Low HDL Cholesterol (Hypoalphalipoproteinemia)

No Results

No Results

processing….

Low levels of high-density lipoprotein cholesterol (HDL), or hypoalphalipoproteinemia (HA), includes a variety of conditions, ranging from mild to severe, in which concentrations of alpha lipoproteins or high-density lipoprotein (HDL) are reduced. The etiology of HDL deficiencies ranges from secondary causes, such as smoking, to specific genetic mutations, such as Tangier disease and fish-eye disease.

HA has no clear-cut definition. An arbitrary cutoff is the 10th percentile of HDL cholesterol levels. A more practical definition derives from the theoretical cardioprotective role of HDL. The US National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) redefined the HDL cholesterol level that constitutes a formal coronary heart disease (CHD) risk factor. The level was raised from 35 mg/dL to 40 mg/dL for men and women. A prospective analysis by Mora et al investigated the link between cholesterol and cardiovascular events in women and found baseline HDL-C level was consistently and inversely associated with incident coronary and CVD events across a range of LDL-C values. ^{[1, 2]}

For the metabolic syndrome in which multiple mild abnormalities in lipids, waist size (abdominal circumference), blood pressure, and blood sugar increase the risk of CHD, the designated HDL cholesterol levels that contribute to the syndrome are sex-specific. For men, a high-risk HDL cholesterol level is still less than 40 mg/dL, but for women, the high-risk HDL cholesterol level is less than 50 mg/dL. ^{[3, 4, 5, 6]}

A low HDL cholesterol level is thought to accelerate the development of atherosclerosis because of impaired reverse cholesterol transport and possibly because of the absence of other protective effects of HDL, such as decreased oxidation of other lipoproteins.

The common, mild forms of HA have no characteristic physical findings, but patients may have premature coronary heart or peripheral vascular disease, as well as a family history of low HDL cholesterol levels and premature CHD.

Therapy to raise the concentration of HDL cholesterol includes weight loss, smoking cessation, aerobic exercise, and pharmacologic management with niacin and fibrates.

This review addresses the pathogenesis and presenting features of, and the diagnostic tests, therapeutic interventions, and follow-up strategies for, low HDL cholesterol levels.

Plasma lipoproteins are macromolecular complexes of lipids and proteins that are classified by density and electrophoretic mobility. The structure of all lipoproteins is the same. The nonpolar lipids (ie, cholesterol ester, triglycerides [TGs]) reside in a core surrounded by more polar components (eg, free cholesterol, phospholipids, proteins). The proteins, termed apolipoproteins, play an important role in lipoprotein metabolism.

The major apolipoproteins of high-density lipoprotein (HDL) are alpha lipoproteins (ie, apolipoprotein A-I [apo A-I], apo A-II, apo A-IV), which are soluble and can move between different classes of lipoproteins. The beta lipoproteins are structural, are never complexed with HDL, and remain throughout the metabolism of the lipoproteins with which they are associated. Apo B-450 is associated with chylomicrons and their remnants, and apo B-100 is associated with low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), VLDL remnants, and intermediate-density lipoprotein.

HDL plays a major role in reverse cholesterol transport, mobilizing cholesterol from the periphery to promote return to the liver. In the general population, lower-than-normal HDL cholesterol levels are closely correlated with coronary heart disease (CHD); the risk of a coronary event is thought to increase 2% for every 1% decrease in HDL cholesterol. However, extreme HDL deficiencies caused by rare autosomal recessive disorders, including familial hypoalphalipoproteinemia (HA), familial lecithin-cholesterol acetyltransferase (LCAT) deficiency, and Tangier disease, do not always correlate with more frequent CHD. ^{[7, 8]}

Results from the Framingham Heart Study offspring cohort, where 3590 individuals without known cardiovascular disease were studied from 1987 to 2011, found that cardiovascular risk was not only associated with high-density lipoprotein cholesterol but also was associated with a combination HDL levels and levels of low-density lipoprotein cholesterol and triglycerides. ^{[9, 10]}

Criteria for the definition of familial HAs are (1) a low HDL cholesterol level in the presence of normal VLDL cholesterol and LDL cholesterol levels, (2) an absence of diseases or factors to which HA may be secondary, and (3) the presence of a similar lipoprotein pattern in a first-degree relative.

