familial hdl deficiency treatment

Thrombocytopenia and hemolytic anemia are sometimes observed. 409(3):400-5. Of the available drugs, niacin results in the largest increase in HDL-C. Fibrates do not increase HDL-C in patients with normal triglycerides. [34] Events increased 50% with HRT during year 1 but then progressively decreased to 33% lower by the study's end. Overall, fibrates reduce the risk for major coronary events by 25%, whereas currently available data for niacin suggest about a 27% reduction. [40] In this investigation, LDL levels fell by 42% (P< 0.001) and HDL levels increased by 26% (P< 0.001). Santamarina-Fojo S, Hoeg JM, Assmann G. Lecithin cholesterol acyltransferase deficiency and fish eye disease. Familial HDL deficiency is a rare genetic condition that causes low levels of "good" cholesterol (HDL) in the blood. [Medline]. John D. Brunzell, in Clinical Lipidology, 2009, In 1992, Genest and colleagues proposed that FHA, a disorder with elevated triglyceride and low HDL cholesterol, was a common genetic dyslipidemia associated with premature CAD.106,107 The HDL Atherosclerosis Treatment Study (HATS) selected middle-aged men and women with premature CAD for an intervention study.108 In HATS, 87 men with low HDL selected to not have diabetes or elevated apoB levels were proposed to have FHA.101 These men had normal levels of apoB compared with FCHL.101 In contrast to FHTG, men with FHA had lower plasma apoA-I levels and did not have triglyceride-rich HDL particles as seen in FHTG. Find out information about familial high-density lipoprotein (HDL) deficiency. 1999 Feb. 8(2):331-6. 1983 Nov 16. 9 (3):206-12. [Full Text]. May 2001. Statins lower total cholesterol and represent the most efficacious way to lower the ratio of total cholesterol to HDL-C. Statins decrease clinical events in patients with low HDL-C.151 As noted earlier, pharmacologic therapies for raising HDL levels, notably niacin and inhibition of CETP, have not yet shown efficacy in cardiovascular outcome trials. In a study, ETC-216, a recombinant form of apo A-I Milano–phospholipid complex, was found to be effective in reducing coronary atheroma volume as measured by intravascular ultrasonography. Multiple studies have shown that niacin, fibrates, and statins can decrease the risk of cardiovascular disease and atherosclerosis progression by affecting multiple lipid parameters. Most patients who receive niacin also have high LDL cholesterol levels that are being managed pharmacologically, and niacin is added to raise their HDL cholesterol level if it is low. Instruct patients who smoke to stop smoking, tell persons who are overweight to manage their weight, and encourage individuals who are sedentary to engage in regular exercise. Assmann G, von Eckardstein A, Brewer HB Jr. Familial analphalipoproteinemia: Tangier disease. Metabolic syndrome is the second target. We report findings in four subjects with severe familial HDL deficiency (HDL-C<<5th percentile for age and sex; 0.08 to 0.38 mmol/L) in three French-Canadian kindreds with autosomal codominant inheritance. [Medline]. [Medline]. 290(17):2292-300. Atherosclerosis. Additionally, the combination products that include simvastatin or lovastatin plus long-acting niacin (ie, Advicor, Simcor) were withdrawn from the U.S. market at the beginning of 2016 and are no longer available. Strongly encourage increased physical activity, especially in persons with sedentary habits. Asztalos BF, Schaefer EJ, Horvath KV, et al. 2012 Oct. 97(10):3399-407. It is still controversial whether patients with homozygous Tangier disease develop premature CHD. [Full Text]. 256(17):2372-7. The early increase may have resulted from prothrombotic and/or pro-inflammatory effects of HRT, while the later decrease may have reflected the 8% increase in HDL cholesterol and/or other antiatherosclerotic mechanisms. A comparison of methods for the estimation of plasma low- and very low-density lipoprotein cholesterol. HDL infusion therapy studied in a group of 40 Italian villagers led to the discovery of a rare type of HDL that seemed to protect against heart disease even when the levels of HDL were not very high. Medscape Reference Feature Series - Lipid Newsletter. These cells have abnormal actin cytoskeletons in association with decreased expression of Cdc42, a member of the RhoGTPases family. Vergani's disease]. Patients with elevated triglyceride levels (>500 mg/dL) commonly have low HDL cholesterol levels; address hypertriglyceridemia first in such patients. It is associated with fat soluble vitamin D deficiency rickets and severe dyslipidemia; however, treatment of these secondary effects remains a challenge. 