Key result
Cumulative LDL-C exposure linked to ~5% higher CVD risk per 100 mg/dL-years.
Why the study?
Data-based demonstration of the area under the LDL-C versus age curve metric was unavailable, and whether the time course of area accumulation modulates incident CVD risk was unknown.
Does cumulative prior exposure to LDL-C and the time course of area accumulation predict incident cardiovascular disease event risk in asymptomatic young adults?
Cohort (n=4,958)
Does cumulative prior exposure to LDL-C and the time course of area accumulation predict incident cardiovascular disease event risk in asymptomatic young adults?
Effect estimate: HR 1.053
p-value: p=<0.0001
Cumulative LDL-C exposure and its accumulation at a younger age independently increase the risk of incident cardiovascular events, highlighting the importance of early optimal LDL-C control.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“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 usual method is to calculate risk by risk factors measured at one point in time.... Even in clinical practice, we still keep working on risks factors measured at a specific day. I think we should really move towards this approach, because it brings new findings, new [perspectives], and new predictions.”
“The resulting quantitative relationships provide information that informs the design of primary prevention strategies and clinical trials to assess those strategies, and as a tool for formulating projections of the likely impact on public health of prevention strategies.”
Hypothesis-generating for prioritizing early LDL-C optimization in young adults; leaves open reversibility of accumulated risk pending RCTs before adoption.
BACKGROUND Incident cardiovascular disease (CVD) increases with increasing low-density lipoprotein cholesterol (LDL-C) concentration and exposure duration. Area under the LDL-C versus age curve is a possible risk parameter. Data-based demonstration of this metric is unavailable and whether the time course of area accumulation modulates risk is unknown. OBJECTIVES Using CARDIA (Coronary Artery Risk Development in Young Adults) study data, we assessed the relationship of area under LDL-C versus age curve to incident CVD event risk and modulation of risk by time course of area accumulation-whether risk increase for the same area increment is different at different ages. METHODS This prospective study included 4,958 asymptomatic adults age 18 to 30 years enrolled from 1985 to 1986. The outcome was a composite of nonfatal coronary heart disease, stroke, transient ischemic attack, heart failure hospitalization, cardiac revascularization, peripheral arterial disease intervention, or cardiovascular death. RESULTS During a median 16-year follow-up after age 40 years, 275 participants had an incident CVD event. After adjustment for sex, race, and traditional risk factors, both area under LDL-C versus age curve and time course of area accumulation (slope of LDL-C curve) were significantly associated with CVD event risk (hazard ratio: 1.053; p < 0.0001 per 100 mg/dl × years; hazard ratio: 0.797 per mg/dl/year; p = 0.045, respectively). CONCLUSIONS Incident CVD event risk depends on cumulative prior exposure to LDL-C and, independently, time course of area accumulation. The same area accumulated at a younger age, compared with older age, resulted in a greater risk increase, emphasizing the importance of optimal LDL-C control starting early in life.
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Domanski et al. (2020) conducted a cohort in Asymptomatic adults (n=4,958). Cumulative LDL-C exposure (area under LDL-C versus age curve) was evaluated on Composite of nonfatal coronary heart disease, stroke, transient ischemic attack, heart failure hospitalization, cardiac revascularization, peripheral arterial disease intervention, or cardiovascular death (HR 1.053, p=<0.0001). Cumulative prior exposure to LDL-C was significantly associated with increased incident cardiovascular disease event risk (HR 1.053 per 100 mg/dl × years; p<0.0001).
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