Linda D. Cowan

Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study.

A cohort of 2270 white women, aged 40-69 years at baseline, were followed for an average of 8.5 years in the Lipid Research Clinics Program Follow-up Study. There were 44 deaths due to cardiovascular disease among the 1677 nonusers of estrogens and six cardiovascular disease deaths among the 593 estrogen users. The age-adjusted relative risk (RR) of cardiovascular disease deaths in users compared with nonusers was 0.34 (95% confidence limits 0.12 to 0.81). After multivariable adjustment for potential confounding factors (age, blood pressure, and smoking), the estimated RR for estrogen use was 0.37 (95% confidence limits 0.16 to 0.88). Analyses were done to explore whether these results could be due to selection bias for estrogen use. However, the prevalence of cardiovascular disease at baseline was slightly higher in estrogen users (12%) than in nonusers (10%); furthermore, the exclusion of all women with prevalent cardiovascular disease at baseline did not alter the apparent protective effect of estrogen...

Rising Tide of Cardiovascular Disease in American Indians The Strong Heart Study

BACKGROUND Although cardiovascular disease (CVD) used to be rare among American Indians, Indian Health Service data suggest that CVD mortality rates vary greatly among American Indian communities and appear to be increasing. The Strong Heart Study was initiated to investigate CVD and its risk factors in American Indians in 13 communities in Arizona, Oklahoma, and South/North Dakota. METHODS AND RESULTS A total of 4549 participants (1846 men and 2703 women 45 to 74 years old) who were seen at the baseline (1989 to 1991) examination were subjected to surveillance (average 4.2 years, 1991 to 1995), and 88% of those remaining alive underwent a second examination (1993 to 1995). The medical records of all participants were exhaustively reviewed to ascertain nonfatal cardiovascular events that occurred since the baseline examination or to definitively determine cause of death. CVD morbidity and mortality rates were higher in men than in women and were similar in the 3 geographic areas. Coronary heart disease (CHD) incidence rates among American Indian men and women were almost 2-fold higher than those in the Atherosclerosis Risk in Communities Study. Significant independent predictors of CVD in women were diabetes, age, obesity (inverse), LDL cholesterol, albuminuria, triglycerides, and hypertension. In men, diabetes, age, LDL cholesterol, albuminuria, and hypertension were independent predictors of CVD. CONCLUSIONS At present, CHD rates in American Indians exceed rates in other US populations and may more often be fatal. Unlike other ethnic groups, American Indians appear to have an increasing incidence of CHD, possibly related to the high prevalence of diabetes. In the general US population, the rising prevalence of obesity and diabetes may reverse the decline in CVD death rates. Therefore, aggressive programs to control diabetes and its risk factors are needed.

Plasma Triglyceride Level and Mortality from Coronary Heart Disease

BACKGROUND Whether the plasma triglyceride level is a risk factor for coronary heart disease has been controversial, and evaluation of the triglyceride level as a risk factor is fraught with methodologic difficulties. METHODS We studied the association between plasma triglyceride levels and the 12-year incidence of death from coronary heart disease in 10 North American populations participating in the Lipid Research Clinics Follow-up Study, while adjusting for the potential confounding effects of other risk factors for cardiovascular disease, including the level of high-density lipoprotein (HDL) cholesterol. All analyses were sex-specific, and separate analyses were performed in high and low strata of HDL cholesterol, low-density lipoprotein (LDL) cholesterol, fasting plasma glucose, and age. RESULTS The rates of coronary death in both men and women increased with the triglyceride level. In Cox proportional-hazards models adjusted for age, in which the natural log of the triglyceride levels was used to give a normal distribution, the relative risk per natural-log unit of triglyceride (e.g., a triglyceride level of 150 mg per deciliter vs. a level of 55 mg per deciliter) was 1.54 (95 percent confidence interval, 1.19 to 1.98; P < 0.001) in men and 1.88 (95 percent confidence interval, 1.19 to 2.98; P < 0.007) in women. After an adjustment for potential covariates, however, these relative risks were not statistically significant. Analyses based on lipoprotein cholesterol levels revealed a positive association between the triglyceride level and coronary mortality in the lower stratum of both HDL and LDL cholesterol, but not in the higher stratum. Conversely, the HDL cholesterol level was unrelated to coronary mortality in the lower stratum of LDL cholesterol, but was strongly inversely associated with coronary death in the higher stratum of LDL cholesterol. The relative risk of coronary death associated with triglyceride level was higher at younger ages. The associations between the triglyceride level and coronary mortality in the lower HDL cholesterol, LDL cholesterol, and age strata were small and were further reduced by an adjustment for the fasting plasma glucose level. CONCLUSIONS Overall, the plasma triglyceride level showed no independent association with coronary mortality. However, in subgroups of subjects with lower HDL and LDL cholesterol levels and in younger subjects, defined a priori, an association between the triglyceride level and coronary mortality was observed, although this association was small and was not statistically significant after an adjustment for the plasma glucose level.

