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- Anderson, JLC, et al.
(author)
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Autoantibodies to Apolipoprotein A-1 as Independent Predictors of Cardiovascular Mortality in Renal Transplant Recipients
- 2019
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In: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 8:7
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Journal article (peer-reviewed)abstract
- Renal transplant recipients (RTRs) are known to have a high cardio-vascular disease (CVD) burden only partly explained by traditional CVD risk factors. The aim of this paper was therefore to determine: i) the prognostic value of autoantibodies against apoA-1 (anti-apoA-1 IgG) for incidence of CVD mortality, all-cause mortality and graft failure in RTR. Four hundred and sixty two (462) prospectively included RTRs were followed for 7.0 years. Baseline anti-apoA-1 IgG were determined and associations with incidence of CVD mortality (n = 48), all-cause mortality (n = 92) and graft failure (n = 39) were tested. Kaplan–Meier analyses demonstrated significant associations between tertiles of anti-apoA-1 IgG and CVD mortality (log rank test: p = 0.048). Adjusted Cox regression analysis showed a 54% increase in risk for CVD mortality for each anti-apoA-1 IgG levels standard deviation increase (hazard ratio [HR]: 1.54, 95% Confidence Interval [95%CI]: 1.14–2.05, p = 0.005), and a 33% increase for all-cause mortality (HR: 1.33; 95%CI: 1.06–1.67, p = 0.01), independent of CVD risk factors, renal function and HDL function. The association with all-cause mortality disappeared after excluding cases of CVD specific mortality. The sensitivity, specificity, positive predictive value, and negative predictive value of anti-apoA-1 positivity for CVD mortality were 18.0%, 89.3%, 17.0%, and 90.0%, respectively. HDL functionality was not associated with anti-apoA-1 IgG levels. This prospective study demonstrates that in RTR, anti-apoA-1 IgG are independent predictors of CVD mortality and are not associated with HDL functionality.
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| 3. |
- Nagy, RA, et al.
(author)
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Anti-oxidative function of follicular fluid HDL and outcomes of modified natural cycle-IVF
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 12817-
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Journal article (peer-reviewed)abstract
- High density lipoproteins (HDL) are the main cholesterol carriers in follicular fluid (FF), the natural environment of oocyte development. Additionally, HDL have critical biological functions such as anti-oxidative capacity, which have not been studied in reproduction. Therefore, this study aimed to investigate whether the anti-oxidative function of FF-HDL is associated with fertility outcomes. From 253 women undergoing modified natural cycle (MNC)- IVF at a single academic centre FF and plasma were collected (n = 375 cycles). Anti-oxidative function of FF was mainly attributable to HDL (n = 8; 83%). FF-HDL had a higher anti-oxidative function than plasma HDL (n = 19, P < 0.001) coinciding with increased vitamin E and sphingosine 1 phosphate content (P = 0.028 each). Proteomic analysis indicated no significant differences in major anti-oxidative proteins such as paraoxonase 1, apolipoprotein (apo) A-I or apoA-IV between FF-HDL and matched plasma-HDL (n = 5), while apoC-III, apoE and apoC-II were relatively lower in FF-HDL. Finally, FF-HDL anti-oxidative function was related to a decrease in the odds of the oocyte undergoing normal fertilization, an association that persisted after adjustment for confounders (odds ratio 0.97 (0.93–1), P = 0.041). In conclusion, FF-HDL has considerable anti-oxidative properties that might be relevant for embryo quality.
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| 6. |
- Szili-Torok, T, et al.
(author)
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HDL Cholesterol Efflux Predicts Incident New-Onset Diabetes After Transplantation (NODAT) in Renal Transplant Recipients Independent of HDL Cholesterol Levels
- 2019
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 68:10, s. 1915-1923
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Journal article (peer-reviewed)abstract
- In renal transplant recipients (RTRs), new-onset diabetes after transplantation (NODAT) is a frequent and serious complication limiting survival of graft and patient. However, the underlying pathophysiology remains incompletely understood. In vitro and in preclinical models, HDL can preserve β-cell function, largely by mediating cholesterol efflux, but this concept has not been evaluated in humans. This study investigated whether baseline cholesterol efflux capacity (CEC) in RTRs is associated with incident NODAT during follow-up. This prospective longitudinal study included 405 diabetes-free RTRs with a functioning graft for >1 year. During a median (interquartile range) follow-up of 9.6 (6.6–10.2) years, 57 patients (14.1%) developed NODAT. HDL CEC was quantified using incubation of human macrophage foam cells with apolipoprotein B–depleted plasma. Baseline CEC was significantly lower in patients developing NODAT during follow-up (median 6.84% [interquartile range 5.84–7.50%]) compared with the NODAT-free group (7.44% [6.46–8.60%]; P = 0.001). Kaplan-Meier analysis showed a lower risk for incident NODAT with increasing sex-stratified tertiles of HDL efflux capacity (P = 0.004). Linear regression analysis indicated that CEC is independently associated with incident NODAT (P = 0.04). In Cox regression analyses, CEC was significantly associated with NODAT (hazard ratio 0.53 [95% CI 0.38–0.76]; P < 0.001), independent of HDL cholesterol levels (P = 0.015), adiposity (P = 0.018), immunosuppressive medication (P = 0.001), and kidney function (P = 0.01). Addition of CEC significantly improved the predictive power of the Framingham Diabetes Risk Score (P = 0.004). This study establishes HDL CEC as a strong predictor of NODAT in RTRs, independent of several other recognized risk factors.
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