The most common presentation of hyperlipidemia is a cardiovascular event. Patients are typically overweight, lethargic and may have one or multiple xanthomas on their skin. They may also be suffering from other diseases like diabetes or pancreatitis. In case of homozygous familial types, presentation is often similar to that of ischemic heart disease. In heterozygous types, the patients are often asymptomatic.

There may also be tendon xanthomas, xanthelasmas (yellow coloured lesions on eyelids) and corneal arcus (gray coloured opacity on periphery of cornea). The most commonly found ophthalmologic abnormalities occurring in patients with hyperlipidemia include corneal arcus, lipemia retinalis, and xanthelasma [7]. Patients may also complain of abdominal pain, nausea, vomiting and sometimes dyspnea.

• Pain

  Analysis of preoperative clinical scores revealed that patients with SEL experienced pain more frequently and showed less walking ability than did those without SEL. [ncbi.nlm.nih.gov]

  Build up of plaque in your arteries may lead to symptoms of heart attack (chest pain, difficulty breathing), stroke or TIA (speech difficulty, weakness or numbness on one side of your body), or claudication (pain in your calves, thigh, or buttocks with [urmc.rochester.edu]

  Some of these symptoms include: Angina/Chest pain Heart attack symptoms like: o Chest pain o Pain or pressure in your shoulders, arms, back, neck or jaw o Shortness of breath Stroke symptoms like: o Sudden and severe headaches o Weakness, numbness, tingling [yourffmg.com]

• Asymptomatic

  In heterozygous types, the patients are often asymptomatic. There may also be tendon xanthomas, xanthelasmas (yellow coloured lesions on eyelids) and corneal arcus (gray coloured opacity on periphery of cornea). [symptoma.com]

  We report the clinical, laboratory, radiographic, histopathologic, immunohistochemical, and ultrastructural studies of a mandibular lesion discovered in an asymptomatic 16-year-old male, and associated with 2 previously unreported comorbidities, namely [ncbi.nlm.nih.gov]

  Hyperlipidemia is usually asymptomatic. However, certain forms may be associated with types of xanthomas. [radiopaedia.org]

  […] converted into LDLs cells with LDL receptor then receive cholesterol from LDLs HDL carries extra cholesterol back to the liver to be metabolized Associated conditions diabetes hypertension hypertriglyceridemia atherosclerosis Presentation Symptoms typically asymptomatic [step2.medbullets.com]

  Clinical description Most patients are asymptomatic. [orpha.net]

• Coronary Atherosclerosis

  atherosclerosis. remnant hyperlipidemia a form in which the accumulated lipoproteins are normally transient intermediates, chylomicron remnants, and intermediate-density lipoproteins; a generic descriptor for the type III hyperlipoproteinemia phenotype [medical-dictionary.thefreedictionary.com]

  Definition / general Term used to denote excess of lipids, mainly cholesterol and triglycerides (TG), in the blood Strong relationship between high plasma lipids and coronary heart disease Lowering LDL and raising HDL decrease the progression of coronary [pathologyoutlines.com]

  Effects of monotherapy with an HMG-CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography: the Canadian Coronary Atherosclerosis Intervention Trial. Circulation.1994; 89:959-968. [ahajournals.org]

• Fever

  She presented at the age of 9 years with fever, headaches, and abnormal lipid profile. Months later, she had clinical manifestations, biochemical findings, and the histologic picture of autoimmune hepatitis. [ncbi.nlm.nih.gov]

  Información en español Title Other Names: Hyper IgD syndrome; Hyperimmunoglobulinemia D and periodic fever syndrome; Periodic fever Dutch type; Hyper IgD syndrome; Hyperimmunoglobulinemia D and periodic fever syndrome; Periodic fever Dutch type; HIDS [rarediseases.info.nih.gov]

  Clinical description The disease usually begins in the first year of life and consists of recurrent attacks of fever along with abdominal pain, vomiting and diarrhea. [orpha.net]

  —Patrick Danner, San Antonio Express-News, 2 Mar. 2021 Bui's medical history included hypertension, rheumatoid arthritis, hyperlipidemia and valley fever, according to the report. [merriam-webster.com]

• Fatigue

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: May 13, 2019 [patientslikeme.com]

