Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of heart disease involving the reduction of blood flow to the cardiac muscle due to the presence of atheromatous plaques in the arteries of the heart. It is the most common of the cardiovascular diseases. CAD can cause stable angina, unstable angina, myocardial ischemia, and myocardial infarction.
A common symptom is angina, which is chest pain or discomfort that may travel into the shoulder, arm, back, neck, or jaw. Occasionally, it may feel like heartburn. In stable angina, 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 heart rhythm.
Risk factors include high blood pressure, smoking, diabetes mellitus, lack of exercise, obesity, high blood cholesterol, poor diet, depression, excessive alcohol consumption and a family history of premature cardiovascular disease. A number of tests may help with diagnosis 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. Although primary prevention strategies involving statin medications reduce the incidence of the sequelae of CAD, there is limited evidence for the efficacy of early detection of CAD itself through screening of low-risk individuals who do not show 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 males than females of a given age.
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 the 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 and has an increased oxygen demand. For some, this causes severe symptoms, while others experience no symptoms at all.
Symptoms in females
Symptoms in females can differ from those in males, and the most common symptom reported by females of all races is shortness of breath. Other symptoms more commonly reported by females than males are extreme fatigue, sleep disturbances, indigestion, and anxiety. However, some females 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 females, but females less commonly report it than males. Generally, females experience symptoms 10 years later than males. Females are less likely to recognize symptoms and seek treatment.
Risk factors
Coronary artery disease is characterized by heart problems that result from atherosclerosis.Institute of Medicine (US) Committee on Social Security Cardiovascular Disability Criteria. (2010). Cardiovascular Disability: Updating the Social Security Listings. "Ischemic Heart Disease". NCBI, National Academies Press (US). Atherosclerosis, a type of arteriosclerosis, is the "chronic inflammation of the arteries which causes them to harden and accumulate cholesterol plaques (atheromatous plaques) on the artery walls".Tenas, M. S. & Torres, M. F. (2018) "What is Ischaemic Heart Disease?" Clinic Barcelona. Several well-determined risk factors contribute to atherosclerosis in CAD, including high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet, depression, family history, psychological stress and excessive alcohol consumption. Other risk factors include "abnormal (high) amounts of cholesterol and other fat in the blood (dyslipidemia)", and being overweight.Nordestgaard, B. G. & Palmer, T. M. & Benn, M. & Zacho, J & Tybjærg-Hansen, A. & Smith, G. D. & Timpson, N. J. (2012). "The Effect of Elevated Body Mass Index on Ischemic Heart Disease Risk: Causal Estimates from a Mendelian Randomisation Approach". PLoS Medicine vol. 9,5 e1001212. . About half of cases are linked to genetics. Apart from these well-established risk factors, several other risk factors have also been studied including high serum fibrinogen, high c-reactive protein (CRP), chronic inflammatory conditions, hypovitaminosis D, high lipoprotein A levels, serum homocysteine etc. 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, females 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, females who had high levels of work-related stress experienced a decrease in the diameter of their blood vessels and significantly increased disease progression.
Air pollution Air pollution, both indoor and outdoor, is responsible for roughly 28% of deaths from CAD. This varies by region: In highly developed areas, this is approximately 10%, whereas in Southern, East and West Africa, and South Asia, approximately 40% of deaths from CAD can be attributed to unhealthy air. In particular, fine particle pollution (PM2.5), which comes mostly from the burning of fossil fuels, is a key risk factor for CAD.
Blood fats Different forms of dietary fats associated with increased atherosclerotic risk include trans-unsaturated fat, present in processed foods made with partially hydrogenated oils, and saturated fat, which are largely derived from animal sources. The linear configurations of trans-unsaturated and saturated fats promote their deposition along the vascular endothelium, leading to the build-up of plaques, which narrow the arterial lumen.
The resultant reduction in the heart's blood supply due to atherosclerosis in the coronary arteries is consistent with the development of CAD.
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 Several RNA Transcripts associated with CAD - FoxP1, ICOSLG, IKZF4/Eos, SMYD3, TRIM28, and TCF3/E2A are likely markers of regulatory T cells (Tregs), consistent with known reductions in Tregs in CAD.
The RNA changes are mostly related to ciliary and endocytic transcripts, which in the circulating immune system would be related to the immune synapse. One of the most differentially expressed genes, fibromodulin (FMOD), which is increased 2.8-fold in CAD, is found mainly in connective tissue and is a modulator of the TGF-beta signaling pathway. However, not all RNA changes may be related to the immune synapse. For example, Nebulette, the most down-regulated transcript (2.4-fold), is found in cardiac muscle; it is a 'cytolinker' that connects actin and desmin to facilitate cytoskeletal function and vesicular movement. The endocytic pathway is further modulated by changes in tubulin, a key microtubule protein, and fidgetin, a tubulin-severing enzyme that is a marker for cardiovascular risk identified by genome-wide association study. 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. Stereocilin is a partner to mesothelin, a related super-helical protein, whose transcript is also modulated in CAD. DCDC2, a double-cortin protein, modulates ciliary length. In the signaling pathways of the immune synapse, numerous transcripts are directly related to T-cell function and the control of differentiation. Butyrophilin is a co-regulator for T cell activation. Fibromodulin modulates the TGF-beta signaling pathway, 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. Several of the transcripts (TMEM98, NRCAM, SFRP5, SHISA2) are elements of the Wnt signaling pathway, which is a major determinant of Treg differentiation.
Other Endometriosis in females 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. Patient-specific vessel ageing or remodelling determines endothelial cell behaviour and thus disease growth and progression. Such 'hemodynamic markers' are patient-specific risk surrogates. HIV is a known risk factor for developing atherosclerosis and coronary artery disease.
Pathophysiology