This document discusses the relationship between blood pressure and metabolic syndrome. It makes three key points: 1. Several factors contribute to hypertension in metabolic syndrome, including obesity, insulin resistance, dyslipidemia, and sympathetic nervous system activation. High insulin levels and an upregulated renin-angiotensin system in adipose tissue may also play a role. 2. Insulin resistance is associated with an 11% lower risk of developing hypertension for each unit increase in insulin sensitivity. Insulin resistance can increase blood pressure through effects on vascular smooth muscle contraction, sodium reabsorption, and activation of the renin-angiotensin system. 3. Insulin resistance and hyperinsulinemia may

1. Metabolic Syndrome 2
Dr. Yousef Elshrek

2. • Recent evidence has shown that adults
with
metabolic
syndrome
have
significantly higher systolic blood pressure
(SBP) than normal during childhood.
• However, it has not been welldocumented the extent to which systolic
blood
pressure
predicts
metabolic
syndrome in male adolescents.
• Early treatment of metabolic syndrome
components decreases morbidity and
mortality.

3. • The obesity epidemic has spread in
children around the world and may
lead to an increased incidence of
metabolic syndrome.
• Furthermore, some evidence suggests
that this metabolic derangement
persists into adulthood.
• Therefore, identification of children at
risk of developing metabolic syndrome
later in life can be critical in the overall
effort to reduce mortality.

4. • Blood pressure measurements tend to be
omitted in routine assessments of children.
• When it is measured, the variation of
normal BP with age can lead to missing
the diagnosis of hypertension.
• Normal ranges are :
1.
2.
3.
Prehypertensive = 90th centile to 120 mmHg
Stage 1 hypertension = 95 th centile upwards
Stage 2 hypertension = 99 th centile + 5 mmHg

5. Any reading equal to or above the readings in the simplified table indicates
potentially abnormal blood pressures in one of three ranges: prehypertension;
stage 1 hypertension; or stage 2 hypertension and identifies blood pressures that
requires additional evaluation

6. • Childhood obesity, can be
identified by high triglyceride
(TG) levels, hyperinsulinemia,
high C-reactive protein* (CRP)
level, and a family history of
hypertension or diabetes as
determinants of adult metabolic
syndrome.
_________________________________________
• *Possible mechanisms by which CRP could provide protection from
SLE. Clearance pathway: CRP binds to nuclear remnants, such as
apoptotic cells, snRNPs or altered chromatin, and then binds to FcγR
on macrophages.
• It activates complement, resulting in the binding of C1q and C3 split
products to CRs.
• This leads to improved opsonization of potential autoantigens and
the secretion of anti-inflammatory cytokines, such as IL-10 and TGFß.

7. Regulatory pathway: CRP binds to activating FcγR on macrophages, inducing the
production of inflammatory cytokines and anti-inflammatory cytokines, such as IL-10
and TGF-ß. These macrophages develop a suppressive phenotype, producing more IL10 and TGF-ß, which downregulate Th1 cells and inflammatory macrophages found in
SLE and may lead to Treg cells that provide long-term suppression in SLE. CR:
Complement receptor; CRP: C-reactive protein; FcγR: Fcγ receptor; snRNP: Small
nuclear ribonucleoprotein particle; SLE: Systemic lupus erythematosus.

8. • Regulatory pathway: CRP binds to activating
FcγR on macrophages, inducing the production
of
inflammatory
cytokines
and
antiinflammatory cytokines, such as IL-10 and TGFß.
• These macrophages develop a suppressive
phenotype, producing more IL-10 and TGF-ß,
which downregulate Th1 cells and inflammatory
macrophages found in SLE and may lead to Treg
cells that provide long-term suppression in SLE.
CR: Complement receptor; CRP: C-reactive
protein; FcγR: Fcγ receptor; snRNP: Small
nuclear ribonucleoprotein particle; SLE: Systemic
lupus erythematosus

9. • During childhood, the adults with
metabolic syndrome had significantly
higher systolic blood pressure (SBP)
than that of normal adults at that age.
• Researchers from Japan showed that
elevated SBP in obese children is
associated with hyperinsulinemia and
visceral fat accumulation regardless of
family history of hypertension.

