Association of cardiovascular health and epigenetic age acceleration

Abstract Background Cardiovascular health (CVH) has been defined by the American Heart Association (AHA) as the presence of the “Life’s Simple 7” ideal lifestyle and clinical factors. CVH is known to predict longevity and freedom from cardiovascular disease, the leading cause of death for women in the United States. DNA methylation markers of aging have been aggregated into a composite epigenetic age score, which is associated with cardiovascular morbidity and mortality. However, it is unknown whether poor CVH is associated with acceleration of aging as measured by DNA methylation markers in epigenetic age. Methods and results We performed a cross-sectional analysis of racially/ethnically diverse post-menopausal women enrolled in the Women’s Health Initiative cohort recruited between 1993 and 1998. Epigenetic age acceleration (EAA) was calculated using DNA methylation data on a subset of participants and the published Horvath and Hannum methods for intrinsic and extrinsic EAA. CVH was calculated using the AHA measures of CVH contributing to a 7-point score. We examined the association between CVH score and EAA using linear regression modeling adjusting for self-reported race/ethnicity and education. Among the 2,170 participants analyzed, 50% were white and mean age was 64 (7 SD) years. Higher or more favorable CVH scores were associated with lower extrinsic EAA (~ 6 months younger age per 1 point higher CVH score, p < 0.0001), and lower intrinsic EAA (3 months younger age per 1 point higher CVH score, p < 0.028). Conclusions These cross-sectional observations suggest a possible mechanism by which ideal CVH is associated with greater longevity.

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Epigenetic Age Acceleration and Change in Frailty in MOBILIZE Boston

The Journals of Gerontology Series A ◽

10.1093/gerona/glac019 ◽

2022 ◽

Author(s):

Benjamin Seligman ◽

Sarah D Berry ◽

Lewis A Lipsitz ◽

Thomas G Travison ◽

Douglas P Kiel

Keyword(s):

Dna Methylation ◽

Smoking Status ◽

Frailty Index ◽

450K Array ◽

Frailty Phenotype ◽

Cross Sectional ◽

Epigenetic Age ◽

Epigenetic Age Acceleration ◽

Frailty Score

Abstract Age-associated changes in DNA methylation have been implicated as one mechanism to explain the development of frailty, however previous cross-sectional studies of epigenetic age acceleration (eAA) and frailty have had inconsistent findings. Few longitudinal studies have considered the association of eAA with change in frailty. We sought to determine the association between eAA and change in frailty in the MOBILIZE Boston cohort. Participants were assessed at two visits 12-18 months apart. Intrinsic, extrinsic, GrimAge, and PhenoAge eAA were assessed from whole blood DNA methylation at baseline using the Infinium 450k array. Frailty was assessed by a continuous frailty score based on the frailty phenotype and by frailty index (FI). Analysis was by correlation and linear regression with adjustment for age, sex, smoking status, and BMI. 395 participants with a frailty score and 431 with a FI had epigenetic and follow-up frailty measures. For the frailty score and FI cohorts, respectively, mean (SD) ages were 77.8 (5.49) and 77.9 (5.47), 232 (58.7%) and 257 (59.6%) were female. All participants with epigenetic data identified as white. Baseline frailty score was not correlated with intrinsic or extrinsic eAA, but was correlated with PhenoAge and, even after adjustment for covariates, GrimAge. Baseline FI was correlated with extrinsic, GrimAge, and PhenoAge eAA with and without adjustment. No eAA measure was associated with change in frailty, with or without adjustment. Our results suggest that no eAA measure was associated with change in frailty. Further studies should consider longer periods of follow-up and repeated eAA measurement.

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Association of Subjective Social Status With Life's Simple 7s Cardiovascular Health Index Among Hispanic/Latino People: Results From the HCHS/SOL

Journal of the American Heart Association ◽

10.1161/jaha.119.012704 ◽

2021 ◽

Author(s):

Lissette M. Piedra ◽

Flavia C. D. Andrade ◽

Rosalba Hernandez ◽

Krista M. Perreira ◽

Linda C. Gallo ◽

...

