Positive correlation of serum adipocyte fatty acid binding protein levels with carotid–femoral pulse wave velocity in geriatric population

The current results reveal that the fasting A-FABP levels were higher in the high
arterial stiffness group than in the low arterial stiffness group, and A-FABP is an
independent predictor for the development of arterial stiffness in the geriatric population.

A systematic review had shown that BP was independently associated with PWV in approximately
90 % of the studies 16]. Cecelja et al. found a dissociation of cfPWV with classic factors, such as gender,
smoke, or lipids other than HTN, and they suggested that aortic stiffing might be
driven by an alternative pathology, which depended on mechanical stretch of the arterial
wall 16]. The pathophysiological correlation between arterial stiffness and HTN is that the
increased arterial stiffness reduces the lumen diameter, for a given smooth muscle
tone and blood pressure, leading to a premature return of the reflected wave in late
systole, thereby increasing the central pulse pressure and SBP, and decreasing DBP
17]. On the other hand, aortic stiffness may affect aortic function, reduce baroreceptor
responsiveness, and increase systolic pressure, making arterial stiffness one of the
leading causes of increased blood pressure 4]. Meta-analysis of studies in the field have demonstrated that an increase in aortic
PWV by 1 m/s corresponded to an age-, sex-, and risk factor-adjusted increase in total
CV events, CV mortality, and all-cause mortality by 14, 15, and 15 %, respectively
2]. In addition, another meta-analysis found that greater arterial stiffness correlated
with cerebral small vessel diseases 18], and Zhang et al. supposed that measuring cfPWV was beneficial to the elderly regarding
the cardiovascular and cerebrovascular diseases, including atherosclerosis, cognitive
dysfunction and mortality 19]. Therefore, arterial stiffness could serve as an independent predictor of coronary
events and adverse CV diseases.

Studies had shown that there is a crosstalk between CV diseases and adipokines, such
as, adiponectin, leptin, and A-FABP 20]–23]. Makowski and colleagues reported that apolipoprotein E deficient mice with A-FABP
+/+ adipocytes and A-FABP ?/? macrophages, showed a comparable reduction in atherosclerotic
lesions to those with total A-FABP deficiency, indicating an independent role for
macrophage A-FABP in atherogenesis 24]. Lee et al. had shown an enhanced expression of A-FABP on aortic endothelium of apolipoprotein
E deficient mice and in cultured human microvascular endothelial cells. This lipid-induced
A-FABP expression was associated with reduced phosphorylated eNOS and NO production,
and was reversed by A-FABP inhibitor 8]. So, the pro-atherogenic potential of A-FABP on the vasculature is possibly mediated
by the pro-inflammatory effects, independent of lipid metabolism and insulin sensitivity.
Further, it contributes to the endothelial dysfunction by potentiating lipid-induced
impairment in eNOS activation, and thus endothelium-dependent vasodilatation.

Clinical reports reveal a significant correlation of baseline serum A-FABP with BMI,
homeostasis model of insulin resistance, and cardio-ankle vascular index, which is
a marker of arterial stiffness 25], 26]. In addition to the associated metabolic risk factors, A-FABP levels were positively
correlated with coronary plaque volume burden as well, and may serve as a biomarker
for the detection of coronary artery disease 22], 23]. An increase in the number of stenotic coronary arteries resulted in a corresponding
increase in the plasma A-FABP levels in patients with coronary heart diseases 23]. In addition to the macrovascular complications (ischemic heart disease, stroke,
or peripheral vascular disease) in diabetic patients, A-FABP show a positive correlation
with albuminuria and negative correlation with glomerular filtration rate, indicating
that the serum level of A-FABP is influenced by impaired renal clearance and activated
macrophages in diabetic nephropathy 27]. In this study, we found that geriatric adults who had high arterial stiffness would
have higher serum A-FABP levels than those with low arterial stiffness. Moreover,
A-FABP was demonstrated to be an independent risk factor for developing high arterial
stiffness.

Classic CV risk factors, including DM, hyperlipidemia, elevated BMI and smoking, had
been implicated in accelerating arterial stiffness. However, Cecelja et al. have indicated
that the prognostic value of cfPWV may be related to a process of arterial ageing,
and probably unrelated to the classic risk factors, other than HTN 16]. Additionally, impaired glucose tolerance and DM in a population-based study was
independently associated with the central arterial stiffness, after adjusting mean
arterial pressure, age and gender 28]. In our geriatric patients, we found that adults who were found to have high arterial
stiffness would have a higher body weight, waist circumference, BMI, SBP, DBP, and
pulse pressure. Furthermore, those who were in the high arterial stiffness group also
had a higher percentage of DM or HTN, as previously reported 16].

Several types of medications had been demonstrated to affect arterial stiffness. Studies
of ?-blockers on arterial stiffness showed less impact on central BP decline compared
with the peripheral BP 29], 30]. Older hypertensive patients treated with calcium channel blockers, showed the lowest
central aortic pressure and less augmentation pressure, when compared with the placebo
31]. Moreover, usage of ACEi or ARB showed significant effects on reducing the central
BP and augmentation index, through the reduction of oxidative stress and inflammation,
and vasodilatation through angiotensin II inhibition 30], 31]. Miyoshi et al. conducted a study which showed that the effects of ARB in HTN patients
could reduce cardio-ankle vascular index as well as serum levels of A-FABP, but the
causal relationship needed to be clarified by further studies 26]. Even though, one systematic review showed controversial effects of statin on the
reduction of aortic PWV 32], recent reports indicated that low dose of atorvastatin in mild HTN and hypercholesterolemia
exerted beneficial effects on arterial stiffness and central aortic pressure 33]. In obese patients without glucose intolerance, treatment with PPAR alpha agonist
(fenofibrate) revealed significant reduction in the augmentation index, PWV, and pro-inflammatory
markers 34]. The results of subgroup analysis in this study suggest that ACEi, ARB, ?-blockers,
CCB, statins, or fibrate had no influence at all, on arterial stiffness.