Gail C. Frank

Conjugated Equine Estrogens and Colorectal Cancer Incidence and Survival: The Women's Health Initiative Randomized Clinical Trial

Background: In separate Womens Health Initiative randomized trials, combined hormone therapy with estrogen plus progestin reduced colorectal cancer incidence but estrogen alone in women with hysterectomy did not. We now analyze features of the colorectal cancers that developed and examine the survival of women following colorectal cancer diagnosis in the latter trial. Participants and Methods: 10,739 postmenopausal women who were 50 to 79 years of age and had undergone hysterectomy were randomized to conjugated equine estrogens (0.625 mg/d) or matching placebo. Colorectal cancer incidence was a component of the monitoring global index of the study but was not a primary study endpoint. Colorectal cancers were verified by central medical record and pathology report review. Bowel exam frequency was not protocol defined, but information on their use was collected. Results: After a median 7.1 years, there were 58 invasive colorectal cancers in the hormone group and 53 in the placebo group [hazard ratio, 1.12; 95% confidence interval (95% CI), 0.77-1.63]. Tumor size, stage, and grade were comparable in the two randomization groups. Bowel exam frequency was also comparable in the two groups. The cumulative mortality following colorectal cancer diagnosis among women in the conjugated equine estrogen group was 34% compared with 30% in the placebo group (hazard ratio, 1.34; 95% CI, 0.58-3.19). Conclusions: In contrast to the preponderance of observational studies, conjugated equine estrogens in a randomized clinical trial did not reduce colorectal cancer incidence nor improve survival after diagnosis. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2609–18)

Fatty acid consumption and risk of fracture in the Women's Health Initiative

BACKGROUND Fatty acids (FAs) may be important dietary components that modulate osteoporotic fracture risk. OBJECTIVE The objective was to examine FA intake in relation to osteoporotic fractures. DESIGN The participants were postmenopausal women enrolled in the Womens Health Initiative (n = 137,486). Total fractures were identified by self-report; hip fractures were confirmed by medical record review. FA intake was estimated from baseline food-frequency questionnaires and standardized to total caloric intake. No data on omega-3 (n-3) FA supplements were available. Cox proportional hazard models were constructed to estimate risk of fracture. RESULTS Higher saturated FA consumption was associated with higher hip fracture risk [quartile 4 multivariate-adjusted hazard ratio (HR): 1.31; 95% CI: 1.11, 1.55; P for trend = 0.001]. Lower total fracture risk was associated with a higher monounsaturated FA intake (quartile 3 HR: 0.94; 95% CI: 0.89, 0.98; P for trend = 0.050) and polyunsaturated FA intake (quartile 4 HR: 0.95; 95% CI: 0.90, 0.99; P for trend = 0.019). Unexpectedly, higher consumption of marine n-3 FAs was associated with greater total fracture risk (quartile 4 HR: 1.07; 95% CI: 1.02, 1.12; P for trend = 0.010), whereas a higher n-6 FA intake was associated with a lower total fracture risk (quartile 4 HR: 0.94; 95% CI: 0.89, 0.98; P for trend 0.009). CONCLUSIONS These results suggest that saturated FA intake may significantly increase hip fracture risk, whereas monounsaturated and polyunsaturated FA intakes may decrease total fracture risk. In postmenopausal women with a low intake of marine n-3 FAs, a higher intake of n-6 FAs may modestly decrease total fracture risk. This trial was registered at clinicaltrials.gov as NCT00000611.

A model of intervention for prevention of early essential hypertension in the 1980s.

The onset of essential hypertension early in life is indicated by the high tracking of blood pressure during adolescence; intervention in adults with mild hypertension has been found successful. How, then, can high blood pressure levels in children be modified to prevent early hypertensive cardiovascular disease in adulthood? In an entire biracial town (population 9000) we surveyed 1604 (89%) of all children aged 8--18 years for blood pressure and reexamined those in the upper decile of mean blood pressure (for each race, sex, and height) on three additional occasions. On each examination nine blood pressures were taken by trained observers. All children consistently in the top decile were randomly allocated into either a treatment (n = 50) or comparison (n = 50) group. These two groups and an additional midrange blood pressure comparison group (n = 50) were followed regularly using school facilities including community and school programs. Treatment consisted of 1) dietary guidance; 2) modifications of school lunches and snacks with healthy substitutes; 3) parental involvement; 4) a low dose diuretic and beta-antagonist given by usual standards. All study groups were monitored for blood pressure in a blind manner. In 6 months of observation, blood pressure in the treatment group remained 5 and 3 mm Hg (systolic and diastolic) less than controls (p less than 0.001 and p less than 0.01). An orchestrated community-wide attack on early-stage hypertension is feasible and seems to offer exciting potential for prevention of early hypertensive disease.

Black-white contrasts as determinants of cardiovascular risk in childhood: Precursors of coronary artery and primary hypertensive diseases☆

Atherosclerosis and hypertension begin in childhood. Studies of children have identified black-white differences in anthropometric, hormonal, enzymatic, and renal mechanisms related to the development of coronary artery disease and hypertension. Black children have greater body density, higher blood pressure, and higher serum total cholesterol, alpha-lipoprotein cholesterol, and insulin levels, whereas white children have a higher percentage of body fat, a faster heart rate, and higher hemoglobin, serum triglyceride, pre-beta-lipoprotein cholesterol, plasma renin, and dopamine-beta-hydroxylase levels. At puberty, white male children have decreased high-density lipoprotein (HDL) levels and increased low-density lipoprotein/HDL ratios. Black children have lower urinary K+ excretion and demonstrate natriuresis when K+ is administered orally. These black-white contrasts provide clues for studying disease development early in life. Rational approaches to primary prevention of atherosclerosis and hypertension may require a diversity of strategies because of these black-white differences.

Dietary Studies of Infants and Children: The Bogalusa Heart Study

Publisher Summary Certain eating behaviors in early life may represent health risks. Excessive energy intake may predispose a person to obesity. A potential elevation of serum lipids may result from abundant animal protein and fat intakes. Iron deficiency anemia may be aggravated by inadequate iron intakes. Early use of alcohol may increase the likelihood of future dependency. Sodium may predispose to later hypertension, and sucrose can increase the risk of dental caries and obesity. All these eating and drinking behaviors may contribute to disease states. This chapter focuses on these and other eating behaviors and describes the prevalence of excessive or inadequate nutrient intake and/or eating patterns as observed in the Bogalusa Heart Study. The chapter also discusses specific dietary components, such as energy, protein, saturated fat, cholesterol, sodium, sucrose, and iron. Correcting an energy imbalance either by a reduction of energy, protein, sucrose, and saturated fat or by an increase in physical activity or by both is an effective method of weight reduction.

Dietary Studies of Ten-year-old Children in the Bogalusa Heart Study

One of the major questions concerning the pathogenesis of atherosclerosis and hypertension is, “What environmental factors influence the development of these major cardiovascular diseases?” Of the environmental factors, nutrition plays a major role. The Bogalusa Heart Study, a large epidemiologic program of the Specialized Center of Research—Arteriosclerosis (SCOR-A) at the Louisiana State University Medical Center, is conducting research on the early natural history of arteriosclerosis (a term used here to encompass both atherosclerosis and hypertension). Risk factor variables, similar to those that have been described in adults, are being studied in Bogalusa, Louisiana, as a total community study of children in a biracial population. Since risk factors in adults have been shown to be predictive of the development of morbid events complicating coronary artery disease and hypertension (American Heart Association, 1973), it is important to observe the early onset and progression of the risk factors.