Abstract
Background
There is increasingly recognized undetected residual cardiovascular (CV) risk in postmenopausal women, suggesting the need for new risk biomarkers in this population. We have previously shown that amyloid-beta (1–40) (Aβ1–40), a proinflammatory and pro-atherosclerotic peptide, is associated with concurrent subclinical cardiovascular disease (CVD) in the general population and with major adverse cardiac events in patients with established cardiac disease. However, the clinical value of Aβ1–40 in menopause or whether this peptide is linked with an increased rate of progression of atherosclerotic disease is unknown.
Purpose
To examine the association of Aβ1–40 levels with the rate of progression of carotid intima-media thickness (IMT) in postmenopausal women.
Methods
In the settings of a Menopause Clinic, postmenopausal women (n=140) without clinically overt CVD or diabetes were consecutively recruited and re-evaluated after a median follow-up period of 24 months. IMT in the carotid arteries was measured by ultrasonography. The average of maximal IMT (mean cIMT) measured at both left and right common carotid, carotid bulb (cb)and internal carotid (ic) artery were used as the main end-point of the analysis. Aβ1–40 was measured in plasma samples at baseline and follow up. Fasting insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR).
Results
Women with increased plasma levels Aβ1–40 in the highest tertile presented the highest probability to have increased mean cIMT (adjusted OR=2.97, 95% CI 1.18–7.52, p=0.021) independently of age, smoke, hypertension, and hyperlipidemia. After adjustment for HOMA-IR, this association remained significant. Similarly, Aβ1–40 levels were associated with increased mean cb and icIMT (adjusted OR=3.34 for highest versus lower tertile, 95% CI 1.27–8.81, p=0.015). Mean cIMT significantly increased across the follow up period (0.73mm (0.065–0.08) to 0.77mm (0.07–0.089), median increase rate per year 0.024mm, p<0.001). By multi-level linear mixed model analysis, changes in Aβ1–40 levels were associated with increased rate of progression of mean cIMT (4.1% increase per 1-SD increase, p<0.001) after adjustment for differences in follow-up duration and age, hypertension, hyperlipidemia, and smoking. When repeated measurements of HOMA-IR were also considered, this association did not materially change (p=0.021). Similarly, longitudinal changes in Aβ1–40 correlated with the progression of mean cb and icIMT (3.9% increase per 1-SD increase, p=0.001), independently of time to re-evaluation and cardiovascular risk factors.
Conclusion
Aβ1–40 is an independent predictor of the rate of progression of subclinical carotid atherosclerosis in menopausal women. This finding supports the clinical value of Aβ1–40 in menopause and warrants further investigation for its prognostic role in this population.
Calcium Channel Blockers, Progression to Dementia, and Effects on Amyloid Beta Peptide Production
