Reproductive history and blood cell DNA methylation later in life: the Young Finns Study

Abstract Background Women with a history of complications of pregnancy, including hypertensive disorders, gestational diabetes or an infant fetal growth restriction or preterm birth, are at higher risk for cardiovascular disease later in life. We aimed to examine differences in maternal DNA methylation following pregnancy complications. Methods Data on women participating in the Young Finns study (n = 836) were linked to the national birth registry. DNA methylation in whole blood was assessed using the Infinium Methylation EPIC BeadChip. Epigenome-wide analysis was conducted on differential CpG methylation at 850 K sites. Reproductive history was also modeled as a predictor of four epigenetic age indices. Results Fourteen significant differentially methylated sites were found associated with both history of pre-eclampsia and overall hypertensive disorders of pregnancy. No associations were found between reproductive history and any epigenetic age acceleration measure. Conclusions Differences in epigenetic methylation profiles could represent pre-existing risk factors, or changes that occurred as a result of experiencing these complications.

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Association of cardiovascular health and epigenetic age acceleration

Clinical Epigenetics ◽

10.1186/s13148-021-01028-2 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Tess D. Pottinger ◽

Sadiya S. Khan ◽

Yinan Zheng ◽

Wei Zhang ◽

Hilary A. Tindle ◽

...

Keyword(s):

Dna Methylation ◽

Cardiovascular Health ◽

Heart Association ◽

The United States ◽

Cross Sectional ◽

Epigenetic Age ◽

Younger Age ◽

Cardiovascular Morbidity And Mortality ◽

Epigenetic Age Acceleration ◽

Linear Regression Modeling

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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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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Risk of post-pregnancy hypertension in women with a history of hypertensive disorders of pregnancy: nationwide cohort study

BMJ ◽

10.1136/bmj.j3078 ◽

2017 ◽

pp. j3078 ◽

Cited By ~ 77

Author(s):

Ida Behrens ◽

Saima Basit ◽

Mads Melbye ◽

Jacob A Lykke ◽

Jan Wohlfahrt ◽

...

Keyword(s):

Cohort Study ◽

Hypertensive Disorders Of Pregnancy ◽

Pregnancy Hypertension ◽

Hypertensive Disorders ◽

History Of

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Cardiovascular risk model performance in women with and without hypertensive disorders of pregnancy

Heart ◽

10.1136/heartjnl-2018-313439 ◽

2018 ◽

Vol 105 (4) ◽

pp. 330-336 ◽

Cited By ~ 3

Author(s):

Veerle Dam ◽

N Charlotte Onland-Moret ◽

W M Monique Verschuren ◽

Jolanda M A Boer ◽

Laura Benschop ◽

...

Keyword(s):

Risk Model ◽

Model Performance ◽

Predictive Performance ◽

Baseline Risk ◽

Hypertensive Disorders Of Pregnancy ◽

Cvd Risk ◽

Hypertensive Disorders ◽

Framingham Risk ◽

History Of ◽

Score Model

ObjectivesCompare the predictive performance of Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs) and Systematic COronary Risk Evaluation (SCORE) model between women with and without a history of hypertensive disorders of pregnancy (hHDP) and determine the effects of recalibration and refitting on predictive performance.MethodsWe included 29 751 women, 6302 with hHDP and 17 369 without. We assessed whether models accurately predicted observed 10-year cardiovascular disease (CVD) risk (calibration) and whether they accurately distinguished between women developing CVD during follow-up and not (discrimination), separately for women with and without hHDP. We also recalibrated (updating intercept and slope) and refitted (recalculating coefficients) the models.ResultsOriginal FRS and PCEs overpredicted 10-year CVD risks, with expected:observed (E:O) ratios ranging from 1.51 (for FRS in women with hHDP) to 2.29 (for PCEs in women without hHDP), while E:O ratios were close to 1 for SCORE. Overprediction attenuated slightly after recalibration for FRS and PCEs in both hHDP groups. Discrimination was reasonable for all models, with C-statistics ranging from 0.70-0.81 (women with hHDP) and 0.72–0.74 (women without hHDP). C-statistics improved slightly after refitting 0.71–0.83 (with hHDP) and 0.73–0.80 (without hHDP). The E:O ratio of the original PCE model was statistically significantly better in women with hHDP compared with women without hHDP.ConclusionsSCORE performed best in terms of both calibration and discrimination, while FRS and PCEs overpredicted risk in women with and without hHDP, but improved after recalibrating and refitting the models. No separate model for women with hHDP seems necessary, despite their higher baseline risk.

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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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Annual body mass index gain and risk of hypertensive disorders of pregnancy in a subsequent pregnancy

Scientific Reports ◽

10.1038/s41598-021-01976-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sho Tano ◽

Tomomi Kotani ◽

Takafumi Ushida ◽

Masato Yoshihara ◽

Kenji Imai ◽

...

Keyword(s):

Body Mass Index ◽

Weight Gain ◽

Body Mass ◽

Body Weight Gain ◽

Subsequent Pregnancy ◽

The Body ◽

Hypertensive Disorders Of Pregnancy ◽

Hypertensive Disorders ◽

Age Related ◽

History Of

AbstractWeight gain during interpregnancy period is related to hypertensive disorders of pregnancy (HDP). However, in interpregnancy care/counseling, the unpredictability of the timing of the next conception and the difficulties in preventing age-related body weight gain must be considered while setting weight management goals. Therefore, we suggest considering the annual change in the body mass index (BMI). This study aimed to clarify the association between annual BMI changes during the interpregnancy period and HDP risk in subsequent pregnancies. A multicenter retrospective study of data from 2009 to 2019 examined the adjusted odds ratio (aOR) of HDP in subsequent pregnancies. The aORs in several annual BMI change categories were also calculated in the subgroups classified by HDP occurrence in the index pregnancy. This study included 1,746 pregnant women. A history of HDP (aOR, 16.76; 95% confidence interval [CI], 9.62 − 29.22), and annual BMI gain (aOR, 2.30; 95% CI, 1.76 − 3.01) were independent risk factors for HDP in subsequent pregnancies. An annual BMI increase of ≥ 1.0 kg/m2/year was related to HDP development in subsequent pregnancies for women without a history of HDP. This study provides data as a basis for interpregnancy care/counseling, but further research is necessary to validate our findings and confirm this relationship.

