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Perspective
Statins: Is It Really Time to Reassess Benefits and Risks?
No drug provides health benefits without some degree of risk, and risk–benefit assessments require ongoing review as new data become available. This is certainly the case for the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors — statins — and the risk of new-onset…
- May 10, 2012
- Goldfine A.B.
- N Engl J Med 2012; 366:1752-1755
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The Food and Drug Administration has added information to statin labels regarding an effect on diabetes, noting reported increases in glycated hemoglobin and fasting serum glucose levels but adding that it believes that the cardiovascular benefits outweigh the risks.
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Clinical Implications of Basic Research
The Monocyte in Atherosclerosis — Should I Stay or Should I Go Now?
Generations of evolutionary pressure have honed a human immune system that is well poised to combat infectious challenges. However, the very same system can turn against us when it is activated by certain noxious stimuli, as is the case with cholesterol-laden meals triggering atherosclerosis.…
- May 3, 2012
- Gerszten R.E. and Tager A.M.
- N Engl J Med 2012; 366:1734-1736
The accrual of cholesterol-laden macrophages in the atherosclerotic plaque is a critical event that precedes plaque rupture. The guidance molecule netrin-1 mediates this accrual in a mouse model of atherosclerosis.
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Original Article
Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol
In 2003, Abifadel and colleagues described two families with autosomal dominant hypercholesterolemia that was associated with gain-of-function mutations in proprotein convertase subtilisin/kexin 9 (PCSK9), one of the serine proteases. These patients had high plasma levels of low-density lipoprotein…
- March 22, 2012
- Stein E.A., Mellis S., Yancopoulos G.D., et al.
- N Engl J Med 2012; 366:1108-1118
A monoclonal antibody to PCSK9 was studied in two single-dose trials in healthy volunteers and one multiple-dose trial in patients with familial or nonfamilial hypercholesterolemia. In all three groups, the antibody reduced levels of LDL cholesterol.
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Editorial
Lowering Plasma Cholesterol by Raising LDL Receptors — Revisited
Thirty-one years ago, Mabuchi and colleagues reported in the Journal that a statin called compactin reduced plasma low-density lipoprotein (LDL) cholesterol levels by 29% in patients with heterozygous familial hypercholesterolemia. This drug inhibits an early step in cholesterol synthesis catalyzed…
- March 22, 2012
- Young S.G. and Fong L.G.
- N Engl J Med 2012; 366:1154-1155
Thirty-one years ago, Mabuchi and colleagues¹ reported in the Journal that a statin called compactin reduced plasma low-density lipoprotein (LDL) cholesterol levels by 29% in patients with heterozygous familial hypercholesterolemia. This drug inhibits an ...
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Images in Clinical Medicine
Eruptive Xanthoma
Figure 1.
- March 1, 2012
- Kala J. and Mostow E.N.
- N Engl J Med 2012; 366:835
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A 30-year-old woman with diabetes who had poor glucose control, hypertension, and hyperlipidemia was referred for evaluation of a rash of 1 month's duration. She reported no fevers, chills, or joint pain, nor had she taken glucocorticoids or had contact with anyone with similar symptoms.
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Perspective
Interpreting the Coronary-Artery Calcium Score
A 55-year-old white man presented with an abnormal coronary-artery calcium (CAC) score. He exercised regularly and was asymptomatic. There was no family history of premature coronary artery disease (CAD). He was not overweight, had never smoked, and did not have diabetes. His blood pressure was 122/…
- January 26, 2012
- Grayburn P.A.
- N Engl J Med 2012; 366:294-296
Though coronary-artery calcium scoring is not helpful in screening for coronary artery disease in many cases, it's advertised to consumers, and those with positive scores are told to see their physician. How should physicians interpret the scores and counsel patients?
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Perspective
Generic Atorvastatin and Health Care Costs
Lipitor (atorvastatin) was the top-selling prescription medication in the United States in 2010, earning its manufacturer, Pfizer, more than $7 billion in total revenue. The overall market for prescription lipid-lowering drugs continues to grow; this drug class had greater prescription volume than…
- January 19, 2012
- Jackevicius C.A., Chou M.M., Ross J.S., Shah N.D., Krumholz H.M.
- N Engl J Med 2012; 366:201-204
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Lipitor (atorvastatin) was the top-selling prescription drug in the United States in 2010, but its patent expired in June 2011, and the first generic version entered the market on November 30. What economic impact will the availability of generic atorvastatin have?
