Study Fuels Debate Over When to Start Cholesterol Screening

–For younger adults, study finds low yield of 10-year risk-based screening

A new study provides ammunition to supporters of a conservative approach to initiating cholesterol tests in younger adults. But proponents of a more aggressive approach argue that the interpretation does not take into account the enormous burden of cardiovascular disease as people grow older.

There are conflicting U.S. guidelines about when to initiate screening. The American College of Cardiology/American Heart Association guideline recommends that all adults have a lipid panel starting at the age of 20 and have repeat tests every 4 to 6 years. The U.S. Preventive Services Task Force (USPSTF) recommends initial screening for men at age 35 and women at 45 if they have no other risk factors.

In a paper published in Annals of Internal Medicine, Krishna Patel (St. Luke’s Hospital, Kansas City) and colleagues sought to “identify subgroups for which cholesterol screening would not provide actionable information.” They analyzed data from 9,608 people ages 20 to 49 without known CV disease who were participants in the National Health and Nutrition Examination Survey (NHANES). They looked for people with a 10-year risk of CV disease greater than 5%, the threshold for considering statin therapy in the ACC/AHA guidelines.

In the NHANES cohort, 9.1% of the participants had an elevated risk for CV disease. Broken down by age, sex, smoking, and hypertension, the percentage of people at high risk ranged from 0% to 75.9%. Among women who did not smoke or have hypertension, only 0.04% had an elevated CV risk. By contrast, three-quarters of men ages 45 to 49 who smoked had an elevated risk.

High LDL cholesterol levels (190 mg/dL or higher) were found in 2.9% of people in the study. In the groups at low risk only, 1.7% had high LDL levels. LDL levels were higher in people who smoked or had high blood pressure. In a subgroup analysis, family history did not identify a group with higher LDL levels.

“Given the low prevalence of patients at elevated cardiovascular risk, our findings would support the targeted approach of the USPSTF over the more general screening of the ACC/AHA,” the authors wrote. They argued that there is no reason to believe that telling patients that “they are at low risk will prompt positive behavior changes, and it might even have the opposite effect.”

10-Year Versus Lifetime Risk

In an accompanying editorial, Paul Ridker and Nancy Cook (both at Brigham and Women’s Hospital) emphasized that high cholesterol levels may be present for decades before a cardiovascular event occurs. For younger people in particular, the lifetime risk may be much higher than their 10-year risk. The study authors acknowledged this issue but pointed out that “no trials have been done to inform such a strategy, and treatment in later years is so effective that it is unclear how much additional benefit would result from initiating treatment early.” They also pointed to the increased risk of developing diabetes with statins, “which might outweigh cardiovascular benefits in younger patients.”

Ridker and Cook wrote that “the conservative stance” from the USPSTF is based on “an absence of formal clinical trial evidence” but they pointed out that “trials of lipid reduction with 25 to 30 years of follow-up are unfeasible.” The short-term perspective “fails to take into account that over the course of a lifetime” interventions in young people will actually have the largest impact.

They also pointed out that failure to screen young people also risks decreasing the likelihood of identifying people with familial hypercholesterolemia (FH), who have a much higher risk than those with acquired hyperlipidemia.

“Absence of evidence is not evidence of absence,” they conclude. They recommended early screening, at least one time, “for all patients in their late teen or early adult years.”

Not All About Statins

“We all hope to live longer than 10 years,” commented James Stein (University of Wisconsin). “The seeds of tomorrow’s atherosclerosis were planted in years past. Shared decision-making is necessary for almost all of these areas where evidence is lacking. We should be more open to discussion and less prescriptive in both directions (under- and over-treatment).”

But Stein also emphasized another point: “The paper assumes that the only response to finding abnormal lipids is starting a statin. For the young adults they looked at, many, if not most, would be counseled about lifestyle interventions. The magnitude of lipid and other metabolic improvements lifestyle changes can achieve, over the course of decades, would be expected to be highly effective at reducing long term ASCVD [atherosclerotic cardiovascular disease] risk. That’s the main reason I disagree with the authors’ conclusions and the USPSTF recommendations.”

“The results of this study could have easily been predicted,” said Amit Khera (University of Texas Southwestern Medical Center, Dallas). “Age is the strongest determining [factor] of ASCVD risk, such that all men ≥67 and women ≥71 have ASCVD risk >7.5% regardless of risk factor levels, including cholesterol levels. Similarly, it is well known that young individuals would have to have extreme or numerous risk factors to approach 5% ASCVD risk. The purpose of assessing lipids at a younger age is not only about statin allocation. Genetic models have demonstrated that relatively small changes in lipids early in life can markedly reduce lifelong [coronary heart disease] incidence. So, if a 35 year old is noted to have an LDL-C of 160 mg/dL, improving LDL-C to say 120 to 130 with lifestyle interventions could have a significant impact on lifetime risk of ASCVD with little harms of the intervention. The benefit of this strategy could never be assessed in a clinical trial, but the sum total of data support a prudent approach.”

Khera calculated that “for every 50 younger subjects screened, one would be identified to have LDL-C >190 which is a treatment threshold and a level where most would agree some intervention is warranted.”

“I agree with the editorialists,” said Marilyn Mann, a patient advocate with family members who have FH. “Heterozygous familial hypercholesterolemia is a common disease and occurs in approximately one out of 250 people. People with FH are at risk for early cardiovascular events, which can be prevented by early diagnosis and treatment. Everyone should be offered the opportunity to have at least one lipid screening early in life in order to identify people with extreme lipid levels. This can also lead to diagnosis of family members who have the disease. Targeted screening is not sufficient as FH can occur in the absence of other risk factors. I have met too many people who have lost family members who were in their 30s or 40s, or who have had an MI or developed advanced atherosclerosis at an early age and worry about living to see their children reach adulthood. Ideally, the decision whether to be screened should occur through shared decision-making.”

“The important thing to keep in mind is whether the screening results in any benefit to the people that undergo it, who are already healthy,” said Rita Redberg (UCSF). “So we need to think about whether undergoing the screening test results in an improvement in their life. As they feel fine, the only improvement would be if they live longer, as a result of the screening. There is no data to suggest benefit from this screening. Best way to help people to avoid heart disease and live longer is to counsel on healthy diet, regular physical activity, and not smoking. Cholesterol testing’s main purpose seems to be to drive people to take statins, and very few, if any will benefit from statins, especially in young people. I think we all agree that we need to focus on healthy lifestyles and we do not need to check cholesterol to do that.”