High HDL Cholesterol (Hyperalphalipoproteinemia)

Updated: Jul 15, 2021

Author: Basma Abdulhadi, MD; Chief Editor: George T Griffing, MD

Overview

Practice Essentials

While it has been proven via multiple studies that elevated levels of low-density lipoprotein (LDL) contribute to the development of atherosclerosis, high-density lipoprotein (HDL) is widely thought to have atheroprotective effects. Results from multiple epidemiologic studies of healthy populations (most importantly, from the Framingham Heart Study) have given rise to the idea that high HDL levels protect against coronary heart disease (CHD). Patients with known CHD have been found to have lower levels of HDL.[1, 2, 3] Currently available blood assays cannot determine the functionality of HDL cholesterol (HDL-C) but can only quantify it in plasma; they may in future be replaced by assays that can assess the composition and functionality of HDL-C.

As defined by the US National Cholesterol Education Program Adult Treatment Panel III guidelines, an HDL-C level of 60 mg/dL or greater is a negative (protective) risk factor.[4] On the other hand, a high-risk HDL-C level is described as being below 40 mg/dL. Randomized, controlled clinical trials have demonstrated that interventions to raise HDL-C levels are associated with reduced CHD events. A prospective analysis by Mora et al investigated the link between cholesterol and cardiovascular events in women and found that the baseline HDL-C level was consistently and inversely associated with incident coronary and coronary vascular disease events across a range of LDL-C values.[5]

Evidence from animal experiments indicates that HDL has anti-atherosclerotic effects. Fatty-streak formation was inhibited by HDL administration in rabbits fed an atherogenic diet. Inhibition of atherogenesis was also found in cholesterol-fed rabbits who received an infusion of apolipoprotein (apo) A-I Milano.[2]

However, although low levels of HDL predict increased cardiovascular risk, particularly in healthy individuals with no history of cardiovascular events, the relationship between HDL and CHD risk is complex, with HDL-C and cardiovascular disease having a nonlinear relationship. For example, research found that HDL levels above approximately 60 mg/dL showed no further improvement in prognosis, and the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk and IDEAL (Incremental Decrease in End Points through Aggressive Lipid Lowering) studies showed that very high levels of HDL may actually be associated with an increased risk of atherosclerotic disease.[6, 7, 2]

A study of over 1 million US veterans showed a U-shaped relationship between HDL and total mortality, with 50 mg/dL as the level associated with the lowest mortality.[8, 2] In addition, an analysis of the Framingham study demonstrated that LDL and triglyceride levels modify HDL’s predictive value; CHD risk was found to be higher when low HDL was combined with high LDL and/or triglycerides as compared with the presence of low HDL levels alone.[9, 2] The relationship between HDL and CHD risk is also confounded by the presence of pro-atherogenic and inflammatory markers.[2]

Moreover, the levels at which HDL confers benefit or risk are not discrete, and the cut points are somewhat arbitrary, especially considering that HDL levels are, on average, higher in US women than in men and higher in blacks than in whites.

Therefore, the practice of measuring HDL levels and using them to predict CHD risk is not accurate, because a high HDL level may not necessarily mean reduced risk.[2]

HDL is plasma’s smallest and densest lipoprotein. The major apolipoproteins of HDL are apo A-I and apo A-II, the alpha lipoproteins. An elevated concentration of apo A-I and apo A-II, known as hyperalphalipoproteinemia (HALP), is associated with a lower risk of CHD. Conversely, hypoalphalipoproteinemia increases the chances of CHD development.[2] HALP generally does not produce any unusual clinical features (although corneal opacity has been associated with the condition), and it should not be considered a disease entity but rather a fortuitous condition that can increase longevity because of the related decrease in CHD incidence.[10]

HDL plays an important role in transporting cholesterol from the peripheral tissues to the liver, where it can be excreted; this process is known as reverse cholesterol transport (RCT). (The liver is the main organ for excretion of cholesterol, doing so either directly or by converting cholesterol into bile acids.) It is important to remember that most HDL measured in the blood is derived from the liver and intestine. Therefore, the concentration of HDL in plasma does not reflect cholesterol efflux from blood vessels or the efficiency of RCT. Moreover, HDL function in RCT is not mirrored by HDL measurements.[2]

