Dianjianyi Sun

An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease.

BackgroundEpigenetic biomarkers of aging (the “epigenetic clock”) have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors.ResultsWe analyzed blood, saliva, and brain samples from seven different racial/ethnic groups. We assessed the intrinsic epigenetic age acceleration of blood (independent of blood cell counts) and the extrinsic epigenetic aging rates of blood (dependent on blood cell counts and tracks the age of the immune system). In blood, Hispanics and Tsimane Amerindians have lower intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African-Americans have lower extrinsic epigenetic aging rates than Caucasians and Hispanics but no differences were found for the intrinsic measure. Men have higher epigenetic aging rates than women in blood, saliva, and brain tissue.ConclusionsEpigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes. These results may help elucidate lower than expected mortality rates observed in Hispanics, older African-Americans, and women.

Impact of Long-Term Burden of Excessive Adiposity and Elevated Blood Pressure From Childhood on Adulthood Left Ventricular Remodeling Patterns : The Bogalusa Heart Study

BACKGROUND Cardiovascular risk factors are associated with left ventricular hypertrophy (LVH), but little is known regarding related impact of longitudinal measures of childhood adiposity and LV hemodynamic variables. OBJECTIVES The aim of this study was to examine the impact of cumulative long-term burden and trends of excessive adiposity and elevated blood pressure (BP) during childhood on adulthood LVH and LV geometric remodeling patterns. METHODS This longitudinal study consisted of 1,061 adults, age 24 to 46 years, who had been examined 4 or more times for body mass index (BMI) and BP starting in childhood, with a mean follow-up of 28.0 years. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI and BP from childhood to adulthood. Four LV geometric types were defined-normal, concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH)-all on the basis of LV mass indexed for body height (m(2.7)) and relative wall thickness. RESULTS Higher values of BMI and systolic and diastolic BP in childhood and adulthood, as well as total AUC and incremental AUC, were all significantly associated with higher LV mass index and LVH, adjusted for race, sex, and age. In addition, higher values of BMI and BP in childhood and adulthood, total AUC, and incremental AUC were significantly associated with EH and CH but not with CR. Importantly, all of these measures of BMI had a consistently and significantly greater influence on EH than did measures of BP. CONCLUSIONS These findings indicate that the adverse influence of excessive adiposity and elevated BP levels on LVH begins in childhood.

Consumption of spicy foods and total and cause specific mortality: population based cohort study

Objective To examine the associations between the regular consumption of spicy foods and total and cause specific mortality. Design Population based prospective cohort study. Setting China Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008. Participants 199 293 men and 288 082 women aged 30 to 79 years at baseline after excluding participants with cancer, heart disease, and stroke at baseline. Main exposure measures Consumption frequency of spicy foods, self reported once at baseline. Main outcome measures Total and cause specific mortality. Results During 3 500 004 person years of follow-up between 2004 and 2013 (median 7.2 years), a total of 11 820 men and 8404 women died. Absolute mortality rates according to spicy food consumption categories were 6.1, 4.4, 4.3, and 5.8 deaths per 1000 person years for participants who ate spicy foods less than once a week, 1 or 2, 3 to 5, and 6 or 7 days a week, respectively. Spicy food consumption showed highly consistent inverse associations with total mortality among both men and women after adjustment for other known or potential risk factors. In the whole cohort, compared with those who ate spicy foods less than once a week, the adjusted hazard ratios for death were 0.90 (95% confidence interval 0.84 to 0.96), 0.86 (0.80 to 0.92), and 0.86 (0.82 to 0.90) for those who ate spicy food 1 or 2, 3 to 5, and 6 or 7 days a week, respectively. Compared with those who ate spicy foods less than once a week, those who consumed spicy foods 6 or 7 days a week showed a 14% relative risk reduction in total mortality. The inverse association between spicy food consumption and total mortality was stronger in those who did not consume alcohol than those who did (P=0.033 for interaction). Inverse associations were also observed for deaths due to cancer, ischemic heart diseases, and respiratory diseases. Conclusion In this large prospective study, the habitual consumption of spicy foods was inversely associated with total and certain cause specific mortality, independent of other risk factors of death.

Association of DNA Methylation at CPT1A Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study

In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10−7 was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6x10-14 and P for cg17058475 = 1.2x10-9). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future.

