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

vessel diseases

Introduction
Both cerebral big artery disease and cerebral small vessel disease have been linked to
cognitive decline and deterioration in brain health. Diseases of the big arteries and the tiny
brain vessels have the same anatomical basis but are associated with distinct pathogenetic
pathways. Previous research suggested a possible difference in the risk factor profile for these
two forms of cerebrovascular illness.
Apolipoprotein B100 and glycoapolipoprotein A(PO) are components of
lipoprotein(a), often known as Lp(a) (a). Prolonged exposure to Lp(a) has been associated
with an increased risk of atherosclerotic cardiovascular disease. In previous research, carotid
atherosclerosis, ischemic stroke, and atherothrombotic stroke have all been linked to elevated
Lp(a) levels. In contrast, Lp(a) level was associated with cerebral minor vascular disorders in
just a few studies (cSVD). Some earlier investigations indicated a reduced Lp(a) level in
patients with cSVD, but the findings were unclear because of the small sample sizes. Recent
Mendelian randomization research has shown that lower Lp(a) levels are associated with an
increased risk of minor vascular stroke. This suggests that Lp(a) concentrations may have
various associations with disorders of the brain's significant and small blood vessels.
However, the connections between Lp(a) and disorders of the big and small blood vessels in
the brain remain poorly understood.

Research overview
Pan et al., (2022) conducted a thorough cross-sectional analysis of the relationships
between Lp(a) concentrations and cerebrovascular illness in a community sample from
southern China. The PRECISE (The PolyvasculaR Evaluation for Cognitive Impairment and
vaScular Events) study provided the information for this investigation. PRECISE's
methodology and starting point data have been made public. The clinical interviews and
physical tests were all performed in person at Lishui Hospital. A team of study coordinators
with experience in data collecting used standardized questionnaires to gather the necessary
information. In the first survey, participants provided basic personal information, medical
history, and current prescription regimens. It was determined that individuals were deemed
current smokers if they had smoked on average at least once per day throughout the previous
month.
 The frequency and percentage of occurrence for categorical variables are shown,
while the mean and standard deviation for continuous variables is shown as appropriate.
When applicable, analysis of variance and the 2 test were used to compare baseline
characteristics among Lp(a) tertile groups. Using the first tertile as a reference, this research
employed multivariable binary logistic regression to analyze the connections between Lp(a)
concentrations, the existence of cerebral atherosclerotic plaque, and cSVD. The ORs and
95% confidence intervals (CIs) were determined for all the models.

Using the first tertile as a reference, multivariable ordinal logistic regression was
utilized to analyze the correlations between Lp(a) and a progression toward a more
significant intracranial atherosclerotic or cSVD load. Ordinary RRs and their 95% confidence
intervals were analysed. Two modified regression models were run for each dependent
variable. With the first model, we just considered age and gender differences. Model 2
included additional adjustments for age, gender, race/ethnicity, education level, marital
status, number of children, smoking status, drinking status, total cholesterol, LDL cholesterol,
HDL cholesterol, and use of antihypertensive, antidiabetic, lipid-lowering, and anticoagulant
agents.

A binary or ordinal logistic regression model with restricted cubic splines for Lp(a)
concentrations was carried out to evaluate the relationship between Lp(a) level and the
presence of intracranial atherosclerotic plaque, cSVD, and the intracranial atherosclerotic and
cSVD burden. The median Lp(a) level was established at 40 mg/L (33rd percentile). This
work used an advanced MRI imaging technique to provide cross-sectional evidence linking
Lp(a) levels to both intracranial atherosclerosis (a positive connection) and cerebral small
vessel disease (cSVD), a negative association. Neuroimaging indicators of cSVD, such as
BG-PVS, WMH, and lacunes, were also less likely to be present in individuals with a high
Lp(a) level.

The limited sample size for each neuroimaging marker of cSVD may explain the
opposite directions of relationship between the second and third tertiles of Lp(a) for lacunes
and WMH, as well as the general lack of significance for the association of these markers.
The study's greatest strength is that it uses cutting-edge imaging methods to do a thorough
evaluation of cSVD and cerebral atherosclerosis in a large community sample. The
demographics of the study's participants were consistent with those of a national survey
conducted in China. This allows the results to be generalized.

Assessing the impact of Lp(a) on cerebral arteries may be more thorough if both
large- and small-vessel disorders are taken into account. In this work, we found that although
an increased Lp(a) level may be harmful to the brain's major arteries, it may actually be
protective to the brain's smaller vessels. The possibility for Lp(a) to play both positive and
negative roles suggest that determining the ideal Lp(a) concentration for therapeutic use
requires further research.

Conclusion
Differential correlations of Lp(a) level with both major artery and small vessel disease
in the brain were found by Pan et al., (2022) in this community-based sample. A high Lp(a)
level was shown to be connected with the prevalence and severity of atherosclerosis in the
brain, but to have the opposite effect on the risk of developing cSVD. These findings imply
that high levels of Lp(a) may be harmful to cerebral big arteries but protective to cerebral
small vessels. More research is necessary to understand the clinical significance and
underlying mechanisms of the opposing effects of Lp(a) level on cerebral arteries.

Reference

Pan, Y., Cai, X., Jing, J., Wang, S., Meng, X., Mei, L., ... & Wang, Y. (2022).
Differential associations of lipoprotein (a) level with cerebral large artery and small vessel
diseases. Stroke and Vascular Neurology, svn-2022.