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

ABSTRACT: Epigenetic 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.We 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.Epigenetic 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.

SUBMITTER: Horvath S

PROVIDER: S-EPMC4980791 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Horvath Steve S Gurven Michael M Levine Morgan E ME Trumble Benjamin C BC Kaplan Hillard H Allayee Hooman H Ritz Beate R BR Chen Brian B Lu Ake T AT Rickabaugh Tammy M TM Jamieson Beth D BD Sun Dianjianyi D Li Shengxu S Chen Wei W Quintana-Murci Lluis L Fagny Maud M Kobor Michael S MS Tsao Philip S PS Reiner Alexander P AP Edlefsen Kerstin L KL Absher Devin D Assimes Themistocles L TL

Genome biology 20160811 1

<h4>Background</h4>Epigenetic 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 i ...[more]

PMID: 27511193

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Project description:ContextIt is unknown whether long-standing disparities in incidence of coronary heart disease (CHD) among US blacks and whites persist.ObjectiveTo examine incident CHD by black and white race and by sex.Design, setting, and participantsProspective cohort study of 24,443 participants without CHD at baseline from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, who resided in the continental United States and were enrolled between 2003 and 2007 with follow-up through December 31, 2009.Main outcome measureExpert-adjudicated total (fatal and nonfatal) CHD, fatal CHD, and nonfatal CHD (definite or probable myocardial infarction [MI]; very small non-ST-elevation MI [NSTEMI] had peak troponin level <0.5 μg/L).ResultsOver a mean (SD) of 4.2 (1.5) years of follow-up, 659 incident CHD events occurred (153 in black men, 138 in black women, 254 in white men, and 114 in white women). Among men, the age-standardized incidence rate per 1000 person-years for total CHD was 9.0 (95% CI, 7.5-10.8) for blacks vs 8.1 (95% CI, 6.9-9.4) for whites; fatal CHD: 4.0 (95% CI, 2.9-5.3) vs 1.9 (95% CI, 1.4-2.6), respectively; and nonfatal CHD: 4.9 (95% CI, 3.8-6.2) vs 6.2 (95% CI, 5.2-7.4). Among women, the age-standardized incidence rate per 1000 person-years for total CHD was 5.0 (95% CI, 4.2-6.1) for blacks vs 3.4 (95% CI, 2.8-4.2) for whites; fatal CHD: 2.0 (95% CI, 1.5-2.7) vs 1.0 (95% CI, 0.7-1.5), respectively; and nonfatal CHD: 2.8 (95% CI, 2.2-3.7) vs 2.2 (95% CI, 1.7-2.9). Age- and region-adjusted hazard ratios for fatal CHD among blacks vs whites was near 2.0 for both men and women and became statistically nonsignificant after multivariable adjustment. The multivariable-adjusted hazard ratio for incident nonfatal CHD for blacks vs whites was 0.68 (95% CI, 0.51-0.91) for men and 0.81 (95% CI, 0.58-1.15) for women. Of the 444 nonfatal CHD events, 139 participants (31.3%) had very small NSTEMIs.ConclusionsThe higher risk of fatal CHD among blacks compared with whites was associated with cardiovascular disease risk factor burden. These relationships may differ by sex.

