public health

Homocysteine, a heart alert

A high level of homocystiene raises the risk of an unstable angina

The link between an excess of homocysteine in the circulation of the blood and heart problems is not news. This amino acid, which forms itself in the organism due to the ingestion of proteins, is the theme of many articles and controversies throughout the international scientific world, but up until now there has been no research done on the blood levels in the Brazilian population.

The Project The Determination of the Levels of Plasmatic Homocysteine in the Population of São Paulo – the Homocysteine as a Risk Factor for Cardiovascular Illnesses will fill this gap: it proves that high levels of homocysteine increase by at least 42% the risk of unstable angina, a cardiac problem which can repeat itself various times.

Diet and vitamins
The good news is that, once identified the excess of homocysteine in the blood, this level can be brought down by way of a controlled diet or, if necessary, of vitamin supplements prescribed through a doctor. At the moment, the examination for homocysteine is carried out by few Brazilian laboratories. The biologist Vania D’Almeida, responsible for the project, alerts that it is not recommended to take the examination without it first being suggested by a doctor, and, much less, to take the vitamin supplements since other illnesses could increase the level of homocysteine and automedication could hide the symptoms.

As well as this, though the Brazilian studies as yet do not point to a high level of homcysteine as a power force of other risk factors, it is fitting to remember that cigarettes, hypertension and high levels of cholesterol and of triglycerines greatly increase the possibilities of vascular illnesses. Vania works at the Center of Genetic Medicine of the Departments of Pediatrics and Morphology of the Federal University of São Paulo (Unifesp), where she coordinates the Laboratory of Innate Errors of Metabolism. The origin of the project was the confirmation, by the coordinator of the Multidisciplinary Clinic of Hereditary Metabolic Illnesses, doctor Ana Maria Martins, that a large number of the children who attended the clinic suffered from homocystinuria (excess of homocysteine).

Homocystinuria is an illness in which a enzymic deficiency impedes the correct metabolism of amino acid, which consequently accumulates in the organism. Over time, the child could develop sight problems, mental retardedness and even suffer vascular accidents. Vania added: “They are highly subject to thrombus embolism of a general form, and we found in the referential scientific literature deaths, sometimes at between 8 and 10 years of age, due to the a cardiovascular situation similar to that of the elderly. “Intrigued by these precocious problems, an American researcher began to investigate the possibility of homocysteine being responsible for cardiovascular problems in general.

“He studied patients with cardiovascular illnesses such as the clogging of myocardium and angina in patients 35 years of age and older, and measured the level of homocysteine in their blood. From that point onwards, the correlation between the high level of homocysteine and cardiovascular illnesses was in a certain way established.” said the biologist.

Vania said that her motivation was, as well as the large number of patients, the lack of data about the Brazilian population. Homocysteine is closely linked to diet. Statistics show that Japan is the country with the lowest indices of deaths from heart disease, whilst the United States has one of the highest indices. “A question became important: could it be that the Brazilian patients with cardiovascular illnesses also have an alteration in their levels of homocysteine? In the future, to work with those who have cardiovascular illnesses, it will be necessary to answer this question.” she explained. The results of the research came from the analysis of blood samples of 115 patients with cardiovascular illnesses and from 129 healthy people, who were used as a control group.

The samples were taken at the Cardiology UTI of the São Paulo Hospital of Unifesp, and from patients of the Oswaldo Cruz Hospital of Recife (PE). The healthy volunteers were people who were attended at the clinics or employees of the institutions. The research, done with the help of students, researchers and professors of Unifesp and of the Federal University of Pernambuco (UFPE), confirmed a risk 4.9 times higher of an increase of homocysteine in the patients with a cardiovascular illness than with the control group.

The highest values were found in the age group between 31 and 40 years. When the healthy individuals only were considered, the lowest level was the children between 8 and 12 years of age, and the highest, those of the age group above 60 years. Both in the patients and in the control group, males showed indices higher than females.

High risk
Another confirmation was that of the higher probability of people with a certain mutation in the gene of the enzyme MTHFR (methylene tetra-hydropholate redutase) who had increased levels of homocysteine. The mutation is known as C677T: it occurs on the nucleotide 677 of this gene by way of the substitution of a cytosine (C) for a thymine (T). As the chromosomes exist in pairs (except the sexual chromosomes), certain people could have this mutation on both the genes of a pair of chromosomes. Consequently, people who are TT are more susceptible to an increase in homocysteine.

It was also concluded that the risk of unstable angina was increased in at least 42% when the level of homocysteine went above the value considered normal world-wide, according to many international references: 15 micromoles per liter. A diet rich in vitamin B6, B12 and folic acid, helps to reduce the level of homocysteine. A slice of liver is an excellent source of these nutrients. Banana and beans are also sources of vitamin B6 and folic acid, whilst cow’s milk provides vitamin B12.

These vitamins are necessary for the correct working of the metabolic process of methionine, an essential amino acid, present principally in proteins of animal origin which we swallow. The organism need to take from methionine the methyl group, important in various functions such as the synthesis of DNA, transcription and the formation of proteins, and for this it transforms methionine into homocysteine which in high levels becomes a toxic product which has to be eliminated.

The elimination has the help of vitamin B6 which participates in the transformation of part of the homocysteine into cystationine (an intermediary compound between homocysteine and cysteine). When the cysteine is formed, part of it goes to make up peptides (such as glutathione, an important antioxidant) and proteins and part of their derivatives and excreted in urine.

Everything would be resolved satisfactorily if it wasn’t for the fact that part of the homocysteine transforms itself into homcysteine thiolactone, an intermediary more reactive than homocysteine itself and which reacts above all with lipoprotein of low density, LDL, known as the evil cholesterol. This reaction forms chemical groupings which obstruct the blood vessels and provoke arteriosclerosis.

However, it is possible to have a happy ending: part of homocysteine thiolactone can return to the form of homocysteine and this, with the help of folic acid and vitamin B12, can add in methyl again and go back to be methionine – a process called remethylation. As we are accustomed to swallowing less methionine than our organism needs, the remethylation is a very useful metabolic pathway. Nevertheless, the work of the biologist from Unifesp serves as an important general alert and a worthwhile contribution towards the prevention of cardiovascular illnesses in Brazil and in the world.

The project
The Determination of the Levels of Plasmatic Homocysteine in the Population of São Paulo – Homocysteien as a Risk Factor for Cardiovascular Illnesses (nº 98/12887-8); Modality Regular Research Awards; Coordinator Vania D’Almeida – Center of Medical Genetics of the Pediatric Department of Unifesp; Investment R$ 21,795.00 and US$ 63,430.00