1. Preventing Cardiovascular Events Primary and Secondary
November 8th 2014
Slides by Dr Dharmesh Patel and Arie Szatkowski
Last Minute Presentation by Dr Arie Szatkowski

3. 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.”

4. Cardiac Stress Tests What is the solution? Or, is there any?
Limitations:
Requires a high level of blockage in one or more coronary arteries for abnormal result. 
Most heart attacks occur in vessels without significant blockage, or stenosis.
What is the solution? Or, is there any?

5. 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

6. Definitions of Different Types of Prevention
Primordial Prevention: Prevention of coronary heart disease risk factors
Primary Prevention: Modification of risk factors in order to prevent or delay the onset of coronary heart disease
Secondary Prevention: Initiation of therapy to reduce recurrent coronary heart disease events and decrease cardiac mortality in patients with established coronary heart disease. 6

7. Advances in CVD Risk Reduction Not Enough
CVD is the leading cause of death in the United States, despite guideline driven care.1
CVD accounts for 33% of all deaths.2
Total CVD healthcare costs are projected to rise from $313 billion in 2009 to $1.48 trillion in
50% of people who have had a heart attack have normal cholesterol.3
Speaker Notes
1.58 billion dollars in stenting
Key Point: CVD remains the leading cause of death in the US and results in billions of dollars in direct and indirect medical costs each year.
Despite advances in the prevention and treatment of cardiovascular disease (CVD), continued efforts to reduce CVD risk is essential.
CVD remains the leading cause of death in the United States in the face of guideline-driven care.1
From 1999 to 2009 the rate of CVD deaths declined by 33% yet in 2009 CVD accounted for 33% of all CVD deaths.2
Additional point: The number of CVD deaths in 2009 (787,931 deaths) was approximately equal to deaths from cancer, chronic lower respiratory disease, accidents and Alzheimer’s disease***** combined (784,102).2
The total CVD healthcare costs in 2009 were $312.6 billion and by 2030 are projected to be about $1.48 trillion.2
On top of these troubling statistics, 50% of people who’ve had a heart attack have normal cholesterol
References
Roger VL, Go AS, Lloyd-Jones DM, et al; for The American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics— 2011 Update: A Report from the American Heart Association. Circulation. 2011;123:e18-e209.
Go AS, Mozaffarian D, Roger VL, et al; for The American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2013 Update: A Report from the American Heart Association. Circulation. 2013;127:e6-e245.
Sachdeva A, Cannon CP, Deedwania PC, et al. Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J. 2009;157: e2.
Roger et al. Circulation. 2011;123(4):e18-e209.
Go AS, Mozaffarian D, Roger VL, et al. Circulation. 2013;127:e2-e245.
Sachdeva et al. Am Heart J. 2009;157(1): e2.
© 2014 Boston Heart Diagnostics Corporation 7

8. Major Risk Factors for Cardiovascular Disease
Smoking – 1964 – 1st Surgeon General ‘s report linking smoking with heart disease, lung cancer, and emphysema– marked decrease
Diet – 1968 – The US food industry replaces lard and tallow in many foods with vegetable oil – beneficial effects on LDL-C and CHD risk.
High Blood Pressure – National High Blood Pressure Education Program and Treatment Guidelines - blood pressure control (JNC 7, get systolic < 130 mmHg, major reduction in CVD, especially stroke)
Cholesterol – National Cholesterol Education Program Adult Treatment Panel Guidelines (latest 2004) – get LDL-C < 100, CVD < 70
Diabetes – Diabetes Control and Complication Trial – 2013 guidelines for the diagnosis and treatment of diabetes – get HbAIc < 7%.
Age Adjusted CVD Rates – have dropped by > 50% since 1964
Emerging Targets – sdLDL, HDL Particles, Lipoprotein(a), and CRP

9. Smoking and Heart Disease
Single most preventable cause of death in the U.S
Causes plaque to form in blood vessels
Reduces HDL (“good”) cholesterol
May cause irregular heart rhythms that could lead to cardiac arrest
Puts women who smoke at a much higher risk of developing cardiovascular disease
Good News: quitting begins to reduce cardiovascular risk immediately

10. Obesity Trends* Among U.S. Adults BRFSS, 1990, 2000, 2010
(*BMI 30, or about 30 lbs. overweight for 5’4” person)
1990
2000
2010
No Data <10% %–14% %–19% %–24% %–29% ≥30%

11. Obesity in Mississippi
2nd Fattest state in the country
Over 2/3 of MS adults are overweight
Over 26% are obese
Only 38 % get recommended physical activity
# 1 in heart disease deaths
# 1 in young adults with diabetes
Annual state costs at least $757 million with overweight and obesity

12. Scope of the Problem (Cont’d)
Prevalence of CHD associated with 3 projections of adult obesity
Excess prevalence of CHD
Population prevalence of CHD
Number of Excess Cases
Prevalence (%)
This study estimated the prevalence of obesity among 35-year-olds in 2020 based on adolescents that were overweight in A coronary heart disease policy model was then used to project the annual excess incidence and prevalence of coronary heart disease. Extrapolation from this data suggests that overweight adolescents will increase rates of coronary heart disease among future young and middle-aged adults, resulting in substantial morbidity and mortality.
Year
Year
Extrapolation from current data suggests that overweight adolescents will increase rates of CHD among future young and middle-aged adults
CHD=Coronary heart disease
Source: Bibbins-Domingo K et al. NEJM 2007;357:

13. 2013 American Heart Association/ American College of Cardiology Guidelines
“dietary pattern that emphasizes fruits and vegetables, whole grains, legumes, fish, poultry, nuts and vegetable oils for fat, and restricted consumption of saturated and trans fats, sugar, sodium, and red meat”.
Dietary pattern evocative of the Mediterranean or DASH-type diet
J. Am. Coll. Cardiol Jan. 28

14. Mediterranean Diet Study
7447 men and women in Spain at high CVD risk (age years) received either: 1) Mediterranean diet with extra-virgin olive oil (140 ml/day), 2) Mediterranean diet with mixed nuts (30 grams/day of walnuts, almonds, and hazelnuts), or 3) a control diet (advice to reduce dietary fat).
Adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) for M diet group with olive oil and 0.72 (95% CI, 0.54 to 0.96) for the M diet group with nuts, respectively, versus the control group. No diet-related adverse effects were reported.
Primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or CVD death)
Conclusions: “ Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events.”
Estruch R et al N Engl J Med Apr 4;368(14): .

15. Associations Between the Percent of
Calories Derived from Specific Foods and
CHD Mortality in the 20 Countries Study*
Food Source Correlation Coefficient†
Butter
All dairy products
Eggs
Meats
Sugar and syrup
Grains, fruits, and vegetables
*1973 data, all subjects. From Stamler J: Population studies. In Levy R: Nutrition, Lipids, and CHD. New York, Raven, †All coefficients are significant at the P<0.05 level.

16. B Dietary Recommendations Primary Prevention
Women should consume a diet rich in fruits and vegetables; choose whole-grain, high-fiber foods; consume fish, especially oily fish,* at least twice a week; limit intake of saturated fat to <10% of energy, and if possible to <7%, cholesterol to <300 mg/d, alcohol intake to no more than 1 drink per day, and sodium intake to <2.3 g/d (approximately 1 tsp salt). Consumption of trans-fatty acids should be as low as possible (eg, <1% of energy) I
IIa
IIb
III B
*Pregnant and lactating women should avoid eating fish potentially high in methylmercury
Source: Mosca L et al. Circulation 2007;115: 16

17. 2013 AHA/ACC Guideline on Lifestyle
For blood pressure lowering, if recommended goals for sodium are not attainable, reducing sodium intake by at least 1,000 mg/day lowers blood pressure.
A reduction in sodium intake of approximately 1,000 mg/day reduces CVD events by approximately 30%.
Combining the DASH dietary pattern with lower sodium intake is recommended for lowering blood pressure.

