Download Evidence Based Cardiovascular Disease

Evidence Based
Cardiovascular Disease
Manju B. Reddy, PhD.
Iowa State University
Food Science and Human Nutrition
Global Causes of Death
# 1cause
http://www.who.int/cardiovascular_diseases
Projected global deaths by cause
: Beaglehole and Bonita, 2008
Prevalence and Incidence
• The United States ranks 13th and 17th,
among industrialized nations for the
prevalence of CVD in women and men,
respectively.
• More than 71 million Americans have at
least one form of CVD.
Forms of CVD
•
•
•
•
•
Hypertension
Coronary Heart Disease (CHD)
Stroke
Rheumatic heart disease
Congestive heart failure
Percentage breakdown of deaths from CVD
(United States:2004)
7
6
4
Coronary Heart
Disease
Stroke
14
HF*
High Blood Pressure
17
52
Source: NCHS and NHLBI
*Not a true underlying cause.
Diseases of the
Arteries
Other
Deaths from Diseases of the Heart
(United States: 1900–2005)
900
Deaths in Thousands
800
700
600
500
400
300
200
100
0
00
10
20
30
40
50
Years
NCHS and NHLBI
60
70
80
90
00 05
Pathology - Atherosclerosis
Atherosclerosis is a major underlying cause of
CVD
• Fatty streaks: Earliest lesion (children)
• Fibrous plaques: more complex lesion that
can occlude the artery (extends into lumen)
• Complicated lesion: Hemorrhage in the
plaque
Progression of Atherosclerosis
(From Harkreader H. Fundamentals. Philadelphia: W.B. Saunders, 2000)
(From Harkreader H. Fundamentals. Philadelphia: W.B. Saunders, 2000)
Plaque Formation
1. Proliferation of smooth muscle cells
2. Accumulation of smooth muscle cells in to
connective tissue matrix
3. Accumulation of lipid and cholesterol around the
cells
4. Plaque or atheromas:
lipid deposits that develop in the innermost layer.
Plaque forms in response to injuries of endothelium
in artery wall (hypercholesterolemia, oxidized LDL,
hypertension, smoking, obesity, diabetes,
homocysteine, high cholesterol or high saturated fat
diets)
Structure of Plaque
Risk Factors
Non modifiable risk factors:
– Age
– Gender
– Family history
Modifiable risk factors:
–
–
–
–
–
–
–
Hyperlipidemia
Adiposity (BMI and Waist circumference)
Inactivity
Cigarette smoking
Hypertension
Diabetes
Atherogenic diet
Per 1,000 Person Years
Incidence of CVD by Age and Sex
80
70
60
50
40
30
20
10
0
74.4
Risk is higher in males
65.2
Less difference at older age
40.2
34.6
21.4
10.1
20.0
8.9
4.2
45-54
59.2
55-64
65-74
75-84
85-94
Age
Men
Women
Includes CHD, HF, stroke or cerebral hemorrhage. Does not include
hypertension alone.
FHS, 1980-2003. NHLBI
Lipids and Lipoprotein Risk Factors
• Total cholesterol: amount in all lipoprotein fractions (High)
• Total triglyceride: amount in all lipoprotein fractions (High)
• Chylomicrons: transport dietary fat and cholesterol from
small intestine to liver and periphery
• VLDL: transport endogenous triglyceride and cholesterol
• LDL (bad cholesterol): major cholesterol transport
lipoprotein (High)
• HDL (good cholesterol): reverse cholesterol transport
(Low)
Cholesterol* Levels and Their Meanings
Optimal Desirable
Borderline
High Risk
Below 200
200-239
240 or
higher
Below 130
130-159
160 or
higher
HDL Cholesterol
Above 60
35-45
Below 40
Ratio
Total cholesterol/HDLs
Below 4.5
4.5-5.5
Above 5.5
Total Cholesterol
LDL Cholesterol
<100
*mg/dL
NCEP STEPIII – NHLBI
Lipid lowering therapy and
stroke
RR= probability of the
event : exposed /non exposed
Example: Developing lung cancer is 10% in
smokers vs 1% non-smokers
RR = (10/100)/1/100 = 10
Smokers have 10% higher risk for
developing cancer compared to nonsmokers
Corvol et al. Arch Intern Med. 2003:163:669
Associations of physical activity and
waist circumference with CHD*
Abdominal adiposity
*Nurses’ health study 1986-2000 (n=88,393; 20-y follow up). RR= Relative Risk adjusted
for age, parental history of CHD, postmenopausal status and hormone use, aspirin use,
BMI and alcohol consumption
Tricia et al. Circulation. 2006;113:499-506
Associations of BMI and waist
circumference with CHD*
*Nurses’ Health Study 1986-2000 (n=88,393; 20-y follow up). RR= Relative Risk
adjusted for age, parental history of CHD, postmenopausal status and hormone use.