Familial HA is a relatively common disorder and is frequently associated with decreased apo A-I production or increased apo A-I catabolism. Severe HDL deficiency can also be associated with a heterogeneous group of rare, autosomal-recessive lipoprotein disorders. The underlying molecular defects involve apo A-I, apo C-III, or apo A-IV. HDL in plasma is almost undetectable in persons with the familial apo A-I deficiency caused by deletions of the APOA1 gene, the HDL level being less than 10 mg/dL. Heterozygotes tend to have less severe reductions in HDL. ^[11]

Some patients with severe genetic HDL reductions manifest corneal opacities and xanthomas and have an increased risk of developing premature coronary atherosclerosis (ie, CHD). ^{[12, 13]} The molecular diagnosis can be made by specialized analysis, including electrophoresis of the plasma apolipoproteins and deoxyribonucleic acid (DNA) analysis to determine the mutation. Because raising plasma apo A-I or HDL-C levels is usually difficult in persons with these disorders, treatment should be directed toward lowering the level of non-HDL cholesterol.

In some patients, this condition occurs as a result of certain nonsense mutations that affect the generation of the apo A-I molecule. These mutations are a very rare cause of low HDL cholesterol levels (usually 15-30 mg/dL). An example is APOA1 Milano, inherited as an autosomal dominant trait, which is not associated with an increased risk of premature CHD despite low HDL levels. Other than corneal opacities, most of these patients do not exhibit many clinical sequelae related to the APOA1 mutations. Certain other APOA1 mutations have been found in association with systemic amyloidosis, and the mutant APOA1 gene has been located within the amyloid plaque.

This is a very rare autosomal recessive disorder characterized by corneal opacities, normochromic anemia, and renal failure in young adults. Approximately 30 kindreds and a number of mutations have been reported. LCAT deficiency results in decreased esterification of cholesterol to cholesteryl esters on HDL particles. This in turn results in an accumulation of free cholesterol on lipoprotein particles and in peripheral tissues, such as the cornea, red blood cells, renal glomeruli, and vascular walls. At present, no effective method has been found to increase plasma LCAT levels; therefore, therapy is limited to (1) dietary restriction of fat to prevent the development of complications and (2) management of complications (eg, renal transplant for advanced renal disease). ^{[14, 15]}

Two kinds of genetic LCAT deficiencies have been reported. The first is complete (or classic) LCAT deficiency. Complete LCAT deficiency is manifested by anemia, increased proteinuria, and renal failure. The diagnosis can be made based on the results of LCAT quantification and cholesterol esterification activity in the plasma in certain specialized laboratories. The second type of deficiency is partial LCAT deficiency (fish-eye disease). ^{[16, 17]} Partial LCAT deficiency has known clinical sequelae. Progressive corneal opacification, very low plasma levels of HDL cholesterol (usually < 10 mg/dL), and variable hypertriglyceridemia are characteristic of partial and classic LCAT deficiency. ^[14]

The risk of atherosclerosis is not usually associated with an increased risk of CHD. Similarly, LCAT-deficient animal models do not demonstrate an increased prevalence of atherosclerosis.

Tangier disease is an autosomal codominant disorder that causes a complete absence or extreme deficiency of HDL. LDL cholesterol levels are also usually reduced. The disease is characterized by the presence of orange tonsils, peripheral neuropathy, splenomegaly, discoloration of the rectal mucosa, hepatomegaly, opacities, premature CHD, and other abnormalities. Although the underlying mutation is not yet well defined, in some subjects the condition is caused by mutations of the adenosine triphosphate (ATP) – binding cassette transporter 1, which is involved in the passage of cholesterol from within the cells to outside the cells (efflux). ^{[18, 19]} Cholesteryl esters are deposited in the reticuloendothelial system.

Patients with Tangier disease also may exhibit accelerated HDL catabolism. Their HDL cholesterol levels are usually lower than 5 mg/dL. Their apo A-I levels are also very low. This condition has no specific treatment. ^{[20, 21]}

Plasma HDL is a small, dense, spherical lipid-protein complex, with the lipid and protein components each making up half. The major lipids are phospholipid, cholesterol, cholesteryl esters, and TGs. The major proteins include apo A-I (molecular weight, 28,000) and apo A-II (molecular weight, 17,000). Other minor, albeit 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 into larger, less dense HDL2 and smaller, denser HDL3. Normally, most HDL is present as HDL3. However, individual variability in HDL levels in humans is usually due to different amounts of HDL2.