Temporal Relationship Between Elevated Blood Pressure and Arterial Stiffening Among Middle-Aged Black and White Adults The Bogalusa Heart Study

This study assessed the temporal relationship between elevated blood pressure (BP) and arterial stiffness in a biracial (black-white) cohort of middle-aged adults aged 32-51 years from the semirural community of Bogalusa, Louisiana. Measurements of aortic-femoral pulse wave velocity (afPWV; n = 446) and large- and small-arterial compliance (n = 381) were obtained at 2 time points between 2000 and 2010, with an average follow-up period of 7 years. A cross-lagged path analysis model was used to examine the temporal relationship of elevated BP to arterial stiffness and elasticity. The cross-lagged path coefficients did not differ significantly between blacks and whites. The path coefficient (ρ2) from baseline BP to follow-up afPWV was significantly greater than the path coefficient (ρ1) from baseline afPWV to follow-up BP (ρ2 = 0.20 vs. ρ1 = 0.07 (P = 0.048) for systolic BP; ρ2 = 0.19 vs. ρ1 = 0.05 (P = 0.034) for diastolic BP). The results for this 1-directional path from baseline BP to follow-up afPWV were confirmed, although marginally significant, by using large- and small-artery elasticity measurements. These findings provide strong evidence that elevated BP precedes large-artery stiffening in middle-aged adults. Unlike the case in older adults, the large-arterial wall is not stiff enough in youth to alter BP levels during young adulthood.

Uric Acid Is Associated with Metabolic Syndrome in Children and Adults in a Community: The Bogalusa Heart Study

Background Elevated serum uric acid (UA) is commonly found in subjects with metabolic syndrome (MetS). This study examined the association of UA with levels of individual MetS components and the degree of their clustering patterns in both children and adults. Methods The study sample consisted of 2614 children aged 4–18 years and 2447 adults aged 19–54 years. MetS components included body mass index (BMI), mean arterial pressure (MAP), triglycerides to high-density lipoprotein cholesterol ratio (TG/HDLC), and homeostasis model assessment of insulin resistance (HOMA). Observed/expected (O/E) ratio and intra-class correlation coefficient (ICC) were used as a measure of the degree of clustering of categorical and continuous MetS variables, respectively. Results UA was positively and significantly associated only with BMI in children but with all four components in adults. The odds ratio for MetS associated with 1 mg/dL increase of UA was 1.74 (p<0.001) in children and 1.92 (p<0.001) in adults. O/E ratios showed a significant, increasing trend with increasing UA quartiles in both children and adults for 3- and 4-variable clusters with p-values for trend <0.001, except for BMI-MAP-TG/HDLC and MAP-TG/HDLC-HOMA clusters in children and MAP-TG/HDLC-HOMA cluster in adults. ICCs of 3 and 4 components increased with increasing UA quartiles in children and adults. Conclusions These results indicate that UA may play a role in the development of MetS in both pediatric and adult populations alike, which may aid in the identification and treatment of high risk individuals for MetS and related clinical disorders in early life.

Tobacco smoking strengthens the association of elevated blood pressure with arterial stiffness: the Bogalusa Heart Study.

Objectives: The study assessed the hypothesis that smoking strengthens the association of adult arterial stiffness with long-term cumulative burden of blood pressure (BP) from childhood to adulthood. Backgrounds: Tobacco smoking and elevated BPs are important risk factors of vascular stiffness. However, the synergistic effect of these two risk factors is not well established, especially for the long-term burden of elevated BP since childhood. Methods: The study cohort consisted of 945 adults (661 whites and 284 blacks, aged 24–43 years) who have BP measured 4–15 times since childhood (aged 4–17 years) in Bogalusa, Louisiana. The adult arterial stiffness was measured as aorta–femoral pulse wave velocity (afPWV); the total area under the curve (AUC) and incremental AUC were used as a measure of long-term burden and trends of BP, respectively. Results: Increased adult afPWV was significantly associated with higher adulthood (P < 0.001), total AUC (P < 0.001) and incremental AUC (P < 0.001) values of SBP and DBP, but not with childhood BP, after adjusting for age, race, sex, BMI and heart rate. Furthermore, smoking was a significant predictor of increased adult afPWV and BP levels. In the interaction analyses, the increasing trend of afPWV with increasing adult SBP (P = 0.009) and its incremental AUC (P = 0.007) were significantly greater among the current smokers than among the nonsmokers. DBP showed a similar pattern regarding the smoking–BP interaction on afPWV. Conclusion: These results, by showing the synergistic effect of tobacco smoking and long-term BP measures from childhood to adulthood on arterial stiffening process, underscore the importance of undertaking preventive strategies early in life and smoking behavior control.

Gender-specific association between tobacco smoking and central obesity among 0.5 million Chinese people: the China Kadoorie Biobank Study.