Adverse Effects of Diabetes on Multiple Cardiovascular Disease Risk Factors in Women: The Strong Heart Study

OBJECTIVE Many studies have shown that diabetes increases the risk of cardiovascular disease (CVD) in women to a greater extent than in men. One explanation could be that diabetes has more adverse effects on CVD risk factors in women than in men. We compared diabetes-associated differences in CVD risk factors in men and women in the Strong Heart Study, a population-based study of CVD and its risk factors in American Indians. RESEARCH DESIGN AND METHODS A total of 1,846 men and 2,703 women between the ages of 45 and 74 years from 13 American Indian communities in three geographic areas underwent an examination that included a medical history; an electrocardiogram; anthropometric and blood pressure measurements; an oral glucose tolerance test; and measurements of fasting plasma lipoproteins, fibrinogen, insulin, HbA1c, and urinary albumin. RESULTS Statistically significantly greater adverse differences in those with diabetes versus those without diabetes were observed in women than in men for waist-to-hip ratio, HDL cholesterol, apolipoprotein (apo)B, apoA1, fibrinogen, and LDL size. In multiple linear regression models adjusting for age, center, sex, and diabetes, the diabetes by sex interaction terms were statistically significant for waist-to-hip ratio, LDL cholesterol, HDL cholesterol, apoB, apoA1, fibrinogen, and LDL size. CONCLUSIONS Compared with diabetes-associated differences in men, diabetes in women was related to greater adverse differences in levels of several CVD risk factors. Although the magnitude of the individual diabetes-related differences between men and women was not large, the combined effects of these risk factor differences in diabetic women may be substantial. The apparent greater negative impact of diabetes on CVD risk factors in women may explain, in part, the greater risk for CVD in diabetic women.

LDL Cholesterol as a Strong Predictor of Coronary Heart Disease in Diabetic Individuals With Insulin Resistance and Low LDL The Strong Heart Study

Diabetes has been shown to increase the risk of coronary heart disease in all populations studied. However, there is a lack of information on the relative importance of diabetes-associated risk factors for cardiovascular disease (CVD), especially the role of lipid levels, because low density lipoprotein (LDL) cholesterol often is not elevated in diabetic individuals. The objective of this analysis was to evaluate CVD risk factors in a large cohort of diabetic individuals and to compare the importance of dyslipidemia (ie, elevated triglycerides and low levels of high density lipoprotein [HDL] cholesterol) and LDL cholesterol in determining CVD risk in diabetic individuals. The Strong Heart Study assesses coronary heart disease and its risk factors in American Indians in Arizona, Oklahoma, and South/North Dakota. The baseline clinical examinations (July 1989 to January 1992) consisted of a personal interview, physical examination, and drawing of blood samples for 4549 study participants (2034 with diabetes), 45 to 74 years of age. Follow-up averaged 4.8 years. Fatal and nonfatal CVD events were confirmed by standardized record review. Participants with diabetes, compared with those with normal glucose tolerance, had lower LDL cholesterol levels but significantly elevated triglyceride levels, lower HDL cholesterol levels, and smaller LDL particle size. Significant independent predictors of CVD in those with diabetes included age, albuminuria, LDL cholesterol, HDL cholesterol (inverse), fibrinogen, and percent body fat (inverse). A 10-mg/dL increase in LDL cholesterol was associated with a 12% increase in CVD risk. Thus, even at concentrations well below the National Cholesterol Education Program target of 130 mg/dL, LDL cholesterol is a strong independent predictor of coronary heart disease in individuals with diabetes, even when components of diabetic dyslipidemia are present. These results support recent recommendations for aggressive control of LDL cholesterol in diabetic individuals, with a target level of <100 mg/dL.

