Cholesterol and Son of J-LIT

The 10 year follow on to the J-LIT study is out. My view and update of the original J-LIT study was that it was one of the better statin studies and provided more information on the effects of pharmacologically lowered cholesterol levels, on a background of the known pleiotropic effects of the statin drugs, than most other studies. At a fixed dose of simvastatin (mostly 5mg per person per day) there is a relative beneficial effect if your statin induced hypocholesterolaemia is mild, with a significant increase in cardiovascular, cancer and all cause mortality if your TC drops below 160mg/dl and/or your LDL-C drops below 80mg/dl.

Well now the 10 year follow up is published.

What happens at the 10 year mark? Well, you are as welcome to try and find out as me, but I've failed.

There is a tabulated display of cardiac "events" vs on-study cholesterol levels in the results section. That's it. They have mortality data, including cardiac deaths and cancer deaths, for each cholesterol grouping, but these are not mentioned (they were there in J-LIT). Perhaps they have decided that we will be so preoccupied with the reduction in cardiac "events" that the risk of dying becomes so unimportant that we won't want to know about it.

Well I'd like to know.

This is the total of the information about all cause mortality by cholesterol level:

"The relative risk of all-cause mortality was also analyzed in relation to the average serum lipid levels during the 10-year treatment period in the primary prevention cohort study (data not shown comment: You bet it's not shown!). The results were the same as those in the previous report.2"

Now of course all studious cardiologists will naturally want to know exactly how lethal low cholesterol levels are, so will look up reference 2. You think not? Well, just to help out, here are the all cause mortality data from the 6 year report cited as ref 2 and plotted by TC intervals. The LDL-C vs all cause mortality curve is the same shape but a bit flatter. Look at the left hand end.



The left hand end is where these cardiologists want you to be. There is no difference between the data at 6 years vs those at 10 years is what they say. Seriously low TC or LDL-C will significantly increase you risk of being dead. Obviously, if you are a cardiologist, that is far better than having a cardiac "event"!

This 10 year report MUST also have the relative risk data for cardiac death in the low cholesterol group but they have forgotten to even mention it. I'd just remind you that in the original J-LIT study cardiac mortality was 6.23 time higher in the group with TC below 160mg/dl vs the reference group with TC of 200-219mg/dl. Again, perhaps having someone dead is less tiresome than having to manage a pesky survival heart attack. I dunno. BTW the LDL-C concentration in the group with TC <160mg/dl and 6.23 times relative risk of cardiac death was <80mg/dl, ie cardiological Nirvana.

Is that it? Not quite.

All cause mortality (irrespective of lipid levels) did get a brief mention:

"However, the overall mortality rate of the primary prevention cohort was higher during the 10-year period (4.47 deaths per 1,000 patient-years) than for the 6-year J-LIT period (3.69 deaths per 1,000 patient-years). The main factor contributing to the increase of mortality in the present study was probably aging, because the mean age had increased by 6 years for this extension study compared with that for the original J-LIT study"

Reading carefully here it seems they were comparing death rate in the first 6 years with death rate in the total 10 years, which included the first 6 years. That is, the all cause mortality in the last 4 years of the study must have been quite a bit higher per year than the overall quoted 10 year value as it is diluted down by the inclusion of the first six year value. Reverse engineering the numbers ties my brain in a knot. But that's how it has to be. What was to stop them adjusting the figures for age? Maybe the result!

They scared themselves with their honesty about mortality in the original J-LIT study and so they have been a lot more cautious with data release this time around.

So how do you sum up Son of J-LIT?

Dead bodies are less worrisome than cardiac "events".

Peter

PS I think I have commented that the original J-LIT study could be repeated on any cohort of people on a fixed dose of a given statin and that this has never been done, for obvious reasons. I think we can add that the exercise is so scary to a statinator that even the original J-LIT investigators have refused to repeat the exercise, even though they are the developers of the methodology and have the same cohort available. Wow.