Low Framingham Risk: Guidelines not a substitute for clinical judgment

The FRS tends to classify women into a much lower risk category for the same number and severity of cardiovascular risk factors as men.

Recent national campaigns focusing on cardiac disease in women, such as the Red Dress Campaign and Go Red for Women, have sought to increase awareness of this condition through identification of unrecognized cardiovascular risk factors.

Currently, the American Heart Association and National Heart, Lung, and Blood Institute recommend office-based risk assessment using the Framingham Risk Score for men and women alike in order to generate a global assessment of cardiovascular risk. Individuals are categorized as being low risk (10%), intermediate risk (10% to 20%), or high risk (20%), based on the likelihood of experiencing a nonfatal MI or fatal coronary event over the next 10 years.

In general, low-risk patients are offered reassurance and guidance on maintaining a healthy lifestyle, while intermediate- and high-risk patients are offered increasingly intensive diet, lifestyle, and pharmacologic interventions. While such an approach seems intuitive, it is only valuable if it correctly identifies those individuals likely to benefit from more intensive therapy.

Roger S. Blumenthal

Identifying women with CVD

Unfortunately, the FRS tends to classify women into a much lower risk category for the same number and severity of cardiovascular risk factors as men. Based on the Framingham cohort and offspring data, 98% of asymptomatic women aged 59 and younger and 92% of those aged 69 and younger are classified as low risk. Even among women aged 70 and older, only 44% are classified as intermediate or high risk.

Unpublished data from several large cohort studies indicate that only about 5% of women without diabetes mellitus who are aged 60 to 69 are identified as having a >10% risk of an MI over the next 10 years. Therefore, even if we are more successful in identifying women with cardiovascular risk factors, the vast majority of them will not receive intensive risk-reducing therapy with aspirin and lipid-lowering therapy.

This becomes more troublesome when applied to individual patients. For example, the FRS currently classifies a 45-year-old woman who is an overweight smoker with mild mixed hyperlipidemia, hypertension, and a family history of premature coronary heart disease as low risk. Based on this, there is strong reason to believe that we are missing opportunities for primary prevention in many women with a low FRS.

Although we are generally reassured by the low cardiac risk that most young women face, it is important to remember that the lifetime risk of coronary disease for a 40-year-old woman is one in three. Furthermore, while rates of cardiovascular mortality in men have declined since the initial National Cholesterol Education Program guidelines, the same has not been true in women.

Recognizing atherosclerosis

Using the coronary artery calcium score as a surrogate for coronary atherosclerosis, it has been recognized that the FRS significantly underestimates the prevalence of subclinical atherosclerosis. This is particularly true among women with a family history of premature CHD and/or metabolic syndrome.

In addition, among asymptomatic female siblings of patients with premature CHD that are classified as low risk, Erin Michos and colleagues have found that one-third have coronary artery calcium scores above the 75th percentile for their age. This indicates that some women classified as low risk by the FRS actually have atherosclerotic vascular disease that should be aggressively treated with more risk factor modification, aspirin, and statin therapy.

One part of the problem with the FRS is that it was designed to predict only “hard” coronary events, namely fatal and nonfatal MIs. While these events are important targets, they represent only a portion of cardiovascular disease events that warrant prevention. Compared with men, women are less likely to have an MI or coronary death as their first manifestation of CHD.

Other cardiovascular events, such as angina pectoris or cerebrovascular disease, predominate in women. While many will ultimately experience an MI or die from a cardiac cause, these events appear to occur later in women. Also, once clinical CHD has developed in women, it is generally associated with a worse prognosis than in men.

No one questions that the FRS is a well-validated epidemiologic measure to assess risk at a population level. Importantly, it appears to accurately predict a low risk of MI among many women in the short term. That being said, it fails to identify a number of women facing increased cardiovascular risk that would benefit from preventive therapies.

Central to the process of improved risk stratification in women is the identification and validation of inexpensive tools and tests that can successfully discriminate higher risk women within the low-risk FRS cohort. One such tool may be the exercise treadmill test. In a recent report by Samia Mora et al, researchers said the combination of below average (for one’s age and gender) heart rate recovery and/or below average exercise capacity prospectively identified 90% of women and men that sustained a major cardiovascular event over the next 20 years.

Another such test is an assessment of coronary calcium. In another recent report, Michos et al identified that 45% of women with a family history of premature CHD and two other cardiovascular risk factors had evidence of coronary atherosclerosis as evidenced by the presence of advanced calcified plaque for their age.

Ultimately, one of the key issues in risk assessment of asymptomatic adults lies in whether antiplatelet and lipid-lowering therapy should be prescribed. While nonpharmacologic interventions figure prominently in recommendations by the NCEP and other groups, they often take a back seat to the decision as to whether pharmacologic therapy is warranted. The risk terminology employed by the FRS unfortunately contributes to this. For example, when the aforementioned patient is told she is low risk (despite her high lifetime risk of CHD), she may not recognize the need to promptly implement major lifestyle changes.

Global risk assessment

Such problems have led some individuals to recommend divorcing pharmacologic risk strategies from global risk prediction equations to remove this mixed message. This proposal would remove age-dependent factors from the global risk assessment, offering patients a risk assessment relative to others of the same age.

Interventions with great lifetime economic impact – primarily drug therapy – would necessarily remain tied to estimation of a patient’s absolute cardiovascular risk. At the same time, the need for interventions requiring greater personal commitment to change – smoking cessation, weight loss, and dietary modification – could be more effectively communicated.

Importantly, studies examining the role of other testing modalities (ie, imaging of subclinical atherosclerosis, as well as genomic, proteomic, and metabolomic assessments) are currently underway. In addition, the NHLBI has initiated a multidisciplinary working group on the integrative approach to identifying patients at high risk of a cardiovascular event.

We are hopeful that the risk assessment process for women and for men can be improved through better utilization of clinical history and physical examination information in conjunction with selective use of emerging risk factors. This may enable clinicians to maximize proven preventive lifestyle and pharmacologic therapies to slow and perhaps halt the progression of atherosclerotic vascular disease throughout the world in a cost-effective manner.

Christopher Sibley, MD, is a fellow in cardiology at Johns Hopkins University and a former chief medical resident at Northwestern.

Ty J. Gluckman, MD, a member of the Cardiology Today Fellows Advisory Board, is a fourth year Johns Hopkins University fellow.

Roger S. Blumenthal, MD, a member of the Preventive Cardiology section of the Cardiology Today Editorial Board, is associate professor of medicine and director of The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease.