Hypertension in obesity cme

Hypertension in Obesity
The Deadly Duo

Obesity
» “A condition in which percentage body fat (PBF) is increased to an
extent in which health and well-being are impaired, and, due to the
alarming prevalence increase, declared it as a “global epidemic”
World J Gastroenterol. 2016 January 14; 22(2):
681-703

Obesity Classification
2016 AACE/ACE Guidelines
Classification
BMI
BMI (kg/m2) Co-morbidity Risk
Underweight <18.5 Low
Normal Weight 18.5-24.9 Average
Overweight 25-29.9 Increased
Obese Class-I 30-34.9 Moderate
Obese Class-II 35-39.9 Severe
Obese Class-III ≥40 Very Severe

1. Obesity and overweight. Fact sheet. Reviewed February 2018. Available at: http://www.who.int/mediacentre/factsheets/fs311/en/. Las accessed. 26/03/2018
2. Adult obesity: applying All Our Health: Updated 9 January 2018: Available at https://www.gov.uk/government/publications/adult-obesity-applying-all-our-health/adult-obesity-applying-all-our-health
Last accessed: 14/03/2018
39% of 18+ are
overweight , &
13% are obese1

Consequences of Obesity: Normal weight vs. Obese
1. Aviva Must. The Disease Burden Associated with Overweight and Obesity Last Update: August 8, 2012. Available at
https://www.ncbi.nlm.nih.gov/books/NBK279095/ Last accessed: 27/03/2018
2. Obes Res. 1998;suppl 2:51S–209S
54% higher risk for
Hypertension1
64% higher risk for
Type-II Diabetes1
34% higher risk for
Arthritis1
17% higher risk for
Asthma1
24% higher risk for
Stroke2

Relative Co-morbidity Risks Related to Obesity/Overweight
Co-morbidity
Overweight Obesity
Male Female Male Female
Hypertension 1.28 1.68 1.84 2.42
Type-II Diabetes 2.40 3.92 6.74 12.41
Coronary artery disease 1.29 1.80 1.72 3.10
Congestive Heart failure 1.31 1.27 1.79 1.78
Stroke 1.23 1.15 1.51 1.49
Osteoarthritis 2.76 1.80 4.20 1.96
Chronic Back Pain 1.59 1.59 2.81 2.81
BMC Public Health. 2009 Mar 25;9:88.

Hypertension in Obesity: Prevalence
42.50%
27.80%
15.30%
0.00%
5.00%
10.00%
15.00%
20.00%
25.00%
30.00%
35.00%
40.00%
45.00%
BMI ≥ 30 BMI 25-29.9 BMI < 25
PrevalenceofHypertensionin%
J Clin Hypertens (Greenwich). 2014 Jan;16(1):14-26.

Body Weight & BP
» 10 kg higher body weight is associated with2
» 12% increased risk for coronary heart disease
» 24% increased risk for stroke
Every 4.53 kg weight gain is associated with an estimated 4.5 mm Hg
increase in systolic blood pressure1
1. Hypertension. 2004 Mar;43(3):518-24
1. J Health Care Poor Underserved. 2011;22(4 Suppl):61-72

2017 CC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA
Guideline for the Prevention, Detection, Evaluation, and
Management of High Blood Pressure in Adults
» Obesity is responsible for about 40% of hypertension, however, it was
even higher in Framingham Offspring Study (78% in men and 65% in
women)
Being obese continuously or acquiring obesity is associated with a
relative risk of 2.7 for developing hypertension
Hypertension. 2017 Nov 13. pii: HYP.0000000000000066.

Pathophysiologic Mechanisms of Hypertension in Obesity
Curr Cardiol Rep. 2017 Aug 24;19(10):98.

