Παχυσαρκία
&
Υπέρταση
Αγριά Βόλου, 11 Σεπτεμβρίου 2015
Κωνσταντίνος Π. Μακαρίτσης
Παθολογική Κλινική
Πανεπιστημίου Θεσσαλίας
ΟΥΔΕΜΙΑ
ΣΥΓΚΡΟΥΣΗ ΣΥΜΦΕΡΟΝΤΩΝ
Διάγραμμα Παρουσίασης
Παχυσαρκία & Υπέρταση
• Definitions & Key facts
• Epidemiology & Clinical Consequences
• Pathophysiology
• Management
Definitions & Key facts
Fact sheet N°311
Updated January 2015
Overweight and obesity are defined as abnormal or excessive
fat accumulation that may impair health.
Body mass index (BMI) is a simple index of weight-for-height
that is commonly used to classify overweight and obesity in
adults.
It is defined as a person's weight in kilograms divided by the
square of his height in meters (kg/m2).
The WHO definition is:
a BMI greater than or equal to 25 is overweight
a BMI greater than or equal to 30 is obesity.
Fact sheet N°311
Updated January 2015
What causes obesity and overweight?
The fundamental cause of obesity and overweight is an
energy imbalance between calories consumed and
calories expended.
Globally, there has been:
• an increased intake of energy-dense foods that are
high in fat;
• and an increase in physical inactivity due to the
increasingly sedentary nature of many forms of work,
changing modes of transportation, and increasing
urbanization.
CMAJ 2005;172:995-998.
CMAJ 2005;172:995-998.
Estimated Hazard Ratios for Death from Any Cause According to Body-Mass Index
1.46 million white adults, 19 to 84 years of age
58% women-median follow-up period of 10 years
N Engl J Med 2010;363:2211-9.
Criteria for Clinical Diagnosis of
the Metabolic Syndrome
Central Obesity
Dyslipidemia
Hypertension
Insulin resistance
Circulation 2009;120:1640-1645.
Epidemiology
Obesity
Fact sheet N°311
Updated January 2015
• In 2014, more than 1.9 billion adults, 18 years and older, (39% of adults 38% of men and 40% of women) were overweight.
• Of these over 600 million were obese (about 13% of the world’s adult
population - 11% of men and 15% of women.
• The worldwide prevalence of obesity more than doubled between 1980
and 2014.
• Overweight and obesity are linked to more deaths worldwide than
underweight.
• In 2013, 42 million children under the age of 5 were overweight or obese.
• In developing countries the rate of increase of childhood overweight and
obesity has been more than 30% higher than that of developed countries.
• Obesity is preventable.
Lancet 2014; 384: 766–81
Worldwide, the proportion of adults with a body-mass index (BMI)
of 25 kg/m² or greater increased between 1980 and 2013 from
28·8% to 36·9% in men, and from 29·8% to 38·0% in women.
Prevalence has increased substantially in children and adolescents
in developed countries; 23·8% of boys and 22·6% of girls were
overweight or obese in 2013.
The prevalence of overweight and obesity has also increased in
children and adolescents in developing countries, from 8·1% to
12·9% in 2013 for boys and from 8·4% to 13·4% in girls.
Since 2006, the increase in adult obesity in developed countries has
slowed down.
Lancet 2014; 384: 766–81
Prevalence of overweight and obesity, ages ≥20 years, by sex, 1980−2013
1980
1996
2013
Lancet 2014; 384: 766–81
Prevalence of obesity alone, ages ≥20 years, by sex, 1980−2013
Lancet 2014; 384: 766–81
Prevalence of overweight and obesity, by age and sex, 2013
Lancet 2014; 384: 766–81
Prevalence of obesity alone, by age and sex, 2013
Among Americans age 20 and older, 154.7 million (two thirds of
US adults) are overweight or obese (BMI of 25.0 kg/m2 and
higher): 79.9 million men, 74.8 million women.
Of these, 78.4 million (one third of US adults) are obese (BMI of
30.0 kg/m2 and higher):- 36.8 million men. - 41.6 million women.
- Costs
- The total excess cost related to the current prevalence of
adolescent overweight and obesity is estimated to be $254
billion ($208 billion in lost productivity secondary to premature
morbidity and mortality and $46 billion in direct medical costs).
- If current trends in the growth of obesity continue, total
healthcare costs attributable to obesity could reach $861 to
$957 billion by 2030, which would account for 16% to 18% of
US health expenditures.
