Cleveland HeartLab 2013 Symposium

1. Case Study Speakers
Carlos Jorge, MD
Dharmesh Patel, MD, Atul Sachdev, MD Amy Doneen, RN,
FACC
BSN, MSN, ARNP

2. NBC’s Tim Russert dies at 58
•
Russert was recording
voiceovers when he
collapsed.
•
Previously diagnosed
with asymptomatic
coronary artery
disease.
Dr. Michael Newman (Russert’s physician) said his
disease was “well-controlled with medication and
exercise, and he had performed well on a stress test.”

3. When asked if he thought he could have done more,
Dr. Newman replied…
“You know, as physicians, we always hope
that we can change people's lives, that we
can make them feel better, live longer,
that we can intervene, and that's what our
role is. Unfortunately, in many instances,
our hopes are not fulfilled. Absolutely, I
wish Tim was alive and with us today. ...
And ... patients die of heart disease or
cancer; we
all struggle with the
fact there are limits to what
we can do.”
Dr. Newman on
The Larry King Show

4. Carlos Jorge, MD
Ballantyne Medical Associates
Medical School
Universidad Nacional Pedro
Henriquez Urena School of Medicine
(UNPHU), Santo Domingo,
Dominican Republic , Doctorate of
Medicine, 1999
Board Certifications
Family Practice
Clinical Lipidology
Memberships
National Lipid Association
American Medical Association
North Carolina Academy of Family
Physicians
North Carolina Medical Society

5. Patient Compliance
• What percentage patients are not compliant
in taking their medications?
a) 35%
b) 40%
c) 75%
d) 55%
Source: PhRMA 2011

6. Patient Compliance
• What percentage patients are not compliant
in taking their medications?
a) 35%
b) 40%
c) 75%
d) 55%
75%
Source: PhRMA 2011

7. “Drugs don’t work in patients
who don’t take them.”
- - C. Everett Koop, MD

8. America’s other drug problem
Each year $290 billion is spent
on avoidable medical costs due
to medication non-adherence
Hospitalizations (33-69%)
Preventable adverse drug events (21%)
Deaths (125,000/year)
Gurwitz J et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA.
2003; 280 (9): 1107-1116.
McCarthy R. The price you pay for the drug not taken. Bus Health. 1998; 16(10): 27-33.
Adapted from a presentation by Crowe, M. “I never miss a dose”: Medication adherence for the practice of pharmacy. 2012

9. Key Learning Points
 LDL/Apo B are important but may not tell the
whole story
 MPO elevations – over other biomarkers –
elucidate further risk and allow for adjustment of
evaluation and compliance

10. Initial Presentation
A 55 y/o Hispanic female initially
presented to my office in October
of 2011 for a wellness visit
Medical History
• Non-smoker and non-drinker
• History of hyperlipidemia, hypothyroidism, HTN, and
pituitary adenoma (2008)
• Mother – Breast cancer and CAD (deceased)
• Father – Type II Diabetes (living)

11. Current Medications
Biometrics
Taking inconsistently
• Simvastatin 20 mg
Height 5’0
Taking consistently
• Aspirin 81 mg/daily
• Toprol XL 50 mg
• Lisinopril/HCTZ 20/12.5 mg
• Synthroid 50 mcg
• Vitamin D3 1000 IU
BMI
36.3
HR
68
BP
122/70
Weight 186

12. Initial Results--10/21/2011
Lipids
Inflammation
Metabolic
TC
171
HbA1c
LDL-C
89
HDL-C
40
Fasting
99
Glucose
TG
212
VLDL-C
42
ApoB
84
Lp(a)
19
6.0
hsCRP
4.5
Lp-PLA2 <100

13. Treatment Options
 Counseled on diet/metabolic syndrome,
exercise, weight loss and to continue taking all
her medications.
 Instructed to return to the office for a CIMT and
2hr. GTT

14. Follow-Up Results
• She did not schedule or
follow-up for her 2hr. GTT
• She returned for her CIMT
3 months later (1/10/2012) CIMT
Vascular age
– no discernible plaque
Max IMT
(Right CCA)
61
0.9

15. Follow-Up Results
• Unfortunately, patient did not return to the office
until 10 months later--11/26/12
– She mentioned she had been trying to
improve her diet and started walking
– She stopped taking her Simvastatin 3 months
prior to the visit b/c she ‘felt her diet had
improved so much’
Ok – Well let’s find out if how she’s
doing with ‘her regimen’…

16. Follow-Up Results--11/26/2012
Biometrics
Initial Results Follow-Up Results
Height
5’0
--
Weight 186
189
BMI
36.3
36.9
HR
68
74
BP
122/70
116/82
• No significant change in her biometrics

