Circulating Amyloid Beta 1–40 Is Associated with Increased Rate of Progression of Atherosclerosis in Menopause: A Prospective Cohort Study

Abstract

Background Accumulating evidence suggests that circulating amyloidβ 1–40 (Αβ1–40), a proatherogenic aging peptide, may serve as a novel biomarker in cardiovascular disease (CVD). We aimed to explore the role of plasma Αβ1–40 and its patterns of change over time in atherosclerosis progression in postmenopausal women, a population with substantial unrecognized CVD risk beyond traditional risk factors (TRFs). Methods In this prospective study, Αβ1–40 was measured in plasma by enzyme-linked immunosorbent assay and atherosclerosis was assessed using carotid high-resolution ultrasonography at baseline and after a median follow-up of 28.2 months in 152 postmenopausal women without history or symptoms of CVD. Results At baseline, high Αβ1–40 was independently associated with higher carotid bulb intima-media thickness (cbIMT) and the sum of maximal wall thickness in all carotid sites (sumWT) (p < 0.05). Αβ1–40 levels increased over time and were associated with decreasing renal function (p < 0.05 for both). Women with a pattern of increasing or persistently high Αβ1–40 levels presented accelerated progression of cbIMT and maximum carotid wall thickness and sumWT (p < 0.05 for all) after adjustment for baseline Αβ1–40 levels, TRFs, and renal function. Conclusion In postmenopausal women, a pattern of increasing or persistently high Αβ1–40 was associated with the rate of progression of subclinical atherosclerosis irrespective of its baseline levels. These findings provide novel insights into a link between Αβ1–40 and atherosclerosis progression in menopause and warrant further research to clarify the clinical value of monitoring its circulating levels as an atherosclerosis biomarker in women without clinically overt CVD.

Beta-Secretase-1 Antisense RNA Is Associated with Vascular Ageing and Atherosclerotic Cardiovascular Disease

“…27,38 These findings are in agreement with recent experimental data showing that BACE1 expression is posi-tively associated with the progression of atherosclerosis and formation of foam cells in an atherosclerosis-prone mouse model 39 and clinical evidence showing the association between circulating Aβ1-40 and accelerated subclinical atherosclerosis. 15 In addition to its association with preclinical disease, BACE1-AS was associated with the presence and severity of clinically overt CAD. These findings provide mechanistic insights into our previous studies showing the association between Aβ1-40 and coronary calcium score, CAD, and ACS.…”

“…42,43 These effects may at least partly explain the accumulating clinical data, indicating that increased circulating levels of Aβ1-40 are associated with multiple CVRFs, arterial stiffening, and the presence of atherosclerosis in multiple vascular beds, as well as accelerated progression of aortic stiffening and atherosclerosis. 14,15 We have previously reported that circulating Aβ1-40 has an independent prognostic and reclassification value for mortality and adverse cardiovascular events in stable CAD and NSTE-ACS patients. 16,17 These findings explain mechanistically the involvement of Aβ1-40 in ASCVD and support its clinical utility.…”

“…CVD risk was calculated as described previously and in the Supplementary Material (available in the online version). [14][15][16][17] The present study was conducted under the principles outlined in the Declaration of Helsinki. All individuals provided written informed consent form, and the ethics committee of the Alexandra Hospital of the University of Athens approved the protocol.…”

“… 7 Aβ1–40 blood levels are associated with CVRFs and atherosclerosis in various vascular beds, while its changes over time are associated with accelerated progression of aortic stiffening and atherosclerosis. 14 15 Importantly, circulating Aβ1–40 is an independent prognostic factor of mortality in stable coronary artery disease (CAD) and non-ST elevation acute coronary syndrome (NSTE-ACS). 16 17 We have recently reported increased expression of BACE1-AS and BACE1 and consequently increased Aβ1–40 deposits in the myocardium of patients with heart failure.…”

Effect of dehydroepiandrosterone on atherosclerosis in postmenopausal women

“…The mean carotid intimamedia thickness (CIMT) of the common carotid artery in postmenopausal women was significantly thicker than that in premenopausal women, with a mean difference of 0.068 mm (7). A recent prospective cohort study (8) also found that an elevated or persistently high level of Aβ1-40, an aging peptide, is related to the rate of progression of subclinical AS in postmenopausal women and negatively correlated with levels of DHEA-S. An increasing number of women are prescribed hormone replacement therapy (HRT) after menopause or ovarian resection to prevent and treat CVD, osteoporosis, Alzheimer's disease, and other related long-term postmenopausal complications (9)(10)(11)(12).…”