12/15/2010

Disclosures
Treating Cardiovascular Risk
► Grants: Novartis, Daiichi
Daiichi--Sankyo
Factors in Medically Complex
► Speaker Bureau: Ortho-
Ortho-McNeil, Abbott,
Patients Novartis, GSK, Sanofi-
Sanofi-Pasteur, DSI, Takeda,
Merck

Wendy L. Wright, MS, RN, ARNP, FNP, FAANP

Owner – Wright & Associates Family Healthcare
Partner – Partners in Healthcare Education

1 2
Wright, 2010

Objectives The Problem:

• Upon completion of this lecture, the participant Cardiovascular Disease is Deadly!
will be able to:
– Discuss the epidemiological impact of CAD in 2011
– List the major
j risk factors impacting
p g aggressive
gg
CAD
– Identify treatment options for the medically
complex patient at risk of cardiovascular disease
•

3 4
www.Hypertensiononline.org

CVD and Other Causes of Death Case Study

900,000
800,000
700,000
Alzheimer
600,000
CLRD
Deaths 500,000 Cancer
400,000 All Other CVD
300,000 Stroke
200,000 Heart Disease
100,000
0
All Ages <85 85+

CVD and other major causes of death: both sexes.

5 6
(United States: 2006). Source: NCHS and NHLBI.

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Bob
47-year-old Caucasian Sales Executive
Bob
• Social History
• Presents for a physical examination – Tobacco use: 1- 2 pack daily; 25 years
• No complaints at present and feels well – Alcohol: 1 – 2 beers nightly
– Exercise: none
• PMH
– Married, 2 children in high school
– Torn ACL (right knee) - 1996 – Sales
S l executive
ti who h ttravels
l (40% off time
ti
– Obesity since young adulthood away from home)
– Bipolar disorder • Medications
– Multivitamin 1 po daily
– Smoker
– ASA 81 mg 1 po daily
• Family History – Lithium 300 mg 1 pill two times daily
– Father – died age 62 - MI 7 8

Bob Bob
Physical Examination Laboratory Parameters
• Height: 5’ 8” • FBS: 106 mg/dL (60 – 99)
• Weight: 287 lbs • BUN: 16 mg/dL (9 – 21)
• BMI: 43.9 • Creatinine: 1.0 mg/dL (0.8- 1.4)
• Waist circumference: 46” • T Cholesterol:
T. 220 mg/dL (< 200)
• BP: 138/90 (2 readings) • HDL: 34 mg/dL (> 40)
• Pulse: 86 bpm and regular • Triglycerides: 156 mg/dL (<150)
• EKG: • LDL: 155 mg/dL (<100)
– Left axis deviation • VLDL: 56 mg/dL ( 2-27)
– No conduction abnormalities or ischemic changes
9 10

Bob
Bob
Laboratory Parameters • Questions for participants:
• hs-CRP: 2.7 mg/L (<3.0) – What, if any, are his risk factors for CAD?
• Hypertension
• AST: 54 mg/dL (0 – 40)
• Obesity
• ALT: 67 mg/dL (0 - 40) • Type 2 diabetes
• D li id i
Dyslipidemia
• 2 hr OGTT: 155 mg/dL (<140)
• Medication usage (Lithium)
• A1C: 6.4 % (<6.0%) • Smoker: COPD
• GFR: 50 mL/min (>60) • Stage III Kidney disease (GFR 30 – 59)

• FEV1: 80% (>80%) • How should we approach these risks?

– Nonpharmacologic treatments
• FEV1/FVC: 62% (>70%) – Pharmacologic management
11 12

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Interrelation Between Atherosclerosis

and Insulin Resistance
Insulin Resistance
• Primarily, the plasma glucose level regulates
Hypertension the physiologic control of insulin secretion
Obesity • When an individual develops insulin resistance,
Hyperinsulinemia the normal amount of insulin is not able to
Insulin Diabetes maintain normal plasma glucose levels
Atherosclerosis
Resistance Hypertriglyceridemia • To compensate, insulin secretion is increased
Small, dense LDL until the plasma glucose levels return to normal
Low HDL • Eventually, the pancreas may NOT be able to
Hypercoagulability compensate
Clinician’s Manual on Insulin Resistance. H E Lebovitz Science Press 2002 London,
13 UK 14
Slide source: Lipidsonline.org http://care.diabetesjournals.org/cgi/content/full/27/2/602

