zzzzzz….all about sleep

So I’m an issue behind, but I had to blog on the sleep-themed Sept 18th issue of Archives of Int Med. (one of my favorite subjects). Just how important is it?

Steptoe et al. found that young adult subjects that slept less than 6 hours per night were almost twice as likely to report their health as being poor – even after adjustment for socioeconomic factors, physical activity, BMI and Beck Depression Inventory scores. However, I cant help be a little cautioned by the fact that both sleep time and health status were based on self-report.

From the basic science side, Irwin et al. found that monocyte production of the proinflammatory cytokines IL-6 and TNF-alpha was significantly higher on the morning after sleep deprivation. (sounds like a bad thing)

Arzt et al warn of a condition that may obscure the diagnosis of obstructive sleep apnea. Their research found that comorbid heart failure resulted in less daytime sleepiness in sufferers of OSA. Unfortumately, the detrimental effects of poor sleep remained present. Because excessive daytime sleepyness is often the presenting symptom leading to the diagnosis of OSA, the researchers caution that physicians may miss the presence of OSA in HF patients.

And in the midst of the obesity epidemic, Kothatsu et al. show that a significant inverse relationship between sleep duration and BMI also exists in a rural population. Other researchers have already shown the same to be true in the urban and suburban populations. But watch out for that giant 70% confidence interval.

Din-o-mite: Intensive Lipid Lowering in CHD

Lancet 9/9 – In the latest set of reccomendations from the NCEP ATP, the panel reccomended that patients with CHD or risk equivalent have a goal LDL of 100mg/dL, with an option of less than 70mg/dL in high-risk patients. Several prior studies have shown that further reductions in LDL may decrese mortality, but further study is needed.

In the most recent issue of the Lancet, Deedwania et al. publish results of the TNT study on the outcomes of this new goal of intensive lipid lowering. The design was a double blind RCT involving 10,000 patients with over a median of 5 years. To fit the inclusion criteria, subjects had to be aged 35-75 with history of MI, revascularization, or angina with objective evidence of atherosclerotic disease. Subjects were randomized to recieve either 10mg or 80mg of atorvastatin.

Mean LDL levels were 99mg/dL in the low dose, and 72.6mg/dL in the high dose group. The outcome was a statistically significant decrease in risk for major cardiovascular events in the high dose group. With an absolute risk reduction of 3.5% which is 29% relative. The levels obtained were convenient because they closely reflected the new LDL goals. It seems as if this study does show data to support those reccomendations. The question remains as to whether the results can be generalized to CHD risk equivalents such as diabetes, because the study only included clinically evident coronary disease.

Revenge of the COX-2 inhibitors ?

NEJM 8/31 – Results of the VIGOR trial in 2001 shook the medical world with controversy as concern over cardiovascular side effects pushed several COX-2 drugs off the market. Cox-2’s were not only interesting for their anti-inflammatory effect, but also due to evidence of protection from colorectal adenomas – the precursor to colorectal cancer. But studies by both Pfizer and Merck regarding this effect ground to a halt after safety concerns sufaced.

A pair of articles by M. M. Bertagnolli et al. and N. Arber et al. in the New England present data on the prevention of colorectal polyps and adenomas with Celecoxib. Both studies were RCT’s in which the subjects had previous adenomatous lesions removed.

Bertagnolli’s RCT followed over 1800 patients from 1-3 years and compared high and low dose celecoxib therapy to placebo. They found a signficant 33% and 45% risk reduction for the formation of colorectal ademonas with the two groups respectively. The downside was that the risk of cardiovascular effects was 2.6 and 3.4 times higher in the celecoxib groups.

The Arber et al. study had similar results with a 46% risk reduction in adenomas and a 50% risk reduction in advanced adenomas. Serious cardiovascular events occurred in 2.5 percent of subjects in the celecoxib group and 1.9 percent of those in the placebo group (relative risk, 1.30).

Many questions remain about COX-2 inhibitors. Some recent data suggests that these drugs are just as dangerous as non-selective NSAIDs. Also the relative risk of harm varies from 1.3 in the Arber studies to 4 in the VIGOR trial. Hopefully the full story will become clear with further research…