Prevalence of Hypertension and Associated Risk Factors in Western Alaska Native People: The Western Alaska Tribal Collaborative for Health (WATCH) Study.

Hypertension is a common chronic disease and a key risk factor in the development of cardiovascular disease. The Western Alaska Tribal Collaborative for Health study consolidates baseline data from four major cohorts residing in the Norton Sound and Yukon-Kuskokwim regions of western Alaska. This consolidated cohort affords an opportunity for a systematic analysis of high blood pressure and its correlates in a unique population with high stroke rates over a wide age range. While the prevalence of hypertension among western Alaska Native people (30%, age-standardized) is slightly less than that of the US general population (33%), cardiovascular disease is a leading cause of mortality in this rural population. The authors found that improvement is needed in hypertension awareness as about two thirds (64%) of patients reported awareness and only 39% with hypertension were controlled on medication. Future analyses assessing risk and protective factors for incident hypertension in this population are indicated.

Discordant association of C-reactive protein with clinical events and coronary luminal narrowing in postmenopausal women: data from the Women's Angiographic Vitamin and Estrogen (WAVE) study.

BACKGROUND: The incidence of cardiovascular events had been shown to be associated with C-reactive protein (CRP). However, it is unclear that the cardiovascular risk associated with CRP is due to progressive coronary narrowing or to other factors such as formation of unstable plaque. This study was designed to determine the effect of baseline CRP on cardiovascular events and on the progression of atherosclerotic narrowing among 423 postmenopausal women with angiographic stenosis between 15% and 75%. HYPOTHESIS: Baseline CRP levels may affect cardiovascular events and progression of atherosclerotic coronary artery narrowing among postmenopausal women. METHODS: Baseline and follow-up (2.8 years) angiographic data were analyzed among 320 women. Women were stratified into 4 quartiles according to baseline CRP levels. The changes in lumen diameter and clinical events in each quartile were compared. RESULTS: The annualized changes in minimal and average lumen diameter in diseased and nondiseased coronary segments were not significantly associated with baseline CRP levels. The composite end point of all-cause mortality and myocardial infarction (MI) increased from 3% (3/107) in the first CRP quartile to 14% (14/98) in fourth CRP quartile (P < 0.001). Similar results were found for cardiovascular death and MI (increased from 1% (2/107) in the first quartile to 11% (11/98) in fourth quartile). The difference remained significant even after adjustment for baseline differences and cardiovascular risk factors. CONCLUSIONS: Higher baseline CRP was associated with increased risk of clinical events but was not associated with annualized change in luminal diameters. Thus, increased risk of adverse events among patients with higher baseline CRP events was independent of progression of atherosclerosis as measured by change in minimal or average luminal diameter.

Effect of cystatin C levels on angiographic atherosclerosis progression and events among postmenopausal women with angiographically decompensated coronary artery disease (from the Women's Angiographic Vitamin and Estrogen [WAVE] study).

End-stage renal disease and mild renal insufficiency are associated with increased cardiovascular risk. Cystatin C, a novel marker of kidney function, was found to be associated with a higher frequency of cardiovascular events and mortality independent of glomerular filtration rate. It remained uncertain, however, whether enhanced cardiovascular risk associated with cystatin C is due to accelerated progression of atherosclerosis or to plaque instability. The aim of this study was to examine the effects of baseline cystatin C on annual change in coronary artery narrowing and clinical events in 423 postmenopausal women with angiographically documented coronary artery disease enrolled in the Women's Angiographic Vitamin and Estrogen (WAVE) trial. Baseline and follow-up (mean 2.8 ± 0.9 years) angiography was performed in 320 women. Angiographic progression of disease and clinical events in each cystatin C quartile were compared. Women with cystatin C levels in the highest quartile were older and more likely to have histories of heart failure and stroke. Annualized changes in minimal and average luminal diameters were similar in diseased and nondiseased segments. All-cause death or myocardial infarction (3.6% vs 15.6%, p <0.001), cardiovascular death or myocardial infarction (2.3% vs 13.5%, p <0.001), and cardiovascular events (3.6% vs 13.5%, p <0.001) were significantly higher in women with baseline cystatin C levels in the highest quartile compared with women with cystatin C levels in the lower 3 quartiles. The risk for clinical events associated with cystatin C remained significantly higher in multivariate logistic regression analysis after adjusting for baseline differences and cardiovascular risk factors. The risk for clinical events was also independent of estimated glomerular filtration rate. In conclusion, in postmenopausal women with angiographically documented coronary artery disease, baseline cystatin C levels were associated with worse clinical outcomes without accelerated progression of atherosclerosis.