(14)
(8)
Greek Financial Crisis is Contributing to Obesity
The Hellenic Medical Association for Obesity (HMAO)
In the last 10 years the level of obesity in children has increased
substantially because of eating habits.
The rate of obesity among boys aged 6 to 12 climbed to 14 percent
in 2012 from 9 percent in 2003, and for girls from 9 percent to 13
percent.
Epidemiology
Hypertension
Hypertension is the most common of the chronic
diseases, affecting an estimated 1 billion adults
worldwide.
The prevalence of hypertension is rising, owing in
part to the increasing age of the population, the
increased rates of obesity and the increased
consumption of sodium in packaged and processed
foods.
Kearney PM et al. Lancet 365, 217–223 (2005).
Fields LE et al. Hypertension 44, 398–404 (2004).
Prevalence of hypertension is high
Prevalence of hypertension in people aged 20 years and older
Prevalence of hypertension (%)
2000
50
40
37,4 37,2
40,7
39,1
35,3
34,8
30
26,9
22
20,6 20,9
23,7
28,3
Men
Women
22,6
19,7
20
17
14,5
10
0
2025
50
45,9
41,6
44,5
42,50
40,2
39,1
40
30
27
27,7 27
27
28,2
24
22,9 23,6
18,8
20
17,1
10
0
Established
market
countries
Former
socialist
economies
India
Latin America
and the
Carribean
Middle
eastern
crescent
China
Other Asia
and islands
Sub-Saharan
Africa
Kearney PM et al.,Lancet. 2005;365:217-223.
Hypertension is a leading cause
for cardiovascular morbidity
36-Year Follow-up in Patients Aged 35-64 Years1,2
Biennial Age-Adjusted Rate
per 1,000
50
Coronary Disease
45.4
Peripheral Arterial
Disease
Stroke
Heart Failure
40
Normotensive
Hypertensive
30
22.7
21.3
20
9.5
10
3.3
0
Men
Women
13.9
12.4
Men
9.9
6.2
2.4
7.3
5.0
2.0
Women
Men
Women
3.5
Men
6.3
2.1
Women
1. Kannel W.B. et al., JAMA 1996; 275: 1571-1576
2. Kannel W.B. et al., J Hum Hypertens 2000; 14: 83-90
Cardiovascular (CV) Mortality Risk Doubles with Each 20/10 mmHg
Increment in Systolic/Diastolic BP (SBP/DBP)*
CV mortality risk
8
8X
risk
6
4
4X
risk
2
1X risk
0
115/75
2X
risk
135/85
155/95
175/105
SBP/DBP (mmHg)
*Individuals aged 40–69 years
Lewington et al. Lancet 2002;360:1903–13
Antihypertensive drug therapy is effective
at reducing risk of CV events
Heart
failure1
Fatal/Nonfatal
stroke1
Fatal/Nonfatal
CHD1
Vascular
deaths
Risk reduction (%)
0
-16%
-10
-21%
-20
-30
-38%
-40
-50
-52%
1. Moser and Herbert. J Am Coll Cardiol. 1996;
2. Collins R et al. Lancet 1990.
Blood pressure reductions of as little as 2 mmHg
reduce the risk of cardiovascular events by up to 10%
• Meta-analysis of 61 prospective, observational studies
• One million adults
• 12.7 million person-years
7% reduction in risk
of ischemic heart
disease mortality
2 mmHg decrease
in mean systolic
blood pressure
10% reduction in
risk of stroke
mortality
Lewington S et al. Lancet. 2002;360:1903–1913.
Epidemiology
OBESITY-RELATED HYPERTENSION
AND CV RISK
Obesity related Hypertension and CV Risk
• Obesity is recognized as a major cause of high BP, and the
combination of obesity and hypertension is recognized as a
pre-eminent cause of CVD.
• It is estimated that at least 75% of the incidence of
hypertension is related directly to obesity. In a survey in
Germany, approximately 75% of the hypertensive patients seen
by general practitioners or internists were overweight or
obese.
• A lot of studies do indicate risk for CVD associated with obesity
independent of other risk factors (diabetes, dyslipidemia, and
hypertension).
• In addition, obesity and hypertension may have additive effects
in increasing risk for CVD.
Am J Hypertens 2004;17:904–910.
Journal of Hypertension 2012;30:1047–1055.