18. Exercise Reduces Cardiac Event Recurrence
Steffen-Batey et al. Change in level of physical activity and risk of all-cause mortality or reinfarction: The Corpus Christi Heart Project. Circulation. 102(18):2204-9, 2000 Oct 31.

19. Physical Activity: Secondary Prevention
Observational study of self-reported physical activity in 772 men with CHD
Age-adjusted mortality rate/1000 person-years
This observational survey of self-reported physical activity in 772 British men with CHD found that those with light or moderate activity had the lowest all-cause and cardiovascular mortality. The adjusted relative risks compared to inactive/occasionally active men were 0.42 for light activity (95% CI ), 0.47 for moderate activity (95% CI, ), and 0.63 for moderately vigorous/vigorous activity (95% CI ).
Physical activity
Moderate exercise is associated with reduced mortality
CHD=Coronary heart disease, CVD=Cardiovascular disease
Source: Wannamethee SG et al. Circulation 2000;102: 19

20. CV Benefits of Lowering BP
Average Percent Reduction
Stroke incidence 35–40%
Myocardial infarction 20–25%
Heart failure 50%

21. mmHg <140/90 <140/90* <150/90*
2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8)
Condition
mmHg
Primary hypertension
<140/90
Diabetes mellitus
<140/90*
Chronic renal disease
Age > 60 years
<150/90*
JAMA.Published online December 18, 2013.

22. JNC VIII Guidelines
For younger patients (age, <60), drug therapy should be considered for diastolic BP ≥90 mm Hg or systolic BP ≥140 mm Hg. The goal is <140/90 mm Hg, but only the diastolic thresholds are based on high-quality evidence.
In the general population <60 years, initiate pharmacologic treatment to lower BP at DBP 90mmHg and treat to a goal DBP<90mmHg
In the general population aged 60 years, if pharmacologic treatment for high BP results in lower achieved SBP (eg, <140mmHg) and treatment is well tolerated and without adverse effects on health or quality of life, treatment does not need to be adjusted.
For older patients (age, ≥60), drug therapy should be considered for diastolic BP ≥90 mm Hg or systolic BP ≥150 mm Hg; the goal is <150/90 mm Hg.
For patients with diabetes and patients with chronic kidney disease, the threshold to initiate drug therapy is 140/90 mm Hg; the goal is <140/90 mm Hg.

23. JNC VIII Guidelines Cont’d
In nonblack patients, acceptable initial drug-class choices are thiazide-type diuretics, calcium-channel blockers (CCBs), angiotensin-converting–enzyme (ACE) inhibitors, and angiotensin-receptor blocker (ARBs).
In black patients, acceptable initial drug-class choices are thiazide-type diuretics or CCBs.
Patients with chronic kidney disease generally should receive ACE inhibitors or ARBs.
When patients require escalation of therapy, either maximizing doses of individual drugs sequentially or combining several drugs at submaximal doses is acceptable. Do not use ACE inhibitors and ARBs together.

24. Changes compared to JNC VII Guidelines
JNC 7 recommended a treatment threshold of 140/90 mm Hg regardless of age, whereas JNC 8 raises the systolic threshold at age 60.
In addition, JNC 7 recommended a lower treatment threshold (130/80 mm Hg) for patients with diabetes or chronic kidney disease, but JNC 8 does not.
In JNC 7, thiazide-type diuretics were recommended as initial drug therapy (unless compelling reasons dictated another drug class), with CCBs, ACE inhibitors, ARBs, and β-blockers as alternates. In JNC 8, the initial drug choice is broadened to four classes for nonblack patients and two classes for black patients.
β-blockers are no longer recommended for initial therapy because they might afford less protection against stroke.

25. On-Treatment LDL-C is Closely Related to CHD Events in Statin Trials – Lower is Better30
4S - Placebo 25
Rx - Statin therapy
PRA – pravastatin
ATV - atorvastatin
Secondary Prevention
4S - Rx 20
Event rate (%)
LIPID - Placebo 15
CARE - Placebo
LIPID - Rx
CARE - Rx
Primary Prevention
HPS - Rx
TNT – ATV10
HPS - Placebo 10
PROVE-IT - PRA
TNT – ATV80
WOSCOPS – Placebo
PROVE-IT – ATV
AFCAPS - Placebo
A number of landmark studies have shown that the reduction of LDL-C with statin therapy improves cardiovascular morbidity and mortality in patients with and without established cardiovascular disease. In both primary and secondary prevention studies a greater reduction in LDL-C resulted in greater reductions in cardiovascular (CV) events. Achieving lower LDL-C levels is now increasingly accepted.
The data clearly show that whether you have CV or not and whatever your baseline LDL-C is, however much you lower LDL-C you reduce CV risk and the lower you can get your LDL-C the better. The international guidelines for screening and intervention are based on evidence such as that presented together with epidemiological data. It is therefore reasonable that the achievement of evidence-based treatment guideline goals can be used as a good surrogate for outcomes data until that becomes available.
References
Ballantyne C. Low-density lipoproteins and risk for coronary artery disease. Am J Cardiol 1998;82:3Q-12Q
Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7–22.
Sever, PS et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial – Lipid Lowering Arm: a multicentre randomised controlled trial. Lancet 2003;361:
Rosensen RS. Exp Opin Emerg Drugs 2004;9(2):
LaRosa JC, Grundy SM, Waters DD et al. N Engl J Med 2005;352:e-version.
Adapted from Am J Cardiol 1998;82:3Q-12Q with permission from Excerpta Medica Inc. 6 5
But, how low should we go?
AFCAPS - Rx
WOSCOPS - Rx
ASCOT - Placebo
ASCOT - Rx 40
(1.0) 60
(1.6) 80
(2.1)
100
(2.6)
120
(3.1)
140
(3.6)
160
(4.1)
180
(4.7)
200
(5.2)
LDL-C achieved mg/dL (mmol/L)
Adapted from Rosensen RS. Exp Opin Emerg Drugs 2004;9(2):
LaRosa JC et al. N Engl J Med 2005;352:e-version

26. Majority of Residual Risk for Cardiovascular Events Remains Despite LDL Lowering Therapy
Reduction in Major Coronary Events (%)
[-100]
[-80]
[-60]
[-40]
[-20]
100 80 60 40 20
Coronary Events (%)
Residual Major
-38%
-25%
-27%
-31%
62%
75%
73%
69%
Speaker Notes
The question remains, what are we doing to reduce the remaining 70-75% of residual risk?
6 out of 10 will still have events
What are we doing to prevent ?
Is LDL the unsinkable ship
Key Point: Treatment for dyslipidemia aimed only at LDL-C lowering does not achieve optimal reductions in risk of CVD events.
This slide shows a number of clinical end point trials that used statin only to lower low-density lipoprotein cholesterol (LDL-C). Lowering of LDL-C resulted in a relative risk reduction in major coronary events between 25% to 38% with an average relative risk reduction of 30%.
4S- Scandinavian Simvastatin Survival trial; LIPID- The Long-Term Intervention with Pravastatin in Ischemic Disease study; CARE- Cholesterol and Recurrent Events trial; HPS- Heart Protection Study; WOSCOPS-The West of Scotland Coronary Prevention Study; AFCAPS/TexCAPS-Air Force/Texas Coronary Atherosclerosis Prevention studies
Reference
Adapted from Libby P. The forgotten majority: unfinished business in cardiovascular risk reduction. J Am Coll Cardiol. 2005;46(7):
Trial N 4S
4,444
LIPID
9,014
CARE
4,159
HPS
20,536
WOSCOPS
6,595
AFCAPS/TexCAPS
6,605
Secondary Prevention
High Risk
Primary Prevention
Adapted from Libby P. The forgotten majority: unfinished business in cardiovascular risk reduction. J Am Coll Cardiol. 2005;46(7):
© 2014 Boston Heart Diagnostics Corporation