17. Follow-Up Results--11/26/2012
Lipids
Initial Results Follow-Up Results
TC
171
232
LDL-C
89
160
HDL-C
40
48
TG
212
120
VLDL-C 42
ApoB
84
Lp(a)
132
19
• Marked improvement in TGs and HDL-C, but worsening of
TC, LDL-C, and Apo B

18. Follow-Up Results--11/26/2012
Metabolic
Initial Results
Follow-Up Results
HbA1c
6.0
5.9
Fasting Glucose
99
101
Inflammation
Initial Results
Follow-Up Results
hsCRP
4.5
--
Lp-PLA2
<100
144
MPO
285
• Worsening of fasting glucose, HbA1C stable

19. Treatment Options
 We reviewed metabolic syndrome/lipid concerns
and counseled her on TLC
 Re-instituted her Simvastatin (20 mg/daily) along
with her other meds
 Re-scheduled her for a 2hr GTT
What do you think happened?

20. Follow-Up Results--7/02/2013
• She once again doesn’t schedule an
appointment or follow-up for her 2hr. GTT
• She returned 8 months later
– States the medicines were not helping her and she
could work on her diet, exercise and weight loss
– Stopped taking Simvastatin 3-4 months prior
– Only came back in to get her thyroid checked
– And…she was having sternal chest pain with twisting
and movement

21. Follow-Up Results--7/02/2013
• No diaphoresis, no dyspnea, no SOB, no n/v,
no jaw or arm pain, no dizziness, no increased
thirst, no HA, no weakness, no polydipsia or
polyphagia
• Reproducible chest wall tenderness over the
L- sternal border
• ECG NSR no ST-T segment changes

22. Follow-Up Results--7/02/2013
Biometrics
Initial Results Follow-Up Results
Height
5’0
--
--
Weight
186
189
192
BMI
36.3
36.9
37.5
HR
68
74
80
BP
122/70
116/82
122/78
• Weight is not improving - - Her ability to control her
diet is not working

23. Follow-Up Results--7/02/2013
Lipids
Initial Results
11/26/12
7/02/13
TC
171
232
208
LDL-C
89
160
140
HDL-C
40
48
42
TG
212
120
131
VLDL-C
42
--
ApoB
84
132
Lp(a)
19
--
120
• TC, LDL-C, and Apo B all improved OFF simvastatin- Maybe her diet has helped?!

24. Follow-Up Results--7/02/2013
Inflammation
Initial Results
11/26/12
hsCRP
4.5
--
Lp-PLA2
<100
7/02/13
144
MPO
285
1913
• Gene expression test for CAD done--score 3; likelihood
of CAD 10%
• Sent her immediately to cardiology colleague where she
underwent a Lexiscan Nuclear Stress Test
– No evidence of myocardial ischemia
– Normal regional wall motion (EF 79%)

25. Treatment Options
 Re-instituted her Simvastatin (20 mg/daily) - again - - and stressed the importance of taking
her aspirin
 Medical management in coordination with
cardiology
What are the next steps?

26. Follow-Up Results--7/11/2013
• Called her for follow-up approximately 1 week
later
– Feels good
– No CP, SOB, diaphoresis, N/V or other sx’s
• Of course, I reminded her about her 2 hr. GTT
and she finally schedules it for 1 month later!

27. Follow-Up Results--7/11/2013
Inflammation
Initial Results
11/26/12
hsCRP
4.5
<100
7/11/13
--
Lp-PLA2
7/02/13
144
MPO
285
1913
• Rechecked her MPO and it’s still elevated
• She returned 1 month later for the 2hr GTT
1553

28. Follow-Up Results--8/27/13
Metabolic
Initial Results
Follow-Up Results
HbA1c
6.0
5.9
Fasting
Glucose
99
101
2 hr. GTT
133/183/159
• Abnormal 2hr. GGT warrants diagnoses of insulin
resistance and diabetes

29. Follow-Up Results--8/27/13
Inflammation
Initial Results
Follow-Up Results
hsCRP
4.5
--
Lp-PLA2
<100
144
MPO
285
1913
1553
• Again, rechecked her MPO and it’s still elevated
846

30. Treatment Options
 We again stressed and reviewed all her risk
factors, diet, exercise, weight and importance of
ALL medications being taken
 Started on Metformin 1000mg
 Sent back to cardiology for further evaluation of
CAD
How did we do?

31. Follow-Up Results
• She of course did not go to the cardiology
follow-up.
• She has a follow up scheduled with me on
10/29/13

32. Conclusions
 Patient compliance with medications or for office
visits is difficult to control
 Biomarker elevations - especially in light of
“improving” Apo B and LDL should guide further
investigation and “encourage” patients to
comply
 Admittedly given her MPO elevations she still is
at high risk--ideally would have loved to get a
CT angio or cath--cost prohibitive??

33. Key Learning Points
 Aggressively exploring and managing her
insulin resistance/diabetes needed to decrease
inflammatory pathway
 High risk for CV event in spite of “normal” gene
expression test for CAD—possible because of
her insulin resistance?

