Atherosclerosis

Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by elevated blood levels of cholesterol, primarily LDL. These lesions may lead to narrowing of the arterial walls due to build

Atherosclerosis[a] is a pattern of the disease arteriosclerosis,[7] characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by elevated blood levels of cholesterol, primarily LDL.[8] These lesions may lead to narrowing of the arterial walls due to buildup of atheromatous plaques.[9][10]

At the onset, there are usually no symptoms, but if they develop, symptoms generally begin around middle age.[1] In severe cases, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney disorders, depending on the body part(s) in which the affected arteries are located.[1]

The exact cause of atherosclerosis is unknown and is proposed to be multifactorial.[1] Risk factors include abnormal cholesterol levels, elevated levels of inflammatory biomarkers,[11] high blood pressure, diabetes, smoking (both active and passive smoking), obesity, genetic factors, family history, lifestyle habits, and an unhealthy diet.[3] Plaque is made up of fat, cholesterol, immune cells, calcium, and other substances found in the blood.[9][8] The narrowing of arteries limits the flow of oxygen-rich blood to parts of the body.[9] Diagnosis is based upon a physical exam, electrocardiogram, and exercise stress test, among others, depending on the affected artery or arteries.[12]

Prevention guidelines include eating a healthy diet, exercising, not smoking, and maintaining a normal body weight.[4] Treatment of established atherosclerotic disease may include medications to lower cholesterol such as statins, blood pressure medication, and anticoagulant therapies to reduce the risk of blood clot formation.[5] As the disease state progresses, more invasive strategies are applied, such as percutaneous coronary intervention, coronary artery bypass graft, or carotid endarterectomy.[5] In some individuals, genetic factors are also implicated in the disease process and cause a strongly increased predisposition to development of atherosclerosis.[13]

Atherosclerosis generally starts when a person is young and worsens with age. Almost all people are affected to some degree by the age of 65.[6] It is the number one cause of death and disability in developed countries.[14][15][16] Though it was first described in 1575,[17] there is evidence suggesting that this disease state is genetically inherent in the broader human population, with its origins tracing back to CMAH genetic mutations that may have occurred more than two million years ago during the evolution of hominin ancestors of modern human beings.[18]

Signs and symptoms

Atherosclerosis is typically asymptomatic for decades because the arteries enlarge at all plaque locations, thus there is no effect on blood flow.[19] Even most plaque ruptures do not produce symptoms until enough narrowing or closure of an artery, due to clots, occurs. Signs and symptoms only happen after severe narrowing or closure impedes blood flow to different organs enough to induce symptoms.[20] Most of the time, patients realize that they have the disease only when they experience other cardiovascular disorders such as stroke or heart attack. These symptoms, however, still vary depending on which artery or organ is affected.[21]

Early atherosclerotic processes likely begin in childhood. Fibrous and gelatinous lesions have been observed in the coronary arteries of children.[22] Fatty streaks have been observed in the coronary arteries of juveniles.[22] While coronary artery disease is more prevalent in men than women, atherosclerosis of the cerebral arteries and strokes equally affect both sexes.[23]

Marked narrowing in the coronary arteries, which are responsible for bringing oxygenated blood to the heart, can produce symptoms such as chest pain of angina and shortness of breath, sweating, nausea, dizziness or lightheadedness, breathlessness or palpitations.[21] Abnormal heart rhythms called arrhythmias—the heart beating either too slowly or too quickly—are another consequence of ischemia.[24]

Carotid arteries supply blood to the brain and neck.[24] Marked narrowing of the carotid arteries can present with symptoms such as a feeling of weakness; being unable to think straight; difficulty speaking; dizziness; difficulty in walking or standing up straight; blurred vision; numbness of the face, arms and legs; severe headache; and loss of consciousness. These symptoms are also related to stroke (death of brain cells). Stroke is caused by marked narrowing or closure of arteries going to the brain; lack of adequate blood supply leads to the death of the cells of the affected tissue.[25]

