<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Glycogen storage disease type V and can you explain it in depth? [/INST] Glycogen storage disease type V (GSD5, GSD-V), also known as McArdles disease, is a metabolic disorder, one of the metabolic myopathies, more specifically a muscle glycogen storage disease, caused by a deficiency of myophosphorylase. Its incidence is reported as one in 100,000, roughly the same as glycogen storage disease type I.The disease was first reported in 1951 by Dr. Brian McArdle of Guys Hospital, London.

Signs and symptoms
The onset of this disease is usually noticed in childhood, but often not diagnosed until the third or fourth decade of life. Symptoms include exercise intolerance with muscle pain, early fatigue, painful cramps, inappropriate rapid heart rate response to exercise, and may include myoglobin in the urine (often provoked by a bout of exercise).  "In McArdles, our heart rate tends to increase in what is called an inappropriate response. That is, after the start of exercise it increases much more quickly than would be expected in someone unaffected by McArdles." Myoglobinuria may be seen due to the breakdown of skeletal muscle known as rhabdomyolysis, a condition in which muscle cells breakdown, sending their contents into the bloodstream. In a recent study of 269 GSD-V patients, 39.4% reported no previous episodes of myoglobinuria and 6.8% had normal CK even with fixed muscle weakness, so an absence of myoglobinuria and normal CK should not rule out the possibility of the disease.As skeletal muscle relies predominantly on glycogenolysis for the first few minutes as it transitions from rest to activity, as well as throughout high-intensity aerobic activity and all anaerobic activity, individuals with GSD-V experience during exercise: sinus tachycardia, tachypnea, muscle fatigue and pain, during the aforementioned activities and time frames. Patients may exhibit a “second wind” phenomenon. This is characterized by the patients better tolerance for aerobic exercise such as walking and cycling after approximately 10 minutes.  This is attributed to the combination of increased blood flow and the ability of the body to find alternative sources of energy, like fatty acids and proteins. In the long term, patients may exhibit kidney failure due to the myoglobinuria, and with age, patients may exhibit progressively increasing weakness and substantial muscle loss.Younger people may display unusual symptoms, such as difficulty in chewing, swallowing or utilizing normal oral motor functions. A number of comorbidities were found in GSD-V patients at a higher rate than found in the general population, including (but not limited to): hypertension (17%), endocrine diseases (15.7%), muskuloskeletal/rheumatic disease (12.9%), hyperuricemia/gout (11.6%), gastrointestinal diseases (11.2%), neurological disease (10%), respiratory disease (9.5%), and coronary artery disease (8.3%). Patients may have hypertrophy, particularly of the legs, and may have lower bone mineral content and density in the legs.GSD-V patients may experience myogenic hyperuricemia (exercise-induced accelerated breakdown of purine nucleotides in skeletal muscle). The Purine Nucleotide Cycle (PNC) is activated when the ATP (energy) reservoir in muscle cells runs low, and is a part of Protein Metabolism. Adenine (a purine) is converted into AMP (adenosine monophosphate), IMP (inosine monophosphate), and S-AMP (adenylosuccinate) in a circular fashion; the byproducts are fumarate (which goes on to produce ATP via oxidative phosphorylation), ammonia (from the conversion of AMP into IMP), and uric acid (from excess IMP).
To avoid health complications, GSD-V patients need to get their ATP (energy) primarily from Free Fatty Acids (Lipid Metabolism) rather than Protein Metabolism.  Over-reliance on protein metabolism can be best avoided by not depleting the ATP reservoir, such as by not pushing through the pain and by not going too fast, too soon. "Be wary of pushing on when you feel pain start. This pain is a result of damaging muscles, and repeated damage will cause problems in the long term. But also this is counterproductive--it will stop you from getting into second wind. By pressing on despite the pain, you start your protein metabolism which then effectively blocks your glucose and fat metabolism. If you ever get into this situation, you need to stop completely for 30 minutes or more and then start the whole process again."Patients may present at emergency rooms with severe fixed contractures of the muscles and often severe pain. These require urgent assessment for rhabdomyolysis as in about 30% of cases this leads to acute kidney injury. Left untreated, this can be life-threatening. In a small number of cases compartment syndrome has developed, requiring prompt surgical referral.

Genetics
"GSDV is inherited in an autosomal recessive manner. At conception, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier."Two autosomal recessive forms of this disease occur, childhood-onset and adult-onset. The gene for myophosphorylase, PYGM (the muscle-type of the glycogen phosphorylase gene), is located on chromosome 11q13. According to the most recent publications, 95 different mutations have been reported.  The forms of the mutations may vary between ethnic groups. For example, the R50X (Arg50Stop) mutation (previously referred to as R49X) is most common in North America and western Europe, and the Y84X mutation is most common among central Europeans.The exact method of protein disruption has been elucidated in certain mutations. For example, R138W is known to disrupt to pyridoxal phosphate binding site. In 2006, another mutation (c.13_14delCT) was discovered which may contribute to increased symptoms in addition to the common Arg50Stop mutation.

Myophosphorylase
Structure
The myophosphorylase structure consists of 842 amino acids. Its molecular weight of the unprocessed precursor is 97 kDa. The three-dimensional structure has been determined for this protein. The interactions of several amino acids in myophosphorylases structure are known. Ser-14 is modified by phosphorylase kinase during activation of the enzyme. Lys-680 is involved in binding the pyridoxal phosphate, which is the active form of vitamin B6, a cofactor required by myophosphorylase. By similarity, other sites have been estimated: Tyr-76 binds AMP, Cys-109 and Cys-143 are involved in subunit association, and Tyr-156 may be involved in allosteric control.

Function
Myophosphorylase is the form of the glycogen phosphorylase found in muscle that catalyses the following reaction:((1→4)-alpha-D-glucosyl) (n) + phosphate = ((1→4)-alpha-D-glucosyl) (n-1) + alpha-D-glucose 1-phosphate
Failure of this enzyme ultimately impairs the operation of ATPases. This is due to the lack of normal pH fall during exercise, which impairs the creatine kinase equilibrium and exaggerates the rise of ADP.

Pathophysiology
Myophosphorylase is involved in the breakdown of glycogen to glucose for use in muscle. The enzyme removes 1,4 glycosyl residues from outer branches of glycogen and adds inorganic phosphate to form glucose-1-phosphate. Ordinarily, the removal of 1,4 glycosyl residues by myophosphorylase leads to the formation of glucose-1-phosphate during glycogen breakdown and the polar, phosphorylated glucose cannot leave the cell membrane and so is marked for intracellular catabolism. In McArdles Disease, deficiency of myophosphorylase leads to accumulation of intramuscular glycogen and a lack of glucose-1-phosphate for cellular fuel.
Myophosphorylase exists in the active form when phosphorylated. The enzyme phosphorylase kinase plays a role in phosphorylating glycogen phosphorylase to activate it and another enzyme, protein phosphatase-1, inactivates glycogen phosphorylase through dephosphorylation.

