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 mm(2) vs 1.05 mm(2); P < .001); and there was greater decrease in left ventricular mass index (-2.4 g/m(2.7) vs -1.2 g/m(2.7); 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.
RCT Entities:
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 mm(2) vs 1.05 mm(2); P < .001); and there was greater decrease in left ventricular mass index (-2.4 g/m(2.7) vs -1.2 g/m(2.7); 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.
Authors: Allen J Taylor; Steven M Kent; Patrick J Flaherty; Louis C Coyle; Thor T Markwood; Marina N Vernalis Journal: Circulation Date: 2002-10-15 Impact factor: 29.690
Authors: B J Hoogwerf; A Waness; M Cressman; J Canner; L Campeau; M Domanski; N Geller; A Herd; A Hickey; D B Hunninghake; G L Knatterud; C White Journal: Diabetes Date: 1999-06 Impact factor: 9.461
Authors: F M Sacks; M A Pfeffer; L A Moye; J L Rouleau; J D Rutherford; T G Cole; L Brown; J W Warnica; J M Arnold; C C Wun; B R Davis; E Braunwald Journal: N Engl J Med Date: 1996-10-03 Impact factor: 91.245
Authors: Anthony Keech; David Colquhoun; James Best; Adrienne Kirby; R John Simes; David Hunt; Wendy Hague; Elaine Beller; Manjula Arulchelvam; Jennifer Baker; Andrew Tonkin Journal: Diabetes Care Date: 2003-10 Impact factor: 19.112
Authors: J R Downs; M Clearfield; S Weis; E Whitney; D R Shapiro; P A Beere; A Langendorfer; E A Stein; W Kruyer; A M Gotto Journal: JAMA Date: 1998-05-27 Impact factor: 56.272
Authors: Peter M Okin; Richard B Devereux; Sverker Jern; Sverre E Kjeldsen; Stevo Julius; Markku S Nieminen; Steven Snapinn; Katherine E Harris; Peter Aurup; Jonathan M Edelman; Hans Wedel; Lars H Lindholm; Björn Dahlöf Journal: JAMA Date: 2004-11-17 Impact factor: 56.272
Authors: Marie Russell; Angela Silverman; Jerome L Fleg; Elisa T Lee; Mihriye Mete; Matthew Weir; Charlton Wilson; Fawn Yeh; Barbara V Howard; W M James Howard Journal: J Clin Lipidol Date: 2010 Sep-Oct Impact factor: 4.766
Authors: Vera Bittner; Marnie Bertolet; Rafael Barraza Felix; Michael E Farkouh; Suzanne Goldberg; Kodangudi B Ramanathan; J Bruce Redmon; Laurence Sperling; Martin K Rutter Journal: J Am Coll Cardiol Date: 2015-08-18 Impact factor: 24.094
Authors: Mary J Roman; Jorge R Kizer; Lyle G Best; Elisa T Lee; Barbara V Howard; Nawar M Shara; Richard B Devereux Journal: Hypertension Date: 2011-11-07 Impact factor: 10.190
Authors: S Eilat-Adar; M Mete; A Fretts; R R Fabsitz; V Handeland; E T Lee; C Loria; J Xu; J Yeh; B V Howard Journal: Nutr Metab Cardiovasc Dis Date: 2012-04-24 Impact factor: 4.222
Authors: Khadijah Breathett; Mario Sims; Marie Gross; Elizabeth A Jackson; Emily J Jones; Ana Navas-Acien; Herman Taylor; Kevin L Thomas; Barbara V Howard Journal: Circulation Date: 2020-05-28 Impact factor: 29.690