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By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Sucampo Pharmaceuticals, Takeda, Boehringer Ingelheim; and is a consultant and on the speaker's bureau for Novo Nordisk, Lilly, Daiichi Sankyo, Forest Pharmaceuticals, Cephalon, Novartis, and Sanofi Aventis.
Getting the most bang for your buck: Predictive value of lipid measurements
Source: The Emerging Risk Factors Collaboration. Major lipids, apolipo-proteins, and risk of vascular disease. JAMA 2009;302:1993-2000.
The emerging risk factors colla-boration collected data from prospective observational studies of persons without CV disease at baseline (n = 69 studies, with 302,430 participants). Lipid fractions measured in these studies included LDL, HDL, apo B, and apo A1. Risk for incurring CV endpoints was stratified for each lipid fraction.
Triglycerides have always been the lipid fraction demonstrating the weakest association with CVD endpoints. In this data set, although the unadjusted hazard ratio for triglycerides demonstrated increased hazard, adjusted hazard ratios were not convincing. In contrast, subjects with the lowest HDL levels showed an almost 3-fold greater hazard ratio for CV events than those in the highest third. The ratio of apo B:apo A1 was also an important CV risk predictor.
Interestingly, measurement of total cholesterol, HDL, apo B, and apo A1 in the non-fasting state did not appear to appreciably alter their predictive value. Sufficient information for risk prediction, according to these data, is obtained by simply measuring cholesterol levels (total and HDL). Additionally, the authors were not able to identify any significant additional CV risk prediction by adding triglyceride levels to their calculations.
The simplicity of focusing upon total and HDL cholesterol, and being able to use non-fasting results, may enable clinicians to more readily gather predictive information on a wider population of patients.
Nortriptyline, gabapentin, or both for neuropathic pain
Source: Gilron I, et al. Nortriptyline and gabapentin, alone and in combination for neuropathic pain: A double-blind, randomised controlled crossover trial. Lancet 2009;374:1252-1261.
Neuropathic pain (npn), such as post-herpetic neuralgia or diabetic peripheral neuropathic pain, often requires what has been described as rational polypharmacy: the combination of multiple agents in an attempt to gain maximum therapeutic advantage while minimizing adverse effects. Both nortriptyline and gabapentin have achieved some success in modulation of NPN as monotherapy. Since the mechanism of action of these agents is complementary, a trial of their combination has intellectual appeal. When choosing among antidepressants for analgesic effects, norepinephrine re-uptake inhibition appears to be a critical component. Hence, SSRIs have minimal effect, but tricyclics (e.g., amitriptyline, nortriptyline), SNRIs (e.g., duloxetine, venlafaxine), and highly selective norepinephrine re-uptake inhibitors (e.g., milnacipran) effectively reduce pain.
Combination nortriptyline and gabapentin provided significantly greater pain reduction than either agent alone. No serious adverse effects were seen in either mono- or combination therapy. Clinicians are already commonly applying combination therapies to neuropathic pain syndromes; it is gratifying to encounter sound evidence supporting this practice.
The relationship of fasting plasma glucose and A1c to diabetic retinopathy
Source: Cheng YJ, et al. Association of A1C and fasting plasma glucose levels with diabetic retinopathy prevalence in the U.S. population. Diabetes Care 2009;32:2027-2032.
The idea that A1c might be a reasonable metric to make the diagnosis of diabetes has been kicking around for more than a decade. Only very recently has there been advocacy from the American Diabetes Association that hemoglobin A1c (A1c) may be an acceptable method for diagnosis of diabetes (A1c 3 6.2%); a primary reason for this shift in perception is the widespread adoption of a nationally standardized A1c testing method. Ultimately, diagnosis is intended to go beyond simply categorizing an individual as diabetic or non-diabetic; rather, it is intended to predict risk for important complications of diabetes like retinopathy.
The NHANES (National Health and Nutrition Examination Survey) is a cross-sectional sampling of non-institutionalized civilian adults. From the NHANES 2005-2006 study population, a group of adults age 3 40 years had assessment of retinopathy, A1c, and fasting plasma glucose (FPG).
There was a steep increase in frequency of retinopathy at an A1c 3 5.5%. Although a similar increased risk was seen at a FPG of 126 mg/dL, overall, the A1c was a better predictor than FPG. Since A1c may be obtained whether or not the subject has fasted, it may become a more convenient (as well as more sensitive) method than FPG for identifying risk of retinopathy.