2000 Sep. 152(1):181-92. According to the NCEP guidelines, daily activity and energy expenditure should include at least moderate physical activity, with the patient expending approximately 840 kJ/d. The radioactivity decay curve of 125 I labelled HDL was used for assessment of kinetics. Nissen and colleagues tested whether a synthetic version of apo A-I Milano (recombinant apo A-1 Milano/phospholipid complexes, ETC-216) infused into the blood of people who did not naturally have this protein would have the same effect. A niacin/statin combination was also evaluated in the HDL-Atherosclerosis Treatment Study (HATS). Control diabetes optimally, and aggressively treat LDL cholesterol, regardless of HDL cholesterol levels. [Full Text]. You will see meanings of Familial HDL Deficiency in many other languages such as Arabic, Danish, Dutch, … [Efficacy of hygienic and dietary therapy in coronary patients with isolated hypoalphalipoproteinemia]. [Medline]. Pinellas County Medical Society (PICOMESO) Journal. [Medline]. The NCEP has recommended a therapeutic lifestyle-change diet, which should be incorporated in the treatment of all patients. 20 Sequencing of his LCAT gene was normal, but the patient was found to be homozygous for an apoA-I frameshift mutation resulting in a truncated … Their cholesterol intake should be reduced to less than 200 mg/d. FEBS Lett. 23(2):160-7. 2011 Dec 15. 2011 Aug 19. [Full Text]. Arch Inst Cardiol Mex. JAMA. Familial HDL Deficiency This inherited disorder causes a person to have abnormally low levels of HDL (“good”) cholesterol circulating in their system. 2008 Sep 5. [Medline]. HDL is a molecule that transports cholesterol and certain fats called phospholipids through the bloodstream from the body's tissues to the liver ... 1 More on Familial HDL deficiency » Accessed: 2/10/09. If you are visiting our English version, and want to see definitions of Familial HDL Deficiency in other languages, please click the language menu on the right bottom. Human HDL deficiency (hypoalphalipoproteinemia) defines a group of dyslipidemias characterized by an HDL cholesterol level below the 10th percentile for age- and sex-matched subjects. JAMA. [Medline]. The disorder frequently manifests during childhood. This drug reportedly does not raise blood pressure. Eur J Haematol. 2500032-overview More studies are needed to understand FHA. Effect of recombinant ApoA-I Milano on coronary atherosclerosis inpatients with acute coronary syndromes: a randomized controlled trial. Here we report six subjects with low HDL, carrying seven ABCA1 mutations, six of … Polyunsaturated fats should constitute up to 10% of total energy intake, and monounsaturated fats, up to 20% of total energy intake. In the Danish general population, two SNPs (V771M and V825I) of ABCA1 gene were associated with increases in HDL-C, one (R1587K) with decreases in HDL-C, whereas three (R219K, I883M, and E1172D) did not affect HDL-C levels. 51(11):1098-103. Such patients can have high ratios of total cholesterol to HDL-C (e.g., >10) despite having a normal plasma cholesterol level. Reproduced with permission from Komuro, R., et al. Although there is no cure for familial LCAT deficiency, there are ways to manage the signs and symptoms including: Dialysis  and kidney transplant as needed for individuals who develop kidney failure Corneal transplantation for individuals with corneal opacities and severely reduced vision … Biochim Biophys Acta. levels of paraoxonase, an HDL-associated, antioxidant enzyme, were also increased by 10%. 2007 Nov 22. HDL helps remove excess cholesterol and fats from your blood. Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. J Am Coll Cardiol. Nonetheless, the treatment strategies appear to be well suited for this subpopulation, which has a high prevalence of HA. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. Always consider secondary causes of low HDL levels, especially medications, smoking habits, dietary patterns, and physical activity. 1998 Aug 19. 2008 Mar. for: Medscape. 2015 Nov 17. 