In the CNSR-III cohort of 15,166 patients with ischemic stroke or TIA, 12,603 patients from 171 sites were entered into a subgroup analysis of Lp(a) levels and functional outcomes. Blood samples from 11,261 of the 12,603 patients were collected and examined at the laboratory. According to the inclusion criteria, a total of 10,422 patients were included in the study, and the remaining 839 patients were excluded (Figure S1). In Table S1, the comparison of the included and excluded patients is shown. Compared with the excluded patients, the included patients showed significantly higher levels of LDL-C, Lp-PLA2, lower rate of current smoker, and higher discharge medication rates of anticoagulant and antiplatelet drugs.
Baseline characteristics
Table 1 shows the baseline characteristics of the 10,422 individuals stratified by Quartiles of baseline plasma Lp(a) levels. With the increment in plasma Lp(a) levels, patients tended to be older and had lower levels of BMI and TG, a higher proportion of LAA, and higher LDL-C, HDL-C, hsCRP, and Lp-PLA2.
Association between the levels of Lp(a) and stroke outcomes at 3 months and 1 year
Figure S2 demonstrates a positive correlation between the levels of Lp(a) and functional outcomes of stroke at 3 months. In the unadjusted model, elevated levels of Lp(a) were positively correlated with the poor clinical outcomes of stroke as evaluated using mRS score ≥ 3 at 3 months [Quartile 4 vs. Quartile 1, HR 1.58, 95% CI 1.35-1.86, p<.0001] (Table 2). Furthermore, elevated Lp(a) levels were significantly associated with the poor clinical outcomes of stroke as evaluated by mRS score ≥ 3 at 1 year [Quartile 4 vs. Quartile 1, HR 1.48, 95% CI 1.25-1.74, p<.0001]. After adjustment for age, sex, BMI, FPG, LDL-C, HDL-C, TG, hsCRP, Lp-PLA2, TOAST subtype, and NIHSS score at admission, similar results were observed. Elevated levels of Lp(a) were positively correlated with the poor clinical outcomes of stroke as evaluated by mRS score ≥ 3 at 3 months [Quartile 4 vs. Quartile 1, HR 1.39, 95% CI 1.11-1.75, p<.0001] and at 1 year [Quartile 4 vs. Quartile 1, HR 1.27, 95% CI 1.02-1.59, p<.0001]. Distribution of mRS scores at 3 months according to Lp(a) levels showed similar trends (Figure 1).
Subgroup analysis for the association between Lp(a) levels and mRS ≥3 at 3 months
Among all the subgroup detection indexes, only the variable Lp-PLA2 was associated with both Lp(a) levels and functional outcomes of stroke (Table 3). We then used Lp-PLA2 for subgroup analysis to further evaluate the relationship between Lp(a) levels and functional outcomes of stroke assessed using mRS ≥3 at 3 months.
Concurrent assessment of Lp(a) levels and Lp-PLA2 on stroke outcomes
Table 4 shows concurrent analysis stratifying Lp(a) and Lp-PLA2 into low vs. high levels (<median value vs. ≥median value). Good outcomes were observed among patients with Lp(a) low/ Lp-PLA2 low group, whereas poor outcomes were observed among patients with Lp(a) high/ Lp-PLA2 high group.
Sensitivity analysis
Association between the levels of Lp(a) and outcomes at 3 months after removing patients with recurrent stroke and TIA
To rule out the effect of recurrence and TIA on the association between the levels of Lp(a) and outcomes at 3 months, we excluded the 3 months recurrent stroke and TIA population for further analysis. As shown in Table S2, in the unadjusted model, elevated levels of Lp(a) were positively correlated with the poor clinical outcomes of stroke as evaluated by mRS score ≥ 3 at 3 months. After adjustment for age, sex, BMI, FPG, LDL-C, HDL-C, TG, hsCRP, Lp-PLA2, TOAST subtype, and NIHSS score at admission, similar results were observed. Elevated levels of Lp(a) were positively correlated with the poor clinical outcomes of stroke as evaluated by mRS score ≥ 3 at 3 months.