Diagnosis
There are some laboratory tests that may aid in diagnosis of GSD-V. A muscle biopsy will note the absence of myophosphorylase in muscle fibers. In some cases, acid-Schiff stained glycogen can be seen with microscopy.Genetic sequencing of the PYGM gene (which codes for the muscle isoform of glycogen phosphorylase) may be done to determine the presence of gene mutations, determining if McArdles is present. This type of testing is considerably less invasive than a muscle biopsy.The physician can also perform an ischemic forearm exercise test as described above. Some findings suggest a nonischemic test could be performed with similar results. The nonischemic version of this test would involve not cutting off the blood flow to the exercising arm. Findings consistent with McArdles disease would include a failure of lactate to rise in venous blood and exaggerated ammonia levels. These findings would indicate a severe muscle glycolytic block.
Serum lactate may fail to rise in part because of increased uptake via the monocarboxylate transporter (MCT1), which is upregulated in skeletal muscle in McArdle disease. Lactate may be used as a fuel source once converted to pyruvate. Ammonia levels may rise given ammonia is a by-product of the adenylate kinase pathway, an alternative pathway for ATP production. In this pathway, two ADP molecules combine to make ATP; AMP is deaminated in this process, producing inosine monophosphate (IMP) and ammonia (NH3).Physicians may also check resting levels of creatine kinase, which are moderately increased in 90% of patients. In some, the level is increased by multitudes - a person without GSD-V will have a CK between 60 and 400IU/L, while a person with the syndrome may have a level of 5,000 IU/L at rest, and may increase to 35,000 IU/L or more with muscle exertion. This can help distinguish McArdles syndrome from carnitine palmitoyltransferase II deficiency (CPT-II), a lipid-based metabolic disorder which prevents fatty acids from being transported into mitochondria for use as an energy source. Also, serum electrolytes and endocrine studies (such as thyroid function, parathyroid function and growth hormone levels) will also be completed. Urine studies are required only if rhabdomyolysis is suspected. Urine volume, urine sediment and myoglobin levels would be ascertained. If rhabdomyolysis is suspected, serum myoglobin, creatine kinase, lactate dehydrogenase, electrolytes and renal function will be checked.Physicians may also conduct an Exercise Stress Test to test for an inappropriate rapid heart rate (Sinus Tachycardia) in response to exercise. Due to the rare nature of the disease, the inappropriate rapid heart rate in response to exercise may be misdiagnosed as Inappropriate Sinus Tachycardia (which is a diagnosis of exclusion). The 12 Minute Walk Test (12MWT) can be used to determine "Second Wind," which requires a treadmill (no incline), heart rate monitor, stop watch, pain scale, and that the patient has rested for 30 minutes prior to the test to ensure that oxidative phosphorylation has stopped.

Treatment
Supervised exercise programs have been shown in small studies to improve exercise capacity by several measures.Oral sucrose treatment (for example a sports drink with 75 grams of sucrose in 660 ml.) taken 30 minutes prior to exercise has been shown to help improve exercise tolerance including a lower heart rate and lower perceived level of exertion compared with placebo.A low dosage treatment with creatine showed a significant improvement of muscle problems compared to placebo in a small clinical study.

History
The deficiency was the first metabolic myopathy to be recognized, when Dr. McArdle described the first case in a 30-year-old man who always experienced pain and weakness after exercise </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Arthus reaction and can you explain it in depth? [/INST] In immunology, the Arthus reaction () is a type of local type III hypersensitivity reaction.  Type III hypersensitivity reactions are immune complex-mediated, and involve the deposition of antigen/antibody complexes mainly in the vascular walls, serosa (pleura, pericardium, synovium), and glomeruli. This reaction is usually encountered in experimental settings following the injection of antigens.

History
The Arthus reaction was discovered by Nicolas Maurice Arthus in 1903. Arthus repeatedly injected horse serum subcutaneously into rabbits.  After four injections, he found that there was edema and that the serum was absorbed slowly.  Further injections eventually led to gangrene.

Process
The Arthus reaction involves the in situ formation of antigen/antibody complexes after the intradermal injection of an antigen.  If the animal/patient was previously sensitized (has circulating antibody), an Arthus reaction occurs </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Benign tumor and can you explain it in depth? [/INST] A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize (spread throughout the body). Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have relatively well differentiated cells. They are often surrounded by an outer surface (fibrous sheath of connective tissue) or stay contained within the epithelium. Common examples of benign tumors include moles and uterine fibroids.
Some forms of benign tumors may be harmful to health. Benign tumor growth causes a mass effect that can compress neighboring tissues. This can lead to nerve damage, blood flow reduction (ischemia), tissue death (necrosis), or organ damage. The health effects of benign tumor growth may be more prominent if the tumor is contained within an enclosed space such as the cranium, respiratory tract, sinus, or bones. For example, unlike most benign tumors elsewhere in the body, benign brain tumors can be life-threatening. Tumors may exhibit behaviors characteristic of their cell type of origin; as an example, endocrine tumors such as thyroid adenomas and adrenocortical adenomas may overproduce certain hormones.
Many types of benign tumors have the potential to become cancerous (malignant) through a process known as tumor progression. For this reason and other possible harms, some benign tumors are removed by surgery. When removed, benign tumors usually do not return. Exceptions to this rule may indicate malignant transformation.

Signs and symptoms
Benign tumors are very diverse; they may be asymptomatic or may cause specific symptoms, depending on their anatomic location and tissue type. They grow outward, producing large, rounded masses which can cause what is known as a "mass effect". This growth can cause compression of local tissues or organs, leading to many effects, such as blockage of ducts, reduced blood flow (ischaemia), tissue death (necrosis) and nerve pain or damage. Some tumors also produce hormones that can lead to life-threatening situations. Insulinomas can produce large amounts of insulin, causing hypoglycemia. Pituitary adenomas can cause elevated levels of hormones such as growth hormone and insulin-like growth factor-1, which cause acromegaly; prolactin; ACTH and cortisol, which cause Cushings disease; TSH, which causes hyperthyroidism; and FSH and LH. Bowel intussusception can occur with various benign colonic tumors. Cosmetic effects can be caused by tumors, especially those of the skin, possibly causing psychological or social discomfort for the person with the tumor. Vascular tissue tumors can bleed, in some cases leading to anemia.

Causes
PTEN hamartoma syndrome
PTEN hamartoma syndrome encompasses hamartomatous disorders characterized by genetic mutations in the PTEN tumor suppressor gene, including Cowden syndrome, Bannayan–Riley–Ruvalcaba syndrome, Proteus syndrome and Proteus-like syndrome. Absent or dysfunctional PTEN protein allows cells to over-proliferate, causing hamartomas. Cowden syndrome is an autosomal dominant genetic disorder characterized by multiple benign hamartomas (trichilemmomas and mucocutaneous papillomatous papules) as well as a predisposition for cancers of multiple organs including the breast and thyroid. Bannayan–Riley–Ruvalcaba syndrome is a congenital disorder characterized by hamartomatous intestinal polyposis, macrocephaly, lipomatosis, hemangiomatosis and glans penis macules. Proteus syndrome is characterized by nevi, asymmetric overgrowth of various body parts, adipose tissue dysregulation, cystadenomas, adenomas, vascular malformation.

Familial adenomatous polyposis
Familial adenomatous polyposis (FAP) is a familial cancer syndrome caused by mutations in the APC gene. In FAP, adenomatous polyps are present in the colon. The polyps progress into colon cancer unless removed. The APC gene is a tumor suppressor. Its protein product is involved in many cellular processes. Inactivation of the APC gene leads to the buildup of a protein called β-catenin. This protein activates two transcription factors: T-cell factor (TCF) and lymphoid enhancer factor (LEF). These factors cause the upregulation of many genes involved in cell proliferation, differentiation, migration and apoptosis (programmed cell death), causing the growth of benign tumors.