27. Groups Recommended for Statin Therapy
Group 1: Subject with evidence of clinical CVD (acute coronary syndrome, history of myocardial infarction, stable or unstable angina, coronary or other revascularization, stroke, transient ischemic attacks, and/or peripheral vascular disease. (should receive high intensity statin and ideally get more 50% LDL-C reduction)
Group 2: Subject with LDL-C > 190 mg/dL. (should receive high intensity statin)
Group 3: Diabetic subject age years with LDL-C of mg/dL and without CVD. (should receive moderate intensity statin, and get % LDL-C reduction)
Group 4: Subject without ASCVD or diabetes and a 10 year ASCVD risk >7.5% (should receive low intensity statin). Use the risk calculator at calculator  (gender, age, sys. Bp, smoking, diabetes, total cholesterol, and HDL cholesterol)
Goff DC Jr et al ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation Nov 12.

28. Definitions of Statin Intensity
High: atorvastatin mg/day, rosuvastatin mg/day;
Moderate: atorvastatin mg/day, rosuvastatin mg/day, simvastatin mg/day, pravastatin 40 mg/day, lovastatin 40 mg/day, fluvastatin XL 80 mg/day, or pitavastatin mg/day;
Low: simvastatin 10 mg/day, pravastatin mg/day, lovastatin 20 mg/day, fluvastatin XL mg/day, or pitavastatin 1 mg/day.  
Stone NJ et al ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation Nov 12.

29. Use of Non-Statin Agents
“Clinicians treating high risk patients who have a less than anticipated responses to statins, who are unable to tolerate a less than recommended intensity of a statin, or who are completely statin intolerant, may consider the addition of a nonstatin cholesterol lowering drug.“
“Clinicians should preferentially prescribe drugs that have been shown in randomized clinical trials to provide ASCVD risk reduction benefits that outweigh the potential for adverse effects and drug-drug interactions. Fibrates, niacin, resins, and the statin/ezetimibe combination have shown ASCVD risk reduction in randomized trials as compared to placebo.”

30. AIM HIGH-Post HOC Analysis
In 3-year follow-up in 3,414 patients with CVD and HDL-C < 40 mg/dL combined niacin + LDL-C lowering therapy did not reduce CV events compared with LDL-C-lowering therapy alone.
In a subset of patients in the top TG tertile (≥ 198 mg/dl) and the bottom HDL-C tertile (< 33 mg/dl), ER niacin showed a trend toward benefit (hazard ratio: 0.74, p = 0.073).
On-trial LDL-C levels, non-HDL-C levels, and the total cholesterol/HDL-C ratio were positively associated with CV events in the control group, but these relationships were absent in the ER niacin
These data suggest that the high TG/low HDL group are highest risk, and may get benefit from niacin on top of statin therapy.
Guyton J et al J Am Col2013; 62:

31. Fibrates: Subgroup Analysis
In ACCORD Lipid – overall event rate was 11.3% in the simvastatin monotherapy group and 10.5% in the simvastatin/ fenofibrate group (p=0.32).
In the subgroup with TG > 200 mg/dL and HDL-C < 35 mg/dL event rate was 17.3% (+53%) in the simvastatin monotherapy group and 12.4% (-28%) in the simvastatin/ fenofibrate group (p=0.03).
Similar observations in BIP and FIELD
Ginsberg HN et al New Engl J Med 2010;362:1563-9

32. Secondary Causes of Dyslipidemia
Secondary Causes of Elevated LDL-C: obesity, increased intake saturated fat & trans fats, hypothyroidism, diuretics, cyclosporin, glucocorticoids, amiodorone, biliary obstruction, nephrotic syndrome, pregnancy, & anorexia  
Secondary Causes of Elevated Triglycerides: obesity, diabetes, high sugar intake, excessive alcohol intake, hypothyroidism, oral estrogens, glucocorticoids, bile acid sequestrants, protease inhibitors, retinoic acid, anabolic steroids, sirolimus, raloxifene, tamoxifen, beta blockers (except carvedilol), thiazides, and pregnancy.

33. Cholesterol-Carrying Lipoproteins
VLDL
0.95
Chylomicron
Chylomicron
VLDL
VLDL
VLDL
Remnants
1.006
IDL
Chylomicron
Remnants
Particle Density, g/mL
1.02
LDL
Heart disease patients often have increased remnants lipoproteins, small dense LDL), and Lp(a), and decreased large HDL)
1.06
HDL2
1.10
Key Point:
Several different atherogenic lipoproteins can carry cholesterol.
Lp(a)
HDL3
1.20 5 10 20 40 60 80
1000
Particle Size - Diameter, nm
Genest et al Circulation 1992;85:2025, Campos et al, ATVB 1992; 12:187, Schaefer et al JAMA 1994;59:32, McNamara et al Atherosclerosis 2001;154:229, Asztalos et al ATVB 2004;24:2181, & Ai et al Clin Chem 2010; 56:

34. Little evidence of disease
IVUS detects angiographically “silent” atheroma – to get regression LDL-C needs to be < 70 mg/dL and HDL-C needs to be raised by > 8% - only 2/3 get regression with aggressive statin treatment
IVUS
Angiogram
Little evidence of disease
No evidence of disease
:57:05 AM 31
MA 1120
MA 1120 7 31 7
:57:05 AM
IVUS
Atheroma
Core slide
This slide shows an example where an atheroma, evident by IVUS, remains undetected by angiography as a result of coronary remodelling.
On the left, the angiogram is completely normal. However, two sites in the anterior descending coronary artery, indicated by arrows, show a varying extent of atherosclerosis by IVUS. The more distal site (top right) has little disease, but the more proximal site (bottom right) has a large crescentic atheroma. The lumen size at both sites is similar because of remodelling, resulting in a false-negative angiogram.
Reference
Nissen SE, Yock P. Intravascular ultrasound: novel pathophysiological insights and current clinical applications. Circulation 2001; 103: 604–616.
Abbreviation
IVUS=intravascular ultrasound
Reproduced from Circulation 2001; 103: 604–616, with permission from Lippincott Williams & Wilkins.
IVUS = intravascular ultrasound, Nissen S, Yock P. Circulation 2001; 103: 604–616, Nicholls S et al ASTEROID and SATURN Studies 2007, 2011.
Reviewed and Approved by Medical Affairs: Slide Deck ID - MA April 2006

35. Statin Meta Analyses – Oxford
“For every 40 mg/dL reduction in LDL-C, there is a 20% reduction in cardiovascular endpoints.”

