Clinical Briefs in Primary Care
Predicting the development of diabetes
Source: Tabak AG, et al. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes. Lancet 2009;373:2215-2221.
In typical prediabetic populations studied to date, approximately 5%-10% per year progress to diabetes. Because diabetes is preventable in the prediabetic state through diet, exercise, pharmacotherapy, or their combination, it would be useful to identify at-risk individuals even before they manifest impaired fasting glucose (IFG) or impaired glucose tolerance (IGT).
The Whitehall II study is a prospective occupational cohort study of British civil servants. Study subjects without diabetes at baseline (n = 6538) had periodic measurement of fasting glucose, oral glucose tolerance tests, insulin resistance, and beta-cell function for as long as 13 years. At a median of 9.7 years follow-up, 505 had developed diabetes.
There was a distinct curvilinear increase seen in fasting glucose, 2-hour post-load glucose, insulin resistance, and beta-cell functional loss noted 3-5 years before the onset of frank diabetes; subjects who did not develop diabetes showed no such steep curvilinear changes.
The presence of IFG and/or IGT heralds onset of diabetes. These observations suggest that by monitoring trends in markers of glucose dysregulation, clinicians might be able to identify persons at risk of developing diabetes even earlier than the currently accepted metrics for prediabetes afford.
OSA in patients with acute MI
Source: Lee CH, et al. Obstructive sleep apnea in patients admitted for acute myocardial infarction. Chest 2009;135:1488-1495.
Obstructive Sleep Apnea (OSA) is inextricably linked with adverse cardiovascular events including stroke, MI, hypertension (HTN), and arrhythmia. A putative mechanism links OSA with CVD: The persistent sympathetic overdrive necessary to stimulate engagement of ventilation in persons with frequent apnea/hypopnea — while effective in sustaining respiratory activity — is toxic to the cardiovascular system. The OSA-CVD relationship may not be uni-directional. For instance, although atrial fibrillation is a much more potent risk factor for stroke than HTN, many more patients have HTN than have atrial fibrillation; therefore, the number of patients who present with stroke on the basis of HTN greatly surpasses those induced by atrial fibrillation. Lee et al studied subjects presenting with acute MI (AMI) to determine the prevalence of OSA.
The study group comprised 105 adult men with uncomplicated AMI, all of whom underwent overnight polysomnography. Essentially two-thirds (65.7%) of all subjects had OSA-positive sleep studies, with the presence of diabetes being a significant risk factor.
Successful treatment of OSA with CPAP has been shown to reduce CV morbidity. Whether treatment of OSA in a population that has recently sustained an MI will reduce events is unknown. On the other hand, since OSA is a well-established risk factor for future CV events, its early identification should be a priority. These prevalence data should encourage more energetic OSA case ascertainment in persons who have sustained coronary events.
High-risk colon cancer subjects and CT colonography
Source: Regge D, et al. Diagnostic accuracy of computed tomographic colonography for the detection of advanced neoplasia in individuals at increased risk of colorectal cancer. JAMA 2009;301:2453-2461.
The most recently released colon cancer screening guidelines from the American Cancer Society (2008) support an increased diversity of appropriate screening tools, including, for the first time since ACS guideline inception, CT colonoscopy (CTC). The largest (n ≥ 6000) head-to-head comparison of CTC with "traditional" (optical) colonoscopy (OTC) found similar colon lesion detection rates with both methods. While such data are reassuring for general screening, no prior trial has compared CTC to OTC in higher-risk populations.
Regge et al studied 973 subjects deemed to be high-risk for colon cancer on the basis of either a positive family history, prior colonic adenoma, or positive FOBT. Each subject underwent CTC and colonoscopy on the same day.
Using OTC as the gold standard, the sensitivity of CTC for advanced neoplasia (defined as adenoma > 6 mm) was 85%, and specificity was 88%; sensitivity of CTC was better for the most concerning lesions (> 10 mm): 91%.
Because some patients prefer the option of CTC to OTC, and because evaluation of populations with CTC is associated with less risk of adverse events (e.g., perforation and bleeding) than OTC, these results support a role for CTC.
Migraine and ischemic brain lesions
Source: Scher AI, et al. Migraine head-ache in middle age and late-life brain infarcts. JAMA 2009;301:2563-2570.