Tuberous sclerosis complex
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in the genes TSC1 and TSC2. TSC1 produces the protein hamartin. TSC2 produces the protein tuberin. This disorder presents with many benign hamartomatous tumors including angiofibromas, renal angiomyolipomas, and pulmonary lymphangiomyomatosis. Tuberin and hamartin inhibit the mTOR protein in normal cellular physiology. Inactivation of the TSC tumor suppressors causes an increase in mTOR activity. This leads to the activation of genes and the production of proteins that increase cell growth.

Von Hippel–Lindau disease
Von Hippel–Lindau disease is a dominantly-inherited cancer syndrome that significantly increases the risk of various tumors. This includes benign hemangioblastomas and malignant pheochromocytomas, renal cell carcinomas, pancreatic endocrine tumors, and endolymphatic sac tumors. It is caused by genetic mutations in the Von Hippel–Lindau tumor suppressor gene. The VHL protein (pVHL) is involved in cellular signaling in oxygen starved (hypoxic) cells. One role of pVHL is to cause the cellular degradation of another protein, HIF1α. Dysfunctional pVHL leads to accumulation of HIF1α. This activates several genes responsible for the production of substances involved in cell growth and blood vessel production: VEGF, PDGFβ, TGFα and erythropoietin.

Bone tumors
Benign tumors of bone can be similar macroscopically and require a combination of a clinical history with cytogenetic, molecular, and radiologic tests for diagnosis. Three common forms of benign bone tumors with are giant cell tumor of bone, osteochondroma, and enchondroma; other forms of benign bone tumors exist but may be less prevalent.

Giant cell tumors
Giant cell tumors of bone frequently occur in long bone epiphyses of the appendicular skeleton or the sacrum of the axial skeleton. Local growth can cause destruction of neighboring cortical bone and soft tissue, leading to pain and limiting range of motion. The characteristic radiologic finding of giant cell tumors of bone is a lytic lesion that does not have marginal sclerosis of bone. On histology, giant cells of fused osteoclasts are seen as a response to neoplastic mononucleated cells. Notably, giant cells are not unique among benign bone tumors to giant cell tumors of bone. Molecular characteristics of the neoplastic cells causing giant cell tumors of bone indicate an origin of pluripotent mesenchymal stem cells that adopt preosteoblastic markers. Cytogenetic causes of giant cell tumors of bone involve telomeres. Treatment involves surgical curettage with adjuvant bisphosphonates.

Osteochondroma
Osteochondromas form cartilage-capped projections of bone. Structures such as the marrow cavity and cortical bone of the osteochondroma are contiguous to those of the originating bone. Sites of origin often involve metaphyses of long bones. While many osteochondromas occur spontaneously, there are cases in which several osteochondromas can occur in the same individual; these may be linked to a genetic condition known as hereditary multiple osteochondromas. Osteochondroma appears on X-ray as a projecting mass that often points away from joints. These tumors stop growing with the closure of the parental bones growth plates. Failure to stop growth can be indicative of transformation to malignant chondrosarcoma. Treatment is not indicated unless symptomatic. In that case, surgical excision is often curative.

Enchondroma
Enchondromas are benign tumors of hyaline cartilage. Within a bone, enchondromas are often found in metaphyses. They can be found in many types of bone, including small bones, long bones, and the axial skeleton. X-ray of enchondromas shows well-defined borders and a stippled appearance. Presentation of multiple enchondromas is consistent with multiple enchondromatosis (Ollier Disease). Treatment of enchondromas involves surgical curettage and grafting.

Benign soft tissue tumors
Lipomas
Lipomas are benign, subcutaneous tumors of fat cells (adipocytes). They are usually painless, slow-growing, and mobile masses that can occur anywhere in the body where there are fat cells, but are typically found on the trunk and upper extremities. Although lipomas can develop at any age, they more commonly appear between the ages of 40 and 60. Lipomas affect about 1% of the population, with no documented sex bias, and about 1 in every 1000 people will have a lipoma within their lifetime. The cause of lipomas is not well defined. Genetic or inherited causes of lipomas play a role in around 2-3% of patients. In individuals with inherited familial syndromes such as Proteus syndrome or Familial multiple lipomatosis, it is common to see multiple lipomas across the body. These syndromes are also associated with specific symptoms and sub-populations. Mutations in chromosome 12 have been identified in around 65% of lipoma cases. Lipomas have also been shown to be increased in those with obesity, hyperlipidemia, and diabetes mellitus.Lipomas are usually diagnosed clinically, although imaging (ultrasound, computed tomography, or magnetic resonance imaging) may be utilized to assist with the diagnosis of lipomas in atypical locations. The main treatment for lipomas is surgical excision, after which the tumor is examined with histopathology to confirm the diagnosis. The prognosis for benign lipomas excellent and recurrence after excision is rare, but may occur if the removal was incomplete.

Mechanism
Benign vs malignant
One of the most important factors in classifying a tumor as benign or malignant is its invasive potential. If a tumor lacks the ability to invade adjacent tissues or spread to distant sites by metastasizing then it is benign, whereas invasive or metastatic tumors are malignant. For this reason, benign tumors are not classed as cancer. Benign tumors will grow in a contained area usually encapsulated in a fibrous connective tissue capsule. The growth rates of benign and malignant tumors also differ; benign tumors generally grow more slowly than malignant tumors. Although benign tumors pose a lower health risk than malignant tumors, they both can be life-threatening in certain situations. There are many general characteristics which apply to either benign or malignant tumors, but sometimes one type may show characteristics of the other. For example, benign tumors are mostly well differentiated and malignant tumors are often undifferentiated. However, undifferentiated benign tumors and differentiated malignant tumors can occur. Although benign tumors generally grow slowly, cases of fast-growing benign tumors have also been documented. Some malignant tumors are mostly non-metastatic such as in the case of basal-cell carcinoma. CT and chest radiography can be a useful diagnostic exam in visualizing a benign tumor and differentiating it from a malignant tumor. The smaller the tumor on a radiograph the more likely it is to be benign as 80% of lung nodules less than 2 cm in diameter are benign. Most benign nodules are smoothed radiopaque densities with clear margins but these are not exclusive signs of benign tumors.

Multistage carcinogenesis
Tumors are formed by carcinogenesis, a process in which cellular alterations lead to the formation of cancer. Multistage carcinogenesis involves the sequential genetic or epigenetic changes to a cells DNA, where each step produces a more advanced tumor. It is often broken down into three stages; initiation, promotion and progression, and several mutations may occur at each stage. Initiation is where the first genetic mutation occurs in a cell. Promotion is the clonal expansion (repeated division) of this transformed cell into a visible tumor that is usually benign. Following promotion, progression may take place where more genetic mutations are acquired in a sub-population of tumor cells. Progression changes the benign tumor into a malignant tumor. A prominent and well studied example of this phenomenon is the tubular adenoma, a common type of colon polyp which is an important precursor to colon cancer. The cells in tubular adenomas, like most tumors that frequently progress to cancer, show certain abnormalities of cell maturation and appearance collectively known as dysplasia. These cellular abnormalities are not seen in benign tumors that rarely or never turn cancerous, but are seen in other pre-cancerous tissue abnormalities which do not form discrete masses, such as pre-cancerous lesions of the uterine cervix.

