Effect of Lipoprotein(a) on Stroke Recurrence Attenuates at Low LDL-C (Low-Density Lipoprotein) and Inflammation Levels

Abstract

BACKGROUND: Lp(a) (lipoprotein(a)) contributes to cardiovascular disease mainly through proatherogenic and proinflammatory effects. Here, we aimed to evaluate whether a residual stroke risk of Lp(a) would remain when the LDL-C (low-density lipoprotein cholesterol) and inflammatory levels are maintained low. METHODS: This prospective cohort study included 9899 patients with ischemic stroke or transient ischemic attack from the Third China National Stroke Registry who had measurements of plasma Lp(a) and were followed up for 1 year. Cutoffs were set at the 50 mg/dL for Lp(a). LDL-C was corrected for Lp(a)-derived cholesterol (LDL-Cc [LDL-C corrected]) and cutoffs were set at 55 and 70 mg/dL.The threshold values of IL-6 (interleukin 6) and hsCRP (high-sensitive C-reactive protein) were the median 2.65 ng/L and 2 mg/L. Multivariable-adjusted hazard ratio (HR) were calculated using Cox regression models for each category to investigate the associations of Lp(a) with stroke recurrence within 1 year. RESULTS: Among all patients, those with Lp(a) ≥50 mg/dL were at higher stroke recurrence risk than those with Lp(a) <50 mg/dL (11.5% versus 9.4%; adjusted HR, 1.20 [95% CI, 1.02–1.42]). However, the risk associated with elevated Lp(a) was attenuated in patients with LDL-Cc <55 mg/dL (high Lp(a) versus low Lp(a): 8.9% versus 9.0%; adjusted HR, 0.92 [95% CI, 0.65–1.30]) or IL-6 <2.65 ng/L (9.0% versus 7.8%; adjusted HR, 1.14 [95% CI, 0.87–1.49]). Notably, in the group with both low LDL-Cc and inflammation levels, the rate of patients with high Lp(a) did not significantly different from the rate of patients with low Lp(a; LDL-Cc <55 mg/dL and IL-6 <2.65 ng/L: 6.2% versus 7.1%; adjusted HR, 0.86 [95% CI, 0.46–1.62]; LDL-Cc <55 mg/dL and hsCRP <2 mg/L: 7.7% versus 7.6%; adjusted HR, 0.97 [95% CI, 0.57–1.66]). However, there was no interaction between the LDL-Cc, IL-6, hsCRP, and Lp(a) levels on stroke recurrence risk. CONCLUSIONS: Increased Lp(a) was significantly associated with stroke recurrence risk in patients with ischemic stroke/transient ischemic attack. However, at low LDL-Cc or IL-6 levels, the elevated Lp(a) -associated stroke recurrence risk was attenuated in a secondary prevention setting.

Associations of Chinese visceral adiposity index and new-onset stroke in middle-aged and older Chinese adults: an observational study

“…The aforementioned DAG facilitated the identification of pertinent adjustment factors, thereby eradicating confounding variables, which in turn mitigated bias in estimating the association between CVAI and the new-onset stroke in the final model. The considered covariates for adjustment included demographic and behavioral factors such as sex [ 32 ], marital status [ 33 ], educational attainment [ 34 , 35 ], geographic location [ 36 ], smoking habits [ 37 ], and alcohol consumption [ 38 ], along with diseases history like presence of diabetes [ 39 ], hypertension [ 40 ], LDL-C [ 41 , 42 ], and CRP levels [ 43 ].…”

Low lipoprotein(a) concentration is associated with atrial fibrillation: a large retrospective cohort study

“…In ischemic stroke patients, the AF-Lp(a) relationship was reversed in the Q3 group. A recent prospective cohort study from China found that high Lp(a) levels are associated with increased stroke recurrence [ 28 ]. A meta-analysis involving 41 studies also found that elevated Lp(a) increases ischemic stroke risk [ 29 ].…”

Elevated Lp(a) Levels Correlate with Severe and Multiple Coronary Artery Stenotic Lesions

“…25 , 26 Recent studies showed that vascular disease recurrence in patients with high levels of Lp(a) (≥50 mg/dL) is attenuated only at very low LDL-C (<55 mg/dL) but not when LDL levels ≥70 mg/dL. 27 , 28 Kinetic studies suggest a preferential accumulation of Lp(a) particles in vessel walls which may increase the artherogenic potential of Lp(a) cholesterol over LDL-C. High levels of Lp(a) are highly correlated with rapid progression of coronary atherosclerosis, a strong predictor of adverse outcome. Patients with high Lp(a) levels develop high risk unstable plaques with complex morphology which are prone to rupture.…”