36. People are diagnosed with type 2 diabetes
Everyday in the U.S.1
People go blind
>55
5200
People are diagnosed with type 2 diabetes
People begin dialysis
>120
People undergo amputations
>230
Diabetes is an epidemic in the U.S. and worldwide. In the U.S.:
26 M people have type 2 diabetes = 1 in 10
79 M have prediabetes = 1 in 3
Approximately 2 M new cases of diabetes diagnosed each year = 1 in 40
References for above:
(Accessed March 2011)
(Accessed September 2011)
“If trends continue, 1 in 3 children born in 2000 will develop diabetes in their lifetime”
Ref:
(Accessed September 2011)
Slide References:
“5,200 people…”: (Accessed March 2011)
Incidence figures re: comorbidities: National Diabetes Fact Sheet of the National Center for Chronic Disease Prevention and Heath Promotion; NCHS; CDC; ADA; AACE (Updated February 2009)
“Every 17 seconds, someone in the U.S. is diagnosed with diabetes”/ “Diabetes now kills…”:
Every 17 seconds, someone in the U.S. is diagnosed with diabetes2
Diabetes now kills more people each year than breast cancer and AIDS combined.2
1. (Accessed March 2011)
2. (Accessed September 2011)

37. Positive Effects of Lifestyle Changes Diabetes Prevention Project
3234 prediabetic subjects with  fasting glucose (100 – 125 mg/dL) and body mass index of 34.0 kg/m2
Lifestyle modification over 3 years: (goal of 7% weight-loss and > 150 min. physical activity /week, fat < 25% of calories, 500 calorie deficit/day vs. metformin vs. placebo
New Development of Diabetes Mellitus
33% over 3 years in usual care group
23% over 3 years in metformin group (-31%)
14% over 3 years in lifestyle group (-58%)
Boston Heart Diagnostics - similar lifestyle program
Diabetes Prevention Program Research Group. New Eng J Med 2002; 346:393-9.

38. Clinical Studies Demonstrate Prevention is Possible
Key Message: Importantly, we have learned that diabetes is preventable. The DPP and DPS studies showed that lifestyle intervention could result in a significant decrease in new onset diabetes. Although not approved for use in patients with pre-diabetes, pharmacologic treatment may also slow or prevent the progression toward diabetes.
Note: Use of oral anti-diabetics is not approved by the FDA for use in patients with pre-diabetes.
References:
Diabetes Prevention Program Research Group. NEJM ; 346:
Tuomilehto J, et al. NEJM ; 344:
DREAM Trial Investigators. Lancet. 2006; 368:
Zinman B, et al. Lancet ; 376:
DeFronzo R, et al. Late Breaking Clinical Presentation: 68th ADA Scientific Sessions, 2008.
*Currently, no medications are FDA-approved for the prevention of diabetes
Diabetes Prevention Program Research Group. NEJM ; 346: Tuomilehto J, et al. NEJM ; 344: DREAM Trial Investigators. Lancet. 2006; 368: Zinman B, et al. Lancet ; 376: DeFronzo R, et al. N Engl J Med. 2011; 365: 9

39. CARDIOMETABOLIC IMPACT
Lancet 1999; 354:
DECODE Study Group
10-year follow-up of Normal Glucose Tolerance, Impaired Glucose Tolerance and Diabetes Mellitus
Two-fold increase risk of CVD for IGT vs. NGT
Four-fold increase risk of CVD for DM vs. NGT
80% of diabetics die of CVD
MI (60%) / CVA (20%)

40. CARDIOMETABOLIC IMPACT
More than 70% of Coronary Artery Disease/Acute Coronary Syndrome sufferers are insulin resistant!
Diabetes Care 2008; 31:
Lancet 2007; 370:
Every 18mg/dl above 140mg/dl at 2-hour plasma glucose increases cardiovascular and all-cause death rates by 26% over 6-7 years
Diabetes Care 2009; 32:

41. LAB CLUES Triglycerides >130 mg/dl Low HDL/LOW HDL2b High sdLDL
FPG>88mg/dl
Fasting Insulin
>16microU/ml
HgB A1C > 5.6%
^ MACR
^ hsCRP
^ Fibrinogen
^ Lp-PLA2
Decreased Vitamin D
Triglyceride/HDL Ratio
(Ethnic variation)
GGTP >21mg/dl women;
>47mg/dl men
ALT > 20mg/dl women
> 34mg/dl men

42. Examples of Coronary Artery ScansNO
CALCIFICATION
“zero score”
MODERATE
CALCIFICATION
SIGNIFICANT
CALCIFICATION
“high score”

43. Primary Prevention of Cardiovascular Disease
For persons aged 50 years or older without symptomatic cardiovascular disease, we suggest low-dose aspirin 75 to 100 mg daily over no aspirin therapy (Grade 2B).
Remarks: Aspirin slightly reduces total mortality regardless of cardiovascular risk profile if taken over 10 years. In people at moderate to high risk of cardiovascular events, the reduction in myocardial infarction (MI) is closely balanced with an increase in major bleeds. Whatever their risk status, people who are averse to taking medication over a prolonged time period for very small benefits will be disinclined to use aspirin for primary prophylaxis. Individuals who value preventing an MI substantially higher than avoiding a GI bleed will be, if they are in the moderate or high cardiovascular risk group, more likely to choose aspirin.

44. Odds Ratio for Vascular Events
Aspirin Evidence: Dose and Efficacy
Indirect comparisons of aspirin doses on vascular events in high-risk patients
Odds Ratio for Vascular Events
Aspirin Dose No. of Trials (%) mg mg mg
<75 mg
Any aspirin
75 mg of aspirin per day results in almost complete inhibition of cyclooxygenase activity in platelets. This slide demonstrates that high doses of aspirin are no more effective than medium or low doses in reducing the odds of vascular events. Trials using doses of <75mg are less conclusive and, therefore, the available evidence supports daily doses of aspirin in the  mg range.
Overall: For secondary prevention of CVD an aspirin dose of  mg/d is recommended.
P<.0001
0.5
1.0
1.5
2.0
Antiplatelet Better
Antiplatelet Worse
Antithrombotic Trialist Collaboration. BMJ 2002;324:71-86

45. Primary Prevention (Women)
Aspirin Recommendations
Primary Prevention (Women) I
IIa
IIb
III B
Aspirin (81 mg daily or 100 mg every other day) in at risk women >65 years of age
Aspirin in at risk women <65 years of age for ischemic stroke prevention
Aspirin in optimal risk women <65 years of age
ACC/AHA primary prevention guidelines for aspirin include a Level B, Class IIa (certainty based on single large RCT trial or several non-RCT’s suggests benefit is greater than risk) recommendation for the use of aspirin in women with an estimated cardiovascular risk score (as calculated in NCEP ATPIII) of > 10% over the next 10 years and over the age of 65 years. A Level B, Class IIb (conflicting evidence based on single large RCT trial or several non-RCT’s suggests benefit is greater than risk) for the use of aspirin in women with an estimated cardiovascular risk score (as calculated in NCEP ATPIII) of > 10% over the next 10 years and less than 65 years old. A Level B, Class III (certainty based on single large RCT trial or several non-RCT’s suggests risk is greater than benefit) for the use of aspirin in women with an estimated cardiovascular risk score (as calculated in NCEP ATPIII) of < 10% over the next 10 years and less than 65 years old.
CHD=Coronary heart disease

46. Primary Prevention (Men*)
Aspirin Recommendations
Primary Prevention (Men*)
Aspirin ( mg daily) in those at intermediate risk (10 year risk of CHD >10%)
ACC/AHA primary prevention guidelines for aspirin include a Level A, Class I (highest level of certainty, greatest risk benefit ratio) recommendation for the use of aspirin (75-162mg/d) in men with an estimated cardiovascular risk score (as calculated in NCEP ATPIII) of > 10% over the next 10 years.
*Specific guideline recommendations for men do not exist, but these guidelines are based on previous general (not gender specific) primary prevention guidelines
CHD=Coronary heart disease

47. Secondary Prevention

48. CVD Risk Prediction
The best predictor of future CHD is the presence of pre-existing disease. There is a high correlation between carotid and coronary artery atherosclerosis. Carotid ultrasound remains the most cost-effective strategy to detect the presence of early atherosclerosis. Another option is cardiac calcium scoring.

