Success!!! got my patient's LDL to 50mg/dl

First question.......What's the benefit of doing the above? We all know that lower the cholesterol..lower the cardiovascular risk. Latest evidence supports lowering it to < 70 mg/dl for the high risk patients. Well...is there a downside to overdoing this? Yes there is... at least theoretically ..for now.
The normal LDL level is 40 - 70 mg/dl. Cholesterol (mainly LDL particles) play a major role..and are the corner stone for synthesis of many steroid hormones including cortisol, tetosterone, androstenidione, Vitamin D etc. So by looking at this...obviously driving LDL to a much lower level can affect these important physiological processes.
There were a few studies done to see if reduction in LDL with statins affect endogenous steroidogenesis. In a cross sectional study of 350 type 2 diabetic patients on a statin (Diabetes care 2009) showed a significant reduction in total testosterone level with atorvastatin compared with no treatment. But the free bio available testosterone levels were normal. A pharmacology study from Holland shows the same above possibility with Statins.(British J of Clin Pharmacology )

A subgroup analysis of reproductive age group women from WISE trial showed no significant decrease in levels of estrogen or progesterone in pts with LDL < 70 Vs pts with LDL >70. (AJM 2002).
An earlier study from 1994 showed no decrease in levels of adrenal and gonadal steroids in patients with a low LDL on a statin. Most of the above studies...didnt drive down the LDL levels to < 70mg/dl.
A recent study published in 2009 comparing gonadal hormones in pts with LDL <70 with LDL <100...in pts on a statin..showed no significant difference in the sex hormone levels..over a period of 12 weeks. This may be a short duration to assess a reasonable outcome.

On the whole...driving the LDL levels to < 70 may have little or no negative effect on sex &/or adrenal hormone levels. But this possibility can be considered if a pt..with a LDL of <70 complains of decreasing libido.(these pts may also be on Spironolactone..which can make this worse).
Statins have shown some benefit in treating prostate cancer( again..may be due to their effect on lowering levels of testosterone!). Another theoretical concern with excessive lowering of cholesterol will be the possibility of a lack of adrenergic response needed during stress (especially in sepsis, ICU admissions etc) due to low cortisol production. Whether this is true remains to be answered !!

Some more indications for Statin

As we all know, we are getting more and more new information on the benefits of Statins independent from their ability to inhibit HMG CoA reductase and reduce LDL cholesterol. 

There has been a great interest in high CRP levels and their relation to increased coronary events, even in the absence of hyperlipidemia. The study done on nearly 500 patients who had MI showed nicely that Pravastatin reduced the median and mean CRP levels significantly, compared to placebo, over a period of 5 years.(E.Braunwald - same person who contributed a lot to Harrison's Textbook). With this background, PROVE IT-TIMI 22 trial recruited nearly 4000 pts, and showed that pts with low CRP levels after statin therapy have a better clinical outcome than if CRP level is high. 
Given these stimulating results, investigators tried to apply this in the primary prevention of CAD. And guess what...two studies with slightly different population (AFCAPS- low risk pts, and JUPITER- intermediate and high risk ...due to 10% 10 yr Framingham risk score) showed significant reduction in the first coronary event in patients whose CRP level decreased while on statin. All the participants didn't have hyperlipidemia. The Canadian Heart Guidelines have already included CRP in risk stratifying pts for primary prvention. 


Statins also reduce the incidence of DVT/PE as shown in a meta analysis of nearly 1 million pts done at U Conn. JUPITER trial was included in this meta analysis, as this is the only randomised trial to show reduction in DVT ( but not significant for reduction in PE).


Now this is the latest on the list of benefits from Statin ---- A meta analysis looking at incidence of ventricular arrhythmias(VF/VT) among pts with CAD on a statin Vs no statin, has shown a 31% reduction in ventricular arrhythmic events in the statin group. This has previously been shown in a subgroup from MADIT-II trial.
So ...what about Atrial Fibrillation. Well there were many studies on Statins and maintaining sinus rythm in A fib...with conflicting results. A recent meta analysis showed that Statins does not help maintain sinus rythm in patients who underwent elective DC cardioversion. 


This list of benefits might increase every day....... keep checking!!