Framingham risk equation underestimates subclinical atherosclerosis risk in asymptomatic women
Introduction
Cardiovascular disease is the leading cause of death of women in the United States, with excess of 500,000 deaths annually [1]. Fifty percent of women will die of cardiovascular disease compared with 4% of breast cancer; yet, in a 1997 survey, only 8% of women considered cardiovascular disease to be their greatest health threat [2]. Whereas the death rate from cardiovascular disease in men has declined steadily over the last 20 years, the rate has remained relatively the same for women [1]. At least 25% of patients with sudden death or nonfatal myocardial infarction experience no prior symptoms, which reinforces the importance of detecting individuals at-risk prior to an initial event to implement primary preventive therapy.
Improved precision in detecting early coronary disease may assist with more targeted preventive therapy. One way to detect subclinical atherosclerosis is by measuring the coronary artery calcium (CAC) using electron beam computed tomography (EBCT). As atherosclerosis develops within the coronary arteries, the majority of plaques become calcified. Because numerous histopathologic studies have shown that CAC linearly correlates with atherosclerotic plaque burden, EBCT is felt to be a useful tool in quantifying coronary atherosclerosis [3]. The CAC score has been shown to predict both the degree of stenosis seen at angiography, [4], [5] as well as predict future cardiovascular events in both symptomatic and asymptomatic patients [6], [7], [8], [9]. Asymptomatic individuals with increased coronary calcification have a greater burden of subclinical atherosclerosis and thus an increased likelihood of future cardiovascular events.
The American Heart Association's (AHA) Prevention V Conference, ‘Beyond Secondary Prevention: Identifying the High Risk Patient for Primary Prevention’, recommends all adults undergo an office-based risk assessment to first establish their ‘global risk’ as measured by a statistical model such as the Framingham risk equation (FRE) [10]. The traditional risk factors identified by the Framingham study include elevated total and LDL-cholesterol, low-HDL cholesterol, hypertension, cigarette smoking, diabetes, and age. Using the Framingham scoring table, a 10-year estimated risk of hard cardiovascular events can be predicted for a given patient based on these major risk factors [11], [12]. Asymptomatic patients are categorized as low, intermediate, or high risk, based upon their respective scores, and then, ideally, subjected to an appropriate risk-modifying intervention. Low-risk patients can be reassured and followed with implementation of therapeutic lifestyle changes. Intermediate-risk patients may require further risk stratification, and high-risk patients should be considered candidates for aggressive intervention.
Lipid lowering trials such as the West of Scotland Coronary Prevention Trial (WOSCOPS) [13] and the Air Force/Texas Coronary Atherosclerosis Prevention Trial (AFCAPS/TexCAPS) [14] have demonstrated that primary prevention of coronary events is possible with statin therapy in patients with elevated cholesterol. The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP)-III guidelines use the FRE to set lipid treatment guidelines based on the FRE-determined 10-year global risk [12], [15], [16]. The NCEP guidelines assist with lipid management in intermediate and high risk women. However, the effectiveness of these guidelines to identify asymptomatic women at presumptively low-risk for a cardiac event is not clear. A small study of 304 asymptomatic women suggested that 47% of women classified as low-risk by NCEP had detectable subclinical atherosclerosis, yet would not meet criteria for pharmacologic therapy [17].
Using a much larger population, we hypothesized that the Framingham risk score and the NCEP ATP III guidelines may fail to identify a sizeable portion of asymptomatic women with low-risk FRE scores but with detectable and significant subclinical atherosclerosis, who may benefit from more aggressive primary prevention.