34. Dharmesh Patel, MD, MBBS, FACC
Chief Medical Officer | HASPA
Stern Cardiovascular Foundation
Medical School
Guy’s & Kings College Hospital Medical School
(London), Medicine MBBS 1996
Board Certifications
Diplomate, American Board of Clinical
Lipidology
Certification, Specialist Clinical Hypertension
Adult Cardiac Echocardiography
Nuclear Cardiology
Cardiac CT Angiography
Cardiovascular Medicine
Internal Medicine
Memberships
American College of Cardiology
American Heart Association (Speaker for Women
and Heart Disease)
National Lipid Association
American Society of Hypertension

35. Initial Presentation
A 75 y/o male referred due to an
abnormal lipid profile
Medical History
•
•
•
•
Former smoker (quit ~50 years ago)
History of HTN, hyperlipidemia, diabetes
Normal carotid ultrasound (12/2012)
Echocardiogram (12/2012) – EF ~60%, type 1 relaxation
abnormality pattern, aortic valve sclerosis, mild aortic insufficiency
• Family history of CAD (Mother, 70s)

36. Current Medications
Biometrics
•
•
•
•
•
•
•
Height 6’1”
Livalo 2mg qhs
Niaspan 1000 mg qhs
Amlodipine Besylate 5 mg qd
Benazepril 10mg qd
Aspirin 325 mg
Vitamin D
Fish Oil 1200 mg
Weight 288
BMI
38
HR
86
BP
142/66

37. Initial Results
Lipids
Inflammation
Initial Results
Initial Results
TC
128
hsCRP
47.5
LDL-C
60
MPO
856*
HDL-C 50
TG
84
Lp(a)
42
ApoB
53
*Up from 350

38. The plot thickens ………
• History of Malignant
Melanoma
• Surgical Removal 10
years ago

39. Treatment Options
• Do nothing?
• CIMT score
• PET/Chest CT scan
• Stress Thallium
• Cardiac catheterization

40. CIMT score
CIMT in association with a calcified plaque in a 75 year old
male with CAD. The presence of plaque increases the
diagnostic significance of CIMT. Arterial age 82 years old.

41. Stress thallium

43. Stress thallium
Stress
•
•
•
•
•
Thallium
6 minutes Bruce protocol
6.9 Mets achieved
No chest pain
2mm horizontal STD in the inferior leads
Thallium images show no reversible ischemia
but moderate sized fixed defect in the inferior
wall

44. Catheterization – Frame 3

45. Catheterization – Frame 6

46. Catheterization – Frame 9

47. Catheterization – Frame 10

48. Cardiac Catheterization Results
• EF 60%
• EDP 10mmHg
• 30% stenosis proximal L anterior
descending artery, 80% first diagonal artery
• R coronary artery completely occluded with
left-to-right collateral flow

49. Complete Blood Count
15.9
7.8
212
43.8
Lymph 23.4%
Mono 8.5%
Eos
1.8%
Baso 0.7%

50. CT Chest and Abdomen

51. Treatment Options
• Hyperlipidemia status acceptable and
inflammation biomarkers extremely elevated
– F/U with dentist
– CT of chest with contrast to rule out recurrence of malignancy
– PSA and CBC with diff. to rule out malignancy
• Obtain exercise thallium study to rule out cardiac
ischemia
– At risk of events/recurrence of events
• Obtain 2hr. OGTT to rule out insulin resistance

52. Treatment Plan
• Patient has documented CAD and complete
occlusion of right coronary artery
– Will prescribe beta blockers for cardiac
prevention
• Hyperlipidemia under NCEP III guidelines
– Recommend optimal LDL of <70 mg/dL
• ASA 81mg-162mg ( already on it )
• ACE Inhibitors/ ARB ( already on it)
• Diet and exercise

53. Key Learning Points
 Additive information gained above and beyond
standard lipid guidelines
 Increased hsCRP and MPO increases risk of
cardiovascular event
 Rule out insulin resistance/diabetes
 Evaluate for dental disease
 Caution regarding history of malignancy

54. Atul Sachdev, MD
Primary Care Physician
Medical School
University of Texas Health Science
Center, Doctorate of Medicine, 1995
Board Certifications
Family Practice
Memberships
Association of American Physicians
and Surgeons
American Academy of Family
Practice
American Medical Association
Texas Medical Association

55. Initial Presentation
A 62 y/o Asian male
presented to my office for an
Annual Wellness Exam
Medical History
•
•
•
•
History of hypercholesterolemia and diabetes
Carotid disease confirmed by CIMT
Family history of HTN, stroke and diabetes
Never-smoker

