By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Sucampo Pharmaceuticals, Takeda, Boehringer Ingelheim; and is a consultant and on the speaker's bureau for Novo Nordisk, Lilly, Daiichi Sankyo, Forest Pharmaceuticals, Cephalon, Novartis, and Sanofi Aventis.
Coronary Calcium Scores enhance risk prediction
Source: Polonsky TS, et al. JAMA 2010; 303:1610-1616.
Probably the most widely recognized scoring system for predicting CV risk is the Framingham Risk Score (FRS). The United States Preventive Services Task Force (USPSTF) has recently published the opinion that novel risk markers such as C-reactive protein do not sufficiently enhance risk prediction enough to justify their routine utilization in addition to traditional scoring systems like FRS. Coronary Calcium Score (CCS) has a number of appealing attributes that suggest consideration as a powerful prediction tool.
In the Multi-Ethnic Study of Atherosclerosis (MESA) trial of persons without known CHD at baseline, a CCS > 300 was associated with a 10-fold increased risk for CHD events. A critical issue, however, is whether new or additional prediction score tools add meaningfully to existing methods. A metric known as Net Reclassification Improvement (NRI) has been recently proposed to distinguish whether the incremental impact of a scoring system or risk factor upon already existing methods is meaningful.
Using the cohort of MESA (n = 6814 adults; age > 45), Polonsky et al compared risk prediction as derived from FRS vs FRS + CCS. The addition of CCS to FRS resulted in a statistically significant NRI. An additional 23% of persons who experienced CHD events but had not been identified by FRS as high risk were correctly reclassified by the addition of CCS. Similarly, an additional 13% of subjects not classified by FRS as low risk (and who did not suffer events), were reclassified as low risk by the addition of CCS. Whether the preferential (or additional) use of CCS for risk prediction can improve outcomes over traditional risk scores alone will require further definition, although many are already sufficiently encouraged by the predictive power of CCS to currently employ it.
Vitamin E, but not pioglitazone, improves NASH
Source: Sanyal AJ, et al. N Engl J Med 2010;352:1675-1685.
Steatosis is the accumulation of fat, derived primarily from triglycerides in hepatic cells. Progressive steatosis can lead to hepatic inflammation, which, when not associated with alcohol, is known as non-alcoholic steatohepatitis (NASH). Obesity and diabetes are the two conditions most commonly associated with NASH. Because as many as 15% of NASH cases may ultimately progress to cirrhosis, effective treatments are eagerly sought.
Since the pathologic underpinnings of NASH often include insulin resistance, hypetriglyceridemia, and type 2 diabetes, pharmacology with thiazolidinediones (TZD) appears logical. Unfortunately, results from pilot trials of TZDs have been conflicting.
The NASH Clinical Research Network, established by the NIDDK, conducted a placebo-controlled trial of pioglitazone or vitamin E in non-diabetic NASH patients (n = 247). Subjects received 800 IU/d vitamin E, 30 mg/d pioglitazone, or placebo for approximately 2 years. The primary outcome was histologic status of NASH.
At 96 weeks, vitamin E did demonstrate a statistically significant rate of NASH histologic improvement, but pioglitazone did not. Even though there were some favorable histologic effects, neither intervention showed a reduction in hepatic fibrosis, so we remain uncertain about whether vitamin E can impact the development of serious long-term liver disease. Pioglitazone did not achieve an effect on the primary outcome, but explanations for why TZDs may still be considered for NASH therapy are presented by the authors.
COPD exacerbations: Not so innocent
Source: Donaldson GC, et al. Chest 2010;137:1091-1097.
Acute exacerbations of copd (ae-COPD) are sometimes misconstrued as minimally consequential "bumps in the road" along the journey of progressive COPD. Unfortunately, the toxicity of ae-COPD has been underappreciated; ae-COPD are associated with hospitalizations, loss of lung function that is typically not regained, and mortality. Donaldson et al direct our attention to a newly recognized additional burden of morbidity associated with ae-COPD: MI and stroke.
The Health Improvement Network (THIN) database contains anonymized medical records of patients seen by GPs in England and Wales. Over a 2-year period, 25,857 COPD patients provided a dataset with which to compare the incidence of MI and stroke during "stable" periods of COPD with the immediate post-ae-COPD period.
The incidence of acute MI was increased more than 2-fold in the 5-day period immediately following an ae-COPD; similarly, stroke incidence was increased more than 2-fold in the 49-day period immediately post-ae-COPD. Both findings were statistically significant.
No pharmacologic treatment of COPD has been proven to be disease-modifying. Yet, since various pharmacotherapies have been shown to reduce ae-COPD, perhaps such treatments will ultimately impact disease outcome by affecting the above-mentioned consequences of ae-COPD: increased stroke and MI.