Available data indicate that cardiovascular disease has become the leading cause of death in American Indians. However, limited information is available on cardiovascular disease incidence, prevalence, and risk factors in this population. Reported cardiovascular disease rates vary greatly among groups in different geographic areas. These rates have been obtained from studies of varying sizes and different methodologies. The Strong Heart Study, which uses standardized methodology, is designed to estimate cardiovascular disease mortality and morbidity rates and the prevalence of known and suspected cardiovascular disease risk factors in American Indians. The study population consists of 12 tribes in three geographic areas: an area near Phoenix, Arizona, the southwestern area of Oklahoma, and the Aberdeen area of North and South Dakota. The study includes three components. The first is a mortality survey to estimate cardiovascular disease mortality rates for 1984-1988 among tribal members aged 35-74 years, and the second is a morbidity survey to estimate incidence of both first and first or recurrent hospitalized myocardial infarction and stroke (cerebrovascular disease) among tribal members aged 45-74 years in 1984-1988, and the third is a clinical examination of 4,500 tribal members aged 45-74 years in order to estimate the prevalence of cardiovascular disease and its associations with risk factors. Family history, diet, alcohol and tobacco consumption, physical activity, degree of acculturation, and socioeconomic status are assessed in personal interviews. The physical examination includes measurements of body fat, body circumferences, and blood pressure, an examination of the heart and lungs, an evaluation of peripheral vascular disease, and a 12-lead electrocardiogram. Laboratory measurements include fasting and postload glucose, insulin, fasting lipids, apoproteins, fibrinogen, and glycated hemoglobin. Also measured are serum and urine creatinine and urinary albumin. DNA from lymphocytes is isolated and stored for future genetic studies.

Previous data suggest that apolipoprotein (apo) CIII may inhibit both triglyceride hydrolysis by lipoprotein lipase (LPL) and apo E-mediated uptake of triglyceride-rich lipoproteins by the liver. We studied apo B metabolism in very low density (VLDL), intermediate density (IDL), and low density lipoproteins (LDL) in two sisters with apo CiII-apo AI deficiency. The subjects had reduced levels of VLDL triglyceride, normal LDL cholesterol, and near absence of high density lipoprotein (HDL) cholesterol. Compartmental analysis of the kinetics of apo B metabolism after injection of '"I-VLDL and 131I-LDL revealed fractional catabolic rates (FCR) for VLDL apo B that were six to seven times faster than normal. Simultaneous injection of V3Hjglycerol demonstrated rapid catabolism of VLDL triglyceride. VLDL apo B was rapidly and efficiently converted to IDL and LDL. The FCR for LDL apo B was normal.In vitro experiments indicated that, although sera from the apo CII-apo-AI deficient patients were able to normally activate purified LPL, increasing volumes of these sera did not result in the progressive inhibition of LPL activity demonstrable with normal sera. Addition of purified apo CIII to the deficient sera resulted in 20-50% reductions in maximal LPL activity compared with levels of activity attained with the same volumes of the native, deficient sera. These in vitro studies, together with the in vivo results, indicate that in normal subjects apo CIII can inhibit the catabolism of triglyceride-rich lipoproteins by lipoprotein lipase.

Peripheral blood C-reactive protein (CRP) is a biomarker used clinically to measure systemic inflammation and is reproducibly increased in a subset of patients with major depressive disorder (MDD). Furthermore, increased peripheral blood CRP in MDD has been associated with altered reward circuitry and increased brain glutamate in relation with symptoms of anhedonia. Nevertheless, the relationship between peripheral CRP and other peripheral and central markers of inflammation in depressed patients has not been established. Plasma (n=89) and CSF (n=73) was collected from medically-stable, currently-unmedicated adult outpatients with MDD. Associations among plasma and CSF CRP and plasma and CSF inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF] and IL-1beta) and their soluble receptors/antagonists were examined. Relationships between plasma and CSF inflammatory markers and depressive symptoms including anhedonia and reduced motivation (RM) were also explored. Plasma CRP was correlated with multiple plasma inflammatory markers (all p<0.05), and a strong correlation was found between plasma and CSF CRP (r=0.855, p<0.001). CSF CRP in turn correlated with CSF cytokine receptors/antagonists (all p<0.05). Principal component analyses revealed clusters of CSF inflammatory markers that were associated with high plasma CRP (>3mg/L) and correlated with depressive symptom severity. These findings were driven by CSF TNF, which correlated with RM (r=0.236, p=0.045), and CSF IL-6 soluble receptor, which correlated with anhedonia (r=0.301, p=0.010) in the sample as a whole and particularly females. CRP appears to be a peripheral biomarker that reflects peripheral and central inflammation and seems well-suited for guiding immunotherapies targeting TNF and IL-6 in patients with MDD.