HDL is more tightly controlled by genetic factors than are the other lipoproteins (ie, LDL, very–low-density lipoprotein (VLDL), intermediate-density lipoprotein [IDL], chylomicrons). For example, in certain families, especially some families with Japanese ancestry, a genetic deficiency of cholesteryl ester transfer protein (CETP) is associated with strikingly elevated HDL-C levels.[11]

However, environmental factors also have a significant impact on HDL levels. Factors that elevate HDL concentrations include chronic alcoholism, treatment with oral estrogen replacement therapy, extensive aerobic exercise, and treatment with niacin, statins, or fibrates.[12, 13, 14] On the other hand, smoking reduces levels of HDL-C, while quitting smoking leads to a rise in the plasma HDL level.

Workup and management

Typically, a fasting plasma lipid profile is ordered to measure LDL, HDL, total cholesterol, and triglyceride levels. Lipids in plasma and in isolated lipoprotein fractions are quantified by enzymatic methods. Prior consumption of food has little effect on the determination of HDL, with postprandial blood samples usually yielding results that can be well interpreted.[15, 2] Current clinically available techniques can determine the cholesterol content, but not the biologic function, of HDL particles.[2]

Additional testing, for metabolic and inflammatory pathologies, should be triggered by the presence of low HDL levels.[2]

Whether or not imaging studies are appropriate depends on the clinical manifestations, if any, associated with HALP.

As previously stated, patients with HALP generally are asymptomatic and require no medical therapy. However, patients with the corneal opacity sometimes associated with the condition may need an ophthalmologic evaluation.

Pathophysiology

Hyperalphalipoproteinemia (HALP) may be familial, including primary (without CETP deficiency) and otherwise (with CETP deficiency), or secondary.[16] Familial HALP (aside from the primary form) is a well-documented genetic form of hypercholesterolemia characterized by a deficiency of CETP, a key protein in the reverse cholesterol transport (RCT) system that facilitates the transfer of cholesteryl esters from high-density lipoprotein (HDL) to beta lipoproteins. Primary HALP is a term used for familial elevated HDL cholesterol levels that are not due to CETP deficiency and for which the cause is unknown. Secondary HALP is due to environmental factors or medications.

Physiology

Plasma HDL is a small, spherical, dense lipid-protein complex that is half lipid and half protein. The lipid component consists of phospholipids, free cholesterol, cholesteryl esters, and triglycerides. The protein component includes apo A-I (molecular weight, 28,000) and apo A-II (molecular weight, 17,000). Other minor, but important, proteins are apo E and apo C, including apo C-I, apo C-II, and apo C-III.

HDL particles are heterogeneous. They can be classified as a larger, less dense HDL2 or a smaller, denser HDL3.[17] Normally, most of the plasma HDL is found in HDL3.[18] To add to the complexity of HDL classification, HDL is composed of 4 apolipoproteins per particle. HDL may be composed of apo A-I and apo A-II or of apo A-I alone. HDL2 is usually made up only of apo A-I, while HDL3 contains a combination of apo A-I and apo A-II. HDL particles that are less dense than HDL2 are rich in apo E.

The reverse cholesterol transport system

HDL serves as a chemical shuttle that transports excess cholesterol from peripheral tissues to the liver. This pathway is called the RCT system. In this system, plasma HDL takes up cholesterol from the peripheral tissues, such as fibroblasts and macrophages. (A study by El Khoury et al indicated that in persons with HALP, macrophages have an increased plasma cholesterol efflux capacity.[19] ) This may occur by passive diffusion or may be mediated by the adenosine triphosphate (ATP)–binding cassette transporter 1. The latter interacts directly with free apo A-I, generating nascent, or so-called discoidal, HDL. Cholesterol undergoes esterification by lecithin-cholesterol acyltransferase (LCAT) to produce cholesteryl ester, which results in the production of the mature spherical HDL. Cholesterol is also taken up from triglyceride-rich lipoproteins in a process mediated by a phospholipid transfer protein (ie, CETP).[20, 21, 22, 23]