Diagnosis
Classification
Benign neoplasms are typically, but not always, composed of cells which bear a strong resemblance to a normal cell type in their organ of origin. These tumors are named for the cell or tissue type from which they originate. The suffix "-oma" (but not -carcinoma, -sarcoma, or -blastoma, which are generally cancers) is applied to indicate a benign tumor. For example, a lipoma is a common benign tumor of fat cells (lipocytes), and a chondroma is a benign tumor of cartilage-forming cells (chondrocytes). Adenomas are benign tumors of gland-forming cells, and are usually specified further by their cell or organ of origin, as in hepatic adenoma (a benign tumor of hepatocytes, or liver cells). Teratomas contain many cell types such as skin, nerve, brain and thyroid, among others, because they are derived from germ cells. Hamartomas are a group of benign tumors that have relatively normal cellular differentiation but exhibit disorganized tissue organization.Exceptions to the nomenclature rules exist for historical reasons; malignant examples include melanoma (a cancer of pigmented skin cells, or melanocytes) and seminoma (a cancer of male reproductive cells).Benign tumors do not encompass all benign growths </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Cardiovascular disease and can you explain it in depth? [/INST] Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, abnormal heart rhythms, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, thromboembolic disease, and venous thrombosis.The underlying mechanisms vary depending on the disease. It is estimated that dietary risk factors are associated with 53% of CVD deaths. Coronary artery disease, stroke, and peripheral artery disease involve atherosclerosis. This may be caused by high blood pressure, smoking, diabetes mellitus, lack of exercise, obesity, high blood cholesterol, poor diet, excessive alcohol consumption,  and poor sleep, among other things. High blood pressure is estimated to account for approximately 13% of CVD deaths, while tobacco accounts for 9%, diabetes 6%, lack of exercise 6%, and obesity 5%. Rheumatic heart disease may follow untreated strep throat.It is estimated that up to 90% of CVD may be preventable. Prevention of CVD involves improving risk factors through: healthy eating, exercise, avoidance of tobacco smoke and limiting alcohol intake. Treating risk factors, such as high blood pressure, blood lipids and diabetes is also beneficial. Treating people who have strep throat with antibiotics can decrease the risk of rheumatic heart disease. The use of aspirin in people, who are otherwise healthy, is of unclear benefit.Cardiovascular diseases are the leading cause of death worldwide except Africa. Together CVD resulted in 17.9 million deaths (32.1%) in 2015, up from 12.3 million (25.8%) in 1990. Deaths, at a given age, from CVD are more common and have been increasing in much of the developing world, while rates have declined in most of the developed world since the 1970s. Coronary artery disease and stroke account for 80% of CVD deaths in males and 75% of CVD deaths in females. Most cardiovascular disease affects older adults. In the United States 11% of people between 20 and 40 have CVD, while 37% between 40 and 60, 71% of people between 60 and 80, and 85% of people over 80 have CVD. The average age of death from coronary artery disease in the developed world is around 80, while it is around 68 in the developing world. CVD is typically diagnosed seven to ten years earlier in men than in women.: 48

Types
There are many cardiovascular diseases involving the blood vessels. They are known as vascular diseases.
Coronary artery disease (also known as coronary heart disease and ischemic heart disease)
Peripheral arterial disease – disease of blood vessels that supply blood to the arms and legs
Cerebrovascular disease – disease of blood vessels that supply blood to the brain (includes stroke)
Renal artery stenosis
Aortic aneurysmThere are also many cardiovascular diseases that involve the heart.

Cardiomyopathy – diseases of cardiac muscle
Hypertensive heart disease – diseases of the heart secondary to high blood pressure or hypertension
Heart failure - a clinical syndrome caused by the inability of the heart to supply sufficient blood to the tissues to meet their metabolic requirements
Pulmonary heart disease – a failure at the right side of the heart with respiratory system involvement
Cardiac dysrhythmias – abnormalities of heart rhythm
Inflammatory heart disease
Endocarditis – inflammation of the inner layer of the heart, the endocardium. The structures most commonly involved are the heart valves.
Inflammatory cardiomegaly
Myocarditis – inflammation of the myocardium, the muscular part of the heart, caused most often by viral infection and less often by bacterial infections, certain medications, toxins, and autoimmune disorders. It is characterized in part by infiltration of the heart by lymphocyte and monocyte types of white blood cells.
Eosinophilic myocarditis - inflammation of the myocardium caused by pathologically activated eosinophilic white blood cells. This disorder differs from myocarditis in its causes and treatments.
Valvular heart disease
Congenital heart disease – heart structure malformations existing at birth
Rheumatic heart disease – heart muscles and valves damage due to rheumatic fever caused by  Streptococcus pyogenes a group A streptococcal infection.

Risk factors
There are many risk factors for heart diseases: age, sex, tobacco use, physical inactivity, non-alcoholic fatty liver disease, excessive alcohol consumption, unhealthy diet, obesity, genetic predisposition and family history of cardiovascular disease, raised blood pressure (hypertension), raised blood sugar (diabetes mellitus), raised blood cholesterol (hyperlipidemia), undiagnosed celiac disease, psychosocial factors, poverty and low educational status, air pollution, and poor sleep. While the individual contribution of each risk factor varies between different communities or ethnic groups the overall contribution of these risk factors is very consistent. Some of these risk factors, such as age, sex or family history/genetic predisposition, are immutable; however, many important cardiovascular risk factors are modifiable by lifestyle change, social change, drug treatment (for example prevention of hypertension, hyperlipidemia, and diabetes). People with obesity are at increased risk of atherosclerosis of the coronary arteries.

Genetics
Cardiovascular disease in a persons parents increases their risk by ~3 fold, and genetics is an important risk factor for cardiovascular diseases. Genetic cardiovascular disease can occur either as
a consequence of single variant (Mendelian) or polygenic influences. There are more than 40 inherited cardiovascular disease that can be traced to a single disease-causing DNA variant, although these conditions are rare. Most common cardiovascular diseases are non-Mendelian and are thought to be due to hundreds or thousands of genetic variants (known as single nucleotide polymorphisms), each associated with a small effect.

Age
Age is the most important risk factor in developing cardiovascular or heart diseases, with approximately a tripling of risk with each decade of life.  Coronary fatty streaks can begin to form in adolescence. It is estimated that 82 percent of people who die of coronary heart disease are 65 and older. Simultaneously, the risk of stroke doubles every decade after age 55.Multiple explanations are proposed to explain why age increases the risk of cardiovascular/heart diseases. One of them relates to serum cholesterol level. In most populations, the serum total cholesterol level increases as age increases. In men, this increase levels off around age 45 to 50 years. In women, the increase continues sharply until age 60 to 65 years.Aging is also associated with changes in the mechanical and structural properties of the vascular wall, which leads to the loss of arterial elasticity and reduced arterial compliance and may subsequently lead to coronary artery disease.

Sex
Men are at greater risk of heart disease than pre-menopausal women. Once past menopause, it has been argued that a womans risk is similar to a mans although more recent data from the WHO and UN disputes this. If a female has diabetes, she is more likely to develop heart disease than a male with diabetes.Coronary heart diseases are 2 to 5 times more common among middle-aged men than women.  In a study done by the World Health Organization, sex contributes to approximately 40% of the variation in sex ratios of coronary heart disease mortality. Another study reports similar results finding that sex differences explains nearly half the risk associated with cardiovascular diseases One of the proposed explanations for sex differences in cardiovascular diseases is hormonal difference.  Among women, estrogen is the predominant sex hormone. Estrogen may have protective effects on glucose metabolism and hemostatic system, and may have direct effect in improving endothelial cell function.  The production of estrogen decreases after menopause, and this may change the female lipid metabolism toward a more atherogenic form by decreasing the HDL cholesterol level while increasing LDL and total cholesterol levels.Among men and women, there are differences in body weight, height, body fat distribution, heart rate, stroke volume, and arterial compliance. In the very elderly, age-related large artery pulsatility and stiffness are more pronounced among women than men. This may be caused by the womens smaller body size and arterial dimensions which are independent of menopause.

