Efficacy and safety of statin therapy in Children with familial hypercholesterolemia: A randomized controlled trial
TL;DR: Two years of pravastatin therapy induced a significant regression of carotid atherosclerosis in children with familial hypercholesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.
Abstract: ContextChildren with familial hypercholesterolemia have endothelial dysfunction
and increased carotid intima-media thickness (IMT), which herald the premature
atherosclerotic disease they develop later in life. Although intervention
therapy in the causal pathway of this disorder has been available for more
than a decade, the long-term efficacy and safety of cholesterol-lowering medication
have not been evaluated in children.ObjectiveTo determine the 2-year efficacy and safety of pravastatin therapy in
children with familial hypercholesterolemia.DesignRandomized, double-blind, placebo-controlled trial that recruited children
between December 7, 1997, and October 4, 1999, and followed them up for 2
years.Setting and ParticipantsTwo hundred fourteen children with familial hypercholesterolemia, aged
8 to 18 years and recruited from an academic medical referral center in the
Netherlands.InterventionAfter initiation of a fat-restricted diet and encouragement of regular
physical activity, children were randomly assigned to receive treatment with
pravastatin, 20 to 40 mg/d (n = 106), or a placebo tablet (n = 108).Main Outcome MeasuresThe primary efficacy outcome was the change from baseline in mean carotid
IMT compared between the 2 groups over 2 years; the principal safety outcomes
were growth, maturation, and hormone level measurements over 2 years as well
as changes in muscle and liver enzyme levels.ResultsCompared with baseline, carotid IMT showed a trend toward regression
with pravastatin (mean [SD], −0.010 [0.048] mm; P = .049), whereas a trend toward progression was observed in the placebo
group (mean [SD], +0.005 [0.044] mm; P = .28). The
mean (SD) change in IMT compared between the 2 groups (0.014 [0.046] mm) was
significant (P = .02). Also, pravastatin significantly
reduced mean low-density lipoprotein cholesterol levels compared with placebo
(−24.1% vs +0.3%, respectively; P<.001).
No differences were observed for growth, muscle or liver enzymes, endocrine
function parameters, Tanner staging scores, onset of menses, or testicular
volume between the 2 groups.ConclusionTwo years of pravastatin therapy induced a significant regression of
carotid atherosclerosis in children with familial hypercholesterolemia, with
no adverse effects on growth, sexual maturation, hormone levels, or liver
or muscle tissue.
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01 Jan 2014
TL;DR: These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care.
Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.
9,618 citations
TL;DR: These standards of care are intended to provide clinicians, patients, researchers, payers, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care.
Abstract: D iabetes mellitus is a chronic illness that requires continuing medical care and ongoing patient self-management education and support to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payers, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. Specifically titled sections of the standards address children with diabetes, pregnant women, and people with prediabetes. These standards are not intended to preclude clinical judgment or more extensive evaluation and management of the patient by other specialists as needed. For more detailed information about management of diabetes, refer to references 1–3. The recommendations included are screening, diagnostic, and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A large number of these interventions have been shown to be cost-effective (4). A grading system (Table 1), developed by the American Diabetes Association (ADA) andmodeled after existingmethods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E. These standards of care are revised annually by the ADA’s multidisciplinary Professional Practice Committee, incorporating new evidence. For the current revision, committee members systematically searched Medline for human studies related to each subsection and published since 1 January 2010. Recommendations (bulleted at the beginning of each subsection and also listed in the “Executive Summary: Standards of Medical Care in Diabetesd2012”) were revised based on new evidence or, in some cases, to clarify the prior recommendation or match the strength of the wording to the strength of the evidence. A table linking the changes in recommendations to new evidence can be reviewed at http:// professional.diabetes.org/CPR_Search. aspx. Subsequently, as is the case for all Position Statements, the standards of care were reviewed and approved by the ExecutiveCommittee of ADA’s Board ofDirectors, which includes health care professionals, scientists, and lay people. Feedback from the larger clinical community was valuable for the 2012 revision of the standards. Readers who wish to comment on the “Standards of Medical Care in Diabetesd2012” are invited to do so at http://professional.diabetes.org/ CPR_Search.aspx. Members of the Professional Practice Committee disclose all potential financial conflicts of interest with industry. These disclosures were discussed at the onset of the standards revisionmeeting. Members of the committee, their employer, and their disclosed conflicts of interest are listed in the “Professional PracticeCommitteeMembers” table (see pg. S109). The AmericanDiabetes Association funds development of the standards and all its position statements out of its general revenues and does not utilize industry support for these purposes.
