The American Heart Association (AHA) and the American College of Cardiology (ACC) have issued a report that discusses approaches to the assessment of cardiovascular risk as a tool for primary prevention of coronary disease. The content of the report is primarily written in the context of information gleaned from the Framingham Heart Study. The report provides guidance for assessing short-and long-term risk and relative risk versus absolute risk in patients without coronary disease. According to the AHA/ACC scientific statement, assessment of total (global) risk has three clinical purposes: (1) to identify high-risk patients who deserve immediate attention and intervention, (2) to motivate patients to adhere to risk-reduction therapies and (3) to modify the intensity of risk-reduction efforts based on the total risk estimate.
The AHA/ACC scientific statement, titled “Assessment of Cardiovascular Risk by Use of Multiple-Risk-Factor Assessment Equations,” appears in the September 28, 1999 issue of Circulation and the October 1999 issue of the Journal of the American College of Cardiology. The statement is also available on the Web sites of the AHA (http://www.americanheart.org) and the ACC (http://www.acc.org). The following highlights the AHA/ACC scientific statement.
Risk Factors for Coronary Disease
The report begins by enumerating the major independent risk factors for coronary disease, as follows: cigarette smoking of any amount, elevated blood pressure, elevated levels of serum total cholesterol and low-density lipoprotein cholesterol (LDL), low levels of serum high-density lipoprotein cholesterol (HDL), diabetes mellitus and advancing age. Absolute risk should be estimated on the basis of these major risk factors. The absolute risk estimate can then be modified on the basis of the presence or absence of conditional and predisposing risk factors.
According to the report, conditional risk factors are associated with an increased risk of coronary disease, although their causative, independent and quantitative contributions to coronary disease have not been well documented. Conditional risk factors include the following: elevated serum triglyceride levels, small LDL particles, elevated serum homocysteine levels, elevated serum lipoprotein(a) levels, prothrombotic factors (e.g., fibrinogen) and inflammatory markers (e.g., C-reactive protein). Predisposing risk factors are those that worsen the independent risk factors. They include obesity, abdominal obesity, physical inactivity, a family history of premature coronary heart disease, ethnic characteristics and psychosocial factors.
Estimating Risk from Framingham Scores
The AHA/ACC report states that the first step in estimating the risk of coronary heart disease is to calculate the number of Framingham points for each risk factor (see the accompanying table).
Risk ratios, relative to the low-risk state, are shown for men in Figure 1 and for women in Figure 2. The report states that relative risk provides an immediate perspective of a patient's overall risk status relative to a low-risk state. In addition, relative risk can probably be used to compare risk among persons in populations in which baseline absolute risk has not been established, because the relative contributions of individual risk factors to total risk appear to be similar among different populations.
As Figures 1 and 2 show, the relative risk declines with advancing age, but the 10-year absolute risk increases with aging. According to the AHA/ACC report, these changes in risk have implications for prevention of coronary disease. Higher relative risk estimates in young adults are an indication of the high long-term risk and point to the need to institute a long-term strategy for risk reduction. The increasing absolute risk that accompanies advancing age attests to the opportunity for reducing absolute short-term risk by an immediate aggressive reduction of risk factors in older people. The report notes that the best candidates for aggressive risk reduction among older patients may be those with a moderately high or a high relative risk.
Absolute Short-Term and Long-Term Risk
The AHA/ACC report states that estimates of short-term risk (absolute risk in the next 10 years) are potentially useful for the identification of patients who need aggressive risk reduction, such as drug therapy to lower lipid levels. The report points out that the National Education Cholesterol Program (NCEP) has taken the lead in adjusting the aggressiveness of cholesterol-lowering therapy according to the patient's absolute risk. For example, NCEP guidelines identify patients with coronary disease and other atherosclerotic disease at very high risk and recommend aggressive therapy in these patients. For primary prevention, LDL goals were established in the NCEP guidelines by counting risk factors, but absolute risk is not defined in precise, quantitative terms.