Insulin Resistance
Causes of Insulin Resistance
• 47 million people in the USA have
• Adiposity and Physical Conditioning
– 25% each……………….50% of IR patients
the insulin resistance syndrome.
– When BMI is >25 = 66% have insulin resistance Age 20 - 74 years old
• Genetic Factors……..…50% of IR Patients Prevalence in men 24%; women 23.8%

Age 60 - 69 years old

First World Congress on Insulin Resistant Syndrome; 2003, Nov20-23, Los Angeles, California, USA
http://care.diabetesjournals.org/cgi/content/full/27/2/602
15
Prevalence in men 43.5%; women 42%
Flegal, KM., Carroll MD., et al. Prevalence and Trends in Obesity Among
US Adults, 1999-2000. JAMA. 2002; 288:1723-1727.
Mokdad, AH, Ford ES. Et al. Prevalence of obesity, diabetes and obesity related 16
health risk factors 2001. JAMA. 2003; 289:76-79.

Metabolic Syndrome Consensus Definition Regardless of Name…

Metabolic Syndrome is:
• Central Obesity > 40 inches male / >35 inches female
• Raised triglycerides • Method to identify those at risk for
– > 150 mg/dL (or treatment of triglycerides) – Early
• Reduced HDL cholesterol
– Aggressive
– <40 mg/dL for men or < 50 mg/dL for women or treatment
toward this goal – Cardiovascular Disease
• Raised blood pressure
– > 130 mm Hg systolic or > 85 mm Hg diastolic or treatment
toward this goal – Patients with Metabolic Syndrome have a 3 X
• Raised fasting plasma glucose level greater chance of developing CAD and dying
– FBS> 99 mg/dL or treatment toward this goal
Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and
from it
Treatment of High Blood Cholesterol in Adults. National Cholesterol Education Program, National Heart, Lung, Diabetes Care. 2001; 24:683-689.
and Blood Institute, National Institutes of Health. NIH Publication No 01-3670. May 2001
JAMA. 2002; 288:2709-2716.
17 18

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Bob
Physical Examination
• Height: 5’ 8”
• Weight: 287 lbs
Coronary Artery Disease • BMI: 43.6
Risk Factor: • Waist circumference: 46”
Obesity • BP: 138/90 (2 readings)
• Pulse: 86 bpm and regular
• EKG:
– Left axis deviation
19
– No conduction abnormalities or ischemic changes 20

Definition of Obesity Practical Diagnosis

• Waist Circumference
– Obtained by taking a measurement between the
Obesity is a chronic disease of iliac crest and the bottom of the rib cage after
multiple etiologies characterized by mild exhalation
th presence off excess adipose
the di tissue
ti – Waist circumference of > 102 cm (> 40 inches) in
men or 88 cm ( > 35 inches) in women is a
important component of the metabolic syndrome
diagnosis
Atkinson RL, Hubbard VS. Report on the NIH Workshop on Pharmacologic
Treatment of Obesity. American Journal of Clinical Nutrition, Vol 60,
153-156, Copyright © 1994 by The American Society for Clinical Nutrition, Inc
The Expert Panel on Detection, Evaluation, and Treatment of
High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.
21 22

Determine Obesity Class Obesity Trends* Among U.S. Adults

and Disease Risk BRFSS, 1985
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

Disease Risk*
BMI Classification (Waist Circumference)
(kg/m2) Men < 40 in >40 in
Women < 35 in >35 in

25 0-29 9
25.0-29.9 Overweight Increased High
30.0-34.9 Obesity I High Very High
35.0-39.9 Obesity II Very High Very High

> 40 Obesity III Extremely High Extremely High

* for type 2 diabetes mellitus, hypertension, and CVD

No Data <10% 10%–14%

NHLBI Practical Guide. Oct 2000 Table 2, pg 10 23 24

Source: CDC Behavioral Risk Factor Surveillance System.

