High density lipoprotein medical therapy
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High Density Lipoprotein Microchapters |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Treatment
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 triglycerides 200-499 mg/dL, achieve non-HDL goal
- If triglycerides <200 mg/dL (isolated low HDL) in CHD or CHD equivalent, consider nicotinic acid or fibrate
Non-pharmacologic Therapies
Weight Loss
In a metanalysis of 70 studies,12% increase in HDL level was observed in subjects with stable reduced weight.[1]
Smoking Cessation
Smoking increases activity of CETP enzyme and lowers activity of LCAT, which results in reduced amount of HDL. In a study done by Gepner et al, smoking cessation increased HDL level by 5.2%.[2]
Alcohol Consumption
Moderate amount of alcohol consumption can result in increased HDL. However, alcohol can also lead to increased triglyceride levels.
Exercise
Physical activity increases HDL level. One of the suggested mechanisms is increased amount of LPL enzyme.[3]
Dietary Measures
| DIET | EFFECT ON HDL |
| Multivitamins | 31% increase in HDL |
| DASH diet | 21% increase in HDL[4] |
| Low carbohydrate diets | 4.5mg/dl increase in HDL[5] |
| Soy protein with isoflavones | 3% increase in HDL[6] |
| Fish oil (omega-3 fatty acid) | Significant increase in HDL2 fraction[7] |
| Fish oil with exercise | 8% increase in HDL[8] |
| Low fat diet | 5-14% increase in HDL when combined with exercise[9] |
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.[10]
Pharmacologic Therapies
Medications
| Drugs | MECHANISM OF ACTION | AVERAGE OBSERVED INCREASE IN HDL-C IN TRIALS | SIDE EFFECTS |
| Nicotinic acid (Niacin) | Decreases VLDL synthesis | 15-35% increase[11] | Cutaneous flushing, hyperglycemia, hyperuricemia, hepatotoxicity |
| Fibric acid derivatives | Increased synthesis of Apo-A1 | 10-20% increase in HDL in[12] | Increased risk of myopathy when combined with statins, gallstones, dyspepsia |
| HMG CoA reductase inhibitors | They increase HDL by increasing level of Apo-A1 | 5-15% increase in HDL [13] | Myopathy, rhabdomyolyisis |
| Ezetimibe | Inhibits cholesterol absorption at intestine level | 3% increase in HDL along with statins[14] | Headache, diarrhea, hypersensitivity |
| Thiazolidinediones | Increase in adiponectin which increases insulin resistance | 14% increase in HDL[15] | Fluid retention |
| Hormone replacement therapy | Increased Apo-A1 and decreased activity of hepatic lipase | 5 to 20% increase | Increased risk of stroke and thromboembolic diseases |
| Bile acid sequestrants | 3-5% increase | GI discomfort, constipation, reduces absorption of other medications |
Algorithm
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.[16] 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.[17][18] The treatment goal for non-HDL-C is 30 mg/dL above the LDL-C treatment target.
| 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[19] Physical exercise Smoking cessation Weight loss[20] Intake of unhydrogenated monounsaturated fat[21][22] 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<200 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 | {{{oice }}} | Negative family history of premature CHD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Target reached | Fenofibrate | Lipid lowering drugs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HDL<40 | HDL>40 | Considar niacin or fibrates | Considar statins or niacin | Continue non-pharmacological approach | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Add niacin or gemfibrozil | Continue statins | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
References
- ↑ 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.
- ↑ Thompson PD (1990). "What do muscles have to do with lipoproteins?". Circulation. 81 (4): 1428–30. PMID 2317921.
- ↑ 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) - ↑ Taylor, AJ.; Sullenberger, LE.; Lee, HJ.; Lee, JK.; Grace, KA. (2004). "Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins". Circulation. 110 (23): 3512–7. doi:10.1161/01.CIR.0000148955.19792.8D. PMID 15537681. Unknown parameter
|month=ignored (help) - ↑ Rubins, HB.; Robins, SJ.; Collins, D.; Fye, CL.; Anderson, JW.; Elam, MB.; Faas, FH.; Linares, E.; Schaefer, EJ. (1999). "Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group". N Engl J Med. 341 (6): 410–8. doi:10.1056/NEJM199908053410604. PMID 10438259. Unknown parameter
|month=ignored (help) - ↑ Schaefer, JR.; Schweer, H.; Ikewaki, K.; Stracke, H.; Seyberth, HJ.; Kaffarnik, H.; Maisch, B.; Steinmetz, A. (1999). "Metabolic basis of high density lipoproteins and apolipoprotein A-I increase by HMG-CoA reductase inhibition in healthy subjects and a patient with coronary artery disease". Atherosclerosis. 144 (1): 177–84. PMID 10381291. 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) - ↑ 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)