Nessun titolo diapositiva

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Early prevention a major issue in renal and
cardiovascular prevention
Carmine Zoccali, Reggio Calabria, Italy
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Happiness.....
Enjoying a long, heathy life....
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A profound change in the epidemiology of human
diseases epidemiologic transition
Infant mortality rate 276 /1000 live births
Infant mortality rate 6.7 /1000 live births
?75 years
?40 years
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epidemiologic transition
human beings phentype transition

• Hypertension
• Dyslipidemia
• Diabetes

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INTERHEART study, Yusuf co September 11,
364937, 2004 a monumental Case-Control study
90 Attributable Risk of MI
Hypertension Abdominal obesity Dyslipidemia
Diabetes Lack of consumption of fruits and
vegetables Lack of regular alcohol consumption
Lack of regular physical activity Smoking
Psychosocial factors
9 risk factors
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epidemiologic transition
human beings phentype transition
Kidney failure eventually acts as a risk
amplifier..
The emergence of chronic diseases
Ist wave
IInd wave
Chronic Kidney Disease is a growing segment in
the disease pattern of the epidemiologic
transition in developed market economies 8-10
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Sympathetic activity
Endothelial dysfunction
Insulin R
? Leptin
Intima thickening-plaque formation Atherosclerosis
Intermediate factors
? Adiponectin
IL-6 , TNF?
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Chronic Diseases Epidemics some figures
Health expenditure 618 billion
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Health expenditure ?100 billion
Health systems in developped countries are
strained by the cost of chronic diseases.
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The approach to prevention in the eighties
A fully developed global approach
Hypertension
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..tackling risk factors produces health benefits
Gain in life expectancy 35 year old man
13 months
Diastolic BP 90-94 mmHg ? 88 mmHg
6 months
Cholesterol 200-239 mg/dl ? 200 mg/dl
28 months
Quitting
with the exception of smoking, these gains
appear less than expected
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.the interventions are not properly
integrated .we start too late
More substantial gain in Life expectancy
Moderate gain in Life expectancy
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Childhood and adolescence
the life phase of joy and hope
Cardiovascular and renal prevention in childhood
and adolescence scarcely investigated
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the transition to the modern obese phenotype
extends to the youngest age groups
Age 6-11 years
Age 12-19 years
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25
Family in poverty
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Family not in poverty
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Val dAosta 14
top GDP region
Campania 36
bottom GDP region
ITALY National Health Institute National
Institute of Census and Statistics 6-13 years
The modern paradox of overweight
the poor suffers the damage of abundance
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Evidence that atherosclerosis starts early in
life and that classical and emerging risk
factors in the adult are already in action in
children and adolescents
Does risk factors modification produce
beneficial effects in children and adolescents?
The challenge of early prevention policies
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Enos WF Coronary disease among US soldiers
killed in action in Korea JAMA 1953 1521090-1093
Advanced lesions Fibrous lesions, not rare
Early lesions fatty streaks, frequent
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..interest in children and adolescents Studies
in the seventies
BP
Non invasive imaging and /or Anatomopathological
features of atherosclerosis
Body weight
LDL Cholesterol
Smoking
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Barenson GS et al., Atherosclerosis of the aorta
and coronary arteries and cardiovascular risk
factors in persons aged 6 to 30 years and studied
at necropsy. Am J Cardiol. 199270(9)851-8.
Average surface covered Aorta Fatty Streaks
Average surface covered by Fibrous
plaques Aorta Coronaries
30 20 10 0
32 Blacks 20 whites
Ante-mortem
Body weight
range
Cholesterol LDL Cholesterol
Aorta Coronaries
BP
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Fatty streaks
... 760 autopsied victims of accidents...
Low HDL
smoking
Fibrous plaques
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20
BMI
men
8
Hypertension
8
women
2
0
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Normal intima in medium-small size renal vessels
Thickened intima in medium-small size renal
vessels
There is a parallelism between heart and renal
lesions of atherosclerosis, in adolescents and
young adults
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Csernus K et al., Effect of childhood obesity and
obesity-related cardiovascular risk factors on
glomerular and tubular protein excretion.
European Journal of Pediatrics 164 44-49, 2004
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..in the nineties
..people enrolled in the seventies
BP
Body weight
LDL Cholesterol
Smoking
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725 adults 33-42 years old
men
? BMI ? Diastolic BP In both sexes
women
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Studies in the nineties
!
! damage in childhood-adolescence may be
irreversible
Almost identical results
5 centers in Finland among 2229 white adults aged
24 to 39 years Raikatari OT et al., JAMA. 2003
Nov 52902277-83
Adjusted for adult LDL Cholesterol Systolic
BP BMI Smoking Age and sex adjusted
! Early prevention
LDL Cholesterol Systolic BP BMI Smoking Age
and sex adjusted
3 to 18 years in 1980
Still significant
September 2001 and January 2002
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Endothelial function assessed both by a
hemodynamic test and by biomarkers
Normal Obese
?
Endothelial dysfunction
Intima thickening-plaque formation Atherosclerosis
Not only risk factors but also intermediate
mechanisms of atherosclerosis appear to be
fully operative in children
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Evidence that atherosclerosis starts early in
life and that classical and emerging risk
factors in the adult are already in action in
children and adolescents
Does risk factors modification produce
beneficial effects in children and adolescents?
The challenge of early prevention policies
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? The best evidence to make recommendations on
cardiovascular and renal prevention in children
and adolescents
A randomised clinical trial that follows
participants to assess development of end
points
also very large scale.. unrealistic
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Surrogate outcome measures Endothelial
Function Intima-media thickness
(carotid artery)
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low saturated fat diet is a feasible
intervention that can be maintained in the long
term in children. Low saturated fat diet
prevents early pathophysiological changes of
atherosclerosis (endothelial dysfunction)
LDL Cholesterol Boys-0.25mm/L (?5 - 8) Girls
0.03 mm/L
1990-2 (n1062) 7 months-old infants
Boys
Girls
Unrestricted diet
low saturated fat diet
2001-3 11 year old children
179
190
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10 reduction in Cholesterol at 40 year
LDL Cholesterol Boys-0.25mm/L (?5 - 8) Girls
0.03 mm/L
Incident Risk of IHD (, 5 year) 1.00 0.80
0.60 0.40 0.20 0
Life time benefits in cholesterol control may be
even greater than 50 if achieved early in life
-50
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82 obese (9-12 year old)
Diet Exercise (n41)
Diet only (n41)
6 months
Diet only (n41)
continuing Exercise (n22)
Detraining
12 months
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1.2
0.6
control
0.7
1.7
Diet and physical exercise improve endothelial
function in children but a combined intervention
is more efficacious and produces greater long
time benefits.
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Evidence that atherosclerosis starts early in
life and that classical and emerging risk
factors in the adult are already in action in
children and adolescents
Does risk factors modification produce
beneficial effects in children and adolescents?
The challenge of early prevention policies
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Ischemic Heart Disease mortality in the USA
men
women
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..we did not consider all causes of changes in
life expectancy that were due to nonmedical
interventions. The most obvious omissions were
the increased rate of obesity..
7 year
CV Death ?5 year

