. Methods: We conducted a cross-sectional analysis of participants aged 45-64 (45.7% male, 100% whites) from the Minnesota Field Center of the Atherosclerosis Risk in Communities (ARIC) Study. Participants were excluded if they did not have an ECG, had a QRS duration ≥ 120 ms, were taking Class I or Class III antiarrhythmic agents, or had prevalent cardiovascular disease. Fish-derived PUFAs were measured in plasma phospholipids as a percentage of total fatty acids, categorized into quartiles, and logistic regression was used to estimate the odds of J-Point Elevation, defined as elevation of greater than 100 microvolts in at least two contiguous leads. Models were adjusted for potential confounders and tests of linear trend were conducted by assigning the median values for each exposure category and modeling as a continuous variable. Results: Among 3,330 eligible individuals, 126 presented J-Point elevation. Median fish-derived fatty acid percentage was 3.2% (range: 0.7-12.2). Using multivariable analyses, plasma measures of fish-derived omega-3 PUFAs were linearly associated with the log odds of J-Point elevation with increasing fatty acid percentages associated with lower odds of J-Point elevation (see Table). Conclusions: In this population, higher plasma levels of fish-derived PUFAs were inversely associated with J-Point elevation. Fish-derived PUFAs could reduce risk of SCD through decreased prevalence of early repolarization.

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