Complexity of the relation between hemoglobin A1C, diabetes mellitus, and progression of coronary narrowing in postmenopausal women.

The aim of this study was to assess the effect of diabetes mellitus (DM) and glycosylated hemoglobin (HbA1c) on the progression of atherosclerosis in postmenopausal women. A retrospective analysis of the Women's Angiographic and Vitamin and Estrogen (WAVE) trial, a multicenter randomized trial on progression of atherosclerosis in postmenopausal women, was performed. Baseline and follow-up angiography was performed in 320 women. Minimum luminal diameter and average luminal diameter at baseline and follow-up were measured in 1,735 coronary segments. Measurements and adverse events were grouped on the basis of history of DM and HbA1c. DM was associated with more total cardiac events but with similar rates of death or myocardial infarction. There were greater reductions in minimum luminal diameter and average luminal diameter in segments from patients with known DM (p <0.001) and with a baseline HbA1c ≥6.5% (p = 0.002 and p = 0.004, respectively). The greater reductions in minimum luminal diameter and average luminal diameter in the higher HbA1c strata were only in patients with known DM. More new lesions, however, appeared with baseline HbA1c ≥5.7%, irrespective of a history of DM. In conclusion, the relation between DM and the progression of coronary narrowing in postmenopausal women is complex. Clinically apparent DM, not elevated HbA1c alone, appears to promote the progression of established coronary lesions even in HbA1c ranges diagnostic of pre-DM and DM. This raises the possibility that coronary narrowing of existing stenosis in women with DM may be due to negative remodeling, a complex process that might be less dependent on hyperglycemia than new lesion formation.

Acute myocardial infarction quality of care: the Strong Heart Study.

OBJECTIVES: Evaluate the quality of care provided patients with acute myocardial infarction and compare with similar national and regional data. DESIGN: Case series. SETTING: The Strong Heart Study has extensive population-based data related to cardiovascular events among American Indians living in three rural regions of the United States. PARTICIPANTS: Acute myocardial infarction cases (72) occurring between 1/1/2001 and 12/31/2006 were identified from a cohort of 4549 participants. OUTCOME MEASURES: The proportion of cases that were provided standard quality of care therapy, as defined by the Healthcare Financing Administration and other national organizations. RESULTS: The provision of quality services, such as administration of aspirin on admission and at discharge, reperfusion therapy within 24 hours, prescription of beta blocker medication at discharge, and smoking cessation counseling were found to be 94%, 91%, 92%, 86% and 71%, respectively. The unadjusted, 30 day mortality rate was 17%. CONCLUSION: Despite considerable challenges posed by geographic isolation and small facilities, process measures of the quality of acute myocardial infarction care for participants in this American Indian cohort were comparable to that reported for Medicare beneficiaries nationally and within the resident states of this cohort.

Relationship of glycemia control to lipid and blood pressure lowering and atherosclerosis: the SANDS experience.

OBJECTIVES: Cardiovascular disease prevention for patients with type 2 diabetes is accomplished through hypertension and dyslipidemia management. Although studies have established strategies for lowering low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP), none have examined whether glycemia influences ability to achieve lipid and BP targets. This post hoc analysis from the Stop Atherosclerosis in Native Diabetics Study examines the role of baseline glycemia in achieving standard and aggressive targets and outcomes after 36 months. METHODS: Diabetic individuals aged > 40 years with no cardiovascular events (n = 499) were randomized to aggressive versus standard targets for LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C) and systolic BP (SBP). Management algorithms were used for both groups. Carotid ultrasound and echocardiography were performed at baseline and after 36 months. RESULTS: No differences were observed in baseline hemoglobin A1c between treatment groups nor any significant change in A1c after 36 months in either group. Baseline A1c, however, was significantly and negatively related to achieving LDL-C (P = .007), non-HDL-C (P = .03) and SBP targets (P = .007) and to changes in LDL-C (P = .007), non-HDL-C (P = .03) and SBP (P = .001) in both groups. Baseline A1c failed to predict progression of carotid intima medial thickness (CIMT) (P = .42) or left ventricular mass index (LVMI) (P = .10), nor was it related to the effects of lipid and BP lowering on CIMT and LVMI over 36 months. CONCLUSIONS: In diabetic adults with no cardiovascular disease events, A1c was negatively associated with ability to achieve LDL-C, non-HDL-C and SBP goals but was not independently related to treatment-associated changes in CIMT or LVMI over 36 months.

