The three-year study of 499 participants is the first to compare two treatment targets for LDL ("bad") cholesterol and systolic blood pressure levels, key risk factors for heart disease, in people with diabetes. Results are published in the April 9 issue of the Journal of the American Medical Association.
"This study provides good news for adults with type 2 diabetes," said Elizabeth G. Nabel, M.D., NHLBI director. "These patients are two to four times more likely than people without diabetes to die from heart disease. For the first time, we have evidence that aggressively lowering LDL cholesterol and blood pressure can actually reverse damage to the arteries in middle-aged adults with diabetes."
In the Stop Atherosclerosis in Native Diabetics Study (SANDS), approximately one-half of the participants (247) were asked to lower to standard levels their LDL cholesterol (to 100 milligrams per deciliter) and blood pressure (systolic blood pressure of 130 mmHg or lower), while the other half (252) aimed for more aggressive lowering of LDL cholesterol to 70 mg/dL or lower and of systolic blood pressure to 115 mmHg or lower. All participants were American Indians 40 years or older (average age of 56) who had diabetes, high blood cholesterol, and high blood pressure but no history of heart attack or other evidence of heart disease. The study was conducted at four clinical centers in southwestern Oklahoma; Phoenix, Ariz.; northeastern Arizona; and South Dakota. All participants continued to receive their medical care, including diabetes management, dietary and exercise counseling, and smoking cessation, from their health care providers with the Indian Health Service. Like the NIH, the Indian Health Service is part of the U.S. Department of Health and Human Services.
"American Indians have a high rate of diabetes and cardiovascular disease related to diabetes, but there are few clinical trials that address these issues in this population," said Barbara V. Howard, Ph.D., of MedStar Research Institute in Hyattsville, Md., lead author of the paper. "These study results provide needed evidence to help develop community-based programs to treat and prevent the epidemic of cardiovascular disease among American Indians. At the same time, we are increasing our understanding of the effects of intensively lowering cholesterol and blood pressure in adults with type 2 diabetes, which might also apply to other populations."
During the three-year study, participants were examined by study clinicians one month after enrollment, then every three months, to assess their blood cholesterol and blood pressure levels and general well being. Food and Drug Administration-approved blood pressure and cholesterol medications were added and adjusted as needed to help participants achieve their treatment goals. The same medications were available to participants in the standard and the aggressive treatment groups. Participants were also encouraged to follow lifestyle approaches to help meet their blood pressure and cholesterol treatment targets, such as following a heart-healthy eating plan, being physically active, maintaining a healthy weight, and not smoking.
To assess the impact of the treatments on the participants' cardiovascular health, researchers used ultrasound to measure the thickness of the carotid (neck) artery -- an indication of hardening of the arteries, a leading effect of high blood pressure and cholesterol and an early sign of cardiovascular disease. In addition, ultrasound was also used to measure the size and function of the left ventricle, the heart's main pumping chamber. Enlarged hearts are known to be predictors of increased risk of heart attack and stroke. These measurements were taken at enrollment, at 18 months, and at 36 months, when the study ended.
On average, participants in both groups reached and maintained their target goals for blood cholesterol and blood pressure levels. The numbers of heart attacks and other cardiovascular events were similar between the two groups and lower than expected.
In addition, carotid artery thickness measurements of participants in the aggressive treatment group were significantly lower than those in the standard treatment group. Researchers report that, compared to baseline, carotid artery thickness increased slightly in the standard group and regressed in the aggressive treatment group, indicating a partial reversal of atherosclerosis. Furthermore, although heart size decreased from baseline in both groups, the beneficial change was significantly greater among participants in the aggressive treatment group.
"Many patients with diabetes do not reach their blood pressure and cholesterol goal levels and thus remain at high risk for heart attacks and stroke," noted Howard. "In our study, participants successfully managed their blood cholesterol and blood pressure to reach their goal levels. Our message to doctors, nurses, and patients is that you can reach your goal levels, and we should work together to help you do that."
As with any therapy, the benefits and risks must be considered for each patient. In SANDS, participants in the aggressive treatment group on average needed more medications and higher doses than the standard treatment group, and they were slightly more likely to have side effects from blood pressure-lowering medications than those in the standard group. Such adverse effects generally resolved, however, after the medication was changed or the dose reduced. There were no differences in side effects related to cholesterol-lowering drugs between the standard and the aggressive treatment groups.
"These encouraging findings from SANDS suggest that more aggressive blood pressure and cholesterol targets than those currently recommended in patients with diabetes may reduce their future cardiovascular risk," said Jerome L. Fleg, M.D., NHLBI project officer of the study and a coauthor of the paper. "Longer term followup of this population as well as additional studies in other populations are needed to confirm the benefit and cost-effectiveness of these lower targets."