aspirin use, and alcohol consumption
Tricia et al. Circulation. 2006;113:499-506
CHD and Physical Activity
0.83
0.65
No training
* Adjusted for age; n=44,452; US Men, Health Professional Follow-up Study
Mahael et al. JAMA. 2002;288 (data collected 1994-2000)
Physical Activity, Smoking and CHD
Lee et al. JAMA 2001, 285:1447-1454
N=39,372, healthy female professionals <45y
Hypertension
• Antihypertensive drug use was more protective
than lipid lowering drugs (RR=1.6 vs 1.1) in a
Prospective Epidemiological study of Myocardial
Infarction (PRIME) with 2,500 men with 5-y
follow up (50-59 y) (Blacher et al. J Hyperten
2004;22:415-23)
• Follow up report with 10-y follow up with 9,649
men showed similar results with CHD, CVD
death and stroke (Blacher et al. 2009. J Human Hyperten)
CVD Mortality and Diabetes
Hazard ratio = How often the event happens in one group compared to other group;
Example: Cancer survival at any point of time in treatment group vs control group
Hazard ratio
Zeymer, U. Int J Cardiol. 2006, 11–20
Diet CVD
Replacement of total, unsaturated, and even possibly
saturated fats with refined, high-glycemic index
carbohydrates is unlikely to reduce CHD risk and may
increase risk in persons predisposed to insulin resistance
Diet that will likely reduce the risk of CHD
1. rich in whole grains and other minimally processed
carbohydrates
2. includes moderate amounts of fats (approximately 30%–
40% of total energy), particularly unsaturated fats and
omega-3 polyunsaturated fats from seafood and plant
sources
3. lower in refined grains and carbohydrates
4. less packaged foods, baked goods, and fast foods
containing trans fatty acids
Mozaffarian, D. Current Atherosclerosis Reports 2005, 7:435–445
Percentage Change in Consumption by Kilocalories per Capita per
Day in Selected Countries from 1980 to 2003, FAOSTAT Food
Consumption Data
Food Type
China
Egypt
India
Mexico
South Africa
Total
Kilocalories
26.3
16.2
25.7
1.5
5.7
Meat
247
48.3
40.0
18.3
6.9
Cereals
−13.9
17.6
13.8
−1.4
4.7
Sugar and
Sweeteners
51.9
8.8
27.2
2.4
−18.3
Fruits
600
103
60.0
19.4
33.3
Vegetables
367
10.3
37.5
40.7
0.0
Palm Oil
640
No Data
730
2100
2400
Soybean Oil
635
35.5
48.2
50.0
189
Vegetable Oil
259
−47.8
84.6
14.7
75.4
Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health.
Institute of Medicine (US) Committee on Preventing the Global Epidemic of Cardiovascular Disease: Meeting the
Challenges in Developing Countries; Fuster V, Kelly BB, editors.
Washington (DC): Academic Press, 2010
Diet and Lipoproteins
• Saturated fat:  LDL receptor LDL uptake from
blood   LDL in circulation
• Fiber: Fiber binds bile acids and  re-absorption of
cholesterol and  excretion in the feces.
