Abstract 033: Epigenetic Clocks And Incident Heart Failure: The Atherosclerosis Risk In Communities (aric)

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Steven Nguyen ◽  
Carin A Northuis ◽  
Weihua Guan ◽  
Jan Bressler ◽  
Megan Grove ◽  
...  

Background: DNA methylation (DNAm)-based measures of aging, termed epigenetic clocks (EC), are associated with aging-related outcomes including cardiovascular disease (CVD) and all-cause mortality. Associations of ECs with heart failure (HF) are unclear. We tested whether ECs were positively associated with risk of incident HF in the Atherosclerosis Risk in Communities (ARIC) study and evaluated whether adding ECs to Pooled Cohort Equation (PCE) variables improved risk prediction. Methods: We measured DNAm in peripheral blood leukocytes in 2,263 African American (mean age=56.3 years) and 925 European American (mean age=59.5 years) participants using the Illumina HM450K and calculated 7 ECs: Horvath, Hannum, extrinsic (EEAA) and intrinsic (IEAA) epigenetic age acceleration, Hannum, PhenoAge, and GrimAge. HF was ascertained by ICD- 9 code 428 and adjudication by an expert panel. We carried out race stratified proportional hazards regression to test associations ECs with incident HF, adjusting for PCE variables: age, sex, smoking, total cholesterol, HDL, systolic blood pressure (SBP), antihypertensive medication use, and diabetes. We calculated area under the curve (AUC) and integrated discrimination index (IDI) to evaluate improvement in risk prediction when adding the ECs to PCE variables. Results: The number of incident HF events and mean follow-up time in African Americans and European Americans were 640 (189 in the first 10 years) and 19.3 years, and 191 and 21.7 years, respectively. All 7 ECs were positively associated with HF in both African Americans and European Americans. In African Americans with follow-up restricted to the first 10 years, the HR for a one SD increment in GrimAge (5.64 years) was 1.57 (95% CI=1.31, 1.88), comparable to that for a one-SD (5.82 years) increment in age (HR=1.58, 95% CI=1.36, 1.83) and greater than that for a one-SD (20.2mmHg) increment in SBP (HR=1.33, 95% CI=1.18, 1.51). In European Americans across the entire follow-up period, the HR for a one-SD increment in GrimAge (6.13 years) was 1.22 (95% CI=1.06, 1.41), smaller than that for a one-SD (5.50 years) increment in age (HR=1.93, 95% CI=1.63, 2.29) and larger than that for a one-SD (17.9 mmHG) increment in SBP (HR=1.13, 95% CI=0.98, 1.30). In African Americans with follow-up restricted to the first 10 years, adding GrimAge to PCE variables increased AUC by 0.019 (95% CI=0.003, 0.035) and the IDI was 0.010 (95% CI=0.002, 0.019). In European Americans, adding GrimAge did not change AUC appreciably (0.004, 95% CI=-0.006, 0.014) and the IDI was 0.002 (95% CI=0.000, 0.005). Conclusion: ECs are positively associated with HF in African American and European American participants independent of traditional CVD risk factors. GrimAge modestly improved heart failure risk prediction in African Americans. HF-specific DNAm-based measures should be developed and evaluated for improvement in risk prediction.

2017 ◽  
Vol 27 (1) ◽  
pp. 31 ◽  
Author(s):  
Kristen M. George ◽  
Aaron R. Folsom ◽  
Anna Kucharska-Newton ◽  
Tom H. Mosley ◽  
Gerardo Heiss

