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Linking Heart and Brain: Association Between Circulating Amyloid-Beta (1-40) Levels and CV Risk | Journal Scan
Study Questions:
What is the clinical value of amyloid-beta 1-40 (Aβ40) in the prediction of cardiovascular (CV) mortality in patients with coronary heart disease (CHD) and progression of arterial stiffness in young healthy subjects?
Methods:
Aβ40 was measured retrospectively from participants who contributed blood samples in three independent prospective cohorts and two case-control cohorts (total n = 1,464). In 107 young healthy subjects without clinically overt CHD, arterial stiffness and Aβ40 were evaluated at baseline and after 5-year follow-up. A total of 394 consecutive subjects underwent peripheral atherosclerosis assessment to evaluate the association of Aβ40 with different stages of atherosclerosis in various arterial beds. Multivariable Cox proportional hazard models were used to assess the association between continuous and quartile-based Aβ40 and incident major adverse cardiovascular events (MACE). Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to determine the incremental reclassification value of Aβ40 over conventional predictors of CV mortality.
Results:
In patients with CHD, Aβ40 was an independent predictor of CV death and MACE, in analyses adjusted for age, sex, estimated glomerular filtration rate, left ventricular ejection fraction (LVEF), high-sensitivity C-reactive protein, and high-sensitivity troponin T. The incidence of CV death was significantly increased in the highest Aβ40 quartile, compared to that in other quartiles, in patients with stable CHD. Using a category-free NRI, Aβ40 performed better than age, sex, and LVEF in reclassifying patients from lower to higher risk and vice versa. Aβ40 correlated independently with common carotid intima-media thickness, lower ankle-brachial index, and higher probability for increased atheromatous burden in the carotid or femoral arteries. Furthermore, changes in Aβ40 levels after 5-year follow-up were independently associated with aortic stiffness progression in initially healthy subjects.
Conclusions:
The authors concluded that Aβ40 is independently associated with the extent of human atherosclerosis and improves the prediction of CV death in patients with stable CHD.
Perspective:
This is a fascinating study that adds to our understanding of the role of Aβ proteins in the pathogenesis of CV disease. The authors, through retrospective measurement of Aβ40 from independent cohorts, demonstrated that this marker may help stratify risk in patients with stable CHD. It is an intriguing possibility that circulating levels of Aβ40 could indicate atherosclerotic plaque burden. While fascinating, these findings require further replication. Nonetheless and as the authors opine, ‘since the proinflammatory effects of Aβ40 can be altered by established CV therapy, these findings may provide a rationale for a novel anti-inflammatory therapeutic target.’
Keywords: Atherosclerosis, Arteriosclerosis, Plaque, Atherosclerotic, Ankle Brachial Index, Carotid Intima-Media Thickness, Coronary Disease, Femoral Artery, Proportional Hazards Models, Prospective Studies, Vascular Stiffness, Vascular Diseases, Risk
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