Lipoprotein phospholipase A2 and cerebral microbleeds in the Framingham Heart Study
- PMID: 22961963
- PMCID: PMC3544291
- DOI: 10.1161/STROKEAHA.112.656744
Lipoprotein phospholipase A2 and cerebral microbleeds in the Framingham Heart Study
Abstract
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.
Conflict of interest statement
Dr Irizarry is a stock and options holding employee of GlaxoSmithKline. Dr Romero received funding grant award from GlaxoSmithKline protocol WEUSRTP3833. The current analysis was partially supported by GlaxoSmithKline.
Similar articles
-
Risk factors, stroke prevention treatments, and prevalence of cerebral microbleeds in the Framingham Heart Study.Stroke. 2014 May;45(5):1492-4. doi: 10.1161/STROKEAHA.114.004130. Epub 2014 Apr 8. Stroke. 2014. PMID: 24713533 Free PMC article.
-
Association of apolipoprotein E epsilon2 with white matter disease but not with microbleeds.Stroke. 2007 Apr;38(4):1185-8. doi: 10.1161/01.STR.0000259816.31370.44. Epub 2007 Feb 22. Stroke. 2007. PMID: 17322072
-
Cerebral microbleeds and risk of incident dementia: the Framingham Heart Study.Neurobiol Aging. 2017 Jun;54:94-99. doi: 10.1016/j.neurobiolaging.2017.02.018. Epub 2017 Mar 6. Neurobiol Aging. 2017. PMID: 28347929 Free PMC article.
-
Genetic associations with brain microbleeds: Systematic review and meta-analyses.Neurology. 2011 Jul 12;77(2):158-67. doi: 10.1212/WNL.0b013e318224afa3. Epub 2011 Jun 29. Neurology. 2011. PMID: 21715706 Free PMC article. Review.
-
Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis.Stroke. 2017 Aug;48(8):2084-2090. doi: 10.1161/STROKEAHA.116.012992. Stroke. 2017. PMID: 28720659 Review.
Cited by
-
Management of intracerebral hemorrhage--use of statins.Vasc Health Risk Manag. 2016 Apr 18;12:153-61. doi: 10.2147/VHRM.S75399. eCollection 2016. Vasc Health Risk Manag. 2016. PMID: 27143909 Free PMC article. Review.
-
Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review.J Cereb Blood Flow Metab. 2016 Jan;36(1):72-94. doi: 10.1038/jcbfm.2015.116. J Cereb Blood Flow Metab. 2016. PMID: 26058695 Free PMC article. Review.
-
Differential Effects of Serum Lipoprotein-Associated Phospholipase A2 on Periventricular and Deep Subcortical White Matter Hyperintensity in Brain.Front Neurol. 2021 Mar 8;12:605372. doi: 10.3389/fneur.2021.605372. eCollection 2021. Front Neurol. 2021. PMID: 33763010 Free PMC article.
-
A Review of Novel Cardiac Biomarkers in Acute or Chronic Cardiovascular Diseases: The Role of Soluble ST2 (sST2), Lipoprotein-Associated Phospholipase A2 (Lp-PLA2), Myeloperoxidase (MPO), and Procalcitonin (PCT).Dis Markers. 2021 Aug 9;2021:6258865. doi: 10.1155/2021/6258865. eCollection 2021. Dis Markers. 2021. PMID: 34422136 Free PMC article. Review.
-
Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease: The Atherosclerosis Risk in Communities Study.Stroke. 2017 Dec;48(12):3196-3202. doi: 10.1161/STROKEAHA.117.018675. Epub 2017 Nov 3. Stroke. 2017. PMID: 29101255 Free PMC article.
References
-
- Chen YF, Chang YY, Liu JS, Lui CC, Kao YF, Lan MY. Association between cerebral microbleeds and prior primary intracerebral hemorrhage in ischemic stroke patients. Clin Neurol Neurosurg. 2008;110:988–991. - PubMed
-
- Won Seo S, Hwa Lee B, Kim EJ, Chin J, Sun Cho Y, Yoon U, et al. Clinical significance of microbleeds in subcortical vascular dementia. Stroke. 2007;38:1949–1951. - PubMed
-
- Yakushiji Y, Nishiyama M, Yakushiji S, Hirotsu T, Uchino A, Nakajima J, et al. Brain microbleeds and global cognitive function in adults without neurological disorder. Stroke. 2008;39:3323–3328. - PubMed
-
- Knudsen KA, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: Validation of the boston criteria. Neurology. 2001;56:537–539. - PubMed
-
- Viswanathan A, Greenberg SM. Intracerebral hemorrhage. Handb Clin Neurol. 2009;93:767–790. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- N01-HC-25195/HC/NHLBI NIH HHS/United States
- R01 NS017950/NS/NINDS NIH HHS/United States
- R01 AG016495/AG/NIA NIH HHS/United States
- 1 R01 AG028321/AG/NIA NIH HHS/United States
- R01 NS17950/NS/NINDS NIH HHS/United States
- AG08122/AG/NIA NIH HHS/United States
- R01 AG008122/AG/NIA NIH HHS/United States
- R01 AG033193/AG/NIA NIH HHS/United States
- AG031287/AG/NIA NIH HHS/United States
- K23 AG038444/AG/NIA NIH HHS/United States
- R01 AG028321/AG/NIA NIH HHS/United States
- 1R01 HL64753/HL/NHLBI NIH HHS/United States
- AG033193/AG/NIA NIH HHS/United States
- R01 HL076784/HL/NHLBI NIH HHS/United States
- N01HC25195/HL/NHLBI NIH HHS/United States
- K23AG038444/AG/NIA NIH HHS/United States
- R01 AG16495/AG/NIA NIH HHS/United States
- R01 AG031287/AG/NIA NIH HHS/United States
LinkOut - more resources
Full Text Sources
Miscellaneous