High density lipoprotein medical therapy
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High Density Lipoprotein Microchapters |
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High density lipoprotein medical therapy On the Web |
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Risk calculators and risk factors for High density lipoprotein medical therapy |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Several clinical trials have demonstrated that raising the serum level of HDL cholesterol is associated with a decreased risk for coronary heart disease. The ATP III guidelines clearly provided a guide on whom to treat (those with CHD or CHD risk equivalents), but the question regarding when to treat was not clearly stated. The treatment of a patient with low HDL cholesterol should be holistic and individualized - involving risk assessment for CHD, ruling out secondary causes, lifestyle modification, achieving LDL and non-HDL cholesterol goals, and then making a choice of the HDL-raising medication to be used based on the drug efficacy, tolerability to patients, interaction with other drugs, and side effects. This page has also provided a step-wise approach to managing a patient with a low HDL.
Who To Treat
The question on whom to treat should be answered on a patient-by-patient basis. According to ATP III guidelines, treating low HDL cholesterol has now become a tertiary target in the management of patients with low HDL, with the primary and secondary goals targeting LDL and non-HDL cholesterol respectively.[1] There are other variables to be considered including the serum triglyceride levels and metabolic abnormalities - diabetes mellitus, metabolic syndrome.
When To Treat
National Cholesterol Education Program (NCEP) has not set a formal goal for HDL levels as a therapeutic target because of lack of evidence for decrease in primary CHD risk reduction with pharmacotherapy. Drug therapy for HDL can be considered in patients in presence of other risk factors for CHD such as hypertension, smoking, family history of premature coronary heart disease. The following are the ATP III guidelines for low HDL management (i.e., HDL-C≤40 mg/dl):
- First LDL goal should be achieved
- Weight reduction and physical exercise
- If serum triglycerides is between 200 and 499 mg/dL, achieve non-HDL goal first
- If triglycerides <150 mg/dL (isolated low HDL) in CHD or CHD equivalent, consider nicotinic acid or fibrate
Treatment
Non-pharmacologic Therapies
| LIFESTYLE MEASURE | EFFECT ON HDL |
| Physical exercise[2] | 5-30% increase |
| Weight reduction | 5-20% increase[3] |
| Smoking cessation | 5% increase[4] |
| Multivitamins | 31% increase in HDL |
| DASH diet | 21% increase in HDL[5] |
| Low carbohydrate diet | 4.5mg/dl increase in HDL[6] |
| Soy protein with isoflavones | 3% increase in HDL[7] |
| Fish oil (omega-3 fatty acid) | Significant increase in HDL2 fraction[8] |
| Fish oil with exercise | 8% increase in HDL[9] |
| Low fat diet | 5-14% increase in HDL when combined with exercise[10] |
Significant increase in HDL was observed when a calorie restricted version of DASH diet was used. Liese et al found a lower level of HDL with DASH diet in diabetic patients.[11]
Pharmacologic Therapy
| DRUGS | MECHANISM OF ACTION | EFFECT ON HDL | SIDE EFFECTS |
| Nicotinic acid (Niacin) | Decreases VLDL synthesis in the liver through diaglycerol acyl transferase-2 (DGAT-2),[12] decreases HDL-apo A-I catabolism[13] | 15-35% increase | Cutaneous flushing, hyperglycemia, hyperuricemia, hepatotoxicity |
| Fibrates | Direct stimulation of apo-A1 and apo-AII synthesis via peroxisome proliferator-activated receptors,[14] | 10-20% increase | Increased risk of myopathy when combined with statins, gallstones, dyspepsia |
| HMG-CoA reductase inhibitor | Increases synthesis of apo-A1 and HDL in the liver,[15] increases ABCA1 mRNA in hepG2 cells,[16] inhibits CETP mass and activities[17] | 5-15% increase | Myopathy, rhabdomyolysis |
| Ezetimibe | Inhibits cholesterol absorption at intestine level | 3% increase in HDL along with statins[18] | Headache, diarrhea, hypersensitivity |
| Thiazolidinediones | Increase in adiponectin which increases insulin resistance | 14% increase in HDL[19] | Fluid retention |
| Hormone replacement therapy | Increases Apo-A1 and decreases activity of hepatic lipase | 5 to 20% increase | Increases risk of stroke and thromboembolic diseases |
| Bile acid sequestrants | Increases apo A-1 production[20] | 3-5% increase | GI discomfort, constipation, reduces absorption of other medications |
Treatment Approach
Non-HDL-Cholesterol Goal
Non-HDL-C represents the cholesterol content present in all the atherogenic lipoproteins i.e., a combination of LDL-C, VLDL-C, IDL-C, and Lipoprotein(a) cholesterol.[21] It is the difference between the total cholesterol and HDL cholesterol (Non-HDL-C = Total cholesterol minus HDL-C). Some studies have demonstrated that non-HDL cholesterol fraction may be a better predictor of future cardiovascular risk than LDL cholesterol.[22][23] The treatment goal for non-HDL-C is 30 mg/dL above the LDL-C treatment target.