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Obesity Trends* Among U.S. Adults Fat Topography in Impaired Glucose Tolerance
BRFSS, 2009
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

25 26
Source: CDC Behavioral Risk Factor Surveillance System. Bays H, Mandarino L, DeFronzo RA. J Clin Endocrinol Metab. 2004;89:463-78..

Adipose Tissue as an Visceral Fat Versus

Endocrine Organ Subcutaneous Fat
↓ Adiponectin Subcutaneous Fat Visceral Fat

Subcutaneous Fat Subcutaneous Fat Visceral Fat

Visceral Fat

↑ Interleukin-6 ↑ Leptin

↑ TNF-alpha ↑ PAI-1 Visceral fat area: 60 cm2 Visceral fat area: 146 cm2
Subcutaneous fat area: 190 cm2 Subcutaneous fat area: 115 cm2
BMI: 24.0 kg/m2 BMI: 23.1 kg/m2
1. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89(6):2548-2556.
2. Després JP, Lemieux I, Prud'homme D. Treatment of obesity: need to focus on high risk abdominally
obese patients. BMJ. 2001;322(7288):716-720.
27 Wajchenberg. Endocr Rev. 2000. 28
Courtesy: Steven Smith, MD
Pennington Biomedical Research Center

Desired End Point

Visceral Adipose Tissue Decreased Adipose Tissue
Diet
Abdominal obesity Exercise Desired end point
Increased waist Pharmacotherapy Reduced waist
circumference circumference
Deteriorated Lipid Profile Improved

Impaired Insulin Sensitivity Improved

Blood Insulin
Blood Glucose

Risk Markers for Thrombosis

Inflammatory Markers

Impaired Endothelial Function Improved

Increased CV Risk Low

Adapted from Després J et al. BMJ. 2001. 29 30

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Guide for Selecting Drugs Approved by FDA

Treatment for Treating Obesity
BODY MASS INDEX (BMI)
25-26.9 27-29.9 30-34.9 35-39.9 >40 Dosage/
Approval
Mechanism of DEA Monthly
Name Year Use Action Schedule Cost
DIET, PHYSICAL ACTIVITY  *  *   
Orlistat
and BEHAVIOR THERAPY Long
Long- 120 mg
g
(X i l)
(Xenical) 1999 term Li
Lipase inhibitor
i hibit N
None
~ $120

PHARMACOTHERAPY  *    Phentermine Short- Norepinephrine

15-37.5
(Adipex, 1973 IV mg/d
lonamin) term reuptake inhibitor
~ $40
SURGERY  * 

Always use as an adjunct to diet and physical activity

* With Comorbidities
NHLBI Practical Guide. Oct 2000 Table 3, pg25 31 FDA approves drugs that have greater than 5% weight loss above placebo
32

Change in Weight and CHD Risk Factor Thoughts to Ponder

Clustering: Framingham Offspring Study

60 Risk factors: • Lithium…..

Men Women • Low HDL-C
– What do you need to consider?
factor sum (%)

40 • High cholesterol
• High systolic BP
• Thyroid
ange in

20 • High TG
• High glucose
• Kidney function
risk facto
Cha

-20
– Worsening insulin resistance?
-40 – Must avoid certain medications:
-60 • NSAIDs
Loss Gain Loss Gain
2.25 kg 2.25 kg 2.25 kg 2.25 kg • HCTZ
Weight Change Over 16-
16-Year Follow Up

Adapted from: Wilson PW, et al. Arch Intern Med. 1999;159:1104- 33 34

1999;159:1104-1109

Lithium Thiazides and Lithium

• Lithium is cleared completely through the
• In fact, concomitant use of diuretics has long
renal system
been associated with the development of
• Drugs and conditions that influence renal lithium toxicity
excretion stand the potential for increasing
– Thiazide diuretics are thought to be the
serum lithium concentrations
worst because they act distally on the renal
• Such drugs include: thiazide diuretics, tubule (same location as lithium is cleared)
NSAIDs, ACE inhibitors, Calcium channel causing an increase in the re-absorption of
blockers (diltiazem and verapamil), Caffeine lithium
35 36

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Think of All the Other Drugs Can Lower Lithium