Fiber
Bile acids
X
Feces
Cholesterol
Bile acids
Absorption
Important qualities of carbohydrates in
reducing CVD risk
Mozaffarian D. Current Atherosclerosis Reports 2005,7:435–445
Adjusted Relative Risk of CHD
according to the whole-grain foods
.45
.89
.82
.72
.76
.86
.77
N=75,521 female nurses
*Adjusted for BMI, smoking, alcohol, family history, hypertension/hypercholesterolemia,
menopausal status, asiprin and multiple vitamin , activity, and energy intake use,
Simin et al. Am J Clin Nutr 1999;70:412–9.
Diet and Heart Diseases
Antioxidants
• Protect from oxidative damage to LDL (oxidized LDL 
atherosclerosis)
• Protective effect of antioxidants (vit E, β carotene and C)
Beta carotene supplementation
and CHD risk
alpha-tocopherol, beta-carotene cancer prevention (ATBC) study.
Tornwall et al. European Heart Journal. 2004, 25, 1171–1178
Fish Consumption on CHD
Omega-3 fatty acids
Precursors of eicosanoid synthesis
 blood clotting
 blood pressure
 blood lipids
Whelton , SP. Am J Cardiol 2004;93:1119–1123 – Meta analysis
Fish Consumption and CVD
Wennberg, et al AJCN 2012
Other Risk Factors
Homocysteine
• High levels may promote atherosclerosis by
damaging the inner lining of arteries and
promoting blood clots
•  homocysteine and folate intake – risk!
• B6, B12 are also important
Hyperhomocysteinemia is not a major risk factor for cardiovascular
disease (AHA)
Metabolism of Homocysteine
Protein synthesis
THF
Vitamin B12
*THF-CH3
Methionine
X
-CH3
Homocysteine
Serine
X
B6
Cysteine
*THF= tetrahydrofolate (folate containing co-enzyme)
Homocysteine and CVD
Parameter
Active group
Placebo group
Homocysteine (mmol/l)
Baseline
2 years
5 years
15.9 ± 7.3
12.7 ± 5.0
11.9 ± 3.3
15.7 ± 5.7
16.1 ± 5.2
15.5 ± 4.5
Folate (nmol/l)
Baseline
2 years
27.8 ± 12.3
41.4 ± 9.2
28.7 ± 11.0
26.1 ± 9.3
Vitamin B6 (nmol/l)
Baseline
2 years
87.4 ± 128.8
275.8 ± 175.3
64.5 ± 82.0
80.3 ± 111.6
Vitamin B12 (pmol/l)
Baseline
2 years
332.3 ± 161.7
768.0 ± 196.9
323.2 ± 166.6
320.9 ± 181.7
Mann et al. Nephrol Dial Transplant. 2008, 23: 645–653
C-Reactive Protein
• Inflammation: Process by which the body
responds to injury or an infection
• Inflammation is involved with atherosclerosis
• C-reactive protein (CRP) is one of the acute
phase proteins that increase during systemic
inflammation
• hs-CRP and CVD risk
< 1.0 mg/L
Low risk
1.0 and 3.0 mg/L
Moderate risk
3.0 mg/L
High risk
CDC and AHA recommend to measure CRP
Framingham Heart Study – CVD Risk
• Population of interest - Individuals 30 to 74 y old and
without CVD at the baseline examination – 10 y risk
Predictors
• Age
• Diabetes
• Smoking
• Treated and untreated Systolic Blood Pressure
• Total cholesterol
• HDL cholesterol
Estimate of CVD in men – CVD Points
Points
Age
HDL
-2
60+
-1
50-59
0
30-34
Total
Cholesterol
SBP Not
Treated
SBP Treated Smoker
<120
0
45-49
<160
120-129
35-44
160-199
130-139
<35
200-239
140-159
120-129
3
240-279
160+
130-139
4
280+
1
2
35-39
5
40-44
6
7
8
9
10
11
12
13
14
15
45-49
50-54
55-59
60-64
65-69
70-74
75+
Diabetic
<120
140-159
160+
No
No
Yes
Yes
Calculating CVD Risk
Points
Risk
Points
Risk
Points
Risk
-3 or less Below 1% 5
3.9%
13
15.6%
-2
1.1%
6
4.7%
14
18.4%
-1
1.4%
7
5.6%
15
21.6%
0
1.6%
8
6.7%
16
25.3%
1
1.9%
9
7.9%
17
29.4%
2
2.3%
10
9.4%
18+
Above 30%
3
2.8%
11
11.2%
4
3.3%
12
13.2%
Evidence Based Information
•
•
•
•
•
Selection of expert panel
Selection of topic and systemic search
Evidence rating and recommendation
Clinical recommendations
Research needs and future directions
Classification of CVD Risk in Women
Risk Status
Criteria
High risk
Established coronary heart disease
Cerebrovascular disease
Peripheral arterial disease
Abdominal aortic aneurysm
End-stage or chronic renal disease
Diabetes mellitus
10-Year Framingham global risk 20%
Mosca et al. Circulation, Evidence-Based Guidelines for Cardiovascular
Disease Prevention in Women: 2007 Update.