HDL removes cholesterol from the peripheral tissues, such as fibroblasts and macrophages, and it is esterified by LCAT. The cholesteryl ester thus produced is transferred from the HDL to apo B – containing lipoproteins, such as VLDL, intermediate-density lipoprotein, and LDL, by a key protein termed cholesteryl ester transport protein in the liver. The HDL itself becomes enriched with TGs and subsequently becomes hydrolyzed by hepatic lipase. By this mechanism, the HDL finally becomes smaller again and is ready to scavenge more cholesterol. This pathway is called the reverse cholesterol transport system.

Therefore, HA represents a clinical condition in which the reverse cholesterol transport system functions suboptimally, causing an increased tendency to develop atherosclerotic lesions. ^[22]

Table. Hypoalphalipoproteinemia (Open Table in a new window)

Variant

Molecular Defect

Inheritance

Metabolic Defect

Lipoprotein Abnormality

Clinical Features

Premature Atherosclerosis

Familial apo A-I

Apo deficiency

Autosomal codominant

Absent apo A-1 biosynthesis

HDL < 5 mg/dL; TGs normal

Planar xanthomas, corneal opacities

Yes

Familial apo A-I structural mutations

Abnormal apo A-I

Autosomal dominant

Rapid apo A-1 catabolism

HDL 15-30 mg/dL; TGs increased

Often none; sometimes corneal opacities

No

Familial LCAT

LCAT deficiency (complete)

Autosomal

recessive

Rapid HDL catabolism

HDL < 10 mg/dL; TGs increased

Corneal opacities, anemia, proteinuria, renal insufficiency

No

Fish-eye disease

LCAT deficiency (partial)

Autosomal recessive

Rapid HDL catabolism

HDL < 10 mg/dL; TGs increased

Corneal opacities

No

Tangier disease

Unknown

Autosomal codominant

Very rapid HDL catabolism

HDL < 5 mg/dL; TGs usually increased

Corneal opacities, enlarged orange tonsils, hepatosplenomegaly, peripheral neuropathy

No to yes

Familial HA

Unknown

Autosomal dominant

Usually rapid HDL catabolism

HDL 15-35 mg/dL; TGs normal

Often none; sometimes corneal opacities

No to yes

The variant apo A-I Milano, as well as the less well-known variants apo A-I Marburg, apo A-I Giessen, apo A-I Munster, and apo A-I Paris, cause HA but do not seem to increase the risk of atherosclerosis.

United States

Hypoalphalipoproteinemia is frequently found in patients with coronary heart disease (CHD). Research indicates that 58% of patients with CHD have high-density lipoprotein (HDL) cholesterol levels below the 10th percentile of normal values.

A National Center for Health Statistics (NCHS) data brief found that the percentage of adults with low HDL cholesterol dropped from 21.3% between 2009 and 2010 to approximately 20% between 2011 and 2014. ^[23]

International

At present, the prevalence of inheritance and of underlying defects in the familial disorder are unknown. Overall, however, primary and secondary hypoalphalipoproteinemia are common.

Hypoalphalipoproteinemia (HA) is associated with an increased risk of recurrent coronary episodes and mortality caused by coronary heart disease (CHD), and it constitutes a significant risk factor for the development of premature (accelerated) atherosclerosis.

In general, approximately 14 million people in the United States have CHD, many of whom exhibit associated HA. CHD remains the most common cause of death in the industrialized world. Approximately 1.5 million acute myocardial infarctions (MIs) occur each year in the United States; of patients experiencing acute MI, 500,000 die (almost 33%). Survivors experience an ever-increasing incidence of congestive heart failure, arrhythmias, and other forms of morbidity.

The incidence of stroke is also quite high. An estimated 600,000 new and recurrent cases of stroke occur each year, with 160,000 deaths per year. Stroke has become a leading cause of serious, long-term disability. Approximately 4.4 million stroke survivors live in the United States today; stroke not only exacts a huge cost in human suffering, it takes a financial toll as well, with the care of patients who have suffered a stroke reaching approximately $45.3 billion.

Peripheral vascular disease also affects many individuals. Approximately 50% of patients who report claudication have peripheral vascular disease.

