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The origin of illnesses

Six states join together in a major survey, to find out how heart diseases and diabetes develop

Eduardo Cesar Lígia Fedeli, head of a testing team: blood and urine samples conserved in liquid nitrogen Eduardo Cesar

Every day, since August of last year, a team of almost 100 specialists attends to 15 to 20 healthy people that turn up voluntarily at the Universitário Hospital of the University of São Paulo (HU-USP) and undergo a series of tests during the course of four hours. This pace of work is to be maintained until March of next year, by which time this team hopes to have completed the five thousand tests of the São Paulo quota of one of the largest epidemiological surveys ever carried out in Brazil, focusing on cardiovascular diseases and diabetes. Nicknamed Elsa, for Estudo Longitudinal da Saúde do Adulto (Longitudinal Study of Adults Health), the survey involves another five teams, in the states of Rio de Janeiro, Minas Gerais, Bahia, Rio Grande do Sul and Espírito Santo, all of which have smaller quotas than São Paulo, although they are just as advanced in terms of having examined their quota of 1 to 2 thousand people.

The Elsa team intends to evaluate and monitor the health of a total of 15 thousand men and women aged 35 to 74 during the course of 20 years. The participants are interviewed about their general health and are then submitted to 35 clinical and laboratory tests. In line with the plan, during the following year they will be contacted to say whether or not they were hospitalized or had any surgery, and every three years they will repeat the same blood, urine and cardiac function tests. We don’t just want to find out who suffers from heart diseases at a specific point in time, but how and why these diseases appear, what is the true weight of the risk factors and how food interferes in terms of providing protection or making matters worse,” says Paulo Lotufo, a professor at the USP Medical School and the Elsa coordinator for São Paulo.

Elsa is a longitudinal study, a laborious type of study because it implies tracking a large group of individuals for many years. Most the epidemiological surveys in Brazil are transversal: they are like a snapshot, albeit a broad one sometimes, of a health problem at a given point in time, without drawing comparisons over time. This is why the project coordinators agreed, as from some of their first meetings, that the people to be examined and monitored should be employees of the institutions in charge of the research. If on the one hand we sacrificed the study’s representativeness, on the other hand we ensured continuity, since civil servants are stable,” says Lotufo. Isabela Benseñor, a professor at the USP Medical School and vice-coordinator of Elsa in São Paulo, adds: “In 20 years, somebody will call the participants” home and they will probably still live there. If they don’t, it won’t be difficult to find out where they’re living. Sometimes, in some epidemiological studies, the houses themselves, and not only their inhabitants, disappear.

By September 21, 300 researchers and assistants, all working in the same way so that the results can be compared at a later date, had seen to 6,680 people, carrying out tests and collecting information about their general state of health. In the next few years, as test results are gathered and analyzed, this study may show what spurs or holds back many chronic illnesses, especially the cardiovascular kind and diabetes, and suggest the types of prevention that suit the country best. Another objective is to find out if the numerical values used to determine if someone really has high blood pressure or is at risk for a heart attack are really appropriate for Brazil’s population, as the possibility that they might not be does exist.

The disease prevention protocols are based on studies conducted in countries with different eating and social relations habits, says Maria del Carmen Bisi Molina, a professor at the Federal University of Espírito Santo (Ufes) and vice-coordinator of the study in that state. We reproduce values based on populations that are different from ours, because we lack indicators that reflect our own situation, adds Sandhi Maria Barreto, a professor at the Medical School of the Federal University of Minas Gerais (UFMG) and state coordinator for Elsa.

Eduardo Cesar Elsa, at present, is a production line of exams being run in six states Eduardo Cesar

The weight of the diet
There is also reason to believe that cardiovascular diseases evolve in Brazil differently from other countries. An Ufes team compared the infarction mortality rates in Brazil and in other countries and concluded that Brazilians die four to five years earlier than Americans or Europeans. Either the risk factors, such as smoking and hypertension, kick in earlier, or when they do, they are more aggressive, ponders José Geraldo Mill, an Ufes professor and coordinator of the study in Espírito Santo. The weight of the so-called effect modifiers, such as diet and social relations, which can magnify or attenuate the risk factors pertaining to heart attacks or strokes, is still little known in Brazil. “Does high cholesterol have the same effect here as in other countries” Only a long-term project can answer, says Mill.

This month a team of interviewers is going out into the field to ask 300 participants in the study (50 from each of the 6 states) what they ate and drank on a specific day. They will repeat these questions in March and August of next year, in order to assess the consumption of calories and of nutrients. “We hope to gain a better understanding of how illnesses appear or of how health is maintained by analyzing eating habits,” says Maria Molina, who is responsible for the eating habits survey.

