High Lipoprotein(a) Levels and Small Apolipoprotein(a) Size Prospectively Predict Cardiovascular Events in Dialysis Patients

Longenecker, J. Craig; Klag, Michael J.; Marcovina, Santica M.; Liu, Yong Mei; Jaar, Bernard G.; Powe, Neil R.; Fink, Nancy E.; Levey, Andrew S.; Coresh, Josef

doi:10.1681/asn.2004110922

Cited by 78 publications

(67 citation statements)

References 25 publications

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“…High levels of Lp(a) are attributed to increased synthesis in nephrotic syndrome patients 73) , while in dialysis patients impaired clearance due to decreased catabolism is believed to be the predominant mechanism 74) . Although high molecular weight isoforms of Lp(a) are increased in CKD patients, CVD risk is primarily associated with high levels of the lower molecular weight isoform in these patients 70) .…”

Section: Tgrl Metabolic Disorders In Ckd Patientsmentioning

confidence: 99%

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Lipid Abnormalities in Patients with Chronic Kidney Disease: Implications for the Pathophysiology of Atherosclerosis

Keane

Tomassini

Neff

2013

JAT

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Cardiovascular disease is increased in patients with chronic kidney disease (CKD) and is the principle cause of morbidity and mortality in these patients. In patients with stage 5 CKD, structural changes in the myocardium have been implicated as the principle cardiovascular processes leading to this increase in morbidity and mortality, while atherosclerotic events including acute myocardial infarction and strokes are responsible for approximately 10-15% of cardiovascular deaths. Dyslipidemia is common in CKD patients and is usually not characterized by elevated cholesterol levels, except in patients with marked proteinuria. Increased triglyceride levels in conjunction with decreased highdensity lipoprotein levels are the commonest qualitative abnormality. Characteristically, abnormalities in the metabolism of apolipoprotein (apo) B-containing lipoproteins have been described, including both gut derived (apoB-48) as well as those produced by hepatic synthesis (apoB-100). A decrease in enzymatic delipidation as well as reduced receptor removal of these lipoproteins both contribute to the increased levels of these apo-B-containing particles and their remnants (which are believed to be highly atherogenic). Abnormalities in the metabolism of apoA-containing lipoproteins are also present and these changes contribute to the lower levels of HDL seen. Qualitative abnormalities of these HDL particles may be associated with cellular oxidative injury and contribute to a proinflammatory, pro-thrombotic milieu that is frequently present in CKD patients. J Atheroscler

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Section: Tgrl Metabolic Disorders In Ckd Patientsmentioning

confidence: 99%

“…Levels of Lp(a) are increased in CKD patients on dialysis and in those with nephrotic syndrome 25,34,70) . Lp(a) is a large protein that consists of an LDL particle linked to apo(a) via a disulfide bond 25,34) .…”

Section: Abnormalities Of Lipoprotein(a)mentioning

confidence: 99%

Lipid Abnormalities in Patients with Chronic Kidney Disease: Implications for the Pathophysiology of Atherosclerosis

Keane

Tomassini

Neff

2013

JAT

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“…The outcomes were all-cause and cardiovascular disease (CVD) mortality. Mortality information was independently adjudicated using information from clinic report, medical records, National Death Index, Centers for Medicare & Medicaid Services death notification forms, and Social Security records as previously described (19).…”

Section: Data Collectionmentioning

confidence: 99%

Serum β-Trace Protein and Risk of Mortality in Incident Hemodialysis Patients

Shafi¹,

Parekh²,

Jaar³

et al. 2012

Clinical Journal of the American Society of Nephrology

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Summary Background and objectives Residual kidney function in dialysis patients is associated with better survival, but there are no simple methods for its assessment. β-Trace protein is a novel endogenous filtration marker of kidney function that is not removed during hemodialysis and may serve as a marker for residual kidney function similar to serum creatinine in patients not on dialysis. The objective of this study was to determine the association of serum β-trace protein with mortality in incident hemodialysis patients. Design, setting, participants, & measurements Serum β-trace protein was measured in baseline samples from 503 participants of a national prospective cohort study of incident dialysis patients with enrollment during 1995–1998 and follow-up until 2004. Outcomes were all-cause and cardiovascular disease mortality analyzed using Cox regression adjusted for demographic, clinical, and treatment factors. Results Serum β-trace protein levels were higher in individuals with no urine output compared with individuals with urine output (9.0±3.5 versus 7.6±3.1 mg/L; P<0.001). There were 321 deaths (159 deaths from cardiovascular disease) during follow-up (median=3.3 years). Higher β-trace protein levels were associated with higher risk of mortality. The adjusted hazard ratio and 95% confidence interval for all-cause mortality per doubling of serum β-trace protein was 1.36 (1.09–1.69). The adjusted hazard ratios (95% confidence intervals) for all-cause mortality in the middle and highest tertiles compared with the lowest tertile were 0.95 (0.69–1.32) and 1.72 (1.25–2.37). Similar results were noted for cardiovascular disease mortality. Conclusions The serum level of β-trace protein is an independent predictor of death and cardiovascular disease mortality in incident hemodialysis patients.