Obesity related Hypertension and CV Risk
Thirty-two year rates of death due to cardiovascular disease in participants (38,000
individuals from 1967 to 1973), of the Chicago Heart Association Detection Project.
Cardiology. 1993;82(2-3):191-222.
Obesity related Hypertension and CV Risk
Data from the long-standing Framingham Heart Study revealed that compared with
normal weight adult men and women, the multivariable-adjusted relative risks for
development of hypertension in long-term follow-up were 1.48 and 1.70 for
overweight men and women and 2.23 and 2.63 for obese men and women,
respectively.
Arch Intern Med. 2002;162(16):1867-1872.
Obesity related Hypertension and CV Risk
Data from NHANES indicate that the prevalence of hypertension among obese individuals,
with a BMI ≥30 kg ⁄m2 is 42.5%
with a BMI 25.0–29.9 kg ⁄m2 is 27.8%
with a BMI <25 kg ⁄m2 is 15.3%
Arch Intern Med. 2004;164:2126-2134.
The lines represent the baseline BMI groups:
solid, baseline BMI of 20.0 to 24.9 kg/m2
dashed, baseline BMI of 25.0 to 29.9 kg/m2
dotted, baseline BMI of 30.0 to 34.9 kg/m2
In CARDIA study (1358 men & 1321
women), young adults (mean age 25
years at baseline)
who maintained a stable BMI (within
2kg⁄m2 of baseline) at 6 examinations
during 15 years had no significant
changes in SBP or DBP,
whereas those who had an increase in
their BMI≥2kg⁄m2 had substantial
increases in BP.
Circulation 2007;115:1004-1011.
1358 men & 1321 women
• Persons who maintained stable BMI had nonsignificant changes in SBP, whereas
persons whose BMI increased had statistically significant average increases in SBP (e.g.
for women) of 9.8 mm Hg to 12.5 mm Hg.
• Of note, this weight gain was more important than the baseline weight.
• Hence, age-related changes in BP may not be inevitable, and may be caused more by
age-related weight gain than aging per se.
CARDIA study, Circulation 2007;115:1004-1011.
1249 students (522 men)
Males’ BP was 129.2/77.0 mmHg, significantly higher than the females’ values of
119.9/73.4 mmHg.
Approximately 17% of the total population were classified as overweight and 3% as
obese.
Of the three lifestyle risk factors examined, only BMI was significantly and directly
associated with systolic and diastolic BP levels. The prevalence of hypertension
(≥140/90 mmHg) was significantly higher in men compared to women, and in obese
and overweight participants compared to normal-weight subjects.
Pathophysiology
ΑΙΜΟΔΥΝΑΜΙΚΕΣ ΠΑΡΑΜΕΤΡΟΙ
ΚΑΡΔΙΑΚΗ
ΠΑΡΟΧΗ
Χ
ΠΕΡΙΦΕΡΙΚΕΣ
ΑΝΤΙΣΤΑΣΕΙΣ
ΑΡΤΗΡΙΑΚΗ
ΠΙΕΣΗ
HOW OBESITY RAISES BLOOD PRESSURE ?
• Obesity-associated hypertension is often characterized by increased cardiac
output which appears to be mediated in part through plasma volume
expansion and sodium retention. Neurohumoral mechanisms are also involved.
• However, a purely hemodynamic etiology, based on increased plasma volume
and increased cardiac output, are not sufficient explanations since the latter
do not account for the increase in peripheral resistance noted in obese
hypertensive patients who exhibit an increase in both kidney and cardiac SNA,
when compared with normotensive obese patients who exhibit an increase in
kidney SNA, whereas sympathetic outflow to the heart is reduced.
• Pharmacological studies and direct sympathetic nerve recordings suggest that
the SNS may be overactivated in obesity-associated arterial hypertension.
• Even though plasma volume and sodium retention are increased, the systemic
RAAS is activated in obesity. Weight loss studies suggest that the local RAAS in
adipose tissue, along with changes in intrarenal physical forces generating from
fat accumulation into the renal medulla, may contribute to the increase in
systemic RAAS activity.
Journal of Hypertension 2012, 30:1047–1055.
Pathogenesis of Obesity-related Hypertension
J Clin Hypertens 2013;15:14–33.
Pathophysiology
Central Obesity - Adipokines
Vague J. The degree of masculine differentiation of obesities: a factor determining
predisposition to diabetes, atherosclerosis, gout, and uric calculous disease.
Am J Clin Nutr. 1956;4:20–34.
