Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for and serves on the speakers bureaus of Abbott, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Forest Pharmaceuticals, Eli Lilly & Co., Novo Nordisk, and Takeda.

What aspect of HTN produces toxicity?

Source: Rothwell PM, et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet 2010;375:895-905.

A well-established body of epidemiologic literature supports a continuous graded risk between systolic blood pressure (SBP) and CV risk. This relationship has held constant whether one considers office BP, home BP, or ambulatory blood pressure monitoring (ABPM). Because BP is variable over time, it is unclear whether the toxicity of BP to the vasculature is more strongly associated with mean BP, maximum BP, pulse pressure (SBP − DBP), or BP variability. Circadian rhythm of BP has also been recognized to be particularly associated with adverse outcomes: ABPM subjects whose BP does not decline overnight (called non-dippers) have greatly increased CV risk, well beyond what would be expected simply by having a greater total number of hours of exposure to elevated BP.

Rothwell et al used a data set comprised of persons who had sustained a TIA in large clinical trials (n = 2006), including the UK TIA Trial and ASCOT. Visit-to-visit BP variability and maximum SBP were better predictors of adverse outcome than mean SBP. Similarly, persons with episodic HTN (normal BP on some occasions, elevated on others) were also at increased stroke risk, surpassing risk for stable BP.

It remains to be elucidated why these subgroups of individuals with BP variability have a greater risk burden. Although the associations between maximum SBP, BP variability, and episodic BP elevations were consistent, this does not establish causation. Perhaps the strongest cautionary message from this trial is that clinicians should not fall prey to false reassurance when they see a mixed BP response pattern including some BP measurements at goal and others elevated; such episodic elevations are consequential.

New short-course topical treatment for actinic keratoses

Source: Swanson N, et al. Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles. J Am Acad Dermatol 2010;62:582-590.

Actinic keratoses (AKS) recently have been recognized as both a cosmetic and a dermatopathologic problem, since they are precursors to squamous cell carcinoma. Indeed, current literature suggests that AKs be considered squamous cell carcinoma in situ. AKs treatment includes cryotherapy, excision, chemical destruction (e.g., 5-fluorouracil, diclofenac), immune activation (imiquimod [IMQ]), and others. Because topical treatment courses are sometimes protracted, and induce unpleasant cutaneous inflammatory changes, clinicians desire simpler, gentler methods.

Swanson et al randomized patients with AKs on the face and scalp to IMQ or placebo (n = 479). IMQ was applied as pulse therapy: qd for 2 weeks, then no treatment for 2 weeks, then repeat (total = 14 days of treatment). Outcomes were measured at 8 weeks.

IMQ produced a 72%-82% reduction in AKs lesions; higher doses produced complete clearing in 59% (vs 6% with placebo). A companion article in the same journal showed similar clearance rates for a longer regimen (3-week treatment courses). This simpler regimen was well tolerated, and provides a quick and effective route for topical treatment of AKs.

Depression and sleep disturbance

Source: Van Mill JG, et al. Insomnia and sleep duration in a large cohort of patients with major depressive disorder and anxiety disorders. J Clin Psychiatry 2010;71:239-246.

Both anxiety and depression disor-ders have a strong association with sleep disturbance. The association between sleep and depression is bidirectional: Depression is often manifest by or leads to sleep disturbance, and persistent insomnia increases risk of depression.

Van Mill et al sought to elucidate further the relationship between sleep disorders and depression by analyzing subjects in the Netherlands Study of Depression and Anxiety cohort (n = 2619).

In this population of subjects (approximately three-fourths suffered from depression and/or anxiety), almost half scored at least 9 on the Insomnia Rating Scale (IRS; the same metric that was employed in the Women's Health Initiative), fulfilling criteria for clinically significant insomnia. Insomnia scores were related to both anxiety and depression, but worse for depression, and highest for comorbid depression and anxiety. Interestingly, even persons with depression or anxiety in remission had elevated scores on the IRS. The authors suggest that, based upon their data, inquiry into sleep status is valuable not only during both depression and anxiety, but even during periods of remission.