Fawn Yeh

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.

Changes in Cardiovascular Disease Risk Factors among American Indians: The Strong Heart Study

PURPOSE This study describes changes in cardiovascular disease (CVD) risk factors in older American Indians over a 4-year period. METHODS The Strong Heart Study, a longitudinal population-based study of CVD and CVD risk factors among American Indians aged 45-74 years, measured CVD risk factors among 3638 members of 13 tribes in three geographic areas during examinations in 1989 to 1991 and 1993 to 1995. RESULTS Changes in mean low-density lipoprotein (LDL) cholesterol and the prevalence of elevated LDL cholesterol were inconsistent. Mean high- density lipoprotein (HDL) cholesterol decreased, and the prevalence of low HDL cholesterol increased throughout. Mean systolic blood pressure and hypertension rates increased in nearly all center-sex groups, and hypertension awareness and treatment improved. Smoking rates decreased but remained higher than national rates except among Arizona women. Mean weight and percentage body fat decreased in nearly all center-sex groups but the prevalence of obesity did not change significantly in any group. Diabetes and albuminuria prevalence rates increased throughout the study population. The prevalence of alcohol use decreased, but binge drinking remained common in those who continued to drink. CONCLUSIONS Improvements in management and prevention of hypertension, diabetes, renal disease, and obesity, and programs to further reduce smoking and alcohol abuse, are urgently needed.

Obesity in Adults Is Associated With Reduced Lung Function in Metabolic Syndrome and Diabetes: The Strong Heart Study

OBJECTIVE The purposes of this study were to investigate whether reduced lung function is associated with metabolic syndrome (MS) and diabetes (DM) in American Indians (AIs) and to determine whether lower pulmonary function presents before the development of DM or MS. RESEARCH DESIGN AND METHODS The Strong Heart Study (SHS) is a multicenter, prospective study of cardiovascular disease (CVD) and its risk factors among AI adults. The present analysis used lung function assessment by standard spirometry at the SHS second examination (1993–1995) in 2,396 adults free of overt lung disease or CVD, with or without DM or MS. Among MS-free/DM-free participants, the development of MS/DM at the SHS third examination (1996–1999) was investigated. RESULTS Significantly lower pulmonary function was observed for AIs with MS or DM. Impaired pulmonary function was associated with MS and DM after adjustment for age, sex, abdominal obesity, current smoking status, physical activity index, hypertension, and SHS field center. Both forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were negatively associated with insulin resistance or DM severity and with serum markers of inflammation (P < 0.05). FVC and FEV1-to-FVC ratio both predicted DM in unadjusted analyses but not when adjusted for covariates, including waist circumference. In the adjusted model, abdominal obesity predicted both MS and DM. CONCLUSIONS Reduced lung function is independently associated with MS and with DM, and impaired lung function presents before the development of MS or DM; these associations may result from the effects of obesity and inflammation.

Urine Arsenic and Prevalent Albuminuria: Evidence From a Population-Based Study

BACKGROUND Long-term arsenic exposure is a major global health problem. However, few epidemiologic studies have evaluated the association of arsenic with kidney measures. Our objective was to evaluate the cross-sectional association between inorganic arsenic exposure and albuminuria in American Indian adults from rural areas of Arizona, Oklahoma, and North and South Dakota. STUDY DESIGN Cross-sectional. SETTING & PARTIPANTS: Strong Heart Study locations in Arizona, Oklahoma, and North and South Dakota. 3,821 American Indian men and women aged 45-74 years with urine arsenic and albumin measurements. PREDICTOR Urine arsenic. OUTCOMES Urine albumin-creatinine ratio and albuminuria status. MEASUREMENTS Arsenic exposure was estimated by measuring total urine arsenic and urine arsenic species using inductively coupled plasma mass spectrometry (ICPMS) and high-performance liquid chromatography-ICPMS, respectively. Urine albumin was measured by automated nephelometric immunochemistry. RESULTS The prevalence of albuminuria (albumin-creatinine ratio ≥30 mg/g) was 30%. Median value for the sum of inorganic and methylated arsenic species was 9.7 (IQR, 5.8-15.6) μg per gram of creatinine. Multivariable-adjusted prevalence ratios of albuminuria (albumin-creatinine ratio ≥30 mg/g) comparing the 3 highest to lowest quartiles of the sum of inorganic and methylated arsenic species were 1.16 (95% CI, 1.00-1.34), 1.24 (95% CI, 1.07-1.43), and 1.55 (95% CI, 1.35-1.78), respectively (P for trend <0.001). The association between urine arsenic and albuminuria was observed across all participant subgroups evaluated and was evident for both micro- and macroalbuminuria. LIMITATIONS The cross-sectional design cannot rule out reverse causation. CONCLUSIONS Increasing urine arsenic concentrations were cross-sectionally associated with increased albuminuria in a rural US population with a high burden of diabetes and obesity. Prospective epidemiologic and mechanistic evidence is needed to understand the role of arsenic as a kidney disease risk factor.

