Risk of Stroke in Patients with Type 2 Diabetes: A Secondary Analysis of the SPARCL Trial

Studies have shown that individuals with type 2 diabetes mellitus (DM) are at increased risk of stroke and coronary heart disease (CHD). Moreover, the presence of metabolic syndrome (MetS) or insulin resistance can identify those at higher risk for developing DM and is associated with an increase in stroke and cardiovascular morbidity. Each of the components of MetS (hypertension, high triglyceride level, low high-density lipoprotein cholesterol [HDL-C] level, high serum glucose level, and abdominal obesity) increases the likelihood of stroke. MetS has also been associated with other conditions associated with increased stroke risk, including symptomatic intracranial stenosis and carotid atherosclerosis. The SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial demonstrated that treatment with statins reduced the risk of stroke in patients with recent stroke or transient ischemic attack and no known CHD. Researchers recently conducted a secondary analysis of the SPARCL trial to examine the impact of having DM or MetS on the effect of statin treatment for secondary stroke prevention. They reported results of the secondary analysis in Archives of Neurology [2011;68(10):1245-1251]. Based on data collected at baseline, the participants in the SPARCL trial (n=4731) were classified as having DM at enrollment (n=794), MetS retrospectively (n=642), or neither DM nor MetS (reference group, n=3295). The primary end point was the combined risk of nonfatal and fatal stroke; secondary end points were major coronary events, major cardiovascular events, any CHD event, and any revascularization procedure. For the secondary analysis, researchers used Cox regression models to determine whether the effect of treatment on any of the end points varied based on the presence of DM or MetS. Patients with DM were, on average, 4 years older than those with MetS. At randomization, there was no difference among the 3 groups in the distribution of ischemic stroke subtypes. Among the 642 patients in the MetS group, 60% were obese, 39% had glycemic abnormalities, 70% had hypertension, 83% had hypertriglyceridemia, and 77% had reduced HDL-C values. Treatment with atorvastatin was associated with similar reductions in low-density lipoprotein cholesterol levels across the 3 groups. In the group with DM, triglyceride levels were reduced by 11.3%, versus 20.2% in the MetS group, and 9.0% in the reference group. HDL-C levels were similar across groups at baseline and during the study period in both the atorvastatin and placebo arms. In the reference group, the risk of stroke was 11.0%, compared with 18.1% in the DM group (P<.001) and 10.7% in the MetS group (P=.78). In addition, patients in the DM group were more likely to have all end points, including death (P<.001). In the MetS group, there was no increase in the risk of major cardiovascular events (P=.38) or major coronary events (P=.19). Patients in the MetS group were more likely to have any CHD event (P=.01) or revascularization procedure (P=.001). There was no treatment × subgroup interaction for the SPARCL primary end point (P=.47). In addition, there was no difference in subtypes of stroke (ischemic or hemorrhagic) between groups. The researchers concluded that, “The SPARCL subjects with type 2 diabetes were at higher risk of recurrent stroke and cardiovascular events. This exploratory analysis found no difference in the effect of statin treatment in reducing these events in subjects with or without type 2 diabetes or MetS.”