scholarly journals Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease

Circulation ◽  
2019 ◽  
Vol 140 (8) ◽  
pp. 645-657 ◽  
Author(s):  
Golareh Agha ◽  
Michael M. Mendelson ◽  
Cavin K. Ward-Caviness ◽  
Roby Joehanes ◽  
TianXiao Huan ◽  
...  

Background: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts. Methods: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts. Results: Among 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate<0.05). These CpGs map to genes with key roles in calcium regulation (ATP2B2, CASR, GUCA1B, HPCAL1), and genes identified in genome- and epigenome-wide studies of serum calcium (CASR), serum calcium-related risk of CHD (CASR), coronary artery calcified plaque (PTPRN2), and kidney function (CDH23, HPCAL1), among others. Mendelian randomization analyses supported a causal effect of DNA methylation on incident CHD; these CpGs map to active regulatory regions proximal to long non-coding RNA transcripts. Conclusion: Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD.

Author(s):  
Abhiram Prasad

Ischemic heart disease, principally myocardial infarction, causes approximately 1 of 3 deaths in the United States, or nearly 800,000 deaths annually. The substantial decrease in the death rate from acute myocardial infarction that has occurred since 1970 is attributed to efforts in primary prevention and new interventions in the treatment of myocardial infarction. The variable presentation of patients with coronary heart disease includes patients who are asymptomatic (with or without silent ischemia), patients who have stable or unstable angina or myocardial infarction, and patients with sudden death.


1998 ◽  
Vol 7 (3) ◽  
pp. 175-182 ◽  
Author(s):  
S Penque ◽  
M Halm ◽  
M Smith ◽  
J Deutsch ◽  
M Van Roekel ◽  
...  

BACKGROUND: Heart disease is the No. 1 killer among women in the United States. Differences in the clinical features of coronary heart disease among men and women have been reported, along with various approaches to the diagnostic workup and therapeutic interventions. PURPOSE: To explore the relationship between descriptors of signs and symptoms of coronary heart disease and follow-up care and to investigate any differences between male and female patients. METHODS: Structured interviews with patients and chart audits were used to assess initial signs and symptoms, associated cardiac-related signs and symptoms, and the diagnostic tests and interventions used for treatment. The sample consisted of 98 patients (51 women and 47 men) who were admitted with a medical diagnosis of myocardial infarction. RESULTS: Chest pain was the most common sign or symptom reported by both men and women. The 4 most common associated signs and symptoms were identical in men and women: fatigue, rest pain, shortness of breath, and weakness. However, significantly more women than men reported loss of appetite, paroxysmal nocturnal dyspnea, and back pain. Women were also less likely than men to have angiography and to receive i.v. nitroglycerin, heparin, and thrombolytic agents as part of acute management of myocardial infarction. CONCLUSION: Chest pain remains the initial symptom of acute myocardial infarction in both men and women. However, women may experience some different associated signs and symptoms than do men. Despite these similarities, men still are more likely than women to have angiography and to receive a number of therapies.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
I Leonova ◽  
S Boldueva ◽  
V Feoktistova ◽  
D Evdokimov

Abstract Funding Acknowledgements Type of funding sources: None. The widespread use of coronary angiography (CAG) in patients with acute coronary syndrome led to the understanding that in some patients myocardial infarction (MI) occurs against angiographically unchanged or slightly modified coronary arteries (CA). In such cases, the so-called "type 2 IM" is diagnosed in some patients, however, to determine the true cause of MI, a modern method of investigation such as optical coherence tomography (OCT) is needed to visualize the intima of the CA and detect a minimal atherosclerotic process.  The purpose of the study was to establish the etiology of MI without obstructive coronary artery disease (MINOCA) using OCT. Materials and methods 160 conclusions of the OCT were analyzed. In 9 (6%) cases, the study was conducted in patients who underwent proven MI (mean age 43,1 ± 13,2, 8 males, 1 female) who had no hemodynamically significant CA stenosis according to CAG data. Results in 2 cases (22%) patients had ST-elevation MI, thrombotic occlusion of the CA (in one case, thrombaspiration was performed). In both patients, spontaneous dissection of the intima of the unmodified CA was detected in the OCT. The remaining 7 patients had non-ST-elevation MI, and in 2 cases, a diagnosis of type 2 MI was established: in both patients, the atherosclerotic plaque was visualized, narrowing the lumen of the CA less than 50%, in one case MI developed against a background of the hypertensive crisis, in another - against a background of spasm of CA. In the remaining 5 patients, OCT revealed subintimal atheromatous, with elements of local dissection of the intima. Thus, in 78% of patients atherosclerosis of CA of different severity (from the subintimal deposition of lipids to the development of atherosclerotic plaque, narrowing the clearance of the SC by less than 50%) was diagnosed. In the analysis of risk factors for coronary heart disease (CHD), 57% of patients with atheromatous CA had more than 2 risk factors for CHD: 3 (42%) smoked, 5 (71%) - obesity, 4 (57% ) - had arterial hypertension, 3 (42%) had dyslipidemia, 1 (14%) had type 2 diabetes. In the group of patients with spontaneous intima dissection of the CA, 1 patient (woman) did not have CHD risk factors, the 2-nd suffered from obesity and hypertension. For all patients a lifestyle correction was recommended; statins, antiplatelets were prescribed, patients with spontaneous dissection of CA had the recommendation of examination in the medical-genetic center. Conclusion Based on the results of the study, in most cases, the cause of IMBOC development was an atherosclerotic lesion of the coronary arteries, which is not always visualized with standard coronary angiography. Basically, the patients were young and middle-aged. Most patients had different risk factors for coronary heart disease.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Benincasa ◽  
C Schiano ◽  
T Infante ◽  
M Franzese ◽  
R Casale ◽  
...  

