Progression of Vascular Calcification Is Increased with Statin Use

The purpose of the study was to determine the effect of statin use on progression of vascular calcification in type 2 diabetes (T2DM).

The results of the study showed that the progression of coronary artery calcification (CAC) and abdominal aortic artery calcification (AAC) was accelerated according to the frequency of statin use in 197 participants with T2DM.

After adjustment for baseline CAC and other confounders, progression of CAC was significantly higher in more frequent statin users than in less frequent users (mean ± SE, 8.2 ± 0.5 mm(3) vs. 4.2 ± 1.1 mm(3); P < 0.01). AAC progression was in general not significantly increased with more frequent statin use; in a subgroup of participants initially not receiving statins, however, progression of both CAC and AAC was significantly increased in frequent statin users.

From the results it was concluded that, more frequent statin use is associated with accelerated coronary artery calcification in T2DM patients with advanced atherosclerosis.

The role of statins in prevention of cardiovascular disease (CVD) in type 2 diabetes (T2DM) is well established. Despite the wide use of statins, however, calcification atherosclerosis is accelerated in T2DM and is associated with increased risk of CVD morbidity and mortality in this population. The purpose of the current study was to determine the effect of statin use on progression of vascular calcification in T2DM participants with advanced atherosclerosis.

In this cohort of T2DM patients with advanced atherosclerosis, we found that more frequent statin use was associated with accelerated progression of CAC. These findings are consistent with those reported in a previous study of T2DMparticipants without previous coronary artery disease. Results of this earlier study were believed to result from higher baseline CAC scores and insufficient lowering of LDL at follow-up in the statin users.

In the study, however, there were no significant differences in baseline CAC or AAC according to statin use. In addition, at the end of the study more frequent statin users had significantly lower and nearly optimal LDL cholesterol levels. Moreover, adjustment for baseline and on-trial risk factors, including LDL cholesterol and baseline CAC, did not explain the greater CAC progression in frequent statin users. Randomized controlled trials in largely nondiabetic populations with no previous CAD demonstrated that, despite potent lipid-lowering effects, statin agents do not reduce the progression of CAC or AAC. In fact, there was a trend toward progression of CAC with statin treatment in several studies. We now demonstrate that even in a setting of optimal lipid lowering and similar baseline CAC and AAC, statin agents promote calcification in T2DM subjects with advanced atherosclerosis.

Because the variation in progression of AAC scores is greater, it is possible that the lack of significantly greater AAC progression with statin use is a sample size issue. Among those not initially on statins at baseline, however, the magnitude of AAC progression in those with subsequent frequent statin use was large enough to achieve statistical significance. Statins have been implicated in calcification of vascular smooth muscle cells and mesenchymal cells. Statins also lower the lipid-rich core of atherosclerotic plaques and may enhance the density of calcification as part of a healing process, potentially contributing to plaque stabilization and decreased CVD events.

Alternatively, accelerated progression of calcified atherosclerosis in T2DM by statins may have the effect of lessening these medications' overall benefit. Long-term follow-up in this cohort will help determine whether accelerated CAC and AAC progression in statin users is associated with more or fewer CVD events compared with statin users with less progression.

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• Abraira C, Duckworth W, McCarren M, et al; VA Cooperative Study of Glycemic Control and Complications in Diabetes Mellitus Type 2. Design of the cooperative study on glycemic control and complications in diabetes mellitus type 2: Veterans Affairs Diabetes Trial. J Diabetes Complications 2003;17:314–322 3. Duckworth W, Abraira C, Moritz T, et al 

Diabetes Care, online August 2012