Obesity
Further Propagates Hypertension
Combination of Enhanced
Sympathetic + RAAS activity
Impaired Natriuresis
Increased renal Na absorption Extracellular volume expansion

Effect of weight loss on BP
Hypertension. 1986 Mar;8(3):223-8.
1kg reduction in weight is associated with 1.79 mm Hg fall in BP
&
A 4-kg weight loss is equivalent to the amount of antihypertensive
medication required for effective control of mild hypertension

Benefits of Modest Weight Loss in Improving Cardiovascular Risk
Factors in Overweight and Obese Individuals With Type 2 Diabetes
Parameters Effects of 5-10% reduction in body weight
HBA1C Increased odds of achieving 0.5% point reduction (OR 3.52)
DBP 5 mmHg decrease
SBP 5 mmHg decrease
HDL-C 5mg/dL increase
Diabetes Care. 2011; 34:1481–1486
Look AHEAD (Action For Health in Diabetes) study
n=5145; d=1 year
Conclusions: Modest weight losses of 5 to <10% is associated with significant improvements in
CVD risk factors at 1 year.

Effects of weight loss interventions for adults who are obese on
mortality, cardiovascular disease: systematic review
and meta-analysis
BMJ. 2017 Nov 14;359:j4849.
54 RCTs with 30, 206 participants
High quality evidence showed that weight loss interventions decrease all cause
mortality (34 trials, 685 events; risk ratio 0.82, 95% confidence interval 0.71 to 0.95),
with six fewer deaths per 1000 participants (95% confidence interval two to 10)
Twenty four trials (15 176 participants) reported high quality evidence on
participants developing new cardiovascular events (1043 events; risk ratio 0.93,
95% confidence interval 0.83 to 1.04)

Management of Obesity: Point to consider
» BMI is a screening measure, not a diagnostic measure
» Diagnosis of obesity is the presence of abnormal excess body fat that
impairs health
» Consider the patient’s genetics and ethnicity as part of BMI & waist
circumference & do not treat on BMI alone
» Consider comorbidities and health risk
» Modest or moderate weight loss can produce health benefits
» More serious complications  more weight loss
» Patients with severe obesity & complications  bariatric surgery
Med Clin North Am. 2018 Jan;102(1):49-63

Management of Obesity: Point to consider
» Prescribe a diet the patient can adhere to and that has health
benefits
» Patients counseling sessions are needed
» Medications approved for chronic weight management can help
patients better adhere to the diet plan and can help sustain hard-won
weight loss
» Medications success to be evaluated at 12-16 weeks
» If successful, medications should be continued
» Obesity is a complex, chronic disease and life-long management is
indicated
Med Clin North Am. 2018 Jan;102(1):49-63

Guideline Recommendation on Obesity Management

2013 AHA/ACC/TOS Obesity guidelines
» Key points:
» BMI is screening tool; waist circumference is a risk factor
» It is not necessary to achieve normal weight; health improvements begin
with modest weight loss
» There is no magic diet
» Lifestyle-intervention counseling conducted face-to-face in 14 or more
sessions over 6 mo is the gold standard for weight loss intervention
» Bariatric surgery should be discussed with patients who meet criteria &
would benefit from it, and referrals should be made
Obesity 2014;22(S2):S1–410.

2015 Endocrine Society Obesity Guidelines
» Key points:
» Weight-centric prescribing should be done for chronic diseases; in prescribing
for chronic diseases, avoid medications that promote weight gain in favor of
those that are weight neutral or are associated with weight loss
» Medications are useful adjuncts to diet and exercise, when prescribed
appropriately
» Choosing which medication to use is a shared decision of prescriber and
patient
J Clin Endocrinol Metab 2015; 100(2):342–62

2016 AACE Obesity Guidelines
» Key points:
» Complications of excess body weight should direct intensity of treatment and
urgency of treatment
» Medications for chronic weight management may be used initially (without
lifestyle-alone attempt) for patients with more severe disease manifestations
as an adjunct to lifestyle (multi-component) measures
» Individuals without comorbidities or risk factors are stage 0 and no medical
intervention is required
Endocr Pract 2016;22(7):842–84.

