ShortCuts-This Week in The Journals

June 25, 2007

PathCommentary By: Sean Cavanaugh MD, Associate Editor Clinical Correlations

Not much in the way of surprise, a lot of the articles in the press this past week focused on cardiovascular health.

In the Lancet, the results of the VALIDD trial (the acronyms are getting a bit ridiculous eh?) were published. Although it seems that valsartan was not more effective than other agents at improving diastolic dysfunction, it seems that lowering the blood pressure aggressively (using any agents) DID effectively improve diastolic functioning. Diastolic function in VALIDD was measured by tissue Doppler imaging, a relatively new echocardiographic technique that assesses the velocity of myocardial wall motion. Patients who entered into VALIDD were men and women aged ≥ 45 years with stage I or II hypertension (blood pressure ≥ 140/90 mm Hg). All patients were screened at baseline for diastolic dysfunction on the basis of mitral annular relaxation velocities. An accompanying editorial points out that inhibitors of the rennin-angiotensin-aldosterone system could very well have particular benefit in people with more severe hypertension, particularly those with left ventricular hypertrophy.

A new analysis of the Strong Heart Study data published early online in Circulation reported that wall-motion abnormalities detected by echocardiography can identify adults with no clinically recognized CVD who are more likely to go on to have cardiovascular events or die of CV disease. The association between wall-motion abnormalities and increased morbidity and mortality was independent of established risk factors. In Cox regression analyses, segmental wall-motion abnormalities were associated with a 2.5-fold increase in cardiovascular events and a slightly higher increase of CV death, even after adjustment for age, gender, systolic blood pressure, waist/hip ratio, and diabetes. Global wall-motion abnormalities carried an apparent 2.4-fold higher risk of cardiovascular events, while the risk of CV death was associated with a hazard ratio of 3.4, after similar adjustment for confounding factors.

Along these lines (with an eye on the future), a multivariate analysis of a study using a five pound, hand-held echocardiography device determined that left atrial volume predicted the risk of cardiovascular events beyond that suggested by clinical history and physical exam (the only one of four echocradiographic parameters studied with independent prognostic value. The other parameters were: LV Mass, LV Diastolic Function, LV Ejection Fraction). The patients were prospectively followed for a year, and the primary endpoints were first cardiovascular event or cardiovascular death. Another study presented at the same conference demonstrated the efficacy of a five-minute echocardiography exam in spotting athletes with a potentially life-threatening heart abnormality. The echo exam consisted of the parasternal long axis, the parasternal short axis at the level of the aortic valve and the mid-left ventricle, an apical four-chamber view, and an apical five-chamber view. Although predictable, the results of this study were the first to demonstrate the value of such a short echo exam.

The New England Journal of Medicine reported on an ancillary substudy of the Women’s Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy. It seems that the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. This is a new twist, and a point for this specific hormone replacement therapy in the perpetual debate over the risks and benefits of such; however, these radiologic findings do not necessarily translate into clinical benefit: estrogen, it was noted, has complex biologic effects and may unduly influence the risk of cardiovascular events and other outcomes through multiple pathways.

On a very different note, The New England Journal reported an observation that Entecavir, a drug approved by the Food and Drug Administration for the treatment of chronic hepatitis B virus (HBV) infection, and previously not believed to inhibit replication of human immunodeficiency virus type 1 (HIV-1) at clinically relevant doses, led to a consistent 1-log10 decrease in HIV-1 RNA in three persons with HIV-1 and HBV coinfection. Supportive in vitro evidence suggests that entecavir is a potent partial inhibitor of HIV-1 replication. Of concern was that analysis showed that in one of these patients, entecavir monotherapy led to an accumulation of HIV-1 variants with the lamivudine-resistant mutation, M184V; in vitro experiments showed that M184V confers resistance to entecavir. And while entecavir may become a useful adjunct in patients who are being co-treated for HIV and HBV, until more is known about HIV-1–resistance patterns and their selection by entecavir, caution is needed with the use of entecavir in persons with HIV-1 and HBV coinfection who are not receiving fully suppressive antiretroviral regimens.

And finally, the FDA approved a drug for fibromyalgia. Pregabalin (Lyrica) is now the first drug approved for treating fibromyalgia. And now a condition that for years has frustrated clinicians and patients alike, has a treatment. The expanded approval was based on two double-blind controlled trials involving about 1800 patients. Lyrica “reduces pain and improves daily functions for some patients,” according to the FDA. The agency says that the drug’s mechanism is unknown. So finally we have a drug whose specific mechanism for this disease is unknown to treat a disease whose cause is a mystery.