<p class="Pa7"><strong>Background: </strong>Few studies have addressed retention of minorities, particularly African Americans, in longitudinal research. Our aim was to determine whether there was differ­ential retention between African Americans and Whites in the ARIC cohort and identify cardiovascular disease (CVD) risk factors and indicators of socioeconomic status (SES) as­sociated with these retention differences.</p><p class="Pa7"><strong>Methods: </strong>15,688 participants, 27% African American and 73% White, were included from baseline, 1987-1989, and classified as having died, lost or withdrew from study contact, or remained active in study calls through 2013. Life tables were created illustrating retention patterns stratified by race, from baseline through visit 5, 2011- 2013. Prevalence tables stratified by race, participation status, and center were cre­ated to examine CVD risk factors and SES at baseline and visit 5.</p><p class="Pa7"><strong>Results: </strong>54% of African Americans com­pared with 62% of Whites were still in follow-up by 2013. This difference was due to an 8% higher cumulative incidence of death among African Americans. Those who remained in follow-up had the lowest baseline CVD risk factors and better SES, followed by those who were lost/withdrew<em>, </em>then those who died. Whites had lower lev­els of most CVD risk factors and higher SES than African Americans overall at baseline and visit 5; though, the magnitude of visit 5 differences was less.</p><p class="Pa7"><strong>Conclusions: </strong>In the ARIC cohort, reten­tion differed among African Americans and Whites, but related more to mortality dif­ferences than dropping-out. Additional re­search is needed to better characterize the factors contributing to minority participants’ recruitment and retention in longitudinal research.</p><p class="Pa7"><em>Ethn Dis. </em>2017;27(1):31-38; doi:10.18865/ed.27.1.31.</p>


Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Elizabeth J Bell

Introduction: Although there is substantial evidence that physical activity reduces risk of cardiovascular disease (CVD), the few studies that included African Americans offer inconclusive evidence and did not study stroke and heart failure separately. Objective: We examined, in African Americans and Caucasians in the Atherosclerosis Risk in Communities study (ARIC), the association of physical activity with CVD incidence (n=1,039) and its major components - stroke (n=350), heart failure (n=633), and coronary heart disease (n=442) - over a follow-up period of 21 years. Methods: ARIC is a population-based biracial cohort study of 45– to 64-yr-old adults at the baseline visit in 1987–89. Physical activity was assessed using the modified Baecke physical activity questionnaire and categorized by the American Heart Association’s ideal CVD health guidelines: poor, intermediate, and ideal physical activity. An incident CVD event was defined as the first occurrence of 1) heart failure, 2) definite or probable stroke, or 3) coronary heart disease, defined as a definite or probable myocardial infarction or definite fatal coronary heart disease. Results: We included 3,707 African Americans and 10,018 Caucasians free of CVD at the baseline visit. After adjustment for age, sex, cigarette smoking, alcohol intake, hormone therapy use, education, and ‘Western’ and ‘Prudent’ dietary pattern scores, higher physical activity was inversely related to CVD, heart failure, and coronary heart disease incidence in African Americans and Caucasians (p-values for trend tests <.0001), and with stroke in African Americans. Hazard ratios (95% confidence intervals) for CVD for intermediate and ideal physical activity, respectively, compared to poor, were similar by race: 0.65 (0.56, 0.75) and 0.59 (0.49, 0.71) for African Americans, and 0.74 (0.66, 0.83) and 0.67 (0.59, 0.75) for Caucasians (p-value for interaction = 0.38). Physical activity was also associated similarly in African Americans and Caucasians for each of the individual CVD outcomes (coronary heart disease, heart failure, and stroke), with an approximate one-third reduction in risk for intermediate and ideal physical activity versus poor physical activity- this reduction was statistically significant. Conclusions: In conclusion, our findings reinforce public health recommendations that regular physical activity is important for CVD risk reduction, including reductions in stroke and heart failure. They provide strong new evidence that this risk reduction applies to African Americans as well as Caucasians and support the idea that some physical activity is better than none.


Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Shakia T Hardy ◽  
Laura R Loehr ◽  
Kenneth R Butler ◽  
Patricia P Chang ◽  
Aaron R Folsom ◽  
...  