Diabetes and Impaired Glucose Tolerance in Three American Indian Populations Aged 45-74 Years: The Strong Heart Study

OBJECTIVE To estimate prevalence rates of diabetes and impaired glucose tolerance (IGT) in three American Indian populations, using standardized diagnostic criteria, and to assess the association of diabetes with the following selected possible risk factors: age, obesity, family history of diabetes, and amount of Indian ancestry. RESEARCH DESIGN AND METHODS This cross-sectional study involved enrolled members, men and women aged 45-74 years, of 13 American Indian tribes or communities in Arizona, Oklahoma, and South and North Dakota. Eligible participants were invited to the clinic for a personal interview and a physical examination. Diabetes and IGT status were defined by the World Health Organization criteria and were based on fasting plasma glucose and oral glucose tolerance test results. Data on age, family history of diabetes, and amount of Indian ancestry were obtained from the personal interview, and measures of obesity included body mass index, percentage body fat, and waist-to-hip ratio. RESULTS A total of 4,549 eligible participants were examined, and diabetes status was determined for4,304(1,446 in Arizona, 1,449 in Oklahoma, and 1,409 in the Dakotas). In all three centers, diabetes was more prevalent in women than in men. Arizona had the highest age-adjusted rates of diabetes: 65% in men and 72% in women. Diabetes rates in Oklahoma (38% in men and 42% in women) and South and North Dakota (33% in men and 40% in women), although considerably lower than in Arizona, were several times higher than those reported for the U.S. population. Rates of IGT among the three populations (14-17%) were similar to those in the U.S. population. Diabetes rates were positively associated with age, level of obesity, amount of Indian ancestry, and parental diabetes status. CONCLUSIONS Diabetes is found in epidemic proportions in Native American populations. Prevention programs and periodic screening should be implemented among American Indians. Standards of care and intervention have been developed by the Indian Health Service for individuals in whom diabetes is diagnosed. These programs shoula be expanded to include those with IGT to improve glycemie control or to reduce the risk of development of diabetes as well as to reduce the risk of diabetic complications.

Clinical Manifestations Associated with Neurocysticercosis: A Systematic Review

Background The clinical manifestations of neurocysticercosis (NCC) are poorly understood. This systematic review aims to estimate the frequencies of different manifestations, complications and disabilities associated with NCC. Methods A systematic search of the literature published from January 1, 1990, to June 1, 2008, in 24 different electronic databases and 8 languages was conducted. Meta-analyses were conducted when appropriate. Results A total of 1569 documents were identified, and 21 included in the analysis. Among patients seen in neurology clinics, seizures/epilepsy were the most common manifestations (78.8%, 95%CI: 65.1%–89.7%) followed by headaches (37.9%, 95%CI: 23.3%–53.7%), focal deficits (16.0%, 95%CI: 9.7%–23.6%) and signs of increased intracranial pressure (11.7%, 95%CI: 6.0%–18.9%). All other manifestations occurred in less than 10% of symptomatic NCC patients. Only four studies reported on the mortality rate of NCC. Conclusions NCC is a pleomorphic disease linked to a range of manifestations. Although definitions of manifestations were very rarely provided, and varied from study to study, the proportion of NCC cases with seizures/epilepsy and the proportion of headaches were consistent across studies. These estimates are only applicable to patients who are ill enough to seek care in neurology clinics and likely over estimate the frequency of manifestations among all NCC cases.