2001 May 16. [Medline]. [Medline]. Vega GL, Grundy SM. Tangier disease (familial high-density lipoprotein deficiency) is an autosomal recessive disorder characterized by hypocholesterolemia (50–125 mg/dL), an almost complete absence of plasma HDL, and massive deposition of cholesterol esters in tissues. N Engl J Med. Abnormal dilatation of the Golgi cisternae speaks to a disruption of intracellular lipid trafficking through vesicular budding, with abnormal ceramide and glycerophospholipid turnover.71,92, Ken-ichi Hirano, ... Yuji Matsuzawa, in Encyclopedia of Endocrine Diseases, 2004. J Am Coll Cardiol. [Medline]. In most cases, hereditary HDL deficiency has been caused by mutations in three different genes: 1. Role of LCAT in HDL remodeling: investigation of LCAT deficiency states. In a study by AIM-HIGH Investigators et al, the addition of niacin to statin therapy did not provide any clear benefit to patients with cardiovascular disease and low HDL levels. With regard to HA, the ATP III report stated, "Low HDL cholesterol is a strong independent predictor of CHD [coronary heart disease]. Completion of trials with clinical endpoints (eg, AIM-HIGH and HPS2-THRIVE clinical trials) have shown that the addition of niacin that decreased TGs and/or increased HDL-C levels in statin-treated patients does not cause further reduction in risk of CV events. Ann Intern Med. The primary endpoint of ARBITER 2 was change in common carotid intima-media thickness (CIMT). How 2020 Changed Diabetes and Primary Care, The Top 10 Trending Clinical Topics of 2019, More Evidence That Vitamin D Sufficiency Equals Less Severe COVID-19, 'On-Demand' Fast Mobilizes Fat; Low-Carb Breakfast Stymies Hunger, Blood Glucose on Admission Predicts COVID-19 Severity in All, Recall Widens for Diabetes Drug Metformin, Clinical Practice Guidelines on Pharmacologic Glycemic Treatment in Type 2 Diabetes (ADA, 2020), AACE Issues 'Cookbook' Algorithm to Manage Dyslipidemia, First-of-Its Kind Guideline on Lipid Monitoring in Endocrine Diseases. Papers overview. 1983 Mar 24. However, five out of six SNPs (V771M, V825I, I883M, E1172D, R1587K) predicted increased risk of CHD. [Full Text]. 63(18):1907-45. Estrogen replacement or hormone replacement therapy (HRT) raises HDL by about 8% in postmenopausal women, but its use is controversial; such treatment is not recommended for CAD prevention due to a demonstrated lack of benefit and the possible risk of increased thrombosis. 1986 Nov 7. Biology the absence of a gene or a region of a chromosome normally present Explanation of familial high-density lipoprotein (HDL) deficiency. Treatment There are drugs that can increase serum HDL such as niacin or gemfibrozil . Familial LCAT deficiency represents a disorder that is characterized by abnormalities in the levels of several different blood lipids that includes decreased levels of LDL, HDL, apoA-I, and apoA-II along with increased levels of free cholesterol, apoE, and triglycerides. The 2 drugs differ in chemical structure. ABCA1 is the cholesterol/phospholipid efflux protein that is defective in patients with Tangier disease and familial HDL deficiency. [Full Text]. 66 (20):2201-10. Fish eye disease, initially described in two families of Swedish origin, is characterized by the absence of LCAT activity towards HDL only. [Full Text]. 2017. Plasma lipoproteins, lipids, LCAT levels, and several measures of renal function and other clinical labs were monitored. Ordovas JM, Schaefer EJ, Salem D, et al. Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III Final Report). 74(12):585-94. in 1961 (Table I). DeLong DM, DeLong ER, Wood PD, et al. The investigation showed that the atherosclerosis in the coronary vessel wall could be modified in a much shorter time than anticipated, ie, within 5-6 weeks. GILMORE N. O'NEILL, MASON W. FREEMAN, in Peripheral Neuropathy (Fourth Edition), 2005, Macrophages and fibroblasts from TD and FHA patients demonstrate a significant defect in lipid-poor apo A-I–stimulated cholesterol and phospholipid efflux.13,30,84,102 As a result, cholesteryl esters accumulate in membrane free droplets. [Medline]. Niacin/lovastatin increased HDL significantly more than did statin alone at all dose combinations (P< 0.001). Frequent occurrence of hypoalphalipoproteinemia due to mutant apolipoprotein A-I gene in the population: a population-based survey. Patients with ABCA1 mutations are thought to have moderately increased risk for CHD. [Medline]. Godin DV, Garnett ME, Hoag G, et al. New York, NY: McGraw-Hill; 2001. Role of the estrogen and progestin in hormonal replacement therapy on apolipoprotein A-I kinetics in postmenopausal women. [Full Text]. 