Guang Hao

Blood Pressure Trajectories From Childhood to Young Adulthood Associated With Cardiovascular Risk: Results From the 23-Year Longitudinal Georgia Stress and Heart Study

The purpose of this study is to identify subgroups of individuals with similar trajectories in blood pressure (BP) from childhood to young adulthood and to determine the relationship of BP trajectories with carotid intima–media thickness (IMT) and left ventricular mass index (LVMI). BP was measured ⩽16 times during a 23-year period in 683 participants from childhood to young adulthood. IMT and LVMI were measured in 551 participants and 546 participants, respectively. Using latent class models, 3 trajectory groups in BP from childhood to young adulthood were identified, including high-increasing, moderate-increasing, and low-increasing groups. We found that trajectory of systolic BP was a significant predictor of both IMT and LVMI with increased rate of growth in systolic BP associated with higher levels of IMT and LVMI (Pfor trend <0.001). Similar to the BP trajectory groups from childhood to young adulthood, 3 trajectory groups in BP during childhood (⩽18 years) were identified, and participants in the high-increasing group had thicker IMT (P<0.001) and increased LVMI (P=0.043) in comparison with those in the low-increasing group. Results were similar for mid-BP trajectories but not for diastolic BP trajectories. Our results suggested that different BP trajectories exist from childhood to young adulthood, and the trajectories were independently associated with IMT and LVMI. We, for the first time, reported the association between systolic BP trajectories derived from childhood with subclinical cardiovascular risk in young adulthood, indicating that monitoring trajectories of BP from childhood may help identify a high cardiovascular risk population in early life.

The role of DNA methylation in the association between childhood adversity and cardiometabolic disease

Growing evidence suggests that adverse environmental stimuli, especially during sensitive periods in early life, may lead to cardiometabolic disease in later life. However, the underlying biological mechanisms remain a mystery. Recent studies inferred that epigenetic modifications are likely involved. We review recent studies, primarily focused on the findings from human studies, to indicate the role of DNA methylation in the associations between childhood adversity and cardiometabolic disease in adulthood. In particular, we focused on DNA methylation modifications in genes regulating the hypothalamus-pituitary-adrenal axis as well as the immune system.

Racial/ethnic differences in the association of childhood adversities with depression and the role of resilience

BACKGROUND Adverse childhood experiences (ACE) including childhood abuse and trauma increase depressive symptoms. The role of resilience and how it interacts with both ACEs and the potential development of depressive symptoms, including how race and ethnicity moderate these effects, are much less studied. The aims of this study were to examine: 1) whether there is a dose-response relationship between trauma and depressive symptoms; 2) whether early trauma affected European Americans (EA) and African Americans (AA) in a similar fashion; and 3) whether resilience mitigates the effect of trauma. METHODS The present study comprised a cross-sectional study of subjects from a longitudinal cohort. All subjects were 19 years or older with traumatic experiences prior to age 18. Subjects were assessed for depressive symptoms as well as resilience. RESULTS In 413 subjects enrolled, ACEs were significantly associated with depression severity in a dose-response fashion (p<0.001). Notably, AAs had lower depression scores at low to moderate levels of ACEs than EAs, but reported comparable levels of depression with severe exposure to ACEs (pInteraction=0.05). In both EAs and AAs, young adults with high and medium levels of resilience showed less depressive symptoms compared to those with low resilience (p<0.05). LIMITATIONS to consider are the cross-sectional design, possibility of other confounders, and potential for recall bias of this study. CONCLUSION While ACEs were significantly associated with severity of depression in a dose-response fashion, higher resilience mitigated the impact of childhood adversities on depressive symptoms in young adults. The results are encouraging, and guides research for therapeutics to boost resilience.

The Effects of Trauma, with or without PTSD, on the Transgenerational DNA Methylation Alterations in Human Offsprings

Exposure to psychological trauma is a strong risk factor for several debilitating disorders including post-traumatic stress disorder (PTSD) and depression. Besides the impact on mental well-being and behavior in the exposed individuals, it has been suggested that psychological trauma can affect the biology of the individuals, and even have biological and behavioral consequences on the offspring of exposed individuals. While knowledge of possible epigenetic underpinnings of the association between exposure to trauma and risk of PTSD has been discussed in several reviews, it remains to be established whether trauma-induced epigenetic modifications can be passed from traumatized individuals to subsequent generations of offspring. The aim of this paper is to review the emerging literature on evidence of transgenerational inheritance due to trauma exposure on the epigenetic mechanism of DNA methylation in humans. Our review found an accumulating amount of evidence of an enduring effect of trauma exposure to be passed to offspring transgenerationally via the epigenetic inheritance mechanism of DNA methylation alterations and has the capacity to change the expression of genes and the metabolome. This manuscript summarizes and critically reviews the relevant original human studies in this area. Thus, it provides an overview of where we stand, and a clearer vision of where we should go in terms of future research directions.