Cholesterol is then returned to the liver by multiple routes. In the first route, cholesterol esters may be transferred from HDL to the apo B–containing lipoproteins, such as very–low-density lipoprotein (VLDL) or intermediate-density lipoprotein (IDL), by CETP. These lipoproteins undergo metabolism and subsequent uptake by the liver, primarily by a process mediated by the B,E receptor. In the second route, HDL particles may be taken up directly by the liver. In the third, free cholesterol may be taken up directly by the liver. Finally, HDL cholesterol esters may be selectively taken up via the scavenger receptor SR-B1.

If the hepatic uptake of VLDL and IDL is impaired, their cholesterol may be delivered back to peripheral tissues.

See Causes.

Epidemiology

Frequency

United States

Hyperalphalipoproteinemia (HALP) is a common entity in the general population. A correct diagnosis would help to avoid unnecessary treatment of hypercholesterolemia in 5% of the population. The overall prevalence rate is 7.8%. In persons with HALP, primary HALP accounts for 92% of cases, and secondary HALP accounts for 7.9% of cases.

International

The incidence of hyperalphalipoproteinemia is unknown. The condition has been described in most populations, but few population-wide data are available.

A pooled analysis by the NCD Risk Factor Collaboration of 458 population-based studies covering 23 Asian and Western countries determined that in a number of Western nations, as well as in Japan and South Korea, the mean ratio of total-to-HDL cholesterol has declined since 1980, with the reduction in Swiss men being approximately 0.7 per decade between 1980 and 2015. (In contrast, China saw an increase in the ratio.) Also from about 1980 to 2015, HDL-C levels in Japan and South Korea saw a per-decade rise of between 0.04 mmol/L (South Korean men) and 0.17 mmol/L (Japanese women).[24]

Mortality/Morbidity

Hyperalphalipoproteinemia (HALP) may be associated with a decreased risk of coronary heart disease (CHD), as well as reduced morbidity and mortality.

The plasma high-density lipoprotein (HDL) level is inversely correlated with the prevalence of and mortality rates for CHD. Despite having HALP, however, some patients may still develop lesions in their coronary arteries. HDL with apo A-I is considered the most reliable parameter for predicting a reduced risk of atherosclerosis.[25, 26]

The most important mechanism by which HDL exerts its antiatherogenic role is the removal of excess cholesterol from peripheral cells and its transport to the liver, a process commonly termed the reverse cholesterol transport system (RCT). Several proteins are involved in this process, including ATP-binding cassette transporter 1, LCAT, CETP, and hepatic triglyceride lipase (see Pathophysiology).[27]

HDL also has antioxidant properties that may directly slow the atherogenic process.

Despite HDL-C’s link to reduced CHD risk, a study by Takaeko et al suggested that extremely high HDL-C levels (80 mg/dL or above) can actually harm vascular function. The report, which involved adult males, found an association between such HDL-C concentrations and a significant decrease in flow-mediated vasodilation.[28]

Race

A somewhat lower prevalence of hyperalphalipoproteinemia (HALP) has been reported in Asian persons and Asian Indian populations.[29] Population studies (Lipid Research Clinic data) in the United States demonstrate racial differences in the prevalence of HALP, as follows[30] :

In randomly screened children aged 6-19 years who had age-, race-, and sex-specific total plasma cholesterol levels greater than or equal to 95th percentile levels, 7.8% of White males, 12.8% of White females, 25% of Black males, and 17.2% of Black females had hypercholesterolemia due to elevated high-density lipoprotein [HDL] cholesterol levels (but not due to elevated low-density lipoprotein [LDL] cholesterol levels) greater than age-, sex-, and race-specific 95th percentile levels. That is, they had HALP.
For adults aged 20-79 years, 4% of White men, 6.9% of White women, 13.3% of Black men, and 13.3% of Black women had predominant HALP, which accounted for their hypercholesterolemia.

