High density lipoprotein medical therapy: Difference between revisions
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|bgcolor="#cccccc"| '''INVESTIGATIONAL DRUGS''' | |bgcolor="#cccccc"| '''INVESTIGATIONAL DRUGS''' | ||
|bgcolor="#cccccc"| '''MECHANISM OF ACTION''' | |bgcolor="#cccccc"| '''MECHANISM OF ACTION''' | ||
|bgcolor="#cccccc"| ''' | |bgcolor="#cccccc"| '''HIGHEST OBSERVED INCREASE ON HDL-C''' | ||
|bgcolor="#cccccc"| '''SIDE EFFECTS''' | |bgcolor="#cccccc"| '''SIDE EFFECTS''' | ||
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Revision as of 14:01, 20 September 2013
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High Density Lipoprotein Microchapters |
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Diagnosis |
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Treatment |
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Clinical Trials |
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Case Studies |
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High density lipoprotein medical therapy On the Web |
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American Roentgen Ray Society Images of High density lipoprotein medical therapy |
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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
Treatment
Risk Assessment
Coronary Heart Disease
It has been established that HDL levels are inversely related to the risk of coronary artery disease and over all mortality caused by cardiovascular diseases. In a review of four important studies, it was documented that with increase in HDL levels by 1mg/dl, risk of coronary heart disease decreased by 2% in men and 3% in women. According to the review, mortality caused by cardiovascular diseases decreased by 3.7% in men and 4.7% in women with an increase in HDL levels by 1mg/dl.[1] American heart association recommends HDL level less than 50 mg/dl in women with increased CHD risk and a level of less than 40 mg/dl in men.
Risk assessment for CHD is done based on following factors:
- Increased total cholesterol and triglyceride level
- Total cholesterol/HDL ratio
- Diabetes mellitus
- Obesity
- Smoking
- Lack of physical activity
- Stress
Non-modifiable risk factors:
- Age
- Gender (male)
- Family history of premature coronary artery disease
Metabolic Syndrome
Metabolic syndrome has been described as a group of disorders, a combination of which increases the risk of cardiovascular disease. These disorders include central obesity, increased waist circumference, hyperglycemia, dyslipidemia and high blood pressure. Low HDL along with hypertension has been identified as the most important metabolic syndrome risk factors for heart failure.[2]
Diabetes Mellitus
Persistently elevated blood glucose is associated with low level of HDL in type 2 diabetes mellitus.[3] According to American Diabetes Association, HDL should be maintained above 40 mg/dl in diabetics.
When To Treat
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
Treatment Options
Non-pharmacologic Therapies
Weight Loss
In a metanalysis of 70 studies,12% increase in HDL level was observed in subjects with stable reduced weight.[4]
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%.[5]
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.[6]
Dietary Measures
| DIET | EFFECT ON HDL |
| Multivitamins | 31% increase in HDL |
| DASH diet | 21% increase in HDL[7] |
| Low carbohydrate diets | 4.5mg/dl increase in HDL[8] |
| Soy protein with isoflavones | 3% increase in HDL[9] |
| Fish oil (omega-3 fatty acid) | Significant increase in HDL2 fraction[10] |
| Fish oil with exercise | 8% increase in HDL[11] |
| Low fat diet | 5-14% increase in HDL when combined with exercise[12] |
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.[13]
Pharmacologic Therapies
Medications
| Drugs | MECHANISM OF ACTION | EFFECT ON HDL-C | SIDE EFFECTS |
| Nicotinic acid (Niacin) | Decreases VLDL synthesis | 21% increase in HDL[14] | Cutaneous flushing, hyperglycemia, hyperuricemia, hepatotoxicity |
| Fibric acid derivatives | Increased synthesis of Apo-A1 | 6% increase in HDL in one year[15] | Increased risk of myopathy with statins |
| HMG CoA reductase inhibitors | They increase HDL by increasing level of Apo-A1 | 13% increase in HDL [16] | Myopathy, rhabdomyolyisis |
| Ezetimibe | Inhibits cholesterol absorption at intestine level | 3% increase in HDL along with statins[17] | Headache, diarrhea, hypersensitivity |
| Thiazolidinediones | Increase in adiponectin which increases insulin resistance | 14% increase in HDL[18] | Fluid retention |
| Hormone replacement therapy | Increased Apo-A1 and decreased activity of hepatic lipase | 5 to 20% increase in HDL | Increased risk of stroke and thromboembolic diseases |
| INVESTIGATIONAL DRUGS | MECHANISM OF ACTION | HIGHEST OBSERVED INCREASE ON HDL-C | SIDE EFFECTS |
| Endocannabinoid receptor blockers | |||
| ApoA-1 Milano | |||
| CETP Inhibitors | |||
| CETi-1 Vaccine | |||
| JTT-705 | |||
| CER-001 | |||
| CSL-112 |
References
- ↑ Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD; et al. (1989). "High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies". Circulation. 79 (1): 8–15. PMID 2642759.
- ↑ Karadag MK, Akbulut M (2009). "Low HDL levels as the most common metabolic syndrome risk factor in heart failure". Int Heart J. 50 (5): 571–80. PMID 19809206.
- ↑ Gatti A, Maranghi M, Bacci S, Carallo C, Gnasso A, Mandosi E; et al. (2009). "Poor glycemic control is an independent risk factor for low HDL cholesterol in patients with type 2 diabetes". Diabetes Care. 32 (8): 1550–2. doi:10.2337/dc09-0256. PMC 2713640. PMID 19487641.
- ↑ 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)