Transcript Primordial Prevention – A Perspective from the Bogalusa Heart Study

Primordial Prevention – A Perspective
from the Bogalusa Heart
Study
G. Berenson MD, for the Bogalusa
Heart Study Group.
Tulane Center for Cardiovascular
Health
Primordial Prevention
• There is about to be a revolution in cardiovascular
health care, better an evolution to one with emphasis
on prevention in early life. Until now, emphasis has
been on secondary prevention of patients with known
CV disease, coronary artery disease and hypertensive
cardiac and renal disease. Yet, primary prevention of
individuals prior to a clinical presentation of cardiac
events has long been of interest with the landmark VA
hypertension study (1) by Fries and the Multicenter
Coronary Drug Project (2).
Secondary prevention
• The emphasis on secondary prevention has been
sparked by advances from the pharmaceutical industry,
particularly with the development of statin drugs, as an
outgrowth of the Nobel Prize to Goldstein and Brown.
Equally so, are tremendous advances with the
development of antihypertensive agents. But, it is only
recent that I have heard the concept of Primordial
Prevention being advocated. This entails the prevention
of the occurrence of CV risk factors, as pioneered by the
Framingham study. William Kannel came up with the
term in the early years of Framingham, and they have
stuck.
Concept of Primordial Prevention
• The Concept was suggested by Tom Strasser from the
World Health Organization (3) , in terms of prevention
strategy. This is a logical approach, since Geoffrey
Rose raised the issue of risk in terms of “sick
individuals vs sick populations” (4) . I participated in
two WHO and two American Health Foundation
symposia , the latter held by Ernst Wynder, and all
indicated the need to address risk factors in early life
(5). For me, it was these meetings that gelled the
concept of primordial prevention, enunciated by
Strasser.
History of Primordial Prevention
• The consideration of primordial prevention is the essence
of population studies at the level of children , that now go
back almost 40 years. The Muscatine study was begun by
Bill Connor who originally suggested to me to “Pick a
Community”, rather than a hospital- based population,
after our original grant application, based on a population
of children enrolled in a psychology study at the Big
Charity Hospital in New Orleans, was turned down by
NHLBI as an award for a Specialized Centers of Research –
Arteriosclerosis (SCORA). This rejection was a lucky break.
To begin studies on children did not seem out of the
ordinary even 40 years ago.
History of Primordial Prevention (2)
• Our Department of Pathology, headed by Russell
Holman and his crew Henry McGill, Jack Strong, Bill
Newman and Richard Tracy, pointed out the
occurrence of atherosclerotic lesions in early life ,
even in infants as young as three years of age (6).
Holman´s disciples later helped form the
multicenter, superb Pathologic Determinants of
Atherosclerosis in Youth (PDAY), with Bob Wissler
from the University of Chicago (7).
Background to begin studies in children
• Autopsy studies of soldiers in the Korean War and later
in the Vietnamese war showing such a high prevalence
of coronary atherosclerosis set the stage to encourage
Congress to fund NHLBI to promote SCOR´s in four
areas: arteriosclerosis, hypertension, pulmonary and
blood diseases. We finally got one for arteriosclerosis
focusing on the community of Bogalusa.
• These observations in Pathology, the much earlier
emphasis on cholesterol in arterial wall plaques by
Anitskow, the analytical ultracentrifuge studies by
Gofman(8) and electrophoretic studies of lipoproteins
in terms of atherosclerosis by Frederickson(9),
provided the background to begin studies in children.
Our previous studies
• Our own studies of acid mucopolysaccharides
(glycosaminoglycans) and proteoglycans of the arterial wall
even studied aortas from 12‐20 year olds in an attempt to
separate the process of early atherosclerosis from the
changes in older individuals. We even provided some
insight into the factors producing atherosclerosis (10). In
our laboratory SR Srinivasan, studying acid
mucopolysaccharides complexing with serum lipoproteins,
led us to the development of a method to quantitate the
serum lipoproteins in small amounts of serum. This method
by Srinivasan gave us the opportunity to do studies of risk
factors. We began by advocating their study in medical
students, our precious commodity in an academic
environment (11). The jump to children and Bogalusa
began when support for a SCOR‐A was funded.
Bogalusa Heart Study
• The beginning of the Bogalusa Heart Study was
mentored by CA McMahon who insisted on us writing
and adhering to protocols. This became very obvious
with the need for long term and secular trend studies,
that were to come. He also emphasized quality controls
by blind duplicates of blood samples that tested the
total process of collection through data analysis, training
the team as a whole, not a nurse or observer
individually, in order not to compress the data. He
stressed not to “contaminate the population or data” by
preliminary studies. Obviously, the usual randomization
and duplication procedures were followed .
