Sustained LDL-C target attainment (<1.8 mmol/L) was associated with lower risk of recurrent ischemic cerebrovascular events after ischemic stroke, with a stronger protective association in patients with significant large-artery disease.
Key Findings
Results
Time-varying LDL-C target attainment was associated with significantly lower risk of recurrent ischemic cerebrovascular events in the overall study population.
Study included 933 patients with ischemic stroke who had baseline LDL-C levels ≥1.8 mmol/L at admission
102 recurrent ischemic cerebrovascular events occurred during follow-up
In the fully adjusted model, HR = 0.399 (95% CI: 0.269–0.593, p < 0.001)
LDL-C target attainment was defined as <1.8 mmol/L and modeled as a time-varying exposure using time-dependent Cox models
Study design was retrospective
Results
The association between LDL-C target attainment and lower recurrence risk was stronger in patients with significant large-artery disease (LAD) than in those without LAD.
369 of 933 patients had LAD, defined as ≥50% intracranial or extracranial atherosclerotic stenosis; 564 did not have LAD
In patients with LAD: HR = 0.282 (95% CI: 0.168–0.475, p < 0.001)
In patients without LAD: HR = 0.530 (95% CI: 0.288–0.976, p = 0.042)
P for interaction = 0.041, indicating statistically significant effect modification by LAD status
Results
Greater proportion of follow-up time spent with LDL-C ≥1.8 mmol/L was associated with higher recurrence risk, with a stronger association in LAD patients.
Each 10% increase in the proportion of follow-up time with LDL-C ≥1.8 mmol/L was associated with HR = 1.189 (95% CI: 1.127–1.254) for recurrent events
The association between time above LDL-C target and recurrence was stronger in patients with LAD (P for interaction = 0.008)
This metric captures the cumulative burden of suboptimal LDL-C control over time
Methods
Patients with ischemic stroke were stratified by the presence of significant large-artery atherosclerotic disease for subgroup analyses of LDL-C target attainment effects.
LAD was defined as ≥50% intracranial or extracranial atherosclerotic stenosis
Of 933 total patients, 369 (39.6%) had LAD and 564 (60.4%) did not
All patients had baseline LDL-C ≥1.8 mmol/L at admission, establishing a population with elevated lipid levels requiring management
Primary outcome was recurrent ischemic cerebrovascular events
Methods
The study used LDL-C target attainment as a time-varying exposure, an approach noted as underutilized in prior research on this population.
Time-dependent Cox models were used to evaluate the association between time-varying LDL-C target attainment and recurrence
Authors noted that 'few studies have evaluated the impact of sustained LDL-C target attainment on recurrent ischemic cerebrovascular events by using LDL-C target attainment as a time-varying exposure'
The proportion of follow-up time with LDL-C ≥1.8 mmol/L was additionally assessed as a secondary exposure metric
The study was retrospective in design
What This Means
This research suggests that keeping LDL cholesterol (often called 'bad' cholesterol) below a target level of 1.8 mmol/L over time is linked to a significantly lower chance of having another stroke or related brain blood vessel event in people who have already had an ischemic stroke. The study followed 933 patients and found that those who consistently maintained their LDL cholesterol below the target had roughly 60% lower risk of a recurrent event compared to those who did not. Importantly, the more time a patient spent above the target cholesterol level, the higher their risk of recurrence became.
The study also found that the benefit of sustained cholesterol control was especially pronounced in patients who had significant narrowing (50% or more) of major arteries supplying the brain — a condition called large-artery disease. In these patients, maintaining LDL below the target was associated with about 72% lower recurrence risk, compared to about 47% lower risk in those without significant artery narrowing. This suggests that patients with large-artery disease may stand to gain the most from tight, sustained cholesterol management.
This research matters because it highlights not just whether patients achieve a cholesterol target at a single point in time, but whether they sustain that control over a longer period. The findings support using sustained LDL cholesterol control as a tool for risk stratification and personalized secondary prevention strategies after ischemic stroke, particularly for those with underlying large-artery atherosclerosis.
Zhang X, Niu D, Li Y, Wang Y, Chen R, Xing G. (2026). Sustained LDL-C target attainment and recurrent ischemic cerebrovascular events after ischemic stroke: effect modification by large-artery disease.. Frontiers in neurology. https://doi.org/10.3389/fneur.2026.1902614