Antihypertensives Levels
• Most antihypertensives now • Osmotic diuretics enhance lithium
have HCTZ in them excretion and are often used for
lithium toxicityy
• Easy for a drug interaction to
• Caffeine and theophylline also
occur
decrease lithium levels and
therefore need to be monitored if
used concomitantly
37 38

Bob
Laboratory Parameters
• FBS: 106 mg/dL (60 – 99)
• BUN: 16 mg/dL (9- 21)
Coronary Artery Disease • Creatinine: 1.0 mg/dL (0.8-1.1)
Ri k F
Risk Factor:
t • T Cholesterol:
T. Ch l l 220 mg/dL
/dL ( 200)
(<
• HDL: 34 mg/dL (> 40)
Diabetes • Triglycerides: 156 mg/dL (<150)
• LDL: 155 mg/dL (<100)
• VLDL: 56 mg/dL (2-27)
39 40

Age-adjusted Percentage of U.S. Adults Who Were Obese

Bob or Who Had Diagnosed Diabetes

Laboratory Parameters Obesity (BMI ≥30 kg/m2)

2008
1994 2000

• hs-CRP: 2.7 mg/L (<3.0)

• AST: 54 mg/dL (0 – 40)
• ALT: 67 mg/dL (0 - 40) No Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% >26.0%

• 2 hr OGTT: 155 mg/dL (<140) Diabetes

1994 2000 2008

• A1C: 6.4 % (<6.0%)

• GFR: 50 mL/min (>60)
No Data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% >9.0%

41 CDC’s Division of Diabetes Translation. National Diabetes Surveillance System available at 42

http://www.cdc.gov/diabetes/statistics

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Screening for Diabetes

A 1C
• According to the ADA, screening should
begin on all individuals 45 years of age and • Recommendations:
older1
– A1C – may be used for screening
– Repeated q 3 years if normal
– >6.5% - consistent with diabetes
• If at risk, can begin
g screening
g at an earlier
– 5.7%
5 7% - 6.4%:
6 4%: prediabetes
age
– i.e. obese, sedentary lifestyle
• **American College of Endocrinology1: • Last 6 weeks of blood sugars is driving factor
– Begin screening at age 25 years, in at risk in the A1C
individuals
www.diabetes.org
www.diabetes.org accessed on 2-2-2008
www.aace.com accessed on 2-2-2008 43 44

Guideline Recommendations Are

Becoming More Aggressive
What Is Good Control? • 2007 ADA standards1
• A1C – “The A1C goal for patients in general is an A1C goal
– AACE: < 6.5% of <7%.”
– ADA: < 7.0% *** – “The A1C goal for the individual patient is an A1C as
close to normal (<6%) as possible without
• FBS significant hypoglycemia.”
– AACE: < 110 mg/dL • ADA/EASD consensus statement2
– ADA: 70 – 130 mg/dL – “If lifestyle intervention and maximal tolerated dose of metformin
• 2 hour postprandial: fail to achieve or sustain glycemic goals, another medication
should be added within 2–3 months of the initiation of therapy
– AACE: <140 mg/dL or at any time when A1C goal is not achieved.”
ADA=American Diabetes Association; EASD=European Association for the Study of Diabetes.
– ADA: < 180 mg/dL 45
1. American Diabetes Association. Diabetes Care. 2007;30(suppl 1):S4–S41.
2. Nathan DM et al. Diabetes Care. 2006;29:1963–1972. 46

Treatment Options

47 48

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Major Targeted Sites of Oral Drug Classes

AACE: Managing Diabetes Pancreas
Beta-cell
Beta-
American Association of Clinical Endocrinologists dysfunction
Sulfonylureas
Meglitinides Muscle
Intensive Liver and fat
DPP-4 inhibitors
Intensive Lifestyle management of
Incretin Memetics
glycemic control intervention comorbid
conditions* Hepatic glucose ↓Glucose level Insulin
overproduction resistance

