Less Is More? Multistage CVD Screening Could Eliminate LDL Lab Tests

January 21, 2014

BOSTON, MA — A screening approach that selectively uses laboratory-based cholesterol testing to assess cardiovascular risk is able to identify patients at risk for cardiovascular disease to a similar extent as a widely used risk model, according to the results of a new study[1].

The multistage primary cardiovascular disease screening approach, in which only patients first identified as at intermediate risk of cardiovascular events are sent to the laboratory to measure cholesterol levels, performed as well as the Framingham Risk Score (FRS), which utilizes laboratory testing in all patients to assess cholesterol levels, in terms of discriminating risk of cardiovascular disease.

"We are always looking at ways to assess a patient's risk—whether it's downtown Boston, India, or anywhere in the world—and make an accurate prediction about risk," senior investigator Dr Thomas Gaziano (Brigham and Women's Hospital, Boston, MA) told heartwire . "We keep adding other risk factors, like C-reactive protein, which is reasonable, but we're not pushing the envelope very far with any of the additional risk factors. So we asked, What if we took something out? We were looking to see if we could develop a practical model and if we'd lose anything if we took [cholesterol] out."

Multistage Screening Approach

Published online January 14, 2014 in Circulation: Cardiovascular Quality and Outcomes, the researchers used a multistage screening strategy that calculated an individual's risk of fatal or nonfatal cardiovascular outcomes using multiple non–laboratory-based risk markers. These included age, sex, smoking status, history of diabetes, blood-pressure treatment, systolic blood pressure, and body-mass index (BMI). From here, patients were classified as high, intermediate, or low risk for cardiovascular disease.

In this multistage-screening approach, those at the polar ends of the risk spectrum would require no further testing and would be assigned treatment with statins (high-risk patients) or monitored without treatment (low-risk patients). Only individuals in the intermediate-risk category would be sent for laboratory tests to assess cholesterol levels.

To heartwire , Gaziano explained that for patients at low risk of cardiovascular disease, cholesterol information doesn't add much to their overall risk assessment. For the low-risk patient assessed without laboratory testing, he'll monitor weight and blood pressure and if these change will then consider cholesterol testing. For those with multiple risk factors, including older patients with elevated blood pressure, diabetes, overweight/obesity, and a smoking history, he'll be aggressive with statin therapy regardless of their LDL-cholesterol levels.

"Of all of the risk factors in the Framingham risk model, cholesterol is the one that requires laboratory testing," said Gaziano. Despite the strengths of the Framingham model, cholesterol testing might not be readily available in some countries or neighborhoods. "Even in my own practice in Boston, I can send a patient for a cholesterol test, and they don't come back. I've lost an opportunity to assess their risk."

I can send a patient for a cholesterol test, and they don't come back. I've lost an opportunity to assess their risk."

Using data from 5998 adults in the National Health and Nutrition Examination Survey (NHANES) III, the researchers compared the multistage approach with the FRS for predicting the 10-year risk of cardiovascular events. In addition, they varied the upper and lower thresholds for initiating treatment in the high- and low-risk patients as well as varied the Framingham 10-year risk thresholds for initiating treatment. These variations altered the percentage of the NHANES population who underwent laboratory testing from 25% to 75%.

In men, a multistage approach that saw 25%, 50%, and 75% of the population undergo laboratory testing depending on the thresholds for risk, the area under receiver operating characteristic (ROC) curve, which provides information about how well the approach is able to discriminate risk compared with the FRS, was 0.780, 0.778, and 0.774. For women, the equivalent area under the ROC curve was 0.812, 0.819, and 0.827, respectively. Overall, there was no significant difference in the area under the curves between the multistage and Framingham-based approaches.

"We should always be wondering if the approach we're using now is the best approach," said Gaziano. "We recognize that using some type of absolute risk measure in trying to gauge the risk of cardiovascular disease is better than just checking cholesterol or checking blood pressure. Multiple risk factors contribute to cardiovascular disease, and in some ways, in identifying people at risk it makes sense to look at all those risk factors."

Cost-effectiveness Analysis

In a cost-effectiveness analysis, the multistage strategy had an incremental cost-effective ratio of $52 000 per quality-adjusted life-year (QALY) for men and $83 000 per QALY for women. A single-stage treatment approach that was based on Framingham but did not measure cholesterol levels had an "unattractive" incremental cost-effectiveness ratio of more than $300 000 per QALY when compared with the multistage approach, report investigators.

In addition to showing the advantages of utilizing the staged approach, Gaziano said the low cost of generic statins makes them extremely attractive in terms of the incremental cost-effectiveness ratio. At roughly $100/year, lowering the threshold for treatment in the intermediate-risk category to less than 7.5%, which is the threshold for treatment in the new cholesterol guidelines, would still make them an attractive option.

"[With] an overall cardiovascular disease risk of 2.5% or 3.0%, if you're paying $100 or less, they're still cost-effective," he said.

The authors report no conflicts of interest.


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