The Use of Statins in Pediatrics: Knowledge Base, Limitations, and Future Directions

Belay, Brook; Belamarich, Peter F.; Tom-Revzon, Catherine

doi:10.1542/peds.2006-0787

Cited by 60 publications

(52 citation statements)

References 103 publications

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“…Similarly, increased physical activity may not be feasible if serious metabolic complications of CKD are present. In such cases, disease-specific management becomes particularly important [82], and secondary causes of dyslipidemia should be sought and treated [81,83]. Sedentary activities should also be minimized by limiting leisure screen time to less than 2 h per day in children older than age 2 years and encouraging children older than age 5 years to participate in at least 1 h of moderate-to-vigorous activity (jogging, baseball) every day and vigorous activity (running, soccer) 3 days per week [18].…”

Section: Non-pharmacologic Managementmentioning

confidence: 99%

“…In the absence of randomized controlled clinical trials of dyslipidemia in CKD patients, these guidelines recommended following the 1992 National Cholesterol Education Program guidelines [89] for dyslipidemia goals in adults and adolescents with estimated glomerular filtration rates (eGFR) values of 15 ml./min/1.73 m 2 or greater (formerly known as CKD stages 1 to 4) and also recommended treatment in dyslipidemic adults and adolescents with eGFR values below 15 ml/min/1.73 m 2 (formerly known as stage 5 CKD) [90]. Recognizing that CKD is associated with pathological and/or clinical evidence of coronary disease before the age of 30 years and that multiple prospective studies show childhood lipid and lipoprotein profiles are predictive of future adult lipoprotein profiles with the strongest statistical correlation occurring between late childhood and the third and fourth decades of life [18,83], two expert pediatric panels published evidence-based guidelines for intensive cardiovascular risk reduction in children with CKD after the 2003 publication of the KDOQI guidelines [18,78]. In general, the cardiovascular risk mitigation strategies outlined in these guidelines rely on expert consensus rather than efficacy data, are largely based on the premise that plasma lipid levels in otherwise healthy children are predictive of future plasma lipid levels and subsequent CV events in adulthood [91][92][93][94], and include recommendations for the non-pharmacologic and pharmacologic management of dyslipidemia.…”

Section: Pharmacologic Managementmentioning

confidence: 99%

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Etiology and management of dyslipidemia in children with chronic kidney disease and end-stage renal disease

Khurana

Silverstein

2015

Pediatr Nephrol

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Lipids are essential components of cell membranes, contributing to cell fuel, myelin formation, subcellular organelle function, and steroid hormone synthesis. Children with chronic kidney disease (CKD) and end-stage renal disease (ESRD) exhibit various co-morbidities, including dyslipidemia. The prevalence of dyslipidemias in children with CKD and ESRD is high, being present in 39-65 % of patients. Elevated lipid levels in children without renal disease are a risk factor for cardiovascular disease (CVD), while the risk for CVD in pediatric CKD/ESRD is unclear. The pathogenesis of dyslipidemia in CKD features various factors, including increased levels of triglycerides, triglyceride-rich lipoproteins, apolipoprotein C3 (ApoC-III), decreased levels of cholesterylester transfer protein and high-density lipoproteins, and aberrations in serum very low-density and intermediatedensity lipoproteins. If initial risk assessment indicates that a child with advanced CKD has 2 or more co-morbidities for CVD, first-line treatment should consist of nonpharmacologic management such as therapeutic lifestyle changes and dietary counseling. Pharmacologic treatment of dyslipidemia may reduce the incidence of CVD in children with CKD/ESRD, but randomized trials are lacking. Lipids are essential components of cell membranes, contributing to cell fuel, myelin formation, subcellular organelle function, and steroid hormone synthesis. Lipids are generally categorized by their density and other physical characteristics [1]. Since lipids such as cholesterol and triglycerides (TG) are insoluble in plasma, lipoproteins are required to transport all sources (e.g., diet) of lipids to areas in which the lipids can either be stored for future use or used immediately [2], although it should be noted that short-and medium-chain fatty acids also flow via the portal system as fatty acids. Specifically, low-density lipoproteins (LDL) carry the majority of cholesterol (forming LDL-C), while very low-density lipoproteins (VLDL) carry the majority of triglycerides.The broad categories of lipoproteins are chylomicrons, VLDL, LDL, and high-density lipoproteins (HDL Prevalence and sub-types of dyslipidemia in pediatric chronic kidney disease (CKD) and end-stage renal disease (ESRD)Children with CKD/ESRD exhibit various co-morbidities, including dyslipidemia. The prevalence of dyslipidemias in children with CKD and ESRD is high (39-65 %), but is significantly dependent on the cause and vintage of CKD (e.g., usually more common and severe with glomerular disease and proteinuria) and the stage of the disease [4,5]. The Chronic Kidney Disease in Children (CKiD) study included an assessment of the relationship between renal function and serum lipid levels. The most common type of dyslipidemia was hypertriglyceridemia. They found an inverse relationship between renal function (measured glomerular filtration rate, or GFR) and serum TG and total cholesterol (TC) levels; that is, as GFR declines, TG and TC levels generally increase. Conversely, there is a ...