Central Obesity in the Pathogenesis of Obesity Hypertension
Vague’s observations attracted little attention until the
1980s when population-based studies in Scandinavia,
using waist to hip ratio as a quantifiable surrogate for
the upper body phenotype, demonstrated significant
CV risk (hypertension, myocardial infarction, and type
2 diabetes mellitus) in association with a high waist to
hip ratio.
It was shown that insulin resistance was also
associated with the upper body phenotype and many
subsequent studies showed an association of insulin
levels and ⁄ or insulin resistance with hypertension in
both obese and non-obese people.
J Clin Hypertens 2013;15:14–33.
Atherosclerosis 2013;227:216-221.
Molecular signaling of leptin
Atherosclerosis 2013;227:216-221.
Molecular signaling responses to leptin. Vascular & Cardiac effects
International Journal of Endocrinology
Volume 2015, Article ID 534320, 13 pages
Adiponectin molecular signaling in endothelium
Atherosclerosis 2013;227:216-221.
Role of adipokines in atherogenesis & hypertension
Hypertension
Atherosclerosis 2013;227:216-221.
Visceral adiposity in obesity hypertension
• Visceral adiposity may have a major role in the occurrence of
hypertension, diabetes mellitus, hyperlipidemia, and atherosclerosis in
obese humans.
• Recent evidence revealed several biological and genetic differences
between intraabdominal visceral fat and peripheral subcutaneous fat.
• Visceral adipose tissue-resident macrophages produce more proinflammatory cytokines, such as TNFα and IL6, but less adiponectin
inducing insulin resistance, endothelial dysfunction and the subsequent
atherosclerosis.
• The rate of visceral fat accumulation is also different according to the
gender and ethnic background, and may explain the variation in the
cardiometabolic risk between different populations.
• Interestingly, visceral obesity elicits greater activation of the sympathetic
nervous system (SNS) than subcutaneous obesity does.
Journal of Endocrinology 2014;223:R63–R78.
Blood. 2013;122(20):3415-3422.
Pathophysiology
SNS Activity
Role of the central SNS in metabolic control
Journal of Diabetes Research
Volume 2015, Article ID 341583, 11 pages
β3-Adrenergic Receptor Stimulation
Ursino MG, et al. Pharmacol Res 2009;59:221-34
Sympathetic Activation in Obesity Hypertension
• Activation of the sympathetic nervous system (SNS) has been
considered to have a crucial function in the pathogenesis of
hypertension among obese individuals.
• Many studies provide evidence of high muscle SNS activity in
obese subjects. High-caloric intake increases norepinephrine
turnover in peripheral tissues and raises resting plasma
norepinephrine concentrations—an indirect measurement of SNS
activity—.
• High dietary content in fat and carbohydrate has been suggested
to acutely stimulate peripheral α1- and β-adrenergic receptors,
leading to elevated sympathetic activity and hypertension.
• The mechanisms that have been proposed to be responsible for
an increased SNA in obesity include insulin and leptin, impaired
function of the baroreceptor sensitivity, increased levels of
circulating FFAs and Ang II.
Hypertension Research 2010;33:386-393.
Insulin and obesity related hypertension
• Insulin has an acute sympatho-excitatory action in both
normotensive and borderline hypertensive subjects, as
indicated by increased muscle SNS activity and heightened
norepinephrine levels after insulin administration in several
studies.
• Insulin might also have a sympatho-excitatory effect directly on
the CNS.
• Insulin release leads to hypoglycemia, which serves as an
activator of the SNS.
• Moreover, vasodilator responses to increased muscular glucose
uptake and oxygen demands lead to activation of the
baroreceptor reflex and to enhanced muscle SNS activity.
Hypertension Research 2010;33:386-393.
Insulin and obesity related hypertension
• Another aspect of insulin infusion is the simultaneous depressor
effect of peripheral vasodilation mediated by a β-adrenergic
mechanism.
• Chronic hyperinsulinemia has been associated with impairment of
the vasodilator action of insulin.
• Vasoconstriction in the forearm was reported during insulin
infusion in severe insulin resistance. This finding suggests that
hyperinsulinemia promotes vascular dysfunction.
• Whether hypertension is caused by excessive amounts of insulin,
resistance to its action or chronically induced trophic vascular
effects remains to be uncovered.
• Insulin also has a direct action on the kidney to stimulate sodium
retention.
Hypertension Research 2010;33:386-393.
