Disclosures: The study authors report no relevant financial disclosures. Please see the editorial for Shapiro’s and Bhatt’s relevant financial disclosures.
September 21, 2020
3 min read

Time course of LDL accumulation may influence CVD event risk

Disclosures: The study authors report no relevant financial disclosures. Please see the editorial for Shapiro’s and Bhatt’s relevant financial disclosures.
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Cumulative years of LDL exposure were significantly associated with risk for CVD events, according to findings published in the Journal of the American College of Cardiology.

Michael J. Domanski, MD, professor of medicine in the division of cardiovascular medicine at the University of Maryland School of Medicine in Baltimore, and colleagues suggest the findings emphasize the importance of LDL control earlier in life.

LDL Test 2019 Adobe
Source: Adobe Stock.

“This study shows that the risk of a future incident CVD event at a given age increases with the total accumulated area under the LDL-C versus age curve. Importantly, this risk is modulated by the time course of area accumulation,” the researchers wrote. “Specifically, the data suggest that area accumulated early confers greater risk than when the same area is accumulated later. Hence, for instance, two individuals age 40 years with the same LDL-C and/or the same area under the LDL-C versus age curve could have different risk for a future incident CVD if the time course of area accumulation was different.

“This underscores the importance of optimal LDL-C early in life, because lower LDL-C later, even when low enough to result in the same area at a landmark age, does not fully reverse risk acquired earlier,” the researchers wrote.

For this prospective analysis, investigators included 4,958 participants who were enrolled in the CARDIA trial from 1985 to 1986 (mean age at enrollment, 25 years; 55.3% women; 51% Black). According to the study, researchers assessed the relationship of area under LDL vs. age curve and incident CVD event risk and whether the increased risk for the same area increment is different at different ages. The primary outcome was a composite of nonfatal CHD, stroke, transient ischemic attack, HF hospitalization, cardiac revascularization, peripheral artery disease intervention or CV death.

“Incorporating both the LDL-C concentration and exposure duration into a single risk parameter for future CVD events is intuitively appealing, although a data-based demonstration of the utility of this metric is not available,” researchers wrote. “Also unclear is whether the time course of area accumulation is important in modulating the risk conferred by a given area. For instance, does the risk of an adverse cardiovascular event in an individual subsequent to a particular landmark age (eg, age 40 years) differ based only on the total area, or is there a different risk (despite the same total area) depending on whether more of the area is accumulated at earlier rather than later ages prior to the landmark age?”

Consider time course of accumulation

Among patients with no CVD events before age 40 years, 275 participants had their first event. The median age for experiencing first CVD event was 49 years. At age 50 years, the CVD event rate was 3.1% and increased to 7.8% at age 60 years.

Investigators observed that after adjustment for sex, race and risk factors, both area under LDL vs. age curve (per 100 mg/dL x years, HR = 1.053; P < .0001) and time course of area accumulation were significantly associated with CVD event risk (per mg/dL per year, HR = 0.797; P = .045).

“Assessment of risk of future CVD events is informed by considering not just the area under the LDL-C versus age curve, but also the time course of accumulation,” the researchers wrote. “Using these data from CARDIA, we developed a risk model that takes into account both of these descriptors of longitudinal LDL-C exposure through young adulthood.”

Low-intensity therapy in young, healthy adults

Michael D. Shapiro
Deepak L. Bhatt

“Although there remain unanswered questions, perhaps the most important issues to focus upon are how much more evidence is needed to recommend initiation of long-term lipid-lowering therapy in young individuals with hypercholesterolemia,” Michael D. Shapiro, DO, MCR, Fred M. Parrish professor of cardiology and molecular medicine and director of the Center for Prevention of Cardiovascular Disease at Wake Forest University School of Medicine, and Cardiology Today Intervention Section Editor Deepak L. Bhatt, MD, MPH, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, wrote in a related editorial. “Does our society have the appetite to start low-intensity therapy in large swaths of young, healthy individuals even if robust randomized trial evidence does not support this approach? Thanks to the authors of this paper, the cholesterol-years model brings us one step closer to imagining this possibility.