The relationship noted between migraine headaches (MIG) and an increased, albeit small, stroke risk has long been an issue of concern. Indeed, classic migraine (migraine with aura), which affects about one-third of migraineurs, has been associated with both stroke and CAD. A 2004 study reported that migraine was associated with increased risk (7-fold) for cerebellar infarcts, especially for persons with frequent migraine.
Scher et al performed a population-based study of midlife adult (mean age, 51 years) men and women (total n = 4689) in Reykjavik, Iceland, who were followed for more than 25 years. Detailed information about headaches including frequency, unilaterality, photophobia, nausea, and aura was obtained. Additionally, all subjects underwent MRI. Mean age at the time of MRI was 76 years.
Study subjects who reported midlife migraine with aura had a 40% greater incidence of late-life infarct on MRI. This increased risk was dominantly driven by an almost 2-fold greater risk of cerebellar infarcts in women. For men, there was no demonstrable increased risk. The risk of cerebellar infarct was independent of traditional risk factors for atherosclerosis. In women, midlife migraine may emerge as an important cerebrovascular risk factor.
Is a prolonged PR interval innocent?
Source: Cheng S, et al. Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block. JAMA 2009;301:2571-2577.
Apr interval prolonged beyond 200 milliseconds — or first degree heart block (FDHB) — can be associated with cardiac pathology, inflammatory diseases, and medications. On the other hand, in ostensibly healthy ambulatory adults without risk factors for or evidence of coronary artery disease (and in the absence of culprit medications), FDHB is often summarily dismissed as being innocent. Well, maybe that designation needs to be reassessed.
Cheng et al evaluated data from the Framingham Heart Study. A population of adults (n = 7575) had a baseline EKG performed at age 47 (in the 1968-1974 time interval); follow-up data obtained in 2007 included incidence of pacemaker implantation, atrial fibrillation, and all-cause mortality.
There was a 2-fold or greater risk for atrial fibrillation, a 3-fold greater incidence of pacemaker implantation, and a 1.4 relative increase in all-cause mortality in persons with FDHB. This risk was linearly related to the degree of PR prolongation: for instance, for every 20 millisecond increment increase in PR interval, there was an 11% greater incidence of atrial fibrillation.
Previous data supporting the benign nature of FDHB were primarily based on data from younger adults. This long-term follow-up indicates that FDHB is indeed associated with adverse CV outcomes. The appropriate interval for follow-up or indicated evaluation (if any) was not suggested by the authors.
Getting a handle on hidradenitis suppurativa
Source: Canoui-Poitrine F, et al. Clinical characteristics of a series of 302 French patients with hidradenitis suppurativa, with an analysis of factors associated with disease severity. J Am Acad Dermatol 2009;61:51-57.
Hidradenitis Suppurativa (HSP) is regarded both in the dermatology and primary care communities as a "heart sink" diagnosis: Patients are generally chronically burdened, we have little successful treatment, the pathophysiology is poorly understood, and the consequences often have an important negative impact on quality of life. As far as is understood at this point, HSP is a recurrent disorder characterized by recurrent, deep, painful abscesses at tissue sites containing apocrine glands (i.e., axillae, breasts, perineum, gluteal area). Since the currently quoted prevalence rate approaches 1%, all primary care clinicians who treat adults or adolescents are likely to encounter the disorder many times.
The Sartorius score is a recognized HSP severity score. It includes number of regions of the body involved, number of lesions (including abscesses, fistulas, scars, pustules), and presence/absence of healthy skin between multiple lesions.
An assessment of 302 HSP patients from a dermatology clinic in Paris provided the opportunity to determine associations between Sartorius score (i.e., disease severity) and risk factors. In this population, BMI and severe acne were associated with a higher Sartorius score. Some of the treatments for acne have been shown to provide improvement in HSP, but it is unknown whether weight loss improves outcomes in HSP. Chronic lesions sometimes motivate patients to resort to surgical solutions for HSP. We continue to look forward to better insight into the pathophysiology of HSP, and more sustainable and effective interventions.
Predicting the development of diabetes; OSA in patients with acute MI; High-risk colon cancer subjects and CT colonography; Migraine and ischemic brain lesions; Is a prolonged PR interval innocent?; Getting a handle on hidradenitis suppurativaSubscribe Now for Access
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