This document summarizes major developments in understanding cardiovascular disease risk factors over three eras. Era 1 focused on traditional risk factors like cholesterol. Era 2 identified additional non-traditional factors. Era 3 explores novel inflammatory markers. While risk calculators only use Era 1 factors, studies increasingly show the significance of Era 2 and 3 markers. However, the 2002 AHA guideline was cautious to fully incorporate newer findings, focusing primarily on traditional risk factors and recommending further research on controversial interventions and use of inflammatory markers in screening.

1. Editorial Slides
VP Watch –July 24, 2002 - Volume 2, Issue 29
AHA 2002 Guideline; 1997 or 2002?

2. Major Eras in Atherosclerosis
Cholesterol
Non-Lipid Risk Factors
Immune Disorder
1950 1970 2002
(Inflammation Era)
Diet
Era 1
Era 2
Era 3

3.  The landmark Seven Countries Study established the
“diet-heart cholesterol theory”.
 This classic diet-heart cholesterol theory is supported
by results from ecological analyses, prospective studies,
animal experiments, clinical observations, controlled
trials, biochemical and nutritional studies.
 Since 1968 extensive epidemiologic and clinical studies
have identified several factors that increase the risk of
CHD and MI, with effects not necessarily involving
serum cholesterol and lipids.

4.  Traditional Risk Factors (Era 1)
 Sex
 Age
 Hypercholesterolemia
 Smoking
 Hypertension
 Diabetes
 Physical Activity
 Family History

5.  Non-Traditional Risk Factors (Era 2)
 Fibrinogen
 Homocysteine
 White Blood Cell Count
 LP(a)
 ApoB/ApoA
 Heart Rate
 Socioeconomic Status
 Stress
 Type A Personality
 Body Mass Index
 …

6.  Novel Risk Factors (Era 3)
 CRP
 IL-6
 CD40/CD40L
 Pathogen burden
 HSP-60
 …

7. • “Risk Calculators” are only based on
traditional risk factors:
• Framingham Risk Assessment
• Sheffield Risk Assessment
• MONICA
• Dundee
• RisCard

8.  The Framingham model uses age, sex, LDL or
total cholesterol, HDL, systolic and diastolic
blood pressure, the presence or absence of
diabetes mellitus, and smoking status to predict
the 10-year risk of CHD events. 10
• Sheffield table for primary prevention of
coronary heart disease shows serum
cholesterol concentration conferring an
estimated risk of coronary events of 3.0% per
year. 5

9. • National Heart, Lung, and Blood Institute
presented the risk assessment tool using
information from the Framingham Heart Study to
predict a person’s chance of having a heart
attack in the next 10 years.
 However, numerous studies have accumulated
abundance of data indicating significance of
non-traditional and emerging risk factors like
CRP, fibrinogen, homocysteine, sLDL, and
calcium score.

10.  As reported in VP Watch of this
week, Pearson et al. in 2002 update of AHA
guidelines for primary prevention of
cardiovascular disease and stroke integrated
other guidelines and consensus statements
developed since the initial Guide’s approval.11
 This Guide is intended to assist primary care
providers in their assessment, management,
and follow-up of patients who may be at risk
for but who have not yet manifested
cardiovascular disease. 11

11.  The aspirin guidelines recommended in
this update agree with the Task Force
Report in the use of aspirin in persons at
high coronary and stroke risk but uses a
10% risk per 10 years rather than >6%
risk over 10 years. 11
 This change slightly restricts use of
aspirin due to its potential adverse
effects.

12. Conclusion:
 Despite the fast growing body of
evidence for significance of non-
traditional risk factors, the AHA 2002
Guideline calls screening tests for occult
atherosclerosis based on non-traditional
risk factors (CRP…) confined in the
research arena, except ankle-brachial
blood pressure index.

13. Conclusion:
 The Guideline also does not appreciate
non-lipid lowering effects of statins and
emphasizes that controversial
interventions, such as very low-fat diets,
dietary supplements, and potentially
cardioprotective drugs other than aspirin
require additional investigation in well-
designed clinical trials in persons without
established cardiovascular disease.

14. Questions:
• Should CRP be added to the package of
screening tests for CVD primary
prevention in asymptomatic populations?
• How about for secondary prevention?
• Should coronary calcium score be
considered as an independent risk factor?

15. Questions:
• Is annual risk calculated based on population studies a
reasonable basis for individual treatment?
• Is 2% annual risk a proper cut point for intervention?
• Do we need multiple risk cut points for different types
of interventions e.g. life-style, conventional drug
therapy, aggressive drug therapy, invasive treatment,
etc?
• Besides aspirin should we add other drug therapies
(such as statins) to the primary intervention therapy?

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2) National Cholesterol Education Program: Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults (Adult Treatment Panel II). Circulation.. 1994;89:1333-1445
3) Diane L. Tribble; Antioxidant Consumption and Risk of Coronary Heart Disease: Emphasis on Vitamin C, Vitamin E, and ß-Carotene : A
Statement for Healthcare Professionals From the American Heart Association; Circulation 1999 99: 591 - 595.
4) Rosamond WD, Folsom AR, Chambless LE, Wang CH; ARIC Investigators. Atherosclerosis Risk in Communities.:Coronary heart
disease trends in four United States communities. The Atherosclerosis Risk in Communities (ARIC) study 1987-1996. Int J Epidemiol.
2001 Oct;30 Suppl 1:S17-22.
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for primary prevention: validation of a new Sheffield table in the 1995 Scottish health survey population.
6) Haq IU, Jackson PR, Yeo WW, Ramsay LE.: Sheffield risk and treatment table for cholesterol lowering for primary prevention of
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7) Luc G, Bard JM, Ferrieres J, Evans A, Amouyel P, Arveiler D, Fruchart JC, Ducimetiere P.:Value of HDL Cholesterol, Apolipoprotein A-
I, Lipoprotein A-I, and Lipoprotein A-I/A-II in Prediction of Coronary Heart Disease: The PRIME Study. Arterioscler Thromb Vasc Biol
2002 Jul 1;22(7):1155-61
8) Nallamothu BK, Fendrick AM, Omenn GS.Homocyst(e)ine and Coronary Heart Disease: Pharmacoeconomic Support for Interventions
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References