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Review Article
Mechanisms of Disease: Proprotein Convertases in Health and Disease
Secretory proteins, such as hormones, enzymes, and receptors, constitute a broad group of biochemically active molecules that are essential for cellular function. Post-translational processing of their precursor molecules, which occurs through endoproteolytic cleavage, results in the formation of…
- December 29, 2011
- Artenstein A.W. and Opal S.M.
- N Engl J Med 2011; 365:2507-2518
Proteases that process larger precursor proteins into smaller functional proteins are involved in a wide range of physiologic processes. Derangements in the function of these enzymes play a role in many diseases.
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Original Article
Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy
More than 18 million North Americans have coronary heart disease, and despite profound advances in both pharmacologic and interventional management, both morbidity and mortality remain appreciable. Elevated low-density lipoprotein (LDL) cholesterol levels are an established predictor of the risk of…
- December 15, 2011
- The AIM-HIGH Investigators
- N Engl J Med 2011; 365:2255-2267
- CME
In this clinical trial involving patients with established cardiovascular disease, the addition of niacin to intensive statin therapy provided no additional clinical benefit over a period of 3 years, despite favorable changes in lipid levels.
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Perspective
Needed: Pragmatic Clinical Trials for Statin-Intolerant Patients
Statins are the most commonly prescribed drugs for lowering low-density lipoprotein (LDL) cholesterol levels. They've been amply studied in phase 3, randomized clinical trials and have been shown in primary and secondary prevention trials to reduce the risk of cardiovascular events. Statin use has…
- December 15, 2011
- Maningat P. and Breslow J.L.
- N Engl J Med 2011; 365:2250-2251
Statins have adverse effects, but it's difficult to design randomized trials of alternative therapies for statin-intolerant patients. Pragmatic clinical trials, performed in the context of usual care with broad eligibility criteria, are well suited to this purpose.
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Editorial
Niacin at 56 Years of Age — Time for an Early Retirement?
A reduction in serum cholesterol with niacin therapy in humans was first described in 1955, when Altschul and colleagues reported, in a letter to the editor, the findings in 11 healthy medical students and 57 patients. Subsequent clinical studies showed multiple favorable effects of niacin therapy…
- December 15, 2011
- Giugliano R.P.
- N Engl J Med 2011; 365:2318-2320
A reduction in serum cholesterol with niacin therapy in humans was first described in 1955, when Altschul and colleagues reported, in a letter to the editor, the findings in 11 healthy medical students and 57 patients.¹ Subsequent clinical studies showed ...
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Review Article
Genomic Medicine: Genomics of Cardiovascular Disease
Cardiovascular disease is the leading cause of death in the United States. Considerable progress has been made in the past 50 years to define, identify, and modify risk factors for cardiovascular disease (e.g. hypertension, dyslipidemia, obesity, type 2 diabetes, cigarette smoking, and physical…
- December 1, 2011
- O'Donnell C.J. and Nabel E.G.
- N Engl J Med 2011; 365:2098-2109
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The authors provide an overview of how genetic and genomic studies have improved our understanding of the cause of cardiovascular disease.
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Original Article
Effect of Two Intensive Statin Regimens on Progression of Coronary Disease
Randomized clinical trials have consistently shown that inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) reduce cardiovascular event rates.– The favorable effects of statins extend across a range of levels of low-density lipoprotein (LDL) cholesterol, with no apparent lower…
- December 1, 2011
- Nicholls S.J., Ballantyne C.M., Barter P.J., et al.
- N Engl J Med 2011; 365:2078-2087
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In this trial, intravascular ultrasonography was used to compare the effects of atorvastatin versus rosuvastatin on regression of coronary atherosclerosis. Both statins led to regression in two thirds of patients, with no significant difference between their effects.
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Original Article
Childhood Adiposity, Adult Adiposity, and Cardiovascular Risk Factors
During the past three decades, the prevalences of overweight and obesity in the pediatric population have increased substantially. Childhood obesity is a predictor of an increased rate of death, owing primarily to an increased risk of cardiovascular disease.– Forecasts suggest that the "obesity…
- November 17, 2011
- Juonala M., Magnussen C.G., Berenson G.S., et al.
- N Engl J Med 2011; 365:1876-1885
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- CME
In four prospective cohort studies, obese adults who were overweight or obese in childhood had increased rates of cardiovascular risk factors. Those who were overweight or obese as children but not as adults had risks similar to the risks among those who were never obese.
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Editorial
Childhood Obesity and Coronary Heart Disease
Obesity is the most common nutritional problem among children in both developed and underdeveloped countries. Despite efforts over the past decade to prevent and control obesity, data from the 2003–2006 National Health and Nutrition Examination Surveys (NHANES) show that 16.3% of children and…
- November 17, 2011
- Rocchini A.P.