Objectives Lifestyle factors are well-known important modifiable risk factors for obesity; the association between tobacco smoking and central obesity, however, is largely unknown in the Chinese population. This study examined the relationship between smoking and central obesity in 0.5 million Chinese adults, a population with a low prevalence of general obesity, but a high prevalence of central obesity. Subjects A total of 487,527 adults (200,564 males and 286,963 females), aged 30-79 years, were enrolled in the baseline survey of the China Kadoorie Biobank (CKB) Study conducted during 2004-2008. Waist circumference (WC) and WC/height ratio (WHtR) were used as measures of central obesity. Results The prevalence of regular smokers was significantly higher among males (60.6%) than among females (2.2%). The prevalence of central obesity increased with age and BMI levels, with a significant gender difference (females>males). Of note, almost all obese adults (99.4%) were centrally obese regardless of gender. In multivariable regression analyses, adjusting for age, education, physical activity, alcohol use and survey site, regular smoking was inversely associated with BMI in males (standardized regression coefficients, β= -0.093, p<0.001) and females (β= -0.025, p<0.001). Of interest, in the BMI stratification analyses in 18 groups, all βs of regular smoking for WHtR were positive in both genders; the βs showed a significantly greater increasing trend with increasing BMI in males than in females. In the analyses with model adjustment for BMI, the positive associations between regular smoking and WHtR were stronger in males (β= 0.021, p<0.001) than in females (β= 0.008, p<0.001) (p<0.001 for gender difference). WC showed considerably consistent results. Conclusions The data indicate that tobacco smoking is an important risk factor for central obesity, but the association is gender-specific and depends on the adjustment for general obesity.

Spicy food consumption is associated with adiposity measures among half a million Chinese people: the China Kadoorie Biobank study

BackgroundFew animal experiments and volunteer-based intervention studies have showed a controversial effect of spicy foods on weight management; however, information is scant on the association between spicy food intake and obesity. This study aims to examine the impact of spicy food on quantitative adiposity measures in the Chinese population; a population with a low prevalence of general obesity, but a high prevalence of central obesity.MethodsA total of 434,556 adults (255,094 females), aged 30–79 years, were included from the China Kadoorie Biobank (CKB) study. Information on spicy food intake was obtained using a questionnaire survey. Body mass index (BMI), percentage body fat (BF%), waist circumference (WC), and WC/height ratio (WHtR) were analyzed as continuous variables.ResultsThe prevalence of daily spicy food eating was 30.4% in males and 30.0% in females, with dramatically geographic diversity (ranging from 99.4% in Hunan to 2.7% in Zhejiang). The covariates-adjusted BMI, BF%, WC, and WHtR significantly increased with increasing frequency, strength, and duration of spicy food eating regardless of gender (p < 0.001). Among regular spicy food consumers, strength of spicy food eating showed significant and positive association with all adiposity measures in both genders (except for BF% in males). Compared with non-consumers, daily spicy food eating was significantly associated with an increase of 0.44 and 0.51 of BMI (kg/m2), 0.79 and 1.01 of BF%, 1.4 and 1.0 of WC (cm), and 0.008 and 0.006 of WHtR in males and females, respectively. In stratified analyses of 18 consecutive BMI subgroups, a significantly increasing trend in the effect of daily spicy food eating on WC and WHtR with increasing BMI was noted in males; whereas a decreasing trend was seen in females.ConclusionsThe data indicate that spicy food intake is a risk factor for obesity in Chinese adult population, especially for central obesity in males. Further studies are needed to elucidate the mechanisms underlying this association.

Temporal Relationship Between Childhood Body Mass Index and Insulin and Its Impact on Adult Hypertension: The Bogalusa Heart Study

Although obesity and insulin resistance are closely correlated, their temporal sequences in early life and influence on adult hypertension are largely unknown. This study aims to delineate the temporal relationship patterns between body mass index (BMI) and insulin in childhood and their impact on adult hypertension. The longitudinal cohort consisted of 990 adults (630 whites and 360 blacks) who had BMI and fasting insulin measured twice 5.4 years apart in childhood (mean age, 10.5 years at baseline and 15.9 years at follow-up) and blood pressure measured 14.7 years later in adulthood (mean age, 30.5 years). Cross-lagged panel and mediation analysis models were used to examine the temporal relationship between childhood BMI and insulin and its impact on adult hypertension. After adjusting for age, race, sex, and follow-up years, the cross-lagged path coefficient (&bgr;=0.33; P<0.001) from baseline BMI to follow-up insulin was significantly greater than the path coefficient (&bgr;=−0.02; P>0.05) from baseline insulin to follow-up BMI in childhood with P<0.001 for the difference in &bgr;s. Blacks and whites showed similar patterns of the temporal relationship. The path coefficient (&bgr;=0.59; P<0.001) from BMI to insulin in the hypertensive group was significantly greater than that (&bgr;=0.24; P<0.001) in normotensive group, with P<0.001 for the difference in &bgr;s between these 2 groups. The mediation effect of childhood insulin on the childhood BMI–adult hypertension association was estimated at 21.1% (P<0.001). These findings provide evidence that higher BMI levels precede hyperinsulinemia during childhood, and this 1-directional relation plays a role in the development of hypertension.