coronary artery disease coronary artery disease coronary artery disease (cad), also called coronary heart disease (chd), ischemic heart disease (ihd), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic plaque in the arteries of the heart. it is the most common of the cardiovascular diseases. types include stable angina, unstable angina, myocardial infarction, and sudden cardiac death. a common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck, or jaw. occasionally it may feel like heartburn. usually symptoms occur with exercise or emotional stress, last less than a few minutes, and improve with rest. shortness of breath may also occur and sometimes no symptoms are present. in many cases, the first sign is a heart attack. other complications include heart failure or an abnormal heartbeat. coronary artery diseaseother namesatherosclerotic heart disease, atherosclerotic vascular disease, coronary heart diseaseillustration depicting atherosclerosis in a coronary arteryspecialtycardiology, cardiac surgerysymptomschest pain, shortness of breathcomplicationsheart failure, abnormal heart rhythms, heart attack, cardiogenic shock, cardiac arrestcausesatherosclerosis of the arteries of the heartrisk factorshigh blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesteroldiagnostic methodelectrocardiogram, cardiac stress test, coronary computed tomographic angiography, coronary angiogrampreventionhealthy diet, regular exercise, maintaining a healthy weight, not smokingtreatmentpercutaneous coronary intervention (pci), coronary artery bypass surgery (cabg)medicationaspirin, beta blockers, nitroglycerin, statinsfrequency110 million (2015)deaths8.9 million (2015) risk factors include high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet, depression, and excessive alcohol consumption. a number of tests may help with diagnoses including: electrocardiogram, cardiac stress testing, coronary computed tomographic angiography, and coronary angiogram, among others. ways to reduce cad risk include eating a healthy diet, regularly exercising, maintaining a healthy weight, and not smoking. medications for diabetes, high cholesterol, or high blood pressure are sometimes used. there is limited evidence for screening people who are at low risk and do not have symptoms. treatment involves the same measures as prevention. additional medications such as antiplatelets (including aspirin), beta blockers, or nitroglycerin may be recommended. procedures such as percutaneous coronary intervention (pci) or coronary artery bypass surgery (cabg) may be used in severe disease. in those with stable cad it is unclear if pci or cabg in addition to the other treatments improves life expectancy or decreases heart attack risk. in 2015, cad affected 110 million people and resulted in 8.9 million deaths. it makes up 15.6% of all deaths, making it the most common cause of death globally. the risk of death from cad for a given age decreased between 1980 and 2010, especially in developed countries. the number of cases of cad for a given age also decreased between 1990 and 2010. in the united states in 2010, about 20% of those over 65 had cad, while it was present in 7% of those 45 to 64, and 1.3% of those 18 to 45; rates were higher among men than women of a given age. clogged artery signs and symptoms the most common symptom is chest pain or discomfort that occurs regularly with activity, after eating, or at other predictable times; this phenomenon is termed stable angina and is associated with narrowing of the arteries of the heart. angina also includes chest tightness, heaviness, pressure, numbness, fullness, or squeezing. angina that changes in intensity, character or frequency is termed unstable. unstable angina may precede myocardial infarction. in adults who go to the emergency department with an unclear cause of pain, about 30% have pain due to coronary artery disease. angina, shortness of breath, sweating, nausea or vomiting, and lightheadedness are signs of a heart attack, or myocardial infarction, and immediate emergency medical services are crucial. with advanced disease, the narrowing of coronary arteries reduces the supply of oxygen-rich blood flowing to the heart, which becomes more pronounced during strenuous activities during which the heart beats faster. for some, this causes severe symptoms, while others experience no symptoms at all. symptoms in women further information: cardiovascular disease in women symptoms in women can differ from those in men, and the most common symptom reported by women of all races is shortness of breath. other symptoms more commonly reported by women than men are extreme fatigue, sleep disturbances, indigestion, and anxiety. however, some women do experience irregular heartbeat, dizziness, sweating, and nausea. burning, pain, or pressure in the chest or upper abdomen that can travel to the arm or jaw can also be experienced in women, but it is less commonly reported by women than men. on average, women experience symptoms 10 years later than men. women are less likely to recognize symptoms and seek treatment. risk factors coronary artery disease is characterized by heart problems that result from atherosclerosis. atherosclerosis is a type of arteriosclerosis which is the "chronic inflammation of the arteries which causes them to harden and accumulate cholesterol plaques (atheromatous plaques) on the artery walls". cad has a number of well determined risk factors that contribute to atherosclerosis. these risk factors for cad include "smoking, diabetes, high blood pressure (hypertension), abnormal (high) amounts of cholesterol and other fat in the blood (dyslipidemia), type 2 diabetes and being overweight or obese (having excess body fat)" due to lack of exercise and a poor diet. some other risk factors include high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet, depression, family history, psychological stress and excessive alcohol. about half of cases are linked to genetics. smoking and obesity are associated with about 36% and 20% of cases, respectively. smoking just one cigarette per day about doubles the risk of cad. lack of exercise has been linked to 7–12% of cases. exposure to the herbicide agent orange may increase risk. rheumatologic diseases such as rheumatoid arthritis, systemic lupus erythematosus, psoriasis, and psoriatic arthritis are independent risk factors as well. job stress appears to play a minor role accounting for about 3% of cases. in one study, women who were free of stress from work life saw an increase in the diameter of their blood vessels, leading to decreased progression of atherosclerosis. in contrast, women who had high levels of work-related stress experienced a decrease in the diameter of their blood vessels and significantly increased disease progression. having