Background: Chronic kidney disease (CKD) and atrial fibrillation (AF) are both risk factors for bleeding, stroke and mortality. The aim of our study was to investigate the interaction between CKD... Show moreBackground: Chronic kidney disease (CKD) and atrial fibrillation (AF) are both risk factors for bleeding, stroke and mortality. The aim of our study was to investigate the interaction between CKD and atrial fibrillation and outcomes. Methods: We included 12,394 subjects referred to the University Medical Center Utrecht (the Netherlands) from September 1996 to February 2018 for an out-patient visit (Utrecht Cardiovascular Cohort Second Manifestation of Arterial disease cohort). Hazard ratios (HRs) with 95% confidence intervals (CIs) for bleeding, ischemic stroke or mortality were calculated with Cox proportional hazard analyses. Presence of interaction between AF and CKD was examined by calculating the relative excess risk due to interaction (RERI), the attributable proportion (AP) due to interaction and the synergy index (S). Results: Of the 12,394 patients, 699 patients had AF, 2,752 patients had CKD and 325 patients had both AF and CKD. Patients with both CKD and AF had a 3.0-fold (95% CI 2.0-4.4) increased risk for bleeding, a 4.2-fold (95% CI 3.0-6.0) increased ischemic stroke risk and a 2.2-fold (95% CI 1.9-2.6) increased mortality risk after adjustment as compared with subjects without atrial fibrillation and CKD. We did not find interaction between AF and CKD for bleeding and mortality. However, we found interaction between AF and CKD for ischemic stroke risk (RERI 1.88 (95% CI 0.31-3.46), AP 0.45 (95% CI 0.17-0.72) and S 2.40 (95% CI 1.08-5.32)). Conclusion: AF and CKD are both associated with bleeding, ischemic stroke and mortality. There is a positive interaction between AF and CKD for ischemic stroke risk, but not for bleeding or mortality. Show less
Sharif, S.; Groenwold, R.H.H.; Graaf, Y. van der; Berkelmans, G.F.N.; Cramer, M.J.; Visseren, F.L.J.; ... ; SMART Study Grp 2019
Aim To quantify the magnitude and specific contributions of known cardiovascular risk factors leading to higher cardiovascular risk and all-cause mortality caused by type 2 diabetes (T2D). Methods... Show moreAim To quantify the magnitude and specific contributions of known cardiovascular risk factors leading to higher cardiovascular risk and all-cause mortality caused by type 2 diabetes (T2D). Methods Mediation analysis was performed to assess the relative contributions of known classical risk factors for vascular disease in T2D (insulin resistance, systolic blood pressure, renal function, LDL-cholesterol, triglycerides and micro-albuminuria), and what proportion of the effect of T2D on cardiovascular events and all-cause mortality these factors mediate in the Second Manifestations of ARTerial disease (SMART) cohort consisting of 1910 T2D patients. Results Only 35% (95% CI 15-71%) of the excess cardiovascular risk caused by T2D is mediated by the classical cardiovascular risk factors. The largest mediated effect was through insulin resistance [proportion of mediated effect (PME) 18%, 95% CI 3-37%], followed by elevated triglycerides (PME 8%, 95% CI 4-14%) and micro-albuminuria (PME 7%, 95% CI 3-17%). Only 42% (95% CI 18-73%) of the excess mortality risk was mediated by the classical risk factors considered. The largest mediated effect was by micro-albuminuria (PME 18%, 95% CI 10-29%) followed by insulin resistance (PME 15%, 95% CI 1-33%). Conclusion A substantial amount of the increased cardiovascular risk and all-cause mortality caused by T2D cannot be explained by traditional vascular risk factors. Future research should focus on identifying non-classical pathways that might further explain the increased cardiovascular and mortality risk caused by T2D. Show less
Toll-Like Receptor (TLR) -2 and -4 expression and TLR-induced cytokine response of inflammatory cells are related to atherogenesis and atherosclerotic plaque progression. We examined whether... Show moreToll-Like Receptor (TLR) -2 and -4 expression and TLR-induced cytokine response of inflammatory cells are related to atherogenesis and atherosclerotic plaque progression. We examined whether immediate TLR induced changes in CD11b and L-selectin (CD62L) expression are able to discriminate the presence and severity of atherosclerotic disease by exploring single dose whole blood TLR stimulation and detailed dose-response curves. Blood samples were obtained from 125 coronary artery disease (CAD) patients and 28 controls. CD11b and L-selectin expression on CD14+ monocytes was measured after whole blood stimulation with multiple concentrations of the TLR4 ligand LPS (0.01-10 ng/ml) and the TLR2 ligand P3C (0.5-500 ng/ml). Subsequently, dose-response curves were created and the following parameters were calculated: hillslope, EC50, area under the curve (AUC) and delta. These parameters provide information about the maximum response following activation, as well as the minimum trigger required to induce activation and the intensity of the response. CAD patients showed a significantly higher L-selectin, but not CD11b response to TLR ligation than controls after single dose stimulations as well as significant differences in the hillslope and EC50 of the dose-response curves. Within the CAD patient group, dose-response curves of L-selectin showed significant differences in the presence of hypertension, dyslipidemia, coronary occlusion and degree of stenosis, whereas CD11b expression had the strongest discriminating power after single dose stimulation. In conclusion, single dose stimulations and dose-response curves of CD11b and L-selectin expression after TLR stimulation provide diverse but limited information about atherosclerotic disease severity in stable angina patients. However, both single dose stimulation and dose-response curves of LPS-induced L-selectin expression can discriminate between controls and CAD patients. Show less