Tobacco
Cigarettes are the major form of smoked tobacco. Risks to health from tobacco use result not only from direct consumption of tobacco, but also from exposure to second-hand smoke. Approximately 10% of cardiovascular disease is attributed to smoking; however, people who quit smoking by age 30 have almost as low a risk of death as never smokers.

Physical inactivity
Insufficient physical activity (defined as less than 5 x 30 minutes of moderate activity per week, or less than 3 x 20 minutes of vigorous activity per week) is currently the fourth leading risk factor for mortality worldwide.  In 2008, 31.3% of adults aged 15 or older (28.2% men and 34.4% women) were insufficiently physically active.
The risk of ischemic heart disease and diabetes mellitus is reduced by almost a third in adults who participate in 150 minutes of moderate physical activity each week (or equivalent). In addition, physical activity assists weight loss and improves blood glucose control, blood pressure, lipid profile and insulin sensitivity. These effects may, at least in part, explain its cardiovascular benefits.

Diet
High dietary intakes of saturated fat, trans-fats and salt, and low intake of fruits, vegetables and fish are linked to cardiovascular risk, although whether all these associations indicate causes is disputed. The World Health Organization attributes approximately 1.7 million deaths worldwide to low fruit and vegetable consumption.  Frequent consumption of high-energy foods, such as processed foods that are high in fats and sugars, promotes obesity and may increase cardiovascular risk.  The amount of dietary salt consumed may also be an important determinant of blood pressure levels and overall cardiovascular risk.  There is moderate quality evidence that reducing saturated fat intake for at least two years reduces the risk of cardiovascular disease. High trans-fat intake has adverse effects on blood lipids and circulating inflammatory markers, and elimination of trans-fat from diets has been widely advocated. In 2018 the World Health Organization estimated that trans fats were the cause of more than half a million deaths per year. There is evidence that higher consumption of sugar is associated with higher blood pressure and unfavorable blood lipids, and sugar intake also increases the risk of diabetes mellitus. High consumption of processed meats is associated with an increased risk of cardiovascular disease, possibly in part due to increased dietary salt intake.

Alcohol
The relationship between alcohol consumption and cardiovascular disease is complex, and may depend on the amount of alcohol consumed. There is a direct relationship between high levels of drinking alcohol and cardiovascular disease.  Drinking at low levels without episodes of heavy drinking may be associated with a reduced risk of cardiovascular disease, but there is evidence that associations between moderate alcohol consumption and protection from stroke are non-causal. At the population level, the health risks of drinking alcohol exceed any potential benefits.

Celiac disease
Untreated celiac disease can cause the development of many types of cardiovascular diseases, most of which improve or resolve with a gluten-free diet and intestinal healing. However, delays in recognition and diagnosis of celiac disease can cause irreversible heart damage.

Sleep
A lack of good sleep, in amount or quality, is documented as increasing cardiovascular risk in both adults and teens. Recommendations suggest that Infants typically need 12 or more hours of sleep per day, adolescent at least eight or nine hours, and adults seven or eight. About one-third of adult Americans get less than the recommended seven hours of sleep per night, and in a study of teenagers, just 2.2 percent of those studied got enough sleep, many of whom did not get good quality sleep.  Studies have shown that short sleepers getting less than seven hours sleep per night have a 10 percent to 30 percent higher risk of cardiovascular disease.Sleep disorders such as sleep-disordered breathing and insomnia, are also associated with a higher cardiometabolic risk.
An estimated 50 to 70 million Americans have insomnia, sleep apnea or other  chronic sleep disorders.
In addition, sleep research displays differences in race and class. Short sleep and poor sleep tend to be more frequently reported in ethnic minorities than in whites. African-Americans report experiencing short durations of sleep five times more often than whites, possibly as a result of social and environmental factors.  Black children and children living in disadvantaged neighborhoods have much higher rates of sleep apnea.

Socioeconomic disadvantage
Cardiovascular disease affects low- and middle-income countries even more than high-income countries. There is relatively little information regarding social patterns of cardiovascular disease within low- and middle-income countries, but within high-income countries low income and low educational status are consistently associated with greater risk of cardiovascular disease. Policies that have resulted in increased socio-economic inequalities have been associated with greater subsequent socio-economic differences in cardiovascular disease implying a cause and effect relationship. Psychosocial factors, environmental exposures, health behaviours, and health-care access and quality contribute to socio-economic differentials in cardiovascular disease. The Commission on Social Determinants of Health recommended that more equal distributions of power, wealth, education, housing, environmental factors, nutrition, and health care were needed to address inequalities in cardiovascular disease and non-communicable diseases.

Air pollution
Particulate matter has been studied for its short- and long-term exposure effects on cardiovascular disease. Currently, airborne particles under 2.5 micrometers in diameter (PM2.5) are the major focus, in which gradients are used to determine CVD risk. Overall, long-term PM exposure increased rate of atherosclerosis and inflammation. In regards to short-term exposure (2 hours), every 25 μg/m3 of PM2.5 resulted in a 48% increase of CVD mortality risk. In addition, after only 5 days of exposure, a rise in systolic (2.8 mmHg) and diastolic (2.7 mmHg) blood pressure occurred for every 10.5 μg/m3 of PM2.5.  Other research has implicated PM2.5 in irregular heart rhythm, reduced heart rate variability (decreased vagal tone), and most notably heart failure.  PM2.5 is also linked to carotid artery thickening and increased risk of acute myocardial infarction.

Cardiovascular risk assessment
Existing cardiovascular disease or a previous cardiovascular event, such as a heart attack or stroke, is the strongest predictor of a future cardiovascular event. Age, sex, smoking, blood pressure, blood lipids and diabetes are important predictors of future cardiovascular disease in people who are not known to have cardiovascular disease. These measures, and sometimes others, may be combined into composite risk scores to estimate an individuals future risk of cardiovascular disease. Numerous risk scores exist although their respective merits are debated. Other diagnostic tests and biomarkers remain under evaluation but currently these lack clear-cut evidence to support their routine use. They include family history, coronary artery calcification score, high sensitivity C-reactive protein (hs-CRP), ankle–brachial pressure index,  lipoprotein subclasses and particle concentration, lipoprotein(a), apolipoproteins A-I and B, fibrinogen, white blood cell count, homocysteine, N-terminal pro B-type natriuretic peptide  (NT-proBNP), and markers of kidney function. High blood phosphorus is also linked to an increased risk.

Depression and traumatic stress
There is evidence that mental health problems, in particular depression and traumatic stress, is linked to cardiovascular diseases. Whereas mental health problems are known to be associated with risk factors for cardiovascular diseases such as smoking, poor diet, and a sedentary lifestyle, these factors alone do not explain the increased risk of cardiovascular diseases seen in depression, stress, and anxiety. Moreover, posttraumatic stress disorder is independently associated with increased risk for incident coronary heart disease, even after adjusting for depression and other covariates.