Hypoalphalipoproteinemia (HA) has been described in persons of all races. While no particular race predilection has been noted, some literature suggests that a higher prevalence of HA exists in Asian Indians.

Women tend to have a somewhat lower frequency of hypoalphalipoproteinemia than do men. Whether this finding is a reflection of hormonal differences is not clear.

Young boys and girls have similar high-density lipoprotein (HDL) cholesterol levels, but after male puberty, these levels decrease in males, remaining lower than those in females for all subsequent age groups.

Yamakawa-Kobayashi K, Yanagi H, Fukayama H, et al. Frequent occurrence of hypoalphalipoproteinemia due to mutant apolipoprotein A-I gene in the population: a population-based survey. Hum Mol Genet. 1999 Feb. 8(2):331-6. [Medline]. [Full Text].

Gebauer SK, Destaillats F, Dionisi F, Krauss RM, Baer DJ. Vaccenic acid and trans fatty acid isomers from partially hydrogenated oil both adversely affect LDL cholesterol: a double-blind, randomized controlled trial. Am J Clin Nutr. 2015 Nov 11. [Medline].

Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001 May 16. 285(19):2486-97. [Medline].

Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III Final Report). May 2001. Available at http://www.nhlbi.nih.gov/guidelines/cholesterol/.

Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004 Jul 13. 110(2):227-39. [Medline]. [Full Text].

Singh VN. New ATP III lipid guidelines update for patients at high risk for cardiovascular events. Medscape Reference Feature Series – Lipid Newsletter. Jul 21, 2005. series 1(9):[Full Text].

Dioguardi N, Vergani C. [Familial alpha lipoprotein deficiency. Tangier disease, familial hypoalphalipoproteinemia and familial deficiency of lecithin cholesterol acyltransferase deficiency]. Minerva Med. 1983 Mar 24. 74(12):585-94. [Medline].

Sorrenson B, Suetani RJ, Bickley VM, George PM, Williams MJ, Scott RS, et al. An ABCA1 truncation shows no dominant negative effect in a familial hypoalphalipoproteinemia pedigree with three ABCA1 mutations. Biochem Biophys Res Commun. 2011 Jun 10. 409(3):400-5. [Medline].

Bartlett J, Predazzi IM, Williams SM, Bush WS, Kim Y, Havas S, et al. Is Isolated Low High-Density Lipoprotein Cholesterol a Cardiovascular Disease Risk Factor? New Insights From the Framingham Offspring Study. Circ Cardiovasc Qual Outcomes. 2016 May. 9 (3):206-12. [Medline].

Hackethal V. Framingham: Low HDL, in Isolation, Not a CV Risk Predictor. http://www.medscape.com/viewarticle/863880. Available at http://www.medscape.com/viewarticle/863880. May 26, 2016; Accessed: November 3, 2016.

Chien KL, Chen MF, Hsu HC, et al. Genetic association study of APOA1/C3/A4/A5 gene cluster and haplotypes on triglyceride and HDL cholesterol in a community-based population. Clin Chim Acta. 2008 Feb. 388(1-2):78-83. [Medline].

van den Bogaard B, Holleboom AG, Duivenvoorden R, Hutten BA, Kastelein JJ, Hovingh GK, et al. Patients with low HDL-cholesterol caused by mutations in LCAT have increased arterial stiffness. Atherosclerosis. 2012 Dec. 225(2):481-5. [Medline].

Savel J, Lafitte M, Pucheu Y, Pradeau V, Tabarin A, Couffinhal T. Very low levels of HDL cholesterol and atherosclerosis, a variable relationship–a review of LCAT deficiency. Vasc Health Risk Manag. 2012. 8:357-61. [Medline]. [Full Text].

Asztalos BF, Schaefer EJ, Horvath KV, et al. Role of LCAT in HDL remodeling: investigation of LCAT deficiency states. J Lipid Res. 2007 Mar. 48(3):592-9. [Medline]. [Full Text].

Tietjen I, Hovingh GK, Singaraja R, Radomski C, McEwen J, Chan E, et al. Increased self-reported risk of coronary artery disease in Caucasians with extremely low HDL cholesterol due to mutations in ABCA1, APOA1, and LCAT. Biochim Biophys Acta. 2011 Aug 19. [Medline].