56. Current Medications
•
•
•
•
•
Simvastatin 20 mg QD; 2 years
Ramipril 5 mg QD; 10 years
Lovaza 2g BID; 1 year
Actos 30 mg QD; 5 years
Declined ASA previously
Biometrics
Height 5’5”
Weight 130
BMI
21.6
BP
106/70
Waist
35.5

57. Initial Results
Lipids
Inflammation
Metabolic
F2-IsoPs 0.29
TC
196
HbA1c
LDL-C
108
HDL-C
65
Fasting
114
Glucose
Non-HDL-C
131
Lp-PLA2 146
TG
140
MPO
ApoB
85
ApoA1
176
Lp(a)
7.0
HDL2b
15
7.1
MACR
23.0
hsCRP
0.9
259
• Some lipid abnormalities
• Suboptimal control of diabetes
• Endothelial dysfunction as
evidenced by an abnormal MACR

58. Treatment Options
 Counseled patient on lifestyle adjustments
including diet and exercise
 Recommended ASA, but he declined

59. Follow-Up Results
Biometrics
Initial Results Follow-Up Results
Height
5’5”
5’5”
Weight 130
126
BMI
21.6
21.0
BP
106/70
106/70
Waist
35.5
35
• Some weight loss, but no other significant changes

60. Follow-Up Results
Lipids
Initial Results Follow-Up Results
TC
196
193
LDL-C
108
122
HDL-C
65
51
Non-HDL-C
131
142
TG
140
87
ApoB
85
92
ApoA1
176
150
Lp(a)
7.0
11.0
HDL2b
15
11

61. Follow-Up Results
Metabolic
Initial Results Follow-Up Results
HbA1c
7.1
6.6
• Improvement in glycemic status – patient
appeared to be motivated by truly watching his
diet as recommended.

62. Follow-Up Results
Inflammation
Initial Results
Follow-Up Results
F2-IsoPs
0.29
0.18
MACR
23.0
11.2
hsCRP
0.9
1.1
Lp-PLA2
146
135
MPO
259
495

63. Treatment Options
 Recommended ASA again, and he agreed to
consider
 A paradoxical increase in MPO levels
– Sample handling
– Vasculitis
– Bone marrow dyscrasias
– RA/SLE
– Periodontal disease

64. PD should be assessed and treated in
programs designed to maintain CV wellness
Level A evidence that Periodontal Disease
is associated with arterial disease
Available evidence shows a trend toward
reducing CV risk with the therapy of PD
Peter B. Lockhart, et. al. Circulation published online April 18, 2012
DOI: 10.1161/CIR.0b013e31825719f3
Copyright Bale/Doneen Paradigm

65. Periodontal Disease
Calculus & plaque accumulation
Space between teeth due to loss
of bone support & gum recession
Red swollen gums
Root exposure due to
plaque & receding gums
Humphrey LL et al. Periodontal disease and coronary heart disease incidence: A systematic review and meta-analysis. J
Gen Intern Med. 2008; 23 (12): 2079-2086.

66. Periodontal Disease
• What percentage of the American population
is affected by periodontal disease?
a) 15%
b) 25%
c) 30%
d) 50%
Eke PI et al. Prevalence of Periodontitis in Adults in the United States: 2009 and 2010. J Dent Res. 2012; 91: 907-908

67. Periodontal Disease
• What percentage of the American population
is affected by periodontal disease?
a) 15%
b) 25%
c) 30%
d) 50%
50%
Eke PI et al. Prevalence of Periodontitis in Adults in the United States: 2009 and 2010. J Dent Res. 2012; 91: 907-908

68. Eke PI et al. Prevalence of Periodontitis in Adults in the United States: 2009 and 2010. J Dent Res. 2012; 91: 907-908

69. The Cross-Reactivity Hypothesis
Periodontal Bacteria
Local Immune Response
Cross-Reactivity with
Vascular Endothelium
Vascular Inflammation
Adapted from Seymour GJ et al. Infection or
inflammation: The link between periodontal disease and
systemic disease. Inside Dentistry. Volume 2 (Special
Issue 1).
Wick G, Perschinka H, Xu Q. Autoimmunity and
atherosclerosis. Am Heart J. 1999; 138:S444-S449.
Atherosclerosis

70. Treatment Options
 Patient was referred to a dental specialist who
performed testing and confirmed the presence
of periodontal disease
 Patient was treated with Clindamycin (Cleocin)
and given hygiene instructions by dentist.
 Patient asked to return in 3 months, but took
extended trip to India and didn’t return until 7
months later.

