Clinical Briefs by Louis Kuritzky, MD
Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.
The Carotids Blow the Whistle on Crimes in the Heart
Vasculopathy knows no compartmentalization. Clinicians expect that patients with peripheral arterial disease will also commonly have comorbid coronary or cerebrovascular disease, even though it may be silent. The last decade has confirmed that the endothelial dysfunction of erectile dysfunction is a harbinger of coronary artery disease. Carotid intima-media thickness is a commonly employed surrogate in hypertension and dyslipidemia trials. What implications then, might a clinician make about an ausculted carotid bruit?
Pickett et al performed a meta-analysis of 17,295 patients in 22 reports which included information about persons with/without carotid bruit and cardiovascular outcomes during followup (mean 4 years).
The odds ratio for MI was more than double for subjects with carotid bruit than without, and even greater for CV death. This meta analysis supports the concept that vascular disease in the carotids, as manifest by carotid bruit, is corroboration of meaningful vascular disease in other tissue compartments, specifically the coronary bed.
National guidelines recognize the presence of diabetes or peripheral arterial disease as a cardiac disease equivalent; ie, associated with > 20% risk of cardiac event within 10 years. These data indicate a similar or greater risk of coronary events in patients with carotid bruit. Based on these observations, clinicians might use the presence of a carotid bruit to help support aggressive risk factor modulation.
Pickett CA, et al. Lancet. 2008;371:1587-1594.
Vitamin Shmitamin
Everything about the homocysteine hypothesis looked so good: a strong association of elevations with vascular disease, prototypic premature vascular disease in youth associated with disordered homocysteine and vitamin B12 metabolism, prompt reductions of homocysteine with folic acid ... UNTIL interventional trials called a screeching halt to homocysteine enthusiasm. Despite consistent failed trials of B vitamin intervention, because women have been under-represented in the interventional trials to date (and might, according to the observational data, benefit more than men), it was worth consideration that a gender-specific trial was in order.
Female health professionals (n=5,442) aged 42 or greater who were considered high risk for CV disease (on the basis of 3 or more coronary risk factors) were randomized to combination folic acid/B12/B6 (VIT) or placebo for 7.3 years. The primary outcome was a composite of MI, stroke, CVD mortality, and coronary revascularization.
Neither the primary endpoint nor any individual endpoint was advantageously impacted by VIT, despite substantial homocysteine lowering. Because female health professionals have a lesser prevalence of vitamin deficiency than the general population, it is possible that had a less vitamin-replete group been studied, the impact of B vitamins may have been more dramatic. In any case, these data are consistent with the growing body of evidence that B vitamin supplementation does not impact cardiovascular disease.
Albert CM, et al. JAMA. 2008;299:2086-2087.
Fracture Risk, Diabetes, and Rosiglitazone
Clinicians probably automatically insert the word "osteoporosis" whenever the words "fracture" and "woman" appear in the same sentence. In the case of diabetes, however, other factors are at play. Diabetic women are at increased risk of fracture in the absence of osteoporosis, although it remains to be discerned why this fracture risk occurs; there has been some suggestion that diabetics, perhaps due to neuropathy, are at greater risk of falls, resulting in more fracture.
Some earlier clinical trials have noted a bone mineral density decrease in diabetic women treated with thiazolidinediones (TZD), providing rationale to examine this issue in the ADOPT trial, a large study (n = 4,351) comparing TZD (rosiglitazone), metformin, and glyburide monotherapy in men and women with newly diagnosed type 2 diabetes.
Over a 4 year treatment period, when compared with metformin or glyburide, rosiglitazone was associated with an increased risk of fracture in women: 1.8 greater relative risk than metformin, and more than a doubling of risk compared to sulfonylurea. Increased risk is discernible as early as 1 year after treatment, but (at least in this data) was not associated with increased falls, and is seen in younger, premenopausal women as well. Although the mechanism by which thiazolidinediones increase fracture risk is unclear, this observation should prompt greater vigilance by clinicians, and should be factored into the decision process of the risk/benefit ratio of oral antidiabetic agents.
Kahn SE, et al. Diabetes Care. 2008;31:845-851.
Vasculopathy knows no compartmentalization. Clinicians expect that patients with peripheral arterial disease will also commonly have comorbid coronary or cerebrovascular disease, even though it may be silent.Subscribe Now for Access
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