Vascular function assessed with cardiovascular magnetic resonance predicts survival in patients with advanced chronic kidney disease

<p>Abstract</p> <p>Background</p> <p>Increased arterial stiffness is associated with mortality in patients with chronic kidney disease. Cardiovascular magnetic resonance (CMR) permits assessment of the central arteries to measure aortic function.</p> <p>Methods</p> <p>We studied the relationship between central haemodynamics and outcome using CMR in 144 chronic kidney disease patients with estimated glomerular filtration rate <15 ml/min (110 on dialysis). Aortic distensibilty and volumetric arterial strain were calculated from cross sectional aortic volume and pulse pressure measured during the scan.</p> <p>Results</p> <p>Median follow up after the scan was 24 months. There were no significant differences in aortic distensibilty or aortic volumetric arterial strain between pre-dialysis and dialysis patients. Aortic distensibilty and volumetric arterial strain negatively correlated with age. Aortic distensibilty and volumetric arterial strain were lower in diabetics, patients with ischaemic heart disease and peripheral vascular disease. During follow up there were 20 deaths. Patients who died had lower aortic distensibilty than survivors. In a survival analysis, diabetes, systolic blood pressure and aortic distensibilty were independent predictors of mortality. There were 12 non-fatal cardiovascular events during follow up. Analysing the combined end point of death or a vascular event, diabetes, aortic distensibilty and volumetric arterial strain were predictors of events.</p> <p>Conclusion</p> <p>Deranged vascular function measured with CMR correlates with cardiovascular risk factors and predicts outcome. CMR measures of vascular function are potential targets for interventions to reduce cardiovascular risk.</p

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Kaplan-Meier survival curves for survival to either CV end point or death with patients stratified by aortic VAS quartile

<p><b>Copyright information:</b></p><p>Taken from "Vascular function assessed with cardiovascular magnetic resonance predicts survival in patients with advanced chronic kidney disease"</p><p>http://www.jcmr-online.com/content/10/1/39</p><p>Journal of Cardiovascular Magnetic Resonance 2008;10(1):39-39.</p><p>Published online 18 Aug 2008</p><p>PMCID:PMC2529284.</p><p></p

Kaplan-Meier survival curves for all cause mortality with patients stratified by aortic distensibilty tertile

<p><b>Copyright information:</b></p><p>Taken from "Vascular function assessed with cardiovascular magnetic resonance predicts survival in patients with advanced chronic kidney disease"</p><p>http://www.jcmr-online.com/content/10/1/39</p><p>Journal of Cardiovascular Magnetic Resonance 2008;10(1):39-39.</p><p>Published online 18 Aug 2008</p><p>PMCID:PMC2529284.</p><p></p

Vascular function assessed with cardiovascular magnetic resonance predicts survival in patients with advanced chronic kidney disease-0

<p><b>Copyright information:</b></p><p>Taken from "Vascular function assessed with cardiovascular magnetic resonance predicts survival in patients with advanced chronic kidney disease"</p><p>http://www.jcmr-online.com/content/10/1/39</p><p>Journal of Cardiovascular Magnetic Resonance 2008;10(1):39-39.</p><p>Published online 18 Aug 2008</p><p>PMCID:PMC2529284.</p><p></p