Santamarina-Fojo S, Hoeg JM, Assmann G. Lecithin cholesterol acyltransferase deficiency and fish eye disease. Scriver CR, Sly WS, Childs B, et al, eds. Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001. vol 2: 2817-33.

Asada S, Kuroda M, Aoyagi Y, Bujo H, Tanaka S, Konno S, et al. Disturbed apolipoprotein A-I-containing lipoproteins in fish-eye disease are improved by the lecithin:cholesterol acyltransferase produced by gene-transduced adipocytes in vitro. Mol Genet Metab. 2011 Feb. 102(2):229-31. [Medline].

Uehara Y, Tsuboi Y, Zhang B, et al. POPC/apoA-I discs as a potent lipoprotein modulator in Tangier disease. Atherosclerosis. 2008 Mar. 197(1):283-9. [Medline].

Nicholls SJ, Ruotolo G, Brewer HB, Kane JP, Wang MD, Krueger KA, et al. Cholesterol Efflux Capacity and Pre-Beta-1 HDL Concentrations Are Increased in Dyslipidemic Patients Treated With Evacetrapib. J Am Coll Cardiol. 2015 Nov 17. 66 (20):2201-10. [Medline].

Assmann G, von Eckardstein A, Brewer HB Jr. Familial analphalipoproteinemia: Tangier disease. Scriver CR, Sly WS, Childs B, et al, eds. Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001. Vol 2: 2937-60.

Herbert PN, Assmann G, Gotto AM Jr, et al. Familial lipoprotein deficiency (abetalipoproteinemia and Tangier disease). Stanbury JB, Wyngaarden JB, Fredrickson DS, et al, eds. The Metabolic Basis of Inherited Disease. New York, NY: McGraw-Hill; 1982.

Brites FD, Bonavita CD, De Geitere C, et al. Alterations in the main steps of reverse cholesterol transport in male patients with primary hypertriglyceridemia and low HDL-cholesterol levels. Atherosclerosis. 2000 Sep. 152(1):181-92. [Medline].

Carroll MD, Fryar CD, Kit BK. Total and High-density Lipoprotein Cholesterol in Adults: United States, 2011-2014. NCHS Data Brief. 2015 Dec. 1-8. [Medline].

Satta MA, Scoppola A, Melina D, et al. [The relationship between high-density lipoproteins, thromboxane B2 and arteriosclerosis in a case of primary hypoalphalipoproteinemia]. Minerva Med. 1989 Dec. 80(12):1345-9. [Medline].

DeLong DM, DeLong ER, Wood PD, et al. A comparison of methods for the estimation of plasma low- and very low-density lipoprotein cholesterol. The Lipid Research Clinics Prevalence Study. JAMA. 1986 Nov 7. 256(17):2372-7. [Medline].

Ordovas JM, Schaefer EJ, Salem D, et al. Apolipoprotein A-I gene polymorphism associated with premature coronary artery disease and familial hypoalphalipoproteinemia. N Engl J Med. 1986 Mar 13. 314(11):671-7. [Medline].

Frohlich J, Westerlund J, Sparks D, et al. Familial hypoalphalipoproteinemias. Clin Invest Med. 1990 Aug. 13(4):202-10. [Medline].

Godin DV, Garnett ME, Hoag G, et al. Erythrocyte abnormalities in a hypoalphalipoproteinemia syndrome resembling fish eye disease. Eur J Haematol. 1988 Aug. 41(2):176-81. [Medline].

Rader DJ, deGoma EM. Approach to the patient with extremely low HDL-cholesterol. J Clin Endocrinol Metab. 2012 Oct. 97(10):3399-407. [Medline]. [Full Text].

Barkowski RS, Frishman WH. HDL metabolism and CETP inhibition. Cardiol Rev. 2008 May-Jun. 16(3):154-62. [Medline].

Barter PJ, Brewer HB Jr, Chapman MJ, et al. Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol. 2003 Feb 1. 23(2):160-7. [Medline]. [Full Text].

de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, et al. Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation. 2002 May 7. 105(18):2159-65. [Medline]. [Full Text].

Nissen SE, Tsunoda T, Tuzcu EM, et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003 Nov 5. 290(17):2292-300. [Medline]. [Full Text].

Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA. 1998 Aug 19. 280(7):605-13. [Medline]. [Full Text].