Introduction: Rates of cerebrovascular disease, heart failure (HF), and coronary heart disease (CHD), increase progressively as blood pressure rises. Several authors have estimated the theoretical effects of shifting the population distribution of blood pressure; however few studies have examined the degree to which modest decrements in blood pressure affect HF incidence, or included a racially diverse population. Methods: Incident HF was identified by a first hospitalization with discharge diagnosis code of 428.X. Incident hospitalized (definite or probable) CHD and stroke were classified according to protocol. We used multivariable regression to estimate incidence rate differences (IRD) for HF, CHD, and stroke that could be associated with a two mm Hg reduction in systolic blood pressure (SBP) in 15,744 participants from the Atherosclerosis Risk in Communities Study. Results: Over a mean of 18.3 years of follow up, age-adjusted incidence rates for HF, CHD, and stroke were higher among African American than Caucasians (Table 1). After adjusting for antihypertensive use, gender, and age, a two mm Hg decrement in SBP across the total population was associated with an estimated 24/100,000 person-years (PY) and 39/100,000 PY fewer incident HF events in Caucasians and African Americans, respectively. The projected disease reductions were of smaller absolute magnitude for incident CHD and incident stroke. Extrapolation to the African American and Caucasian U.S. populations age greater than 45 years suggests that a two mmHg decrement in SBP could result in approximately 22,000 fewer incident HF events, 15,000 fewer incident CHD events, and 5,000 fewer incident stroke events annually. Conclusion: Our results suggest that modest shifts in SBP, consistent with what could theoretically be achieved through population level lifestyle interventions, could substantially decrease the incidence of HF, stroke, and CHD in the United States, especially among African American populations.


Author(s):  
Ramachandran S. Vasan ◽  
Solomon K. Musani ◽  
Kunihiro Matsushita ◽  
Walter Beard ◽  
Olushola B. Obafemi ◽  
...  

Background Black individuals have a higher burden of risk factors for heart failure (HF) and subclinical left ventricular remodeling. Methods and Results We evaluated 1871 Black participants in the Atherosclerosis Risk in Communities Study cohort who attended a routine examination (1993–1996, median age 58 years) when they underwent echocardiography. We estimated the prevalences of 4 HF stages: (1) Stage 0 : no risk factors; (2) Stage A : presence of HF risk factors (hypertension, diabetes mellitus, obesity, smoking, dyslipidemia, coronary artery disease without clinical myocardial infarction), no cardiac structural/functional abnormality; (3) Stage B : presence of prior myocardial infarction, systolic dysfunction, left ventricular hypertrophy, regional wall motion abnormality, or left ventricular enlargement; and (4) Stage C/D : prevalent HF. We assessed the incidence of clinical HF, atherosclerotic cardiovascular disease events, and all‐cause mortality on follow‐up according to HF stage. The prevalence of HF Stages 0, A, B, and C/D were 3.8%, 20.6%, 67.0%, and 8.6%, respectively, at baseline. On follow‐up (median 19.0 years), 309 participants developed overt HF, 390 incurred new‐onset cardiovascular disease events, and 651 individuals died. Incidence rates per 1000 person‐years for overt HF, cardiovascular disease events, and death, respectively, were Stage 0, 2.4, 0.8, and 7.6; Stage A, 7.4, 9.7, and 13.5; Stage B 13.6, 15.9, and 22.0. Stage B HF was associated with a 1.5‐ to 2‐fold increased adjusted risk of HF, cardiovascular disease events and death compared with Stages 0/A. Conclusions In our large community‐based sample of Black individuals, we observed a strikingly high prevalence of Stage B HF in middle age that was a marker of high cardiovascular morbidity and mortality.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Magnus O Wijkman ◽  
Marcus Malachias ◽  
Brian Claggett ◽  
Susan Cheng ◽  
Kunihiro Matsushita ◽  
...  