Occupational exposure
Little is known about the relationship between work and cardiovascular disease, but links have been established between certain toxins, extreme heat and cold, exposure to tobacco smoke, and mental health concerns such as stress and depression.

Non-chemical risk factors
A 2015 SBU-report looking at non-chemical factors found an association for those:
with mentally stressful work with a lack of control over their working situation — with an effort-reward imbalance
who experience low social support at work; who experience injustice or experience insufficient opportunities for personal development; or those who experience job insecurity
those who work night schedules; or have long working weeks
those who are exposed to noiseSpecifically the risk of stroke was also increased by exposure to ionizing radiation. Hypertension develops more often in those who experience job strain and who have shift-work. Differences between women and men in risk are small, however men risk having and dying of heart attacks or stroke twice as often as women during working life.

Chemical risk factors
A 2017 SBU report found evidence that workplace exposure to silica dust, engine exhaust or welding fumes is associated with heart disease. Associations also exist for exposure to arsenic, benzopyrenes, lead, dynamite, carbon disulphide, carbon monoxide, metalworking fluids and occupational exposure to tobacco smoke. Working  with  the  electrolytic production of  aluminium  or  the  production  of  paper  when  the  sulphate pulping  process  is  used  is  associated with heart disease. An association was also found  between  heart  disease  and  exposure  to  compounds  which  are  no  longer  permitted  in certain  work  environments,  such  as  phenoxy acids containing TCDD(dioxin) or asbestos.Workplace exposure to silica dust or asbestos is also associated with pulmonary heart disease. There is evidence that workplace  exposure to lead, carbon disulphide, phenoxyacids containing  TCDD, as well as working in an environment where aluminum is being electrolytically produced, is associated with stroke.

Somatic mutations
As of 2017, evidence suggests that certain leukemia-associated mutations in blood cells may also lead to increased risk of cardiovascular disease. Several large-scale research projects looking at human genetic data have found a robust link between the presence of these mutations, a condition known as clonal hematopoiesis, and cardiovascular disease-related incidents and mortality.

Radiation therapy
Radiation treatments for cancer can increase the risk of heart disease and death, as observed in breast cancer therapy.  Therapeutic radiation increases the risk of a subsequent heart attack or stroke by 1.5 to 4 times; the increase depends on the dose strength, volume, and location.
Side-effects from radiation therapy for cardiovascular diseases have been termed radiation-induced heart disease or radiation-induced vascular disease. Symptoms are dose-dependent and include cardiomyopathy, myocardial fibrosis, valvular heart disease, coronary artery disease, heart arrhythmia and peripheral artery disease. Radiation-induced fibrosis, vascular cell damage and oxidative stress can lead to these and other late side-effect symptoms.

Pathophysiology
Population-based studies show that atherosclerosis, the major precursor of cardiovascular disease, begins in childhood. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study demonstrated that intimal lesions appear in all the aortas and more than half of the right coronary arteries of youths aged 7–9 years.Obesity and diabetes mellitus are linked to cardiovascular disease, as are a history of chronic kidney disease and hypercholesterolaemia.  In fact, cardiovascular disease is the most life-threatening of the diabetic complications and diabetics are two- to four-fold more likely to die of cardiovascular-related causes than nondiabetics.

Screening
Screening ECGs (either at rest or with exercise) are not recommended in those without symptoms who are at low risk. This includes those who are young without risk factors. In those at higher risk the evidence for screening with ECGs is inconclusive. Additionally echocardiography, myocardial perfusion imaging, and cardiac stress testing is not recommended in those at low risk who do not have symptoms. Some biomarkers may add to conventional cardiovascular risk factors in predicting the risk of future cardiovascular disease; however, the value of some biomarkers is questionable. Ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP), and coronary artery calcium, are also of unclear benefit in those without symptoms as of 2018.The NIH recommends lipid testing in children beginning at the age of 2 if there is a family history of heart disease or lipid problems. It is hoped that early testing will improve lifestyle factors in those at risk such as diet and exercise.Screening and selection for primary prevention interventions has traditionally been done through absolute risk using a variety of scores (ex. Framingham or Reynolds risk scores). This stratification has separated people who receive the lifestyle interventions (generally lower and intermediate risk) from the medication (higher risk). The number and variety of risk scores available for use has multiplied, but their efficacy according to a 2016 review was unclear due to lack of external validation or impact analysis. Risk stratification models often lack sensitivity for population groups and do not account for the large number of negative events among the intermediate and low risk groups. As a result, future preventative screening appears to shift toward applying prevention according to randomized trial results of each intervention rather than large-scale risk assessment.

Prevention
Up to 90% of cardiovascular disease may be preventable if established risk factors are avoided. Currently practised measures to prevent cardiovascular disease include:

Maintaining a healthy diet, such as the Mediterranean diet, a vegetarian, vegan or another plant-based diet.
Replacing saturated fat with healthier choices: Clinical trials show that replacing saturated fat with polyunsaturated vegetable oil reduced CVD by 30%. Prospective observational studies show that in many populations lower intake of saturated fat coupled with higher intake of polyunsaturated and monounsaturated fat is associated with lower rates of CVD.
Decrease body fat if overweight or obese. The effect of weight loss is often difficult to distinguish from dietary change, and evidence on weight reducing diets is limited. In observational studies of people with severe obesity, weight loss following bariatric surgery is associated with a 46% reduction in cardiovascular risk.
Limit alcohol consumption to the recommended daily limits. People who moderately consume alcoholic drinks have a 25–30% lower risk of cardiovascular disease. However, people who are genetically predisposed to consume less alcohol have lower rates of cardiovascular disease suggesting that alcohol itself may not be protective. Excessive alcohol intake increases the risk of cardiovascular disease and consumption of alcohol is associated with increased risk of a cardiovascular event in the day following consumption.
Decrease non-HDL cholesterol. Statin treatment reduces cardiovascular mortality by about 31%.
Stopping smoking and avoidance of second-hand smoke. Stopping smoking reduces risk by about 35%.
At least 150 minutes (2 hours and 30 minutes) of moderate exercise per week.
Lower blood pressure, if elevated. A 10 mmHg reduction in blood pressure reduces risk by about 20%. Lowering blood pressure appears to be effective even at normal blood pressure ranges.
Decrease psychosocial stress. This measure may be complicated by imprecise definitions of what constitute psychosocial interventions. Mental stress–induced myocardial ischemia is associated with an increased risk of heart problems in those with previous heart disease. Severe emotional and physical stress leads to a form of heart dysfunction known as Takotsubo syndrome in some people. Stress, however, plays a relatively minor role in hypertension. Specific relaxation therapies are of unclear benefit.
Not enough sleep also raises the risk of high blood pressure. Adults need about 7–9 hours of sleep. Sleep apnea is also a major risk as it causes breathing to stop briefly, which can put stress on the body which can raise the risk of heart disease.Most guidelines recommend combining preventive strategies. There is some evidence that interventions aiming to reduce more than one cardiovascular risk factor may have beneficial effects on blood pressure, body mass index and waist circumference; however, evidence was limited and the authors were unable to draw firm conclusions on the effects on cardiovascular events and mortality.There is additional evidence to suggest that providing people with a cardiovascular disease risk score may reduce risk factors by a small amount compared to usual care. However, there was some uncertainty as to whether providing these scores had any effect on cardiovascular disease events. It is unclear whether or not dental care in those with periodontitis affects their risk of cardiovascular disease.