Leptin and obesity related hypertension
• Leptin regulates energy intake and expenditure decreasing food
intake and upregulating thermogenesis and energy expenditure
through the stimulation of SNA.
• The effects of leptin are mediated by two major pathways,
positive regulation of anorexigenic α-MSH and negative
regulation of NPY having an orexigenic effect combined with a
reduction of thermogenesis.
• In obesity, leptin resistance and hyperleptinemia develop
because of disrupted signaling in leptin receptor-containing
neurons in brain areas involved in food intake regulation, namely
the hypothalamic nucleus arcuatus.
• Leptin action in the nucleus arcuatus is also important for the
control of sympathetic outflow to both brown adipose tissue and
the kidney.
Journal of Endocrinology 2014;223:R63–R78.
Leptin and obesity related hypertension
• Selective resistance to the metabolic actions of leptin seems
to be present in obesity, whereas its action in stimulation of
sympathetic tone remains unaltered.
• SNS-stimulating effects of leptin are mainly demonstrated in
the kidney, adrenal gland, and brown adipose tissue.
• Hyperleptinemia and leptin resistance thus may be the cause
of chronically elevated SNS in obesity via activation of leptin
receptors in hypothalamus and brainstem.
• Moreover, in the leptin resistant state, NPY is overexpressed
and it is released from neural sites by sympathetic activation
and acts as a vasoconstrictor and thus could play a role in
obesity related hypertension.
Journal of Endocrinology 2014;223:R63–R78.
(nucleus arcuatus)
Y1-Y6-R
+
NPY
SNS
AgRP
ACTH
Selective resistance to insulin (metabolic syndrome) or leptin (obesity)
and sympathetic nervous system (SNS) hyperactivity
Journal of Endocrinology 2014;223:R63–R78.
Sympathetic Activation in Obesity Hypertension
Reduced sensitivity of the arterial baroreceptors
• The arterial baroreceptors acutely respond to increases in BP by
parasympathetic activation and sympathetic inhibition.
• A reduced sensitivity of the arterial baroreflex may occur in longstanding hypertension and obesity, because of a concomitant
increase in central sympathetic outflow and of the effects of
arteriosclerotic lesions leading to an increased stiffness of the
large arteries in which the receptors are located.
• Impaired baroreflex sensitivity leads to withdrawal of
parasympathetic cardiac modulation, which occurs in obesity
even in the absence of an elevation in arterial pressure.
• Elevated sympathetic activity did not seem to account for the
increased heart rate in obesity but it appears to be the effect of
decreased parasympathetic activity.
Hypertension Research 2010;33:386-393.
Sympathetic Activation in Obesity Hypertension
Elevated levels of FFAs
• Elevated levels of FFAs have been reported in obese
hypertensives.
• Abnormal distribution of FFAs in obese patients has been found
to enhance vascular a-adrenergic sensitivity and consequently to
increase a-adrenergic tone.
• FFAs inhibit Na+, K+-ATPase modifying the sodium pump raising
vascular smooth muscle tone and resistance.
• FFAs act as potent activators of phosphorylation of protein kinase
C (PKC).
• Other studies have reported a direct action of FFAs released from
phospholipids on ion channels at the cellular membranes of
smooth muscle cells and other tissues.
Hypertension Research 2010;33:386-393.
Sympathetic Activation in Obesity Hypertension
Angiotensin II (Ang II) effects
• Even though plasma volume and sodium retention are
increased, the systemic RAAS is activated in obesity.
• Moreover, studies in patients under sodium restriction, which
activates the renin–Ang system (RAS), provided evidence for a
presynaptic potentiating effect of Ang II on sympathetic
neurotransmission.
Hypertension Research 2010;33:386-393.
Pathophysiology
RAAS Activity
RAAS Activity in Obesity Hypertension
Several studies have shown predominantly high levels of plasma
renin activity, plasma angiotensinogen, Ang II and aldosterone
values in association with human obesity.
Despite remarkable volume expansion and sodium retention in
obesity, several mechanisms are responsible for the RAS activation.
Renin secretion by the kidney seems to be induced by changes in
intrarenal physical forces, generating from fat accumulation around
and into the renal medulla.
Owing to the actual histologic changes that cause compression of
the medulla, flow rate of the filtrate is diminished at the loop of
Henle leading to prolongation of the time given for sodium
reabsorption.
Detection of the decreased amount of sodium, reaching the distal
tubular cells, by the macula densa leads to a rise in renin secretion,
through tubuloglomerular feedback.