Epigenome‐Wide Association Study of Dietary Fiber Intake in African American Adolescents

SCOPE Low fiber intake is associated with increased risk for cardiovascular disease (CVD) and cancer. However, the underlying mechanisms are not well understood. Two hypotheses are tested: 1) dietary fiber would be associated with DNA methylation levels; 2) those DNA methylation changes would be associated with visceral adiposity and inflammation. Also the possibility that the associations between fiber and DNA methylation levels might be confounded with folic acid intake as sensitivity analysis are explored. METHODS AND RESULTS An epigenome-wide association study is conducted using Illumina 450K Bead-Chip on leukocyte DNA in 284 African American adolescents. Linear regression is performed to identify differentially methylated CpG sites associated with fiber. The methylation levels of 3 CpG sites (cg15200711, cg19462022, and cg07035602) in LPCAT1 and RASA3 genes are associated with fiber (false discovery rate [FDR] < 0.05) after adjustment for covariates including folic acid. The methylation levels of cg07035602 and cg19462022 are also associated with visceral adiposity and inflammation. CONCLUSIONS The data show that DNA methylation levels at LPCAT1 and RASA3 genes are associated with dietary fiber intake as well as with adiposity and inflammation. Future studies are warranted to determine whether epigenetic regulation may underlie the beneficial effects of fiber intake on adiposity and inflammation.

Body mass index trajectories in childhood is predictive of cardiovascular risk: Results from the 23-year longitudinal georgia stress and heart study

The childhood high body mass index (BMI) is associated with cardiovascular risk, but the association between childhood BMI trajectory patterns and cardiovascular risk remains unclear. The purposes of this study are to identify subgroups of individuals with similar trajectories in BMI during childhood, and to determine the relationship of childhood BMI trajectories with subclinical cardiovascular disease in young adulthood, indexed by intima-media thickness (IMT) and left ventricular mass index (LVMI). The participants were from the Georgia Stress and Heart (GSH) study. A total of 626 participants with BMI measured 3–12 times during childhood (5–18 years old) were included. By using latent class models, three trajectory groups in BMI were identified, including high increasing (HI), moderate increasing (MI) and normal group. We found that childhood trajectory of BMI was significantly associated with IMT and LVMI in young adulthood even after adjustment for BMI in young adulthood. Our results suggested that different BMI trajectory patterns exist during childhood. We for the first time reported the association between childhood BMI trajectory patterns and subclinical cardiovascular risk in young adulthood, indicating that monitoring trajectories of BMI from childhood may help to identify a high cardiovascular risk population in early life.

A national study of the prevalence and risk factors associated with peripheral arterial disease from China: The China Hypertension Survey, 2012–2015

BACKGROUND Peripheral arterial disease (PAD) is the third leading cause of atherosclerotic vascular morbidity after coronary heart disease and stroke. Epidemiology data of PAD is very limited in low-income and middle-income countries. A national wide survey was conducted from October 2012 to December 2015 to assess the prevalence of PAD in China. METHODS Data from the China Hypertension Survey (CHS). In total, 56,000 people aged 35 years or older were enrolled in this sub-survey for PAD, and 30,025 participants were eligible for analysis. Ankle-brachial index was measured using an automated ABI device (WatchBP Office device Microlife, China). PAD was defined by ABI and Edinburgh Claudication Questionnaire. RESULTS AND CONCLUSIONS Overall, 6.6% (estimated 45.3 million) of the Chinese adult population age 35 years or older had PAD. The weighted prevalence of PAD increased significantly after aged ≥75 years. There were no significant differences in PAD prevalence between urban and rural residents, as well as between males and females. Among individuals with PAD, only 4.9% (95% CI: 0%-10.1%) were aware of their condition, 1.9% (95% CI: 0%-4.0%) received revascularization, and 0.2% (95% CI: 0%-0.4%) achieved ABI >0.9. Older age, Han population, current smokers, education level, hypertension, CAD, diabetes, dyslipidemia, and rural residences all were significantly associated with an increased risk of PAD. In China, there is an increasing prevalence of PAD, but the awareness, treatment, and control were very low. Special attention should be paid to prevent and control PAD in China. CLINICAL TRIAL REGISTRATION NUMBER ChiCTR-ECS-14004641.