CA McMahon’ Role
• His mission, as he stated, was to see we “collect reliable
data”. His insistence on these principles and telling us
we did not know how to measure blood pressure and
having us work and train one year in Franklinton, 20
miles from Bogalusa, made a difference in our study.
Such diligence got us in “trouble”. Our first set of blood
pressure data was 15 mmHg lower than that of the first
Pediatric Task Force. We promoted 4th phase diastolic
pressure until adult stature is reached and we noted a
linear relation of blood pressure to height. Such
observations are still neglected even though four
Pediatric task force reports have occurred. Similarly,
with the availability of publications on the Internet in
the mid 1980´s , other findings related to risk factors in
children are ignored.
The aim of the Bogalusa Heart Study
was to study and determine risk
factors as defined in adults and apply
to children.
We came up with four questions:
• What are the risk factors in children and how
to define abnormal ones?
• What is the interrelation of risk factors?
• Do risk factors persist over time and predict
adult levels?
• And what are the genetic and metabolic
characteristics of young individuals with high
or low levels? (12,13)
Basis for primordial prevention
• Basically, after we screened over 4000 children,
spanning an age of birth to 17 years, our goal was
really to understand the early onset (a natural
history) of atherosclerosis, hypertension and even
target organ changes, and type II diabetes mellitus.
Our publications now attest to the fact that all of
these adult diseases begin in childhood and can be
diagnosed in childhood, at least with some
limitations, long before CV –renal events occur in
adulthood. Herein lies the basis for primordial
prevention.
Fundings
• There are several observation most germane to the
Bogalusa Heart Study. The autopsy studies were
probably the most critical and these set the later stage
for the more elegant PDAY studies. Blacks have higher
blood pressure, more progressive CV disease,
myocardial, vascular and renal; white women have a lag
in developing coronary disease; a greater development
of coronary artery disease occurs in younger white men;
and there are a host of hemodynamic, metabolic, and
fluid and electrolyte racial and gender contrasts. Most
important what occurs in childhood is predictive of
findings in adulthood.
Conclusion
• Primordial prevention will have to recognize the
fundamental observations from pediatric population
studies, namely Bogalusa, Muscatine, Finland and others.
Twenty years ago we were funded to develop and
demonstrate prevention based on the findings from
Bogalusa. The most successful has been the development
of a comprehensive health education program (K‐6 Health
Ahead/Heart Smart) that addresses the entire school
environment. Strongly behavioral oriented, it successfully
achieves a control of obesity, improves healthy life styles,
and promotes healthy decision making, beginning at least
by Kindergarten. It addresses both risk factors and
equally, social problems.
Conclusion (2)
• The program also provides attention to role models,
teachers, and parents (14). Many splintered trials
and programs are now beginning to address health
and prevention in children, but most are single
focused, like obesity, or exercise, or smoking. These
need to change in order to address the total health
of children and incorporating education and learning
to deal with the toxic environment in which we live.
To us, early and broad health education and health
promotion are the beginning of primordial
prevention.
References
• 1. Veterans Administration Cooperative Study on
Antihypertensive agents (1970): Effects Of treatment on
morbility in hypertension II. Results in patients with
diastolic blood pressure 90 through 114 mmHg. JAMA,
213:1143‐1152
• 2. Canner PL, Berge KG, Wenger NK et al (1986). Fifteen
year mortality in Coronary Drug Project patients:
long‐term benefit with niacin. JACC; 8: 1245‐55.
• 3. WHO Expert Committee (1990). Prevention in
childhood and youth of adult cardiovascular diseases:
Time for action. Geneva, Switzerland WHO: Tech Report
Series 792
References (2)
• 8. Gofman, J.W., Lindgren, R.T., Elliot, H.A., Mantz, W.,
and Hewitt, B. (1950): The role of lipids and
lipoproteins in atherosclerosis . Science, 111:166‐171
• 9. Frederickson, D.S., Levy, R.I., and Lees, R.S. (1967):
Fat transport in lipoproteins: An integrated approach
to mechanism and disorders. N. Engl. J. Med, 276:
148‐156
• 10. Berenson GS, Radhakrishnamurthy B, Srinivasan
SR, Vijayagopal P, Dalferes ER Jr (1988): Arterial wall
injury and preteoglycan changes in atherosclerosis.
Arch Pathol Lab Med 112:: 1002‐1010