Editorial Slides VP Watch –July 24, 2002 - Volume 2, Issue 29

AHA 2002 Guideline; 1997 or 2002?

Major Eras in Atherosclerosis

Cholesterol

Non-Lipid Risk Factors

Immune Disorder

1950 1970 2002

(Inflammation Era)

DietEra 1

Era 2

Era 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.

Traditional Risk Factors (Era 1)

Sex Age Hypercholesterolemia Smoking Hypertension Diabetes Physical Activity Family History

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 …

Novel Risk Factors (Era 3)

CRP IL-6 CD40/CD40L Pathogen burden HSP-60 …

• “Risk Calculators” are only based on traditional risk factors:

• Framingham Risk Assessment• Sheffield Risk Assessment• MONICA• Dundee• RisCard

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

• 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.

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

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.

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.

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.

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?

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?

1) Grundy SM, Balady GJ, Criqui MH, et al. Guide to primary prevention of cardiovascular diseases: a statement for healthcare professionals from the Task Force on Risk Reduction. American Heart Association Science Advisory and Coordinating Committee. Circulation. 1997; 95: 2329–2331

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.

5) Wallis EJ, Ramsay LE, Ul Haq I, Ghahramani P, Jackson PR, Rowland-Yeo K, Yeo WW: Coronary and cardiovascular risk estimation 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 coronary heart disease. Lancet 1995 Dec 2;346(8988):1467-71

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 to Lower Hyperhomocyst(e)inaemia.Pharmacoeconomics 2002;20(7):429-42

9) Gerber Y, Goldbourt U, Cohen H, Harats D.:Association Between Serum Apolipoprotein C(II) Concentration and Coronary Heart Disease. Prev Med 2002 Jul;35(1):42-7

10) Wilson PW, D'Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-47.

11) Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP, Franklin BA, Goldstein LB, Greenland P, Grundy SM, Hong Y, Miller NH, Lauer RM, Ockene IS, Sacco RL, Sallis JF Jr, Smith SC Jr, Stone NJ, Taubert KA. : AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. : Circulation. 2002 Jul 16;106(3):388-91.

References