  —Ashley Andreou, Scientific American, 26 May 2022 Next were breathing difficulties, like shortness of breath (affecting 3.5% of patients); hyperlipidemia, or high levels of triglycerides or cholesterol in the blood (3%); malaise and fatigue (2.9%); and [merriam-webster.com]

  Key side effects include headache, fatigue, altered bowel habit. A signature side effect of statins is inflammation of muscles which can cause muscle pain and renal damage. [healthybutsmart.com]

  Some sleep problems can lead to serious health issues such as heart attack, stroke, high blood pressure, fatigue-related motor vehicle accidents, and decreased quality of life. [excelahealth.org]

  Symptoms include cold intolerance, fatigue, and weight gain. Signs may include a typical facial appearance, hoarse slow speech, and dry skin. [msdmanuals.com]

• Dyspnea

  Patients may also complain of abdominal pain, nausea, vomiting and sometimes dyspnea. [symptoma.com]

  Symptoms include chest discomfort with or without dyspnea, nausea, and diaphoresis. [msdmanuals.com]

  Recurrent episodes of ill-defined abdominal pain that may be accompanied by nausea and vomiting are the most common presenting symptom, but chest pain and dyspnea may sometimes occur. [emedicine.medscape.com]

  Very high triglyceride levels can also cause hepatosplenomegaly, paresthesias, dyspnea, and confusion. High levels of LDL can cause arcus corneae and tendinous xanthomas at the Achilles, elbow, and knee tendons and over metacarpophalangeal joints. [merckmanuals.com]

• Overeating

  Eventually muscle cells enlarge and form a fibrous cap over the fatty plaque, resulting in narrowing of the artery. [tocris.com]

  Over time, this can cause atherosclerosis, or hardening of the arteries. Cholesterol is a waxy fat-like substance that your body needs to make hormones and vitamin D. It also aids digestion. [upmc.com]

  […] three kinds of lipoproteins in the body: Low-density lipoprotein (or LDL) High-density lipoprotein (or HDL) Triglycerides Too much LDL, or “bad” cholesterol, can build up in the arteries (the blood vessels that carry blood throughout the body) and, over [academic.oup.com]

  Hyperlipidemia has been seen in over half of the eighteen cases reported in the literature. We report an unusual presentation of granulomatous PPD seen in a 71 year-old Caucasian female with hyperlipidemia. [ncbi.nlm.nih.gov]

  Be a patron at: https://www.patreon.com/LYMED Welcome to LY Med, where I go over everything you need to know for the USMLE STEP 1, with new videos every day. [youtube.com]

• Failure to Thrive

  Symptoms, which usually appear early, mainly consist of failure to thrive, steatorrhea, and signs of vitamin E deficiency. The treatment includes supplementation of vitamin E. [amboss.com]

  There is a more severe condition, known as Mevalonate Aciduria (MA) that also involves a mutation in the MVK gene, but it is associated with significant, chronic inflammation, dysmorphic facial features, failure to thrive,systemic organ involvement and [autoinflammatory.org]

  Niacin can cause liver enzyme elevations and occasionally liver failure, insulin resistance, and hyperuricemia and gout. It may also increase homocysteine levels. [merckmanuals.com]

• Choking

  If a clot lodges in an artery and completely chokes off the blood supply, the cells don’t get the nutrients and oxygen they need – and die. If a clot gets to the brain and blocks blood flow, it can cause a stroke. [gnet.org]

• Hypertension

  NCDs include all lifestyle-induced conditions such as CVD (cardiovascular disease), diabetes, hypertension and hyperlipidaemia (high cholesterol) that lead to health complications requiring hospitalisation and are life-threatening. [medical-dictionary.thefreedictionary.com]

  —Patrick Danner, San Antonio Express-News, 2 Mar. 2021 Bui's medical history included hypertension, rheumatoid arthritis, hyperlipidemia and valley fever, according to the report. [merriam-webster.com]

  This study explores knowledge, attitudes, and beliefs regarding hypertension and hyperlipidemia management among 34 African-American men with hypertension and/or hyperlipidemia, age 40-65, living in the Southeastern United States. [ncbi.nlm.nih.gov]

  Hypertension and hyperlipidemia are well-established and partially overlapping risk factors for cardiovascular disease. [portal.findresearcher.sdu.dk]