• Diabetes
• Hypertension
• Hypercholesterolemia
• CKD

Cutler D et al. N Engl J Med 2006355920-927
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Chronic diseases (diabetes, CV diseases and other
diseases)
WHO Chronic diseases a worldwide problem
Promoting Healthy Life styles a worldwide
priority
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Unlimited access to food has been the dream of
mankind for millennia
Choosing appropriate prevention policies is
fundamental.
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research .covering the years 1982-2003 13.158
scientific and non-scientific papers
Fundamental recommendations
147 programmes adressing prevention and
treatment of child obesity
early age adiposity (adiposity rebound) is
known to be a risk factor for later obesity
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Problems with current policies
..a (quite) limited number of interventions in
home and community settings and a lack of
upstream population-based interventions
..a tantalizing task. A goal for the new
millennium
United Millennium Development Goals
Nations
..immigrants new to developed countries, no
programmes were identified that specifically
targeted their potentially specialized needs..
(limited) stakeholders involvement in
programme design, implementation and
evaluation..
...(small efforts at) calibrating programmes
. according to population subgroups, age,
ethnicity, setting, leadership..
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S C
Establishing prevention policies targeting at
obesity and obesity related risk factors at
childhood or at adolescence is a major public
health challenge.
Stakeholders and professionals should be vocal
for focusing attention on the need of
establishing prevention policies for
cardiovascular and renal diseases in the early
years of life.
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carmine.zoccali_at_tin.it
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Stages of Life
More substantial gain in Life expectancy
Moderate gain in Life expectancy
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Overweight obesity A risk factors clustering
phenotype ..hypertension ..diabetes
1.32
2010