DNA methylation signatures of incident coronary heart disease: findings from epigenome-wide association studies

Coronary heart disease (CHD) is a type of cardiovascular disease (CVD) that affects the coronary arteries, which provide oxygenated blood to the heart. It is a major cause of mortality worldwide. Various prediction methods have been developed to assess the likelihood of developing CHD, including those based on clinical features and genetic variation. Recent epigenome-wide studies have identified DNA methylation signatures associated with the development of CHD, indicating that DNA methylation may play a role in predicting future CHD. This narrative review summarises recent findings from DNA methylation studies of incident CHD (iCHD) events from epigenome-wide association studies (EWASs). The results suggest that DNA methylation signatures may identify new mechanisms involved in CHD progression and could prove a useful adjunct for the prediction of future CHD.

Serum Uric Acid: A Murderer or Bystander for Cardiac-related Mortality?

In this issue of The Journal of Rheumatology, Colantonio, et al1 conducted a case-cohort study from the REGARDS study to evaluate whether the association between serum uric acid (SUA) and sudden cardiac death, and between SUA and incident coronary heart disease (CHD) events, is confounded by SLC2A9 single-nucleotide polymorphisms (SNPs). Incident CHD events were the composites of nonfatal myocardial infarction (MI) or CHD deaths.

External validation of integrated genetic-epigenetic biomarkers for predicting incident coronary heart disease

Aim: The Framingham Risk Score (FRS) and ASCVD Pooled Cohort Equation (PCE) for predicting risk for incident coronary heart disease (CHD) work poorly. To improve risk stratification for CHD, we developed a novel integrated genetic-epigenetic tool. Materials & methods: Using machine learning techniques and datasets from the Framingham Heart Study (FHS) and Intermountain Healthcare (IM), we developed and validated an integrated genetic-epigenetic model for predicting 3-year incident CHD. Results: Our approach was more sensitive than FRS and PCE and had high generalizability across cohorts. It performed with sensitivity/specificity of 79/75% in the FHS test set and 75/72% in the IM set. The sensitivity/specificity was 15/93% in FHS and 31/89% in IM for FRS, and sensitivity/specificity was 41/74% in FHS and 69/55% in IM for PCE. Conclusion: The use of our tool in a clinical setting could better identify patients at high risk for a heart attack.

Maternal Coronary Heart Disease, Stroke, and Mortality Within 1, 3, and 5 Years of Delivery Among Women With Hypertensive Disorders of Pregnancy and Pre‐Pregnancy Hypertension

Background Pre‐pregnancy hypertension and hypertensive disorders of pregnancy (HDP; preeclampsia, eclampsia, gestational hypertension) are major health risks for maternal morbidity and mortality. However, it is unknown if racial/ethnic differences exist. We aimed to determine the impact of HDP and pre‐pregnancy hypertension on maternal coronary heart disease, stroke, and mortality risk ≤1, 3, and 5 years post‐delivery and by race/ethnicity ≤5 years. Methods and Results This retrospective cohort study included women aged 12 to 49 years with a live, singleton birth between 2004 to 2016 (n=254 491 non‐Hispanic White; n=137 784 non‐Hispanic Black; n=41 155 Hispanic). Birth and death certificates and International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification ( ICD‐9‐CM and ICD‐10‐CM ) diagnosis codes in hospitalization/emergency department visit data defined HDP, pre‐pregnancy hypertension, incident coronary heart disease and stroke, and all‐cause mortality. During at least 1 pregnancy of the 433 430 women, 2.3% had pre‐pregnancy hypertension with superimposed HDP, 15.7% had no pre‐pregnancy hypertension with HDP, and 0.4% had pre‐pregnancy hypertension without superimposed HDP, whereas 81.6% had neither condition. Maternal deaths from coronary heart disease, stroke, and all causes totaled 2136. Within 5 years of delivery, pre‐pregnancy hypertension, and HDP were associated with all‐cause mortality (hazard ratio [HR], 2.21; 95% CI, 1.61–3.03), incident coronary heart disease (HR, 3.79; 95% CI, 3.09–4.65), and incident stroke (HR, 3.10; 95% CI, 2.09–4.60). HDP alone was related to all outcomes. Race/ethnic differences were observed for non‐Hispanic Black and non‐Hispanic White women, respectively, in the associations of pre‐pregnancy hypertension and HDP with all‐cause mortality within 5 years of delivery (HR, 2.34 [95% CI, 1.58–3.47]; HR, 2.11 [95% CI, 1.23–3.65]; P interaction=0.001). Conclusions Maternal cardiovascular outcomes including mortality were increased ≤5 years post‐delivery in HDP, pre‐pregnancy hypertension, or pre‐pregnancy hypertension with superimposed HDP. The race/ethnic interaction for all‐cause mortality ≤5 years of delivery warrants further research.