Evidence of accelerated epigenetic aging in patients diagnosed with coronary artery disease: Results of the LipidCardio study

DNA methylation (DNAm) age acceleration, defined as the deviation of chronological and epigenetic age determined by an epigenetic clock, has been proposed as a biomarker of biological aging. To address the above hypothesis in the context of cardiovascular disease, we evaluated whether patients (N=827, mean chronological age: 69.82±11.01 years, DNAm age: 71.91±16.11, residual DNAm age acceleration: 0.00±9.65 years), who were diagnosed with obstructive coronary artery disease (CAD) by coronary angiography were aged prematurely, i.e. had an increase in the DNAm age acceleration, in comparison with patients for whom obstructive CAD was ruled out (controls). Stratified analysis yielded a significant acceleration in DNAm age (determined by a seven cytosine-phosphate-guanine epigenetic clock) in patients diagnosed with obstructive CAD, defined by at least one >50% coronary stenosis (N=588, rDNA age acceleration=0.58±9.47, corrected p= 2.05⨯10 −3 ) compared to control subjects (N=145, residual (r)DNAm age acceleration= -3.11±10.51 years). Moreover, rDNAm age acceleration was significantly associated with systolic blood pressure (ß=0.069, 95% CI 0.027 – 0.112, p= 1.44⨯10 −3 ), sex (ß=-2.438, 95% CI -4.591 - -0.285, p= 2.65⨯10 −2 ), estimated glomerular filtration rate (eGFR, ß=0.040, 95% CI 0.011 – 0.069, p= 6.87⨯10 −9 ) and smoking status (ß=-8.538, 95% CI -10.772 - -6.303, p= 2,45⨯10 −13 ). Across studies, assessing CAD and its risk factors in the context of epigenetic age acceleration findings are remarkably inconclusive. While the here employed seven-cytosine-phosphate-guanine epigenetic clock suggests premature biological aging in CAD patients, compared to controls without coronary stenosis, its association with cardiovascular risk factors was limited.