• Vascular Disease

  […] for vascular diseases and shed new light on regenerative medicine. [ncbi.nlm.nih.gov]

  Type III HLP is a serious disorder with lifelong consequences of premature vascular disease and recurrent pancreatitis. Early presentation of disease in our patients was associated with additional precipitating factors. [doi.org]

• Chest Pain

  It is characterised by chest pain, discomfort or a squeezing pressure. Angina occurs as a result of a reduction or a lack of blood supply to a part or the entire heart muscle. [fertilitypedia.org]

  Build up of plaque in your arteries may lead to symptoms of heart attack (chest pain, difficulty breathing), stroke or TIA (speech difficulty, weakness or numbness on one side of your body), or claudication (pain in your calves, thigh, or buttocks with [urmc.rochester.edu]

  Complications may include: Early atherosclerotic heart disease Heart attack Stroke Seek medical care right away if you have chest pain or other warning signs of a heart attack. [medlineplus.gov]

  Some of these symptoms include: Angina/Chest pain Heart attack symptoms like: o Chest pain o Pain or pressure in your shoulders, arms, back, neck or jaw o Shortness of breath Stroke symptoms like: o Sudden and severe headaches o Weakness, numbness, tingling [yourffmg.com]

  However, if it results in coronary heart disease (CHD) or atherosclerosis, symptoms in adults can include: Chest pain or pressure (angina) Blockage of blood vessels in brain and heart High blood pressure Heart attack Stroke Diagnosis If hyperlipidemia [baptisthealth.com]

• Palpitations

  In patients with hypercholesterolemia, palpitate all pulses and elicit carotids and femoral bruits. [physio-pedia.com]

• Myalgia

  […] with diabetes are considered as secondary prevention Hypercholesterolemia Statins are the drugs of choice for the treatment of hypercholesterolemia They inhibit HMG CoA reductase required for cholesterol synthesis in the liver Possible side effects: myalgia [pathologyoutlines.com]

  While effective, this combination increases the possibility of abnormal biochemical liver function tests and myalgia. Concentrated omega-3 fatty acids can lower serum triglyceride levels by up to 38% in a dose-dependent manner. [mendeley.com]

  Type 3 hypersensitivity reactions were similar to Type 1 hypersensitivity reactions but were likely to be delayed from the time of injection and included symptoms such as rash, urticaria, polyarthritis, myalgia's, polysynovitis, fever and if severe then [clinicaltrials.gov]

  […] pain 0002829 Elevated erythrocyte sedimentation rate High ESR 0003565 Gastrointestinal hemorrhage Gastrointestinal bleeding 0002239 Hepatomegaly Enlarged liver 0002240 Increased circulating IgA level 0003261 Lymphadenopathy Swollen lymph nodes 0002716 Myalgia [rarediseases.info.nih.gov]

• Back Pain

  Patient data of age at surgery, body mass index, prevalence of common noncommunicable diseases, blood tests, arteriosclerotic index, and preoperative clinical scores (assessed using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire [ncbi.nlm.nih.gov]

  Chronic pancreatitis may result in back pain, diarrhea, yellow-colored skin (jaundice), and potentially the development of diabetes. [rarediseases.org]

• Alopecia

  Some examples: Psoriasis Crohn disease Inflammatory bowel disease Chronic obstructive pulmonary disease Depression Chronic pain Pediatric alopecia areata Chronic kidney disease Histopathology In the presence of hyperlipidemia, not only the vascular structures [ncbi.nlm.nih.gov]

• Stroke

  Your doctor may also recommend medicine to help lower your cholesterol to reduce your risk of stroke or heart attack. [urmc.rochester.edu]

  Other risk factors Family history of early stroke or heart disease Complications Heart disease – angina and heart attack Stroke and transient ischemic attack Peripheral arterial disease Diagnosis A blood test called the serum lipid profile measures the [news-medical.net]

  CAD (causing ischemic heart disease) is the leading cause of death worldwide, followed by stroke-related deaths. [physio-pedia.com]

  Left untreated, hypercholesterolemia can eventually lead to a heart attack due to CHD or a stroke due to narrowed arteries supplying the brain. [healthcommunities.com]

  Both heart attack and stroke involve the interruption of blood flow to an organ due to a blockage within an artery. [rxlist.com]