A study by Ozaki et al of emergency department patients with an acute coronary syndrome found high HDL cholesterol levels (>40 mg/dL; measured within 72 hours of presentation) to occur more frequently in women and Blacks than in men and Whites.[31]

Sex

Population studies have demonstrated a female predominance for hyperalphalipoproteinemia (Lipid Research Clinic data).[30, 32]

The aforementioned study by Ozaki and colleagues of emergency department patients with an acute coronary syndrome found that although in Whites, HDL cholesterol levels differed significantly between males and females, the same was not true for Blacks. Higher HDL cholesterol levels were also associated with the absence coronary artery disease and diabetes in the study subjects.[31]

Age

The incidence of hyperalphalipoproteinemia appears to decrease with age. In a population survey, the following rates were reported:

In persons aged 20-29 years, the prevalence rate was 15.8%.
In persons aged 30-39 years, the prevalence rate was 8.4%.
In persons older than 40 years, the prevalence rate averaged 7.8%.

Presentation

History

Hyperalphalipoproteinemia (HALP) has no specific symptoms. It is usually identified through the routine assessment of a lipid profile. Another member of a patient's family may have been found to have elevated high-density lipoprotein (HDL) cholesterol levels. Aside from its cardioprotective role, HALP is occasionally associated with the following symptoms and signs:

Juvenile corneal opacification
Multiple symmetric lipomatosis[33]
History related to secondary causes
- History of alcohol abuse
- Treatment with medications such as oral estrogens, statins, niacin (ie, nicotinic acid), phenytoin, or fibrates (eg, bezafibrate, clofibrate, fenofibrate, gemfibrozil)[12, 14]
- History of vigorous, sustained aerobic exercise (eg, long-distance running)

Physical

Patients with asymptomatic hyperalphalipoproteinemia (HALP) do not present with any significant physical findings. Rare patients may exhibit the following:

Juvenile corneal opacification - This is described in patients with marked HALP.
Multiple systemic lipomatosis - In rare cases, the development of multiple lipomas has been reported.

Causes

Causes of hyperalphalipoproteinemia (HALP) may be primary or acquired (secondary). Primary factors can include familial syndromes of elevated high-density lipoprotein (HDL) cholesterol levels, which in some cases may be associated with a decreased risk for coronary artery disease .

Primary causes
- Familial HALP - Familial HALP includes CETP deficiency, familial hepatic lipase deficiency, and primary HALP. A selective up-regulation of apo A-I production is one metabolic cause of familial HALP and leads to high plasma concentrations of HDL cholesterol, apo A-I, and lipoprotein A-I. It possibly may also result in protection from atherosclerotic coronary heart disease (CHD).[34, 35] Familial HALP can involve premature corneal opacity, reduced hepatic lipase activity, and reduced uptake of HDL by lymphocytes.
- Primary HALP - This is a term used for familial elevated HDL cholesterol levels that are not due to CETP deficiency. Epidemiologic studies have suggested that this syndrome is associated with a decreased risk for coronary artery disease and with increased longevity.
- CETP deficiency - This asymptomatic, hereditary syndrome is caused by low CETP levels. Decreased CETP activity slows the transport of cholesteryl esters from HDL to apo B–containing lipoproteins. The condition is frequently observed in Japanese Americans. Clinical features include marked elevations of plasma HDL cholesterol in homozygotes (usually >100 mg/dL) and probably lower rates of CHD. In heterozygotes, the HDL levels are only moderately elevated. CETP deficiency has not yet been demonstrated to be associated with a decreased risk for atherosclerotic cardiovascular disease, and some experts do not consider this condition protective against cardiovascular disease.[36]
- LCAT overexpression - Rarely, HALP has been reported to be due to LCAT overexpression. The activity of LCAT is increased in blood plasma and is associated with high levels of HDL. Reduction in the fractional catabolic rate of HDL is considered to be the predominant mechanism by which LCAT overexpression modulates HDL concentrations. Such patients may have reduced risk of developing CHD.
- Up-regulation of apo A-I production - Selective up-regulation of apo A-I production is another cause of familial HALP. Affected individuals have elevated HDL cholesterol and apo A-I levels. Additionally, many patients have a reduced risk of atherosclerotic CHD.
Secondary causes[12, 14]
- Vigorous and sustained aerobic exercise (eg, long-distance running)
- Regular, substantial alcohol consumption
- Treatment with oral estrogens, particularly if not opposed by progestins
- Treatment with statins
- Treatment with nicotinic acid (niacin) at doses greater than 1 g/d
- Treatment with phenytoin
- Primary biliary cirrhosis
- Treatment with fibrates (eg, bezafibrate, clofibrate, fenofibrate, gemfibrozil)

