Lower target levels for blood pressure and ldl-cholesterol could provide early cardiovascular benfits but may not work forever


Lower target levels for blood pressure and ldl-cholesterol could provide early cardiovascular benfits but may not work forever


When American Indian patients with diabetes reduced their blood pressure and LDL-cholesterol to below a standard target level had a greater decrease in cartoid artery wall thickness in a study published no April 9, 2008 in JAMA. According to the same study, there was no decrease in cardiovascular disease events in comparison with those who still had the recommended blood pressure and LDL-cholesterol levels.

Diabetic patients have an increased risk of developing cardiovascular disease (CVD). In fact, coronary heart disease (CHD) is the leading cause of death in diabetic adults. This is largely caused by higher instances of other CVD risk factors, such as: dyslipidemia, a group of lipoprotein metabolism disorders that often include high cholesterol levels; and hypertension. Notably, American Indians have a high frequency of diabetes and diabetes-related CVD.

One indication of CVD is subclinical atherosclerotic disease, in which plaque builds up on the inner lining of the arteries. This is often gagued using the intimial medial thickness (IMT), which is a measurement of the thickness in the wall of the artery.

Previous studies have indicated that a decreased systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) levels could be beneficial in discouraging CVD. To find out if this was true, Barbara V. Howard, Ph.D., of MedStar Research Institute, Hyattsville, Md., and colleagues conducted SANDS (Stop Atherosclerosis in Native Diabetics Study), which the progression of subclinical atherosclerotic disease in 499 American Indian men and women with type 2 diabetes in four clinical centers in Oklahoma, Arizona, and South Dakota over a three year period. The patients were randomly assigned to one of two groups: to reach an aggressive target LDL-C level of 70 mg/dL or lower and SBP of 115 mmHG or lower; or, in a group to reach the standard targets of LDL-C of 100 mg/dL or lower and an SBP of 130 mmHg or lower.

Both the group targeting the aggressively low levels and the group targeting the standard treatment levels were able to reach their goals and maintain them. In comparison with the baseline at the start of the study, the IMT regressed in the aggressive treatment group while continuing to progress in the standard treatment. This might indicate that the levels of athersclerosis were decreasing. However, the cross sectional area of the cartoid artery also regressed.

In the end, the rates of adverse events in general and in related to blood pressure medications were greater in the aggressive group compared to the standard group. the Clinical CVD adverse events did not differ significantly.

The authors indicate that this more aggressive treatment may not be a good option in the long term. "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."

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), wrote an accompanying comment in which they describe the difficulties in translating these results into practical terms. "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."

Effect of Lower Targets for Blood Pressure and LDL Cholesterol on Atherosclerosis in Diabetes: The SANDS Randomized Trial

Barbara V. Howard; Mary J. Roman; Richard B. Devereux; Jerome L. Fleg; James M. Galloway; Jeffrey A. Henderson; Wm. James Howard; Elisa T. Lee; Mihriye Mete; Bryce Poolaw; Robert E. Ratner; Marie Russell; Angela Silverman; Mario Stylianou; Jason G. Umans; Wenyu Wang; Matthew R. Weir; Neil J. Weissman; Charlton Wilson; Fawn Yeh; Jianhui Zhu

JAMA. 2008;299(14):1678-1689.

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The Great Debate of 2008 - How Low to Go in Preventive Cardiology?

Eric D. Peterson; Tracy Y. Wang

JAMA. 2008;299(14):1718-1720.

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Section Issues On Medicine: Cardiology