According to the AHA/ACC report, an important aim of primary prevention is to reduce coronary disease over a long term, not just over 10 years. For example, a 20-year projection of absolute risk may be of interest when patients are 50 to 54 years of age.
The AHA/ACC report notes that Framingham scoring takes into account gradations in risk factors when the absolute risk is estimated. The scoring does not adequately account for severe abnormalities in risk factors, such as severe hypertension, severe hypercholesterolemia and heavy smoking. Under such circumstances, the Framingham scores can underestimate absolute risk, particularly when only one severe risk factor is present. Thus, heavy smoking or severe hypercholesterolemia can lead to premature coronary disease even when the total score for absolute risk is not high.
Diabetes Mellitus as a Special Case in Risk Assessment
Most patients with diabetes mellitus, especially type 2 diabetes mellitus (formerly known as non–insulin-dependent diabetes mellitus), can be considered to have high short-term risk. The risk in patients with diabetes often approaches that of patients with established coronary disease. According to the AHA/ACC report, the absolute risk of patients with type 2 diabetes usually exceeds the Framingham score for hyperglycemia because other risk factors are almost always present. In addition, patients with diabetes probably merit a higher risk category than suggested by Framingham scoring because of the poor prognosis once coronary disease develops in a patient with diabetes.
Risk Assessment in Elderly and Non-White Patients
As seen in Figures 1 and 2, a feature of the Framingham risk scoring is the progressive increase in absolute risk with advancing age, a reflection of the cumulative nature of atherogenesis. However, according to the AHA/ACC report, average scores mask the extent of variability in plaque burden in the general population. Risk may be miscalculated when average risk scores for age are applied to individual patients, and such a miscalculation may lead to inappropriate selection of patients for aggressive risk-reduction interventions. Thus, according to the report, flexibility is needed in adapting treatment guidelines to older patients, particularly those more than 65 years of age.
The report points out that most of the subjects in the Framingham study were whites of European origin. It is unknown whether absolute risk is different in other ethnic groups, although evidence suggests that it varies among different populations. For example, studies indicate that Indians and Pakistanis living in Western cultures have an absolute risk that is approximately twice that of whites, even when the two populations are matched for major risk factors. Available data suggest that non-Hispanic white, non-Hispanic black and Hispanic Americans have a comparable absolute risk status, indicating that absolute risk estimates seem applicable to non-Hispanic white, Hispanic and black Americans. Results of the Honolulu Heart Study indicate that Hawaiians of East Asian ancestry have only about two thirds the absolute risk of Framingham subjects. Similarly, in the Seven Countries Study, the population of Japan was found to have a much lower risk of coronary heart disease for a given set of risk factors than other populations.
Hypertriglyceridemia, Insulin Resistance and Homocysteine Levels
A reduction in elevated triglyceride levels may be a target of therapy independent of lowering the LDL level. The AHA/ACC report points out that the Framingham scoring does not ascribe independence to triglyceride levels in risk assessment. Nevertheless, hypertriglyceridemia has been found by Framingham investigators, as well as others, to be an independent risk factor. However, the report states that the degree of independent predictive power is difficult to assess.
Insulin resistance has been found to correlate with an increased risk of coronary disease, and a large proportion of patients who are candidates for global risk assessment have insulin resistance and its accompanying metabolic risk factors, such as elevated triglyceride levels, small LDL particles, low HDL levels, elevated blood pressure, a prothrombotic state and impaired fasting glucose. The AHA/ACC report notes that the risk accompanying the metabolic syndrome can largely be assessed by Framingham scoring.
Whether a reduction in serum homocysteine levels will reduce the risk of coronary disease awaits the results of controlled clinical trials. However, patients with elevated homocysteine levels may benefit from folic acid, vitamin B6 and vitamin B12 to reduce elevated homocysteine levels. While routine measurement of homocysteine levels is not recommended in the report for the purposes of risk assessment, the report states that determining the homocysteine level is an optimal approach in high-risk patients.