Hypertension Research 2010;33:386-393.
ΡΥΘΜΙΣΗ ΕΠΑΝΑΡΡΟΦΗΣΗΣ Νa και Η2Ο
DISTAL
TUBULE
Na+
EFFERENT
Macula
Densa
AFFERENT
JG Cells
RAAS Activity in Obesity Hypertension
• Adipose cells may represent a major site in which all
components of the RAS are formed. Renin, Ang II,
angiotensinogen and Ang II receptors are found in abundance
in adipose mass suggesting that a local tissue Ang system is
settled at the adipocytes level.
• Angiotensinogen production serves as both a cause and effect
of adipocyte hypertrophy and leads to elevation of BP through
the actions of Ang II, which induce systematic vasoconstriction,
direct sodium and water retention and increased aldosterone
production.
• Another potential mechanism of RAS activation could be a
chronic elevation of sympathetic tone, causing renal
vasoconstriction and renin-dependent chronic hypertension.
Hypertension Research 2010;33:386-393.
ANGIOTENSIN
N Engl J Med
Pathophysiology
Salt Sensitivity - Increased renal Na reabsorption
Salt Sensitivity - Increased renal Na reabsorption
• Obesity predisposes the kidney to reabsorb sodium by neural
(SNS), hormonal (aldosterone and insulin), and renovascular
(angiotensin II) mechanisms.
• This enhanced sodium avidity shifts the pressure natriuresis
curve to the right, thereby necessitating higher arterial
pressure to excrete the day’s salt intake and maintain sodium
balance and volume homeostasis.
• This is the basis for the documented salt sensitivity of obesity
related hypertension and underlines the need for diuretics in
the therapeutic regimen.
J Clin Hypertens 2013;15:14–33.
Regulation of ENaC membrane expression
α β γ
MR
Insulin
MR, Aldosterone and Obesity
Plasma aldosterone in women correlated directly
with visceral adipose tissue, and higher plasma
aldosterone values have also been reported in
patients with metabolic syndrome, which is
independent of plasma renin activity.
Accumulating studies have elucidated the close
relationship between aldosterone and obesity.
Molecular and Cellular Endocrinology 350 (2012) 273–280.
Mineralocorticoid Receptor-MR
Hypertens Res 2004; 27: 781–789.
MR, Aldosterone and Obesity
The adipose tissue is an endocrine organ that
secretes a variety of adipokines.
Adipocytes are capable of stimulating adrenal
aldosterone synthesis through the secretion of
potent aldosterone-releasing factors (ARFs),
which are not yet identified.
Nonetheless, the adipose tissue does not
express 11βHSD2, and MR in adipocytes are
predominantly occupied by glucocorticoids which
have an essential function in adipocytes.
Molecular and Cellular Endocrinology 350 (2012) 273–280.
MR, Aldosterone and Metabolic Syndrome
Aldosterone-releasing factors (ARFs)
Molecular and Cellular Endocrinology 350 (2012) 281–288.
MR, Aldosterone and Metabolic Syndrome
Adipocyte
Hypertension 2010;55:813-818.
___
Ouabain
Aldosterone
N Engl J Med. 2007;356:1966-78.
Hypertension Research 2010;33:386-393.
Management
Μanagement of Οbesity Related Ηypertension
• Remarkably, current hypertension guidelines do not provide
specific recommendations for the choice of antihypertensive
medications in obese patients.
• Indeed, there are no large trials addressing the issue.
• Since a large proportion of hypertensive patients are
overweight or obese, data gathered in large clinical trials with
hard clinical endpoints, which is the foundation of the ESH
Guidelines,
are
at
least
in
part
applicable.
• However, to address the specific needs of obese patients,
these recommendations have to be modified on the basis of
few existing data and our current understanding of the
mechanisms involved in obesity-associated arterial
hypertension.
Journal of Hypertension 2012, 30:1047–1055.
J Clin Hypertens 2013;15:14–33.
Journal of Hypertension 2012, 30:1047–1055.
Journal of Hypertension. 2013;31:1281–1357.
Life style management of obesity hypertension
J Clin Hypertens 2013;15:14–33.
Life style management of obesity hypertension
Weight Loss
Systematic reviews consistently report a decrease in SBP of about 1
mm Hg per kg of weight loss with follow-up of 2 to 3 years.
There is attenuation in the longer-term, with a decrease of about 6
mm Hg in SBP per 10 kg of weight loss.