10. • The cause of hypertension in Metabolic
Syndrome is multifactorial and likely
includes all the elements of the syndrome,
including obesity, insulin resistance, and
dyslipidemia.
• Obesity may be the most important factor,
however, the other elements of the
syndrome also play a role in creating and
mediating the changes that ultimately
result in hypertension

11. • However, the potential of SBP in male
adolescents to predict the incidence of
metabolic syndrome later in life remains
unknown.
• Therefore SBP in male adolescents is an
independent predictor for metabolic syndrome
in male adolescents and could be included in
routine metabolic risk assessment.

14. • Taller children have slightly higher average
BPs. Centile values shown are for 50th height
centile: average BPs vary by ± 3-5mmHg for
5th 95th height centiles (so range typically
varies 6-10mmHg for height at any age).

15. Proposals of Definition of Metabolic
Syndromein Children and Adolescents
• The first proposal of definition was published in 2003.
• It was elaborated by assessing adolescents from 12 to
19 years old using modified criteria, based on the
criteria
of
NCEP/ATP-III,
including
abdominal
circumference over percentile 90, blood pressure over
the limits established by the National Blood Pressure
Education Program, lipids over the limits established
by the National Cholesterol
• Education Program for children, and glycemia over the
• values for adults.
• The general prevalence found in this population of 1219 years old patients was 4.2%, and when only obese
patients over the percentile 95 were considered, the
prevalence was 28.7% .

16. • The second proposal of definition is very
similar to the previous one, but the cut
offs were inferior regarding abdominal
circumference and lipid profile.
• Thus, prevalence is higher (when
considering patients with BMI percentile
adjusted over the percentile 85.

17. • The third proposal chose BMI to serve
as a base, justifying that it would be
less dependent on ethnical variations –
It should be aware that abdominal
circumference may vary according to
the race.
• The prevalence in moderately obese
patients (considering those who had Z
of 2 and 2.5) and in severe obese
patients (with Z over 2.5 of pattern
deviations (Table 1).

18. • The most appropriate definition that
include SBD that is the proposed by the
IDF.
• It divided children into age groups.
• There was not a well defined proposal for
children under
• 6 years of age, due to the lack of data.
• Differently from the criteria presented
above, in this proposal, for a matter of
convenience, the cut-offs were fixed for
pressure, lipids and glycaemia, and
abdominal circumference points were
assessed by percentile.

19. • In children aged 6-10, the cut-offs of
metabolic and blood pressure variables were
not well defined, assessing simply adiposity
(considering abdominal circumference over
the 90 percentile).
• The same criteria would be used for children
aged 10-16; regarding glycemic metabolism,
1. Fasting glycaemia ≥100 mg/ dL,
2. Triglycerides ≥150 mg/ dL,
3. HDL cholesterol below 40 mg/ dL or
using a hypolipemiant drug, and blood
pressure limits ≥130 or ≥85 mmHg or
using a antihypertensive drug.

20. • If the patient had altered abdominal circumference
and two more factors, the metabolic syndrome
diagnosis would be
• established.
• The difference is that, for adolescents over 16
• years of age, there is a differentiation between
HDL ≤40 for men and ≤50 for women (Table 2)
• Thus, discussions and doubts exist about which
criterion to use.
• Evidently, the IDF criterion, though more
convenient, could fail to include some children in
the diagnosis of Metabolic Syndrome.
• On the other hand, it would be of easier acceptance
as it does not use multiple tables to assess several
anthropometric and metabolic criteria.

22. Blood Pressure Levels for the 50th, 90th, 95th and 99th Percentiles of Systolic and Diastolic
Blood Pressure by Percentiles of Height in Boys and Girls of Age 3 to 18 years

26. The Relation between blood
pressure and Metabolic syndrome
• Several epidemiologic studies have shown that
obesity represents an independent risk factor
for the development of cardiovascular
diseases, including hypertension, myocardial
ischemic disease, and cardiac arrhythmias.
One of the most appealing concepts in obesityrelated hypertension is that a specific etiology
can be identified. There is now substantial
evidence that human obesity is characterized
by abnormalities in sympathetic cardiovascular
control.