2000 Jun. Furthermore, the FHA patients had a selective decrease in the HDL2 apoA-I (without apoA-II) particle.109. Ghassem Pourmotabbed, MD, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Endocrine SocietyDisclosure: Nothing to disclose. Whenever possible, eliminate medications associated with low HDL cholesterol levels. Gebauer SK, Destaillats F, Dionisi F, Krauss RM, Baer DJ. Next-generation anti-CD20 monoclonal antibodies in autoimmune disease treatment. Ordovas, in Encyclopedia of Human Nutrition (Third Edition), 2013. Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug ReferenceDisclosure: Received salary from Medscape for employment. Uehara Y, Tsuboi Y, Zhang B, et al. Most individuals are diagnosed with hypoalphalipoproteinemia (HA) based on the results of a routine lipid profile measurement. The Metabolic Basis of Inherited Disease. However, mutations in these candidate genes are rare and account for little FHA. For example: In the patients with established CHD or a CHD risk equivalent (10-year risk for CHD >20%), the LDL goal is under 100 mg/dL, and the goal for non-HDL cholesterol (LDL plus very–low-density lipoprotein [VLDL]) is below 130 mg/dL. Vaccenic acid and trans fatty acid isomers from partially hydrogenated oil both adversely affect LDL cholesterol: a double-blind, randomized controlled trial. Barkowski RS, Frishman WH. Hulley S, Grady D, Bush T, et al. 40(3):486-94. 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). 51(11):1104-9. [Medline]. Treatment for isolated low HDL cholesterol is provided mainly to patients with CHD and CHD risk equivalents. 1989 Jan-Feb. 59(1):9-18. Identify and correct secondary factors. CIMT progression was 68% lower in the niacin/statin group than in the other patients. ABCA1 was expressed on the basolateral plasma membrane of polarized cultured gallbladder epithelial cells. It is unclear whether pharmacologic agents should be used to raise the HDL cholesterol level in otherwise healthy persons, because no published clinical trials are available that demonstrate a benefit. Biochem Biophys Res Commun. Singh VN. [Medline]. CETP helps to exchange cholesterol between lipoproteins and can transfer it from HDL to LDL and VLDL. Diseases & Conditions, Low HDL Cholesterol (Hypoalphalipoproteinemia), encoded search term (Low HDL Cholesterol (Hypoalphalipoproteinemia)) and Low HDL Cholesterol (Hypoalphalipoproteinemia), Dyslipidaemia: Recommendations on the Role of PCSK9 Inhibitors in Lipids Management. The glitazones, which are PPAR (peroxisome proliferator-activated receptor) agonists, act by lowering free fatty acid (FFA) and TG levels and by raising HDL. In fact, increasing the fat content of a patient's diet is not recommended. This phenotype is present in approximately 4% of kindred with premature CHD. An Med Interna. Arterioscler Thromb Vasc Biol. Statins have only a modest effect. [Medline]. [Medline]. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. This is, ... that have been shown to increase circulating levels of HDL, ... Familial LCAT Deficiency: FLD (Fish Eye Disease) Lipoprotein(a) and Atherogenesis; Low HDL levels often reflect a genetic abnormality, although they can also be pushed downward by a high blood level of TGs or by cigarette smoking, inactivity, or hypertension, as well as by a diet very high in carbohydrates or polyunsaturated fats. Grundy SM, Cleeman JI, Merz CN, et al. Primary and familial hypoalphalipoproteinemia. George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine Gemfibrozil, nicotinic acid and combination therapy in patients with isolated hypoalphalipoproteinemia: a randomized, open-label, crossover study. [Medline]. Arterioscler Thromb Vasc Biol. Primary hypoalphalipoproteinemia is seen in approximately 4% of people with CAD. Minerva Med. 290(17):2292-300. Although this points researchers in a promising direction, therapy with torcetrapib needs to be tested in a larger population; it must be shown through outcome studies that the drug not only to increases HDL levels, but that it also prevents heart problems. Share cases and questions with Physicians on Medscape consult. However, because no data are available that show a reduction in the risk of coronary heart disease (CHD) upon raising HDL cholesterol levels, no particular dietary interventions are needed for this specific purpose. [Medline]. 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