Project description:BACKGROUND:National heart failure (HF) hospitalization rates have not been appropriately age standardized by sex or race/ethnicity. Reporting hospital utilization trends by subgroup is important for monitoring population health and developing interventions to eliminate disparities. METHODS AND RESULTS:The National Inpatient Sample (NIS) was used to estimate the crude and age-standardized rates of HF hospitalization between 2002 and 2013 by sex and race/ethnicity. Direct standardization was used to age-standardize rates to the 2000 US standard population. Relative differences between subgroups were reported. The national age-adjusted HF hospitalization rate decreased 30.8% from 526.86 to 364.66 per 100?000 between 2002 and 2013. Although hospitalizations decreased for all subgroups, the ratio of the age-standardized rate for men compared with women increased from 20% greater to 39% (P trend=0.002) between 2002 and 2013. Black men had a rate that was 229% (P trend=0.141) and black women, 240% (P trend=0.725) with reference to whites in 2013 with no significant change between 2002 and 2013. Hispanic men had a rate that was 32% greater in 2002 and the difference narrowed to 4% (P trend=0.047) greater in 2013 relative to whites. For Hispanic women, the rate was 55% greater in 2002 and narrowed to 8% greater (P trend=0.004) in 2013 relative to whites. Asian/Pacific Islander men had a 27% lower rate in 2002 that improved to 43% (P trend=0.040) lower in 2013 relative to whites. For Asian/Pacific Islander women, the hospitalization rate was 24% lower in 2002 and improved to 43% (P trend=0.021) lower in 2013 relative to whites. CONCLUSIONS:National HF hospitalization rates have decreased steadily during the recent decade. Disparities in HF burden and hospital utilization by sex and race/ethnicity persist. Significant population health interventions are needed to reduce the HF hospitalization burden among blacks. An evaluation of factors explaining the improvements in the HF hospitalization rates among Hispanics and Asian/Pacific Islanders is needed.

Project description:ObjectivesThis study sought to describe the health status of outpatients with heart failure and reduced ejection fraction (HFrEF) by sex, race/ethnicity, and socioeconomic status (SES).BackgroundAlthough a primary goal in treating patients with HFrEF is to optimize health status, whether disparities by sex, race/ethnicity, and SES exist is unknown.MethodsIn the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, the associations among sex, race, and SES and health status, as measured by the Kansas City Cardiomyopathy Questionnaire-overall summary (KCCQ-os) score (range 0 to 100; higher scores indicate better health status) was compared among 3,494 patients from 140 U.S. clinics. SES was categorized by total household income. Hierarchical multivariate linear regression estimated differences in KCCQ-os score after adjusting for 31 patient characteristics and 10 medications.ResultsOverall mean KCCQ-os scores were 64.2 ± 24.0 but lower for women (29% of sample; 60.3 ± 24.0 vs. 65.9 ± 24.0, respectively; p < 0.001), for blacks (60.5 ± 25.0 vs. 64.9 ± 23.0, respectively; p < 0.001), for Hispanics (59.1 ± 21.0 vs. 64.9 ± 23.0, respectively; p < 0.001), and for those with the lowest income (<$25,000; mean: 57.1 vs. 63.1 to 74.7 for other income categories; p < 0.001). Fully adjusted KCCQ-os scores were 2.2 points lower for women (95% confidence interval [CI]: -3.8 to -0.6; p = 0.007), no different for blacks (p = 0.74), 4.0 points lower for Hispanics (95% CI: -6.6 to -1.3; p = 0.003), and lowest in the poorest patients (4.7 points lower than those with the highest income (95% CI: 0.1 to 9.2; p = 0.045; p for trend = 0.003).ConclusionsAmong outpatients with HFrEF, women, blacks, Hispanics, and poorer patients had worse health status, which remained significant for women, Hispanics, and poorer patients in fully adjusted analyses. This suggests an opportunity to further optimize treatment to reduce these observed disparities.