Achieving lipid targets in adults with type 2 diabetes: the Stop Atherosclerosis in Native Diabetics Study.

BACKGROUND: Although lipid management in diabetes is standard practice, goals often are neither met nor maintained. Strategies for achieving lower targets have not been explored. The Stop Atherosclerosis in Native Diabetics Study randomized patients with diabetes to standard versus aggressive lipid and blood pressure goals for 36 months. OBJECTIVE: To report strategies used to achieve and maintain lipid goals and to report adverse events (AEs). METHODS: Adults with type 2 diabetes and no history of cardiovascular disease (N = 499) were randomized to standard (low-density lipoprotein cholesterol [LDL-C] ≤ 100 mg/dL, non-high-density lipoprotein cholesterol [non-HDL-C] ≤ 130 mg/dL) or aggressive (LDL-C ≤ 70 mg/dL, non-HDL-C ≤ 100 mg/dL) targets. An algorithm was started with statin monotherapy, with intestinally acting agents added as required to reach LDL-C targets.Triglyceride [TG]-lowering agents were next used to reach non-HDL-C goals. Lipid management was performed by mid-level practitioners, with physician consultation, by the use of point-of-care lipid determinations. RESULTS: On average, both groups achieved the LDL-C and non-HDL-C goals within 12 months and maintained them throughout the study. At 36 months, mean (SD) LDL-C and non-HDL-C were 72 (24) and 102 (29) mg/dL in the aggressive group (AGG) and 104 (20) and 138 (26) mg/dL, respectively, in the standard group (STD); systolic blood pressure targets were 115 and 130 mmHg, respectively. A total of 68% of participants reached target LDL-C for greater than 50% of the visits and 46% for greater than 75% of visits. At 36 months, the AGG averaged 1.5 lipid lowering medications and the STD 1.2. Statins were used in 91% and 68% of the AGG and STD; ezetimibe by 31% and 10%; fibrates by 8% and 18%. No serious AEs were observed; AEs occurred in 18% of the AGG and 14% of the STD. CONCLUSION: Standard and aggressive lipid targets can be safely maintained in diabetic patients. Standardized algorithms, point-of-care lipid testing, and nonphysician providers facilitate care delivery.

Cost-effectiveness of lower targets for blood pressure and low-density lipoprotein cholesterol in diabetes: the Stop Atherosclerosis in Native Diabetics Study (SANDS) .

BACKGROUND: The Stop Atherosclerosis in Native Diabetics Study (SANDS) reported cardiovascular benefit of aggressive versus standard treatment targets for both low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) in diabetic individuals. OBJECTIVE: In this analysis, we examined within trial cost-effectiveness of aggressive targets of LDL-C ≤70 mg/dL and systolic BP ≤115 mmHg versus standard targets of LDL-C ≤100 mg/dL and systolic BP ≤130 mmHg. DESIGN: Randomized, open label blinded-to-endpoint 3-year trial. DATA SOURCES: SANDS clinical trial database, Quality of Wellbeing survey, Centers for Medicare and Medicaid Services, Wholesale Drug Prices. TARGET POPULATION: American Indians ≥ age 40 years with type 2 diabetes and no previous cardiovascular events. TIME HORIZON: April 2003 to July 2007. PERSPECTIVE: Health payer. INTERVENTIONS: Participants were randomized to aggressive versus standard groups with treatment algorithms defined for both. OUTCOME MEASURES: Incremental cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: Compared with the standard group, the aggressive group had slightly lower costs of medical services (-$116) but a 54% greater cost for BP medication ($1,242) and a 116% greater cost for lipid-lowering medication ($2,863), resulting in an increased cost of $3,988 over 3 years. Those in the aggressively treated group gained 0.0480 quality-adjusted life-years (QALY) over the standard group. When a 3% discount rate for costs and outcomes was used, the resulting cost per QALY was $82,589. RESULTS OF SENSITIVITY ANALYSIS: The use of a 25%, 50%, and 75% reduction in drug costs resulted in a cost per QALY of $61,329, $40,070, and $18,810, respectively. LIMITATIONS: This study was limited by use of a single ethnic group and by its 3-year duration. CONCLUSIONS: Within this 3-year study, treatment to lower BP and LDL-C below standard targets was not cost-effective because of the cost of the additional medications required to meet the lower targets. With the anticipated availability of generic versions of the BP and lipid-lowering drugs used in SANDS, the cost-effectiveness of this intervention should improve. Published by Elsevier Inc on behalf of the National Lipid Association.