71. Follow-Up Results
Inflammation
Initial Results
Follow-Up Results
F2-IsoPs
0.29
0.18
0.43
MACR
23.0
11.2
54.2
hsCRP
0.9
1.1
0.9
Lp-PLA2
146
135
152
MPO
259
495
226
• Treatment of periodontal disease reduced MPO
levels and subsequent vascular risk

72. Follow-Up Results
Lipids/Metabolic
Initial Results
Follow-Up Results
TC
196
193
200
LDL-C
108
122
114
HDL-C
65
51
71
Non-HDL-C
131
142
129
TG
140
87
62
ApoB
85
92
79
ApoA1
176
150
195
Lp(a)
7.0
11.0
9.0
HDL2b
15
11
12
HbA1c
7.1
6.6
7.6

73. Treatment Options
• States he WILL start ASA QD (we’ll see).
• Increase Ramipril to 10mg (HOPE trial)?
• Switch to Rosuvastatin (JUPITER trial)?
• LDL goal <70
• Stay on top of dental hygiene.
• Recheck CIMT, ABI, AAA screen, etc.
• Continue monitoring vascular inflammation!

74. Key Learning Points
 Vascular inflammation testing can help identify
unexplained inflammation
 Periodontal disease is a documented cause of
vascular inflammation
 Appropriate periodontal measures can lead to
CV risk reduction

75. Amy Doneen, RN, BSN, MSN, ARNP
Medical Director, Heart Attack and Stroke Prevention
Center, Spokane, WA
Graduate School/NP/ARNP
Bachelors of Science, Masters of Nursing
Practice & Advanced Registered Nurse
Practitioner Family Practice (Suma Cum Laude)
Gonzaga University, Spokane, WA, 2002
Doctorate of Nursing Practice, Gonzaga
University, Spokane, WA, Current
Memberships
National Lipid Association
American Heart Association
American Stroke Association
American Diabetic Association
American Medical Association
Preventative Cardiology Nursing Association

76. “Pneumonia? Really?” Juli
Copyright Bale/Doneen Paradigm

77. “I went to the emergency room and I was
surprised to find out that I had pneumonia with
no fever, no cough, no respiratory symptoms”
October 6, 2011
October 7, 2011
October 13, 2011
Shortness of breath
w/ fatigue
Shortness of breath
& fatigue worse,
anxiety
Went in again –
FINALLY Echo,
EKG, CXR, Abd CT
Diagnosed with MI
10/7 and 10/13
GP: Pneumonia, no
CXR, no blood
work, no EKG
Copyright Bale/Doneen Paradigm
ER: Given different
antibiotic – sent
home with cough
med, “but I wasn’t
coughing”
CT Angiogram :
Angioplasty,
medical
management

78. Symptoms: Women are unique
Prior to a heart
attack
At time of a heart
attack
•Unusual fatigue
•Sleep disturbance
•Unexplained anxiety
•Shortness of breath
•Abdominal pain
•Sweating
Copyright Bale/Doneen Paradigm

79. Initial Presentation
A 37 y/o Caucasian female
and mother of a 3 y/o
daughter
Initially presented to the
Heart Attack and Stroke
Prevention Center on
11/25/2011 - nearly a month
after experiencing multiple
heart attacks.

80. Current Medications
• Metoprolol 25 mg BID
• Simvastatin 40 mg daily
• Aspirin 81 mg daily
• CoQ10 100 mg
• Omega-3 2 gm daily
Biometrics
Height 5’6”
Weight 153
BMI
24.7
Waist
37
Why does Juli have heart disease?

81. There is a better way!
Bale/Doneen Method: EDFROG
•
•
•
•
•
•
E – Education
D – Disease
F – ‘Fire’ Arterial Inflammation
R – Root Causes
O – Optimal Goals
G – Genetics

82. “How come I was fine one day and not
the next day?”
Lumen
Thrombus
Plaque

83. Juli and Red Flags
Migraine
PCOS
Pre-eclampsia

84. Middle-age females who have migraine
with Aura (MWO) are at increased risk
for late-life brain infarcts
• 4689 subjects; 57% female; mean age 51 when surveyed for
HA; approx. 26 yrs. later MRIs of brain MWO > 1/mo. in 361
subjects
• Prevalence of infarct in women: 23% MWO; 14.5% non-MWO
• OR for women to have late life brain infarct if they have midlife MWO: 1.9 (95% CI 1.4-2.6)
• Mid-life MWO women reported more CAD or TIA/Strokes than
non-MWO women
Scher, A. I., JAMA. June 24th, 2009,
Vol. 301, No. 24:2563-2570.

85. Women with polycystic ovaries are at
higher CV risk
• Women with the hallmark symptoms of polycystic ovary
syndrome (PCOS) hirsutism and oligomenorrhea may also be
at higher risk of cardiovascular disease
• Women with PCOS may be at risk for early-onset
cardiovascular disease. Based on these findings, women
who suffer from PCOS should be closely monitored for CVD
risk factors.”
Taponen S et al. J Clin Endocrinol Metab 2004 May; 89:2114-2118.
Boulman N et al. J Clin Endocrinol Metab 2004 May; 89:2160-2165.