4,266 citations
TL;DR: These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care.
Abstract: D iabetes is a chronic illness that requires continuing medical care and ongoing patient self-management education and support to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude clinical judgment or more extensive evaluation and management of the patient by other specialists as needed. For more detailed information about management of diabetes, refer to references 1–3. The recommendations included are screening, diagnostic, and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was used to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E. These standards of care are revised annually by the ADA multidisciplinary Professional Practice Committee, and new evidence is incorporated. Members of the Professional Practice Committee and their disclosed conflicts of interest are listed in the Introduction. Subsequently, as with all position statements, the standards of care are reviewed and approved by the Executive Committee of ADA’s Board of Directors.
3,405 citations
TL;DR: The recommendations included are screening, diagnostic, and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes that have been shown to be costeffective.
2,862 citations
TL;DR: I. Screening and management of chronic complications in children and adolescents with type 1 diabetes i.e., screenings for type 2 diabetes and risk of future diabetes in adults, and strategy for improving diabetes care in the hospital, are outlined.
Abstract: I. CLASSIFICATION AND DIAGNOSIS OF DIABETES, p. S12 A. Classification of diabetes B. Diagnosis of diabetes C. Categories of increased risk for diabetes (prediabetes) II. TESTING FOR DIABETES IN ASYMPTOMATIC PATIENTS, p. S13 A. Testing for type 2 diabetes and risk of future diabetes in adults B. Testing for type 2 diabetes in children C. Screening for type 1 diabetes III. DETECTION AND DIAGNOSIS OF GESTATIONAL DIABETES MELLITUS, p. S15 IV. PREVENTION/DELAY OF TYPE 2 DIABETES, p. S16 V. DIABETES CARE, p. S16 A. Initial evaluation B. Management C. Glycemic control 1. Assessment of glycemic control a. Glucose monitoring b. A1C 2. Glycemic goals in adults D. Pharmacologic and overall approaches to treatment 1. Therapy for type 1 diabetes 2. Therapy for type 2 diabetes E. Diabetes self-management education F. Medical nutrition therapy G. Physical activity H. Psychosocial assessment and care I. When treatment goals are not met J. Hypoglycemia K. Intercurrent illness L. Bariatric surgery M. Immunization VI. PREVENTION AND MANAGEMENT OF DIABETES COMPLICATIONS, p. S27 A. Cardiovascular disease 1. Hypertension/blood pressure control 2. Dyslipidemia/lipid management 3. Antiplatelet agents 4. Smoking cessation 5. Coronary heart disease screening and treatment B. Nephropathy screening and treatment C. Retinopathy screening and treatment D. Neuropathy screening and treatment E. Foot care VII. DIABETES CARE IN SPECIFIC POPULATIONS, p. S38 A. Children and adolescents 1. Type 1 diabetes Glycemic control a. Screening and management of chronic complications in children and adolescents with type 1 diabetes i. Nephropathy ii. Hypertension iii. Dyslipidemia iv. Retinopathy v. Celiac disease vi. Hypothyroidism b. Self-management c. School and day care d. Transition from pediatric to adult care 2. Type 2 diabetes 3. Monogenic diabetes syndromes B. Preconception care C. Older adults D. Cystic fibrosis–related diabetes VIII. DIABETES CARE IN SPECIFIC SETTINGS, p. S43 A. Diabetes care in the hospital 1. Glycemic targets in hospitalized patients 2. Anti-hyperglycemic agents in hospitalized patients 3. Preventing hypoglycemia 4. Diabetes care providers in the hospital 5. Self-management in the hospital 6. Diabetes self-management education in the hospital 7. Medical nutrition therapy in the hospital 8. Bedside blood glucose monitoring 9. Discharge planning IX. STRATEGIES FOR IMPROVING DIABETES CARE, p. S46
2,827 citations
References
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TL;DR: Increases in the thickness of the intima and media of the carotid artery, as measured noninvasively by ultrasonography, are directly associated with an increased risk of myocardial infarction and stroke in older adults without a history of cardiovascular disease.