There are already indications that food throughout Brazil is not of the healthiest sort – and it is fostering the rise of heart disease and diabetes. In 1999 and 2000, as part of an international survey on cardiovascular diseases, the Espirito Santo team analyzed the habits and the health of 1,661 inhabitants from the city of Vitoria, aged 25 to 64. Excess weight afflicted 52% of them and their salt consumption was twice the recommended level. Inhabitants of other states may also be gaining weight or slowly advancing toward a heart attack. Excess weight or obesity in Brazil’s population rose from 16% to 41% among men and from 29% to 40% among women in the last 30 years, according to an Elsa summary published in Revista de Saúde Pública [Public Health Journal]. Cardiovascular diseases are the main cause of death, accounting for 32% of the total in 2003, and of hospital stays, accounting for 22% of the total of R$6 billion spent on hospitalization in Brazil in 2005.

We’re collecting data for future generations of researchers and awakening the interviewers scientific research vocation, says Dora Chor, a professor at ENSP, the National School of Public Health at the Oswaldo Cruz Foundation and the study’s coordinator in Rio de Janeiro. More consistent information on how illnesses appear and what could be done to keep them in check should start to emerge in three years time, but other gains are immediate. One of them was born out of the need to manage a lot of tests continuously: after a preliminary test with 94 people, the team from Espirito Santo showed that a 12-hour collection of urine will do, rather than the habitual 24-hour collection, thus simplifying the life of those who have to turn up on the following day on an empty stomach for other tests. When it comes to assessing kidney function, the filtration rate and the excretion of sodium and creatinine, the 12-hour test yields virtually the same results as the 24 hour one, says Mill. Now we want nephrologists to see this, issue an opinion, try to repeat the results and adopt this system or not. The Elsa team manual, which explains how to organize this type of project, how to train and maintain the teams and how to conduct the tests can also be shared with other groups.

No delays
The group’s discussions took the form of a work plan, approved in 2005 by the Ministries of Health and of Science and Technology, which released R$22 million for this study. We formed a syndicate of people and institutions, with a steering committee that encompasses all the participants, who make the decisions jointly, Isabela tells us. Now, what is just as important as the production of quality information, so that, for instance, the data collected in Porto Alegre can be compared to the data from Salvador, is the ability to keep up the pace of the work: until it starts generating epidemiological information, Elsa is a rigorous ongoing production line of tests and information.

Eduardo Cesar Elsa, at present, is a production line of exams being run in six states Eduardo Cesar

I can’t allow tests to pile up, says Lígia Fedeli, head of the blood and urine tests team. All the material of the day must be identified and organized by 7:00 p.m. of the same day. Lígia and her 10 assistants distribute the blood of each of the 15 to 20 people that they see daily into seven flexible plastic specimen tubes, each of which gets a bar code label.

The logistics are impressive. Once a month, Lígia receives 1,000 tests carried out in other states, produces 20 thousand flexible plastic specimen tubes and dispatches all this to liquid nitrogen tanks. Once a month the tubes are defrosted and the blood examined at the USP hospital laboratories. This material may also come to show who had mental illnesses such as dementia or Alzheimer’s disease, as well as why and how, since part of the questionnaires aims to evaluate eventual memory loss. The Universitario Hospital also stores the urine samples, which get the same care and go through the same procedures, and the ultrasound exams of the diameter of the carotid artery and of the liver artery, used to assess heart problems. In turn, the Minas Gerais team gets 55 electrocardiograms produced on that same day at the five other centers, while the Porto Alegre team gets an equal number of retina exams that help one identify eye lesions from diabetes.

If we had to stop the work today, this would already be the epidemiological survey with the largest number of adult participants ever carried out in Brazil, says Lotufo. A study on psychiatric conditions in the São Paulo Metropolitan Area reached 5,037 interviews conducted by 2007. A survey more similar to Elsa consisted in evaluating 15 thousand children born in 1982, 1993 and 2005 in the city of Pelotas, in the state of Rio Grande do Sul.

Major undertakings such as this one usually yield more than planned. One of the pioneering heart disease surveys, conducted in 1948 with 5,209 men and women from Framingham, a town near the city of Boston, in the United States, revealed what now seems obvious: the association between smoking, which until then had only been linked to lung cancer, with a higher risk of having a heart attacks. This relation became evident after tracking the health of the study’s participants for a few years. “It was a surprise, but at that time films often showed smoking as something that reduced stress, which, therefore, should have benefited the heart,” says Mill.

However, the conclusions of such studies are not always transformed into public policies promptly. We have known for a long time that soda pop and fried snack foods are not good for children, but only now has national law been enacted prohibiting them from being sold in schools, comments Maria Molina. So far, progress has been gradual and continuous. Something that is difficult, but that we are achieving, says Lotufo, is to persuade others that a university hospital should engage in original and relevant research, with dedicated space and dedicated teams, as opposed to merely extracting information from patients medical records.