Off target effects of statins shape total mortality?

Re: Kazerooni R, Lim J. Predictors of long-term mortality in new start statin users. J Drug Assess 2015;4:7-11

Dear Editor,

Kazerooni and Lim report several independent predictors of mortality in new start statin users after long-term follow-up [age, race, number of medications, comorbidities, and body mass index (BMI)]; however, differences in lipid groups and adherence to statin treatment after 1 year were not predictive of long-term mortality in the veteran population studied . This may be due to the low adherence rates to statin therapy . This interpretation would fit in well with polypharmacy being more common in the mortality group . In turn, the latter observation suggests the need to decrease the number of administered drugs by prescription reviews and use of combination formulations .

In this context, it should be mentioned that specific statin treatment (atorvastatin) improves renal function and ameliorates chronic kidney disease (CKD) with an independent beneficial effect on morbidity and mortality , . Also, treatment with atorvastatin lowers the levels of serum uric acid (SUA) , , which may be an independent cardiovascular disease (CVD) risk factor , ; this translated into a benefit in morbidity and mortality rates . Furthermore, resolution of non-alcoholic fatty liver disease (NAFLD)-non alcoholic steatohepatitis (NASH), by atorvastatin , or rosuvastatin , was associated with an independent reduction in vascular events at a level almost double that in those with normal liver function on the same dose , . In this context, do the authors have any information on the effect of CKD, SUA, or NAFLD/NASH on vascular events in their population? Also, did any of these factors improve on statin treatment?

Is there any evidence of a role for metabolic syndrome (MetS)? Two diagnostic characteristics of MetS, high density lipoprotein cholesterol (HDL-C) and hypertension , were significantly lower and higher, respectively, in the mortality group in the Kazerooni and Lim study. Triglyceride levels, another MetS diagnostic characteristic , were higher in the mortality group, but this did not achieve significance. BMI, which reflects waist circumference, a key MetS diagnostic characteristic , was lower in the mortality group. Obesity followed the same pattern as BMI. There are no glucose (the 5th and final MetS diagnostic characteristic) levels. Is there an explanation for the possible BMI/obesity paradox? Was there a greater number of patients in the mortality group who were so ill that they had some degree of “cachexia”?

The high tobacco consumption in both studied groups (survival and mortality) is of interest and may explain why this strong predictor, second after abnormal lipids, accounting for most of the risk of vascular events worldwide , did not differ significantly between these groups.