USPSTF: Nontraditional CVD risk factors not ready for prime time

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CAC improves risk assessment

These conclusions are understandable from the policy perspective but do not fully address the issues faced by individual patients and clinicians in decisions about the relative merits of primary preventive therapies.

Dr. Donald M. Lloyd-Jones is a professor and chairman of preventive medicine at Northwestern University in Chicago.

Dr. Donald M. Lloyd-Jones

The evidence is strong that CAC scores effectively reclassify many patients to high or low risk and can therefore contribute important information for decision making in individual patients.

In middle-aged and older U.S. adults whose estimated absolute risks of developing CVD events are near a treatment threshold (e.g., 7.5%), the presence of CAC scores greater than 100, or higher than the 75th percentile for a given age, accurately reclassifies individuals to a higher category of risk. Even individuals with low estimated 10-year risks and high CAC scores (more than 100 Agatston units) have substantially greater observed risks than do those with CAC scores of 0. Thus, the presence of CAC in these patients effectively identifies those at higher risk who may benefit from statin therapy. Avoidance of statin therapy in the majority of intermediate-risk patients who have a CAC score of 0 also is desirable.

Meanwhile, a low ABI represents an advanced form of atherosclerosis. Clinicians should be aware of PAD and, if it is present, should strongly consider statin therapy. Use of the ABI in routine clinical practice to screen for PAD in at-risk patients is reasonable, but its routine use in estimation of CVD risk is limited. Measurement of subclinical inflammation with hsCRP has been shown to reclassify some individuals at intermediate levels of risk. However, the utility of hsCRP measurement in routine assessment of CVD risk for primary prevention is limited.

John Wilkins, MD, is an assistant professor of cardiology and preventive medicine and Donald Lloyd-Jones, MD, is the chair of the Department of Preventive Medicine at Northwestern University, Chicago. They had no disclosures, and made their comments in an editorial (JAMA. 2018 Jul 10. doi: 10.1001/jama.2018.9346 ).



Current evidence is insufficient to assess the balance harms and benefits of adding ankle-brachial index, high-sensitivity C-reactive protein, or coronary artery calcium burden to traditional cardiovascular disease risk scores for asymptomatic adults, according to the United States Preventive Services Task Force.

There is adequate evidence that they slightly improve assessment models without adding much risk, but “the clinical meaning of these changes is largely unknown,” the group said in a recommendation statement (JAMA. 2018 Jul 10. doi: 10.1001/jama.2018.8359).

USPSTF did note that many of the comments to its draft document “provided evidence that risk assessment with CAC [coronary artery calcium] was strong enough to warrant a separate, more positive recommendation” and “is useful for patients whose risk stratification is unclear or for those who fall into intermediate-risk groups.” However, evidence is inadequate that this would translate into improved health outcomes in asymptomatic patients.

Meanwhile, treatment decisions guided by the markers have not been shown to reduce cardiovascular events or mortality. There are no trials evaluating the additional benefit of adding the ankle-brachial index (ABI), high-sensitivity C-reactive level (hsCRP), or CAC score to traditional risk assessment models.

The USPSTF recommended “that clinicians use the Pooled Cohort Equations to assess CVD risk and to guide treatment decisions until further evidence is available,” noting that these equations, introduced in 2013, were developed using more contemporary and diverse cohort data than were the older Framingham Risk Score. Traditional CVD risk factors include age, sex, high blood pressure, current smoking, abnormal cholesterol levels, diabetes, obesity, and physical inactivity.

The work replaces the group’s 2009 statement on nontraditional risk factors, which also was considered an I statement, for inadequate evidence. Unlike that document, the new work focused on ABI, hsCRP level, and CAC because these offer the most promising evidence base and are independently associated with CVD events.

The group noted that testing for hsCRP level and ABI is noninvasive, with little direct harm. Harms of testing for CAC score include exposure to radiation and incidental findings on CT of the chest, such as pulmonary nodules, that may lead to further invasive testing and procedures, among other problems.

The ABI is the ratio of the systolic blood pressure at the ankle to the systolic blood pressure in the arm while the patient is lying down; a value less than 1 is abnormal. High-sensitivity CRP is a serum protein involved in inflammatory and immune responses. Coronary artery calcium score is a measure of calcium content in the coronary arteries.

Good-quality studies that compare traditional risk assessment with ABI, hsCRP level, or CAC scores “are needed to measure the effect of adding nontraditional risk factors on clinical decision thresholds and patient outcomes, especially in more diverse populations (women, racial/ethnic minorities, persons of lower socioeconomic status), in whom assessment of nontraditional risk factors may help address the shortcomings of traditional risk models,” USPSTF said.

The group is funded by the Agency for Healthcare Research and Quality.

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