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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 1
Functional Diagnostic Medicine
Training Program
Mod 5 * FDMT 545A
Cardiovascular Disease:
A Comprehensive Approach to Evaluation and Management
Dr. Wayne L. Sodano
&
Dr. Ron Grisanti
Cardiovascular Disease:
A Comprehensive Functional Medicine Approach
to Evaluation and Management
2010 Update from the American Heart
Association
• 2006 overall death rate for CVD - 262.5 per 100,000
• 2300 Americans die of CVD each day
• 2006 - CAD caused approximately 1 out of 6 deaths in the U.S.
• 2003-2006 Data from NIH & NHANES - 33.6% of US adults ≥20 years have hypertension.
• 2008 - Americans ≥18 years: 23.1% men & 18.3% women continued to be cigarette smokers. Grades 9 - 12: 21.3% male students & 18.7% female students reported tobacco use.
• 2006 - Estimated 17,200,000 Americans had diagnosed diabetes; 6,100,000 had undiagnosed diabetes; 29% had pre-diabetes
• 2006 - Estimated prevalence of overweight & obesity in US adults -66.3%
• Children 2 - 19 years - 31.9% are overweight & obese
• 2008 – National Health Interview Survey: 59% of adults - no vigorous activity
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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 2
The arteries contain three layers: the intima, the media, and the adventitia.
Valve
Tunica intima
(endothelial cells)
Elastin
Tunica medic
(smooth muscle)
Anatomy of a Vein
www.google.com
The Atherosclerosis Timeline
www.images.md.com
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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 3
Manifestations of atherosclerosis include:
– TIA
– Ischemic stoke
– STEMI (ST segment elevation myocardial infarction)
– NSTEMI (Non-ST segment elevation myocardial infarction)
– Unstable angina pectoris
– Renovascular hypertension
– Erectile dysfunction
– Claudication
– Critical limb ischemia, rest pain, gangrene,
amputation
2010©CSDesigns
Endothelial Cell Smooth Muscle Cell
ADMA
L-arginine
NO Synthase
L-citrulline
O2¯
Oxidative degradation of
NO by superoxide radicals
Guanylyl
Cyclase
NO cGMP
relaxation
NO
Biochemical Pathways for Generation, Elimination, and Degradation of ADMA
Protein
with ADMA residues
hydrolysis
ADMAinhibition
NOS
NO
+citrulline
L-arginine
Renal
excretion
D
D
A
H
Citrulline +
dimethylamine
Cholesterol (ox LDL)
Homocysteine
Hyperglycemia
CMV-infection
Cigarette smoke extr.
inhibition
* DDAH = dimethylamine dimethylaminolydrolase 2010©CSDesigns
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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 4
NO
vasodilatation
platelet aggregation
monocyte adhesion
superoxide radicalrelease
smooth muscle cellproliferation
LDL oxidation
L-arginine
ADMA
NO synthase
NO
vasodilatation
platelet aggregation
monocyte adhesion
superoxide radicalrelease
smooth muscle cellproliferation
LDL oxidation
L-arginine
ADMA
NO synthase
Low
High
A.
B.
2010©CSDesigns
Pro-Inflammatory Stimuli That Trigger
Endothelial Cells
• Obesity
• Insulin resistance
• Hypertension
• Oxidative stress
• Smoking
• Hyperglycemia
• Dietary factors
• Infections
P-selectin
E-selectin
VCAM-1
ICAM-1
MCP-1
CCR-2
oxLDL
Circulating monocyte
Rolling
Firm Adhesion
Migration
Endothelial
cells
M-CSF
Macrophage
Tunica
media
Tunica
intima
2010©CSDesigns
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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 5
VLDL
ChylomicronLDL
Remnant
formationoxLDL
*LPL
Oxidation15-LO
iNOS
MPO
NADPHox
Macrophage/Foam Cell2010©CSDesigns
*Lipoprotein Lipase
↑Proinflammatory mediators,
e.g. IL-1, IL-6, TNF-α
↑Monocyte recruitment
↑LDL oxidaKon
↑MMP producKon
Lesion instability
and plaque rupture
2010©CSDesigns
Vasoconstrictors and Vasodilators
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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 6
Thrombin
SMC
Activated platelet
CRP, SAA,
Fibrinogen,
PAI-1
Il-6 Cytokines
(esp. IL-6)
CD40-ligand,
RANTES
Sampling for
biomarkers
Cytokines,
ROS, MMPs
AGE Ang II
EC
Cytokines
PAI-1
Leukocyte
adhesion
molecules
ROS
Macrophage
Cytokines
Ox LDL
Liver
2010©CSDesigns
Endothelial Activation/Dysfunction in
Arthrosclerosis
• Dyslipidemia
• Increased angiotensin II
• Insulin resistance and diabetes
• Estrogen deficiency
• Hyperhomocysteinemia
• Advanced age
• Infection
• Smoking
• Obesity
• Oxidative stress
Infectious Agents as Triggers of Inflammation in
Atherosclerosis
• Viruses
• Bacteria
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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 7
Prevalence of PAD in At-Risk Patients
The PARTNERS* program evaluated 6,979 patients in physicians’
offices. The criteria was: ≥70 years, or 50-69 years with a history
of smoking and/or diabetes
*PARTNERS = PAD Awareness, Risk, and Treatment: New Resources for SurvivalRef:Hirsh AT, et al, JAMA, 2001;286;1317-1324