Abstract Aims Immune endothelial inflammation, underlie coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features. Methods Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score=0, uninjured coronaries and with no obstructive CHD were considered as control subjects (Ctrls) (n=18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software. Results For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p=0.05) of HLA-G gene in CHD patients compared to Ctrl group; 2) hypomethylation level of one specific fragment positively correlated with coronary Ca score, a relevant parameter of CCTA (p&lt;0.05) between two groups. Conclusions Our results showed that reduced levels of circulating HLA-G molecules could derive from epigenetic marks inducing hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive coronary stenosis vs non critical stenosis group. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Minister of Health


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2513
Author(s):  
Xiaowen Wang ◽  
Jun Lv ◽  
Canqing Yu ◽  
Liming Li ◽  
Yonghua Hu ◽  
...  

Randomized controlled trials showed that soy intervention significantly improved blood lipids in people with diabetes. We sought to prospectively examine the association of soy consumption with the risk of cardiovascular death among individuals with diabetes. A total of 26,139 participants with a history of diabetes were selected from the Chinese Kadoorie Biobank study. Soy food consumption was assessed by a food frequency questionnaire. Causes of death were coded by the 10th International Classification of Diseases. The Cox proportional hazard regression was used to compute the hazard ratios. During a median follow-up of 7.8 years, a total of 1626 deaths from cardiovascular disease (CVD) were recorded. Compared with individuals who never consumed soy foods, the multivariable-adjusted risks (95% confidence intervals) of CVD mortality were 0.92 (0.78, 1.09), 0.89 (0.75, 1.05), and 0.77 (0.62, 0.96) for those who consumed soy foods monthly, 1–3 days/week, and ≥4 days/week, respectively. For cause-specific cardiovascular mortality, significant inverse associations were observed for coronary heart disease and acute myocardial infarction. Higher soy food consumption was associated with a lower risk of cardiovascular death, especially death from coronary heart disease and acute myocardial infarction, in Chinese adults with diabetes.


2019 ◽  
pp. 204748731989467 ◽  
Author(s):  
Liu Miao ◽  
Guo-Xiong Deng ◽  
Rui-Xing Yin ◽  
Rong-Jun Nie ◽  
Shuo Yang ◽  
...  

Background Although many observational studies have shown an association between plasma homocysteine levels and cardiovascular diseases, controversy remains. In this study, we estimated the role of increased plasma homocysteine levels on the etiology of coronary heart disease and acute myocardial infarction. Methods A two-sample Mendelian randomization study on disease was conducted, i.e. “coronary heart disease” ( n = 184,305) and “acute myocardial infarction” ( n = 181,875). Nine single nucleotide polymorphisms, which were genome-wide significantly associated with plasma homocysteine levels in 57,644 subjects from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium genome-wide association study and were known to be associated at p < 5×10–8, were used as an instrumental variable. Results None of the nine single nucleotide polymorphisms were associated with coronary heart disease or acute myocardial infarction ( p > 0.05 for all). Mendelian randomization analysis revealed no causal effects of plasma homocysteine levels, either on coronary heart disease (inverse variance weighted; odds ratio = 1.015, 95% confidence interval = 0.923–1.106, p = 0.752) or on acute myocardial infarction (inverse variance weighted; odds ratio = 1.037, 95% confidence interval = 0.932–1.142, p = 0.499). The results were consistent in sensitivity analyses using the weighted median and Mendelian randomization-Egger methods, and no directional pleiotropy ( p = 0.213 for coronary heart disease and p = 0.343 for acute myocardial infarction) was observed. Sensitivity analyses confirmed that plasma homocysteine levels were not significantly associated with coronary heart disease or acute myocardial infarction. Conclusions The findings from this Mendelian randomization study indicate no causal relationship between plasma homocysteine levels and coronary heart disease or acute myocardial infarction. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.


Author(s):  
Mehdi Rasouli ◽  
Asadollah Mohseni Kiasari

AbstractThe associations of serum calcium and phosphorus concentrations as well as other cardiovascular risk factors were investigated in relation to the existence and severity of coronary heart disease (CHD) in 260 clinically stable, angiographically defined CHD patients aged 40–70years. The subjects were classified as CHD


2013 ◽  
Vol 5 ◽  
pp. CMT.S7824 ◽  
Author(s):  
Mohammed Aldakkak ◽  
David F. Stowe ◽  
Amadou K.S. Camara

Coronary heart disease is a global malady and it is the leading cause of death in the United States. Chronic stable angina is the most common manifestation of coronary heart disease and it results from the imbalance between myocardial oxygen supply and demand due to reduction in coronary blood flow. Therefore, in addition to lifestyle changes, commonly used pharmaceutical treatments for angina (nitrates, β-blockers, Ca2+ channel blockers) are aimed at increasing blood flow or decreasing O2 demand. However, patients may continue to experience symptoms of angina. Ranolazine is a relatively new drug with anti-anginal and anti-arrhythmic effects. Its anti-anginal mechanism is not clearly understood but the general consensus is that ranolazine brings about its anti-anginal effects by inhibiting the late Na+ current and the subsequent intracellular Ca2+ accumulation. Recent studies suggest other effects of ranolazine that may explain its anti-anginal and anti-arrhythmic effects. Nonetheless, clinical trials have proven the efficacy of ranolazine in treating chronic angina. It has been shown to be ineffective, however, in treating acute coronary syndrome patients. Ranolazine is a safe drug with minimal side effects. It is metabolized mainly in the liver and cleared by the kidney. Therefore, caution must be taken in patients with impaired hepatic or renal function. Due to its efficacy and safety, ranolazine was approved for the treatment of chronic angina by the Food and Drug Administration (FDA) in 2006.


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