Lamon-Fava S, Postfai B, Diffenderfer M, et al. Role of the estrogen and progestin in hormonal replacement therapy on apolipoprotein A-I kinetics in postmenopausal women. Arterioscler Thromb Vasc Biol. 2006 Feb. 26(2):385-91. [Medline]. [Full Text].

Eslick GD, Howe PR, Smith C, et al. Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta-analysis. Int J Cardiol. 2008 Sep 5. [Medline].

AIM-HIGH Investigators, Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011 Dec 15. 365 (24):2255-67. [Medline]. [Full Text].

HPS2-THRIVE Collaborative Group, Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014 Jul 17. 371 (3):203-12. [Medline]. [Full Text].

Patrice Wending. FDA Pulls Approval of Niacin, Fibrate in Combo with Statins. Heartwire from Medscape Medical News. 2016 Apr 15. Available at http://www.medscape.com/viewarticle/862022.

HDL-Atherosclerosis Treatment Study (HATS). Cardiosource: American College of Cardiology. Available at http://www.cardiosource.com/clinicaltrials/trial.asp?trialID=486. Accessed: 2/10/09.

Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 2 (ARBITER 2). Cardiosource: American College of Cardiology. Available at http://www.cardiosource.com/clinicaltrials/trial.asp?trialID=1144. Accessed: 2/10/09.

Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007 Nov 22. 357(21):2109-22. [Medline]. [Full Text].

Nissen SE, Tsunoda T, Tuzcu EM, et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis inpatients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003 Nov 5. 290(17):2292-300. [Medline]. [Full Text].

Parolini C, Marchesi M, Lorenzon P, et al. Dose-related effects of repeated ETC-216 (recombinant apolipoprotein A-I Milano/1-palmitoyl-2-oleoyl phosphatidylcholine complexes) administrations on rabbit lipid-rich soft plaques: in vivo assessment by intravascular ultrasound and magnetic resonance imaging. J Am Coll Cardiol. 2008 Mar 18. 51(11):1098-103. [Medline].

Ibanez B, Vilahur G, Cimmino G, et al. Rapid change in plaque size, composition, and molecular footprint after recombinant apolipoprotein A-I Milano (ETC-216) administration: magnetic resonance imaging study in an experimental model of atherosclerosis. J Am Coll Cardiol. 2008 Mar 18. 51(11):1104-9. [Medline].

Vega GL, Grundy SM. Comparison of lovastatin and gemfibrozil in normolipidemic patients with hypoalphalipoproteinemia. JAMA. 1989 Dec 8. 262(22):3148-53. [Medline].

Ahumada Ayala M, Jimenez Villanueva C, Cardoso Saldana G, et al. [Hypoalphalipoproteinemia and atherosclerosis. Genetic and biochemical profile of 10 families]. Arch Inst Cardiol Mex. 1989 Jan-Feb. 59(1):9-18. [Medline].

Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011 Dec 15. 365(24):2255-67. [Medline].

Daum U, Leren TP, Langer C, et al. Multiple dysfunctions of two apolipoprotein A-I variants, apoA- I(R160L)Oslo and apoA-I(P165R), that are associated with hypoalphalipoproteinemia in heterozygous carriers. J Lipid Res. 1999 Mar. 40(3):486-94. [Medline]. [Full Text].

Dioguardi N. [Familial hypoalphalipoproteinemia. Vergani’s disease]. Minerva Med. 1983 Nov 16. 74(44):2659-64. [Medline].

Hersberger M, von Eckardstein A. Low high-density lipoprotein cholesterol: physiological background, clinical importance and drug treatment. Drugs. 2003. 63(18):1907-45. [Medline].

Jones PJ, Ntanios FY, Raeini-Sarjaz M, et al. Cholesterol-lowering efficacy of a sitostanol-containing phytosterol mixture with a prudent diet in hyperlipidemic men. Am J Clin Nutr. 1999 Jun. 69(6):1144-50. [Medline].

Kort EN, Ballinger DG, Ding W, et al. Evidence of linkage of familial hypoalphalipoproteinemia to a novel locus on chromosome 11q23. Am J Hum Genet. 2000 Jun. 66(6):1845-56. [Medline]. [Full Text].

Meco JF, Pinto X, Quintana E, et al. [Efficacy of hygienic and dietary therapy in coronary patients with isolated hypoalphalipoproteinemia]. An Med Interna. 1999 Dec. 16(12):620-5. [Medline].

