Diagnosing Familial Combined Hyperlipidemia
Absolute apolipoprotein B levels along with triglyceride and total cholesterol measurements adjusted for age and gender are the best predictors of familial combined hyperlipidemia, said researchers in a report in this week’s issue of the journal Circulation (Circulation. 2004;109:2980–2985OpenUrl). It can be calculated by a nomogram and is a good predictor of cardiovascular risk in familial combined hyperlipidemia.
The researchers, led by Mario J. Veerkamp, MD, of University Medical Center Nijmegen, Nijmegen, the Netherlands, were in search of a better diagnostic tool after showing that the traditional method of total plasma cholesterol and/or triglyceride levels above the 90 percentile adjusted for age and gender was inaccurate in 26% of subjects during a 5-year period. In their study, they evaluated 299 subjects in 32 families in 1994 and 1999 for familial combined hyperlipidemia. They were considered to have the disorder when they met the traditional lipid criteria. However, the researchers also measured apolipoprotein B and small dense low-density lipoprotein at the same time.
They found that 40% or 121 subjects had familial combined hyperlipidemia. Using multivariate analysis, they found that absolute apolipoprotein B levels combined with levels of triglyceride and total cholesterol were the best predictors of the disorder.
“Using the proposed new diagnostic criteria included in a nomogram will make it easier to identify patients and test relatives to diagnose FCH [familial combined hyperlipidemia],” the authors wrote.
Liposuction Takes the Fat, Not the Abnormalities
Liposuction in the abdominal area can be used to reduce the percentage of fat in an area, but it does not reduce metabolic abnormalities associated with obesity, said researchers in a report in the June 17, 2004, issue of The New England Journal of Medicine (N Engl J Med. 2004;350:2549–2557OpenUrlCrossRefPubMed).
In the study led by Samuel Klein, MD, of Washington University School of Medicine in St Louis, Mo, the scientists enrolled 15 obese women. All underwent large-volume abdominal liposuction. The insulin sensitivity of liver, skeletal muscle, and adipose tissue were evaluated for insulin sensitivity. They also measured the levels of inflammatory mediators and coronary heart disease risk factors. The measurements were made first before the liposuction and then 10 to 12 weeks after the procedure. Eight of the women had normal glucose tolerance, and 7, type 2 diabetes.
The liposuction reduced the subcutaneous abdominal fat by 44% in the women with normal glucose tolerance and 28% in those with diabetes. The women with normal glucose tolerance lost an average of 9.1 kg of fat and those with type 2 diabetes 10.5 kg. Despite this, however, the procedure did not significantly alter insulin sensitivity in any of the tissue. Nor were the concentrations of C-reactive protein, interleukin-6, tumor necrosis factor, and adiponectin affected. Nor were any other heart disease risk factors such as blood pressure, plasma glucose, insulin, or lipid concentration affected. “However, fat removal by liposuction did decrease the plasma leptin concentration, which is a marker of adipose-tissue mass,” they wrote.
“The results of the present study suggest that abdominal liposuction should not, by itself, be considered a clinical therapy for obesity. Aspiration of large amounts of subcutaneous abdominal fat in women with abdominal obesity may have cosmetic benefits, but the procedure does not significantly improve insulin sensitivity in the liver, skeletal muscle, or adipose tissue; serum concentrations of markers of inflammation; or other risk factors for coronary heart disease. These findings offer important insights into the mechanisms responsible for the metabolic benefits observed with moderate diet-induced weight loss, which decreases hepatic and muscle fat content, fat-cell size, visceral fat mass, and circulating concentrations of proinflammatory cytokines,” they said.
In an accompanying perspective, David Kelley, MD, of the Obesity and Nutrition Research Center at the University of Pittsburgh Medical Center in Pennsylvania, wrote, “Amidst the growing public concern about the high prevalence of obesity and the interest within the medical community in developing effective treatments for obesity and its many health consequences, there has been a pronounced increase in the use of surgical approaches to weight loss and the removal of adipose tissue. It is important to ascertain the health benefits and risks of such surgical interventions. The clinical investigation by Klein et al provides useful objective evidence that even large-volume liposuction has little effect on insulin sensitivity or cardiovascular risk factors and offers a new perspective on the interaction between the loss of adiposity and a negative energy balance in mediating the salutary effect of weight-loss interventions for obesity” (N Engl J Med. 2004;350:2542–2543OpenUrlCrossRefPubMed).
Gene Variations Weaken Statins
People with 2 specific polymorphisms in the HMG-CoA reductase gene do not respond as well to treatment with statins designed to reduce overall cholesterol levels, said researchers from the Brigham and Women’s Hospital in Boston in a report in the July 16, 2004, issue of the Journal of the American Medical Association (JAMA. 2004;291:2821–2827OpenUrlCrossRefPubMed). These gene variations could explain the variations found in individual responses to treatment with statins, the researchers noted.
In the study, the researchers led by Daniel I. Chasman, PhD, of the Brigham and Women’s Hospital and Harvard Medical School evaluated 1536 individuals treated with 40 mg daily of pravastatin. The scientists evaluated their DNA for 148 single-nucleotide polymorphisms in 10 genes associated with lipid metabolism. They found 2 common and closely linked polymorphisms in the HMG-CoA reductase gene that were associated with a 22% smaller reduction in total cholesterol and a 19% smaller reduction in low-density lipoprotein cholesterol while the patients took the pravastatin. The therapy continued for 24 weeks during the study.
The researchers noted that the gene variations should be studied further to determine if the patients’ cholesterol could be reduced more if the statin dose is increased or if it is necessary to treat the patients with an alternative medicine designed to lower cholesterol levels.
Crestor (Rosuvastatin) Warning Issued
A revised package insert from Astra-Zeneca Pharmaceuticals for use in the 22 states of the European Union warns that certain patient populations may be at an increased risk of serious myopathy associated with use of the drug Crestor (rosuvastatin), particularly when it is taken in the highest dosage of 40 mg.
Although the US Food and Drug Administration noted that much of the new verbiage in the European label is already contained in the US packaging, the agency wants physicians to read the Crestor labels carefully and adhere closely to recommended starting doses, dose adjustments, and maximum daily doses to reduce the risks to patients. Crestor was approved for use in the United States in August 2003.
The United States approved labeling notes that patients aged 65 or older, those who are hypothyroid, and those who have kidney failure are at increased risk of developing myopathy in association with the use of a statin such as Crestor. The label warns that Crestor prescribing should be done cautiously, particularly in higher doses, in these patients. Also, Crestor poses an increased myopathy risk in certain populations such as some subgroups of Asians and those taking cyclosporine and gemfibrozil. For that reason, the drug is available in a 5-mg dose in the United States. That dosage may be used in patients who need less aggressive cholesterol lowering or who were taking concurrent cyclosporine. Patients with kidney failure and those on gemfibrozil should take no more than 10 mg of rosuvastatin daily. The Food and Drug Administration is not changing the rosuvastatin recommendations at this time.