Sleepiness, quality of life, and sleep maintenance in REM versus non-REM sleep-disordered breathing.

RATIONALE: The impact of REM-predominant sleep-disordered breathing (SDB) on sleepiness, quality of life (QOL), and sleep maintenance is uncertain. OBJECTIVE: To evaluate the association of SDB during REM sleep with daytime sleepiness, health-related QOL, and difficulty maintaining sleep, in comparison to their association with SDB during non-REM sleep in a community-based cohort. METHODS: Cross-sectional analysis of 5,649 Sleep Heart Health Study participants (mean age 62.5 [SD = 10.9], 52.6% women, 22.6% ethnic minorities). SDB during REM and non-REM sleep was quantified using polysomnographically derived apnea-hypopnea index in REM (AHI(REM)) and non-REM (AHI(NREM)) sleep. Sleepiness, sleep maintenance, and QOL were respectively quantified using the Epworth Sleepiness Scale (ESS), the Sleep Heart Health Study Sleep Habit Questionnaire, and the physical and mental composites scales of the Medical Outcomes Study Short Form (SF)-36. MEASUREMENTS AND MAIN RESULTS: AHI(REM) was not associated with the ESS scores or the physical and mental components scales scores of the SF-36 after adjusting for demographics, body mass index, and AHI(NREM) x AHI(REM) was not associated with frequent difficulty maintaining sleep or early awakening from sleep. AHI(NREM) was associated with the ESS score (beta = 0.25; 95% confidence interval [CI], 0.16 to 0.34) and the physical (beta = -0.12; 95% CI, -0.42 to -0.01) and mental (beta = -0.20; 95% CI, -0.20 to -0.01) components scores of the SF-36 adjusting for demographics, body mass index, and AHI(REM). CONCLUSIONS: In a community-based sample of middle-aged and older adults, REM-predominant SDB is not independently associated with daytime sleepiness, impaired health-related QOL, or self-reported sleep disruption.

Cardiovascular disease prevalence and its relation to risk factors in Alaska Eskimos.

BACKGROUND AND AIMS: Although Eskimos were thought to be protected from cardiovascular disease (CVD), state health data show a large proportion of deaths from CVD, despite traditional lifestyles and high omega-3 fatty acid intake. This article explores CVD prevalence and its relation to risk factors in Alaska Eskimos. METHODS AND RESULTS: A population-based cohort of 499 Alaska Eskimos > age 45 from the Norton Sound region was examined in 2000-2004 for CVD and associated risk factors as part of the Genetics of Coronary Artery Disease in Alaska Natives study. CVD and atherosclerosis were evaluated and adjudicated using standardized methods. Average age was 58 years; diabetes prevalence was low and high-density lipoprotein cholesterol (HDL-C) concentrations were high, but a large proportion smoked and had high pathogen burden. CVD was higher in men (12.6%) than in women (5.3%) (prevalence ratio 2.4, CI 1.3-4.4). Rates of stroke (6.1% in men, 1.8% in women) were similar to those for coronary heart disease (CHD) (6.1% men, 2.5% women). MI prevalence was low in both genders (1.9% and 0.7%). CVD was higher in men and in those >60 years. Hypertension, diabetes, high LDL-C, high apoB, and low HDL-C were all strong correlates (<.002) and albuminuria and CRP were also correlated with CVD (p<.05) after adjustment for age and gender. Carotid atherosclerosis was correlated with CVD (p=.0079) independent of other risk factors. CONCLUSION: These data show high CHD and stroke prevalence in Alaska Eskimos, despite low average LDL-C and high HDL-C. Hypertension and high LDL-C were independent correlates; identifying these risk factors early and treating to target is recommended.