Diets
Meta-analyses and systematic reviews that compare various dietary
approaches do not favor a specific diet for weight reduction.
Appropriate diets for the management of obesity related
hypertension are rich in potassium, calcium and magnesium, and
fiber and low in salt and saturated fat.
In terms of foods, these diets promote consumption of vegetables,
fruits, low-fat dairy products, whole grains, nuts, poultry, and fish
and discourage salt, red meats, sweet foods, and sugary drinks.
Mediterranean diet is also associated with benefits in relation to CV
risk, weight control, and BP.
J Clin Hypertens 2013;15:14–33.
Life style management of obesity hypertension
Low-Salt Diets
Salt sensitivity is commonly associated with obesity.
The usual salt intake is between 9 and 12 g/day in many countries
and it has been shown that reduction to about 5 g/day has a
modest (1–2mmHg) SBP-lowering effect in normotensive
individuals and a somewhat more pronounced effect (4–5mmHg)
in hypertensive individuals.
A daily intake of 5– 6 g of salt is thus recommended for the general
population.
The effect of sodium restriction is greater in black people, older
people and in individuals with diabetes, metabolic syndrome or
CKD, and salt restriction may reduce the number and doses of
antihypertensive drugs.
The effect of reduced dietary salt on CVD events remains unclear,
although the long-term follow-up showed a reduced salt intake to
be associated with lower risk of CV events.
Journal of Hypertension. 2013;31:1281–1357.
Life style management of obesity hypertension
Physical Activity
Aerobic exercise can reduce weight and BP, but when exercise is
the only intervention, weight losses are small, with an estimated
change of 1.6 kg in moderate-intensity programs continued for 6
to 12 months.
In a meta-analysis that included assessment of ambulatory BP it
was reported that in studies lasting 4 to 52 weeks, with physical
activity as the only intervention, aerobic exercise reduced BP by
3 ⁄ 2.4 mm Hg.
The change affected daytime (3.3 ⁄ 3.5 mm Hg) but not nighttime
(0.6 ⁄ 1.0 mm Hg) BP.
The effect on BP was independent of the estimated weight loss
of 1.2 kg.
However, when aerobic exercise is combined with calorie
restriction for weight control, the effects on ambulatory BP can
be substantial.
J Clin Hypertens 2013;15:14–33.
Life style management of obesity hypertension
Alcohol
The pressor effect of alcohol has been established in clinical trials,
with an estimated increase in SBP of 1 mm per 10 g of alcohol.
Drinking alcohol at low to moderate levels is associated with lower
risk of atherosclerotic disease.
Moderation of heavier daily alcohol intake to no more than one
standard drink in women and two standard drinks in men appears
prudent, with potential benefits for both weight gain and BP.
Combination of alcohol moderation and weight reduction in
overweight and obese hypertensive drinkers, achieved a 14 ⁄ 9 mm
Hg BP reduction compared with controls who maintained usual
weight and drinking habits.
Smoking
Although smokers tend to have lower body weight, they may gain
weight because of clustering of adverse health behaviors.
Smoking increases BP acutely, with an associated rise in arterial
stiffness that lasts longer in hypertensive men. J Clin Hypertens 2013;15:14–33.
Adoption of lifestyle changes
Drug Treatment for Obesity Related Hypertension
J Clin Hypertens 2013;15:14–33.
β-blockers ?
ACEi
CCBs
Diuretics
Nature Reviews
Endocrinology
2014;10:364–376.
Drug Treatment for Obesity Related Hypertension
• Inhibitors of the renin-angiotensin-system are considered firstline antihypertensive agents for most patients.
• Because of their broad spectrum of beneficial effects,
angiotensin-converting enzyme inhibitors are currently
considered to be the most appropriate drug for
antihypertensive treatment of obese patients.
• Angiotensin receptor blockers can be utilized in patients who
do not tolerate angiotensin-converting enzyme inhibition.
• Cleary, renin-angiotensin system blockade in patients with
obesity-related hypertension is unlikely to worsen glucose or
lipid metabolism.
Journal of Hypertension 2012; 30:1047–1055.
Drug Treatment for Obesity Related Hypertension
• Beta-blockers reduce cardiac output and renin activity,
both of which are frequently increased in obese patients.
• Beta-blockers alone, or in combination with alphaadrenoreceptor blockers, were more effective in decreasing
blood pressure in obese than in lean hypertensive
individuals.
