Association of Catalytic Iron With Cardiovascular Disease

Rajapurkar, Mohan; Shah, Sudhir V.; Lele, Suhas S.; Hegde, Umapati; Lensing, Shelly; Gohel, Kalpesh; Mukhopadhyay, Banibrata; Gang, Sishir; Eigenbrodt, Marsha L.

doi:10.1016/j.amjcard.2011.09.032

Cited by 37 publications

(29 citation statements)

References 30 publications

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“…54 However, not all studies implicate iron as responsible for inducing oxidative stress of uremia, and perhaps differences in the way iron is measured (ie, total versus catalytic) explain the discrepancies. 101 Whether the oxidative stress of uremia is a primary driver of CVD or a secondary phenomenon is unclear. Small randomized trials in ESRD patients have not shown any significant benefit of antioxidant treatment, 102 suggesting that oxidative stress may not be a primary mediator of cardiovascular risk.…”

Section: Oxidative Stressmentioning

confidence: 99%

Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease

2016

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Abstract-Patients with chronic kidney disease and end-stage renal disease are at 5-to 10-fold higher risk for developing cardiovascular disease (CVD) than age-matched controls. Clinically, CVD in this population manifests as coronary artery disease, arrhythmias, stroke, or congestive heart failure. Beyond the traditional risk factors (eg, diabetes mellitus and hypertension), uremia-specific factors that arise from accumulating toxins also contribute to the pathogenesis of CVD.In this review, we summarize the literature on the epidemiology of both traditional and uremia-related CVD and focus on postulated mechanisms of the latter. P. Jousset, MD, 1 describing common causes of death among patients with Bright disease C hronic kidney disease (CKD) is an increasingly urgent public health concern that is projected to grow worldwide at a rate of 8% annually, with the fastest growth expected in developing nations.2,3 It has long been known that patients with kidney failure are predisposed to cardiovascular disease (CVD) that manifests clinically in various forms, including coronary artery disease, atrial or ventricular arrhythmias, myocardial infarction, stroke, or congestive heart failure. Over the last 30 years, it has become clear that the risk of CVD increases early in the course of progressive kidney disease and that the epidemiology, pathophysiology, prevention, and treatment of CVD and CKD are closely related and interdependent. 4 In this review, we initially describe the epidemiology of CVD among people with CKD, noting the limitations of available research. We then discuss common risk factors for CVD (traditional and nontraditional) and key shared aspects of its pathophysiology with CKD. Next we describe emerging diagnostic tools and novel therapies that may help to delay or prevent end-stage renal disease (ESRD) and to curtail the escalating burden of cardiorenal disease. In the final section, we discuss the health services and health policy challenges that CKD and its inextricably linked CVD morbidities pose worldwide, particularly for low-and middle-income countries (LMICs). Phenotypes and Epidemiology of CVD in Patients With CKDPatients with CKD and some forms of CVD share a number of risk factors and underlying pathophysiological mechanisms that, by virtue of their similarities, offer opportunities to improve their management. The epidemiology of 4 of the commonest clinical phenotypes of CVD associated with CKD is discussed below. Coronary Artery DiseaseCoronary artery disease (CAD) is a leading cause of death among people with advanced CKD. Clinical syndromes compatible with CAD (including angina and myocardial infarction) are exceedingly common in patients with nondialysis-dependent CKD, and the incidence of myocardial

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Section: Oxidative Stressmentioning

confidence: 99%

Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease

2016

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“…Iron is also considered as a cardiovascular risk marker [32]. Furthermore hepcidin, an inflammatory marker, has a key role in iron metabolism [7].…”

Section: Discussionmentioning

confidence: 99%

Is Hepcidin a New Cardiovascular Risk Marker in Polycystic Ovary Syndrome?

Gözdemir

Kaygusuz²,

Kafalı³

2013

Gynecol Obstet Invest

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Background/Aims: Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic abnormalities and carries a number of cardiovascular risk factors. Low-grade chronic inflammation has been thought to play a role in the pathogenesis of atherosclerosis and PCOS patients have an increased rate of subclinical inflammation. In the present study, considering the major role that hepcidin plays in the regulation of iron metabolism and as an inflammatory marker, we investigated hepcidin in PCOS patients and its role in predicting cardiovascular disease (CVD) development. Methods: Forty patients with PCOS and 40 age- and body mass index-matched healthy controls were included in the study. Iron metabolites, insulin resistance (IR), inflammatory markers and hepcidin levels were analyzed. Results: IR parameters, inflammatory markers, iron parameters and hepcidin levels were similar between the PCOS and control groups. While the inflammatory markers were significantly high in the overweight and obese PCOS subgroup, the hepcidin levels were also high but this elevation was not statistically significant. Conclusion: Obesity is the principle mechanism of chronic inflammation and IR in PCOS patients. C-reactive protein and interleukin-6 should be used to predict and follow the risk of CVD development in PCOS cases. Hepcidin may be used as an additional marker in the follow-up of PCOS patients in the future.

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“…In humans, the release of intracellular stores of iron under conditions of tissue injury (3) or hemolysis (11) results in elevated circulating levels of catalytic iron. High plasma catalytic iron levels, in turn, may have a pathologic role in a variety of disease states, including coronary artery disease (12,13) and acute coronary syndrome (14)(15)(16); however, the association with AKI has not been well studied in humans.…”

Section: Introductionmentioning

confidence: 99%

Plasma Catalytic Iron, AKI, and Death among Critically Ill Patients

Leaf

Rajapurkar²,

Lele

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Catalytic iron has been hypothesized to be a key mediator of AKI. However, the association between plasma catalytic iron levels and AKI has not been well studied in humans.Design, settings, participants, & measurements A single-center, prospective, nonconsecutive cohort study of 121 critically ill patients admitted to intensive care units (ICUs) between 2008 and 2012 was performed. Plasma catalytic iron, free hemoglobin, and other iron markers were measured on ICU days 1 and 4. The primary end point was in-hospital mortality or AKI requiring RRT. Secondary end points included mortality (assessed during hospitalization, at 30 days, and 1 year) and incident AKI, defined by modified Kidney Disease Improving Global Outcomes criteria.Results ICU day 1 plasma catalytic iron levels were higher among patients who reached the primary end point (median, 0.74 mmol/l [interquartile range, 0.31-3.65] versus 0.29 mmol/l [0.22-0.46]; P,0.01). ICU day 1 plasma catalytic iron levels were associated with number of packed red blood cell transfusions before ICU arrival (r s =0.29; P,0.001) and plasma free hemoglobin levels on ICU day 1 (r s =0.32; P,0.001). Plasma catalytic iron levels on ICU day 1 were significantly associated with in-hospital mortality or AKI requiring RRT, even after adjusting for age, enrollment eGFR, and number of packed red blood cell transfusions before ICU arrival (13 events; adjusted odds ratio per 1-SD higher ln[catalytic iron], 3.33; 95% confidence interval, 1.79 to 6.20). ICU day 1 plasma catalytic iron levels were also significantly associated with incident AKI, RRT, hospital mortality, and 30-day mortality.Conclusions Among critically ill patients, elevated plasma catalytic iron levels on arrival to the ICU are associated with a greater risk of incident AKI, RRT, and hospital mortality.

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Association of Catalytic Iron With Cardiovascular Disease

Cited by 37 publications

References 30 publications

Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease

Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease

Is Hepcidin a New Cardiovascular Risk Marker in Polycystic Ovary Syndrome?

Plasma Catalytic Iron, AKI, and Death among Critically Ill Patients

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