Incidence and Risk Factors for Stroke in American Indians The Strong Heart Study

Background— There are few published data on the incidence of fatal and nonfatal stroke in American Indians. The aims of this observational study were to determine the incidence of stroke and to elucidate stroke risk factors among American Indians. Methods and Results— This report is based on 4549 participants aged 45 to 74 years at enrollment in the Strong Heart Study, the largest longitudinal, population-based study of cardiovascular disease and its risk factors in a diverse group of American Indians. At baseline examination in 1989 to 1992, 42 participants (age- and sex-adjusted prevalence proportion 1132/100 000, adjusted to the age and sex distribution of the US adult population in 1990) had prevalent stroke. Through December 2004, 306 (6.8%) of 4507 participants without prior stroke suffered a first stroke at a mean age of 66.5 years. The age- and sex-adjusted incidence was 679/100 000 person-years. Nonhemorrhagic cerebral infarction occurred in 86% of participants with incident strokes; 14% had hemorrhagic stroke. The overall age-adjusted 30-day case-fatality rate from first stroke was 18%, with a 1-year case-fatality rate of 32%. Age, diastolic blood pressure, fasting glucose, hemoglobin A1c, smoking, albuminuria, hypertension, prehypertension, and diabetes mellitus were risk factors for incident stroke. Conclusions— Compared with US white and black populations, American Indians have a higher incidence of stroke. The case-fatality rate for first stroke is also higher in American Indians than in the US white or black population in the same age range. Our findings suggest that blood pressure and glucose control and smoking avoidance may be important avenues for stroke prevention in this population.

Relation of LDL Size to the Insulin Resistance Syndrome and Coronary Heart Disease in American Indians The Strong Heart Study

Small, dense LDL has been shown to be associated with the insulin resistance syndrome and coronary heart disease (CHD). We examined the distribution of LDL size and phenotype within a population-based sample of American Indians to determine the relationships with prevalent CHD and to examine associations with hyperinsulinemia and other components of the insulin resistance syndrome. Data were available for 4505 men and women between 45 and 74 years of age who are members of 13 American Indian communities in three geographic areas. Diabetes, CHD, and CHD risk factors were assessed by standardized techniques, and LDL size was measured by gradient gel electrophoresis. LDL size was smaller in men than in women and in individuals with diabetes than in those without diabetes. In multivariate analysis, LDL size was significantly related to several components of the insulin resistance syndrome, including triglycerides (inversely) and HDL cholesterol (positively). Although univariate relations were positive, LDL size was not significantly related to fasting insulin concentrations or body mass index in the multivariate model. LDL size also showed no relationship to apolipoprotein E phenotype. When LDL size was compared in individuals with and without CHD, no significant differences were observed, either in nondiabetic or diabetic individuals. We conclude that LDL size is most strongly related to lipoprotein components of the insulin resistance syndrome, especially plasma triglycerides. However, in this population with low LDL, it is not related to cardiovascular disease.

Risk Factors for Coronary Heart Disease in Diabetic and Nondiabetic Native Americans: The Strong Heart Study

The Strong Heart Study is a study of cardiovascular disease and its risk factors among diabetic and nondiabetic Native Americans. The study includes 12 tribes in Arizona, Oklahoma, and North and South Dakota. Phase I, initiated in October 1988, included a mortality survey to determine CVD death rates in individuals 35–74 yr old between 1984 and 1988, and a medical record review to determine rates of myocardial infarction and stroke for individuals ages 45–74 during the same time. In addition, a physical examination was performed on persons 45–74 yr old to measure the prevalence of cardiovascular and peripheral vascular diseases and known and suspected risk factors, in Phase II, CVD mortality and morbidity rates will be determined in the examined cohort by surveillance. CVD risk factors, changes in risk factors over time, and the relationship between risk factors and CVD incidence will be assessed longitudinally. This study provides data on the relative importance of cardiovascular risk factors in nondiabetic and diabetic Native Americans and will provide insight into possible variations in the quantitative or qualitative importance of CVD risk factors among diverse population groups.