NEWS & EVENTS

NEWS ARCHIVE | EDUCATIONAL RESOURCES

HOMOCYSTEINE AND HEART DISEASE

Nearly one-half of the annual deaths in the United States are attributed to cardiovascular disease (CVD). The most commonly accepted "risk" factors for prediction of cardiovascular morbidity and mortality (heart attacks and strokes) include heredity, gender (male), cigarette smoking, hypertension, diabetes, obesity, lack of exercise, and abnormal blood lipid levels. One major problem is that, taken together, these risk factors will only predict about one-half of the eventual cardiovascular disorders that Americans will experience. Though heredity and gender cannot be altered as "risk" factors, the other factors can be modified, and the central effort in managing cardiovascular disease in the western world has focused on these modifications.

Much research effort over the last two to three decades has been focused upon the search for other causes or markers of CVD. Of the many that have been proposed, those potential that have withstood scrutiny include the infectious agents Chlamydia pneumoniae and Helicobacter pylori, inflammatory mediators such as C-reactive protein and interleukins-6, several hemostatic markers, and the amino acid homocysteine.

Homocysteine (Hcy) is a demethylation product of the essential amino acid methionine, a sulfur-bearing amino acid that is critical to good health in supplying methyl groups and sulfur for many metabolic processes. Hcy blood levels are associated with gender (higher in males and postmenopausal females), increasing age, nutritional intake of vitamins B 6, B 12, and folate, renal function, thyroid function, some medications, and genetic predisposition. The physical sequelae of a related genetic predisposition (homocystinuria) were a stimulus for early consideration of elevated blood levels of Hcy as a potential cause of atherosclerosis. Multiple mechanisms for the toxicity of Hcy have been proposed, but little proof is yet available. It has been shown, however, that Hcy, particularly in elevated amounts, is toxic to endothelial cells and also alters coagulation.

Epidemiologic data linking elevated Hcy levels to atherosclerosis in case-controlled studies is extensive, yet, in prospective studies, this association is weaker than would be expected. Consequently, there has been reticence by authors of large studies and health organizations to state definitively that Hcy screening and establishing desirable blood levels are appropriate. "Normal" levels of blood Hcy are currently being defined as below the 90th percentile for the population studied, or about 12 micromoles/L. There is considerable debate about what is "normal", "desirable", or "high". However, multiple large, controlled studies have demonstrated that high levels of Hcy, by whatever reasonable definition, are associated with higher risk of CVD.

It is most gratifying that, given a patient with an elevated Hcy level, therapeutic intervention with folate, Vit B6 and Vit B12 appears to be quite effective in decreasing the blood Hcy level. (Note: Vit B12 is recommended because folate alone may mask a Vit B12 deficiency, with resulting irreversible neurological sequelae). The question unanswered as yet is whether decreasing the Hcy level will, over time, alter the increased CVD risk associated with the initial elevated level. Early evidence does give room for optimism, however. For example, one recent study shows that, in matched controls, the probability of post- PTCA restenosis is lessened in patients whose blood Hcy levels have been maintained at lower levels.

Finally, it should be mentioned that blood Hcy levels have clinical associations with diabetes mellitus, Alzheimer's disease and other dementias, and hypercoagulopathies.

PRL is delighted to announce the routine availability of blood quantitation of homocysteine. Testing parameters require EDTA plasma or Lithium-heparin plasma, spun and removed from the cells as soon as possible, then frozen.

Kenneth C. Cummings, MD
Chief, Clinical Pathology
April 1, 2002