An epigenome-wide study of obesity in African American youth and young adults: novel findings, replication in neutrophils, and relationship with gene expression

BackgroundWe conducted an epigenome-wide association study (EWAS) on obesity in healthy youth and young adults and further examined to what extent identified signals influenced gene expression and were independent of cell type composition and obesity-related cardio-metabolic risk factors. Genome-wide DNA methylation data from leukocytes were obtained from 700 African Americans aged 14–36. We also measured genome-wide DNA methylation data from neutrophils as well as genome-wide gene expression data from leukocytes in a subset of samples (n = 188).ResultsThe EWAS identified 76 obesity-related CpG sites in leukocytes with p < 1 × 10−7. In silico replication in the ARIC study of 2097 African Americans aged 47–70 validated 54 CpG sites. Out of the 54 CpG sites, 29 associations with obesity were novel and 37 were replicated in neutrophils. Fifty one CpG sites were associated with at least one cardio-metabolic risk factor; however, the number reduced to 9 after adjustment for obesity. Sixteen CpG sites were associated with expression of 17 genes in cis, of which 5 genes displayed differential expression between obese cases and lean controls. We also replicated 71.5% of obesity-related CpG sites previously reported.ConclusionIn this study of youth and young adults, we identified 29 novel CpG sites associated with obesity and replicated the majority of the CpG sites previously identified. We further demonstrated that the majority of the obesity-related CpG sites in leukocytes were not driven by cell composition or obesity-related cardio-metabolic risk factors. We also provided the direct link between DNA methylation-gene expression-obesity for 5 genes.

Blood Pressure Trajectories From Childhood to Young Adulthood Associated With Cardiovascular Risk

The purpose of this study is to identify subgroups of individuals with similar trajectories in blood pressure (BP) from childhood to young adulthood and to determine the relationship of BP trajectories with carotid intima–media thickness (IMT) and left ventricular mass index (LVMI). BP was measured ⩽16 times during a 23-year period in 683 participants from childhood to young adulthood. IMT and LVMI were measured in 551 participants and 546 participants, respectively. Using latent class models, 3 trajectory groups in BP from childhood to young adulthood were identified, including high-increasing, moderate-increasing, and low-increasing groups. We found that trajectory of systolic BP was a significant predictor of both IMT and LVMI with increased rate of growth in systolic BP associated with higher levels of IMT and LVMI (Pfor trend <0.001). Similar to the BP trajectory groups from childhood to young adulthood, 3 trajectory groups in BP during childhood (⩽18 years) were identified, and participants in the high-increasing group had thicker IMT (P<0.001) and increased LVMI (P=0.043) in comparison with those in the low-increasing group. Results were similar for mid-BP trajectories but not for diastolic BP trajectories. Our results suggested that different BP trajectories exist from childhood to young adulthood, and the trajectories were independently associated with IMT and LVMI. We, for the first time, reported the association between systolic BP trajectories derived from childhood with subclinical cardiovascular risk in young adulthood, indicating that monitoring trajectories of BP from childhood may help identify a high cardiovascular risk population in early life.

Blood Pressure Trajectories From Childhood to Young Adulthood Associated With Cardiovascular RiskNovelty and Significance: Results From the 23-Year Longitudinal Georgia Stress and Heart Study

The purpose of this study is to identify subgroups of individuals with similar trajectories in blood pressure (BP) from childhood to young adulthood and to determine the relationship of BP trajectories with carotid intima–media thickness (IMT) and left ventricular mass index (LVMI). BP was measured ⩽16 times during a 23-year period in 683 participants from childhood to young adulthood. IMT and LVMI were measured in 551 participants and 546 participants, respectively. Using latent class models, 3 trajectory groups in BP from childhood to young adulthood were identified, including high-increasing, moderate-increasing, and low-increasing groups. We found that trajectory of systolic BP was a significant predictor of both IMT and LVMI with increased rate of growth in systolic BP associated with higher levels of IMT and LVMI (Pfor trend <0.001). Similar to the BP trajectory groups from childhood to young adulthood, 3 trajectory groups in BP during childhood (⩽18 years) were identified, and participants in the high-increasing group had thicker IMT (P<0.001) and increased LVMI (P=0.043) in comparison with those in the low-increasing group. Results were similar for mid-BP trajectories but not for diastolic BP trajectories. Our results suggested that different BP trajectories exist from childhood to young adulthood, and the trajectories were independently associated with IMT and LVMI. We, for the first time, reported the association between systolic BP trajectories derived from childhood with subclinical cardiovascular risk in young adulthood, indicating that monitoring trajectories of BP from childhood may help identify a high cardiovascular risk population in early life.