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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






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






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






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






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






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






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%






Diagnosis of Peripheral Arterial Disease

The Edinburgh Claudication Questionnaire

Diagnostic Studies for the Evaluation of Venous

and Arterial Disease






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






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






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






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






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






Advanced Functional Medicine Testing

Recommended Cardiovascular Functional Medicine

Tests

– Cardiovascular Health Profile (Metametrix)

– Cardio/ION Profile (Metametrix)






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

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