HDL-The Cardioprotective Cholesterol

HDL ─The Highly Desirable Lipoprotein

  • High blood levels of HDL-C and apoA-I are inversely related to the risk of CAD (coronary artery disease) and CVD (cardiovascular disease) events in both men and women. High levels of this lipoprotein are associated with reduced risk for atherosclerosis, CVD and its clinical sequelae, such as heart attack, ischemic stroke, and death. Low levels of HDL are also associated with worse prognosis after a heart attack. 
  • A 1% increase in HDL-C confers a 2% decrease in CVD risk and a 1 mg/dL decrease confers a 4% decrease in CVD risk.1, 2 
  • A graded association exists between lower levels of HDL-C and CAD across the full range of LDL-C levels including <100 mg/dl but not <50 mg/dl. As interventions targeting HDL levels are developed, the combinatorial effects of lower HDL levels with various levels of LDL-cholesterol should be examined.3
  • Almost one-fifth of patients with ACS (acute coronary syndromes) have very low HDL levels (10-29 mg/dl)─a finding that adds incrementally to a greater burden of atherosclerosis and a higher risk of mortality; 35% had low HDL levels (30-39 mg/dL), 39% had normal HDL levels (40-59 mg/dL), and 9.0% had high HDL levels (60-100 mg/dL).4 Consequently, strategies for mitigating the adverse prognosis associated with very low HDL levels warrant further exploration in patients with ACS.4

HDL levels

  • The mean HDL-C in the U.S. adult population, on the basis of data from the NHANES (National Health and Nutrition Examination Survey) 2003–2004, was 54 mg/dL. HDL-C was lower than “normal” (defined as ≥40 mg/dL in men and ≥50 mg/dL in women) in 27% of NHANES subjects overall and 35% of NHANES subjects with CVD.5
  • The mean HDL level varies by gender and ethnicity: white men 48 mg/dL; white women 60 mg/dL; black men 52 mg/dL; black women 61 mg/dL. 5

HDL Subclasses

  • HDL particles can be categorized into 12 subclasses. The largest α-1 particle is the most cardioprotective and 1 mg/dl increase confers a 26% decrease in CAD risk compared to 4% decreased risk with I mg/dL increase in HDL-C.6
  • In a comparative study of Asian Indians in the US with Framingham Heart study, the HDL-C levels were similar. However, Asian Indians had lower concentrations of large HDL cholesterol and higher concentrations of small HDL cholesterol than whites.  HDL particle size was smaller in Asian Indians. Levels of LDL-C, LDL particle size, and prevalence of small dense LDL (pattern B) were similar in the two groups.7

HDL, Cancer, and Alzheimer’s Disease

  • There is a significant inverse association between HDL-C and the risk of incident cancer.8 In a model that controlled for other variables, including LDL-C, age, body-mass index (BMI), sex, and smoking status, there was a significant 36% lower risk of cancer for every 10-mg/dL increase in HDL-C.8
  • A recent study, published in the Archives of Neurology, found that people who had low levels of HDL had a 60 percent greater risk of developing Alzheimer’s disease after the age of 65 than those who had higher levels.8


1. Enas E.A., Hancy Chennikkara Pazhoor MD, Arun Kuruvila MBBS, Krishnaswami Vijayaraghavan MD F. Intensive Statin Therapy for Indians:Part I Benefits. Indian Heart J 2011; 63: 211-227.

2. Grover SA, Kaouache M, Joseph L, Barter P, Davignon J. Evaluating the incremental benefits of raising high-density lipoprotein cholesterol levels during lipid therapy after adjustment for the reductions in other blood lipid levels. Arch Intern Med. Oct 26 2009;169(19):1775-1780.

3. Muntner P, Lee F, Astor BC. Association of high-density lipoprotein cholesterol with coronary heart disease risk across categories of low-density lipoprotein cholesterol: the atherosclerosis risk in communities study. Am J Med Sci. Mar 2011;341(3):173-180.

4. Roe MT, Ou FS, Alexander KP, et al. Patterns and prognostic implications of low high-density lipoprotein levels in patients with non-ST-segment elevation acute coronary syndromes. Eur Heart J. Oct 2008;29(20):2480-2488.

5. Ghandehari H, Kamal-Bahl S, Wong ND. Prevalence and extent of dyslipidemia and recommended lipid levels in US adults with and without cardiovascular comorbidities: the National Health and Nutrition Examination Survey 2003-2004. Am Heart J. Jul 2008;156(1):112-119.

6. Asztalos BF, Cupples LA, Demissie S, et al. High-density lipoprotein subpopulation profile and coronary heart disease prevalence in male participants of the Framingham Offspring Study. Arterioscler Thromb Vasc Biol. Nov 2004;24(11):2181-2187.

7. Bhalodkar NC, Blum S, Rana T, et al. Comparison of levels of large and small high-density lipoprotein cholesterol in Asian Indian men compared with Caucasian men in the Framingham Offspring Study. Am J Cardiol. Dec 15 2004;94(12):1561-1563.

8. Jafri H, Alsheikh-Ali AA, Karas RH. Baseline and on-treatment high-density lipoprotein cholesterol and the risk of cancer in randomized controlled trials of lipid-altering therapy. J Am Coll Cardiol. Jun 22 2010;55(25):2846-2854.

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