Clinical Presentations of PAD
50% Asymptomatic
~15%
Classic (Typical)
Claudication
~33%
Atypical Leg
Pain
(Functionality
Limited)
1-2% Critical
Limb Ischemia
Typical vs. Atypical Symptoms in Patients With
Symptomatic PAD
Typical Symptoms
Intermittent Claudication
Exertional calf pain that
•Causes the patient
to stop walking
•Resolves within 10
minutes of rest
Atypical Symptoms
Exertional leg pain that
•May involve areas
other than the calves
•May not stop the
patient from walking
•May not resolve within
10 minutes of rest
Other nonspecific
leg symptoms that
may be indicative
of PAD
>50%
33%
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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 8
Diagnosis of Peripheral Arterial Disease
The Edinburgh Claudication Questionnaire
Diagnostic Studies for the Evaluation of Venous
and Arterial Disease
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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 9
Diagnostic Venous Tests
Diagnostic Tests Obstruction Insufficiency Location of
obstruction
Continuous Wave
Doppler
+ + +/-
Duplex Ultrasound + + +
Plethysmography + +
D-dimer +*
Contrast
Venography
+ + +
MRI + +
* Acute DVT only
Diagnostic Arterial Testing
Diagnostic Test Skin
perfusion
Patency Determine
location
stenosis/
obstruction
Evaluate
aneurysm
Monitor
disease
progression
Accurate in
presence of non-
compressible
calcified arteries
ABI + + -
Segmental
pressures+ +/- + -
Continuous wave
doppler+ + + +
Pulse volume
recording
+ + +
Photo-
plethysmography
+ +/- +
Transcutaneous
Oximetry [Tc PO2]
+ + +
Duplex scan + + + + +
Computer
tomography+ + + + + +
MRA + + + + +
Contrast
angiography+ + + + +
Review of Doppler Waveforms
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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 10
-
FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 11
Hypertension
Systolic pressure is governed by:
– Cardiac action
– The elasticity and distensibility of conducting arteries
– Arteriosclerosis - Loss of distensibility → increase systolic
pressure
Diastolic pressure is maintained by:
– Resistance (TONE) of arterioles
– Blood viscosity
Angiotensinogen
Angiotensin I
Angiotensin II
ReninDecreased
renal
perfusion ACE
(lung & kidney)
↑SympatheKc
nervous
system
Aldosterone
secretion
[NACL resorption]
[K+ excretion]
[H2O retention]
vasoconstriction ADH secretion
H2O absorption
2010©CSDesigns
Renin-Angiotensin-Aldosterone System
Hormone and Other Chemical Messengers that
Affect Blood Pressure
• Epinephrine and norepinephrine
• Aldosterone
• Antidiuretic Hormone
• Angiotensin II
• Nitric Oxide
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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 12
Classification and management of blood pressure for adults*
BP ClassificationSBP*
mmHg
DBP*
mmHg
Lifestyle
Modification
Initial Drug Therapy
Without Compelling
Indication
With Compelling
Indications (See Table 8)
Normal
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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 13
Laboratory Tests
Considerations for CVD (including hypertension)
• CMP
• GGT
• Complete blood count and examination of
peripheral blood smear
Lipid profile
Chylomicron VLDL LDL HDL
% Protein 1.5 – 2.5 5 - 10 20 - 25 40 – 55
%Phospholipid 7 - 9 15 - 20 15 - 20 20 – 35
%Cholesterol 1 - 3 5 - 10 7 - 10 3 – 4
%Triacylglycerol 84 - 89 50 - 65 7 - 10 3 – 5
%Cholesteryl ester 3 - 5 10 - 15 35 - 40 1 - 2
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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 14
Lipoprotein (a)
• Is a lipoprotein subclass
• Is a low-density lipoprotein, LDL-like particle
with a cholesterol rich core and a molecule of
apolipoprotein B linked by a disulphide bridge
to apolipoprotein A.
• Completes with plasminogen for binding sites
on the cell surface, decreasing plasminogen
activation and inhibiting clot lysis.
• VAP Test
• Urinalysis
• hs-CRP
• Ferritin
• Homocysteine
• Fibrinogen
• Vitamin D
• Vitamin K
• Testosterone
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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 15
Advanced Functional Medicine Testing
Recommended Cardiovascular Functional Medicine
Tests
– Cardiovascular Health Profile (Metametrix)
– Cardio/ION Profile (Metametrix)
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FMD Training Program: FDMT 545A: Cardiovascular Disease: A Comprehensive Approach to
Evaluation and Management
Wayne L. Sodano, D.C., D.A.B.C.I. & Ron Grisanti, D.C., D.A.B.C.O., M.S.
©Sequoia Education Systems, Inc.
http://www.FunctionalMedicineUniversity.com 16
Minerals
• Salt (sodium chloride)
• Potassium Deficiency
• Calcium Deficiency
• Magnesium Deficiency
Specific Cardiovascular Disease Treatment
Considerations
• High Triglycerides
• High Total Cholesterol
• High LDL
• High Lipoprotein (a)
• Low HDL
• High Fibrinogen
In Summary