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.

Uric Acid and CV Risk: Not Ready Yet

Source: Feig DI, et al. Uric acid and cardiovascular risk. N Engl J Med 2008;359:1811-1821.

The relationship between uric acid (URA) and cardiovascular (CV) risk has been the subject of controversy for decades. Even if one were to fully accept that the various associations between URA and unfavorable CV outcomes have a causal relationship, the hurdle of prospectively proving that reduction of URA will improve outcomes has yet to be addressed.

URA elevation has been identified as a harbinger of hypertension, as well as obesity, diabetes, and kidney disease, but that may only be part of the story. For instance, that renal disease develops disproportionately in gouty patients is certainly true, but so does hypertension, which is more often the cause of renal disease than uric acid stones or urate nephropathy. The Framingham Heart Study suggests that the relationship of URA and CV risk is not independent of hypertension, hence, it does not qualify as an independent risk factor.

URA may play an etiologic role in development of metabolic syndrome. Even though insulin resistance is regarded by some as a sine qua non of metabolic syndrome, URA often precedes the insulin resistance; indeed, animal studies suggest that decreasing URA forestalls metabolic syndrome.

URA is also associated with vascular disease in the carotids and peripheral circulation. Some even attribute favorable CV effects seen in the LIFE study (utilizing losartan) to its favorable effects on lowering uric acid (losartan is the only antihypertensive agent known to lower uric acid).

The pathophysiologic underpinnings linking URA to CV misadventure have some plausibility. All-in-all, the relationship between URA and CV risk is tantalizingly close to compelling. However, even though we have expanded the old aphorism that "close only counts in horse shoes and hand grenades" to include archery, darts, lawn bowling, etc., close still doesn't count in science.

CPAP for OSA in Metabolic Syndrome

Source: Dorkova Z, et al. Effects of continuous positive airway pressure on cardiovascular risk profile in patients with severe obstructive sleep apnea and metabolic syndrome. Chest 2008;134: 686-692.

The association of obstructive sleep apnea (OSA) with adverse cardiovascular (CV) outcomes is strong. Encouraging data from persons with OSA who have been treated with continuous positive airway pressure (CPAP) have demonstrated that effective CPAP treatment reduces blood pressure. Whether CPAP might have favorable effects on other CV risk factors such as glucose, lipids, and markers of inflammation is less clear. Individuals with metabolic syndrome, who are at increased risk for CV events, provide an appropriate population to study the impact of CPAP treatment for OSA upon CV risk factors.

Dorkova et al studied 32 metabolic syndrome patients with OSA. At baseline and after 8 weeks of CPAP for OSA, risk factors associated with CVD were measured and compared: BP, cholesterol, triglycerides, HDL, fibrinogen, CRP, insulin resistance, and others. Subjects who used their CPAP for at least 4 hours nightly were considered compliant.

Compliant CPAP users enjoyed reduced BP, cholesterol, and insulin resistance. Non-compliant CPAP subjects (i.e., < 4 hrs/night) did not demonstrate these favorable changes. CPAP has been shown, in the high-risk group of patients with metabolic syndrome, to improve the CV risk factor profile.

Documentation of Coronary Ischemia Prior to PCI

Source: Lin GA, et al. Frequency of stress testing to document ischemia prior to elective percutaneous coronary intervention. JAMA 2008;300: 1765-1773.

For the sake of discussion, let's momentarily agree that percutaneous coronary intervention (PCI) is an appropriate step for persons suffering symptomatic coronary artery disease. The reason to establish this premise is that whether PCI actually offers any meaningful advantage over simple medical management is a matter of great debate. Indeed, the majority of PCIs in the United States are performed for patients with stable coronary disease, despite lack of evidence that outcomes with PCI in this setting are superior to intensive risk factor modification combined with medical therapy. Guidelines for PCI in stable CAD patients suggest that documentation of ischemia (most commonly by treadmill testing) should be obtained prior to PCI.

This study looked at Medicare beneficiaries undergoing elective PCI to see how often PCI had been preceded by stress testing. Of 23,887 Medicare recipients who underwent PCI in 2004, slightly less than half had any record of stress testing within the 90 days immediately preceding their PCI. The authors comment that in the absence of corroboration of ischemia, PCI may have been performed in patients who may not have benefited.