USFDA Approved Medications for Obesity: long Term Use

Orlistat: Lipase Inhibitor
Approved
for
MOA
Common side
effects
Warnings
Adults and
children ages
12 and older
Works in gut to
reduce the amount of
fat body absorbs from
the food
• Diarrhea
• Gas
• Leakage of
oily stools
• Stomach
pain
1. Rare cases of severe liver
injury have been reported.
2. Avoid taking with cyclosporine
3. Take a multivitamin pill daily to
make sure enough intake of
certain vitamins that body may
not absorb from the food
Weight Management: Prescription Medications to Treat Overweight and Obesity
Available at: https://www.niddk.nih.gov/health-information/weight-management/prescription-medications-treat-overweight-obesity

Lorcaserin: Serotonin receptor agonists
Approved
for
MOA
Common side
effects
Warnings
Adults Serotonin
receptor
agonists
• Constipation
• Cough
• Dizziness
• Dry mouth
• Feeling tired
• Headaches
• Nausea
Serotonin Syndrome or Neuroleptic Malignant
Syndrome (NMS)- like Reactions: The safety of
coadministration with other serotonergic or
antidopaminergic agents has not been established.
Manage with immediate discontinuation & provide
supportive treatment

Phentermine (sympathomimetic amine)-topiramate (anti-
epileptic or anti-seizure) : Combination
Approved
for
MOA
Common side
effects
Warnings
Adults A mix of two
medications:
phentermine, which
lessens appetite, &
topiramate, used to
treat seizures or
migraine headaches,
may make you less
hungry or feel full
sooner
• Constipation
• Dizziness
• Dry mouth
• Taste changes,
especially with
carbonated
beverages
• Tingling of your
hands and feet
• Trouble sleeping
• Can cause an increase in resting
heart rate
Contraindicated in
1. Pregnancy
2. Glaucoma
3. Hyperthyroidism
4. During or within 14 days of taking
monoamine oxidase inhibitors
5. Patients with hypersensitivity or
idiosyncrasy to
sympathomimetic amines

Naltrexone (Opiate antagonist)-bupropion (Dopamine &
Norepinephrine Reuptake inhibitor)
Approved
for
MOA
Common side
effects
Warnings
Adults A mix of two medications:
naltrexone, used to treat
alcohol & drug
dependence & bupropion,
used to treat depression or
help people quit smoking.
Induces early satiety
• Constipation
• Diarrhea
• Dizziness
• Dry mouth
• Headache
• Increased BP
• Increased HR
• Insomnia
• Liver damage
• Nausea
• Vomiting
Do not use in following conditions
• Uncontrolled high blood
pressure, seizures or a history
of anorexia or bulimia nervosa
• If dependent on opioid pain
medications or withdrawing
from drugs or alcohol
• Taking bupropion
MAY INCREASE SUICIDAL
THOUGHTS OR ACTIONS

Liraglutide: Glucagon-like peptide-1 receptor agonist
Approved for MOA Common side effects Warnings
Adults Decreases calorie
intake, delayed
gastric emptying &
GLP-1 agonist
action in areas of
brain involved in
appetite regulation
• Nausea
• Diarrhea
• Constipation
• Abdominal pain
• Headache
• Raised pulse
• May increase the chance
of developing pancreatitis
• Has been found to cause a
rare type of thyroid tumor
in animals

Other medications: Short Term Use
Weight-loss
medication
Approved for
Common side
effects
Warnings
Medications that curb
desire to eat include
1. Phentermine
2. Benzphetamine
3. Diethylpropion
4. Phendimetrazine
Adults
Note: FDA-
approved only for
short-term use—up
to 12 weeks
• Dry mouth
• Constipation
• Difficulty sleeping
• Dizziness
• Feeling nervous
• Feeling restless
• Headache
• Raised blood
pressure
• Raised pulse
Do not use if you have
heart disease,
uncontrolled high blood
pressure,
hyperthyroidism, or
glaucoma. Tell your
doctor if you have
severe anxiety or other
mental health problems.