86. PCOS may place women at higher CV risk
• Women with PCOS may be at increased risk for CAD and
stroke
• Polycystic ovary syndrome is probably the most common
hormone disorder in human beings. One of my concerns is
that many women will be frightened to hear that they have
abnormal arteries.
• PCOS appears to be an important risk factor for
cardiovascular disease in women.
2002; 106:DOI:10.116101.CIR.0000020681.19400.8A

87. Pre-eclampsia an indicator of increased
CV risk
• Meta-analysis: 200,000 pre-eclampsia versus
3.3 million without
• Pre-eclamptics had doubling of risk of CHD &
stroke in 10 to 12 years and venous
thromboembolism in 4 to 5 years
• Pre-eclamptics need CV risk assessment 3 to
6 mos. after delivery
BMJ, doi:10.1136/bmj.39335.385301.BE 11/1/2007

88. Vit D
I.R
Genetics
Oral
Health
Lipids
Psycho
social
Lipo(a)

89. Initial Results
What caused Juli’s disease?
Metabolic
Lipids
Lp(a)
34
Met Synd
0/5
TC/HDL
2.6
TG/HDL
0.8
FBS
94
HbA1c
4.8
Insulin
5
OGTT
1 hr. 130 2 hr. 97
Inflammation
MPO
344

90. Initial Results (cont’d)
Misc. tests
Vitamin D, 25 OH
16
KIF6
Negative
ApoE
3/4
9p21
Positive
Anxiety: Yes; with hx eating disorder
Sleep, dental, nicotine: No

91. Initial Results (cont’d)
Inflammation
Oxidation
F2-Isoprostanes 0.2
Endothelial
hsCRP
1.3
Microalb/creat
11.0
Intima
Lp-PLA2
204
MPO
344

92. MACR cut points for marking increased
CV risk
Risk when MACR >7.5 in women and >4.0 in men
End point
Hazard ratio
CV event
2.92
p
<0.001
Fram. Offspring healthy pts. ; mean age 55; 58% women
Followed 6 yrs.
Ärnlöv J et al. Circulation 8/16/2005; 112:969-975.

93. Fire makes the cat jump!
hsCRP >1.0
MACR >7.5
Lp-PLA2 >180

94. Cardiovascular disease and recidivism
50% of annual major coronary events are
recidivistic
50% of these recurrent events are fatal
Briffa, T. G., & Tonkin, A. (2013). Put Disease Prevention First. Circulation,
128(6), 573-575.

95. Copyright Bale/Doneen Paradigm

96. How can we follow
Juli’s disease?

97. Initial cIMT Report:
Carotid Intima-Media Thickness Testing
Mean CCA IMT
0.508 mm = age match
Plaque
Right internal 1.26 mm (soft/het)
Left internal
1.05 mm (het)

98. Echolucent (Soft) carotid plaque predicts
coronary event risk
•
•
•
•
•
215 stable CAD patients; followed monthly X 30 months
or until an event
112 had echolucent (soft) plaques
29 coronary events
103 without soft plaques
4 coronary events
Presence of soft carotid plaques associated with higher
risk of coronary events – p<0.001
11 strokes – 10 in group with soft plaque
Honda O, et.al. Journal of ACC. 2004:43(7):1177-1184.

99. Arterial inflammation precedes calcification
• 137 pts; age-61±13 yrs; 48.1% men; serial PET/CT scans
1–5 yrs apart; thoracic aorta focal arterial inflammation was
prospectively (baseline) determined by PET/FDG
• A blinded investigator evaluated calcium deposition on the
baseline and follow-up computed tomographic scans along
the same standardized sections of the aorta.
• A vascular segment was classified as either with or without
subsequent calcification.
Abdelbaky, A., et. al. (2013). Focal Arterial Inflammation Precedes Subsequent Calcification in the Same
Location: A Longitudinal FDG-PET/CT Study. Circulation: Cardiovascular Imaging, 6(5), 747-754.

100. Arterial inflammation precedes calcification
• Across all patients, subsequent Ca deposition was
associated with the underlying inflammatory signal
• Measured as standardized uptake value with OR
of 2.94 (95%CI-1.27-6.89) 0.01– adjusted for CV
risk factors.
• First-in-human evidence that arterial inflammation
precedes subsequent Ca deposition.
Abdelbaky, A., et. al. (2013). Focal Arterial Inflammation Precedes Subsequent Calcification in the Same
Location: A Longitudinal FDG-PET/CT Study. Circulation: Cardiovascular Imaging, 6(5), 747-754.

101. Arterial inflammation precedes calcification
Inflammation is an important driver of plaque
progression.
•Human studies have shown that high aortic and
carotid FDG uptake is related to subsequent risk of
plaque rupture and clinical events.
Abdelbaky, A., et. al. (2013). Focal Arterial Inflammation Precedes Subsequent Calcification in the Same
Location: A Longitudinal FDG-PET/CT Study. Circulation: Cardiovascular Imaging, 6(5), 747-754.