Keyword(s):

Social Status ◽

Cardiovascular Health ◽

Fasting Blood Glucose ◽

Heart Association ◽

The United States ◽

Health Study ◽

Cross Sectional ◽

Glucose Levels ◽

Latino People ◽

Latino Adults

Background Evidence suggests that subjective (perceived) social status (SSS) may predict health outcomes more strongly than objective social status, but little is known about the relationship between SSS and cardiovascular health (CVH). This study focuses on this relationship among diverse Hispanic/Latino adults because while poor CVH profiles are prevalent in this population, immigration complicates attempts to measure their social status. Methods and Results We analyzed baseline HCHS/SOL (Hispanic Community Health Study/Study of Latinos) data on 15 374 Hispanic/Latino adults aged 18 to 74 years in 2008 to 2011. SSS was assessed using the McArthur Scale, a 10‐rung “social ladder.” CVH was based on levels of 7 metrics defined by the American Heart Association. Linear and logistic regressions were used to examine cross‐sectional associations of SSS with CVH (overall and single metrics) after adjusting for objective social status, demographic, and health factors. Less than half of the population (46%) had Ideal scores in ≥4 metrics of CVH. In multivariable‐adjusted models, an increase in SSS was associated with a higher overall CVH score (β=0.04; 95% CI, 0.01–0.06) and greater likelihood of Ideal levels of body mass index, physical activity, and fasting blood glucose levels. Nativity and time in the United States modified the association between SSS and Ideal smoking. Conclusions Subjective measures of social status can enhance an understanding of CVH among Hispanic/Latino people. Future studies should explore the stability of SSS over time in comparison with objective social status and the mechanisms through which SSS may influence CVH.

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DNA methylation aging clocks and pancreatic cancer risk: Pooled analysis of three prospective nested case-control studies

10.1101/2020.01.30.20019174 ◽

2020 ◽

Cited By ~ 1

Author(s):

Mei Chung ◽

Mengyuan Ruan ◽

Naisi Zhao ◽

Devin C. Koestler ◽

Immaculata De Vivo ◽

...

Keyword(s):

Pancreatic Cancer ◽

Dna Methylation ◽

Cancer Risk ◽

Dose Response ◽

The United States ◽

Pooled Analysis ◽

Health Study ◽

Pancreatic Cancer Risk ◽

Epigenetic Age ◽

Epigenetic Age Acceleration

Structured AbstractBackgroundPancreatic cancer is projected to become the second leading cause of cancer-related death by 2030 in the United States. DNA methylation (DNAm) age may reflect age-related variations in the biological changes and abnormalities related to cancer development.MethodWe conducted a pooled analysis using prediagnostic blood samples of pancreatic cancer cases and matched controls selected from the Nurses’ Health Study (NHS), the Physician’s Health Study (PHS), and the Health Professionals Follow-up Study (HPFS). We used three DNAm aging clocks (Hannum, Horvath, and PhenoAge) to estimate subjects’ DNAm age, epigenetic age acceleration (AA) and intrinsic epigenetic age acceleration (IEAA) metrics. We performed conditional logistic regression and multivariable Cox proportional hazard regression to examine associations between six AA and IEAA metrics and risk of pancreatic cancer and survival, respectively.ResultsA total of 393 incidence pancreatic cancer cases and 431 matched controls from the NHS, PHS, and HPFS cohorts were included in this analysis. The medians of all three epigenetic AA and three IEAA metrics were consistently above zero (indicating accelerated age) among cases, while they were below zero (indicating decelerated age) among the matched controls. Comparing participants in the highest quartile of age acceleration metrics, the pancreatic cancer risks were significantly increased by 67% to 83% for Hannum and PhenoAge AA or IEAA metrics with minimal of 7- to 9-years accelerated ages. Except for Hovarth AA and IEAA metrics, there were significant dose-response trends, such that higher age accelerations were associated with higher pancreatic cancer risk, but the relationships were nonlinear. Stratified analyses showed heterogeneous associations, varying by participants’ characteristics and by epigenetic AA or IEAA metrics. As time to diagnosis increased, the ORs of pancreatic cancer for the Hannum AA and Horvath AA or IEAA metrics trended upwards, while the ORs for the PhenoAge AA or IEAA and Hannum IEAA metrics trended downward. Overall, we observed no significant association between pancreatic cancer survival and any of the prediagnostic epigenetic AA or IEAA metrics.ConclusionOur results indicate DNAm age acceleration is associated with an increased risk of pancreatic cancer in a nonlinear, dose-response manner. Epigenetic IEAA metrics may be a useful addition to current methods for pancreatic cancer risk prediction.