Diet
A diet high in fruits and vegetables decreases the risk of cardiovascular disease and death.A 2021 review found that plant-based diets can provide a risk reduction for CVD if a healthy plant-based diet is consumed. Unhealthy plant-based diets do not provide benefits over diets including meat. A similar meta-analysis and systematic review also looked into dietary patterns and found "that diets lower in animal foods and unhealthy plant foods, and higher in healthy plant foods are beneficial for CVD prevention". A 2018 meta-analysis of observational studies concluded that "In most countries, a vegan diet is associated with a more favourable cardio-metabolic profile compared to an omnivorous diet."Evidence suggests that the Mediterranean diet may improve cardiovascular outcomes. There is also evidence that a Mediterranean diet may be more effective than a low-fat diet in bringing about long-term changes to cardiovascular risk factors (e.g., lower cholesterol level and blood pressure).The DASH diet (high in nuts, fish, fruits and vegetables, and low in sweets, red meat and fat) has been shown to reduce blood pressure, lower total and low density lipoprotein cholesterol  and improve metabolic syndrome; but the long-term benefits have been questioned. A high-fiber diet is associated with lower risks of cardiovascular disease.Worldwide, dietary guidelines recommend a reduction in saturated fat, and although the role of dietary fat in cardiovascular disease is complex and controversial there is a long-standing consensus that replacing saturated fat with unsaturated fat in the diet is sound medical advice. Total fat intake has not been found to be associated with cardiovascular risk. A 2020 systematic review found moderate quality evidence that reducing saturated fat intake for at least 2 years caused a reduction in cardiovascular events.  A 2015 meta-analysis of observational studies however did not find a convincing association between saturated fat intake and cardiovascular disease.  Variation in what is used as a substitute for saturated fat may explain some differences in findings. The benefit from replacement with polyunsaturated fats appears greatest,  while replacement of saturated fats with carbohydrates does not appear to have a beneficial effect. A diet high in trans fatty acids is associated with higher rates of cardiovascular disease, and in 2015 the Food and Drug Administration (FDA) determined that there was no longer a consensus among qualified experts that partially hydrogenated oils (PHOs), which are the primary dietary source of industrially produced trans fatty acids (IP-TFA), are generally recognized as safe (GRAS) for any use in human food. There is conflicting evidence concerning whether dietary supplements of omega-3 fatty acids (a type of polysaturated fat in oily fish) added to diet improve cardiovascular risk.The benefits of recommending a low-salt diet in people with high or normal blood pressure are not clear. In those with heart failure, after one study was left out, the rest of the trials show a trend to benefit. Another review of dietary salt concluded that there is strong evidence that high dietary salt intake increases blood pressure and worsens hypertension, and that it increases the number of cardiovascular disease events; both as a result of the increased blood pressure and probably through other mechanisms. Moderate evidence was found that high salt intake increases cardiovascular mortality; and some evidence was found for an increase in overall mortality, strokes, and left ventricular hypertrophy.

Intermittent fasting
Overall, the current body of scientific evidence is uncertain on whether intermittent fasting could prevent cardiovascular disease. Intermittent fasting may help people lose more weight than regular eating patterns, but was not different than energy restriction diets.

Medication
Blood pressure medication reduces cardiovascular disease in people at risk, irrespective of age, the baseline level of cardiovascular risk, or baseline blood pressure. The commonly-used drug regimens have similar efficacy in reducing the risk of all major cardiovascular events, although there may be differences between drugs in their ability to prevent specific outcomes. Larger reductions in blood pressure produce larger reductions in risk, and most people with high blood pressure require more than one drug to achieve adequate reduction in blood pressure. Adherence to medications is often poor, and while mobile phone text messaging has been tried to improve adherence, there is insufficient evidence that it alters secondary prevention of cardiovascular disease.Statins are effective in preventing further cardiovascular disease in people with a history of cardiovascular disease. As the event rate is higher in men than in women, the decrease in events is more easily seen in men than women. In those at risk, but without a history of cardiovascular disease (primary prevention), statins decrease the risk of death and combined fatal and non-fatal cardiovascular disease. The benefit, however, is small. A United States guideline recommends statins in those who have a 12% or greater risk of cardiovascular disease over the next ten years.  Niacin, fibrates and CETP Inhibitors, while they may increase HDL cholesterol do not affect the risk of cardiovascular disease in those who are already on statins. Fibrates lower the risk of cardiovascular and coronary events, but there is no evidence to suggest that they reduce all-cause mortality.Anti-diabetic medication may reduce cardiovascular risk in people with Type 2 diabetes, although evidence is not conclusive. A meta-analysis in 2009 including 27,049 participants and 2,370 major vascular events showed a 15% relative risk reduction in cardiovascular disease with more-intensive glucose lowering over an average follow-up period of 4.4 years, but an increased risk of major hypoglycemia.Aspirin has been found to be of only modest benefit in those at low risk of heart disease, as the risk of serious bleeding is almost equal to the protection against cardiovascular problems. In those at very low risk, including those over the age of 70, it is not recommended. The United States Preventive Services Task Force recommends against use of aspirin for prevention in women less than 55 and men less than 45 years old; however, it is recommended for some older people.The use of vasoactive agents for people with pulmonary hypertension with left heart disease or hypoxemic lung diseases may cause harm and unnecessary expense.Antibiotics for secondary prevention of coronary heart disease
Antibiotics may help patients with coronary disease to reduce the risk of heart attacks and strokes. However, evidence in 2021 suggests that antibiotics for secondary prevention of coronary heart disease are harmful, with increased mortality and occurrence of stroke; the use of antibiotics is not supported for preventing secondary coronary heart disease.

Physical activity
Exercise-based cardiac rehabilitation following a heart attack reduces the risk of death from cardiovascular disease and leads to less hospitalizations. There have been few high-quality studies of the benefits of exercise training in people with increased cardiovascular risk but no history of cardiovascular disease.A systematic review estimated that inactivity is responsible for 6% of the burden of disease from coronary heart disease worldwide. The authors estimated that 121,000 deaths from coronary heart disease could have been averted in Europe in 2008 if people had not been physically inactive. Low-quality evidence from a limited number of studies suggest that yoga has beneficial effects on blood pressure and cholesterol. Tentative evidence suggests that home-based exercise programs may be more efficient at improving exercise adherence.

Dietary supplements
While a healthy diet is beneficial, the effect of antioxidant supplementation (vitamin E, vitamin C, etc.) or vitamins has not been shown to protect against cardiovascular disease and in some cases may possibly result in harm. Mineral supplements have also not been found to be useful. Niacin, a type of vitamin B3, may be an exception with a modest decrease in the risk of cardiovascular events in those at high risk. Magnesium supplementation lowers high blood pressure in a dose-dependent manner. Magnesium therapy is recommended for people with ventricular arrhythmia associated with torsades de pointes who present with long QT syndrome, and for the treatment of people with digoxin intoxication-induced arrhythmias. There is no evidence that omega-3 fatty acid supplementation is beneficial.