49. Copyright © 2014 American Medical Association. All rights reserved.
Effect of Smoking Cessation on Mortality After Myocardial Infarction:  Meta-analysis of Cohort Studies
Arch Intern Med. 2000;160(7): doi: /archinte
Table Title:
Benefit of Smoking Cessation on Mortality After Myocardial Infarction: Results of the Primary Studies*
Date of download: 11/2/2014
Copyright © 2014 American Medical Association. All rights reserved.

50. Aspirin Recommendations (Cont’d)
Secondary Prevention
Aspirin ( mg daily) if known CHD/ASVD
Aspirin ( mg daily) for at least 3 months after sirolimus-eluting stent implantation and at least 6 months after paclitaxel-eluting stent implantation after which aspirin ( mg daily) should be continued indefinitely
ACC/AHA secondary prevention guidelines for aspirin include a Level A, Class I (highest level of certainty, greatest risk benefit ratio) recommendation for the use of aspirin (75-162mg/d) in men and women with known coronary heart disease/atherosclerotic vascular disease. A Level B, Class I (certainty based on single large RCT trial or several non-RCT’s, greatest risk benefit ratio) recommendation for the use of aspirin following coronary artery bypass grafting.
ASVD=Atherosclerotic vascular disease, CABG=Coronary artery bypass graft, CHD=Coronary heart disease

51. C Aspirin Recommendations (Cont’d) Secondary Prevention
IIa
IIb
III C
Aspirin ( mg daily) as the initial dose after stent implantation in those at higher bleeding risk
Aspirin ( mg daily) following CABG surgery*
ACC/AHA secondary prevention guidelines for aspirin include a Level A, Class I (highest level of certainty, greatest risk benefit ratio) recommendation for the use of aspirin (75-162mg/d) in men and women with known coronary heart disease/atherosclerotic vascular disease. A Level B, Class I (certainty based on single large RCT trial or several non-RCT’s, greatest risk benefit ratio) recommendation for the use of aspirin following coronary artery bypass grafting.
*To be administered within the first 48 hours after surgery in order to reduce the risk of saphenous vein graft failure. Doses >162 mg/day may be continued for up to one year

52. B C B P2Y12 Receptor Antagonist Recommendations Secondary Prevention
IIa
IIb
III B
Clopidogrel (75 mg daily; Class I, Level B), prasugrel* (10 mg daily; Class I, Level C), or ticagrelor (90 mg twice daily; Class I, Level C) if aspirin intolerance or a true aspirin allergy following a NSTE-ACS
Clopidogrel (75 mg daily) or ticagrelor (90 mg twice daily) in addition to aspirin for up to 1 year following a NSTE-ACS managed conservatively I
IIa
IIb
III C I
IIa
IIb
III B
*In PCI treated patients
NSTE-ACS=Non ST-segment elevation acute coronary syndrome; PCI=Percutaneous coronary intervention, STEMI=ST-segment elevation myocardial infarction
Source: Jneid H et al. JACC 2012;60:

53. B A C P2Y12 Receptor Antagonist Recommendations Secondary Prevention
IIa
IIb
III B
Clopidogrel (75 mg daily), prasugrel (10 mg daily), or ticagrelor (90 mg twice daily) in addition to aspirin for 1 year following PCI for a NSTE-ACS† or a STEMI‡
Clopidogrel (75 mg daily) in addition to aspirin for a minimum of 14 days (Class I, Level A) and up to 1 year (Class I, Level C) following fibrinolytic therapy for a STEMI‡ I
IIa
IIb
III A I
IIa
IIb
III C
NSTE-ACS=Non ST-segment elevation acute coronary syndrome; PCI=Percutaneous coronary intervention, STEMI=ST-segment elevation myocardial infarction
Sources:
†Jneid H et al. JACC 2012;60:
‡O’Gara PT et al. JACC 2013;61:e78-e140

54. C C P2Y12 Receptor Antagonist Recommendations (Cont’d)
Secondary Prevention I
IIa
IIb
III C
If the risk of morbidity because of bleeding outweighs the anticipated benefit afforded by a P2Y12 receptor antagonist, earlier discontinuation should be considered
Continuation of a P2Y12 receptor antagonist beyond 1 year may be considered in patients undergoing drug eluting stent placement I
IIa
IIb
III C
Sources:
Kushner F et al. JACC 2009;54:
Jneid H et al. JACC 2012;60:
O’Gara PT et al. JACC 2013;61:e78-e140

55. A B ACE Inhibitor Recommendations Secondary Prevention
IIa
IIb
III A
An ACE inhibitor should be started and continued indefinitely in all patients with left ventricular ejection fraction <40% and in those with hypertension, DM, or CKD, unless contraindicated
An ACE inhibitor in all other patients I
IIa
IIb
III B
ACE=Angiotensin converting enzyme, CKD=Chronic kidney disease, DM=Diabetes mellitus, LVSD=Left ventricular systolic dysfunction
Source: Smith SC Jr. et al. JACC 2011;58:

56. A B A Angiotensin Receptor Blocker Recommendations
Secondary Prevention I
IIa
IIb
III A
An ARB in patients who have HF or who have had a MI with left ventricular ejection fraction <40% and who are ACE-inhibitor intolerant
An ARB in other patients who are intolerant of an ACE inhibitor
Use of an ARB in combination with an ACE inhibitor is not well established in those with systolic heart failure I
IIa
IIb
III B I
IIa
IIb
III A
ACE=Angiotensin converting enzyme, ARB=Angiotensin receptor blocker, HF=Heart failure, MI=Myocardial infarction
Source: Smith SC Jr. et al. JACC 2011;58:

57. A B B Beta-Blocker Recommendations Secondary Prevention
Beta-blocker should be used in all patients with LVSD (ejection fraction <40%) with HF or prior MI, unless contraindicated*. (Use should be limited to carvedilol, metoprolol succinate, or bisoprolol, which have been shown to reduce mortality.)
Beta-blocker for 3 years in all patients with normal left ventricular function who have had a MI or ACS
Beta-blocker beyond 3 years as chronic therapy in all patients with normal left ventricular function who have had a MI or ACS I
IIa
IIb
III A I
IIa
IIb
III B I
IIa
IIb
III B
*Relative contraindications include asthma, chronic obstructive pulmonary disease, insulin dependent diabetes mellitus, severe peripheral arterial disease, and a PR interval >0.24 seconds
ACS=Acute coronary syndrome, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction
Source: Smith SC Jr. et al. JACC 2011;58:

58. Myocardial infarction (%)
Cardiac Rehabilitation:
Greater Benefit with Greater Attendance
Observational study of 30,161 Medicare patients attending at least 1 phase II cardiac rehabilitation session
Death (%)
Myocardial infarction (%)
In this study, after adjustment for demographic characteristics, comorbid conditions, and subsequent hospitalization, patients attending 36 sessions of cardiac rehabilitation had a 14% lower risk of death (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.77 to 0.97) and a 12% lower risk of MI (HR, 0.88; 95% CI, 0.83 to 0.93) than those who attended 24 sessions; a 22% lower risk of death (HR, 0.78; 95% CI, 0.71 to 0.87) and a 23% lower risk of MI (HR, 0.77; 95% CI, 0.69 to 0.87) than those who attended 12 sessions; and a 47% lower risk of death (HR, 0.53; 95% CI, 0.48 to 0.59) and a 31% lower risk of MI (HR, 0.69; 95% CI, 0.58 to 0.81) than those who attended only 1 session.
Years after Index Date
Years after Index Date
There is a strong dose-response relationship between the number of cardiac rehabilitation sessions attended and long-term CV outcomes
CV=Cardiovascular
Source: Hammill BG et al. Circulation 2010;121:63-70

59. What Diagnoses are Covered?
Medicare Guidelines: 36 sessions per year after cardiac event
Angina
Myocardial Infarction
Coronary Artery Bypass Graft
Heart Transplant
Valve Surgery
Stent
Coronary Artery Disease (CAD)
Private insurance coverage may vary and may cover
PAD - CHF
Cardiomyopathy - Valvular disease
Medicare currently covers MI, stable angina and CABG patients for entry in Cardiac Rehab.
Some private insurance carriers provide coverage for other diagnoses, such as heart failure, valve replacement/repair, transplant and PTCA/Stent.
Verification of coverage prior to program initiation should be done by the patient or cardiac rehab staff. A letter of medical necessity from the referring physician may be necessary.