Below is a table showing the non-HDL and LDL cholesterol goals to be achieved in the management of patients with a low HDL cholesterol according to the ATP III guidelines:
| RISK CATEGORY | NON-HDL-GOAL mg/dl | LDL GOAL mg/dl |
| 0 to 1 CHD risk factor | <190 | <160 |
| Two or more CHD risk factors (10-year risk for CHD≤20%) | <160 | <130 |
| Coronary heart disease (CHD) and CHD risk equivalent (10-year risk for CHD risk>20% ) | <130 | <100 |
| Low HDL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rule out secondary causes Hypothyroidism Diabetes mellitus Uremia Liver disease Medications - diuretics, progestin, androgens, beta blockers Acute illness - MI, burns, surgery | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lifestyle modification Diet[24] Physical exercise Smoking cessation Weight loss[25] Intake of unhydrogenated monounsaturated fat[26][27] e.g., olive oil, canola oil | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Coronary heart disease | No Coronary heart disease | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lipid profile | Assess risk | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Low density lipoprotein | Triglyceride | High risk HDL<40 mg/dl HDL<40 mg/dl (men) and HDL<50 (women) in patients with metabolic syndrome | Low risk | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Low LDL | High LDL | TG<150 mg/dl | TG 200-499 mg/dl | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Consider fibrates/niacin or statins | Statins | Assess non-HDL goals | Statins or Niacin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assess LDL goal | Isolated low HDL-C (with established CHD or CHD equivalent | Achieved non-HDL goal but TG>200 | Not achieved | Positive family history of premature CHD | Negative family history of premature CHD | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Target reached | Fenofibrate | Lipid lowering drugs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HDL<40 | HDL>40 | Considar niacin,[28] fibrates or niacin/gemfibrozil[29] | Considar statins or niacin | Continue non-pharmacological approach | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Add niacin or gemfibrozil | Continue statins | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
References
- ↑ "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. 285 (19): 2486–97. 2001. PMID 11368702. Unknown parameter
|month=ignored (help) - ↑ Thompson PD (1990). "What do muscles have to do with lipoproteins?". Circulation. 81 (4): 1428–30. PMID 2317921.
- ↑ Dattilo AM, Kris-Etherton PM (1992). "Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis". Am J Clin Nutr. 56 (2): 320–8. PMID 1386186.
- ↑ Gepner AD, Piper ME, Johnson HM, Fiore MC, Baker TB, Stein JH (2011). "Effects of smoking and smoking cessation on lipids and lipoproteins: outcomes from a randomized clinical trial". Am Heart J. 161 (1): 145–51. doi:10.1016/j.ahj.2010.09.023. PMC 3110741. PMID 21167347.
