Clinical Briefs in Primary Care
Have people with HTN reduced salt intake?
Source: Ayala C, et al. Actions taken to reduce sodium intake among adults with self-reported hypertension. J Clin Hypertens2010;12:793-799.
The most recent advice from the U.S. Department of Agriculture (2005) recommends that the general population of adults not consume > 2300 mg/day of sodium, and that persons with hypertension (HTN) consume ≤ 1500 mg/day. In contrast to these recommendations, NHANES data from 2005-2006 indicate that U.S. adults consume essentially 1.5 times the recommended ceiling. One would hope that with all the health information available to consumers that persons with HTN would be particularly attuned to restricting their sodium intake, especially as awareness and treatment of HTN have increased over the last two decades.
The HealthStyles survey is sent annually to thousands of randomly selected homes in the United States by an international research organization. Surveys in 2005 (n = 6168) and 2008 (n = 7000) from non-pregnant adults who self-identified as hypertensive and also as having received advice from their clinician to reduce salt intake were analyzed for responses to questions about their sodium habits.
Over the 3-year interval, the percentage of adults who reported reading food labels increased from 49.1% to 53.0%; persons who reduced the amount of sodium in their diet increased from 48.3% to 56.6%. Overall, women more often read food labels than men, and blacks more often than Hispanics or whites.
Lifestyle intervention can have a meaningful impact on an individual- or population-wide basis. Although it is encouraging to note that a majority of adults with HTN currently do read food labels for sodium content, and have reduced their sodium intake, there remains much room for more widespread adoption of such potentially healthful habits.
The P450 system and CV outcomes with clopidogrel
Source: Pare G, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med 2010;363:1704-1714.
A great deal of controversy has surrounded the clinical relevance of the P450 system and efficacy of clopidogrel. The basic story line is as follows: To reduce CV events in persons with atrial fibrillation or post-ACS, clopidogrel must reduce platelet aggregation. This inhibition of platelet aggregation (IPA) is dependent not upon clopidogrel itself, but on a metabolite of clopidogrel, which is generated through the CYP2C19 pathway. In vitro, it is clear that genetic variations in CYP2C19 activity can impact IPA: Loss-of-function genetic alleles have been shown to produce reduced IPA in vitro. Similarly, things that block activity of the CYP2C19 system also reduce IPA in vitro. End of story? Not so fast.
Initial retrospective studies reported a concerning increase in events in person on clopidogrel who were concomitantly receiving CYP2C19-inhibiting proton pump inhibitors. Two subsequent prospective analyses, however, failed to demonstrate reduced efficacy when clopidogrel and PPI were used concomitantly.
This study compared CV outcomes in post-ACS or atrial fibrillation subjects (total n = 5059) who had undergone genetic testing and been found to have a variety of genetic CYP2C19 loss-of-function variants. No meaningful impact of CYP2C19 genotype upon CV outcomes (or bleeding risk) was found.
For the time being, use of CYP2C19 genotyping does not seem to help us decide how to better provide IPA for our patients. Whether this reflects inaccuracy of currently available testing methods, recognition that other forces are at play beyond simple aggregation of platelets, or other as-yet undefined issues remains to be determined.
Risk assessment for bleeding during warfarin therapy
Source: Pisters R, et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation. Chest 2010;138:1093-1100.
The Chads2 score has proven to be very useful in stratifying risk of stroke for patients with atrial fibrillation (AF). The risk reduction for stroke provided by warfarin anticoagulation in AF is about 66%. Yet, at lower baseline risks (e.g., CHADS2 score 0-1), the risk of bleeding starts to counterbalance stroke risk reduction. To date, there has been no comparably simple tool to predict risk of bleeding while on warfarin.
HAS-BLED incorporates seven readily available risk factors to predict bleeding risk from warfarin in persons with AF with the following number of points: hypertension (1 point), abnormal renal/hepatic function (1 point each), stroke (1 point), bleeding history/diathesis (1 point), labile INR (1 point), elderly > 65 (1 point), and drugs/alcohol use (1 point each). Whenever the HAS-BLED score is greater than the CHADS score, bleeding risk may outweigh clinical benefit. Clinicians may want to consider refining their bleeding risk prediction for patients with potential indications for warfarin based upon the HAS-BLED stratification tool.
Coenzyme Q10 for Peyronie's disease
Source: Safarinejad MR. Safety and efficacy of coenzyme Q10 supplementation in early chronic Peyronie's disease. Int J Impot Res 2010;22:298-309.