60. Utilization Benefits:
Reduced risk of fatal MI (<25%)
Decreased severity of angina & need for anti-angina meds
Decreased hospitalizations
Decreased cost of physician office visits & hospitalizations (<35%)
Fewer ER visits
Cost of health care is a national, state and local issue providers and patients deal with every day.
Cardiac rehab programs have shown statistical improvement in utilization and cost of health care.
By providing education on prevention and signs and symptoms of their cardiac disease, patients are able to make better judgments about obtaining access and entry to the appropriate health care provider.
Ades, PA, et al (2000) Medical Clinics of North America
Sudlow, C, et al (1999) Clinical Evidence
Lavie, CJ, et al (1999) Cardiology Clinics

61. Patient Benefits: Improved functional capacity
Increased knowledge of heart disease
Improved adherence to positive lifestyle changes
Better compliance with medical regime
Increased self-esteem and confidence
Reduced subsequent morbidity & mortality r/t CAD
Patients in a cardiac rehab program improve their heart health through exercise, education and lifestyle modification. It has been shown that patient adherence to suggested lifestyle changes improved as the understanding of the importance and impact of each lifestyle change is explained to patients.
Monitored progressive exercise/activity is conducted based on patient tolerance (hemodynamics and symptoms) as well as pre-event/procedure status and goals.
Education during cardiac rehab includes:
CAD physiology
Signs & symptoms (and appropriate actions—NTG, 911, etc)
Smoking cessation
Diabetes management
Stress management
Lipid control
Medication compliance
Exercise parameters/benefits
Nutrition guidance (HTN, hyperlipidemia, weight loss, diabetes control)
Please identify any specific educational topics not listed that your program provides to further personalize this information to your program.

62. Lifestyle Benefits: Risk Factor and Lifestyle Modification
Smoking cessation
Lipid improvement
Blood pressure control
Exercise guidance
Weight management
Diabetes control
Stress management
A well known fact is the multi-dimensional needs of patients with coronary artery disease. Although heredity, gender and age play a role in the development and progression of CAD, it is primarily a disease of lifestyle. Lifestyle intervention (secondary prevention) is a key factor in altering this progression.
Cardiac Rehab focuses on the specific risk factors of each patient and establishes goals to achieve positive patient outcomes through therapeutic lifestyle changes. Patients benefit by having many health and lifestyle issues addressed in a supportive, individual/group environment.

63. A Antioxidant Vitamin Guidelines Secondary Prevention
IIa
IIb
III A
Antioxidant vitamin supplements (e.g., vitamins E, C, or beta carotene) should not be used for secondary prevention in NSTE-ACS.
NSTE-ACS=Non-ST-segment elevation acute coronary syndrome
Anderson JL et al. JACC 2007;50:

64. A B Vitamins and Folic Acid Guidelines Secondary Prevention
IIa
IIb
III A
Folic acid, with or without B6 and B12, should not be used for secondary prevention in NSTE-ACS
NSTE-ACS=Non-ST-segment elevation acute coronary syndrome
Anderson JL et al. JACC 2007;50:

65. A B Hormone Replacement Therapy Guidelines Secondary Prevention
IIa
IIb
III A
HRT with estrogen plus progestin, or estrogen alone, should not be given de novo to postmenopausal women after NSTE-ACS for secondary prevention of coronary events.
Postmenopausal women who are already taking estrogen plus progestin, or estrogen alone, at the time of NSTE-ACS in general should not continue HRT. Women who are more than 1-2 years past the initiation of HRT who wish to continue therapy for another compelling indication should weigh the risks and benefits, recognizing the greater risk of CV events and breast cancer (combination therapy) or stroke (estrogen). I
IIa
IIb
III B
CV=Cardiovascular, HRT=Hormone replacement therapy, NSTE-ACS=Non-ST-segment elevation acute coronary syndrome
Anderson JL et al. JACC 2007;50:

66. C C Nonsteroidal Anti-inflammatory Drug Guidelines
Secondary Prevention
At hospital discharge, the patient’s need for treatment of chronic musculoskeletal discomfort should be assessed, and a stepped-care approach to treatment should be used, starting with acetaminophen, small doses of narcotics, or nonacetylated salicylates.
It is reasonable to use nonselective NSAIDs, such as naproxen, if initial therapy with acetaminophen, small doses of narcotics, or nonacetylated salicylates is insufficient. I
IIa
IIb
III C I
IIa
IIb
III C
NSAIDs=Nonsteroidal anti-inflammatory drugs
Anderson JL et al. JACC 2007;50:

67. C Nonsteroidal Anti-inflammatory Drug Guidelines (Cont’d)
Secondary Prevention
It is reasonable to use nonselective NSAIDs, NSAIDs with increasing degrees of relative COX-2 selectivity may be considered for pain relief only for situations in which intolerable discomfort persists despite attempts at stepped-care therapy with acetaminophen, small doses of narcotics, nonacetylated salicylates, or nonselective NSAIDs. In all cases, the lowest effective doses should be used for the shortest possible time I
IIa
IIb
III C
COX-2-Cyclooxygenase 2, NSAIDs=Nonsteroidal anti-inflammatory drugs
Anderson JL et al. JACC 2007;50:

68. Aldosterone Antagonist Guidelines
Secondary Prevention
Use of aldosterone blockade in post-MI patients without significant renal dysfunction* or hyperkalemia** is recommended in patients who are already receiving therapeutic doses of an ACE inhibitor and beta-blocker, who have a LV EF <40%, and who have either DM or HF I
IIa
IIb
III A
*Estimated creatinine clearance should be >30 ml/min **Potassium should be <5.0 mEq/L
ACE=Angiotensin converting enzyme, DM=Diabetes mellitus, EF=Ejection fraction, HF=Heart failure, LV=Left ventricular, MI=Myocardial infarction
Source: Smith SC Jr. et al. JACC 2011;58:

69. Digoxin Guidelines B C Secondary Prevention
IIa
IIb
III B
Digoxin in those with symptomatic HF and LVSD (EF <45%) to reduce hospitalizations for HF*
Digoxin in those with asymptomatic LVSD and normal sinus rhythm I
IIa
IIb
III C
*Contraindications include significant sinus or atrioventricular block unless a permanent pacemaker is present
EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic function
Source: Hunt SA et al. Circulation 2005;112:e