102. Arterial inflammation precedes calcification
Baseline (PET) and sequential (CT) images of incident calcium deposition.
Abdelbaky, A., et. al. (2013). Focal Arterial Inflammation
Precedes Subsequent Calcification in the Same Location:
A Longitudinal FDG-PET/CT Study. Circulation:
Cardiovascular Imaging, 6(5), 747-754.

103. Juli’s missing diagnoses could have led
to a recidivistic event
• The mortality rate among women aged 35 to 44 has
been increasing on average by 1.3% per year since
1997.
Julie’s missing diagnoses
1. Insulin resistance
2. lipo(a)
3. Vitamin D deficiency
4. Apo E 4
5. KIF 6 negative
6. Anxiety
7. 9p21 positive
Roger, V. L., et al. Heart disease and stroke statistics—
2011 update. Circulation 12/15/2010;
DOI:10.1161/CIR.0b013e3182009701
.

104. Treatment options
 Disease treatment paradigm
• Statin – Is her simvastatin an ok option?

105. Clinical significance of KIF6 testing
KIF6 carriers- may have higher life time CV risk
1. Maintain a disease treatment platform. (EDFROG)
2. Any statin is beneficial
KIF6 noncarriers
1. Still can be at risk: monitor for disease
2. May want to favor statin therapy with simva or rosuva

106. Treatment options
 Disease treatment paradigm
• Juli is of childbearing age
• Currently using IUD
• Would like to have another child – council
 Statin: Continue with simvastatin 40mg
 Aspirin 81 mg: f/u testing shows effective
 ACE-I: Prevent recidivism! (concern: preg)
 Omega-3: Fish daily or supplement 1 gm/d

107. Treatment options
 Root causes
• Insulin resistance
• Goal: Try to treat with lifestyle – exercise and nutrition counseling.
LIFESTYLE to TREATMENT
• If treatment necessary, consider metformin (preg), *Pioglitazone
• Fine tune: Consider metoprolol to carvedilol for IR
• Vitamin D deficiency
• Goal: Supplement to levels 40-60 ng/dL
• Lp(a)
• Add: Niacin therapy at 1000-1500mg/day
• Anxiety with history of eating disorder
• Counseling for nutrition and anxiety

108. What to follow to know if treatment is
working?
•
•
•
•
•
•
Risk Factor improvement - lipid, IR, Lp(a), Vit D
Inflammation improvement/stability
Heart Muscle – NT-ProBNP (baseline 266)
Fitness – emotional, sleep, diet recall, fear
Disease – monitor cIMT
Safety – liver, kidney, electrolytes, etc.
Honda O, et.al. Journal of ACC. 2004:43(7):1177-1184.

109. Follow-Up Results
Lipids
Baseline
Year One
2/4/2013
TC/HDL
2.6
2.2
2.1
ApoB
60
59
50
Lp(a)
34
33
21
266
194
159
Cardiac
NTproBNP

110. Follow-Up Results
Metabolic
Baseline
FBS
94/4.8
OGTT
Year One
89/5.2
130/97
2/4/2013
85/5.1
Due for repeat
Inflammation
hsCRP
1.3
0.5
37.6**
MACR
11.0
10.0
10.0
Lp-PLA2
204
154
287**

111. Periodontal disease associated with
elevated levels of Lp-PLA2
• 421 healthy adult family members of pts hospitalized with
CVD
• Screened for traditional CV risk factors including hsCRP
and Lp-PLA2
• Those with periodontal disease were 1.8 times more
likely to have Lp-PLA2 levels >215 ng/mL
• 37% of individuals with no CV risk factors except
periodontal disease had elevated Lp-PLA2
Am J Cardiol 12/1/2008; 102:1509-1513

112. Oral pathogens and acute heart attack
• 101 acute heart attack pts; 76% male; ~63 yo
• Oral viridans streptococci found in 78% of
thrombi; PD pathogens found in 35% of thrombi
Pessi, T., PhD, et. al. Circulation. published online February 15, 2013
http://circ.ahajournals.org/content/early/2013/02/14/CIRCULATIONAHA.112.001254

113. Oral pathogens and acute heart attack
• 30 pts had panoramic CT imaging
• ~50% showed periapical abscess
• If patients thrombus was positive for strep viridans
DNA, they were 13 times more likely to have a
periapical abscess
OR 13.2 (95% CI 2.11 – 82.5) p=0.004
Pessi, T., PhD, et. al. Circulation. published online February 15, 2013
http://circ.ahajournals.org/content/early/2013/02/14/CIRCULATIONAHA.112.001254

114. Oral pathogens and acute heart attack
• Electron microscopy performed on 9
thrombi
• Bacteria-like structures detected in all 9
thrombi
• Whole bacteria in 3/9 (1/3)
• Dental infection and oral bacteria are
associated with the development of
acute coronary thrombosis
Pessi, T., PhD, et. al. Circulation. published online February 15, 2013
http://circ.ahajournals.org/content/early/2013/02/14/CIRCULATIONAHA.112.001254

115. Treatment options/changes
 Appointment 2/4/2013
 Changes:
• Sent to dentist – Painful tooth (root canal &
Antibiotics 2/12/2013)
• Change to Rosuvastatin 10mg and increase
Niaspan to 1500 mg
• Next appointment: 3/5/2013 to recheck
inflammatory markers, liver and CK.