Abstract: Background The combined thickness of the intima and media of the carotid artery is associated with the prevalence of cardiovascular disease. We studied the associations between the thickness of the carotid-artery intima and media and the incidence of new myocardial infarction or stroke in persons without clinical cardiovascular disease. Methods Noninvasive measurements of the intima and media of the common and internal carotid artery were made with high-resolution ultrasonography in 5858 subjects 65 years of age or older. Cardiovascular events (new myocardial infarction or stroke) served as outcome variables in subjects without clinical cardiovascular disease (4476 subjects) over a median follow-up period of 6.2 years. Results The incidence of cardiovascular events correlated with measurements of carotid-artery intima–media thickness. The relative risk of myocardial infarction or stroke increased with intima–media thickness (P<0.001). The relative risk of myocardial infarction or stroke (adjusted for age ...
4,634 citations
TL;DR: In this paper, the authors determined whether greater carotid artery intima-media thickness (IMT) in asymptomatic individuals is associated with increased risk of coronary heart disease (CHD).
Abstract: Few studies have determined whether greater carotid artery intima-media thickness (IMT) in asymptomatic individuals is associated prospectively with increased risk of coronary heart disease (CHD). In the Atherosclerosis Risk in Communities Study, carotid IMT, an index of generalized atherosclerosis, was defined as the mean of IMT measurements at six sites of the carotid arteries using B-mode ultrasound. The authors assessed its relation to CHD incidence over 4-7 years of follow-up (1987-1993) in four US communities (Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland) from samples of 7,289 women and 5,552 men aged 45-64 years who were free of clinical CHD at baseline. There were 96 incident events for women and 194 for men. In sex-specific Cox proportional hazards models adjusted only for age, race, and center, the hazard rate ratio comparing extreme mean IMT (> or = 1 mm) to not extreme (< 1 mm) was 5.07 for women (95% confidence interval 3.08-8.36) and 1.85 for men (95% confidence interval 1.28-2.69). The relation was graded (monotonic), and models with cubic splines indicated significant nonlinearity. The strength of the association was reduced by including major CHD risk factors, but remained elevated at higher IMT. Up to 1 mm mean IMT, women had lower adjusted annual event rates than did men, but above 1 mm their event rate was closer to that of men. Thus, mean carotid IMT is a noninvasive predictor of future CHD incidence.
1,969 citations
"Efficacy and safety of statin thera..." refers background or methods in this paper
...Carotid IMT represents the combined intima and media thickness of the arterial wall, and numerous studies have shown that this surrogate marker of atherosclerotic vessel wall change is sensitive to risk intervention and constitutes a reliable indicator of clinical outcomes.(17-19)...
[...]
...Also, we used only a surrogate marker of future vascular disease and could not assess clinical end points, but solid evidence exists that changes in arterial wall IMT are predictive of cardiovascular outcome.(17-19) To limit IMT measurement variability, a single ultrasound machine was used, 1 experienced sonographer performed all ultrasonagraphy, and images were analyzed by a single reader....
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TL;DR: Estimates of body surface area were made based on measurement of 81 subjects, ranging from premature infants to adults, and closer agreement was obtained with the equations and nomograms of Body, Brody, Faber and Melcher, and Sendroy and Cecchini, although minor deviations were noted in some age ranges.
1,561 citations
TL;DR: This long-term follow-up of the Cholesterol Lowering Atherosclerosis Study cohort indicated that progression of coronary artery disease was predictive of coronary events, and the objective was to determine whether carotid arterial intima-media thickness predicts coronary events.
Abstract: Background: Carotid arterial intima-media thickness is used as a noninvasive surrogate end point to measure progression of atherosclerosis, but its relation to coronary events has not been fully ex...
1,226 citations
"Efficacy and safety of statin thera..." refers background or methods in this paper
...Carotid IMT represents the combined intima and media thickness of the arterial wall, and numerous studies have shown that this surrogate marker of atherosclerotic vessel wall change is sensitive to risk intervention and constitutes a reliable indicator of clinical outcomes.(17-19)...
[...]
...Also, we used only a surrogate marker of future vascular disease and could not assess clinical end points, but solid evidence exists that changes in arterial wall IMT are predictive of cardiovascular outcome.(17-19) To limit IMT measurement variability, a single ultrasound machine was used, 1 experienced sonographer performed all ultrasonagraphy, and images were analyzed by a single reader....
[...]
TL;DR: The results show that aggressive LDL-cholesterol reduction by atorvastatin was accompanied by regression of carotid intima media thickness in patients with familial hypercholesterolaemia, whereas conventional LDL lowering was not.
939 citations