70. A B Implantable Cardioverter Defibrillator Guidelines
Secondary Prevention
Patients with an ejection fraction of <35% who are at least 40 days post-MI and are in NYHA functional Class II or III
Patients with an ejection fraction of <30% who are at least 40 days post-MI and are in NYHA functional Class I
Patients with nonsustained VT due to prior MI, an ejection fraction of <40%, and inducible sustained VT or VF at EP study I
IIa
IIb
III A I
IIa
IIb
III B
EP=Electrophysiology, MI=Myocardial infarction, NYHA=New York Heart Association, VF=Ventricular fibrillation, VT=Ventricular tachycardia
Epstein AE et al. Circulation 2008;117:e

71. Influenza Vaccination Guidelines
Secondary Prevention I
IIa
IIb
III B
Patients with cardiovascular disease should have an annual influenza vaccination
Source: Smith Jr SC et al. JACC 2011;58:

72. Evidence for Current Cardiovascular Disease Prevention Guidelines
Room for Improvement

73. ACTION Registry/Get With The Guidelines (GWTG) Data
Utilization of Risk Reducing Medications
at Discharge in Acute Coronary Syndromes
ACTION Registry/Get With The Guidelines (GWTG) Data
86%
NSTEMI
STEMI
NSTEMI=Non-ST-segment elevation myocardial infarction, STEMI=ST-segment elevation myocardial infarction
Source: ACTION Registry-GWTG DATA: January 1, 2010 – December 31, Courtesy of NCDR 10/21/2011

74. Strategies for Initiating and Optimizing Cardiovascular Therapies
Hospital based performance improvement systems
In-hospital initiation of CV protective therapies
Pay for performance/financial incentives
Nurse or pharmacist managed outpatient CV prevention programs
Preventive cardiology and cardiac rehabilitation centers
Virtual prevention clinics using electronic medical record systems
Combination of CV protective medications
CV=Cardiovascular

75. Thank You

76. THANK YOU !

77. If you’re just measuring basic lipids…
You may think
your patients
are healthy.
Speaker Notes
Compelling message to deliver to HCPs:
If you’re just measuring basic lipids and treating with statins to lower LDL…
You may think your patients are healthy (by reducing some CVD risk).
Advance slide to reveal ‘hidden risk’
But you’d be missing the whole picture.
Key Point: Better diagnostic methods are needed to adequately identify all individuals at risk of CVD.
A key question for clinicians is how do we address the remaining 70% to 75% residual risk for CVD in a patient who is receiving a statin for dyslipidemia?
Clinical trials using tests not found on a routine lipid panel have identified multiple additional markers that identify CVD risk; and advanced CVD risk markers are needed to identify disorders that contribute to the remaining 70-75% residual risk.1-3
The tests developed by Boston Heart can help to identify underlying factors that contribute significantly to increased risk of CVD.
References
Asztalos BF, Cupples LA, Demissie S, et al. High-density lipoprotein subpopulation profile and coronary heart disease prevalence in male participants of the Framingham Offspring Study. Arterioscler Thromb Vasc Biol ;24(11):
Asztalos BF, Collins D, Cupples LA, et al. Value of high-density lipoprotein (HDL) subpopulations in predicting recurrent cardiovascular events in the Veterans Affairs HDL Intervention Trial. Arterioscler Thromb Vasc Biol ;25(10):
Lamon-Fava S, Herrington DM, Reboussin DM, et al. Plasma levels of HDL subpopulations and remnant lipoproteins predict the extent of angiographically-defined coronary artery disease in postmenopausal women. Arterioscler Thromb Vasc Biol. 2008;28(3):
You’d be missing the whole picture.
© 2014 Boston Heart Diagnostics Corporation 77

79. What About Desoto County in Mississippi????

80. Secondary Causes OSA Primary Aldosteronism Renal Parenchymal Diseases
Common
OSA
Primary Aldosteronism
Renal Parenchymal Diseases
Renal Artery Stenosis

81. Secondary Causes Uncommon Pheochromocytoma Cushing’s disease
Hyperparathyroidism
Coarctation of aorta

82. Exercise Reduces Mortality in MI Survivors
Steffen-Batey et al. Change in level of physical activity and risk of all-cause mortality or reinfarction: The Corpus Christi Heart Project. Circulation. 102(18):2204-9, 2000 Oct 31.

83. DIAGNOSIS GOLD STANDARD TECHNIQUES
IV INSULIN TOLERANCE TEST
INSULIN SUPPRESSION TEST
EUGLYCEMIC INSULIN CLAMP
“POOR MAN’S TEST” TRIGLYCERIDE/HDL RATIO
PRESENT ON EVERY LIPID PROFILE
CAUCASIAN >3.5
MEXICAN-AMERICAN >3.0
NON-HISPANIC BLACK >2.0
CLINICAL TECHNIQUES
BIOCHEMICAL MARKERS
Test Value Sensitivity Specificity
TRIGLYCERIDE >130mg/dl % %
TRIGLYCERIDE/HDL > % %
FASTING INSULIN >16 microU/ml % % 
Ann Int Med 2003; 139:802
McLaughlin et al.

84. DART TRIAL
In the Diet and Reinfarction Trial (DART) in 2033 men with CHD increased intake of fish or use of 2 fish oil caps/day (provided) reduced CHD mortality 29% over 2 years
No benefit from other diet interventions in this trial including restriction of total fat and animal fat
Burr et al Lancet 2; ,1989

85. Lipoprotein(a) Definition & Clinical Significance
Lipoprotein (a) [Lp(a)]
Lp(a) is a plasma lipoprotein that is composed of two parts
LDL-like particle
Apolipoprotein (a) [apo(a)] protein that is made in the liver and is attached to the apoB portion of this particle
Low risk <20 mg/dL
Medium risk mg/dL
High risk >30 mg/dL
Elevated levels are an independent risk factor for
Myocardial infarction
Coronary artery disease
Cerebral vascular disease
Vein graft stenosis
Retinal artery occlusion
LpA – independent risk factor for MI, CVD, lots of bad things; clogs arteries
Schaefer E J et al. JAMA 1994;271:
Genest JJ, Jr. et al. Circulation 1992;85:
Clarke R et al. N Engl J Med 2009;361:
Ballantyne CM (Ed.) Clinical Lipidology. Philadelphia:
Saunders, (pg.130).

86. JELIS TRIAL
In JELIS (Japanese EPA Lipid Intervention Study) 18,645 hypercholesterolemic subjects (>6.5 mmol/L or 250 mg/dl off medication) randomized to 1800 mg/day of EPA versus placebo – all patients were placed on pravastatin 20 mg/day at onset – 4.7 yr. followup.
Major coronary events (fatal MI, MI, angioplasty, bypass) and were reduced by 19% (p=0.01). No effect on sudden death, No effect on lipids, except that statin lowered LDL C 25% in both groups* - particular benefit noted in group with TG > 150 mg/dL and HDL-C < 40 mg/dL risk reduction – 51% risk reduction, especially if EPA level > 150 ul/mL).**
Subanalysis of JELIS indicated no risk reduction for stroke (1.3% vs. 1.5% in placebo), but significant reduction in recurrent stroke from 10.5% in placebo to 6.8%, 20% reduction (p=0.01).***
*Yokohama et al Lancet 2007; 369: , **Saito et al Atherosclerosis 2008 (epub), ***Tanaka et al Stroke 2008;39:2052-8 .

