Clinical Briefs
Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville
Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.
An Unexpected Connection Between PTSD, ACE Inhibitors, and ARBs
Source: Khoury NM, et al. The renin-angiotensin pathway in posttraumatic stress disorder: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are associated with fewer traumatic stress symptoms. J Clin Psychiatry 2012;73:849-855.
SEVERAL LINES OF EVIDENCE SUGGEST that modulation of the renin-angiotensin-aldosterone system with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) might potentially have positive effects on post-traumatic stress disorder (PTSD). Preclinical data indicate favorable cerebral effects of ARBs, such as stress reduction and anxiolysis. Some ARB trials have reported positive effects on cognition, quality of life, and depression or anxiety.
Khoury et al performed a cross-sectional observational data analysis of PTSD patients (n = 505) comparing symptoms in those who were being treated with an ARB/ACE vs controls (no ARB/ACE treatment). Overall, PTSD symptom scores were almost 25% lower among patients treated with ACE or ARB therapy (P = 0.04).
The better symptom scores among PTSD patients treated with ARB or ACE therapy were not simply due to the fact that hypertension (which is more common in PTSD patients) was treated; no other antihypertensive medications (e.g., calcium channel blockers, diuretics, beta-blockers) were found to have similar favorable effects.
The mechanism through which ACE/ARB treatments impact PTSD is not well established, but may be through modulation of the noradrenergic system.
The Right Amount of Vitamin D to Prevent Fractures
Source: Bischoff-Ferrari HA, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med 2012;367:40-49.
INCLUSION OF VITAMIN D (VTD) IN THE regimen for fracture prevention is time honored and condoned by major guidelines. Intuitively, VTD should be helpful, but the analyses of data in reference to this topic are mixed. For instance, although one meta-analysis indicated an 18% reduction in hip fracture if a minimum of 482 IU/d VTD was prescribed, equally prominent data concluded that VTD alone was of no benefit. So, how about further investigation of the subject?
Bischoff-Ferrari et al performed an analysis of 11 double-blind, randomized, controlled trials of oral VTD supplementation (n = 31,022) seeking to determine if supplementation (with or without calcium) reduced hip fracture. According to their analysis, there was no statistically significant reduction in fracture risk in subjects assigned to VTD. Story over? Well, maybe not quite.
First, although hip fracture was not reduced, there was a marginally statistically significant 7% reduction of total non-vertebral fractures. Additionally, when analyzed from the viewpoint of the actual intake of VTD instead of what subjects were assigned to, the picture looks quite different. Specifically, subjects in the highest quartile of actual VTD intake (prescribed supplementation plus dietary intake) enjoyed a statistically significant 30% reduction in hip fracture. For the time being, at least 800 IU/d VTD supplementation is recommended in persons ≥ age 65.
Prevention of Diabetes
Source: Perreault L, et al. Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet 2012; 379:2243-2251.
IT APPEARS THAT ONE’S OUNCE OF PREvention may have to be weighed more carefully to attain the fullest pound of cure. Why? The answer lies in subgroup analysis of recent trials in diabetes prevention.
There have been many diabetes prevention trials, essentially all of which have been successful to a varying degree. Overall, diet and exercise appear to be as efficacious as any other intervention. Pharmacologically, numerous classes of agents have been successfully tried (metformin, thiazolidinedione, alpha-glucosidase inhibitor, etc.). What has been learned is that successful incorporation of diet/exercise or pharmacotherapy over a 4- to 6-year period reduces the likelihood of progressing from prediabetes to diabetes (typically, 6-10%/year) by half or more. But there is more to the story.
After successful treatment (pharmacotherapy or lifestyle), the majority of those who are prevented from progressing to frank diabetes still fulfill criteria for prediabetes (A1c 5.7-6.4). Between 20-50% of treated subjects are restored to currently recognized normal glucose levels.
The analysis by Perrault et al indicates that persons with prediabetes in whom normal glucose homeostasis was restored are half as likely to progress to frank diabetes over a 3-year, post-trial observation period as individuals whose glucose control was improved, but still reflected prediabetes. Striving for the best glucose control in prediabetes may have long-term benefits.
Clinical Briefs: An Unexpected Connection Between PTSD, ACE Inhibitors, and ARBs, The Right Amount of Vitamin D to Prevent Fractures, Prevention of DiabetesSubscribe Now for Access
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