Classification of CVD Risk in Women
Risk Status
At risk
Criteria
>1 major risk factors for CVD, including:
Cigarette smoking
Poor diet
Physical inactivity
Obesity, especially central adiposity
Family history of premature CVD (CVD at 55 years
of age in male relative and 65 years of age in female relative)
Hypertension
Dyslipidemia
Evidence of subclinical vascular disease (eg, coronary calcification)
Metabolic syndrome
Poor exercise capacity on treadmill test and/or abnormal heart rate
recovery after stopping exercise
Mosca et al. Circulation, Evidence-Based Guidelines for Cardiovascular
Disease Prevention in Women: 2007 Update.
Classification of CVD Risk in Women
Risk Status
Optimal risk
Criteria
Optimal risk Framingham global risk <10% and a
healthy lifestyle, with no risk factors
Mosca et al. Circulation, Evidence-Based Guidelines for Cardiovascular
Disease Prevention in Women: 2007 Update.
Classification Levels
Class I
Class II
IIa
IIb
Class III
Conditions for which there is evidence for and/or general
agreement that the procedure or treatment is useful and
effective.
Conditions for which there is conflicting evidence and/or
a divergence of opinion about the usefulness/efficacy of a
procedure or treatment.
The weight of evidence or opinion is in favor of the
procedure or treatment.
Usefulness/efficacy is less well established by evidence or
opinion.
Conditions for which there is evidence and/or general
agreement that the procedure or treatment is not
useful/effective and in some cases may be harmful.
Level of Evidence
B
Data derived from multiple
randomized clinical trials.
Data derived from a single randomized
trial or nonrandomized studies.
C
Consensus opinion of experts.
A
Guidelines for prevention of CVD in
Women: Clinical Recommendations
A few examples….
1. Life Style Interventions

Cigarette Smoking - should not smoke

and should avoid environmental smoke
(class I, level B)
Physical activity – minimum of 30 min
brisk walking every day (class I, level B)
Loose weight or sustain weight loss. 6090 min brisk walking every day (class I,
level C)
Life Style interventions…
 Dietary intake – Fruits and vegetable-rich
diet, whole grain, high-fiber foods, fish
(2x/wk), Saturated fat intake <10% of
energy (<7%, if possible), cholesterol <300
mg/d, alcohol not more than 1 drink/d,
sodium <2.3 g/d (1 tsp), and trans fatty
acids <1% energy (class I, level B)
2. Major Risk Factor Interventions
A few examples…..
• Blood Pressure
Optimal level and life style - <120/80 mm Hg
through life style approaches (weight control,
physical activity, alcohol, sodium, other
healthy diet (class I, level B)
Pharmacotherapy – If >140/90 mm Hg or
even lower with kidney disease or diabetes
(class I, level A)
• Lipids and lipoprotein levels
– Optimal levels and life style approaches –
LDL-C <100 mg/dL; HDL-C >50 mg/dL; TG
<150 mg/dL; and non HDL-C <130 mg/dL
(class I, level B)
– Pharmacotherapy (high risk women) – drug
therapy + life style approach in women with
CHD (class I, level A) or atherosclerotic CVD
or diabetes or 10 y absolute risk (class I, level
B). Low HDL or elevated non-HDL – Niacin
or fibrate therapy after LDL-C goal is reached
(class IIa, level B)
– Diabetes - Life style and pharmacotherapy
(class I, level B) to achieve an HbA1c <7%
3. Preventive Drug Interventions
• Aspirin (75 -325 mg/d) in high risk women
unless contraindicated (class I, level A).