Management of Hypertension in Obesity: A Challenge

Obesity & Resistant Hypertension: Link
58.1% of resistant hypertensive were having BMI >30
Indian Heart J. 2017 Jul - Aug;69(4):442-446
Obese patient had significantly increased odds (OR: 1.84, 95% CI 1.04–3.26)
for having resistant hypertension
BMC Res Notes. 2013 Sep 21;6:373
Refractoriness among obese hypertensives is frequently caused by obstructive sleep
apnea and/or inappropriately high plasma aldosterone levels
Hypertension. 2004;43:518-524

Hypertension: GOAL
BP Goal of Pharmacological Therapy in Patients With Hypertension & Co-morbidity

Management of Hypertension in Obesity
» Non Pharmacologic
a) Weight loss
b) Low Salt Diets
c) Increase physical activity
d) Smoking & Alcohol cessation
e) Behavioral modification

Management of Hypertension in Obesity: Pharmacologic
J Clin Hypertens (Greenwich). 2013 Jan;15(1):14-33

Contd…
Drug Classes Comments
ACEi/ARBs Angiotensin is over expressed in obesity & directly contribute to obesity related
hypertension making these 1st line agents; do not increase weight or insulin
resistance; reno-protective in diabetes
B-Blocker Not recommended; associated with increased insulin resistance, new cases of
diabetes & weight gain
CCBs Effective in BP management in obese & not associated with weight gain
Diuretic • Recommended as first-line agents, but known dose-related side effects
(dyslipidemia & insulin resistance) are undesirable
• Low-dose thiazides (12.5 to 25 mg of HCTZ) recommended with close lipid and
glucose monitoring
• Loop diuretics and ⁄or potassium-sparing agents should be considered if greater
diuretic effect is required to control BP
J Clin Hypertens (Greenwich). 2013 Jan;15(1):14-33

Management of Obesity with Hypertension

Treating Obesity with Hypertension
Clinical Component Intervention/ Weight-Loss Goal
Hypertension 5% to ≥ 15%
Endocr Pract 2016;22(7):842–84.

Common Medications & their Effect on Weight

Medications & their Effect on Weight
Indication or Class Weight Gain Weight Loss or Weight Neutrality
(Weight Reduction in Parentheses)
Antihypertensive medications a-blocker?
b-blocker?
ACE inhibitors?
Calcium channel blockers?
Angiotensin-2 receptor antagonists
Antidiabetic medications Insulin (weight gain differs
with type and regimen
used)
Sulfonylureas
Thiazolidinediones
Sitagliptin?
Metformin
Acarbose
Exenatide
Liraglutide
SGLT 2 inhibitors
Chronic inflammatory diseases Glucocorticoids NSAIDs
DMARDs
Pharmacologic management of obesity: an Endocrine Society clinical practice guideline 2015
?=Effect Unknown

Medications & their Effect on Weight
Indication or Class Weight Gain Weight Loss or Weight Neutrality
(Weight Reduction in Parentheses)
Antidepressants, mood stabilizers,
or tricyclic antidepressants
Amitriptyline
Doxepin
Imipramine
Nortriptyline
Trimipramine
Mirtazapine
(Bupropion)
Nefazodone
Fluoxetine (short-term)
Sertraline (<1 y)
Antidepressants, mood stabilizers,
or MAO Inhibitors
Phenelzine
Tranylcypromine
Contraceptives Injectable
progesterone
Oral progesterone
Barrier methods
Intrauterine devices
Oral contraceptives preferable to
injectable
Pharmacologic management of obesity: an Endocrine Society clinical practice guideline 2015

Conclusion
Rising concern of the
globe predisposing to
adverse consequences
such as high BP
Increase in weight is
directly associated
with increase in BP
Obesity
Highly prevalent
condition amongst
obese
Difficult to treat
condition for
clinicians
Associated with
significant resistant
hypertension
Hypertension
in Obesity
Weight reduction has
profound effect on
reduction of BP
1kg weight loss = 1.79 mm
Hg fall in BP
Consideration should be
given to effect on weight
while choosing drugs
Management

Hypertension in obesity cme

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