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- Almquist, Tora
(författare)
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Effects of lipid-lowering treatment on platelet function and hemostatic mechanisms in diabetic patients : influence of chronic kidney disease and inflammatory parameters
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diabetes mellitus (DM) and chronic kidney disease (CKD) are both associated with increased cardiovascular morbidity and mortality, and the risk is even higher when they are concurrent. Both diseases are considered to be prothrombotic states with increased inflammatory activity and major disturbances in the hemostasis. Lipid-lowering treatment (LLT) may have beneficial effects on inflammation, platelet activation and atherothrombotic mechanisms. We evaluated the prognostic implications of impaired renal function, measured as estimated creatinine clearance (eCrCl), in 808 patients with stable angina pectoris in a post hoc analysis of the Angina Prognosis Study In Stockholm (APSIS), which compared metoprolol and verapamil treatment in stable angina with a median follow-up of 40 months. A multivariate Cox analysis showed an independent prognostic importance of eCrCl for cardiovascular (CV) death and for CV death or myocardial infarction (MI). Patients with eCrCl <60 ml/min had a doubled risk of suffering CV death or MI, compared to patients with eCrCl ≥90 ml/min. We investigated the effects of LLT with simvastatin alone or in combination with ezetimibe in 18 patients with an estimated GFR (eGFR) of 15-59 ml/min/1.73m2 (DM-CKD) and 21 DM patients with eGFR >75 ml/min/1.73m2 (DM-only) in a randomized, double blind, cross- over study. Parameters reflecting platelet activity, microparticles (MP) formation and inflammatory parameters were measured. At baseline, after a placebo run-in period, we found signs of increased inflammatory activity, increased platelet activation and hypercoagulability in DM-CKD compared to DM-only patients with increased formation of platelet-leukocyte aggregates (PLA), elevated levels of proinflammatory cytokines and soluble CD40L (sCD40L) in plasma, as well as elevated levels of MPs derived from platelets (PMPs), monocytes (MMPs) and endothelial cells. Simvastatin treatment alone reduced the expression of P-selectin, tissue factor (TF) and CD40L on PMPs, and TF on MMPs in both patient groups. Simvastatin also reduced levels of total procoagulant MPs, PMPs and MMPs as well as IFNγ and MCP-1 in DM-CKD but not in DM-only patients. Furthermore, the combination of simvastatin+ezetimbe reduced PLA formation and sCD40L levels in DM patients with CKD compared to DM-only patients. Most differences between DM-CKD and DM-only patients were reduced or disappeared with LLT despite similar lipid levels in the two groups both before and during LLT. In conclusion, impaired renal function carries independent prognostic information in patients with stable angina pectoris, in agreement with findings in other patient categories. Patients with CKD should be identified early, as there is need for improved CV risk reduction therapy in these high-risk patients. DM patients with CKD stages 3-4 (eGFR 15-59 mL/min/1.73m2) have signs of increased inflammatory activity and platelet activation, and hypercoagulability compared to DM-patients with normal eGFR. LLT counteracted the differences between DM-CKD and DM-only patients, with reduced inflammatory activation and a less procoagulant milieu especially in the presence of CKD. This may contribute to the beneficial effects of LLT on atherothrombotic complications in DM patients with concurrent CKD.
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| 2. |
- Chesnaye, Nicholas C., et al.
(författare)
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Association of Longitudinal High-Sensitivity Troponin T With Mortality in Patients With Chronic Kidney Disease
- 2022
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 79:4, s. 327-336
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Cardiac troponin T (cTnT) is associated with mortality in chronic kidney disease (CKD). However, the association between longitudinal cTnT measurements and survival has not previously been assessed. OBJECTIVES This study determined whether various parameterizations of longitudinal cTnT measurements were associated with patient survival in the older population with advanced CKD. METHODS The EQUAL (European QUALity) study is an observational prospective cohort study that includes subjects with stage 4-5 CKD aged $65 years and not on dialysis. The study includes 176 participants in Sweden, where longitudinal information of cTnT was collected. The study uses joint models for longitudinal and time-to-event data to assess the longitudinal association between cTnT and survival. RESULTS There were 927 cTnT measurements (median 6 per patient) collected over a median follow-up of 2.4 years. The overall 5-year survival was 57% (95% CI: 46%-69%). Longitudinally measured cTnT was associated with mortality risk, with every SD increase in cTnT, at any time point, associated with a 3.3-fold increase in mortality risk (HR: 3.3; 95% CI: 2.5-4.6). The slope of the cTnT trajectory was also associated with increased mortality risk (HR: 3.2; 95% CI: 2.06.0), as was the area under the cTnT trajectory (HR: 4.2; 95% CI: 2.6-7.2), which reflected the cumulative cTnT exposure. CONCLUSIONS Longitudinally measured cTnT is independently associated with mortality risk in older patients with stage 4 and 5 CKD, which suggests that monitoring patients with cTnT could be a valuable tool for the identification of subjects with a high mortality risk.
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| 3. |
- de Laval, Philip, et al.
(författare)
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Acute effects of haemodialysis on circulating microparticles
- 2019
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 12:3, s. 456-462
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Tidskriftsartikel (refereegranskat)abstract
- Background. Microparticles (MPs) are small cell membrane-derived vesicles regarded as both biomarkers and mediators of biological effects. Elevated levels of MPs have previously been associated with endothelial dysfunction and predict cardiovascular death in patients with end-stage renal disease. The objective of this study was to measure change in MP concentrations in contemporary haemodialysis (HD).Methods. Blood was sampled from 20 consecutive HD patients before and 1h into the HD session. MPs were measured by flow cytometry and phenotyped based on surface markers.Results. Concentrations of platelet (CD41(+)) (P = 0.039), endothelial (CD62E(+)) (P = 0.004) andmonocyte-derived MPs (CD14(+)) (P<0.001) significantly increased during HD. Similarly, endothelial-(P = 0.007) and monocyte-derived MPs (P = 0.001) expressing tissue factor (TF) significantly increased as well as MPs expressing Klotho (P = 0.003) and receptor for advanced glycation end products (RAGE) (P = 0.009). Furthermore, MPs expressing platelet activationmarkers P-selectin (P = 0.009) and CD40L (P = 0.045) also significantly increased. The increase of endothelial (P = 0.034), monocyte (P = 0.014) and RAGE(+) MPs (P = 0.032) as well as TF+ platelet-derived MPs (P = 0.043) was significantly higher in patients treated with low-flux compared with high-flux dialysers.Conclusion. Dialysis triggers release of MPs of various origins with marked differences between high-flux and low-flux dialysers. The MPs carry surface molecules that could possibly influence coagulation, inflammation, oxidative stress and endothelial dysfunction. The clinical impact of these findings remains to be established in future studies.
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