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Lipoprotein phospholipase A2 and cerebral microbleeds in the Framingham Heart Study
José Rafael Romero1, Sarah R Preis, Alexa S Beiser
1Department of Neurology, School of Medicine, Boston University, 715 Albany Street, B-608, Boston, MA 02118-2526, USA. joromero@bmc.org
Background And Purpose:
Cerebral microbleeds (CMB) attributable to cerebral amyloid angiopathy generally occur in lobar regions, whereas those attributable to hypertensive vasculopathy are deep. Inflammation may be an underlying mechanism for CMB, with varying associations according to CMB location. Lipoprotein phospholipase-A2 (Lp-PLA2) is a circulating enzyme marker of vascular inflammation associated with risk of ischemic stroke and dementia. We hypothesized that higher Lp-PLA2 levels would be related to higher prevalence of CMB, with possible regional specificity.
Methods:
Framingham Offspring participants aged 65 years or older with available Lp-PLA2 measures and brain magnetic resonance imaging were included. Logistic regression models were used to relate Lp-PLA2 activity and mass to presence of CMB, adjusted for age, sex, medication use (aspirin, anticoagulants, and statins), systolic blood pressure, APOE, current smoking, and diabetes.
Results:
Eight-hundred nineteen participants (mean age, 73 years; 53% women) were included; 106 (13%) had CMB, 82 (10%) were lobar, and 27 (3%) were deep. We did not observe significant associations of CMB and LpPLA2 measures in multivariable adjusted analyses. However, there was a significant interaction between APOE genotype and Lp-PLA2 activity in their relation to presence of deep CMB (P interaction=0.01). Among persons with APOE ε3/ε3, the odds ratio for deep CMB was 0.95 (confidence interval, 0.59-1.53; P=0.83), whereas among those with at least 1 ε2 or ε4 allele, odds ratio was 3.46 (confidence interval, 1.43-8.36; P=0.006).
Conclusions:
In our community-based sample of older adults, there was no significant association of Lp-PLA2 with total or lobar CMB. The association of higher levels of Lp-PLA2 activity with deep CMB among those with at least 1 APOE ε2 or ε4 allele merits replication.
Insights
Lipoprotein phospholipase-A2 (Lp-PLA2) did not correlate with cerebral microbleeds (CMB) overall. However, higher Lp-PLA2 levels were linked to deep CMB in older adults with specific APOE genotypes, suggesting a potential link between vascular inflammation and deep CMB in this subgroup.
Area of Science:
- Neurology
- Vascular Biology
- Biomarkers
Background:
- Cerebral microbleeds (CMB) location can indicate underlying cause (lobar for amyloid angiopathy, deep for hypertensive vasculopathy).
- Vascular inflammation, potentially indicated by Lipoprotein phospholipase-A2 (Lp-PLA2), may contribute to CMB.
- Lp-PLA2 is a marker of vascular inflammation linked to stroke and dementia risk.
Purpose of the Study:
- To investigate the association between Lipoprotein phospholipase-A2 (Lp-PLA2) levels and the prevalence of cerebral microbleeds (CMB).
- To explore if this association differs based on CMB location (lobar vs. deep).
- To examine potential interactions with APOE genotype.
Main Methods:
- Inclusion of Framingham Offspring participants aged 65+ with Lp-PLA2 measures and brain MRI.
- Logistic regression models to assess the relationship between Lp-PLA2 (activity and mass) and CMB presence.
- Adjustments for age, sex, medications, blood pressure, APOE, smoking, and diabetes.
Main Results:
- 106 (13%) of 819 participants had CMB; 82 lobar, 27 deep.
- No significant association found between Lp-PLA2 measures and total or lobar CMB.
- A significant interaction between APOE genotype and Lp-PLA2 activity was observed for deep CMB (P=0.01).
- Individuals with APOE ε2 or ε4 alleles and higher Lp-PLA2 showed increased odds of deep CMB (OR=3.46).
Conclusions:
- No significant association between Lp-PLA2 and total or lobar CMB in older adults.
- Higher Lp-PLA2 activity is associated with deep CMB in individuals with at least one APOE ε2 or ε4 allele.
- This specific association warrants further investigation and replication.