116. Follow-Up Results
Endodonic Tx – Root canal and ABO
Inflammation
2/4/2013
3/5/2013
5/7/2013 8/8/2013
hsCRP
37.6
3.2
1.8
0.7
Lp-PLA2
287
236
218
202
Improvement of hsCRP and Lp-PLA2
results following root canal, increase in
Niaspan and change to Rosuvastatin

117. Follow-Up Results
Carotid Intima-Media Thickness Testing
12/7/2011
Mean CCA IMT
0.508 mm
12/3/2012
0.530 mm
Plaque
Right internal
1.26 mm (soft/het)
Left internal
1.05 mm (het)
<0.6 mm

118. Juli’s next journey: Living with heart disease
• Planning to have another baby
• So – the journey continues…..
– Working with Perionatologist, Cardiologist,
myself and her OBGYN – Juli remains on the
following medications: baby aspirin, Omega 3,
Niacin, Vitamin D, Metoprolol, Prenatal Vitamin
– She is OFF HER STATIN and ACE-I
– She is HIGH RISK – Inflammatory labs
frequently
• On September 17, 2013: + Pregnancy Test
Honda O, et.al. Journal of ACC. 2004:43(7):1177-1184.

120. Initial Presentation
A 62 y/o male district
superintendant referred for
abnormal labs
Medical History
• History of HTN, obesity, hyperlipidemia
• BP difficult to treat
• Fatigue

121. Initial Results
Current Medications
Biometrics
•
•
•
•
Height 5’10”
Valsartan-HCTZ 320/25
Amlodipine
Toprol XL 25 mg
ASA 81 mg
Weight 267
BMI
38.3
HR
75
BP
150/75

122. Initial Results
Lipids
Inflammation
Initial Results
Initial Results
TC
211
OxLDL
52
LDL-C
142
MPO
457
HDL-C 35
TG
180
Lp(a)
85
ApoB
97
Other
Initial Results
NT-proBNP
426
TSH
3.724
Testosterone
225

123. Initial Results2
Metabolic
2 hr. GTT
hour OGTT
110/189/201
INSULIN RESISTANCE

124. Atrial Fibrillation

125. Echo showing mild LVH and mild left
atrial enlargement
Two-dimensional
echocardiogram
(parasternal long axis
view) from a 62-year-old
woman showing
concentric left ventricular
hypertrophy and left atrial
enlargement.

126. Tricuspid Regurgitation

127. Echo Results
•
•
•
•
•
•
Normal LV size. Ejection Fraction 60%.
Mild concentric left ventricular hypertrophy
Type I Relaxation Abnormality Pattern
Mild left atrial dilation
Mild tricuspid regurgitation
Moderate pulmonary hypertension.

128. Sleep Results
• Severe Sleep Apnea
• Severe: AHI ≥ 30 per hypopneic spells
• Oxygen desaturation 82%

129. Clinical Features of Sleep Apnea
•
•
•
•
•
•
•
•
•
•
•
•
Daytime sleepiness
Nonrestorative sleep
Witnessed apneas by bed
partner
Awakening with choking
Nocturnal restlessness
Insomnia with frequent
awakenings
Lack of concentration
Cognitive deficits
Changes in mood
Morning headaches
Vivid, strange, or threatening
dreams
Gastroesophageal reflux
•
•
•
•
•
•
•
•
•
•
•
•
Obesity
Large neck circumference
Systemic hypertension
Hypercapnia
Cardiovascular disease
Cerebrovascular disease
Cardiac dysrhythmias
Narrow or "crowded" airway
Pulmonary hypertension
Cor pulmonale
Polycythemia
Floppy eyelid syndrome

130. Treatment Options
•
•
•
•
•
•
•
Diet and Exercise
Start metformin 500 mg po bid
Add Lasix 40mg Kdur 20meq
Wear CPAP mask
Start statin + nicotinic acid
Start coumadin vs novel anticoagulant
Enquire about family History

131. Key Learning Points
 Resistant HTN
 High NT-proBNP suggestive of OSA
 OSA link with atrial fibrillation
 Ox LDL increased risk of metabolic syndrome/
diabetes
 Lipoprotein (a) is independent risk factor for CAD

132. In Memory of
Dr. Nirav Patel
1968-2012