88. Elevated Lipoprotein(a) Treatment Considerations
Primary goal is to optimize LDL-C, sdLDL-C, and apoB levels
Secondary goal is to lower Lp(a) below 20 mg/dL (as of yet not documented by intervention studies)
Primary pharmacologic options
Niaspan 2,000 mg lowers Lp(a) by a mean of 24%
Immediate release (IR) niacin lowers Lp(a) by about 30%
Effects of therapy may not be seen for several months
Other Lp(a) lowering modalities
Estrogen & androgens significantly lower Lp(a)
Tamoxifen lowers Lp(a) in post-menopausal women
Aspirin 81 mg QD can lower Lp(a) levels slightly
LDL apheresis
Statins do not lower Lp(a)
Diet & exercise have little to no effect on Lp(a) levels
High Lp(a) necessitates a combination therapy b/c statins do not lower Lp(a) (in fact, increase it slightly)
Niaspan is the only drug that will lower Lp(a), but creates side effects so doctors don’t like to use it unless really necessary
Other drugs do lower but are not common and not as effective
Kwiterovich PO, Jr .(Ed.) The Johns Hopkins Textbook of Dyslipidemia
Philadelphia: Wolters Kluwer, (pp ).

89. sdLDL-C and CHD Risk A better marker of CHD risk than LDL-C
MESA (n = 4,387)1
Top quartile*
>140 mg/dL
>50 mg/dL
Hazard ratio (P), new CHD†
1.75 (0.019)
2.41 (0.0037)
ARIC (n = 11,419)2
Top quartile
>146 mg/dL
>50 mg/dL‡
1.56 (<0.0001)
2.0 (<0.0001)
* In MESA neither top quartile small LDL-P or total LDL-P was associated with new CHD (P >0.05) in normoglycemic, non-diabetic individuals.
† Top quartile compared with lowest quartile.
‡ In ARIC sdLDL-C levels >50 mg/dL were predictive of risk even in individuals with LDL-C <100 mg/dL (HR 1.61).
1 Tsai MY et al. ATVB 2014; 34:
2 Hoogeveen RC et al. ATVB 2014; 34:
© 2014 Boston Heart Diagnostics Corporation

90. CHD Risk Prediction
sdLDL > apoB > non-HDL-C > LDL-P > LDL-C
sdLDL-C
amount of cholesterol in sdLDL particles (LDL d g/mL)
apoB
concentration of total apoB in plasma (number of apoB containing/atherogenic particles)
Non-HDL-C
amount of cholesterol in all apoB containing/atherogenic particles
LDL-P
number of LDL particles determined by NMR
LDL-C
amount of cholesterol in all LDL particles (d g/mL)
1 Tsai MY et al. Arterioscler Thromb Vasc Biol 2014; 34:
2 Hoogeveen RC et al. Arterioscler Thromb Vasc Biol 2014; 34:
3 Ai M et al. Clin Chem 2010; 56:
4 Emerging Risk Factors Collaboration. JAMA 2009; 302:

92. Calcium
Soft plaques

93. Prevalence of Cardiovascular Disease in the United States
One in three Americans has some form of cardiovascular disease. It is expected that the prevalence of CV disease will increase as our population ages.
Go AS et al. Circulation 2003;127:e6-e245 93

94. Rates of Death from Cardiovascular Disease in the United States
Calendar Year ( )
This graph displays the rates of death from cardiovascular disease in the United States between Over the first 70 years, the death rate steady increased. Over the last 36 years, however, the death rate has fallen, particularly since 2000.
Go AS et al. Circulation 2003;127:e6-e245 94

95. Patients Experiencing
Residual Cardiovascular Risk (70%) in Major Statin Trials (Risk Lowered around 30%)
CHD events occur in patients treated with statins
28.0
Patients Experiencing
Major CHD Events, %
19.4
15.9
12.3
11.8
13.2
10.9
10.2
7.9
8.7
6.8
5.5
Residual Cardiovascular Risk in Major Statin Trials.
In all of these major statin trials,1-6 significant residual cardiovascular risk remains even after reducing LDL-C. According to Libby, in the best of circumstances, the decrease in cardiovascular events due to statin treatment still allows two-thirds of cardiovascular events to occur. Libby concludes, “To address the majority of cardiovascular events that still occur despite our most powerful existing therapies, we must combine lifestyle change and evaluate new pharmacological strategies that will move us toward the goal of eradicating cardiovascular disease in the future.”7
Reference
4S Group. Lancet. 1994;344:
LIPID Study Group. N Engl J Med. 1998;339:
Sacks FM, et al. N Engl J Med. 1996;335:
HPS Collaborative Group. Lancet. 2002;360:7-22.
Shepherd J, et al. N Engl J Med. 1995;333:
Downs JR, et al. JAMA. 1998;279:
Libby PJ, et al. J Am Coll Cardiol, 2005:46:
4S1
LIPID2
CARE3
HPS4
WOSCOPS5
AFCAPS/
TexCAPS6 N
4444
9014
4159
20 536
6595
6605
 LDL-C
-35%
-25%
-28%
-29%
-26%
-25%
Secondary
High Risk
Primary
1 4S Group. Lancet. 1994;344:
2 LIPID Study Group. N Engl J Med. 1998;339:
3 Sacks FM, et al. N Engl J Med. 1996;335:
4 HPS Collaborative Group. Lancet. 2002;360:7-22.
5 Shepherd J, et al. N Engl J Med. 1995;333:
6 Downs JR, et al. JAMA. 1998;279:

96. HR 0.21 if LDL C < 70 mg/dl and CRP < 1.0 mg/L
JUPITER
Primary Trial Endpoint : MI, Stroke, UA/Revascularization, CV Death
Ridker et al NEJM 2008
HR 0.56, 95% CI
P <
HR 0.21 if LDL C < 70 mg/dl and CRP < 1.0 mg/L
Placebo 251 / 8901
0.08
- 44 %
0.06
Cumulative Incidence
0.04
Rosuvastatin 142 / 8901
0.02
0.00 1 2 3 4
Follow-up (years)
Number at Risk
Rosuvastatin
8,901
8,631
8,412
6,540
3,893
1,958
1,353
983
544
157
Placebo
8,901
8,621
8,353
6,508
3,872
1,963
1,333
955
534
174

97. Atherosclerosis Timeline
Foam
Cells
Fatty
Streak
Intermediate
Lesion
Fibrous
Plaque
Complicated
Lesion/Rupture
Atheroma
Endothelial Dysfunction
From first decade
From third decade
From fourth decade
Smooth muscle
and collagen
Thrombosis,
hematoma
Growth mainly by lipid accumulation
Stary HC, et al. Circulation. 1995;92: Artery wall often gets larger with increasing plaque-Glagov NEJM 1987

98. Optimizing CVD Risk Smoking Cessation – use of Chantix if necessary
Lifestyle : decrease animal and full fat dairy, trans fats, sugars, and increase essential fats, vegetables, and fruits, and daily exercise
High Blood Pressure - goals vary
Diabetes - get HbAIc < 7%, lifestyle change is the optimal therapy in overweight or obese insulin resistant patients.
LDL-C, sdLDL-C - In CVD and high risk patients reduce LDL-C to < 70 mg/dL and sdLDL-C to < 20 mg/dL with lifestyle, statins, and if necessary ezetimibe
HDL-C and ApoA-I in alpha-1 HDL – smoking cessation, weight loss, niaicin therapy at 2 grams/day are all ways to increase HDL-C > 50 mg/dL and especially to raise apoA-I in alpha-1 HDL to > 20 mg/dL.
Lp(a) – optimize all other risk factors, and in CVD patients who also have low HDL-C and alpha-1 HDL consider niacin 2 grams/day

99. Cumulative incidence of death by number of cardiac rehabilitation sessions attended.
Cumulative incidence of death by number of cardiac rehabilitation sessions attended. Reproduced from Hamill et al,8 with permission of the publisher.
Kwan G , and Balady G J Circulation. 2012;125:e369-e373
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