Aging and the Prevalence of Cardiovascular Disease Risk Factors in Older American Indians: The Strong Heart Study

OBJECTIVES: To describe longitudinal changes in the prevalence of major cardiovascular disease (CVD) risk factors in aging American Indians.

The Association of Urine Arsenic with Prevalent and Incident Chronic Kidney Disease: Evidence from the Strong Heart Study

Background: Few studies have evaluated associations between low to moderate arsenic levels and chronic kidney disease (CKD). The objective was to evaluate the associations of inorganic arsenic exposure with prevalent and incident CKD in American Indian adults. Methods: We evaluated the associations of inorganic arsenic exposure with CKD in American Indians who participated in the Strong Heart Study in 3,851 adults ages 45–74 years in a cross-sectional analysis, and 3,119 adults with follow-up data in a prospective analysis. Inorganic arsenic, monomethylarsonate, and dimethylarsinate were measured in urine at baseline. CKD was defined as estimated glomerular filtration rate ⩽ 60 ml/min/1.73 m2, kidney transplant or dialysis. Results: CKD prevalence was 10.3%. The median (IQR) concentration of inorganic plus methylated arsenic species (total arsenic) in urine was 9.7 (5.8, 15.7) &mgr;g/L. The adjusted odds ratio (OR; 95% confidence interval) of prevalent CKD for an interquartile range in total arsenic was 0.7 (0.6, 0.8), mostly due to an inverse association with inorganic arsenic (OR: 0.4 [0.3, 0.4]). Monomethylarsonate and dimethylarsinate were positively associated with prevalent CKD after adjustment for inorganic arsenic (OR: 3.8 and 1.8). The adjusted hazard ratio of incident CKD for an IQR in sum of inorganic and methylated arsenic was 1.2 (1.03, 1.41). The corresponding HRs for inorganic arsenic, monomethylarsonate, and dimethylarsinate were 1.0 (0.9, 1.2), 1.2 (1.00, 1.3), and 1.2 (1.0, 1.4). Conclusions: The inverse association of urine inorganic arsenic with prevalent CKD suggests that kidney disease affects excretion of inorganic arsenic. Arsenic species were positively associated with incident CKD. Studies with repeated measures are needed to further characterize the relation between arsenic and kidney disease development.

Tobacco use among American Indians in Oklahoma: An epidemiologic view

Objectives. With the exception of national surveys that sample the entire U.S. population, little information exists on tobacco habits among American Indians. This study is a comparison of tobacco use findings in the 1990s among American Indians in Oklahoma, a state with a large and diverse American Indian population (39 tribes). Methods. Data on current tobacco use are presented from two statewide surveys, the Oklahoma Youth Tobacco Survey and the Native American Behavioral Risk Factor Survey, as well as two large epidemiologic studies of chronic disease among American Indians—the Cherokee Diabetes Study and the Strong Heart Study. Three of these four sources of data involve research/surveys exclusively about American Indians. Results. Nontraditional use of tobacco by American Indians occurs frequently, according to each instrument. Initiation to this habit begins in middle school and increases dramatically during high school. After age 50, reporting by individuals that they currently smoke declines steadily. Conclusions. Despite sampling different individuals for the surveys and different tribes for the epidemiologic research, results were comparable in age groups that overlapped. These findings support national data indicating that American Indians have higher prevalence rates of smoking than other racial/ethnic groups. American Indians report smoking on average about a half a pack of cigarettes per day. Individuals reporting using tobacco solely for ceremonial purposes were far fewer than habitual users. Buying tobacco products in American Indian smoke shops helps tribal economies; this fact needs to be considered for prevention programs to succeed.

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 (≤115/75 mm Hg vs ≤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.

Effect of Lower Targets for Blood Pressure and LDL Cholesterol on Atherosclerosis in Diabetes

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.

Insulin Resistance, Incident Cardiovascular Diseases, and Decreased Kidney Function Among Nondiabetic American Indians: The Strong Heart Study

OBJECTIVE Prevalence of insulin resistance is high in the American Indian population, likely as a result of the high prevalence of obesity. This condition may be influential for clinical outcomes such as cardiovascular disease (CVD) and decreased kidney function. RESEARCH DESIGN AND METHODS Normal glucose tolerant (NGT) participants free of hypertension and CVD at the baseline examination (1989–1992) (N = 964) of the Strong Heart Study were selected to explore the cross-sectional association between insulin resistance quantified by homeostasis model assessment (HOMA-IR) and demographic, behavioral, and cardiometabolic variables. The longitudinal association between baseline HOMA-IR and the development of CVD was also explored. The longitudinal association between baseline HOMA-IR and the development of high urinary albumin-to-creatinine ratio was explored among nondiabetic participants (N = 1,401). RESULTS Cross-sectionally, HOMA-IR was associated with sex, residence location, smoking, and high-risk cardiometabolic profile. Prospectively, insulin resistance is associated with the development of CVD and decreased kidney function in this population. CONCLUSIONS Insulin resistance may have an important role in the pathogenesis of CVD and chronic kidney disease. Since obesity contributes to the development of insulin resistance, intervention focusing on modifiable factors such as physical activity and weight control may reduce the development of these diseases.