Lower LDL = reduced IMT

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Effect of Lower Targets for Blood Pressure and LDL Cholesterol on

Atherosclerosis in Diabetes

The SANDS Randomized Trial

Barbara V. , PhD; J. Roman, MD; B. Devereux, MD;

Jerome L. Fleg, MD; M. Galloway, MD; A. , MD,

MPH; Wm. , MD; T. Lee, PhD; Mihriye Mete, PhD; Bryce

Poolaw, MD; E. Ratner, MD; Marie , MD; Silverman,

MSN, CANP; Stylianou, PhD; G. Umans, MD, PhD; Wenyu Wang,

PhD; R. Weir, MD; Neil J. Weissman, MD; Charlton , MD;

Fawn Yeh, PhD; Jianhui Zhu, MD

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

Context Individuals with diabetes are at increased risk for

cardiovascular disease (CVD), but more aggressive targets for risk

factor control have not been tested.

Objective To compare progression of subclinical atherosclerosis in

adults with type 2 diabetes treated to reach aggressive targets of

low-density lipoprotein cholesterol (LDL-C) of 70 mg/dL or lower and

systolic blood pressure (SBP) of 115 mm Hg or lower vs standard

targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower.

Design, Setting, and Participants A randomized, open-label,

blinded-to-end point, 3-year trial from April 2003-July 2007 at 4

clinical centers in Oklahoma, Arizona, and South Dakota. Participants

were 499 American Indian men and women aged 40 years or older with

type 2 diabetes and no prior CVD events.

Interventions Participants were randomized to aggressive (n=252) vs

standard (n=247) treatment groups with stepped treatment algorithms

defined for both.

Main Outcome Measures Primary end point was progression of

atherosclerosis measured by common carotid artery intimal medial

thickness (IMT). Secondary end points were other carotid and cardiac

ultrasonographic measures and clinical events.

Results Mean target LDL-C and SBP levels for both groups were reached

and maintained. Mean (95% confidence interval) levels for LDL-C in the

last 12 months were 72 (69-75) and 104 (101-106) mg/dL and SBP levels

were 117 (115-118) and 129 (128-130) mm Hg in the aggressive vs

standard groups, respectively. Compared with baseline, IMT regressed

in the aggressive group and progressed in the standard group (–0.012

mm vs 0.038 mm; P < .001); carotid arterial cross-sectional area also

regressed (–0.02 mm2 vs 1.05 mm2; P < .001); and there was greater

decrease in left ventricular mass index (–2.4 g/m2.7 vs –1.2 g/m2.7; P

= .03) in the aggressive group. Rates of adverse events (38.5% and

26.7%; P = .005) and serious adverse events (n = 4 vs 1; P = .18)

related to blood pressure medications were higher in the aggressive

group. Clinical CVD events (1.6/100 and 1.5/100 person-years; P = .87)

did not differ significantly between groups.

Conclusions Reducing LDL-C and SBP to lower targets resulted in

regression of carotid IMT and greater decrease in left ventricular

mass in individuals with type 2 diabetes. Clinical events were lower

than expected and did not differ significantly between groups. Further

follow-up is needed to determine whether these improvements will

result in lower long-term CVD event rates and costs and favorable

risk-benefit outcomes.

Trial Registration clinicaltrials.gov Identifier: NCT00047424

Author Affiliations: MedStar Research Institute, Hyattsville, land

(Drs B. V. , Mete, Ratner, Umans, Weissman, and Zhu, and Ms

Silverman); Weill Cornell Medical College, New York, New York (Drs

Roman and Devereux); National Heart, Lung, and Blood Institute,

Bethesda, land (Drs Fleg and Stylianou); University of Arizona

Health Science Center, Tucson (Dr Galloway); Black Hills Center for

American Indian Health, Rapid City, South Dakota (Dr );

Washington Hospital Center, Washington, DC (Dr W. J. );

University of Oklahoma Health Sciences Center, Oklahoma City (Drs Lee,

Wang, and Yeh); Lawton Indian Hospital, Lawton, Oklahoma (Dr Poolaw);

Phoenix Indian Medical Center, Phoenix, Arizona (Drs and

); and University of land School of Medicine, Baltimore (Dr

Weir).