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"Homocysteine The New Vascular Villain" by Charles I. Okorie, MD

Heart attack also called acute myocardial infarction(MI) is a clinical condition resulting from blockage of the blood vessels (coronary arteries) that supply oxygen rich blood to the body pump(heart muscle). This blockage leads to death of the heart muscle cells which manifests as a heart attack.

The most common presentation of this condition is chest pain. In some patients, this chest pain may mimick indigestion. Other manifestations of this syndrome include but are not limited to difficulty breathing, fainting spells, profuse sweating, dizziness, and nausea. It is estimated that about 1.5 million people get heart attacks every year in the US. To drive this point home that translates to one heart attack every 20 seconds. Of this number about a third or more will die from their first heart attack. Another chilling statistic. Interpreted in another way, it behoves us all - patients and healthcare providers alike to continue to find ways to prevent heart attacks. The purpose of this article is therefore to alert us to a lesser known risk factor for heart attacks - high levels of an amino acid, homocysteine (pronounced home-o-sis-teen).

In the past few years, considerable advances have been made in our understanding of the processes leading to the blockage of blood vessels that supply blood to the heart. Risk factors that put individuals at increased risk for heart attacks include: family history of heart attacks, hypertension, diabetes, smoking, elevated cholesterol levels, male sex and post-menopausal women. The final common pathway for all these factors appears to be damage to the inner lining of the blood vessels. Such damage triggers complex mechanisms that ultimately result in blood clots that occlude the arteries supplying blood to the heart muscle which can result in heart attack. Until recently the focus on this inner lining damage had been placed entirely on the interplay of high cholesterol levels in the blood and the blood vessels. However, numerous instances exist where this inner lining damage still occurs despite near to normal cholesterol levels in some patients. We are now beginning to appreciate that cholesterol may not always be the 'bad cop' in all cases. Within the past decade, an explosion of studies and an avalanche of new findings have begun to emerge proving that a substance in our blood, homocysteine, when in abnormal high amount is an independent risk factor for heart attacks and other blood clotting disorders. Homocysteine when present in high concentration in the blood appears to damage the inner lining of blood vessels and thus promote clotting that leads to blockage. In fact, some studies are suggesting that above normal levels of homocysteine have been noted in about 25% of patients with heart attacks and 40% of patients with stroke (brain attacks).

What is Homocysteine?
Homocysteine is an amino acid. Amino acids are the building blocks of proteins. When we eat food rich in protein, the body breaks it down into these building blocks in our stomach so that absorption can take place in the intestine. One of the amino acids we absorb through this process is methionine. After absorption, some of the methionine gets converted in the liver to homocysteine. When the body needs the methionine again, it can be regenerated through chemical conversion (remethylation) of homocysteine back to methionine through complex chemical reactions. These chemical reactions lower the levels of homocysteine in our blood and require adequate supplies of vitamins B12 and folic acid. Another way the body can lower the homocysteine level in our blood is by breaking it down to another substance, cysteine, which is further degraded into products excreted in the urine. The chemical breakdown of homocysteine to cysteine requires a vitamin called vitamin B6(pyridoxine).

Causes of high homocysteine levels:

  • Absence or low levels of enzymes (body chemicals) needed to convert homocysteine to methionine.
  • Absence or low levels of enzymes needed to breakdown homocysteine to excretable products of cysteine.
  • Acquired conditions leading to high levels of homocysteine such as chronic kidney failure, leukemia, Psoriasis, diabetes and post-transplant patients.
  • Reduced levels of vitamins B12, B6 and folic acid - the cofactors needed in metabolism of homocysteine.
  • Drugs like methotrexate, dilantin, tegretol, theodur and Isoniazid(INH) which can induce high homocysteine levels through their negative effects on vitamins:B12, B6 and folic acid (pre-requisites in the disposition of homocysteine).

Dangers of high homocysteine levels
The dangers of high blood levels of homocysteine first came to light following the observation that persons with homocystinuria (a rare genetic disorder) characterized by high levels of homocysteine were showing various forms of occlusive diseases of the blood vessels, ranging from heart attacks (due to blood clots of arteries of the heart), stroke (due to blood clots of arteries of the brain) and pulmonary embolism (due to blood clots of arteries of the lung).

Following this observation, a growing body of population studies both within and outside the US continue to show that low levels of folic acid and vitamin B6(cofactors required to lower blood levels of homocysteine) are associated with heart attacks. Lower levels of these vitamins are associated with higher homocysteine levels which have the potential to promote and induce damage to inner linings of blood vessels, ultimately leading to clot formation and heart attacks.

Homocysteine - 'The new vascular villain' - How do we fight it?
'Chance Favors Only the Prepared Mind' by Louis Pasteur.

One of the most important goals of our urgent care center is to keep our patients well informed on various health conditions. We hope you are now aware of another risk factor for heart attacks and other clotting disorders. If you are, our message has been heard. The next logical step is to review your personal risk factors for heart attacks with your doctor, starting of course with the most common: smoking (this one is really big), diabetes even when borderline, hypertension, high LDL cholesterol( the bad cholesterol) and low HDL cholesterol(the good cholesterol). Once you have ruled all these out, it may be necessary to consider blood homocysteine level - an established risk factor for heart attacks particularly if there is an unexplained personal history of heart attacks or other clotting disorders. Unexplained family history of heart attacks, strokes(brain attacks), sudden deaths or blood clots in lungs and extremities should also warrant evaluation for abnormal homocysteine levels. The consideration should be much greater if these conditions are occuring at a young age (less than 50 years of age) with no other identifiable risk factors.

Conclusion
In the years to come, the benefits of homocysteine approach on health and longevity will be more evident. Already some authorities are attributing the declines in the risk of stroke and heart attacks since 1960s to increased vitamin B6 in the nation's food supply. Recent studies have suggested that the addition of folic acid to the food supply have the potential to save at least 50,000 American lives from heart disease alone. Rich sources of vitamins B6, B12 and folic acid - the cofactors needed to lower levels of homocysteine in our blood include:green leafy vegetables, beans and fruits. We feel that making these food items part of your daily meal could be of immense benefit in the prevention of heart attacks and other clotting disorders considering their unique roles in lowering the levels of homocysteine (the new vascular villain) in our blood.

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