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Epigenetic Age Acceleration Reflects Long-Term Cardiovascular Health

Circulation Research ◽

10.1161/circresaha.121.318965 ◽

2021 ◽

Author(s):

Brian Joyce ◽

Tao Gao ◽

Yinan Zheng ◽

Jiantao Ma ◽

Shih-Jen Hwang ◽

...

Keyword(s):

Blood Pressure ◽

Dna Methylation ◽

Cardiovascular Health ◽

Clinical Score ◽

Chronological Age ◽

Cvd Risk ◽

Cross Sectional ◽

Age Related ◽

Epigenetic Aging ◽

Epigenetic Age

Rationale: Epigenetic aging is a novel measure of biological age, reflecting exposures and disease risks independent of chronological age. It may serve as a useful biomarker of cardiovascular health (CVH) and/or cardiovascular disease (CVD) risk for early detection or prevention. Objective: To examine associations between GrimAge acceleration (GrimAA), a measure of epigenetic aging calculated from the residuals of GrimAge regressed on chronological age, and two repeated CVH measures: a full score for the AHA "Life's Simple 7" (diet, smoking, physical activity, BMI, blood pressure, total cholesterol, and glucose) and a clinical CVH score (BMI, blood pressure, cholesterol, and glucose). Methods and Results: We used Illumina array DNA methylation data from two prospective cohort studies: The Coronary Artery Risk Development in Young Adults (CARDIA) study and Framingham Heart Study (FHS), to calculate GrimAA and model associations with CVH. CARDIA randomly selected 1,118 participants for assays at Y15 (2000-2001; mean age 40) and/or Y20 (2005-2006); in FHS, 2,106 Offspring participants had DNA methylation measured at exam 8 (2005-2008; mean age 66). We examined multiple cross-sectional and longitudinal models of GrimAA and each CVH score measured at CARDIA Y0-Y20 and FHS exams 7-8. In CARDIA clinical CVH score from Y0-Y20 was associated with Y15 and Y20 GrimAA (β range -0.41 to -0.21 years per 1-point increase in CVH; p range <0.01 to 0.01), as was full score (β range -0.65 to -0.67 years; p<0.01 for all). These findings were validated in FHS (clinical score β range -0.51 to -0.54 years; full score β range -0.76 to -0.83 years; p<0.01 for all). Conclusions: Our data demonstrate that faster GrimAA is associated with the loss of CVH from young age. Epigenetic age may be a useful biomarker of CVD risk and provides biological insight into the role of epigenetic mechanisms linking age-related CVH loss and CVD.

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Associations Between Blood Pressure and Accelerated DNA Methylation Aging

Journal of the American Heart Association ◽

10.1161/jaha.121.022257 ◽

2022 ◽

Author(s):

Lili Xiao ◽

Gaohui Zan ◽

Chaoqun Liu ◽

Xia Xu ◽

Longman Li ◽

...

Keyword(s):