Other risk and healthy women, >65y age
(81-100 mg/d) if BP is controlled (class IIa,
level B)
Class III Interventions for CVD or
MI prevention
 Menopausal therapy - Hormone therapy and SERMs
should not be used for primary or secondary
prevention (class III, level A)
 Antioxidant supplements (Vitamin E, C and 
carotene) for primary or secondary prevention (class
III, level A)
 Folic acid + B6 and B12 should not be used for primary
or secondary prevention (class III, level A)
 Aspirin for MI in women <65 y: routine use is not
recommended to prevent MI (class III, level A)
Mortality in Younger and Older women
Associated with Hormone Therapy
CHD mortality
Mean age, less than 65 years
Mean age, 65 years or over
0.98 (0.75, 1.30)
1.00 (0.77, 1.31)
All stroke
Mean age, less than 65 years
Mean age, 65 years or over
1.35 (1.14, 1.60)
1.20 (0.95, 1.51)
Non-fatal AMI
Mean age, less than 65 years
Mean age, 65 years or over
1.04 (0.79, 1.38)
0.94 (0.75, 1.17)
All-cause mortality
Mean age, less than 65 years
Mean age, 65 years or over
1.02 (0.90, 1.15)
1.03 (0.86, 1.24)
Magliano et al. Int.Journal of Obst Gyn 2006; 113:5–14. Meta analysis
Diet and CVD –Evidence Based
Assessment
• Dietary advice regarding cardiovascular disease
(CVD) prevention is complex
• American Heart Association (AHA) recommendation
for low-fat diet of:
55% of total calories from carbohydrates
30% from fat
15% from protein
cholesterol restricted to 300 mg/day
Low fat recommendations lead to refined CHO intake
Popular Dietary Approaches
for Cardiovascular Health
• Low CHO diets (5-30% CHO)
• Very-low-fat diets (< 15% total calories from fat,
70% CHO)
• Low glycemic diets (lower postprandial glucose
response)
• The Mediterranean Diet (plant foods, minimally
processed, seasonally fresh, olive oil, dairy,
fish/poultry, etc)
• DASH diet (similar to Med. Diet with high K, Ca,
Mg, fiber to control hypertension)
Summary of Diets
• Very-Low-Fat Diet
Possible decrease in cardiac events
Concerns about universal applicability and sustainability
• Mediterranean Diet
Secondary prevention
Prevention of sudden cardiac death
Healthy overall approach to dieting
Long-term sustainability
• DASH
Decreased hypertension
Similar to Mediterranean Diet
Optimal Diet
Recommendations
None of the diets are independently perfect
for cardiovascular health but the
recommendations are:
1. Low CHO intake, especially high GI foods
2. Increased consumption of fruits and
vegetables, whole grains
3. Increased intake of PUFA (plant oils and fish)
4. Low fat dairy products and nuts
Parikh et al. J Am Coll Cardiology 2005
Suggested Readings
• Mozaffarin. Effects of dietary fats versus
carbohydrates on coronary heart disease: A
review of the evidence. Curr Athero reports
2005;7:435.
• http://circ.ahajournals.org/cgi/content/full/109/5/6
72
• http://www.framinghamheartstudy.org/risk/genca
rdio.html
• http://content.onlinejacc.org/cgi/content/full/45/9/
1379
Suggested Readings
• http://circ.ahajournals.org/cgi/content/full/1
09/5/672
• http://www.framinghamheartstudy.org/risk/
gencardio.html
• http://content.onlinejacc.org/cgi/content/full
/45/9/1379