• Confusion

  The renowned authors, acknowledging the confusion surrounding the place of statins, carefully unpick clinical trial evidence and discuss guideline recommendations. The result is a clear and logical approach to the management of hyperlipidemia. [karger.com]

  Confusion or trouble speaking. Weakness, often in your arm. Doctors at the Center for Inherited Heart Disease use blood tests to diagnose hyperlipidemia. They'll also ask you about your family history and any other health problems you have. [upmc.com]

  Discomfort or pain in your back, neck, jaw, stomach, or arm Shortness of breath Nausea or vomiting Lightheadedness or a sudden cold sweat You have any of the following signs of a stroke: Numbness or drooping on one side of your face Weakness in an arm or leg Confusion [drugs.com]

  As hyperlipidemia progresses, it may lead to any of these symptoms: Chest pain (angina) High blood pressure Cramps in the calves Pain in the feet Confusion or trouble speaking Shortness of breath Muscle weakness Fatty deposits of cholesterol around the [ucfhealth.com]

• Dizziness

  stomach, or arm Shortness of breath Nausea or vomiting Lightheadedness or a sudden cold sweat You have any of the following signs of a stroke: Numbness or drooping on one side of your face Weakness in an arm or leg Confusion or difficulty speaking Dizziness [drugs.com]

  […] number [ more ] 0001974 Neutrophilia Increased blood neutrophil counts 0011897 Nyctalopia Night blindness Night-blindness Poor night vision [ more ] 0000662 Optic disc pallor 0000543 Skin rash 0000988 Splenomegaly Increased spleen size 0001744 Vertigo Dizzy [rarediseases.info.nih.gov]

• Lethargy

  Poor feeding, lethargy, hyperglycemia, and hyperlipidemia were resolved with the normalization of triglyceride level. References Raupp P, Keenan C, Dowman M, Nath R, Hertecant J. [web.archive.org]

  […] assess for proteinuria Making the diagnosis based on laboratory studies Differential Hypothyroidism distinguishing factors abnormal thyroid function tests often presents with other symptoms of hypothyroidism, including weight gain, cold intolerance, and lethargy [step2.medbullets.com]

  […] raw conversion factor, since we usually talk in approximations anyway. mmol/l mg/dl interpretation ------ ----- -------------- 2.0 35 extremely low, danger of unconciousness 3.0 55 low, marginal insulin reaction 4.0 75 slightly low, first symptoms of lethargy [faqs.org]

• Vertigo

  […] leukocyte number [ more ] 0001974 Neutrophilia Increased blood neutrophil counts 0011897 Nyctalopia Night blindness Night-blindness Poor night vision [ more ] 0000662 Optic disc pallor 0000543 Skin rash 0000988 Splenomegaly Increased spleen size 0001744 Vertigo [rarediseases.info.nih.gov]

Laboratory tests

• Complete blood count
• Complete lipid panel
• Resting and fasting blood sugar levels
• Thyroid function tests
• Renal function tests

Imaging 

• ECG
• Echocardiography 
• CT coronary angiography

Test results

All potential underlying diseases should be tested and methodically excluded with the help of history and laboratory tests. The elevated lipids should be checked with the help of a lipid analysis and imaging studies should be conducted to reveal the extent of damage to the vasculature and other organs.

• Hypercholesterolemia

  Table of Contents: • Lipids and lipoprotein particles • Epidemiology and pathophysiology • Familial hypercholesterolemia • Polygenic hypercholesterolemia and combined hyperlipidemia • Hypertriglyceridemia • Familial dysbetalipoproteinemia • Dyslipidemia [karger.com]

  Interestingly anorexia nervosa has long been associated with severe but reversible hypercholesterolemia. Several classes of drugs need to be considered as common causes of altered lipid profiles. [ncbi.nlm.nih.gov]

  Hypercholesterolemia is especially dangerous when HDL (“good”) cholesterol levels are low. Left untreated, hypercholesterolemia can eventually lead to a heart attack due to CHD or a stroke due to narrowed arteries supplying the brain. [healthcommunities.com]

  One is associated with a deficiency of δ-aminoadipic semialdehyde synthase. hyperlipidemia /hy·per·lip·id·emia/ ( -lip″ĭ-de´me-ah ) elevated concentrations of any or all of the lipids in the plasma, including hypertriglyceridemia, hypercholesterolemia [medical-dictionary.thefreedictionary.com]