Introduction: Apparent resistant hypertension (ARH) is a common marker of risk in patients with established cardiovascular disease. We ascertained the prevalence and prognostic significance of ARH in patients without prior cardiovascular disease. Methods: This prospective observational cohort study included 9669 community-based participants without a history of heart failure, myocardial infarction, or stroke, who completed the Atherosclerosis Risk in Communities (ARIC) study visit 4 between 1996-1998. The definition of ARH was blood pressure (BP) above goal (traditional goal <140/90mmHg, more stringent goal <130/80mmHg) despite use of ≥3 antihypertensive drug classes, or any BP with ≥4 antihypertensive drug classes. Participants with controlled hypertension (CH), defined as BP at goal with use of 1-3 antihypertensive drug classes, constituted the reference group. The outcome was a composite endpoint of heart failure, myocardial infarction, stroke, or death. Cox regression models were adjusted for age, sex, race, BMI, heart rate, smoking, eGFR, LDL, HDL, triglycerides, glucose, and diabetes. Results: Applying the traditional BP goal, 154/9669 participants (1.6%) had ARH, and there were 2311 participants with CH (23.9%). Using the more stringent BP goal, 218/9669 participants (2.3%) had ARH, and 1523 participants (15.8 %) had CH. The median follow-up time was 19 years. Apparent resistant hypertension was associated with an increased risk for the composite endpoint (adjusted hazard ratio 1.58 [95% CI 1.32-1.90] with the traditional BP goal, and adjusted hazard ratio 1.51 [95% CI 1.28-1.79] with the more stringent BP goal). Conclusions: Apparent resistant hypertension had a low prevalence but was independently associated with adverse outcome during long term follow-up, compared to controlled hypertension and even compared to uncontrolled hypertension. This was observed for both traditional and more stringent BP goals.


2019 ◽  
Vol 29 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Kristen M. George ◽  
Aaron R. Folsom ◽  
Lyn M. Steffen ◽  
Lynne E. Wagenknecht ◽  
Thomas H. Mosley

Geographic differences in cardiovascular disease (CVD) mortality among African Americans (AAs) are well-established, but not well-characterized. Using the Minnesota Heart Survey (MHS) and Atherosclerosis Risk in Communities (ARIC) Study, we aimed to assess whether CVD risk factors drive geographic disparities in CVD mortal­ity among AAs.ARIC risk factors were measured be­tween1987-1989 from a population-based sample of AAs, aged 45 to 64 years, living in Jackson, MS and Forsyth County, NC. Simi­lar measures were made at MHS baseline, 1985, in AAs from Minneapolis-St. Paul, MN. CVD mortality was identified using ICD codes for underlying cause of death. We compared MHS and ARIC on CVD death rates using Poisson regression, risk factor prevalences, and hazard ratios using Cox regression.After CVD risk factor adjustment, AA men in MHS had 3.4 (95% CI: 2.1, 4.7) CVD deaths per 1000 person-years vs 9.9 (95% CI: 8.7, 11.1) in ARIC. AA women in MHS had 2.7 (95% CI: 1.8, 3.6) CVD deaths per 1000 person-years vs 6.7 (95% CI: 6.0, 7.4) in ARIC. A 2-fold higher CVD mortality rate remained in ARIC vs MHS after additional adjustment for education and income. ARIC had higher total cholesterol, hypertension, diabetes, and BMI, as well as less education and income than MHS. Risk factor hazard ratios of CVD death did not differ.The CVD death rate was lower in AAs in Minnesota (MHS) than AAs in the South­east (ARIC). While our findings support maintaining low risk for CVD preven­tion, differences in CVD mortality reflect unidentified geographic variation.Ethn Dis. 2019;29(1):47-52; doi:10.18865/ ed.29.1.47


Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Rebecca L Molinsky ◽  
Faye L Norby ◽  
Bing Yu ◽  
Amil M Shah ◽  
Pamela L Lutsey ◽  
...  

Introduction: Periodontal disease, resulting from inflammatory host-response to dysbiotic subgingival microbiota, has been associated with incident hypertension, heart attack, stroke and diabetes. Limited data exist investigating the prospective relationship between periodontal disease and incident heart failure (HF) and HF subtypes. We hypothesize that periodontal disease is associated with increased risk for heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Methods: We studied 6,707 participants enrolled in the Atherosclerosis Risk in Communities Study who received a full-mouth clinical periodontal examination at visit 4 (1996-1998) and had longitudinal follow-up starting in 2005. Participants were classified as being periodontally healthy, having periodontal disease (based on the Periodontal Profile Classification (PPC)), or being edentulous. Hospitalization records were reviewed, and HF events were adjudicated and classified as HFpEF, HFrEF or HF of unknown ejection fraction (HFunknownEF) from 2005-2018. We used multivariable-adjusted Cox proportional hazards models to assess the association between periodontal disease or edentulism and incident HF. Results: Among participants 58% had periodontitis and 19% were edentulous. During a median follow-up time of 13 years, 1,178 cases of incident HF occurred (350 HFpEF, 319 HFrEF and 509 HFunknownEF). Periodontal disease and being edentulous were both associated with increased risk for both HFpEF and HFrEF (Table). Conclusion: Periodontal disease measured in mid-life was associated with both incident HFpEF and HFrEF. Adverse microbial exposures underlying periodontal disease might represent a modifiable risk factor for inflammation-induced heart failure pathophysiology.


Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Amir Azeem ◽  
Solomon K Musani ◽  
Walter L Beard ◽  
Thomas H Mosley ◽  
Kenneth R Butler ◽  
...  

Background: Heart failure (HF) affects a large number of Americans with an estimated lifetime risk of over 20% among individuals over the age of 40 years. Heart failure is associated with significant morbidity, mortality and health care cost. Epidemiological data suggests that HF disproportionately affects African Americans. Existing risk prediction models may not accurately predict the risk of incident HF in this population limiting the implementation of screening and preventive strategies. We sought to examine the predictors of incident heart failure in a community-based African American cohort. Methods: The study population consisted of 2244 African American participants from the Jackson cohort of the Atherosclerosis Risk in Communities (ARIC) study. Participants with prevalent HF and missing data at the baseline were excluded. Cox proportional regression with backward elimination was used to assess the association of risk markers with first clinical HF event as follows: Model 1 - standard cardiovascular risk factors (age, gender, body mass index [BMI], systolic blood pressure, use of anti-hypertensive medication, diabetes status, current smoking, total cholesterol-HDL ratio [TC:HDL], logarithmically transformed-triglyceride); Model 2 - significant standard risk factors and biomarkers (logarithmically transformed-brain natriuretic peptide [BNP], logarithmically transformed-troponin, logarithmically transformed-albumin-creatinine ratio); Model 3 - significant standard risk factors and subclinical disease markers (estimated glomerular filtration rate [eGFR], ankle-brachial index, forced expiratory volume in one second [FEV1], forced vital capacity, left ventricular ejection fraction < 50%, left ventricular mass indexed to height2.7); Model 4 - significant standard risk factors, significant biomarkers, and significant subclinical disease markers. Results: The mean age and BMI were 58 years and 30 kg/m2 respectively. During a median follow-up of 18.1 years (maximum 19.8), there were 268 incident HF events. Triglyceride from Model 1, Troponin and Albumin-Creatinine ratio from Model 2, and eGFR from Model 3 were eliminated. In the final model, diabetes status (Hazard Ratio [95% Confidence Interval]: 1.76 [1.07, 2.89]), use of anti-hypertensive medication (2.38 [1.40, 4.06]), TC:HDL (1.34 [1.18, 1.52]) and BNP (1.28 [1.14, 1.44]) were significant predictors of incident HF. Higher FEV1 was associated with reduced risk of HF in this study (0.29 [0.11, 0.76]). Conclusion: In this community-dwelling African American population, diabetes status, use of anti-hypertensive medication, TC:HDL ratio, BNP and FEV1 were independent predictors of incident HF. This information may be useful to identify and target high risk individuals for aggressive preventive interventions.


2021 ◽  
pp. 1-27
Author(s):  
Marie Bissell ◽  
Walt Wolfram

This study considers the dynamic trajectory of the back-vowel fronting of the BOOT and BOAT vowels for 27 speakers in a unique, longstanding context of a substantive, tri-ethnic contact situation involving American Indians, European Americans, and African Americans over three disparate generations in Robeson County, North Carolina. The results indicate that the earlier status of Lumbee English fronting united them with the African American vowel system, particularly for the BOOT vowel, but that more recent generations have shifted towards alignment with European American speakers. Given the biracial Southeastern U.S. that historically identified Lumbee Indians as “free persons of color” and the persistent skepticism about the Lumbee Indians as merely a mixed group of European Americans and African Americans, the movement away from the African American pattern towards the European American pattern was interpreted as a case of oppositional identity in which Lumbee Indians disassociate themselves from African American vowel norms in subtle but socially meaningful ways.


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