Elsevier

Atherosclerosis

Volume 184, Issue 1, January 2006, Pages 201-206
Atherosclerosis

Framingham risk equation underestimates subclinical atherosclerosis risk in asymptomatic women

https://doi.org/10.1016/j.atherosclerosis.2005.04.004Get rights and content

Abstract

Background

Coronary heart disease (CHD) is the leading cause of death among American women. Currently, global risk assessment derived by Framingham risk equation (FRE) is used to identify women at increased risk for CHD. Electron-beam computed tomography (EBCT) derived coronary artery calcium (CAC) scores are validated markers for future CHD events among asymptomatic individuals. However, the adequacy of FRE for identifying asymptomatic women with CAC is unknown.

Methods and results

We studied 2447 consecutive non-diabetic asymptomatic females (55 ± 10 years). Based upon FRE, 90% were classified as low-risk (FRE ≤9% 10-year risk of hard CHD events), 10% intermediate-risk (10–20%), and none were considered as high-risk (>20%). Coronary artery calcium was present in 33%, whereas CAC ≥100 and CAC ≥400 were seen in 10 and 3% of women, respectively. Overall, 20% of women had age-gender derived ≥75th percentile CAC. According to FRE, the majority (84%) of women with significant CAC ≥75th percentile were classified as low-risk. Approximately half (45%) of low-risk women with ≥2 CHD risk factors and a family history of premature CHD had significant CAC.

Conclusion

Framingham risk equation frequently classifies women as being low-risk, even in the presence of significant CAC. Determination of CAC may provide incremental value to FRE in identifying asymptomatic women who will benefit from targeted preventative measures.

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.

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