Project description:BACKGROUND:Although racial/ethnic and sex disparities have been examined in health care generally and pain management more specifically, the combined influence of these sociodemographic factors together has not been well documented. The aim of this study was to examine the association between administration of opioid analgesics in the emergency department (ED) and interaction of race/ethnicity and sex. METHODS:We conducted a retrospective cohort study using 2010-2014 Center for Disease Control-National Hospital Ambulatory Medical Care Survey data for patients 12-55 years of age presenting to EDs with a primary diagnosis of appendicitis or gallbladder disease as defined by International Classification of Diseases, Ninth Revision codes. The primary outcome was the receipt of opioid analgesic medications. Secondary outcomes included: receipt of nonopioids, receipt of antiemetic medications, wait time to see a provider, and length of visit in the ED. The association between sex and analgesic receipt within Caucasian non-Hispanic and non-Caucasian groups was evaluated adjusting for pain score on presentation, patient age, emergent status, number of comorbidities, time of visit (month, day of the week, standard versus nonstandard working hours, year), and US region. RESULTS:After exclusions, a weighted sample of 553 ED visits was identified, representing 2,622,926 unique visits. The sample population was comprised of 1,858,035 (70.8%) females and 1,535,794 (58.6%) Caucasian non-Hispanics. No interaction was found in adjusted sampling-weighted model between sex and race/ethnicity on the odds of receiving opioids (P = .74). There was no difference in opioid administration to males as compared to females (odds ratio [OR] = 0.96, 95% CI, 0.87-1.06; P = .42) or to non-Caucasians as compared to Caucasians (OR = 0.99, 95% CI, 0.89-1.10; P = .84). In adjusted weighted models, non-Caucasian males, 123,121/239,457 (51.4%) did not differ from Caucasian non-Hispanic males, 317,427/525,434 (60.4%), on odds of receiving opioids, aOR = 0.88, 95% CI, 0.39-1.99; P = .75. Non-Caucasian females, 547,709/847,675 (64.6%) also did not differ from Caucasian females, 621,638/1,010,360 (61.5%), on odds of receiving opioids, aOR = 1.01, 95% CI, 0.53-1.90; P = .98. Across both sexes, non-Caucasians did not differ from Caucasians on receipt of nonopioid analgesics or antiemetics. Neither wait time to see a provider nor the length of the hospital visit was significantly different between sexes or race/ethnicities. CONCLUSIONS:Based on National Hospital Ambulatory Medical Care Survey data from 2010 to 2014, there is no statistically significant interaction between race/ethnicity and sex for administration of opioid analgesia to people presenting to the ED with appendicitis or gallbladder disease. These results suggest that the joint effect of patient race/ethnicity and sex may not manifest in disparities in opioid management.

Project description:ObjectivesIn this study, we aimed to establish whether age-sex-specific percentiles of coronary artery calcium (CAC) predict cardiovascular outcomes better than the actual (absolute) CAC score.BackgroundThe presence and extent of CAC correlates with the overall magnitude of coronary atherosclerotic plaque burden and with the development of subsequent coronary events.MethodsMESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort study of 6,814 asymptomatic participants followed for coronary heart disease (CHD) events including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death. Time to incident CHD was modeled with Cox regression, and we compared models with percentiles based on age, sex, and/or race/ethnicity to categories commonly used (0, 1 to 100, 101 to 400, 400+ Agatston units).ResultsThere were 163 (2.4%) incident CHD events (median follow-up 3.75 years). Expressing CAC in terms of age- and sex-specific percentiles had significantly lower area under the receiver-operating characteristic curve (AUC) than when using absolute scores (women: AUC 0.73 versus 0.76, p = 0.044; men: AUC 0.73 versus 0.77, p < 0.001). Akaike's information criterion indicated better model fit with the overall score. Both methods robustly predicted events (>90th percentile associated with a hazard ratio [HR] of 16.4, 95% confidence interval [CI]: 9.30 to 28.9, and score >400 associated with HR of 20.6, 95% CI: 11.8 to 36.0). Within groups based on age-, sex-, and race/ethnicity-specific percentiles there remains a clear trend of increasing risk across levels of the absolute CAC groups. In contrast, once absolute CAC category is fixed, there is no increasing trend across levels of age-, sex-, and race/ethnicity-specific categories. Patients with low absolute scores are low-risk, regardless of age-, sex-, and race/ethnicity-specific percentile rank. Persons with an absolute CAC score of >400 are high risk, regardless of percentile rank.ConclusionsUsing absolute CAC in standard groups performed better than age-, sex-, and race/ethnicity-specific percentiles in terms of model fit and discrimination. We recommend using cut points based on the absolute CAC amount, and the common CAC cut points of 100 and 400 seem to perform well.

Dataset Information

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

Publications

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

Similar Datasets

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