Accurate CV Lifetime Risk Calculators Need Further Development

Brian Ference, MD, MPhil, MSc

When it comes to cardiovascular (CV) disease risk assessment and prevention, there still remains a great need to develop predictive algorithms that can more accurately estimate both lifetime risk and lifetime benefit of early intervention in order to lower such risk.

In his state-of-the-art lecture presented at the European Society of Cardiology (ESC 2020) Congress, Brian Ference, MD, MPhil, MSc, professor and Director of Research in Translational Therapeutics at the University of Cambridge, discussed the shortcomings of current guidelines and calculators for assessing lifetime risk for CV disease in patients with developing atherosclerosis.

Current risk estimating equations use immediate risk factors to determine which individuals are at highest risk and who would most benefit from intervention.

Ference stressed that current guidelines emphasize that decision to treat and intensity of treatment should be based on assessment of the patient’s next 10 years.

“That has the practical effect of inviting us to wait until we develop a sufficiently large underlying atherosclerotic plaque burden that were at high risk of a short-term event” Ference told HCPLive® in an interview. “That really is somewhat inconsistent with our understanding of how atherosclerosis slowly develops over time. And therefore, it may not be the optimal strategy for estimating risk.”

Thus, estimating overall lifetime risk may be a better strategy in identifying patients who are at high risk earlier in life. Doing so can allow early intervention by slowing the progression of the atherosclerotic plaque development and ultimately prolong onset of CV disease.

Such short-term prevention strategies can potentially overlook patients with high lifetime risk and low short-term risk, he noted. Furthermore, counting the number of risk factors may be inadequate—it fails to account for the log-linear relationship between low-density lipoprotein (LDL) and systolic blood pressure (SBP).

He cited new developments in lifetime risk calculators that estimate risk in patients with any level of LDL and SBP as well as adjust for competing risk so as to not overestimate lifetime risk.

Additionally, these new algorithms attempt to estimate the lifetime benefit of reduced LDL and SBP on CV disease.

However, there are still shortcomings in these new predictive models.

According to Ference, they fail to use causal estimates of the effects of LDL and SBP on CV disease as well as their cumulative effects over time. Benefit must then be estimated by using the effects observed in short-term randomized trials.

“Mandelian randomization studies suggest that long-term exposure to both LDL and blood pressure have not only a causal effect on atherosclerosis, but those effects accumulate over time,” Ference said. “This suggests that earlier interventions of lowering LDL or blood pressure can dramatically reduce the lifetime risk of cardiovascular disease.”

Although, unresolved questions still remain as to when it is appropriate to lower LDL and blood pressure, by how much, and for how long.

In spite of these lingering uncertainties, Ference concluded his lecture by addressing the ideal lifetime risk calculator.

“Indeed, [it] would tell each person why they are at risk for cardiovascular disease, how they can effectively reduce that risk, and how much they would benefit if they followed the recommendations.”

The lecture, “Lifetime risk assessment for cardiovascular disease,” was presented at ESC 2020.