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Left ventricular mass and myocardial scarring in women with hypertensive disorders of pregnancy

Open Heart ◽

10.1136/openhrt-2020-001273 ◽

2020 ◽

Vol 7 (2) ◽

pp. e001273

Author(s):

Odayme Quesada ◽

Ki Park ◽

Janet Wei ◽

Eileen Handberg ◽

Chrisandra Shufelt ◽

...

Keyword(s):

Vascular Dysfunction ◽

Obstructive Coronary Artery Disease ◽

Left Ventricular ◽

Hypertensive Disorders Of Pregnancy ◽

Similar Frequency ◽

Hypertensive Disorders ◽

Lv Mass ◽

Scar Size ◽

History Of ◽

And Function

AimsHypertensive disorders of pregnancy (HDP) predict future cardiovascular events. We aim to investigate relations between HDP history and subsequent hypertension (HTN), myocardial structure and function, and late gadolinium enhancement (LGE) scar.Methods and resultsWe evaluated a prospective cohort of women with suspected ischaemia with no obstructive coronary artery disease (INOCA) who underwent stress/rest cardiac magnetic resonance imaging (cMRI) with LGE in the Women’s Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction study. Self-reported history of pregnancy and HDP (gestational HTN, pre-eclampsia, toxaemia and eclampsia) were collected at enrollment. In our cohort of 346, 20% of women report a history of HDP. HDP history was associated with 3.2-fold increased odds of HTN. Women with a history of both HDP and HTN had higher cMRI measured left ventricular (LV) mass compared with women with HDP only (99.4±2.6 g vs 87.7±3.2 g, p=0.02). While we found a similar frequency of LGE scar, we observed a trend towards increased LGE scar size (5.1±3.4 g vs 8.0±3.4 g, p=0.09) among the women with HDP history compared to women without.ConclusionIn a high-risk cohort of women with suspected INOCA, 20% had a history of HDP. Women with HDP history were more likely to develop HTN. Our study demonstrates higher LV mass in women with HDP and concomitant HTN. Although the presence of LGE scar was not different in women with and without HDP history, we observed a trend towards larger scar size in women with HDP. Future studies are needed to better assess the relationship of HDP and cardiac morphology and LGE scarring in a larger cohort of women.

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Intrinsic and extrinsic epigenetic age acceleration are associated with hypertensive target organ damage in older African Americans

BMC Medical Genomics ◽

10.1186/s12920-019-0585-5 ◽

2019 ◽

Vol 12 (1) ◽

Author(s):

Jennifer A. Smith ◽

Jeremy Raisky ◽

Scott M. Ratliff ◽

Jiaxuan Liu ◽

Sharon L. R. Kardia ◽

...

Keyword(s):

Blood Pressure ◽

Dna Methylation ◽

African Americans ◽

Target Organ Damage ◽

Organ Damage ◽

Left Ventricular ◽

Effect Modification ◽

Target Organ ◽

Epigenetic Age ◽

Epigenetic Age Acceleration

Abstract Background Epigenetic age acceleration, a measure of biological aging based on DNA methylation, is associated with cardiovascular mortality. However, little is known about its relationship with hypertensive target organ damage to the heart, kidneys, brain, and peripheral arteries. Methods We investigated associations between intrinsic (IEAA) or extrinsic (EEAA) epigenetic age acceleration, blood pressure, and six types of organ damage in a primarily hypertensive cohort of 1390 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. DNA methylation from peripheral blood leukocytes was collected at baseline (1996–2000), and measures of target organ damage were assessed in a follow-up visit (2000–2004). Linear regression with generalized estimating equations was used to test for associations between epigenetic age acceleration and target organ damage, as well as effect modification of epigenetic age by blood pressure or sex. Sequential Oligogenic Linkage Analysis Routines (SOLAR) was used to test for evidence of shared genetic and/or environmental effects between epigenetic age acceleration and organ damage pairs that were significantly associated. Results After adjustment for sex, chronological age, and time between methylation and organ damage measures, higher IEAA was associated with higher urine albumin to creatinine ratio (UACR, p = 0.004), relative wall thickness (RWT, p = 0.022), and left ventricular mass index (LVMI, p = 0.007), and with lower ankle-brachial index (ABI, p = 0.014). EEAA was associated with higher LVMI (p = 0.005). Target organ damage associations for all but IEAA with LVMI remained significant after further adjustment for blood pressure and antihypertensive use (p < 0.05). Further adjustment for diabetes attenuated the IEAA associations with UACR and RWT, and adjustment for smoking attenuated the IEAA association with ABI. No effect modification by age or sex was observed. Conclusions Measures of epigenetic age acceleration may help to better characterize the functional mechanisms underlying organ damage from cellular aging and/or hypertension. These measures may act as subclinical biomarkers for damage to the kidney, heart, and peripheral vasculature; however more research is needed to determine whether these relationships remain independent of lifestyle factors and comorbidities.

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