Differential associations of lipoprotein(a) level with cerebral large artery and small vessel diseases

Abstract

Background and purpose: Cerebral large artery and small vessel diseases are related to different pathogenetic mechanisms and have different risk factor profile. Lipoprotein(a) (Lp(a)) was shown to promote atherosclerosis but data was limited on its association with cerebral small vessel diseases (cSVD). The objective of this study was to assess the associations of Lp(a) level with the two types of cerebrovascular diseases.

Methods: Community-dwelling subjects aged 50-75 years from the baseline survey of The PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study were included. Lp(a) concentrations was measured and categorised into three groups according to the tertiles. Eligible participants were scanned by a 3.0T MRI scanner and assessed for intracranial atherosclerosis and cSVD burden based on four imaging markers.

Results: This study included 3059 subjects. The average age of the participants was 61.2±6.7 years, and 53.5% (1636) were female. Compared with the first tertile, subjects with the second and third tertiles of Lp(a) concentrations were associated with an increased odds of presence of intracranial plaque (18.7% vs 15.4%, adj.OR 1.37, 95% CI 1.08 to 1.75; 18.9% vs 15.4%, adj.OR 1.34, 95% CI 1.05 to 1.72). Similar associations were observed for intracranial atherosclerotic burden. Whereas, subjects with the third tertile of Lp(a) level had a decreased odds of presence of cSVD (25.9% vs 31.7%, adj.OR 0.74, 95% CI 0.60 to 0.92) and lower cSVD burden (adj.cOR 0.76, 95% CI 0.62 to 0.94).

Conclusions: In this study, Lp(a) concentrations were positively associated with presence and burden of intracranial atherosclerosis, but was inversely associated with cSVD.

Trial registration number: NCT03178448.

Keywords: Magnetic Resonance Imaging; atherosclerosis; cerebrovascular disorders; plaque.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Flow chart of the participant selection. CSVD, cerebral small vessel disease; Lp(a), lipoprotein(a); PRECISE, PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events.

Figure 2

Distribution of intracranial atherosclerotic and cSVD burden by tertiles of Lp(a) level. Grades 0–4 indicate intracranial atherosclerotic burden score of 0, 1, 2–3 and ≥4, or total cSVD burden score of 0, 1, 2, 3–4, respectively. cSVD, cerebral small vessel disease; Lp(a), lipoprotein(a); T, tertile.

Figure 3

Association of intracranial plaque and cSVD with Lp(a) level. *Model 1 adjusted for age and sex. †Model 2 adjusted for age, sex, body mass index, histories of hypertension, diabetes and atrial fibrillation, current smoking, current drinking, TC, LDLC, HDLC, antihypertensive, antidiabetic, lipid-lowering and anticoagulant agents use. ‡OR and 95% CI for the presence of intracranial plaque and cSVD by binary logistic regression, whereas COR and 95% CI for intracranial atherosclerotic burden and cSVD burden by ordinal logistic regression. §The degree of intracranial atherosclerotic burden was graded as scores of 0, 1, 2–3 and ≥4, respectively. ||The degree of cSVD burden was graded as scores of 0, 1, 2 and 3–4, respectively. COR, common OR; cSVD, cerebral small vessel disease; HDLC, high-density lipoprotein cholesterol; Lp(a), lipoprotein(a); LDLC, low-density lipoprotein cholesterol; Ref., reference; T, tertile; TC, total cholesterol.

Figure 4

Forest plots for the association between Lp(a) level and cSVD imaging markers. The plots showed the OR and their 95% CIs. BG-PVS, basal ganglia-enlarged perivascular spaces; CMBs, cerebral microbleeds; cSVD, cerebral small vessel disease; Lp(a), lipoprotein(a); T, tertile; WHM, white matter hyperintensities.

Figure 5

ORs/ common ORs of intracranial plaque and cSVD according to Lp(a) level. (A) Presence of intracranial plaque; (B) intracranial atherosclerotic burden; (C) presence of cSVD; (D) cSVD burden. Lp(a) level of 40 mg/L (33rd percentile) was set as reference. Data were fitted using a binary or ordinal logistic regression with restricted cubic spline. cSVD, cerebral small vessel disease; Lp(a), lipoprotein(a).