Table 1.

Major types of circulatory disease.

Disease endpoint	International Classification of Diseases 10th revision (ICD10) coding	Description
Arteriosclerosis	I25.0, I25.1, I70	Arteriosclerosis is characterized by a thickening, hardening and loss of elasticity of the walls of arteries. This process gradually restricts the blood flow to organs and tissues. and comprises three main types, (a) Monckeberg (medial calcific) sclerosis, (b) arteriolosclerosis, and (c) atherosclerosis. Monckeberg sclerosis is caused by calcium build-up in the arterial walls, and results in them becoming stiffer, and is often asymptomatic. Arteriolosclerosis is the process of artery thickening and hardening in the small arteries and arterioles. Hyaline arteriolosclerosis results from (a) lumenal protein leakage into and build-up in the arterial walls, resulting in thickening and stiffening of the arterial wall and reduced blood flow through the lumen or (b) diabetes, which causes high levels of blood sugar that directly damages the endothelial cell layer, likely via alterations in carbohydrate and fat metabolism, resulting in damage to the basement membrane of the blood vessels. Hyperplastic arteriolosclerosis results from extreme hypertension and compensatory thickening, via build up of smooth-muscle cells in the arterial wall. In contrast, atherosclerosis is caused by build-up of cholesterol-rich atheromatous plaques in the tunica intima (the part of the arterial wall immediately behind the endothelial cell layer) and is a disease of the large arteries (e.g., coronary, carotid). Plaque build-up and rupture, which results in clotting of the blood at the site of rupture, reduces blood-flow in the affected arteries. If blood flow to the kidneys is reduced for whatever reason (whether due to atherosclerosis or arteriolosclerosis), the kidney interprets this as low blood pressure and activates the renin-angiotensin-aldosterone system, raising blood volume and so blood pressure, causing hypertension (high blood pressure). When arteriolosclerosis leads to chronically reduced blood flow to the kidney arteriolonephrosclerosis is produced, which if untreated can lead to chronic renal failure. Atherosclerosis is also caused by hypertension, as well as by smoking, by elevated levels of low density lipoprotein (LDL) cholesterol, or by reduced levels of high density lipoprotein (HDL) cholesterol. The weakening of the arterial wall that results from atherosclerosis can lead to aneurysms in many parts of the body, in particular the intestine (e.g., abdominal aortic aneurysms). The term arteriosclerosis is sometimes (incorrectly) used interchangeably with the term atherosclerosis. Arteriosclerosis is mostly subsumed within IHD, but a substantial component (atherosclerosis, ICD10 I70) is independent of that. It is a relatively common type of cardiovascular disease, and the substantial part subsumed within IHD accounts for about a third of all IHD deaths, so about 4% of all deaths in the UK [104,105].
Cardiac valve diseases	I05-I09, I34-I39	This rubric includes a variety of abnormalities to one or more of the heart valves (tricuspid, pulmonary, mitral, and aortic valves). Problems in all four valves are typically of three types (a) regurgitation or backflow - when the valve doesn’t close properly (b) stenosis - when the valve flaps stiffen or fuse and (c) atresia - when a valve lacks an opening for blood to flow through. Cardiac valve disease can be congenital, but can also be acquired over the course of life. This is a less common type of circulatory disease mortality, and accounts for about 0.6% of all deaths in the UK [104,105].
Cardiac arrythmias	I47-I49	Cardiac arrhythmia, also known as cardiac dysrhythmia or irregular heartbeat, is a group of conditions in which the heartbeat is irregular, too fast, or too slow. This is a less common type of circulatory disease mortality, and accounts for about 0.6% of all deaths in the UK [104,105]. A heart rate that is too fast - above 100 beats per minute in adults - is called tachycardia and a heart rate that is too slow - below 60 beats per minute - is called bradycardia. Many types of arrhythmia have no symptoms. When symptoms are present these may include palpitations or feeling a pause between heartbeats. More seriously there may be lightheadedness, fainting, shortness of breath, or angina. While most types of arrhythmia are not serious, some predispose a person to complications such as stroke or heart failure. Others may result in cardiac arrest. There are four main types of arrhythmia: (a) extra beats, (b) supraventricular tachycardias, (c) ventricular arrhythmias, and (d) bradyarrhythmias. Extra beats include premature atrial contractions and premature ventricular contractions. Supraventricular tachycardias include atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia. Ventricular arrhythmias include ventricular fibrillation and ventricular tachycardia. Arrhythmias are due to problems with the electrical conduction system of the heart. Arrhythmias may occur in children; however, the normal range for the heart rate is different and depends on age.