A study by Wakabayashi indicated that LDL cholesterol differs from HDL cholesterol in its sensitivity to alcohol. Dividing subjects into three tertiles based on blood HDL cholesterol levels, the study found that in the first tertile group, HDL cholesterol seemed to have relatively low sensitivity to alcohol, while LDL cholesterol levels in this tertile were clearly lower in alcohol consumers than in nonconsumers.[37]

A study by Jan et al found HDL cholesterol levels to be positively correlated with weekly exercise durations of both 2.5 hours or more and under 2.5 hours. The correlation in both exercise groups was found to be more significant in males than in females.[38]

However, a study by Pitanga et al reported that although a positive association was found between leisure-time physical activity in adults and greater HDL cholesterol levels, men require more physical activity than women do to demonstrate such increases. In females, it was noted, walking and moderate or vigorous physical activity correlated with raised HDL cholesterol levels, while in males, only vigorous exercise was associated with a rise in HDL cholesterol levels. It was suggested that this may be partly because men have higher resting homeostasis parameters (eg, heart rate, blood pressure, glycemic levels, caloric expenditure) than women and therefore require a greater amount of physical activity to disrupt resting homeostasis and activate the physiologic means of cardiovascular protection, such as HDL cholesterol increases.[39]

DDx

Differential Diagnoses

CETP deficiency
Familial hyperalphalipoproteinemia (HALP)
Frequent and vigorous sustained aerobic exercise
Heavy alcohol consumption
Juvenile corneal opacification
LCAT overexpression
Longevity syndrome
Multiple systemic lipomatosis
Primary Biliary Cholangitis (Primary Biliary Cirrhosis)
Primary HALP
Treatment with fibrates (eg, bezafibrate, clofibrate, fenofibrate, gemfibrozil)
Treatment with statins
Use of high-dose nicotinic acid
Use of oral unopposed estrogens
Use of phenytoin

Workup

Laboratory Studies

Several studies have found that the vascular effects of high-density lipoprotein (HDL) vary widely and do not always correlate with HDL concentrations in blood. In contrast to healthy individuals’ HDL, research found that HDL in patients with CHD, kidney disease, or diabetes demonstrated no protective vascular effects and was even thought to have some harmful effects. In acute and chronic diseases, the HDL composition itself changes, undergoing modification in complex ways. This needs to be remembered when interpreting lipid panel results, as it may be misleading to assume an equivalence between HDL levels and “good cholesterol.”[2] Currently available blood assays cannot determine the functionality of HDL cholesterol (HDL-C) but can only quantify it in plasma; they may in future be replaced by assays that can assess the composition and functionality of HDL-C.

Prior consumption of food has little effect on the determination of HDL, with postprandial blood samples usually yielding results that can be well interpreted.[2, 15]

Plasma fasting lipid profile

A plasma fasting lipid profile measures low-density lipoprotein (LDL), HDL, total cholesterol, and triglyceride levels.

Lipids in plasma and in isolated lipoprotein fractions are quantified by enzymatic methods. HDL cholesterol levels are determined using a phosphotungstic/magnesium chloride reagent to precipitate the apo B–containing lipoproteins; cholesterol is enzymatically measured in the supernatant. LDL cholesterol levels are calculated using the Friedewald formula or may be measured directly using enzymatic methods.