OBJECTIVE: To determine the effect of exercise training (ET) on components of the insulin resistance syndrome (IRS) in obese children. DESIGN: Randomized, modi®ed cross-over study, with subjects assigned to one of two conditions: (1) 4 months of ET followed by 4 months of no-ET; or (2) 4 months of no-ET followed by 4 months of ET. Measurements were made at three time points: 0, 4 and 8 months. SUBJECTS: 79 obese, but otherwise healthy children (age: 7 ± 11 y, percent fat (%fat) 27 ± 61%). MEASUREMENTS: Plasma lipid and lipoprotein concentrations, plasma insulin and glucose concentrations; %fat; submaximal heart rate (HR) as an index of ®tness. EXERCISE TRAINING: ET was offered 5 daweek 40 minad. For the 73 children who completed 4 months of ET, the mean attendance was 80% (that is, 4 daweek) and the average HR during ET was 157 bpm. RESULTS: Signi®cant (P`0.05) group x time interactions were found for plasma triglyceride (TG) and insulin concentrations and %fat. The average change for both groups, from just before ET to just after the 4 month ET was À0.24 mmol Á l À1 for TG, À25.4 pmol Á l À1 for insulin and À1.6 units for %fat. When Group 1 ceased ET, over the following 4 month period the average change for insulin was 26.6 pmol Á l À1 and for %fat 1.3 units. CONCLUSION: Some components (plasma TG, insulin, %fat) of the IRS are improved as a result of 4 months of ET in obese children. However, the bene®ts of ET are lost when obese children become less active.

The Strong Heart Study, a study of cardiovascular disease among American Indians, was conducted to determine cardiovascular disease rates and the prevalence of risk factors among members of 13 tribal groups in South Dakota/North Dakota (SD/ND), southeastern Oklahoma, and Arizona. From 1989 to 1992, 4,549 tribal members aged 45-74 years (62% of eligible participants) were surveyed and examined for cardiovascular disease and its risk factors. Mean total cholesterol concentrations were over 20 mg/dl lower among the men and 27 mg/dl lower among the women than national mean levels for the same age groups. Cholesterol levels varied by tribal group; Arizona Indians had mean levels more than 20 mg/dl lower than those of SD/ND Indians. The prevalence of hypercholesterolemia was almost twice as high among SD/ND Indians as among Arizona Indians, but the rates for all three groups were much lower than total US rates (all races). Mean levels of high density lipoprotein cholesterol were lower among Indian men and women than in the US population as a whole. The prevalence of hypertension among Arizona and Oklahoma Indians was higher than that for the entire United States. SD/ND Indians had significantly lower mean blood pressures and prevalence rates of hypertension than Oklahoma and Arizona Indians and the United States as a whole. The prevalence of cigarette smoking was higher for all Indian groups except Arizona women in comparison with US rates. Smoking rates were highest in SD/ND and lowest in Arizona. Indian smokers smoked fewer cigarettes per day than the average US smoker. Arizona Indians had the highest prevalence of diabetes mellitus; over 60% of those participants were diabetic. In Oklahoma and SD/ND, one third of the men and over 40% of the women were diabetic. In addition, 13-20% of the participants had impaired glucose tolerance. Proteinuria was also a common problem; almost half of the Arizona Indians had micro- or macroalbuminuria, and 20% of Oklahoma and SD/ND Indians had significant proteinuria. The prevalence of obesity was high in all three groups, with Arizona Indians having the highest rates and the highest mean body mass indices. The prevalence of current alcohol use was lower among Indians than in the nation as a whole, but binge drinking was common among those who used alcohol. These results indicate that cardiovascular disease risk factors vary significantly among tribal groups. Prevention programs tailored toward decreasing the prevalence of risk factors are recommended for long-term reduction of cardiovascular disease rates in American Indian communities.