  Hypercholesterolemia. InStatPearls [Internet] 2019 Feb 16. [physio-pedia.com]

• Hypertriglyceridemia

  In those with an underlying primary hypertriglyceridemia and associated obesity, estrogenic medications can depress triglyceride removal mechanisms, leading to the chylomicronemia syndrome and pancreatitis. [ncbi.nlm.nih.gov]

  Table of Contents: • Lipids and lipoprotein particles • Epidemiology and pathophysiology • Familial hypercholesterolemia • Polygenic hypercholesterolemia and combined hyperlipidemia • Hypertriglyceridemia • Familial dysbetalipoproteinemia • Dyslipidemia [karger.com]

  Hypertriglyceridemia often requires treatment with a combination of a fibrate and a statin. [healthcommunities.com]

• Lactescent Serum

  He had a lactescent serum and hypertriglyceridemia. Lethargy, hepatomegaly, and hyperglycemia increased with time. Increasing hyperglycemia in spite of having insulin therapy indicated the existence of insulin-resistant diabetes type. [web.archive.org]

Primary medication used to effectively treat the condition is statins. Statins are a class of drugs that lower circulating cholesterol levels by inhibiting HMG-CoA reductase , which is the rate-limiting enzyme in hepatic cholesterol biosynthesis [8]. Other drugs include fibrates, to control high triglyceride levels, bile resins and sequestrants for hypercholesterolemia, and niacin. Lipid apheresis may also be used to treat patients with severe hyperlipidemia by reducing low-density lipoprotein cholesterol (LDL-C) levels [9]. The parallel mode of treatment includes lifestyle modifications and a carefully controlled diet.

Prognosis depends heavily on management. If the hyperlipidemia, be it familial or secondary, is appropriately managed with drugs, appropriate diet and lifestyle modifications, the prognosis is fairly positive. However, if the condition is not managed, there is a negative prognosis and a high rate of mortality. Epidemiologic studies found a direct relationship between the total cholesterol levels and risk of coronary disease [6]. Indeed the high mortality can be attributed to cardiovascular diseases.

Hyperlipidemia may be primary [1], for example familial hyperlipidemia (FH), or secondary meaning it occurs as a consequence of other diseases that disturb lipid metabolism [2], for example diabetes mellitus. Hyperlipidemia in association with insulin resistance is a common occurrence in patients suffering from diabetes mellitus type II (DM 2) [2].

In case of FH, the causative factors are inherited mutations in genes like APOB, APOC2 etc, deficiency of the lipoprotein lipase enzyme (LPL) or disturbed functioning of LDL receptors. Acquired hyperlipidemias are caused by diseases that interfere with lipid metabolism and uptake into cells.

Incidence

CDC conducted a survey of the prevalence of hyperlipidemia with respect to body mass index (BMI) between 1999 and 2006 and it reported a prevalence of 14.2% in normal weight individuals, 22.3% in overweight individuals and 42.9% in the obese [3].

Age

Hyperlipidemia may present in the youth in familial cases but non-familial cases usually present much later in life.

Sex

Hyperlipidemia tends to be slightly more common in men than women.

Primary hyperlipidemias can be classified on the basis of the type of elevated lipoproteins found in the blood, using the Fredrickson criteria [4]:

• Type I hyperlipoproteinemia: It is of three subtypes: A, b and c. All three result in elevation of chylomicrons in the blood. It is a rare type of hyperlipidemia with an incidence of only 1 out of 1000,000 births and can be easily managed with a controlled diet and regular exercise.
• Type II hyperlipoproteinemia: It is of two subtypes: Type IIa has increased levels of LDL and Type IIb has elevated LDL as well as VLDL. It is much more common with an incidence of 1 out of 500 births for Type IIa and 1 out of 100 births for TYPE IIb.
• Type III hyperlipoproteinemia: It has no subtype. It results in elevated IDL in blood and occurs in 1 out of 10,000 births.
• Type IV hyperlipoproteinemia: It is an autosomal-dominant condition that results in increased levels of VLDL in the blood and is estimated to occur in 1 out of 10,000 births (approximately 1% of the population) [5].
• Type V hyperlipoproteinemia: It is a rare type which results in elevated chylomicrons and VLDL in the blood.