Blood Pressure ◽

Dna Methylation ◽

Systolic Blood Pressure ◽

Pulse Pressure ◽

Chronological Age ◽

Cross Sectional ◽

High Systolic Blood Pressure ◽

Aging Rate ◽

Epigenetic Age ◽

Epigenetic Age Acceleration

Background Individuals of the same chronological age may exhibit diverse susceptibilities to death. However, few studies have investigated the associations between blood pressure and the accelerated aging. Methods and Results A cross‐sectional study was conducted in 288 adults aged ≥50 years. We assessed the DNA methylation‐based measures of biological age using CpG sites on the Illumina HumanMethylationEPIC BeadChip. Epigenetic age acceleration metrics were derived by regressing residuals (ΔAge) and ratios (aging rate) of DNA methylation age on chronological age. Dose‐response relationships between blood pressure and epigenetic age acceleration were quantified using multiple linear regression and restricted cubic regression models. We found that each 10–mm Hg increase in systolic blood pressure was associated with 0.608 (95% CI, 0.231–0.984) years increase in ΔAge and 0.007 (95% CI, 0.002–0.012) increase in aging rate; meanwhile, for pulse pressure, the increase was 1.12 (95% CI, 0.625–1.61) years for ΔAge and 0.013 (95% CI, 0.007–0.020) for aging rate. Subgroup analysis showed that the significant associations of systolic blood pressure and pulse pressure with epigenetic age acceleration appeared to be limited to women, although interactions between blood pressure and sex were not significant ( P values for interaction >0.05). The combination of women and hypertension was associated with a much higher increase in ΔAge (β [95% CI], 4.05 [1.07–7.02]) and aging rate (β [95% CI], 0.047 [0.008–0.087]), compared with male participants without hypertension. Conclusions Our findings suggested that high systolic blood pressure and pulse pressure were associated with the epigenetic age acceleration, providing important clues for relationships between blood pressure and epigenetic aging.

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Accelerated Epigenetic Age in Normal Cognitive Aging of Korean Community-Dwelling Older Adults

Biological Research For Nursing ◽

10.1177/1099800420983896 ◽

2021 ◽

pp. 109980042098389

Author(s):

Jongmin Park ◽

Chang Won Won ◽

Leorey N. Saligan ◽

Youn-Jung Kim ◽

Yoonju Kim ◽

...

Keyword(s):

Older Adults ◽

Dna Methylation ◽

Cognitive Function ◽

Cognitive Aging ◽

Community Dwelling ◽

Test Results ◽

Cohen’S D ◽

Epigenetic Age ◽

Epigenetic Age Acceleration ◽

Community Dwelling Older Adults

Background: Epigenetic age acceleration has been studied as a promising biomarker of age-related conditions, including cognitive aging. This pilot study aims to explore potential cognitive aging-related biomarkers by investigating the relationship of epigenetic age acceleration and cognitive function and by examining the epigenetic age acceleration differences between successful cognitive aging (SCA) and normal cognitive aging (NCA) among Korean community-dwelling older adults (CDOAs). Methods: We used data and blood samples of Korean CDOAs from the Korean Frailty and Aging Cohort Study. The participants were classified into two groups, SCA (above the 50th percentile in all domains of cognitive function) and NCA. The genome-wide DNA methylation profiling array using Illumina Infinium MethylationEPIC BeadChip was used to calculate the following: the DNA methylation age, universal epigenetic age acceleration, intrinsic epigenetic age acceleration (IEAA), and extrinsic epigenetic age acceleration (EEAA). We also used Pearson correlation analysis and independent t-tests to analyze the data. Results: Universal age acceleration correlated with the Frontal Assessment Battery test results ( r = −0.42, p = 0.025); the EEAA correlated with the Word List Recognition test results ( r = −0.41, p = 0.027). There was a significant difference between SCA and NCA groups in IEAA ( p = 0.041, Cohen’s d = 0.82) and EEAA ( p = 0.042, Cohen’s d = 0.78). Conclusions: Epigenetic age acceleration can be used as a biomarker for early detection of cognitive decline in Korean community-dwelling older adults. Large longitudinal studies are warranted.

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Abstract P003: Distribution of Ideal Cardiovascular Health Metrics in US and Non-US populations: A Meta-Analysis of Proportions

Circulation ◽

10.1161/circ.131.suppl_1.p003 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Adnan Younus ◽

Ehimen Aneni ◽

Oluseye Ogunmoroti ◽

Omar Jamal ◽

Shozab Ali ◽

...