Plasma HDL apolipoproteins

Studies of HDL apolipoproteins are not routinely performed clinically, but they may be useful research assays. Some clinicians use ratios of apo A-I to apo B-100 for risk assessment, but these measurements are quite expensive and have proven to be no more accurate than the measurement of the ratio of total cholesterol to HDL cholesterol. Measurement of apo C, apo D, and apo E concentrations is not clinically useful.

Apo A lipoproteins include apo A-I, apo A-II, and apo A-IV. Apo C lipoproteins include apo C-I, apo C-II, and apo C-III.

Other apolipoproteins

Other apolipoproteins include apo D and apo E.

Imaging Studies

Whether or not imaging studies are appropriate depends on the clinical manifestations associated with hyperalphalipoproteinemia (HALP), if any. Patients with HALP-related corneal opacification may require ophthalmoscopic examination and corneal or intraocular imaging.

Other Tests

Studies to assess CTEP or hepatic lipase activity are not routinely performed clinically, but they may be useful research assays.

Density ultracentrifugation can be used to isolate and measure high-density lipoprotein (HDL) levels directly.

Nuclear magnetic resonance measurements of HDL levels are used in some specialized laboratories. HDL2 and HDL3 subfraction measurements can also be performed in the specialized laboratories involved in research studies.

A study by Minhas et al suggested that in patients with hyperalphalipoproteinemia, evaluation of cardiovascular disease risk using the QRISK2 calculator be performed using standard population mean HDL values rather than actual measured HDL to avoid underestimation of disease risk. The report found a statistically significant difference between scores using the two types of measurements.[40]

Procedures

No procedures are usually required.

Histologic Findings

In rare cases of hyperalphalipoproteinemia in which patients have multiple lipomatosis syndrome, histologic examinations may be performed on biopsy specimens. The findings are usually consistent with lipoma.

Treatment

Medical Care

Most patients with hyperalphalipoproteinemia (HALP) are incidentally diagnosed following blood testing. Generally, patients are asymptomatic and no medical therapy is required. However, patients with corneal opacity may need an evaluation by an ophthalmologist.

Patients in whom excessive alcohol consumption is a cause of elevated high-density lipoprotein cholesterol levels should be assessed for the possible consequences of this practice.

Chest pain syndromes and other manifestations of ischemic heart disease in persons with hyperalphalipoproteinemia must be thoroughly evaluated in the usual manner.

Surgical Care

Surgical care is not usually required.

Consultations

No consultations are usually required.

Diet

Certain forms of dietary therapy, including the consumption of a diet low in fat content, have been shown to influence the levels of alpha lipoproteins and high-density lipoprotein (HDL) cholesterol in plasma. A low-fat diet may cause some reduction in HDL cholesterol levels, while high-fat diets are associated with higher HDL cholesterol levels.

Activity

Most patients with hyperalphalipoproteinemia are healthy and asymptomatic. No restrictions on activity are required.

Medication

Medication Summary

Persons with hyperalphalipoproteinemia are generally asymptomatic. The condition is associated with a lower prevalence of atherosclerosis and requires no treatment.

Follow-up

Further Outpatient Care

Outpatient care of an individual with hyperalphalipoproteinemia may include periodic monitoring of his/her lipid profile and/or a determination of the lipid profile of the index patient's first-degree relatives.

Complications

Rarely, corneal opacity is associated with hyperalphalipoproteinemia.

Prognosis

The prognosis is excellent. In fact, hyperalphalipoproteinemia is associated with longevity.

Patient Education

The benefit of atherosclerosis prevention associated with hyperalphalipoproteinemia (HALP) should be discussed with the patient.

Any significant manifestations of ischemic heart disease must be evaluated seriously, despite the protective role of HALP.

If appropriate, the consequences of excessive alcohol intake must be discussed.

For excellent patient education resources, see eMedicineHealth's patient education articles High Cholesterol, Understanding Your Cholesterol Level, Lifestyle Cholesterol Management, and Cholesterol-Lowering Medications.

Questions & Answers

Overview

What is the relationship between high-density lipoprotein (HDL) cholesterol and coronary heart disease (CHD)?