Cardiomyopathy	I25.5, I42-I43	Cardiomyopathy is characterized by the heart muscle becoming enlarged, thick, or rigid. In rare cases, the muscle tissue in the heart is replaced with scar tissue. This is a less common type of circulatory disease mortality, and accounts for about 0.3% of all deaths in the UK [104,105]. As cardiomyopathy worsens, the heart becomes weaker, and less able to pump blood through the body and maintain a normal electrical rhythm. This can lead to heart failure or irregular heartbeats called arrhythmias. In turn, heart failure can cause fluid to build up in the lungs, ankles, feet, legs, or abdomen. The weakening of the heart also can cause other complications, such as heart valve problems. The four main types of cardiomyopathy are (a) hypertrophic cardiomyopathy, (b) dilated cardiomyopathy, (c) restrictive cardiomyopathy, and (d) arrhythmogenic right ventricular dysplasia. Cardiomyopathy can be congenital or acquired over the course of life.
Cerebrovascular disease (CeVD)	I60-I69	CeVD, commonly termed stroke, arises because of problems with the circulation of blood in the blood vessels of the brain. This is the second most common type of circulatory disease mortality, and accounts for about 7% of all deaths in the UK [104,105]. A blockage with effects lasting less than 24 hours is referred to as a transient ischemic attack (TIA). Loss of blood and oxygen to areas of the brain can lead to cell death and consequently permanent brain dysfunction. Two major forms of stroke are recognised (a) ischemic stroke, caused by narrowing of blood vessels, and (b) hemorrhagic stroke, cause by bursting of a blood vessel in the brain. Ischemic stroke is divided into those caused (a) by blockage due to blood clots forming locally (thrombotic stroke) or (b) fragments from distant clots lodging in the brain vasculature (embolic stroke).
Hypertensive disease	I10-I15	Hypertension (high blood pressure) has a number of adverse effects on the circulatory system; in particular, as the heart pumps against this pressure, it must work harder, causing the heart muscle to thicken, and eventually heart failure may develop. This is a less common type of circulatory disease mortality, and accounts for about 0.7% of all deaths in the UK [104,105]. With increasing blood pressure risk of hemorrhagic stroke increases. The major types of hypertensive disease include (a) hypertensive heart disease, (b) hypertensive chronic kidney disease, and (c) hypertensive heart and chronic kidney disease. Hypertension also results in damage to and thickening of the arterial walls, resulting in arteriosclerosis (see above), also increased prevalence of atheromatous plaques (degenerative cholesterol deposits) in the large arterial walls, resulting in increased risk of myocardial infarction and stroke. Hypertensive heart disease is the leading cause of illness and death from hypertension.
Ischemic heart disease (IHD)	I20-I25	IHD, also known as coronary artery disease (CAD), is the most common type of cardiovascular disease in most developed countries. This is the most common type of circulatory disease, and accounts for about 12% of all deaths in the UK [104,105]. It is characterized by problems with the arterial blood supply to the heart. A partial blockage of one or more of the coronary arteries (e.g. resulting from atheromatous plaque rupture and consequent blood clotting) can result in myocardial ischemia (oxygen starvation of myocardial (heart muscle) cells) thus causing symptoms such as angina (chest pain) and dyspnea (shortness of breath). A partial or complete blockage of an artery causes necrosis (damage to the myocardial cells) and if sufficiently severe a myocardial infarction (heart attack). The underlying mechanism involves atherosclerosis of the arteries of the heart (see above). Risk factors for IHD include: hypertension, smoking, diabetes, lack of exercise, obesity, high levels of LDL cholesterol, low levels of HDL cholesterol, poor diet, excessive alcohol consumption, and depression. This rubric includes a number of common types of heart disease, including arteriosclerosis (stiffening/thickening of arterial walls - see above), and angina (chest pain).
Pericarditis	I01.0, I09.2, I30-I32	Inflammation of the pericardium, the membrane that surrounds the heart, is most frequently attributable to infectious agents but is also well established to be caused by high doses of ionizing radiation (> 35 Gy to heart) [14]. This is a very uncommon type of circulatory disease mortality, and accounts for about 0.04% of all deaths in the UK [104,105].