a type a behavior pattern, a group of personality characteristics including time urgency, competitiveness, hostility, and impatience, is linked to an increased risk of coronary disease. blood fats the consumption of different types of fats including trans unsaturated, saturated and trans in a diet "influences the level of cholesterol that is present in the bloodstream". unsaturated fats originate from plant sources (such as oils). there are two types of unsaturated fats, cis and trans isomers. cis unsaturated fats are bent in molecular structure and trans are linear in structure. saturated fats originate from animal sources (such as animal fats) and are also molecularly linear in structure. the linear configurations of unsaturated trans and saturated fats allow them to easily accumulate and stack at the arterial walls when consumed in high amounts (and other positive measures towards physical health are not met). fats and cholesterol are insoluble in blood and thus are amalgamated with proteins to form lipoproteins for transport. low density lipoproteins (ldl) transport cholesterol from the liver to the rest of the body and therefore raise blood cholesterol levels. the consumption of "saturated fats increases ldl levels within the body, thus raising blood cholesterol levels". high density lipoproteins (hdl) are considered 'good' lipoproteins as they search for excess cholesterol in the body and transport it back to the liver for disposal. trans fats also "increase ldl levels whilst decreasing hdl levels within the body, significantly raising blood cholesterol levels". high levels of cholesterol in the bloodstream lead to atherosclerosis. with increased levels of ldl in the bloodstream, "ldl particles will form deposits and accumulate within the arterial walls, which will lead to the development of plaques, restricting blood flow". the resultant reduction in the heart's blood supply due to atherosclerosis in coronary arteries "causes shortness of breath, angina pectoris (chest pains that are usually relieved by rest), and potentially fatal heart attacks (myocardial infarctions)". genetics the heritability of coronary artery disease has been estimated between 40% and 60%. genome-wide association studies have identified over 160 genetic susceptibility loci for coronary artery disease. transcriptome transcripts associated with cad (tracs) - foxp1, icoslg, ikzf4/eos, smyd3, trim28, and tcf3/e2a that are likely markers of regulatory t cells (treg), consistent with known reductions in tregs in cad. schematic representation of treg-related tracs identified by rnaseq. the differentially expressed genes (degs) identified by rnaseq were curated by automated and manual analysis to identify the molecular pathways involved. the resulting pattern points to changes in the 'immune synapse', which involves both endocytic pathways of t cell receptor (tcr)-containing vesicles, as well as ciliary protrusions that couple to intracellular signaling pathways. the rna changes are mostly related to ciliary and endocytic transcripts, which in the circulating immune system would be related to the immune synapse. the immune synapse is the contact-dependent mode of communication between t cells and b cells, on one side, and a variety of antigen-presenting and immunomodulating cells on the other side. one of the most differentially expressed genes, fibromodulin (fmod, increased 2.8-fold in cad). several other regulated transcripts encode for proteins related to the structure and function of the immune synapse. nebulette, the most down-regulated transcript (2.4-fold), is an important 'cytolinker' that connects actin and desmin to facilitate cytoskeletal function and vesicular movement. the endocytic pathway is further modulated by changes in tubulin, which is a key microtubule protein, and fidgetin, which is a tubulin-severing enzyme that is a gwas marker for cv risk. protein recycling would be modulated by changes in the proteasomal regulator siah3, and the ubiquitin ligase marchf10. on the ciliary aspect of the immune synapse, several of the modulated transcripts are related to ciliary length and function. steriocilin (strc) has been studied principally in outer sensory hair cells, and mutations lead to deafness. steriocilin is a partner to mesothelin (msn), a related super-helical protein, whose transcript is also modulated in cad. likewise, dcdc2, a double-cortin protein, is a known modulator of ciliary length. in the signaling pathways of the immune synapse, there were numerous transcripts that related directly to t cell function and the control of differentiation. butyrophilin (btn1a1) is a known co-regulator for t cell activation. fibromodulin is a well-known modulator of the tgf-beta signaling pathway, which is a primary determinant of tre differentiation. further impact on the tgf-beta pathway is reflected in concurrent changes in the bmp receptor 1b rna (bmpr1b), because the bone morphogenic proteins are members of the tgf-beta superfamily, and likewise impact treg differentiation. as noted, several of the transcripts (tmem98, nrcam, sfrp5, shisa2) are known elements of the wnt signaling pathway, which is major determinant of treg differentiation. other endometriosis in women under the age of 40. depression and hostility appear to be risks. the number of categories of adverse childhood experiences (psychological, physical, or sexual abuse; violence against mother; or living with household members who used substances, mentally ill, suicidal, or incarcerated) showed a graded correlation with the presence of adult diseases including coronary artery (ischemic heart) disease. hemostatic factors: high levels of fibrinogen and coagulation factor vii are associated with an increased risk of cad. low hemoglobin. in the asian population, the b fibrinogen gene g-455a polymorphism was associated with the risk of cad. pathophysiology micrograph of a coronary artery with the most common form of coronary artery disease (atherosclerosis) and marked luminal narrowing. masson's trichrome. illustration depicting coronary artery disease limitation of blood flow to the heart causes ischemia (cell starvation secondary to a lack of oxygen) of the heart's muscle cells. the heart's muscle cells may die from lack of oxygen and this is called a myocardial infarction (commonly referred to as a heart attack). it leads to damage, death, and eventual scarring of the heart muscle without regrowth of heart muscle cells. chronic high-grade narrowing of the coronary arteries can induce transient ischemia which leads to the induction of a ventricular arrhythmia, which may terminate into a dangerous heart rhythm known as ventricular fibrillation, which often leads to death. typically, coronary artery disease occurs when part of the smooth, elastic lining inside a coronary