Clinical Briefs

By Louis Kuritzky, MD

Ultralow-Dose Estrogen and Bone in Older Women

Hormone replacement therapy (HRT), has been found to have favorable effects upon osteoporosis and fracture risk in postmenopausal women. Unfortunately, this bone benefit is at the expense of increased risk for breast cancer, heart disease, stroke, and DVT. The increased risks are generally acknowledged to outweigh benefits for most women, though the jury is still out on estrogen replacement (ERT) without progesterone (in hysterectomized women).

In an effort to reduce risk, decrements in estrogen dose have been evaluated, usually in combination with supplements of calcium and vitamin D. This randomized, double-blind placebo controlled trial evaluated the provision of 0.25 mg/d of 17-beta estradiol (17-ERT), which is one-fourth to one-half the "conventional" dose previously used, daily for 4 years. End points included bone mineral density (BMD) and markers of bone turnover. Women were all menopausal, and in those women who had not undergone hysterectomy, 100 mg/d micronized progesterone was given for 2 weeks every 6 months. All study subjects were given supplemental vitamin D (1000 IU/d) and calcium (1300 mg/d).

In participants who received this low-dose estrogen, BMD by DEXA scanning showed favorable effects at the femoral neck, hip, spine, and total body. Bone turnover markers were also favorably affected.

At this low dose, the adverse effect profile was essentially indistinguishable from placebo, including breast tenderness. It is encouraging to note that ultra-low-dose estrogen has favorable bone effects. Ultimately, it will be essential to ascertain whether the BMD changes found will be reflected in fracture risk reduction. Additionally, though lower estrogen dose might be anticipated to reduce risk of serious adverse events, this remains to be determined.

Prestwood KM, et al. JAMA. 2003;290:1042-1048.

Effect of Intensity of Oral Anticoagulation in Atrial Fibrillation

The value of warfarin anticoagulation (WAC) in atrial fibrillation (AF) to prevent ischemic stroke is well established. Despite therapeutic levels of WAC, however, some AF patients still suffer ischemic stroke. In persons who do suffer stroke while on WAC, it is unclear whether their stroke severity is related to degree of anticoagulation. To clarify that question, this investigation studied acute ischemic stroke (n = 596) among persons with nonvalvular AF who were being treated at the time of stroke with WAC (32%), aspirin (27%), or were on no prophylactic treatment. In patients on WAC, stroke severity was assessed in relation to INR, comparing those with an INR > 2 to patients having an INR < 2.

For the end point of mortality or discharge with severe stroke, there was a dramatic disadvantage demonstrated for stroke patients with an INR < 2 (15% vs 5%). The relative hazard for death within 30 days for patients with an INR < 2 was increased over 3-fold.

Stroke that occurs while on WAC in AF is less severe, and has more favorable mortality outcome, when the INR is maintained at a level of > 2. Since increased risk of intracranial hemorrhage was not seen until INR levels rose to > 3.9, maintenance of the traditionally accepted INR 2-3 range appears to maximize benefit, and minimize risk.

Hylek EM, et al. N Engl J Med. 2003;349:1019-1026.

Patient Knowledge and Awareness of Hypertension

Despite a diversity of excellent pharmacotherapeutic tools for treating hypertension (HTN), national population surveys continue to indicate that there is much room for improvement in HTN detection, awareness, and control. Of course, if patients are unaware of BP goals, or their own BP and its adequacy of control, there is substantially less likelihood that they will achieve all the potential benefits of antihypertensive treatment.

Based upon a recent survey of hypertensive patients in the Northern California Kaiser Permanente Medical Care system (n = 2500), there remains a great deal of room for improvement in patients’ knowledge about blood pressure. Among this population, almost 80% of persons with BP >140/90 did not recognize their BP as "high," although 38.5% identified this level of BP as "borderline high;" a similar number of individuals were not able to recall their BP levels taken at the most recent clinic visit. Perhaps most distressing is that the majority of patients neither knew a goal for their BP treatment, nor was able to appropriately identify whether systolic or diastolic BP levels were a greater risk factor.

Encouragingly, more than 85% of patients recognized that HTN increased risk for stroke and MI, but only half as many individuals knew that HTN might increase risk of kidney disease. The message that patients need to know their BP, BP goals, and the greater relative risk of elevated systolic than diastolic blood pressure will have to be given greater attention by clinicians and other patient educators.

Alexander M, et al. J Clin Hypertens. 2003;5:254-260.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.