May 2010: Volume 36, Number 5

An analysis by researchers at the University of North Carolina School of Medicine indicates that multiple inflammatory markers are strongly and positively associated with increasing body mass index in children, starting as young as age 3 (Pediatrics 2010;125:e1–9). The results suggest that further research is needed to determine whether inflammation starts a cascade that, over many years, leads to cardiovascular disease (CVD) and related events, according to the researchers.

Prior studies have shown a clear relationship between adult obesity and high-sensitivity C-reactive protein (CRP) levels, and that CRP is predictive of future CVD, independent of obesity. However, these relationships have not been well-defined in children or adolescents. This prompted the researchers to explore associations between three markers of inflammation and weight status in children, with the goal of isolating any effects according to age. The investigators hypothesized that inflammation and obesity would be highly associated throughout childhood and that the association would begin earlier than had been previously reported.

The researchers analyzed data for children ages 3–17 years and ages 1–17 years in the 1999–2002 and 2003–2006 National Health and Nutrition Examination Surveys (NHANES), respectively. They examined three markers of inflammation, including CRP, absolute neutrophil count (ANC) and ferritin level controlled for iron status, measured via the ratio of ferritin to transferrin (F/T) saturation. The latter has not been used previously, but the researchers tested it in this study as a biologically plausible measure of inflammation that could have a relationship to obesity.

Prevalence in elevation of each of the three markers increased with increasing weight, but the elevation was observed at different ages depending on the marker. For example, the prevalence of CRP levels >1.0 mg/L was significantly greater at age 3, while the prevalence of elevated F/T >4.81 was not significantly greater in obese children than in those with a healthy weight until age 6, and increased prevalence of abnormal ANC >6.6 x 103 µL did not appear until age 9.

The results raise concerns about the entire population of overweight children’s risk for long-term CVD, according to the researchers. 

New research indicates that human papillomavirus (HPV)-based screening is more effective than cytology in preventing invasive cervical cancer because it detects persistent high-grade lesions earlier and facilitates a longer low-risk period (Lancet Oncology 2010; 11:249–57). The study also concludes that in younger women age 25–34 years, HPV screening leads to over-diagnosis of regressive cervical intraepithelial neoplasia (CIN) grade 2.

This two-phase randomized trial involved >94,000 women age 25–60 years. During the first recruitment phase, participants were assigned to either conventional cytology or HPV testing in combination with liquid-based cytology, and those age 35–60 years who were HPV-positive were referred for colposcopy, whereas subjects age 25–34 years were referred for colposcopy only if both an HPV test was positive and cytology abnormal or if HPV test results were persistently positive. During phase two, women were assigned to conventional cytology or HPV testing alone, and those in the HPV testing arm were referred for colposcopy solely on the basis of a positive HPV test result.

The researchers found a significant decrease in cases of invasive cancer detected during the second phase in the HPV group compared with the cytology group (0 versus 9, p=0.004). In addition, while the incidence of invasive cancer was similar between both study arms in the first phase, there was a significantly lower number of cases in the HPV group versus cytology group over the two screening rounds (7 versus 18, p=0.28). According to the researchers, this finding indicates that HPV-based screening is more effective than cytology in preventing invasive cervical cancer.  

A new study by Australian researchers adds to the growing body of evidence on the relationship between tight glycemic control and morbidity and mortality in intensive care (ICU) patients (Mayo Clin Proc 2010;85:217–24). The investigators found that an association exists between even mild or moderate hypoglycemia and mortality in ICU patients, and that even after adjustment for insulin therapy or timing of hypoglycemic episode, the more severe the hypoglycemia, the greater the risk of death.

The study involved 4,946 patients admitted to ICUs in two teaching hospitals, 1,109 of whom had at least one episode of hypoglycemia with blood glucose level <81 mg/dL measured via arterial blood gas analyzer. Hospital mortality in the patients with hypoglycemia was 36.6% compared with 19.7% in those with normoglycemia (p<0.001). Mortality increased significantly with increasing severity of hypoglycemia, and after adjustment for insulin therapy, hypoglycemia remained independently associated with increased risk of death, cardiovascular-related death and death due to infectious disease.

The researchers proposed three possible explanations for the observed association between hypoglycemia and adverse outcomes, including that severity of hypoglycemia may be associated with severity of illness, that hypoglycemia may be a marker of imminent death, or that it might cause biologic toxicity through a variety of mechanisms such as systemic inflammatory response, inhibition of the corticosteroid response to stress or by impairing sympathetic system responsiveness. The findings suggest that clinicians should avoid even mild or moderate hypoglycemia in ICU patients, according to the researchers. 

Primary care physicians may have a poor perception of their patients’ cardiovascular risk, and as a result may not set or achieve appropriate low-density lipoprotein (LDL) targets, new research indicates (Eur Heart J doi:10.1093/eurheart/ehq026). The findings also suggest that assignment of correct target values differs markedly depending on patients’ co-morbidities and sex. Women with a documented history of myocardial infarction (MI) or diabetes, in particular, were much less frequently assigned correctly to a high-risk LDL target than men with comparable clinical circumstances.

The study involved 907 primary care physicians who were asked to subjectively estimate guideline-recommended LDL target values for 25,250 patients (30 for each practice). Physicians had the discretion to use risk assessment charts or scoring tables to calculate National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP-III) LDL target values, which are <100 mg/dL for patients with coronary artery disease (CAD), a CAD equivalent condition such as non-coronary vascular diseases and diabetes, or a 10-year risk of a CVD event >20%. Lipid profiles for all patients were documeted centrally.

Overall, physicians estimated NCEP ATP-III-recommended LDL target values correctly in 52.4% of patients, including 55.1% of men and 49.1% of women. Physicians were most likely to assign correct LDL targets to male patients with a history of MI (77.1%). In contrast, increasing probabilities for incorrect assignment of LDL values were found in patients with documented CAD without a history of MI, CAD-equivalent conditions, and with a 10-year risk >20% based on calculated risk scores.