Homocysteine, HIV, and Heart Disease.

[Note: Abnormally high levels of homocysteine in the blood are associated with increased risk of heart disease, and a number of other diseases as well. These high levels can be detected by a blood test, and are often caused by dietary deficiencies that can be corrected.

[Reducing disease risk by controlling homocysteine level is today considered experimental; for example, it is not part of the new NCEP (National Cholesterol Education Program) guidelines published May 16, 2001, probably because much of the data is just emerging and is sometimes contradictory. But because excessive homocysteine is strongly suspected to be unhealthy in many ways, because it can be easily controlled in many cases, and because vitamin B12 deficiency (which can cause excess homocysteine) is already an important risk for persons with HIV, we believe there should be more attention to this potential medical strategy.

[Therefore we asked Jennifer Cohn, a medical student in Philadelphia, to look into the literature on homocysteine and cardiovascular risk and prepare a brief report, to help raise awareness in the HIV community. JSJ]

Homocysteine is a non-essential amino acid; high levels have been associated with cardiovascular disease. Excessive homocysteine levels can be caused by a deficiency of folate and/or vitamin B12. Deficiencies of folate can arise because a person is not eating enough fruits and leafy green vegetables. Vitamin B12 deficiency can occur in vegetarians (since this vitamin is not found in plant sources), but deficiencies are more commonly caused by poor absorption, which can result from HIV disease, aging, and other causes.

Excess homocysteine may have varying effects on an individual's health. For example, increased levels of homocysteine have been associated with both increased risk of Alzheimer's and cardiovascular disease. [1,2] Furthermore, some preliminary studies have demonstrated that a certain form of homocysteine, called "reduced homocysteine," may increase HIV viral replication. [3] However, the literature on homocysteine levels and viral replication is inconsistent [3,4] -- so this article will focus on one of the better documented effects of homocysteine: its effect on the cardiovascular system.

Many studies of non-HIV infected individuals have shown elevated serum homocysteine levels to be a risk factor for vascular disease. In particular, a review article by Boushey et al. (1995) highlighted homocysteine as a causal factor for arteriosclerotic vascular disease. [1] Individuals with a high level of serum homocysteine had 2.5 times the risk of developing vascular disease as those with a normal level; this makes serum homocysteine levels a stronger risk factor for vascular disease than serum cholesterol. In another study, Stubbs et al. (2000) demonstrated that for patients being admitted for acute cardiac events, serum homocysteine levels were an excellent predictor of later cardiac events such as another heart attack or death from a heart attack. [5]

The mechanism by which homocysteine acts is still unclear. However, research suggests that it affects the lining of blood vessels. [6] Increased serum homocysteine levels may damage this lining or make it hard for blood vessels to relax, making it easier for arteriosclerotic plaques to develop. Homocysteine may also change factors in blood itself so that the blood becomes more prone to clot. [1,6]

How does homocysteine affect people with HIV? Unfortunately, at the present time few studies are investigating this question. However, it is probably a reasonable assumption that homocysteine increases the risk of vascular disease in people with HIV in the same way as it does in people without HIV -- but if persons have already developed other risk factors for cardiovascular disease, high homocysteine levels may be even riskier for them. And persons with HIV may have a more difficult time absorbing Vitamin B12, leading to an increase in serum homocysteine. [7]

Some drugs may also increase homocysteine levels. Examples of such drugs include nicotinic acid (niacin), theophylline (used for asthma. emphysema and bronchitis), methotrexate and L-Dopa. [8]

The most important and easiest treatment is taking dietary supplements of Vitamin B12, Vitamin B6, folic acid and TMG (betadine), in addition to eating a balanced diet including fruits and green leafy vegetables. [1,7] While there are suggested daily amounts of supplements, the only reliable way to know if a patient is taking the right amounts to control a high serum homocysteine level is by having a blood test for homocysteine.

References

(1.) Boushey CJ, Beresford SA, Omenn GS, and others. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: Probable benefits of increasing folic acid intakes. JAMA. October 4, 1995; volume 274, number 13, pages 1049-57.

(2.) Muller F, Svardal AM, Aukrust P, and others. Elevated plasma concentration of reduced homocysteine in patients with human immunodeficiency virus infection. American Journal of Clinical Nutrition. February 1996; volume 63, number 2, pages 242-8.

(3.) Simon G, Moog C and Obert G. Effects of glutathione precursors on human immunodeficiency virus replication. Chemical Biological Interactions. June 1994; volume 91, numbers 2-3, pages 217-24.

(4.) Balzarini J, De Clercq E, Serafinowski P, and others. Synthesis and antiviral activity of some new S-adenosyl-L-homocysteine derivatives. Journal of Medical Chemistry. November 27, 1992; volume 35, number 24, pages 4576-83.

(5.) Stubbs PJ, Al-Obaidi MK, Conroy RM and others. Effect of plasma homocysteine concentration on early and late events in patients with acute coronary syndromes. Circulation. August 8, 2000; volume 102, number 6, pages 605-10.

(6.) AI-Obaidi MK, Philippou H, Stubbs PJ, and others. Relationships between homocysteine, factor VIIa, and thrombin generation in acute coronary syndromes. Circulation. February 1, 2000; volume 101, number 4, pages 372-7.

(7.) Remacha AF, Riera A, Cadafalch J and others. Vitamin B-12 abnormalities in HIV-infected patients. European Journal of Haematology. July 1991; volume 47, number 1, pages 60-4.

(8.) Cardiovascular Consultants Medical Group: Homocysteine and the Heart, July 30, 2001, http://www.cardiacconsultants.com/homocysteine.htm.