27. • The application of sensitive techniques to
assess sympathetic nervous system (SNS)
activity in humans, including catecholamine
levels, norepinephrine (NE) spill over
techniques, and microneurography have
furthered this concept.
• Catecholamine levels in obesity have been
conflicting, with high, normal, and low levels
reported.
• However, studies examining weight loss have
found that the fall in blood pressure (BP) was
highly correlated with reductions in plasma
NE.

28. • Examination of NE spill over in obesity has
shown regional over activity in the kidneys.
• High renal SNS activity could lead to
sodium retention and abnormal glomerular
hemodynamic that could raise BP.
• Microneurography,
which
determines
muscle sympathetic outflow, has shown
consistent elevation in obesity, but no
difference between normotensive and
hypertensive obesity.

29. • However, the hyperinsulinemia of obesity
may act in concert with the SNS to elevate
BP, as the combination of the two seems
to produce vascular constriction.
• Leptin also has several cardiovascular
actions that may contribute to BP
regulation.
• Epidemiologic studies also found that SNS
activity predicts hypertension in obese
subjects

30. • The Insulin Resistance Atherosclerosis
Study, a large prospective study, set out to
determine the association between insulin
sensitivity
and
risk
factors
for
cardiovascular disease.
• There is an 11% lower risk of developing
incident hypertension with every one unit
greater of insulin sensitivity measured by
the frequently sampled intravenous glucose
tolerance test (FSIGT).
• The association between in insulin
resistance and hypertension relates to
several different mechanisms.

31. • Insulin is a vasodilator when given IV to
persons of normal weight and also increases
renal sodium reabsorption .
• The cellular mechanisms of vascular smooth
muscle contraction may be altered in insulin
resistance.
• Normally, insulin has been shown to reduce
intracellular calcium ions by inhibiting the
voltage operated channel and by activating Ca
ATPase resulting in the efflux of Ca ions from
the cell, thus decreasing cytosolic Ca ions and
decreasing vascular resistance.
• In the environment of insulin resistance, this
vasodilatory effect is lost whereas the sodium
reabsorption is preserved.

32. • In addition, angiotensinogen, angiotensin
converting enzyme and angiotensin type 1
receptors are present within human adipose tissue.
Studies suggest that the regulation of the adipose
renin-angiotensin system is correlated with the
degree of obesity and that angiotensin II may
modulate adipose tissue blood flow, growth and
metabolism. Thus, an up regulated adipose reninangiotensin system may contribute to insulin
resistance and hypertension in obese individuals
(Prasad & Quyyumi, 2004, p.1509).

33. • In addition, angiotensinogen, angiotensin
converting enzyme and angiotensin type 1
receptors are present within human adipose
tissue.
• Studies suggest that the regulation of the
adipose renin-angiotensin system is correlated
with the degree of obesity and that angiotensin
II may modulate adipose tissue blood flow,
growth and metabolism.
• Thus, an up regulated adipose reninangiotensin system may contribute to insulin
resistance and hypertension in obese
individuals.

34. • Several studies suggest that angiotensin II
may modulate the actions of insulin.
• Insulin and the renin-angiotensin system
share the P13 kinase and MAP kinase
signaling
pathways
and
tyrosine
phosphorylation of the insulin receptor
substrate 1 (IRS1) and substrate 2 (IRS2).
• Insulin receptor mediated activation of
IRS1 and IRS2 activates the P13 kinase
pathways where the angiotensin II mediated
activation inhibits the P13 kinase pathway.

35. • When activated, the renin-angiotensin
system may inhibit the metabolic actions of
insulin but promote the mitogenic actions of
the MAP kinase pathway.
• Further, both hyperglycemia and insulin
activate the renin-angiotensin system by
increasing
the
expression
of
angiotensinogen, angiotensin II and the
angiotensin I receptor which may contribute
to the development of hypertension in
patients with insulin resistance.

38. • There is also evidence that insulin resistance
and hyperinsulinemia lead to SNS
activation, which may contribute to the
pathogenesis of hypertension.
• As a result of sympathetic activation, the
kidneys increase sodium reabsorption, the
heart increases cardiac output, and the
arteries respond with vasoconstriction
resulting in hypertension