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“…It structurally resembles plasminogen and interferes with fibrinolysis, and it binds to macrophages and promotes foam cell formation and the deposition of cholesterol in atherosclerotic plaques (104,105). An elevated level predicted vascular events (106) and was found to be an independent risk factor for CVD in hemodialysis patients (107). The levels of lipoprotein(a) are especially high in peritoneal dialysis patients (89) and seem to decrease after kidney transplantation (90).…”

Section: Pathophysiology Of Cvd In Ckdmentioning

confidence: 99%

The Unique Character of Cardiovascular Disease in Chronic Kidney Disease and Its Implications for Treatment with Lipid-Lowering Drugs

Nogueira

Weir

2007

Clinical Journal of the American Society of Nephrology

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D uring the past several decades, the advent and refinement of maintenance dialysis and kidney transplantation have essentially eliminated kidney failure per se as a cause of death in developed countries. However, as patients survive many years after the development of renal failure, comorbidities develop, progress, and ultimately cause death in these individuals. Cardiovascular disease (CVD) has ranked prominent among these comorbidities, accounting for nearly half of the deaths (1). All along the continuum of chronic kidney disease (CKD)-from microalbuminuria to ESRD-a higher risk for CVD has been observed (see Epidemiology of CVD in CKD). In fact, individuals with early CKD are more likely to die of CVD than to develop ESRD (2,3). Then, among those who survive to ESRD, the all-cause CVD mortality in patients with ESRD is many-fold higher than in the general population (4). Unfortunately, the reasons for the association of CKD with CVD are not clearly understood, and the role of various clinical interventions in stemming the CVD epidemic are not well defined. Complicating the issue is the potential variation in the pathophysiology and clinical behavior of CVD through the stages of CKD.3-Hydroxyl-3-methylglutaryl CoA reductase inhibitors (statins) and other lipid-lowering drugs (LLD) have been clearly demonstrated to lessen the morbidity and mortality of CVD in the general population; therefore, there is hope that the use of these drugs may likewise help patients with CKD (In addition, it has been theorized that dyslipidemia may contribute to the progression of CKD, such that LLD may prove to slow CKD progression.) Nevertheless, given differences in epidemiology and pathophysiology of CVD in CKD, there are reasons to question whether the cardiovascular benefits of LLD that are observed in the general population will also be realized in the CKD population. It is widely acknowledged that the current medical literature provides insufficient data to guide the use of LLD in the CKD population, in large part because renal insufficiency has been an exclusion criterion for most of the randomized, controlled studies that have addressed this issue. Although consensus-based guidelines on the treatment of dyslipidemias in individuals with CKD and with kidney transplants have been published by the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) Work Groups, the nephrology and cardiology communities recognize the urgent need for high-quality clinical studies on this issue, and this has fueled the publication of subgroup analyses of previous large studies in the general population and the launching of large-scale clinical trials in the CKD population, as summarized in Table 1. To provide the reader with a better appreciation of the important issues that are germane to management of dyslipidemia in CKD, this article (1) briefly summarizes the literature on the benefits of LLD in the general population, (2) demonstrates the limited involvement of individuals with CKD in the studies in the ge...

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High Lipoprotein(a) Levels and Small Apolipoprotein(a) Size Prospectively Predict Cardiovascular Events in Dialysis Patients

Cited by 78 publications

References 25 publications

Lipid Abnormalities in Patients with Chronic Kidney Disease: Implications for the Pathophysiology of Atherosclerosis

Lipid Abnormalities in Patients with Chronic Kidney Disease: Implications for the Pathophysiology of Atherosclerosis

Serum β-Trace Protein and Risk of Mortality in Incident Hemodialysis Patients

The Unique Character of Cardiovascular Disease in Chronic Kidney Disease and Its Implications for Treatment with Lipid-Lowering Drugs

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