Management
Cardiovascular disease is treatable with initial treatment primarily focused on diet and lifestyle interventions. Influenza may make heart attacks and strokes more likely and therefore influenza vaccination may decrease the chance of cardiovascular events and death in people with heart disease.Proper CVD management necessitates a focus on MI and stroke cases due to their combined high mortality rate, keeping in mind the cost-effectiveness of any intervention, especially in developing countries with low or middle-income levels. Regarding MI, strategies using aspirin, atenolol, streptokinase or tissue plasminogen activator have been compared for quality-adjusted life-year (QALY) in regions of low and middle income </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Anterior spinal artery syndrome and can you explain it in depth? [/INST] Anterior spinal artery syndrome (also known as "anterior spinal cord syndrome") is syndrome caused by ischemia of the anterior spinal artery, resulting in loss of function of the anterior two-thirds of the spinal cord. The region affected includes the descending  corticospinal tract, ascending spinothalamic tract, and autonomic fibers. It is characterized by a corresponding loss of motor function, loss of pain and temperature sensation, and hypotension.
Anterior spinal artery syndrome is the most common form of spinal cord infarction. The anterior spinal cord is at increased risk for infarction because it is supplied by the single anterior spinal artery and has little collateral circulation, unlike the posterior spinal cord which is supplied by two posterior spinal arteries.

Signs and symptoms
Complete motor paralysis below the level of the lesion due to interruption of the corticospinal tract
Loss of pain and temperature sensation at and below the level of the lesion due to interruption of the spinothalamic tract
Retained proprioception and vibratory sensation due to intact dorsal columns
Autonomic dysfunction may be present and can manifest as hypotension (either orthostatic or frank hypotension), sexual dysfunction, and/or bowel and bladder dysfunction
Areflexia, flaccid internal and external anal sphincter, urinary retention and intestinal obstruction may also be present in individuals with anterior cord syndrome.Symptoms usually occur very quickly and are often experienced within one hour of the initial damage.  MRI can detect the magnitude and location of the damage 10–15 hours after the initiation of symptoms.  Diffusion-weighted imaging may be used as it is able to identify the damage within a few minutes of symptomatic onset.Clinical features include paraparesis or quadriparesis (depending on the level of the injury) and impaired pain and temperature sensation.  Complete motor paralysis below the level of the lesion due to interruption of the corticospinal tract, and loss of pain and temperature sensation at and below the level of the lesion. Proprioception and vibratory sensation is preserved, as it is in the dorsal side of the spinal cord.

Causes
Due to the branches of the aorta that supply the anterior spinal artery, the most common causes are insufficiencies within the aorta </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Vogt–Koyanagi–Harada disease and can you explain it in depth? [/INST] Vogt–Koyanagi–Harada disease (VKH) is a multisystem disease of presumed autoimmune cause that affects melanin-pigmented tissues. The most significant manifestation is bilateral, diffuse uveitis, which affects the eyes. VKH may variably also involve the inner ear, with effects on hearing, the skin, and the meninges of the central nervous system.

Signs and symptoms
Overview
The disease is characterised by bilateral diffuse uveitis, with pain, redness and blurring of vision. The eye symptoms may be accompanied by a varying constellation of systemic symptoms, such as auditory (tinnitus, vertigo, and hypoacusis), neurological (meningismus, with malaise, fever, headache, nausea, abdominal pain, stiffness of the neck and back, or a combination of these factors; meningitis, CSF pleocytosis, cranial nerve palsies, hemiparesis, transverse myelitis and ciliary ganglionitis), and cutaneous manifestations, including poliosis, vitiligo, and alopecia. The vitiligo often is found at the sacral region.

Phases
The sequence of clinical events in VKH is divided into four phases - prodromal, acute uveitic, convalescent, and chronic recurrent.The prodromal phase may have no symptoms, or may mimic a nonspecific viral infection, marked by flu-like symptoms that typically last for a few days. Fever, headache, nausea, meningismus, dysacusia (discomfort caused by loud noises or a distortion in the quality of the sounds being heard), tinnitus, and/or vertigo may occur. Eye symptoms can include orbital pain, photophobia, and tearing. The skin and hair may be sensitive to touch. Cranial nerve palsies and optic neuritis are uncommon.The acute uveitic phase occurs a few days later and typically lasts for several weeks. This phase is heralded by bilateral panuveitis causing blurring of vision. In 70% of VKH cases, the onset of visual blurring is bilaterally contemporaneous; if initially unilateral, the other eye is involved within several days. The process can include bilateral granulomatous anterior uveitis, variable degree of vitritis, thickening of the posterior choroid with elevation of the peripapillary retinal choroidal layer, optic nerve hyperemia and papillitis, and multiple exudative bullous serous retinal detachments.The convalescent phase is characterized by gradual tissue depigmentation of skin with vitiligo and poliosis, sometimes with nummular depigmented scars, as well as alopecia and diffuse fundus depigmentation resulting in a classic orange-red discoloration ("sunset glow fundus") and retinal pigment epithelium clumping and/or migration.The chronic recurrent phase may be marked by repeated bouts of uveitis, but is more commonly a chronic, low-grade, often subclinical, uveitis that may lead to granulomatous anterior inflammation, cataracts, glaucoma, and ocular hypertension. Full-blown recurrences, though, are rare after the acute stage is over. Dysacusia may occur in this phase.

Cause
Although sometimes a viral infection, or skin or eye trauma precedes an outbreak, the exact underlying initiator of VKH disease remains unknown. VKH is attributed, however, to aberrant T-cell-mediated immune response directed against self-antigens found on melanocytes. Stimulated by interleukin 23 (IL-23), T helper 17 cells and cytokines, such as interleukin 17, appear to target proteins in the melanocytes.

Risk factors
Affected individuals are typically 20 to 50 years old. The female-to-male ratio is 2:1. By definition, affected people have no history of either surgical or accidental ocular trauma. VKH is more common in Asians, Latinos, Middle Easterners, American Indians, and Mexican Mestizos; it is much less common in Caucasians and in Blacks from sub-Saharan Africa.VKH is associated with a variety of genetic polymorphisms that relate to immune function. For example, t has been associated with human leukocyte antigens (HLA) HLA-DR4 and DRB1/DQA1, copy-number variations of complement component 4, a variant IL-23R locus and with various other non-HLA genes. HLA-DRB1*0405 in particular appears to play an important susceptibility role.

Diagnosis
If tested in the prodromal phase, cerebrospinal fluid pleocytosis is found in more than 80% of cases, with mainly lymphocytes. This pleocytosis resolves in about 8 weeks even if chronic uveitis persists.Functional tests may include electroretinogram and visual field testing. Diagnostic confirmation and an estimation of disease severity may involve imaging tests such as retinography, fluorescein or indocyanine green angiography, optical coherence tomography and ultrasound. For example, indocyanine green angiography may detect continuing choroidal inflammation in the eyes without clinical symptoms or signs. Ocular MRI may be helpful and auditory symptoms should undergo audiologic testing. Histopathology findings from eye and skin are discussed by Walton.The diagnosis of VKH is based on the clinical presentation; the diagnostic differential is extensive, and includes sympathetic ophthalmia, sarcoidosis, primary intraocular B-cell lymphoma, posterior scleritis, uveal effusion syndrome, tuberculosis, syphilis, and multifocal choroidopathy syndromes.

Types
Based on the presence of extraocular findings, such as neurological, auditory, and integumentary manifestations, the "revised diagnostic criteria" of 2001 classify the disease as complete (eyes along with both neurological and skin), incomplete (eyes along with either neurological or skin), or probable (eyes without either neurological or skin) . By definition, for research homogeneity purposes, the two exclusion criteria are previous ocular penetrating trauma or surgery, and other concomitant ocular disease similar to VKH disease.

Management
The acute uveitis]phase of VKH is usually responsive to high-dose oral corticosteroids; parenteral administration is usually not required </s>