Section snippets
Subjects
This is a cross-sectional study on a consecutive sample of 13,389 physician-referred individuals who presented to a single EBCT scanning facility (Columbus, OH) between the dates of July 1999 and June 2003 for CHD risk stratification. We excluded patients who reported any personal history of CHD defined by prior myocardial infarction or coronary/peripheral revascularization (n = 322) or any current symptoms potentially suggestive of angina (n = 4518) defined by self-reports of chest pain, chest
Results
The final study population consisted of 2,447 asymptomatic non-diabetic women (55 ± 10 years). None of the women were considered high risk (FRE > 20%). Based upon FRE, 10% (n = 249) were candidates for further evaluation (intermediate-risk) and 90% (n = 2198) were classified as low-risk requiring no further intervention. Detectable CAC (>0) was observed in 33% (n = 803) of the cases, whereas moderate (CAC ≥100) and severe (CAC ≥400) was seen in 10% (n = 247) and 3% (n = 83) women, respectively. Overall, 20%
Discussion
In our study population, 90% of the women had 10-year global risk for hard events less than 10%, but we found that over a third had detectable coronary atherosclerosis. Twenty percent of the population had significant subclinical atherosclerosis ≥75th of the percentile for their age and gender, despite the fact that 84% of these women were classified as low-risk by FRE. As per AHA primary prevention guidelines, these patients would not have been eligible for low dose aspirin therapy [22].
The
Limitations
The results of our study should be interpreted in the context of several limitations. The authors acknowledge that the purpose of risk assessment in NCEP is to predict CHD events and not coronary atherosclerosis. However, recent studies have provided strong support for the relationship between increasing CAC and risk of future CHD events. In our study, CHD risk factors were self-reported. However, the validity of self-reported histories of hypercholesterolemia, diabetes, and hypertension in
Conclusion
FRE scoring based on traditional risk factor assessment frequently classifies women as being low-risk CHD status, even in the presence of moderate burden of subclinical atherosclerotic disease as measured by CAC. Assessment of CAC burden may provide incremental value to global risk assessment in identifying asymptomatic women who may benefit from more aggressive primary preventive therapy. Low-risk women with multiple CHD risk factors, especially in presence of a FH of premature CHD, are
Acknowledgement
This work was supported by an unrestricted educational grant by the Maryland Athletic Club Charitable Foundation, Lutherville, Maryland.
References (30)
- et al.
Quantification of coronary artery calcium by electron beam computed tomography for determination of severity of angiographic coronary artery disease in younger patients
J Am Coll Cardiol
(1995) - et al.
Correlation of coronary calcification and angiographically documented stenoses in patients with suspected coronary artery disease: results of 1,674 patients
J Am Coll Cardiol
(2001) - et al.
Use of electron beam tomography data to develop models for prediction of hard coronary events
Am Heart J
(2001) - et al.
Prediction of coronary events with electron beam computed tomography
J Am Coll Cardiol
(2000) - et al.
Coronary artery calcium evaluation by electron beam computed tomography and its relation to new cardiovascular events
Am J Cardiol
(2000) - et al.
Electron beam tomography and National Cholesterol Education Program guidelines in asymptomatic women
J Am Coll Cardiol
(2001) - et al.
Quantification of coronary artery calcium using ultrafast computed tomography
J Am Coll Cardiol
(1990) - et al.
Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons
Mayo Clin Proc
(1999) - et al.
Coronary artery calcium volume scores on electron beam tomography in 12,936 asymptomatic adults
Am J Cardiol
(2004) - et al.
Conventional coronary artery disease risk factors and coronary artery calcium detected by electron beam tomography in 30,908 healthy individuals
Ann Epidemiol
(2003)
Preventing myocardial infarction in the young adult in the first place: how do the National Cholesterol Education Panel III guidelines perform?
J Am Coll Cardiol
Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area: a histopathologic correlative study
Circulation
Predictive value of electron beam computed tomography of the coronary arteries: a 19-month follow-up of 1173 asymptomatic subjects
Circulation
Cited by (213)
Association of cardiovascular health and risk prediction algorithms with subclinical atherosclerosis identified by carotid ultrasound
2023, Cardiovascular Digital Health JournalCardiovascular and renal health: Preeclampsia as a risk marker
2023, NefrologiaAn Alternative, Simple Approach to Confirming Subclinical Cardiovascular Disease
2023, American Journal of MedicineEffects of Diet on 10-Year Atherosclerotic Cardiovascular Disease Risk (from the DASH Trial)
2023, American Journal of CardiologyMajor Global Coronary Artery Calcium Guidelines
2023, JACC: Cardiovascular ImagingImpact of low/no-charge coronary artery calcium scoring on statin eligibility and outcomes in women: The CLARIFY study
2022, American Journal of Preventive Cardiology