• A1C ≤6.5% • Optimal nutrition • Lipid modifying Biguanides Gut TZDs

• Glucose (mg/dL) • Physical activity • BP lowering
– Preprandial ≤110 • Smoking cessation • ASA for prevention of TZDs Biguanides
– Postprandial ≤140 • Weight control vascular events Alpha-
DPP-4 inhibitors
Glucose glucosidase
Incretin Memetics absorption inhibitors
Biguanides
*Dyslipidemia, hypertension, early renal disease AACE. Endocr Pract. 2002;8(suppl 1):40-65. DPP-4=dipeptidyl peptidase-4; TZDs=thiazolidinediones. Bile Acid
49
DeFronzo RA. Ann Intern Med. 1999;131:281–303. Sequestrants
Buse JB et al. In: Williams Textbook of Endocrinology. 10th ed. Philadelphia: WB Saunders; 2003:1427–1483. 50

Managing diabetes as a CHD risk equivalent:

Treatment of Patient Based on AIC ABCs of coronary prevention
A1C is less than 7.3% A1C is 7.3% - 9.2% A Aspirin
ACE inhibition
A1C control
B -blockade
ood p
Blood pressure
essu e co
control
o

C Cholesterol management

D Diet
Don’t smoke
Decrease diabetes risk

Monnier L, Lapinski, H, Colette C. Contributions of fasting and postprandial plasma glucose increments to
the overall diurnal hyperglycemia of type 2 diabetic patients: Variations with increasing levels of HbA(1c). E Exercise
Diabetes Care. 2003;26:881-885.
51 Adapted from Cohen JD. Lancet. 2001;357:972-3.
52

AHA/ACC/ADA:
Multiple risk reduction in diabetes Would You Treat?
Target Recommendations • If no, why?
<6% if possible without inducing
A1C <7%
hypoglycemia • If yes, with what intervention?
BP (mm Hg) <130/<80
ACEI or ARB in BP-lowering • Any concerns?
eg e
regimen
Lipids (mg/dL) – Stage 3 kidney disease (moderate)
Statin for CV history or age >40 yr
LDL-C <100 (<70 optional) – Metformin – when do you limit usage?
(regardless of baseline LDL) to
HDL-C >40 men, >50 women
lower LDL 30%–40%
TG <150

• ASA: Age >40 yr or with other risk factors, all with CV disease history
• ACE inhibitor: Age >55 yr with another CV risk factor
Pearson T et al. Circulation 2002.
Grundy SM et al. Circulation 2004.
53 54
ADA. Diabetes Care 2006.

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Bob
Laboratory Parameters
• FBS: 101 mg/dL (60 – 99)
• BUN: 16 mg/dL (9 – 21)
• Creatinine: 1.0 mg/dL (0.8-1.1)
Coronary Artery Disease • T Cholesterol:
T. 220 mg/dL (< 200)
Risk Factor • HDL: 34 mg/dL (> 40)
• Triglycerides: 156 mg/dL (<150)
Dyslipidemia • LDL: 155 mg/dL (<100)
• VLDL: 56 mg/dL (2-27)
55 56

Bob Lipids
Laboratory Parameters LDL
HDL
• hs-CRP: 2.7 mg/L (<3.0)
• AST: 54 mg/dL (0 – 40)
• ALT: 67 mg/dL (0 - 40) Inherited Disease
• LDL Pattern B
• 2 hr OGTT: 155 mg/dL (<140) • Lp(a)
• HDL Size
• A1C: 6.4 % (<6.0%)
• Particle
• GFR: 85 mL/min (>60) concentration
• PLAC testing

57
Lipoproteins 58

Most LDL is CALCULATED

• LDL = Triglyceride / 5 + HDL, subtract from total cholesterol.

• Tot Chol 234 206

• HDL 36 41
• TG 310 110

• LDL 103 141 (LDL Calculated)

59 BUT…You can order a direct LDL!! 60

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NCEP Interim Report:

