Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Abbott, AstraZeneca, Boehringer Ingelheim, Daiichi, Sankyo, Forest Pharmaceuticals, Lilly, Novo Nordisk, Takeda.

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 Hypertens 2010;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 hypertension 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 persons 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.