Secondary hyperlipidemias or acquired hyperlipidemias are a consequence of underlying disease such as hypothyroidism, renal failure, excessive intake of alcohol, diabetes, metabolic syndrome or chronic pancreatitis. The elevated lipids are either a consequence of direct damage to the liver, and thus the lipid metabolism, or due to nonenzymatic glycosylation of blood vessel as in diabetes, pancreatitis due to alcoholism or high absorption from the gut due to increased intake as in obese individuals.

Hyperlipidemia can easily be prevented by exhibiting a healthy lifestyle. Good cholesterol (HDL) should be kept elevated and bad cholesterol (LDL) should be kept in reduced limits. Exercise and moderate consumption of ethanol raise HDL levels, whereas obesity and smoking lower it [10]. So a healthy lifestyle demonstrated by regular exercise, controlled diet and avoiding smoking and excessive alcohol can go a long way in both preventing the occurrence of, as well as the progress of hyperlipidemia.

Hyperlipidemia is a disorder of increased lipid or lipoprotein levels and is the most common form of dyslipidemia. Lipids are a group of biological organic compounds that are insoluble in water but soluble in organic solvents. For the purpose of adhering strictly to the human body and the phenomenon of hyperlipidemia, lipids are classified into 6 types. They are: High density lipids (HDL), low density lipids (LDL), Intermediate density lipids (IDL), very low density lipids (VLDL), triglycerides and cholesterol. If any one or more of these types become abnormally elevated in the blood, it is known as hyperlipidemia.

Definition

Hyperlipidemia is a group of conditions where there is an abnormally increased level of lipids (fats) in the blood.

Cause

It can be genetic, known as primary or familial hyperlipidemia due to inherited mutations or it can be acquired; as a consequence of an extravagant lifestyle or underlying disease.

Signs and symptoms

It may be asymptomatic initially and typically presents late in the form of a cardiovascular event. Infants may present with signs similar to ischemic heart disease and small raised yellow coloured lesions on the skin (xanthomas). Adults may also have xanthomas either on the skin or in their tendons.

Diagnosis

Diagnosis is based on excluding or identifying underlying disease, and measuring lipid levels in the blood. A detailed history also helps in diagnosing familial types.

Treatment

Treatment includes dietery and lifestyle modifications and drugs.

1. Chait A, Brunzell JD. Acquired hyperlipidemia (secondary dyslipoproteinemias). Endocrinol. Metab. Clin. North Am. June 1990, 19 (2): 259–78. PMID 2192873.
2. Zavaroni I, Dall'Aglio E, Alpi O, et al. Evidence for an independent relationship between plasma insulin and concentration of high density lipoprotein cholesterol and triglyceride. Atherosclerosis 1985; 55:259.
3. Centers for Disease Control and Prevention. Prevalence of abnormal lipid levels among youths: United States, 1999–2006. MMWR Morb Mortal Wkly Rep. 2010;59:29–33.
4. Fredrickson DS, Lees RS. A system for phenotyping hyperlipoproteinemia (PDF). Circulation, 1965, 31 (3): 321–7.
5. Boman H, Hazzard WR, AlbersJJ, et al. Frequency of monogenic forms of hyperlipidemia in a normal population. Am J ttum Genet 27:19A,1975. 
6. Wallis EJ, Ramsay LE, Ul Haq I, et al. Coronary and cardiovascular risk estimation for primary prevention: validation of a new Sheffield table in the 1995 Scottish health survey population. BMJ 2000; 320:671.
7. Wu CW, Lin PY, Liu YF, Liu TC, Lin MW, Chen WM, et al. Central corneal mosaic opacities in Schnyder's crystalline dystrophy. Ophthalmology. Apr 2005;112(4):650-3
8. Glassberg H, Rader D. Management of lipids in the prevention of cardiovascular events. Annu Rev Med 59:79-94, 2008
9. Lui M, Garberich R, Strauss C, Davin T, Knickelbine T. Usefulness of lipid apheresis in the treatment of familial hypercholesterolemia. J Lipids. 2014;2014:864317. 
10. Ridker P, Libby P. Risk factors for atherothrombotic disease. In Zipes D, et al (eds). Braunwald’s Heart Disease, 7th ed. Philadelphia, ElsevierSaunders, 2005, p 939.