• Limitations for the use of beta-blockers are related to their
potential negative effects on glucose metabolism and body
weight.
• Beta-blockers with vasodilating properties, such as
carvedilol or nebivolol, may be less likely to worsen glucose
metabolism.
Journal of Hypertension 2012; 30:1047–1055.
Drug Treatment for Obesity Related Hypertension
• Dihydropyridine calcium channel blockers are effective in
lowering blood pressure in obese related hypertension.
• The ACCOMPLISH trial compared combination therapies
amlodipine/benazepril vs. hydrochlorothiazide/benazepril in a
hypertensive patient population with a considerable number
of obese patients (mean BMI 31.0 kg/m2 in both groups).
• The trial was terminated early due to reduced cardiovascular
mortality with the amlodipine/benazepril combination.
• The observation that obese patients are more likely to
experience peripheral edema with dihydropyridine calcium
channel blocker treatment compared with lean patients is a
potential limitation.
Journal of Hypertension 2012; 30:1047–1055.
ARR: 2.2%
RRR: 19.6%
HR: 0.80, 95% CI (0.72 to 0.90); P<0.001
ACCOMPLISH – ΠΑΧΥΣΑΡΚΟΙ
RAS + CCB vs. RAS + Diuretic
αποδεικνύεται ανώτερο σε όλες τις υπoομάδες του BMI
Drug Treatment for Obesity Related Hypertension
• Diuretic agents could be used with respect to the well
described hypervolemia and sodium retention in obesity.
• Combination of low-dose thiazide diuretics with renin–
angiotensin system blockers may reduce hyperkalemia risk
while improving blood pressure control.
• Consideration should be given to the impairment of insulin
sensitivity and deterioration of glucose metabolism that could
be caused by high dose thiazide diuretics.
• Overall, thiazide diuretics may not be the first choice for most
obese hypertensive patients.
• However, in patients not responding to monotherapy, thiazide
diuretics are a reasonable second or third antihypertensive
drug.
Journal of Hypertension 2012; 30:1047–1055.
Drug Treatment for Obesity Related Hypertension
• MR blockers
• More than half of the obese hypertensive patients are treated
with two or more antihypertensive drugs.
• A recent study in obese patients with resistant hypertension,
adding the mineralocorticoid antagonist spironolactone in
doses of 25–100 mg/day showed a 16/9mmHg reduction in
ambulatory blood pressure performed after a median interval
of 7 months.
• Remarkably, higher waist circumference was associated with
better response to spironolactone.
• These findings point to the special role of aldosterone in obesity
associated hypertension.
Journal of Hypertension 2012; 30:1047–1055.
Treatment strategies in hypertensive patients with metabolic syndrome
TREATMENT OF OBESITY IN HYPERTENSIVE PATIENTS
Bariatric Surgery
J Clin Hypertens 2013;15:14–33.
Summary & Conclusions (1)
Obesity-related hypertension is an important public health issue.
As the prevalence of obesity increases, the prevalence of
hypertension with its associated CV risk will increase as well.
Primary prevention is the long-term goal for diminishing the
prevalence of obesity, control of both obesity and hypertension in
the population at risk is the overriding current challenge.
Treating hypertension in the obese requires addressing the obesity
as part of the therapeutic plan.
Lifestyle management is required in every case, with a focus on
weight loss and risk reduction.
J Clin Hypertens 2013;15:14–33.
Summary & Conclusions (2)
• Treatment of obesity with caloric restriction and sodium
restriction works if extreme enough, but it is not a feasible longterm strategy.
• In most patients, additional therapies including medications,
aggressive diet counseling and behavioral techniques, and
sometimes bariatric surgery will be required.
• Given the volume expansion and the neurohumoral activation in
obesity-associated arterial hypertension, renin-angiotensin
system inhibitors, calcium channel blockers, diuretics, and beta
blockers are reasonable choices, along with MR inhibitors
(spironolactone) in resistant obese hypertension.
• However, when choosing antihypertensive medications
metabolic side effects should be taken into consideration.
J Clin Hypertens 2013;15:14–33.
Journal of Hypertension 2012; 30:1047–1055.
Thank You - Ευχαριστώ
The Ancient Theatre of Larissa, Greece
3rd Century B.C.
Arch Intern Med 2002;162:2074-9
Central sympathetic nerve overactivity
as a consequence and cause of metabolic abnormalities
Journal of Diabetes Research
Volume 2015, Article ID 341583, 11 pages