LDL-C Goals and Drug Cut Points for High-Risk Patients Key Lipid Lowering Agents
LDL-C to
LDL-C Consider Drug
Goal Therapy* Agent Target of Impact Other
Risk Level Risk Category (mg/dL) (mg/dL)
2 Risk Factors;
HMG-CoA reductase Liver Decrease manufacturing
Moderately <130 130**
High Risk 10-Year Risk 10%-20% <100† 100-
inhibitors LDL – lower LDL
129‡
Bile acid sequestrants Gut Absorb bile acid – Lower
High Risk CHD or CHD Risk LDL
Equivalents;
E i l <100 100
00**
10-Year Risk >20%
Cholesterol absorption Brush border small intestine Block re-absorption of bile
Very High Established CVD Plus: inhibitors acid – Lower LDL
Risk • Multiple Major Risk Factors <100 100**
• Severe and Poorly <70† <100‡
Nicotinic acid derivative Liver Increase HDL
Controlled Risk Factors
• Multiple Risk Factors of Decrease triglycerides
the Metabolic Syndrome
• Acute Coronary Syndromes Fibrates Liver Decrease triglycerides
*When LDL-C–lowering drug therapy is used, the intensity of therapy should be sufficient to achieve a 30%-40%
reduction in LDL-C; **Therapeutic lifestyle changes (TLC) should be initiated when LDL-C is at or above goal; any Omega-3 acid ethyl esters Liver Decreased triglycerides
high-risk or moderately high-risk patient who has lifestyle-related risk factors is a candidate for TLC regardless
of LDL-C level; †Optional LDL-C goal; ‡Consider drug options.
61 62
Grundy et al. Circulation. 2004;110:227-239. www.lipidsonline,org

PROVE IT-22
Statins LDL Lowering Power Cumulative Incidence of Recurrent MI or CHD Death
by Achieved Levels of LDL-C and CRP
0.10 LDL-C ≥ 70 mg/dL, CRP ≥ 2 mg/L
3A4 3A4 3A4 2C9

Simvastatin Lovastatin Atorvastatin Pravastatin 0.08

or CHD Death
10 mg 22% 10 mg 22% 10 mg 34% 10 mg 20% LDL-C < 70 mg/dL, CRP ≥ 2 mg/L

20 mg 31% 20 mg 25% 20 mg 41% 20 mg 25%

LDL-C ≥ 70 mg/dL, CRP < 2 mg/L
0.06
40 mg 48%
Cumulative Rate of

40 mg 38% 40 mg 31% 40 mg 30%

80 mg 45% 80 mg 41% 80 mg 51% 80 mg 34%
LDL C < 70 mg/dL,
LDL-C mg/dL CRP < 2 mg/L
Recurrent MI o

0.04
2C9 3A4 2C9

Fluvastatin Lovastatin ER Rosuvastatin 0.02

20 mg 20% 20 mg 30% 10 mg 46%

40 mg 27% 40 mg 36% 20 mg 52% 0.00
0.0 0.5 1.0 1.5 2.0 2.5
80 mg 32% 60 mg 41% 40 mg 55% Follow-up (years)
PROVE IT = PRavastatin or AtOrVastatin Evaluation and Infection Therapy N=3745; pravastatin 40 mg vs
atorvastatin 80 mg Ridker RM, et al. N Engl J Med. 2005;352:20-28.
Product Inserts 63 64
www.lipidsonline.org

Landmark Coronary Prevention Studies

Can HMG Co-A

Study Drug N Duration Main Findings
(Years)

4S† simvastatin 4,444 5 30% total mortality

34% coronary events*

Reductase Therapy WOS‡ pravastatin 6,595 5 31% coronary events

22% total mortality
y

Decrease Events? CARE† ** pravastatin 4,159 5 24% coronary events

31% stroke

AFCAPS/ lovastatin 6,605 5 37% coronary events/unstable angina

TexCAPS‡ ** Low HDL population

LIPID† pravastatin 9,014 6 22% total mortality

24% death from CHD
The Lancet 1994;344:1383-1389 JAMA 1998:279:1615-1622. * Nonfatal MI/CHD death
N Engl J Med 1995;333:1301-1307. N Engl J Med 1998;339:1329-1357 ‡ Primary Prevention
65 N Engl J Med 1996;335:1001-1009 † Secondary Prevention 66
** Normal cholesterol levels

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ASCOT-
Lipid Lowering Arm
• LDL starting value…………………133 mg/dL
• Aggressive LDL lowering………….88 mg/dL

• Major CV events @ 3 years….. 36%

• Major vascular events…………. 27%
• Total coronary events…………. 29%

Lancet 2003; 361:1149-115867 68

The HDL Molecules(s)

Industrial Strength 2b
Vacuum
2a

3a
Dust Buster
3b

3c
69 www.lipidsonline.com 70
Adapted from Berkley Heart Lab

What Does He Need?