Keyword(s):

American Heart Association ◽

Cardiovascular Health ◽

American Heart ◽

Meta Analysis ◽

Heart Association ◽

The United States ◽

Free Text ◽

Significant Heterogeneity ◽

Ideal Cardiovascular Health ◽

Us Studies

Introduction: With the development of new health metrics to define ideal cardiovascular health (CVH), several studies have examined the distribution of the American Heart Association (AHA) 2020 ideal CVH metrics both within and outside the United States (US). In this meta-analysis of proportions, we synthesized available data on ideal CVH metrics distribution in US cohorts and compared them with non-US populations. Methods: A MEDLINE database search was conducted using relevant free text terms such as “life’s simple 7”, “AHA 2020”, “American Heart Association 2020” and “ideal cardiovascular health” between January 2000 and October 2014. Studies were included in the meta-analysis if the proportions achieving ideal for 0, 1, 2, 3, 4, 5 or ≥6 ideal CVH metrics were known or could be estimated. A meta-analysis of proportions was conducted for US and non-US studies using a random effect model (REM). REM models were chosen because of the significant heterogeneity among studies. Results: Overall the pooled data consisted of 10 US cohorts with a total population of 94,761 participants and 6 non-US cohorts with a total of 130,242 participants. The table shows the pooled prevalence of ideal CVH factors in this population. Overall the pooled estimates of US cohorts showed 15% had 0-1 ideal CVH metrics (inter-study range: 7-22%), while 3% (inter-study range: 1-10%) had 6-7 ideal CVH metrics. This is comparable to 12% (inter-study range 1-17%) and 2% (inter-study range: 1-12%) for 0-1 and 6-7 ideal CVH metrics in the non-US studies. Conclusion: The proportion of persons achieving 6 or more ideal CVH metrics in both US and non-US cohorts is very low and the distribution of CVH metrics is similar in both US and non-US populations. Considering the strong association with worse outcomes, a coordinated global effort at improving CVH should be considered a priority.

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Epigenetic Age Acceleration and Hearing: Observations From the Baltimore Longitudinal Study of Aging

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.790926 ◽

2021 ◽

Vol 13 ◽

Author(s):

Pei-Lun Kuo ◽

Ann Zenobia Moore ◽

Frank R. Lin ◽

Luigi Ferrucci

Keyword(s):

Dna Methylation ◽

Longitudinal Study ◽

Smoking History ◽

Future Research ◽

Age Related ◽

Epigenetic Age ◽

Epigenetic Age Acceleration ◽

Baltimore Longitudinal Study ◽

Age Related Hearing Loss ◽

The Relationship

Objectives: Age-related hearing loss (ARHL) is highly prevalent among older adults, but the potential mechanisms and predictive markers for ARHL are lacking. Epigenetic age acceleration has been shown to be predictive of many age-associated diseases and mortality. However, the association between epigenetic age acceleration and hearing remains unknown. Our study aims to investigate the relationship between epigenetic age acceleration and audiometric hearing in the Baltimore Longitudinal Study of Aging (BLSA).Methods: Participants with both DNA methylation and audiometric hearing measurements were included. The main independent variables are epigenetic age acceleration measures, including intrinsic epigenetic age acceleration—“IEAA,” Hannum age acceleration—“AgeAccelerationResidualHannum,” PhenoAge acceleration—“AgeAccelPheno,” GrimAge acceleration—“AgeAccelGrim,” and methylation-based pace of aging estimation—“DunedinPoAm.” The main dependent variable is speech-frequency pure tone average. Linear regression was used to assess the association between epigenetic age acceleration and hearing.Results: Among the 236 participants (52.5% female), after adjusting for age, sex, race, time difference between measurements, cardiovascular factors, and smoking history, the effect sizes were 0.11 995% CI: (–0.00, 0.23), p = 0.054] for Hannum’s clock, 0.08 [95% CI: (–0.03, 0.19), p = 0.143] for Horvath’s clock, 0.10 [95% CI: (–0.01, 0.21), p = 0.089] for PhenoAge, 0.20 [95% CI: (0.06, 0.33), p = 0.004] for GrimAge, and 0.21 [95% CI: (0.09, 0.33), p = 0.001] for DunedinPoAm.Discussion: The present study suggests that some epigenetic age acceleration measurements are associated with hearing. Future research is needed to study the potential subclinical cardiovascular causes of hearing and to investigate the longitudinal relationship between DNA methylation and hearing.

