Should the LDL target be the same for prediabetes as overt diabetes?

The target could be even lower.

Ideally, one would aim for an LDL target of less than 70 mg/dL in all patients at risk for CVD — both prediabetes and diabetes, as well as those with documented coronary or vascular disease. The JUPITER trial results help support this, in which participants achieved a goal of 50 mg/dL. In general, we aim as low as possible on reasonable dosing, and match the intensity of statin therapy and LDL-lowering to the risk of the patient.

Christopher Cannon, MD
Christopher Cannon

Patients with prediabetes are lower risk than those with overt diabetes, so one could tolerate slightly higher LDL levels; a target LDL of less than 100 mg/dL is probably fine for this group.

For people with prediabetes, I begin with standard statin dosing, usually simvastatin 40 mg. If the LDL is less than 70 mg/dL, I am thrilled; if less than 100 mg/dL, that is OK. If LDL is greater than 100 mg/dL, then I would increase the statin to a strong one, such as atorvastatin 80 mg or rosuvastatin 20 mg or 40 mg. My reasoning for ‘lower is better’ is based on many studies, including PROVE IT-TIMI 22, which showed that a high-dose statin (with average LDL less than 70 mg/dL) was better than a regular-dose statin (average LDL less than 100 mg/dL) in patients after acute coronary syndromes (ACS). Four other trials have shown the same in patients with coronary artery disease or ACS.

Diabetes is close to a CAD equivalent, so one tries to do roughly the same for patients with diabetes without CAD as for patients with CAD, although they are actually at lower risk. The REACH 4 study, which was published in the Journal of the American Medical Association in September, is one example of this.

Christopher Cannon, MD, is associate professor of medicine at Harvard Medical School and associate physician in the cardiovascular division at Brigham and Women’s Hospital.

Target should be the same as for diabetes, plus lifestyle intervention.

The question of how statins should be used in the estimated 57 million people with prediabetes in the United States, most of whom do not have CVD, is a complex one. First, a recent review of studies indicates that their overall 5- to 10-year risk for CVD is only modestly increased compared with the general population. Second there is increasing evidence that most patients with diabetes do not have a CVD risk equivalent, and this is likely to be especially true of people with newly developing diabetes. Third, there seems little doubt that within this population there is a wide variation in CVD risk. Finally a significant proportion of dysglycemic individuals do not develop diabetes even after 10 years.

Ronald B. Goldberg, MD
Ronald B. Goldberg

Clearly, people with prediabetes and evident CVD should be aggressively treated with maximum statin therapy in most cases. It also seems reasonable based on the JUPITER results that men over 50 years and women over 60 years who have high sensitivity C-reactive protein values >2 mg/L — a common finding in dysglycemic individuals — should be managed in the same way.

There are no data available to assist us in developing statin treatment guidelines in the rest of the population and especially for glucose intolerant men under 50 or women under 60. However it is likely that CVD risk factors other than glucose are primarily driving CVD events in these individuals. Accordingly, a reasonable proposal would be to recommend that these individuals be followed regularly and assessed for statin therapy in the same way as would their euglycemic counterparts, with the additional strong recommendation that measures that have been shown to prevent progression to diabetes as well as ameliorate CVD risk factors, such as lifestyle change, and in selected cases, metformin treatment, be actively instituted in this population.

Ronald B. Goldberg, MD, is professor of medicine in the division of endocrinology, diabetes and metabolism at the Diabetes Research Institute, University of Miami Miller School of Medicine.