- N Engl J Med 2011; 365:1927-1929
Obesity is the most common nutritional problem among children in both developed and underdeveloped countries. Despite efforts over the past decade to prevent and control obesity, data from the 2003–2006 National Health and Nutrition Examination Surveys (...
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Review Article
Mechanisms of Disease: The Human Plasma Lipidome
Cholesterol and triglyceride levels are now assessed routinely, and physicians regularly prescribe lipid-lowering drugs to patients found to have dyslipidemia. However, the increase in the number of patients with metabolic diseases (including type 2 diabetes and obesity, which are associated with…
- November 10, 2011
- Quehenberger O. and Dennis E.A.
- N Engl J Med 2011; 365:1812-1823
Biochemical analyses reveal that plasma contains over 600 structural forms of lipid molecules. This review summarizes known correlations between levels of lipid moieties and disease and describes potential therapeutic targets relevant to CVD, cancer, and neurologic disease.
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Perspective
Fibrates in the Treatment of Dyslipidemias — Time for a Reassessment
Lowering the concentration of low-density lipoprotein (LDL) cholesterol with statins substantially reduces the rate of cardiovascular events among patients with underlying cardiovascular disease or other risk factors. Yet a substantial risk persists, suggesting that additional lipid-modifying…
- August 11, 2011
- Goldfine A.B., Kaul S., Hiatt W.R.
- N Engl J Med 2011; 365:481-484
No clinical benefit from modulating high triglyceride levels and low high-density–lipoprotein cholesterol levels with fibrates has been firmly established, though benefit for patients with diabetes and mixed dyslipidemia remains possible.
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Perspective
Weighing the Benefits of High-Dose Simvastatin against the Risk of Myopathy
Statins are the most widely prescribed class of drugs for treating dyslipidemia — in particular, elevated levels of low-density lipoprotein (LDL) cholesterol. Nearly 20 years of research provide convincing evidence that statin-related reductions in LDL cholesterol decrease the risk of major…
- July 28, 2011
- Egan A. and Colman E.
- N Engl J Med 2011; 365:285-287
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Having reviewed the data on the risk of myopathy, the FDA recommends that the 80-mg dose of simvastatin be used only in patients who have been taking this dose for an extended period without signs or symptoms of clinically significant muscle toxicity.
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Review Article
Drug Therapy: n–3 Fatty Acids in Cardiovascular Disease
Cardiovascular disease is the leading cause of death worldwide, and preventive approaches, particularly achievable dietary changes, have major public health implications. An increased dietary intake of n–3 (polyunsaturated) fatty acids is one such dietary approach. This review discusses advances…
- June 23, 2011
- De Caterina R.
- N Engl J Med 2011; 364:2439-2450
CVD is the leading cause of death worldwide; preventive approaches can have major public health implications. An increased dietary intake of n–3 fatty acids is one such approach. This review discusses current knowledge of n–3 fatty acids.
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Review Article
Mechanisms of Disease: The Hemostatic System as a Modulator of Atherosclerosis
Cardiovascular disease is one of the leading causes of death and complications worldwide. The classic concept of atherosclerosis assigns a pivotal role to inflammation in the onset and progression of this disease. Various inflammatory cell types (e.g. macrophages, neutrophils, and lymphocytes) play…
- May 5, 2011
- Borissoff J.I., Spronk H.M.H., ten Cate H.
- N Engl J Med 2011; 364:1746-1760
Experimental data suggest that the hemostatic system can accelerate plaque vulnerability to thrombosis in vivo. However, clinical support for these findings remains weak. This comprehensive summary reviews the evidence.
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Medical Meetings Pediatrics Conferences and Meetings

2012 Certifying Examinations of the American Board of Pediatrics

The general pediatrics examination will be held in various cities, Oct. 16-18. Registration for first-time applicants is ongoing through May 3. Registration for re-registrants is ongoing through May 24. The following subspecialty examinations will be held in various cities: "Hospice and Palliative Medicine" (Oct. 4); "Pediatric Transplant Hepatology" (Oct. 11); "Pediatric Cardiology" (Nov. 7); "Pediatric Pulmonology" (Nov. 8); "Medical Toxicology" (Nov. 12); and "Pediatric Critical Care Medicine" (Nov. 14). Registration for first-time applicants is ongoing through April 30. Registration for re-registrants is ongoing through June 15.

Contact the American Board of Pediatrics, 111 Silver Cedar Court, Chapel Hill, NC 27514-1513; or call (919) 929-0461; or fax (919) 918-7114 or (919) 929-9255; or see http://www.abp.org .

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