Achieving Lower Target Levels for Blood Pressure, LDL-Cholesterol May Provide Cardiovascular Benefits

Patients with diabetes who reduced their blood pressure and LDL-cholesterol to below standard target levels had a greater decrease in carotid artery wall thickness, but did not have a significant difference in cardiovascular disease events than patients who had recommended blood pressure and LDL-cholesterol levels, according to a study in the April 9 issue of JAMA.1


Individuals with diabetes are at increased risk for developing cardiovascular disease (CVD), and coronary heart disease (CHD) is the leading cause of death in adults with diabetes, according to background information in the article. The increased diabetes-associated CVD risk is due in large part to higher prevalences of other major CVD risk factors, such as dyslipidemia (disorders of lipoprotein metabolism, which includes high cholesterol levels) and hypertension. Some studies have suggested that lowering systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) below recommended levels in patients with diabetes may be beneficial regarding CVD.


Barbara V. Howard, Ph.D., of MedStar Research Institute, Hyattsville, Md., and colleagues conducted SANDS (Stop Atherosclerosis in Native Diabetics Study), a clinical trial that compared the progression of subclinical atherosclerotic disease (process in which plaque builds up in the inner lining of the arteries) in 499 American Indian men and women with type 2 diabetes, randomly assigned either to reach aggressive targets of LDL-C of 70 mg/dL or lower plus SBP of 115 mm Hg or lower or to reach standard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower. American Indians have a high prevalence of diabetes and diabetes-related CVD. The 3-year trial was conducted at four clinical centers in Oklahoma, Arizona and South Dakota.


Average target LDL-C and SBP levels for both groups were reached and maintained. Compared with baseline, intimal medial thickness (IMT; measurement of thickness of the wall in an artery and a marker for atherosclerosis) regressed in the aggressive treatment group and progressed in the standard treatment group; carotid arterial (one of two major arteries) cross-sectional area also regressed. Rates of adverse events (38.5 percent and 26.7 percent) and serious adverse events (n = 4 vs. 1) related to blood pressure medications were higher in the aggressive group. Clinical CVD events did not differ significantly between groups.


“Although there were no differences in clinical CVD outcomes, event rates were low in both groups, and progression of subclinical disease in the standard treatment group was lower than expected. The data suggest that targeted treatment of LDL-C and SBP improved surrogate measures of CVD, with greater benefits being attributable to the lower target levels. Conversely, the lack of difference in occurrence of events and the increase in adverse events and serious adverse events attributable to the BP lowering raise the possibility that there may not be favorable long-term outcomes. Whether the strategy of more aggressive targets for either LDL-C or BP will result in lower long-term CVD event rates or economic benefit remains to be determined.”


In an accompanying editorial, Eric D. Peterson, M.D., M.P.H., and Tracy Y. Wang, M.D., M.S., of Duke University Medical Center, Durham, N.C., (Dr. Peterson is also Contributing Editor, JAMA), comment on the findings of Howard and colleagues.2


“What are the take-home messages from SANDS? For the true believers, the study confirms that aggressive lipid and hypertension treatment has a favorable effect on proven ‘early markers’ of disease. Thus, with longer duration of follow-up (which will hopefully be the case), the study would most assuredly demonstrate improved patient outcomes. For the therapeutic nihilists, however, SANDS took high-risk patients with type 2 diabetes, studied them under idealized circumstances, and still found no clinical benefit after 3 years of follow-up. In fact, an aggressive approach involved greater polypharmacy and costs and had a higher risk of adverse effects.”


“In conclusion, SANDS is an important step forward in discovering whether lower goals are truly better for primary prevention. While the study results can be interpreted to support both viewpoints on the ideal target of therapy, such debates are healthy and will ultimately drive physicians to search for more definitive evidence as well as to seek system-wide strategies to effectively reach therapeutic goals in community practice,” they write.


1. JAMA. 2008; 299[14]:1678-1689.


2. JAMA. 2008; 299[14]:1718-1720.