Peyronie's disease is an uncommon penile fibrotic disorder that most commonly affects young and middle-aged men. It is characterized by pain, deformity, or decreased capacity for intromission as a result of penile angulation. In contrast to chordee, the congenital abnormality in which ventral penile tissue defects prevent full expansion of the underside of the penis, resulting in a downward curvature upon erection, Peyronie's disease is an acquired fibrosis of the penis, which results in thickened penile plaques that prevent full erection. In whatever area of the penis such fibrotic plaques occur, that area will be unable to achieve full dilation and erection, resulting in angulation of the penis. There is no uniformly effective treatment for Peyronie's disease, although surgical correction is often effective.
Fibrotic plaque analysis in Peyronie's disease has demonstrated early oxidative inflammation, followed by creation of fibrotic scar. Since coenzyme Q10 has been shown to have antioxidant capacity, a clinical trial of its efficacy in early Peyronie's was intuitively appealing.
Men with early Peyronie's disease (n = 186) were randomized to coenzyme Q10 300 mg/day or placebo for 24 weeks. At trial end, there was a statistically significant reduction in plaque size, penile curvature, and improvement in sexual function in the active treatment group. Because coenzyme Q10 is a very well tolerated intervention with no known serious adverse effects (there were no reported drug-related adverse events or discontinuations), it offers a promising alternative for persons with Peyronie's disease.
Impact of using A1c to diagnose pre-diabetes
Source: Mann DM, et al. Impact of A1c screening criterion on the diagnosis of pre-diabetes among U.S. adults. Diabetes Care 2010;33:2190-2195.
The dramatic increase in type 2 diabetes (DM2) seen in the last decade is predictably going to become even more evident: Although 24 million Americans currently have DM2, more than twice as many have pre-diabetes (p-DM2). Historically, persons with p-DM2 who are untreated progress to frank DM2 at a rate of 7%-10% per year.
Until 2010, p-DM2 was diagnosed based upon the presence of either impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both. Since 2010, the ADA has indicated that an A1c of 5.7%-6.4% qualifies as p-DM2. This tool has been welcomed by the primary care community because it does not require fasting, and can be obtained during any routine office visit. The limitation of A1c, however, is that it does not necessarily capture all the persons who would have been identified had either a fasting blood glucose or postprandial glucose (or both) been obtained; data from NHANES indicate that a substantial number of persons with IFG will not have an abnormal A1c, and vice versa. For instance, of 51.7 million NHANES subjects with IFG, only 23 million have an A1c that meets p-DM2 criteria.
All of the diagnostic markers for p-DM2 are used in an effort to identify the pathophysiologic derangements at a point in time where intervention might change disease progression. IFG, IGT, and A1c identify overlapping, but not identical, populations. Because clinicians will commonly have access to fasting glucose levels obtained concomitantly with other labs (e.g., CMP), it appears that few cases of p-DM2 will be missed by utilizing an A1c measurement.
Should tiotropium be a maintenance asthma medication?
Source: Peters SP, et al. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med 2010;363:1715-1726.
Traditional maintenance pharmacotherapy for persistent asthma includes inhaled corticosteroids (ICS), leukotriene modulators, andwhen used concomitantly with ICSlong-acting beta agonists (LABA). Except for the acute care setting, anticholinergic treatment, like tiotropium (TIO) has been generally thought of as a treatment for COPD rather than asthma.
Peters et al performed a double-blind, crossover trial in asthmatics (n = 210) who were poorly controlled on ICS alone. As add-on treatment, patients were randomized to tiotropium (ICS + TIO), the long-acting beta agonist salmeterol (ICS + LABA), or a doubling of ICS (ICS + ICS).
ICS + TIO was found to be superior to ICS + ICS for morning peak expiratory flow (the primary endpoint of the trial). ICS + TIO was demonstrated to be non-inferior to ICS + LABA for morning peak expiratory flow, prebronchodilator FEV1, and proportion of asthma-control days (the secondary endpoint of the trial). These results support the consideration of TIO as a maintenance medication for asthma when used in conjunction with ICS. Because the study duration was brief (14 weeks), the durability of anticholinergic treatment for asthmafor instance, is TIO useful in preventing asthma exacerbations?remains to be determined.Have people with HTN reduced salt intake?; The P450 system and CV outcomes with clopidogrel; Risk assessment for bleeding during warfarin therapy; Coenzyme Q10 for Peyronie's disease; Impact of using A1c to diagnose pre-diabetes; Should tiotropium be a maintenance asthma medication?
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