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Section: Non-pharmacologic Managementmentioning

confidence: 99%

Section: Pharmacologic Managementmentioning

confidence: 99%

Etiology and management of dyslipidemia in children with chronic kidney disease and end-stage renal disease

Khurana

Silverstein

2015

Pediatr Nephrol

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“…112,113 Statins are effective for the small fraction of children with genetically programmed hypercholesterolemia. 114 …”

Section: Hyperlipidemiamentioning

confidence: 99%

Preventing Heart Disease in the 21st Century

McMahan²,

2008

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W e could prevent 90% of heart attacks. Such a claim would have seemed outrageous in the 1960s, as the coronary heart disease (CHD) epidemic reached new heights and accounted for one third of all deaths in the United States and most other developed countries. 1 The identification of conditions that predicted the probability of CHD (known as "risk factors") stimulated hope that modification of these risk factors would reduce the frequency of CHD. Long before this idea was validated in clinical trials, individual physicians 2,3 and voluntary health agencies 4 began in the 1960s to promote the concept to the public. Many individuals accepted the idea, and many physicians adopted the recommendations in their practices.The US CHD mortality rate declined to approximately half its former level by 1990. 5 The associated favorable changes in risk factors accounted for about half of this decline, whereas improved treatment of CHD accounted for the other half. 6 The extent and severity of atherosclerosis also declined during this period. 7,8 CHD mortality continued to decline after 1990 but at a slower rate, and CHD remained the leading cause of death in the United States. 9 A convergence of evidence from diverse sources in the last 2 decades now indicates that the claim that we can prevent 90% of CHD should no longer be thought of as outrageous but as achievable. For example, the absence of the major established CHD risk factors at 50 years of age has been shown to indicate a 90% lower lifetime risk (to age 95 years) for men and a 79% lower risk for women. 10 * Subjects in several large cohorts without any of the major risk factors who were followed up for 16 to 22 years had 77% to 92% lower (men) or 79% lower (women) CHD mortality. 11 † A mutation in PCSK9, a gene that regulates low-density lipoprotein (LDL) cholesterol, has been shown to result in a 28% reduction in LDL cholesterol and an 88% lower risk of CHD. 12 The present report reviews the benefits and limitations of CHD prevention efforts in adults and attempts to expand prevention efforts to young people. We summarize evidence showing that CHD risk factors are associated with both the early and advanced stages of atherosclerosis. This evidence supports the need to maintain a low lifetime risk by preventing development of risk factors in youth or controlling risk factors if they do develop, measures that will prevent atherosclerosis and thereby prevent CHD. Risk Factor Control in Adults Reduces but Does Not Eliminate CHDA number of controlled clinical trials of fat-modified diets 13 and drugs 14 yielded mixed results, but ultimately, modification of individual risk factors in adults was shown to reduce CHD risk. Cholestyramine was proven to lower LDL cholesterol levels and reduce CHD incidence 15 ; a decade later, a statin was shown to lower LDL cholesterol and CHD incidence more effectively. 16 Smoking cessation has also been shown to reduce the incidence of CHD. 17 Pharmacological treatment of hypertension lowers both the incidence of CHD and the incidence of is...

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“…mg/day for those aged 14-18 years. 4 Reduction in LDL-C levels varies from 21 to 41%. 2 Rosuvastatin, a new statin, proved to be effective and safe in the treatment against hyperlipidemia in adults with primary dyslipidemia, though studies with children are currently lacking.…”

Section: New Recommendations For Drug Treatment Of Children and Adolementioning

confidence: 99%

“…This plaque, depending on its stability, may cause ischemic and thrombotic events, such as coronary heart disease and acute myocardial infarction, respectively. 4 Studies on atherosclerosis began through autopsies of young individuals killed in combat. In individuals at mean age 22 years, 45% of the autopsies showed evidence of coronary atherosclerosis, and 5% of these at a severe stage.…”

Section: Introductionmentioning

confidence: 99%

Prevenção da aterosclerose e tratamento medicamentoso de anormalidades lipídicas de alto risco em crianças e adolescentes

Castro¹,

Oliveira²

2009

J. Pediatr. (Rio J.)

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Objective: To discuss risk factors of atherosclerosis in pediatrics, dietary and physical activity guidelines, and, mainly, drug treatment of high-risk lipid abnormalities.Sources: Data were obtained from articles indexed in MEDLINE, published over the last 5 years. Summary of the findings:Children with severe dyslipidemia or additional risk factors such as family history of early cardiovascular disease or other signs of metabolic syndrome may need treatment with hypolipidemic drugs. New recommendations from the U.S. guidelines indicate drug treatment before the age of 10 years according to the magnitude of the additional risk factors for cardiovascular disease. Pediatricians should know when to diagnose dyslipidemia, when to indicate drug treatment and which medication can be used in children and adolescents with the least risk or harm to their development. Conclusions:The first-line treatment of dyslipidemia consists of lifestyle changes, focusing on prevention. Children with high-risk lipid abnormalities should be considered for drug treatment. Decisions to be made together with the parents must be evaluated taking into consideration risks and benefits of the medication to the patient.

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The Use of Statins in Pediatrics: Knowledge Base, Limitations, and Future Directions

Cited by 60 publications

References 103 publications

Etiology and management of dyslipidemia in children with chronic kidney disease and end-stage renal disease

Etiology and management of dyslipidemia in children with chronic kidney disease and end-stage renal disease

Preventing Heart Disease in the 21st Century

Prevenção da aterosclerose e tratamento medicamentoso de anormalidades lipídicas de alto risco em crianças e adolescentes

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