High density lipoprotein medical therapy

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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]

Metabolic Syndrome

Metabolic syndrome has been described as 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 factor for heart failure.[2]

Diabetes Mellitus

Persistently elevated blood glucose is associated with low level of HDL in type 2 diabetes mellitus.[3]

When To Treat

The American Heart Association, NIH and NCEP provides a set of guidelines for male fasting HDL levels and risk for heart disease.

Level mg/dL Level mmol/L Interpretation
<40 <1.03 Low HDL cholesterol, heightened risk for heart disease, <50 is the value for women
40–59 1.03–1.52 Medium HDL level
>60 >1.55 High HDL level, optimal condition considered protective against heart disease

More sophisticated laboratory methods measure not just the total HDL but also the range of HDL particles, e.g. "lipoprotein subclass analysis", typically divided into several groups by size, instead of just the total HDL concentration as listed above. The largest groups (most functional) of HDL particles have the most protective effects. The groups of smallest particles reflect HDL particles which are not actively transporting cholesterol, thus not protective.

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. Following are the ATP III guidelines for low HDL management (,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
  • According to American diabetes association HDL should be maintained above 40 mg/dl in diabetics.
  • 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

Treatment Options

Non-pharmologic

STUDY INTERVENTION METHOD HDL Effect
  • Weight loss

In a metanalysis of 70 studies,12% increase in HDL 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, it also leads to increased triglycerides.

  • Exercise:

Physical activity increases HDL level, increased amount of LPL enzyme is one of the suggested mechanism.[6]

Medications

References

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. Thompson PD (1990). "What do muscles have to do with lipoproteins?". Circulation. 81 (4): 1428–30. PMID 2317921.


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