Safety and feasibility of achieving lower systolic blood pressure goals in persons with type 2 diabetes: the SANDS trial.

The Stop Atherosclerosis in Native Diabetics Study (SANDS) was a randomized open-label clinical trial in type 2 diabetics designed to examine the effects of intensive reduction of blood pressure, aggressive vs standard goals (< or =115/75 mm Hg vs < or =130/80 mm Hg), and low-density lipoprotein (LDL) cholesterol on the composite outcome of change in carotid intimal-medial thickness and cardiovascular events. The study demonstrated that in conjunction with a lower LDL cholesterol target of 70 mg/dL, aggressive systolic blood pressure-lowering resulted in a reduction in carotid intimal-medial thickness and left ventricular mass without measurable differences in cardiovascular events. The blood pressure treatment algorithm included renin-angiotensin system blockade, with other agents added if necessary. The authors conclude that both standard and more aggressive systolic blood pressure reduction can be achieved with excellent safety and good tolerability in patients with type 2 diabetes mellitus.

PREVENTION OF ATHEROSCLEROSIS WITH LDL-C LOWERING - LIPOPROTEIN CHANGES AND INTERACTIONS: THE SANDS STUDY.

BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) with statins reduces atherosclerosis. LDL and high-density lipoprotein (HDL) are commonly measured by their cholesterol content, but non-HDL cholesterol, LDL particle number (LDL-P), or total apolipoprotein B (apoB) may better predict cardiovascular risk. Few studies have examined relations among lipoprotein levels and composition before and after interventions to lower LDL-C and non-HDL-C. OBJECTIVE: To measure changes in carotid artery intimal media thickness (CIMT) and lipid concentration and composition during 36 months of statin therapy. METHODS: Analyses were conducted on 418 diabetic individuals, with complete data and no prior cardiovascular events, who were randomized to aggressive (AG) versus standard (STD) treatment for LDL-C, non-HDL-C, and systolic blood pressure (SBP) as part of the Stop Atherosclerosis in Native Diabetics Study (SANDS). RESULTS: The AG group achieved average LDL-C and non-HDL-C of 71mg/dL and 100mg/dL and a decrease in CIMT. No significant interactions were observed between treatment effect and initial levels of LDL-C, non-HDL-C, HDL-C, triglycerides, apoB, or LDL-P. Decreases in LDL-C (p<.005) and non-HDL-C (p<.001) were independently correlated with CIMT regression in the AG group. Changes in apoB and LDL-P showed borderline correlations with CIMT regression (p=.07 and p=.09). CONCLUSIONS: In diabetic adults with no prior cardiovascular events, treatment to current targets for lipids and SBP reduces atherosclerosis progression and when more aggressive targets are met, atherosclerosis regresses. The aggressive targets for LDL-C and non-HDL-C appeared to be the main determinants of CIMT regression and were more predictive of this outcome than changes in LDL-P or apoB.

Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in type 2 diabetes: the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial.

OBJECTIVES: This secondary analysis from the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial examines the effects of lowering low-density lipoprotein cholesterol (LDL-C) with statins alone versus statins plus ezetimibe on common carotid artery intima-media thickness (CIMT) in patients with type 2 diabetes and no prior cardiovascular event. BACKGROUND: It is unknown whether the addition of ezetimibe to statin therapy affects subclinical atherosclerosis. METHODS: Within an aggressive group (target LDL-C 40 years of age receiving statins plus ezetimibe versus statins alone. The CIMT changes in both aggressive subgroups were compared with changes in the standard subgroups (target LDL-C

C-Reactive protein, insulin resistance, and metabolic syndrome in a population with a high burden of subclinical infection: insights from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study.