- ↑ Azadbakht, L.; Mirmiran, P.; Esmaillzadeh, A.; Azizi, T.; Azizi, F. (2005). "Beneficial effects of a Dietary Approaches to Stop Hypertension eating plan on features of the metabolic syndrome". Diabetes Care. 28 (12): 2823–31. PMID 16306540. Unknown parameter
|month=ignored (help) - ↑ Nordmann, AJ.; Nordmann, A.; Briel, M.; Keller, U.; Yancy, WS.; Brehm, BJ.; Bucher, HC. (2006). "Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials". Arch Intern Med. 166 (3): 285–93. doi:10.1001/archinte.166.3.285. PMID 16476868. Unknown parameter
|month=ignored (help) - ↑ Zhan, S.; Ho, SC. (2005). "Meta-analysis of the effects of soy protein containing isoflavones on the lipid profile". Am J Clin Nutr. 81 (2): 397–408. PMID 15699227. Unknown parameter
|month=ignored (help) - ↑ Sacks FM, Hebert P, Appel LJ, Borhani NO, Applegate WB, Cohen JD; et al. (1994). "The effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the Trials of Hypertension Prevention. Trials of Hypertension Prevention Collaborative Research Group". J Hypertens Suppl. 12 (7): S23–31. PMID 7769501.
- ↑ Herrmann W, Biermann J, Kostner GM (1995). "Comparison of effects of N-3 to N-6 fatty acids on serum level of lipoprotein(a) in patients with coronary artery disease". Am J Cardiol. 76 (7): 459–62. PMID 7653444.
- ↑ Varady KA, Jones PJ (2005). "Combination diet and exercise interventions for the treatment of dyslipidemia: an effective preliminary strategy to lower cholesterol levels?". J Nutr. 135 (8): 1829–35. PMID 16046704.
- ↑ Liese, AD.; Bortsov, A.; Günther, AL.; Dabelea, D.; Reynolds, K.; Standiford, DA.; Liu, L.; Williams, DE.; Mayer-Davis, EJ. (2011). "Association of DASH diet with cardiovascular risk factors in youth with diabetes mellitus: the SEARCH for Diabetes in Youth study". Circulation. 123 (13): 1410–7. doi:10.1161/CIRCULATIONAHA.110.955922. PMID 21422385. Unknown parameter
|month=ignored (help) - ↑ Wierzbicki, AS. (2011). "Niacin: the only vitamin that reduces cardiovascular events". Int J Clin Pract. 65 (4): 379–85. doi:10.1111/j.1742-1241.2011.02630.x. PMID 21401825. Unknown parameter
|month=ignored (help) - ↑ Kamanna, VS.; Kashyap, ML. (2008). "Mechanism of action of niacin". Am J Cardiol. 101 (8A): 20B–26B. doi:10.1016/j.amjcard.2008.02.029. PMID 18375237. Unknown parameter
|month=ignored (help) - ↑ Vu-Dac, N.; Schoonjans, K.; Kosykh, V.; Dallongeville, J.; Fruchart, JC.; Staels, B.; Auwerx, J. (1995). "Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor". J Clin Invest. 96 (2): 741–50. doi:10.1172/JCI118118. PMID 7635967. Unknown parameter
|month=ignored (help) - ↑ Yamashita, S.; Tsubakio-Yamamoto, K.; Ohama, T.; Nakagawa-Toyama, Y.; Nishida, M. (2010). "Molecular mechanisms of HDL-cholesterol elevation by statins and its effects on HDL functions". J Atheroscler Thromb. 17 (5): 436–51. PMID 20513953. Unknown parameter
|month=ignored (help) - ↑ Maejima, T.; Sugano, T.; Yamazaki, H.; Yoshinaka, Y.; Doi, T.; Tanabe, S.; Nishimaki-Mogami, T. (2011). "Pitavastatin increases ABCA1 expression by dual mechanisms: SREBP2-driven transcriptional activation and PPARα-dependent protein stabilization but without activating LXR in rat hepatoma McARH7777 cells". J Pharmacol Sci. 116 (1): 107–15. PMID 21521932.
