Hypocholesterolemia

Hypocholesterolemia is the presence of abnormally low (hypo-) levels of cholesterol in the blood (-emia). Although the presence of high cholesterol (hyper-cholesterolemia) has been linked strongly with cardiovascular disease, a defect in the body's production of cholesterol can lead to adverse consequences as well. Cholesterol is an essential component of mammalian cell membranes and is required to establish proper membrane permeability and fluidity. It is not clear if a lower than average cholesterol level is directly harmful; it is often encountered in particular illnesses.

Classification

According to the American Heart Association in 1994, only total cholesterol levels below 160 mg/dL or 4.1 mmol/l are to be classified as "hypocholesterolemia".^[1] However, this is not agreed on universally and some put the level lower.

Causes

Possible causes of low cholesterol are:^{[citation needed]}

• statins
• hyperthyroidism, or an overactive thyroid gland
• adrenal insufficiency
• liver disease
• malabsorption (inadequate absorption of nutrients from the intestines), such as in celiac disease
• malnutrition
• abetalipoproteinemia - a rare genetic disease that causes cholesterol readings below 50 mg/dl. It is found mostly in Jewish populations.
• hypobetalipoproteinemia - a genetic disease that causes cholesterol readings below 50 mg/dl
• manganese deficiency
• Smith-Lemli-Opitz syndrome
• Marfan syndrome
• leukemias and other hematological diseases^[2]

Role in disease

With the increased use of medication to suppress cholesterol, some have expressed concern that lowering cholesterol levels excessively will itself cause disease.

Specific disease entities

Demographic studies suggest that cholesterol levels form an U-shape curve when plotted against mortality; this suggests that low cholesterol is associated with increased mortality, mainly due to depression, cancer, hemorrhagic stroke, aortic dissection and respiratory diseases.^[3] It is possible that whatever causes the low cholesterol level also causes mortality, and that the low cholesterol is simply a marker of poor health.^[1]

Links with depression have been supported by studies.^[4] In contrast, no evidence was found for a link with hemorrhagic stroke (although higher cholesterol levels conferred a relative protection), and neither did statin drugs worsen the risk.^[5]

The Heart Protection Study found no increase in either respiratory disease or neuropsychiatric illness in a large trial population taking a statin drug.^[6]

Elderly

In the elderly, low cholesterol may confer a health risk that may not be offset by the beneficial effects of cholesterol lowering.^[7] Similarly, for elderly patients admitted to hospital, low cholesterol may predict short-term mortality.^[8]

Critical illness

In the setting of critical illness, low cholesterol levels are predictive of clinical deterioration, and are correlated with altered cytokine levels.^[9]

References

1. ^ ^{a b} Criqui MH. (1994). Very Low Cholesterol and Cholesterol Lowering. Leaflet 71-0059. American Heart Association.
2. ^ Marini A, Carulli G, Azzarà A, Grassi B, Ambrogi F (1989). "Serum cholesterol and triglycerides in hematological malignancies". Acta Haematol. 81 (2): 75–9. doi:10.1159/000205530. PMID 2496554. 
3. ^ Jacobs D, Blackburn H, Higgins M, et al. (1992). "Report of the Conference on Low Blood Cholesterol: Mortality Associations". Circulation 86 (3): 1046–60. PMID 1355411. 
4. ^ Suarez EC (1 May 1999). "Relations of trait depression and anxiety to low lipid and lipoprotein concentrations in healthy young adult women". Psychosom Med 61 (3): 273–9. PMID 10367605. http://www.psychosomaticmedicine.org/cgi/content/full/61/3/273. 
5. ^ Woo D, Kissela BM, Khoury JC, et al. (2004). "Hypercholesterolemia, HMG-CoA reductase inhibitors, and risk of intracerebral hemorrhage: a case-control study". Stroke 35 (6): 1360–4. doi:10.1161/01.STR.0000127786.16612.A4. PMID 15087556. http://stroke.ahajournals.org/cgi/content/full/35/6/1360. 
6. ^ Heart Protection Study Collaborative Group (2002). "MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial". Lancet 360 (9326): 7–22. doi:10.1016/S0140-6736(02)09327-3. PMID 12114036. 
7. ^ Schatz IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD (2001). "Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study". Lancet 358 (9279): 351–5. doi:10.1016/S0140-6736(01)05553-2. PMID 11502313. 
8. ^ Onder G, Landi F, Volpato S, et al. (2003). "Serum cholesterol levels and in-hospital mortality in the elderly". Am. J. Med. 115 (4): 265–71. doi:10.1016/S0002-9343(03)00354-1. PMID 12967690. 
9. ^ Gordon BR, Parker TS, Levine DM, et al. (2001). "Relationship of hypolipidemia to cytokine concentrations and outcomes in critically ill surgical patients". Crit. Care Med. 29 (8): 1563–8. doi:10.1097/00003246-200108000-00011. PMID 11505128.