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Per- and polyfluoroalkyl substances, epigenetic age and DNA methylation: a cross-sectional study of firefighters

Epigenomics ◽

10.2217/epi-2021-0225 ◽

2021 ◽

Author(s):

Jaclyn M Goodrich ◽

Miriam M Calkins ◽

Alberto J Caban-Martinez ◽

Todd Stueckle ◽

Casey Grant ◽

...

Keyword(s):

Dna Methylation ◽

Cross Sectional Study ◽

Serum Concentrations ◽

Sectional Study ◽

Cross Sectional ◽

Toxicity Biomarkers ◽

Epigenetic Age ◽

Polyfluoroalkyl Substances ◽

Blood Leukocyte ◽

Epic Array

Background: Per- and polyfluoroalkyl substances (PFASs) are persistent chemicals that firefighters encounter. Epigenetic modifications, including DNA methylation, could serve as PFASs toxicity biomarkers. Methods: With a sample size of 197 firefighters, we quantified the serum concentrations of nine PFASs, blood leukocyte DNA methylation and epigenetic age indicators via the EPIC array. We examined the associations between PFASs with epigenetic age, site- and region-specific DNA methylation, adjusting for confounders. Results: Perfluorohexane sulfonate, perfluorooctanoate (PFOA) and the sum of branched isomers of perfluorooctane sulfonate (Sm-PFOS) were associated with accelerated epigenetic age. Branched PFOA, linear PFOS, perfluorononanoate, perfluorodecanoate and perfluoroundecanoate were associated with differentially methylated loci and regions. Conclusion: PFASs concentrations are associated with accelerated epigenetic age and locus-specific DNA methylation. The implications for PFASs toxicity merit further investigation.

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Evaluation of Cardiovascular Variables in a Calchaquí Population in the Middle and High Mountains of Tucumán

10.7775/rac.v89.i1.19095 ◽

2021 ◽

Vol 89 (1) ◽

pp. 20-26

Author(s):

Sebastián Galdeano ◽

Damián Holownia ◽

Darío Palavecino ◽

José Daniel Abregú ◽

María Silvina Rivas Jordan ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Health ◽

Posterior Wall ◽

Left Ventricular ◽

High Mountains ◽

Urban Centers ◽

Cross Sectional ◽

The Third ◽

Posterior Wall Thickness ◽

Cardiovascular Morbidity And Mortality

Background: The Quilmes community includes 2,400 inhabitants of the middle and high mountains of Tucumán (1,800 to 4,000 meters above sea level). The purpose of the present study was to know their cardiovascular health status. Methods: A cross-sectional descriptive quantitative investigation was carried out in people belonging to the Quilmes community who voluntarily attended the planned evaluation on September 27-29, 2018. Results: Two hundred and two settlers were studied (125 women and 77 men; 48±1.4 years), 23% of them had hypertension (HTN); 14% were smokers; 4.9% had diabetes; 18% had dyslipidemia (DLP) and 25% usually consumed alcohol (1.0 ± 0.4 L/day). Also, 29% were overweight and 36% obese. High blood pressure (BP) was recorded in 48 individuals at the time of the study. Blood pressure decreased in the third compared to the first measurement, whereas heart rate increased in the third assessment (74±1 beats per minute vs. 77±1; p <0.01). Oxygen saturation (95.0±0.2%) was negatively correlated with age (Pearson r: -0.266; p <0.001). In individuals with normal BP, ultrasound E/ratio was higher (1.2±0.0) and left ventricular posterior wall thickness was lower (8.5±0.5 mm) than in those with elevated BP (0.92±0.1 and 9.0±0.3, respectively, p <0.001). Twenty-four percent of individuals had atherosclerotic plaques and 120 had DLP. Conclusions: The Quilmes population presents a prevalence of cardiovascular risk factors similar to that of urban centers, which could lead to an increase in cardiovascular morbidity and mortality in the coming years

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