Plasma Klotho Levels Were Inversely Associated with Subclinical Carotid Atherosclerosis in HIV-Infected Patients Receiving Combined Antiretroviral Therapy

Abstract

Combined antiretroviral therapy (cART) has significantly improved the survival rate in HIV-infected individuals, but it contributes to the development of various metabolic complications. Klotho is a novel antiaging gene that encodes a protein with pleiotropic functions, including an emerging role in cardiovascular disease (CVD). The protective effect of higher plasma klotho levels against CVD was recently observed in non-HIV-infected adults. We aimed to assess whether plasma-secreted α-klotho is associated with subclinical carotid atherosclerosis in HIV-infected patients receiving cART. We prospectively examined the association of circulating plasma α-klotho in 120 HIV-infected patients who had received cART for ≥6 months with intima-media thickness (IMT) in the carotid artery and other metabolic variables. The subclinical carotid atherosclerosis was defined as an increased mean IMT level of ≥75th percentile for the matched age, sex, and race and/or the presence of carotid plaque. Thirty-four (28.3%) of 120 had subclinical carotid atherosclerosis. The higher plasma levels of α-klotho had protective effect against subclinical carotid atherosclerosis (OR 0.006, p=0.034) in multivariate regression analysis. Plasma α-klotho levels had a significantly negative correlation with fasting glucose levels (r=-0.216, p=0.018) and mean IMT (r=-0.258, p=0.004) in multiple stepwise regression analyses. The optimal cutoff values of plasma α-klotho levels for the greatest sensitivity and specificity were calculated as 2.83 log10 [pg/ml] (sensitivity, 48.7%; specificity, 90.5%). These results show that plasma klotho levels were inversely associated with subclinical carotid atherosclerosis in HIV-infected patients receiving cART.

Klotho ameliorates oxidized low density lipoprotein (ox-LDL)-induced oxidative stress via regulating LOX-1 and PI3K/Akt/eNOS pathways

“…Klotho, which is a kind of anti-aging protein [9], is involved in various pathologies, such as atherosclerosis, heart damage, hypertension, acute kidney injury, chronic kidney disease, diabetes mellitus, and even cancer [7, 8, 10, 11]. In a Klotho-deficient mouse aging-model study, Kuro-o et al reported that Klotho deficiency is closely related to cardiovascular diseases, such thatit enhances arteriosclerosis, extensive medial calcification of the aorta, and medial calcification and intimal thickening of medium-sized muscular arteries [9].…”

Prevalence and risk of subclinical carotid atherosclerosis in the global population with HIV: a systematic review and meta-analysis

“…Fourteen studies were conducted from Europe, 20,22–26,30,31,34,35,39,41–43 followed by America (4 studies), 10,27,28,38 Asia (4 studies), 11,21,29,32 and Africa (4 studies). 33,36,37,40 There are four studies using CIMT ≥ 0.78 mm criteria, 32,36,37,40 eight studies with CIMT ≥ 0.80 mm, 10,22,27,28,30,31,34,35 10 studies with CIMT ≥ 0.90 mm, 11,21,23–26,38,41,43 and four studies with CIMT ≥ 75th.…”

“…33,36,37,40 There are four studies using CIMT ≥ 0.78 mm criteria, 32,36,37,40 eight studies with CIMT ≥ 0.80 mm, 10,22,27,28,30,31,34,35 10 studies with CIMT ≥ 0.90 mm, 11,21,23–26,38,41,43 and four studies with CIMT ≥ 75th. 20,29,33,39…”

“…We included nine studies 21,24,28,29,32,35,36,41,42 in the meta-analysis for the measurement of the association between SCA and HIV infection. The prevalence of SCA was significantly higher among PLWH than in their HIV-negative counterparts (pooled OR 2.66, 95% CI 1.57–4.50; Figure 2).…”

Is there a role for newer biomarkers in chronic kidney disease‐mineral and bone disorder management?

“…An inverse association to mortality has been reported, with higher circulating levels of sKl associated with increased survival in the general population as well as those with dialysis‐dependent kidney disease . sKl has also been linked to improved cardiovascular outcomes, inverse associations of sKl levels with both carotid artery intimal thickness and coronary artery disease in adults with normal renal function. Similarly in patients with CKD, sKl has shown inverse correlations to arterial stiffness, carotid artery intimal thickness and left ventricular dysfunction …”