Mingpeng S, Zongli W. The protective role of high-density lipoproteins in atherosclerosis. Exp Gerontol. 1999. 34(4):539-48. [Medline].

Mora S, Buring JE, Ridker PM, Cui Y. Association of high-density lipoprotein cholesterol with incident cardiovascular events in women, by low-density lipoprotein cholesterol and apolipoprotein b100 levels: a cohort study. Ann Intern Med. 2011 Dec 6. 155(11):742-50. [Medline]. [Full Text].

Mott S, Yu L, Marcil M, et al. Decreased cellular cholesterol efflux is a common cause of familial hypoalphalipoproteinemia: role of the ABCA1 gene mutations. Atherosclerosis. 2000 Oct. 152(2):457-68. [Medline].

Rader DJ. High-density lipoproteins as an emerging therapeutic target for atherosclerosis. JAMA. 2003 Nov 5. 290(17):2322-4. [Medline].

Saku K, Zhang B, Shirai K, et al. Hyperinsulinemic hypoalphalipoproteinemia as a new indicator for coronary heart disease. J Am Coll Cardiol. 1999 Nov 1. 34(5):1443-51. [Medline].

Schaefer EJ. Clinical, biochemical, and genetic features in familial disorders of high density lipoprotein deficiency. Arteriosclerosis. 1984 Jul-Aug. 4(4):303-22. [Medline].

Singh VN. Need for more aggressive statin use in various ethnic groups: Latino, Asian, and African American populations. Medscape Reference Feature Series – Lipid Newsletter. Oct 20, 2005. series 1(12):[Full Text].

Singh VN. The USDA “Food Pyramid” needs to go on a diet. Pinellas County Medical Society (PICOMESO) Journal. 2004. 43(4):3, 18-19.

Tall AR. Plasma high density lipoproteins. Metabolism and relationship to atherogenesis. J Clin Invest. 1990 Aug. 86(2):379-84. [Medline]. [Full Text].

Third JL, Montag J, Flynn M, et al. Primary and familial hypoalphalipoproteinemia. Metabolism. 1984 Feb. 33(2):136-46. [Medline].

Zema MJ. Gemfibrozil, nicotinic acid and combination therapy in patients with isolated hypoalphalipoproteinemia: a randomized, open-label, crossover study. J Am Coll Cardiol. 2000. 35(3):640-6. [Medline].

Variant

Molecular Defect

Inheritance

Metabolic Defect

Lipoprotein Abnormality

Clinical Features

Premature Atherosclerosis

Familial apo A-I

Apo deficiency

Autosomal codominant

Absent apo A-1 biosynthesis

HDL < 5 mg/dL; TGs normal

Planar xanthomas, corneal opacities

Yes

Familial apo A-I structural mutations

Abnormal apo A-I

Autosomal dominant

Rapid apo A-1 catabolism

HDL 15-30 mg/dL; TGs increased

Often none; sometimes corneal opacities

No

Familial LCAT

LCAT deficiency (complete)

Autosomal

recessive

Rapid HDL catabolism

HDL < 10 mg/dL; TGs increased

Corneal opacities, anemia, proteinuria, renal insufficiency

No

Fish-eye disease

LCAT deficiency (partial)

Autosomal recessive

Rapid HDL catabolism

HDL < 10 mg/dL; TGs increased

Corneal opacities

No

Tangier disease

Unknown

Autosomal codominant

Very rapid HDL catabolism

HDL < 5 mg/dL; TGs usually increased

Corneal opacities, enlarged orange tonsils, hepatosplenomegaly, peripheral neuropathy

No to yes

Familial HA

Unknown

Autosomal dominant

Usually rapid HDL catabolism

HDL 15-35 mg/dL; TGs normal

Often none; sometimes corneal opacities

No to yes

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.

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.

Yoram Shenker, MD Chief of Endocrinology Section, Veterans Affairs Medical Center of Madison; Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison

Yoram Shenker, MD is a member of the following medical societies: American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

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 the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

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.

Low HDL Cholesterol (Hypoalphalipoproteinemia)

Research & References of Low HDL Cholesterol (Hypoalphalipoproteinemia)|A&C Accounting And Tax Services
Source

Share on Facebook

Tweet

Follow us