• Statin?

Treatment •
•
Bile Acid Sequestrant?
Niacin?

Alternatives •
•
Fibrate?
Omega 3?
• Any worries?
– Kidney function – statins?

71 72

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Bob
Physical Examination
• Height: 5’ 8”
• Weight: 287 lbs
• BMI: 43.9
• Waist circumference: 46”
Coronary Artery Disease
• BP: 138/90 (2 readings)
Risk Factor: • Pulse: 86 bpm and regular
Hypertension • EKG:
– Left axis deviation
– No conduction abnormalities or ischemic changes
73 74

Bob
Laboratory Parameters
• FBS: 106 mg/dL (60 – 99)
Blood Pressure Treatment
• BUN: 16 mg/dL (9-21-) in the Patient with the
• Creatinine: 1.0 mg/dL (0.8-1.1) Metabolic Syndrome

Is
• T. Cholesterol: 220 mg/dL (< 200)
• HDL: 34 mg/dL (> 40)
• Triglycerides: 156 mg/dL (<150)

Different
• LDL: 155 mg/dL (<100)
• VLDL: 56 mg/dL (2-27)
75 76

CV Disease Risk Doubles with

Each 20/10 mm Hg BP Increment*
8
7
6

CV 5
Therapy aimed at avoiding target organ damage disease 4
not just reducing a number risk
3
2
1
0
115/75 135/85 155/95 175/105
SBP/DBP (mm Hg)
*Individuals aged 40-70 years, starting at BP 115/75 mm Hg.
CV, cardiovascular; SBP, systolic blood pressure; DBP, diastolic blood pressure
Lewington S, et al. Lancet. 2002; 60:1903-1913.
77 78
www.Hypertensiononline.org JNC 7. JAMA. 2003;289:2560-2572.

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JNC 7: Classification and Management Hypertension Management:

of Blood Pressure Old Approach
Considerations for Initial Therapy
SBP* DBP* Lifestyle Hypertension= systemic disease
Category Without Compelling With Compelling
mm Hg mm Hg modification
Indications Indications

Normal <120 and <80 Encourage

Hemodynamics Altered
Prehypertension 120-139 or 80-89 Yes No antihypertensive Drug(s) for compelling
drug indicated indications†

Stage 1 140-159 or 90-99 Yes Thiazide-type diuretics Drug(s) for the

Hypertension for most. May consider compelling indications† Treat the Blood Pressure
ACEI, ARB, BB, CCB,
or combination. Other antihypertensive
drugs (diuretics, ACEI,
Stage 2 ≥160 or ≥100 Yes 2-drug combination for ARB, BB, CCB) as
Hypertension most** (usually thiazide- needed
type diuretic and ACEI Therapeutic Options
or ARB or BB or CCB)

Beta
SBP, systolic blood pressure; DBP, diastolic blood pressure; ACEI, angiotensin-converting enzyme inhibitor; ARB, ACE ARB Diuretics CCB Others
angiotensin receptor blocker; BB, beta-blocker; CCB, calcium channel blocker. Blockers
*Treatment determined by highest BP category.
**Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.
†Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mm Hg. 79 80
Adapted from Vascular Biology Working Group, University of Florida
College of Medicine, Carl Pepine, MD, Director

Hypertension Management: Drug Classifications

New Approach Hypertension
Hypertension = Disease of the
blood vessels

• Beta Blockers • Calcium Channel

Vascular Biology Altered
• Diuretics Blockers
– Dihydropyridine
• Alpha Blockers
Treat the vasculature – Non-dihydropyridine
Non dihydropyridine
• Alpha Beta Blockers
• ARB’s
• Centrally Acting
Therapeutic Options • ACE Inhibitors
Agents
• Direct Renin Inhibitor
• Direct vasodilators
Beta
ACE ARB Diuretics CCB Others
• Combination agents
Blockers

81 82
Adapted from Vascular Biology Working Group, University of Florida
College of Medicine, Carl Pepine, MD, Director