- ↑ van Venrooij, FV.; Stolk, RP.; Banga, JD.; Sijmonsma, TP.; van Tol, A.; Erkelens, DW.; Dallinga-Thie, GM. (2003). "Common cholesteryl ester transfer protein gene polymorphisms and the effect of atorvastatin therapy in type 2 diabetes". Diabetes Care. 26 (4): 1216–23. PMID 12663600. Unknown parameter
|month=ignored (help) - ↑ Ballantyne, CM.; Houri, J.; Notarbartolo, A.; Melani, L.; Lipka, LJ.; Suresh, R.; Sun, S.; LeBeaut, AP.; Sager, PT. (2003). "Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial". Circulation. 107 (19): 2409–15. doi:10.1161/01.CIR.0000068312.21969.C8. PMID 12719279. Unknown parameter
|month=ignored (help) - ↑ Szapary, PO.; Bloedon, LT.; Samaha, FF.; Duffy, D.; Wolfe, ML.; Soffer, D.; Reilly, MP.; Chittams, J.; Rader, DJ. (2006). "Effects of pioglitazone on lipoproteins, inflammatory markers, and adipokines in nondiabetic patients with metabolic syndrome". Arterioscler Thromb Vasc Biol. 26 (1): 182–8. doi:10.1161/01.ATV.0000195790.24531.4f. PMID 16284192. Unknown parameter
|month=ignored (help) - ↑ Shepherd, J. (1989). "Mechanism of action of bile acid sequestrants and other lipid-lowering drugs". Cardiology. 76 Suppl 1: 65–71, discussion 71-4. PMID 2713876.
- ↑ Ballantyne, CM.; Grundy, SM.; Oberman, A.; Kreisberg, RA.; Havel, RJ.; Frost, PH.; Haffner, SM. (2000). "Hyperlipidemia: diagnostic and therapeutic perspectives". J Clin Endocrinol Metab. 85 (6): 2089–112. PMID 10852435. Unknown parameter
|month=ignored (help) - ↑ Ridker, PM.; Rifai, N.; Cook, NR.; Bradwin, G.; Buring, JE. (2005). "Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women". JAMA. 294 (3): 326–33. doi:10.1001/jama.294.3.326. PMID 16030277. Unknown parameter
|month=ignored (help) - ↑ Di Angelantonio, E.; Sarwar, N.; Perry, P.; Kaptoge, S.; Ray, KK.; Thompson, A.; Wood, AM.; Lewington, S.; Sattar, N. (2009). "Major lipids, apolipoproteins, and risk of vascular disease". JAMA. 302 (18): 1993–2000. doi:10.1001/jama.2009.1619. PMID 19903920. Unknown parameter
|month=ignored (help) - ↑ Wood, PD.; Stefanick, ML.; Dreon, DM.; Frey-Hewitt, B.; Garay, SC.; Williams, PT.; Superko, HR.; Fortmann, SP.; Albers, JJ. (1988). "Changes in plasma lipids and lipoproteins in overweight men during weight loss through dieting as compared with exercise". N Engl J Med. 319 (18): 1173–9. doi:10.1056/NEJM198811033191801. PMID 3173455. Unknown parameter
|month=ignored (help) - ↑ Berns, MA.; de Vries, JH.; Katan, MB. (1989). "Increase in body fatness as a major determinant of changes in serum total cholesterol and high density lipoprotein cholesterol in young men over a 10-year period". Am J Epidemiol. 130 (6): 1109–22. PMID 2589304. Unknown parameter
|month=ignored (help) - ↑ Oh, K.; Hu, FB.; Manson, JE.; Stampfer, MJ.; Willett, WC. (2005). "Dietary fat intake and risk of coronary heart disease in women: 20 years of follow-up of the nurses' health study". Am J Epidemiol. 161 (7): 672–9. doi:10.1093/aje/kwi085. PMID 15781956. Unknown parameter
|month=ignored (help) - ↑ Mensink, RP.; Katan, MB. (1990). "Effect of dietary trans fatty acids on high-density and low-density lipoprotein cholesterol levels in healthy subjects". N Engl J Med. 323 (7): 439–45. doi:10.1056/NEJM199008163230703. PMID 2374566. Unknown parameter
|month=ignored (help) - ↑ Guyton, JR.; Blazing, MA.; Hagar, J.; Kashyap, ML.; Knopp, RH.; McKenney, JM.; Nash, DT.; Nash, SD. (2000). "Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol. Niaspan-Gemfibrozil Study Group". Arch Intern Med. 160 (8): 1177–84. PMID 10789612. Unknown parameter
|month=ignored (help) - ↑ Zema, MJ. (2000). "Gemfibrozil, nicotinic acid and combination therapy in patients with isolated hypoalphalipoproteinemia: a randomized, open-label, crossover study". J Am Coll Cardiol. 35 (3): 640–6. PMID 10716466. Unknown parameter
|month=ignored (help)