What are the major apolipoproteins of high-density lipoprotein (HDL) cholesterol, and what are the associated risks?

How does high-density lipoprotein (HDL) transport cholesterol to the liver?

Is high-density lipoprotein (HDL) cholesterol genetic?

Which environmental factors affect high-density lipoprotein (HDL) cholesterol levels?

Which lipids does a plasma fasting lipid profile measure, and do postprandial blood samples yield accurate results?

What additional testing should be triggered by low high-density lipoprotein (HDL) levels, and when are imaging studies appropriate?

Is medical treatment indicated for high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

What causes high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

What is the cellular makeup of plasma high-density lipoprotein (HDL)?

How are high-density lipoprotein (HDL) particles classified?

How does high-density lipoprotein (HDL) transfer excess cholesterol from peripheral tissues?

How is cholesterol returned to the liver once picked up by high-density lipoprotein (HDL) from peripheral tissues?

What is the prevalence of high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP]) in the US?

What is the global incidence of high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

How does high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP]) influence mortality and morbidity?

What is the racial predilection of high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

Is high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP]) more common in males or females?

What is the prevalence of high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP]) among different age groups?

Presentation

Which signs and symptoms suggest high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

Which physical findings are associated with high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

What causes high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

What is familial high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

What is primary high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

What is the role of cholesteryl ester transfer protein (CETP) deficiency in high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

What is the role of lecithin-cholesterol acyltransferase (LCAT) overexpression in high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

What is the role of up-regulation of apo A-I production in high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

What are secondary causes of high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

DDX

What are the differential diagnoses for High HDL Cholesterol (Hyperalphalipoproteinemia)?

Workup

How do the vascular effects of high-density lipoprotein (HDL) vary, and what is the role of a plasma fasting lipid profile in the diagnosis of high HDL cholesterol (hyperalphalipoproteinemia [HALP])?

What is the role of plasma HDL apolipoproteins studies in the diagnosis of high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

Are imaging studies indicated in the diagnosis of high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

Other than plasma tests and imaging studies, which studies may be used in the diagnosis of high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

Are any procedures required in the diagnosis of high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

Which studies may be performed in patients with multiple lipomatosis syndrome and high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

Treatment

When is further evaluation required in high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

Is surgery required for high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

Are consultations necessary in the treatment of high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

What is the role of dietary fat in high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

Are any restrictions on physical activity needed for high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

Medications

Are any medications used in the treatment of high HDL (high-density lipoprotein) cholesterol (hyperalphalipoproteinemia [HALP])?

Author

Basma Abdulhadi, MD Fellow, Department of Medicine, Division of Endocrinology, University of Alabama School of Medicine

Basma Abdulhadi, MD is a member of the following medical societies: Alpha Omega Alpha, American Association of Clinical Endocrinologists, Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Catherine Anastasopoulou, MD, PhD, FACE Associate Professor of Medicine, The Steven, Daniel and Douglas Altman Chair of Endocrinology, Sidney Kimmel Medical College of Thomas Jefferson University; Einstein Endocrine Associates, Einstein Medical Center

Catherine Anastasopoulou, MD, PhD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American Society for Bone and Mineral Research, Endocrine Society, Philadelphia Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Don S Schalch, MD Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics

Don S Schalch, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for Physician Leadership, American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society, International Society for Clinical Densitometry, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Ghassem Pourmotabbed, MD, MD

Ghassem Pourmotabbed, MD, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Endocrine Society

Disclosure: Nothing to disclose.

Vibhuti N Singh, MD, MPH, FACC, FSCAI Clinical Assistant Professor, Division of Cardiology, University of South Florida College of Medicine; Director, Cardiology Division and Cardiac Catheterization Lab, Chair, Department of Medicine, Bayfront Medical Center, Bayfront Cardiovascular Associates; President, Suncoast Cardiovascular Research

Vibhuti N Singh, MD, MPH, FACC, FSCAI is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Heart Association, American Medical Association, Florida Medical Association

Disclosure: Nothing to disclose.

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