Outcomes for Hypertension ACE Inhibitor Trials

• Early trials 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 2000

– Determine if lowering blood pressure was CHF CONSENSUS I

ValHeFT II
impactful on risk LVD SOLVD treatment
Post-AMI SAVE
– Identify parameters for blood pressure goals AIRE
• ACCORD, SHEO, HOT, AASK, MDRD, UKPDS TRACE
Anterior SMILE
• Later trials AMI CATS
CONSENSUS II
– Impact of different classes of medications on AMI GISSI-3

select target organ damage ISIS-4

CCS-1
• ALLHAT and multi-interventional therapies CAD PEACE
HOPE

83 84
Latini, et al. Curr Perspect. 1995;92:3132-7

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ARB Trials Newer Trials

1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

ELITE I ValHeFT • Combination therapy

HF
ELITE II CHARM – ACE/HCTZ, ARB/HCTZ, ACE/CCB\
LIFE
CV
ON TARGET
• Triple therapy
y
MI
OPTIMAAL
– Becoming norm
VALIANT

Renal/CV IRMA II • Direct Renin Inhibitors and combination

MARVAL

VALUE
therapy
Renal
IDNT
– Aliskirin + HCTZ, ACE, ARB, CCB
RENAAL
IPreserve – ARB + CCB
85 86

What Does He Need? Case Study

• Think:
– LVH
– Smoker
– Prediabetes
– Bipolar
p Disorder
• ACE inhibitor
• Beta blocker
• CCB
• DRI
• ARB
• Thiazide
87 88

Bob Bob
Physical Examination Laboratory Parameters
• Height: 5’ 8” • FBS: 106 mg/dL (60 – 99)
• Weight: 287 lbs • BUN: 16 mg/dL (9-21)
• BMI: 43.9 • Creatinine: 1.0 mg/dL (0.8-1.1)
• Waist circumference: 46” • T Cholesterol:
T. 220 mg/dL (< 200)
• BP: 138/90 (2 readings) • HDL: 34 mg/dL (> 40)
• Pulse: 86 bpm and regular • Triglycerides: 156 mg/dL (<150)
• EKG: • LDL: 155 mg/dL (<100)
– Left axis deviation • VLDL: 56 mg/dL (2-27)
– No conduction abnormalities or ischemic changes
89 90

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Bob
What Drugs Do You Use?
Laboratory Parameters
• hs-CRP: 2.7 mg/L (<3.0) • What would you use?
• AST: 54 mg/dL (0 – 40) • What would you avoid?
• ALT: 67 mg/dL (0 - 40) • Bob is a smoker….does that matter in your
• 2 hr OGTT: 155 mg/dL (<140) t t
treatment?
t?
• A1C: 6.4 % (<6.0%)
• GFR: 50 mL/min (>60)

91 92

Bob Approaches to CVD prevention

• Assessment
– Obesity Lipid Central
modification Obesity Reduction
– Prediabetes
– Hypertension Optimal
– Dyslipidemia CV risk
reduction
– COPD
Glucose BP
– Bipolar Disorder
lowering lowering
He is at a significant risk for the development
of Coronary Artery Disease
93 Vascular Biology Working Group, University 94
of Florida
College of Medicine, Carl Pepine, MD, Director

Bob – Priorities and Alternatives

Goals of Intervention • Lifestyle Changes
• Reduction of risk to delay Coronary Artery – Diet, exercise, alcohol intake
Disease – Will he attain goals in all 4 categories with
– Obesity: decrease waist to < 40 inches lifestyle?
– Prediabetes: Normalize A1C • If not, what categories of medications would
– Lipids:
Li id help?
• LDL < 100 mg/dL (consideration < 70 mg/dL) – Agents for obesity treatment
• HDL > 40 mg/dL – TZD, Biguanide, Incretins, sulfonylurea
• Triglycerides <150 mg/dL
– ACE / ARB vs. ACE / ARB combo, CCB, BB
– Hypertension:
– Statin vs. Statin / Niacin Combo, Omega 3
• Systolic < 130 mmHg with diastolic < 80mmHg
• Absence of proteinuria and LVH
– ASA
95 96

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Conclusions
• Nurse Practitioners and Physician
Assistants are in an excellent position to
identify the individual at risk for CAD
• The risk factors must be identified early
• Once identified, aggressive treatment for
modify obesity, hypertension, dyslipidemia
and diabetes must be employed to reduce
the risk of CAD

97

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