Risk Factors for Peripheral Arterial Disease Among Patients With Chronic Kidney Disease
ABSTRACT Patients with chronic kidney disease (CKD) have an increased risk for developing peripheral arterial disease (PAD). The aim of this study was to examine the cross-sectional association between novel risk factors and prevalent PAD in patients with CKD. A total of 3,758 patients with estimated glomerular filtration rates of 20 to 70 ml/min/1.73 m(2) who participated in the Chronic Renal Insufficiency Cohort (CRIC) study were included in the present analysis. PAD was defined as an ankle-brachial index <0.9 or a history of arm or leg revascularization. After adjustment for age, gender, race, cigarette smoking, physical activity, history of hypertension and diabetes, pulse pressure, high-density lipoprotein cholesterol, estimated glomerular filtration rate, and CRIC clinical sites, several novel risk factors were significantly associated with PAD. For example, odds ratios for a 1-SD higher level of risk factors were 1.18 (95% confidence interval [CI] 1.08 to 1.29) for log-transformed high-sensitivity C-reactive protein, 1.18 (95% CI 1.08 to 1.29) for white blood cell count, 1.15 (95% CI 1.05 to 1.25) for fibrinogen, 1.13 (95% CI 1.03 to 1.24) for uric acid, 1.14 (95% CI 1.02 to 1.26) for glycosylated hemoglobin, 1.11 (95% CI 1.00 to 1.23) for log-transformed homeostasis model assessment of insulin resistance, and 1.35 (95% CI 1.18 to 1.55) for cystatin C. In conclusion, these data indicate that inflammation, prothrombotic state, oxidative stress, insulin resistance, and cystatin C were associated with an increased prevalence of PAD in patients with CKD. Further studies are warranted to examine the causal effect of these risk factors on PAD in patients with CKD.
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ABSTRACT: The ankle-brachial blood pressure index (ABPI) has been recognized to have a predictive value for cardiovascular (CV) events and mortality in general or dialysis populations. However, the associations between ABPI and those outcomes have not been fully investigated in predialysis patients. The present study aimed to clarify the relationships between ABPI and both CV events and mortality in Japanese chronic kidney disease (CKD) patients not on dialysis. In this prospective observational study, we enrolled 320 patients with CKD stages 3-5 who were not on dialysis. At baseline, ABPI was examined and a low ABPI was defined as <0.9. CV events and all-cause deaths were examined in each patient. A Cox proportional hazards model was applied to determine the risk factors for CV events, as well as for mortality from CV and all causes. The median follow-up period was 30 months. CV events occurred in 56 patients and all-cause deaths occurred in 48, including 20 CV deaths. Multivariate analysis showed that age and low ABPI were risk factors for CV events. It was demonstrated that age, a history of cerebrovascular disease and low ABPI were determined as independent risk factors for CV mortality. In addition, age, body mass index and low ABPI were independently associated with all-cause mortality. In patients with CKD, low ABPI during the predialysis period is independently associated with poor survival and CV events, suggesting the usefulness of measuring ABPI for predicting CV events and patient survival in CKD.Hypertension Research advance online publication, 24 July 2014; doi:10.1038/hr.2014.120.Hypertension Research 07/2014; 37(12). DOI:10.1038/hr.2014.120 · 2.94 Impact Factor
Article: Fibrin(ogen) and thrombotic disease[Show abstract] [Hide abstract]
ABSTRACT: Fibrinogen is an abundant plasma protein that, when converted to fibrin by thrombin, provides the main building blocks for the clot. Dys-, a-, and hypo-fibrinogenemias have been variably linked to a normal phenotype, bleeding or even thrombosis. Meanwhile, increased fibrinogen concentrations in the blood have been associated with risk for thrombosis. More recently, studies have focussed on abnormal fibrin structure as a cause for thrombosis. Fibrin clots that have high fiber density and increased resistance to fibrinolysis have been consistently associated with risk for thrombosis. Fibrin structure measurements can (i) provide an overall assessment of hemostatic capacity of a sample, (ii) include effects of thrombin generation and fibrinogen concentrations, (iii) include effects of fibrinogen mutations, polymorphisms, and modifications, and (iv) give an indication of clot mechanical strength and resistance to fibrinolysis. A fibrinogen splice variation of the γ-chain (γ') is discussed as a model for changes in fibrin structure in relation to thrombosis. Results from prospective studies on fibrin structure are awaited. Studies of fibrin formation under flow, interactions of fibrin with blood cells, the mechanical properties of the fibrin clot, and nanoscale/molecular characterization of fibrin formation are likely to expose new causal mechanisms for the role of fibrin in thrombotic disease. Future studies into the causality and mechanisms may lead to new opportunities using fibrin structure in the diagnosis or treatment of thrombosis.Journal of Thrombosis and Haemostasis 06/2013; 11(s1). DOI:10.1111/jth.12229 · 5.55 Impact Factor
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ABSTRACT: Persons with CKD are at a higher risk of developing peripheral artery disease (PAD) and its adverse health outcomes than individuals in the general population who have normal renal function. Classic atherosclerosis risk factors (eg, age, smoking, diabetes, hypertension, and hyperlipidemia) are common in patients with CKD, but CKD also imposes additional unique risk factors that promote arterial disease (eg, chronic inflammation, hypoalbuminemia, and a procalcific state). Current nephrology clinical practice is adversely affected by PAD diagnostic challenges, the complexities of managing 2 serious comorbid diseases, delayed vascular specialist referral, and slow PAD treatment initiation in patients with CKD. Persons with CKD are less likely to be provided recommended “optimal” PAD care. The knowledge that both limb and mortality outcomes are significantly worse in patients with CKD, especially those on dialysis, is not just a biologic fact but can serve as a care delivery call to action. Nephrologists can facilitate positive change. This article proposes that patients with PAD and CKD be strategically comanaged by care teams that encompass the skills to create and use evidence-based care pathways. This proposed collaborative multidisciplinary approach will include vascular medicine specialists, nephrologists, wound specialists, and mid-level providers. Just as clinical care quality metrics have served as the base for ESRD and acute MI quality improvement, it is time that such quality outcomes metrics be initiated for the large PAD-CKD population. This new system will identify and resolve key gaps in the current care model so that clinical outcomes improve within a cost-effective care frame for this vulnerable population.Advances in Chronic Kidney Disease 11/2014; 21(6):460. DOI:10.1053/j.ackd.2014.07.005 · 1.94 Impact Factor