Peripheral arteries, which supply blood to the legs, arms, and pelvis, also experience marked narrowing due to plaque rupture and clots. Symptoms of the narrowing are pain and numbness in the arms or legs. Another significant location for plaque formation is the renal arteries, which supply blood to the kidneys. Plaque occurrence and accumulation lead to decreased kidney blood flow and chronic kidney disease, which, like in all other areas, is typically asymptomatic until late stages.[21]

In 2004, US data indicated that in ~66% of men and ~47% of women, the first symptom of atherosclerotic cardiovascular disease was a heart attack or sudden cardiac death (defined as death within one hour of onset of the symptom).[26]

Case studies have included autopsies of U.S. soldiers killed in World War II and the Korean War. A much-cited report involved the autopsies of 300 U.S. soldiers killed in Korea. Although the average age of the men was 22.1 years, 77.3 percent had "gross evidence of coronary arteriosclerosis".[27]

Risk factors

The atherosclerotic process is not well understood.[needs update] Atherosclerosis is associated with inflammatory processes in the endothelial cells of the vessel wall associated with retained low-density lipoprotein (LDL) particles.[28][29] This retention may be a cause, an effect, or both of the underlying inflammatory process.[30]

The presence of the plaque induces the muscle cells of the blood vessel to stretch, compensating for the additional bulk. The endothelial lining then thickens, increasing the separation between the plaque and lumen. The thickening somewhat offsets the narrowing caused by the plaque's growth, but moreover, it causes the wall to stiffen and become less compliant to stretching with each heartbeat.[31]

Modifiable

• Western pattern diet[32]
• Abdominal obesity[32]
• Diabetes[32]
• Dyslipidemia[32]
• High blood cholesterol[32]
• High blood pressure[32]
• Elevated concentrations of apolipoprotein B (ApoB)-containing lipoproteins (such as LDL particles), for which LDL-cholesterol (LDL-C) is the most commonly used surrogate marker[33][34]
• High saturated fat diet[32]
• Trans fat[35]
• Tobacco smoking[32]
• Bacterial infections[36]
• HIV/AIDS[37]
• Psychological stress[38]
• Sedentary lifestyle[32]

Nonmodifiable

• Biological sex[39]
• South Asian descent[40][41]
• Advanced age[32][42]
• Genetic abnormalities[32]
• Family history[32]
• Coronary anatomy and branch pattern[43]

Lesser or uncertain

• Thrombophilia[44][45][46]
• Elevated triglycerides[32]
• Systemic inflammation[47]
• Hyperinsulinemia[48]
• Sleep deprivation[49]
• Air pollution[50][51]
• Arsenic poisoning[52]
• Hypothyroidism[53]
• Periodontal disease[54]

Dietary

The relation between dietary fat and atherosclerosis is controversial. The USDA, in its food pyramid, promotes a diet of about 64% carbohydrates from total calories. The American Heart Association, the American Diabetes Association, and the National Cholesterol Education Program make similar recommendations. In contrast, Prof Walter Willett (Harvard School of Public Health, PI of the second Nurses' Health Study) recommends much higher levels of fat, especially of monounsaturated and polyunsaturated fat.[55] These dietary recommendations reach a consensus, though, against consumption of trans fats.[citation needed]

The role of eating oxidized fats (rancid fats) in humans is not clear. Rabbits fed rancid fats develop atherosclerosis faster.[56] Rats fed DHA-containing oils experienced marked disruptions to their antioxidant systems, and accumulated significant amounts of phospholipid hydroperoxide in their blood, livers and kidneys.[57]

Rancid fats and oils taste very unpleasant in even small amounts, so people avoid eating them.[58] Measuring or estimating the actual human consumption of these substances is challenging.[59] Highly unsaturated omega-3 rich oils such as fish oil, when being sold in pill form, can hide the taste of oxidized or rancid fat that might be present. In the US, the health food industry's dietary supplements are self-regulated and outside of FDA regulations.[60] To protect unsaturated fats from oxidation, it is best to keep them cool and in oxygen-free environments.[61]