OBJECTIVE: To explore relationships between C-reactive protein (CRP), subclinical infection, insulin resistance, and metabolic syndrome. RESEARCH DESIGN AND METHODS: Data from 1,174 Eskimos, aged >/=18 years, from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study were analyzed; 40 participants with diabetes were eliminated. Baseline assessment included interviews, physical exam, and blood and urine sampling. Metabolic syndrome was assessed using Adult Treatment Panel III criteria. CRP and antibodies to common pathogens were measured. RESULTS: Although CRP was related in univariate analyses to insulin resistance and metabolic syndrome, relations were attenuated or eliminated after adjustment for relevant covariates. CRP was not higher among those with impaired fasting glucose (IFG), and pathogen burden was not related to insulin resistance, metabolic syndrome, or IFG. CONCLUSIONS: Pathogen burden and inflammation do not seem to be related to insulin resistance, metabolic syndrome, or IFG in this population. The inflammatory process may reflect insulin resistance or its correlates but most likely is not causative.

Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes: the SANDS randomized trial.

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.

Examination of lower targets for low-density lipoprotein cholesterol and blood pressure in diabetes--the Stop Atherosclerosis in Native Diabetics Study (SANDS).

Diabetes incidence is increasing rapidly in the United States. Diabetes increases the risk for cardiovascular disease, the major cause of death in diabetic individuals. The conventional cardiovascular risk factors of hyperlipidemia and hypertension worsen diabetic vascular disease. Treatment targets for low-density lipoprotein cholesterol (LDL-C) and blood pressure in diabetic individuals are being debated. The SANDS is a randomized, open-label, 3-year trial to examine the effects of aggressive LDL-C (goal <70 mg/dL) and blood pressure (BP) (goal <115/75 mm Hg) reduction versus the standard goals of <100 mg/dL for LDL-C and <130/85 mm Hg for BP. Five hundred forty-nine American-Indian men and women >40 years old with type 2 diabetes were randomized to 1 of 2 groups. Lipids and BP are managed using Food and Drug Administration-approved medications in an algorithmic approach. The presence and progression of atherosclerosis are evaluated by carotid ultrasonography; echocardiography assesses cardiac function. The primary end point is the composite outcome of change in carotid artery intimal medial thickness and fatal/nonfatal cardiovascular events. These outcomes are combined by using a ranked analysis for carotid thickness and assigning a "worst rank" for a cardiovascular event. Secondary end points include carotid plaque score, left ventricular geometry and function, serum C-reactive protein, and safety measures. Unique aspects of the study design and analysis plan involve the use of a composite outcome and changes during the trial of LDL-C treatment goals for participants with baseline or incident cardiovascular disease in the conventional group because of changes in the standard of care. Study results will further understanding of the effects of aggressive risk factor reduction on atherosclerosis burden and cardiac function in diabetic individuals in US populations and will help determine optimal LDL-C and BP treatment goals for diabetic patients.

Postmenopausal hormone therapy is associated with atherosclerosis progression in women with abnormal glucose tolerance.

BACKGROUND: Abnormal glucose tolerance (AGT; diabetes or impaired glucose tolerance) is associated with increased risk of cardiovascular disease, especially in women. Cardiovascular disease rates in women increase after menopause. The Women's Health Initiative found that postmenopausal hormone therapy (PHT) increased the risk of cardiovascular disease and that effects in diabetic women did not differ from those in women without diabetes. In this study, we hypothesized that PHT would have a worse effect on disease among women with AGT. METHODS AND RESULTS: We randomly assigned 423 postmenopausal women with angiographically defined atherosclerosis (321 women had exit angiograms) with (n=140) or without (n=181) AGT to receive estrogen, estrogen plus progestin, or a placebo for 2.8+/-0.9 years. LDL was lower and HDL and triglycerides were higher after PHT in non-AGT and AGT women, but more adverse changes occurred in C-reactive protein and fibrinogen in women with AGT (P=0.11 and P=0.02 for interactions). PHT had no effect on fasting glucose or insulin concentrations in women without AGT, but in women with AGT, fasting glucose levels, insulin concentration, and insulin resistance as assessed by the HOMA (homeostasis model) calculation decreased slightly (P=0.28, P=0.25, P=0.14 for interaction, respectively). Atherosclerotic progression was greater in women with AGT. Atherosclerotic progression in previously nondiseased segments was enhanced by PHT to a greater extent in women with AGT (P=0.11 for interaction). CONCLUSIONS: PHT is associated with a worsening of coronary atherosclerosis and exacerbation of the profile of inflammatory markers in women with AGT. Therefore, PHT is not warranted for use in diabetic women. Further study is needed to explore the improvement in insulin resistance and glycemia that appears to occur with PHT in women with AGT.