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Biomedical subjects

Kathryn M Rexrode

Publications and source records attributed to Kathryn M Rexrode.

At least 19 recordsLinked to original sources

Effects of lymphotoxin-alpha gene and galectin-2 gene polymorphisms on inflammatory biomarkers, cellular adhesion molecules and risk of coronary heart disease.

The pro-inflammatory cytokine LTA (lymphotoxin-alpha) has multiple functions in regulating the immune system and may contribute to inflammatory processes leading to CHD (coronary heart disease). The aim of the present study was to investigate whether the common C804A (resulting in a Thr(26)-->Asp amino acid substitution) and A252G polymorphisms of the LTA gene and the C3279T polymorphism of the galectin-2 (LGALS2) gene, which affects LTA secretion, are associated with inflammatory parameters and cell adhesion molecules, and whether these polymorphisms are related to CHD in American women and men. We conducted a prospective nested case-control study within the Nurses' Health Study and Health Professionals Follow-Up Study. Among participants free of cardiovascular disease at baseline, 249 women and 266 men developed CHD during 8 and 6 years of follow-up respectively, and we matched controls 2:1 based on age and smoking. The LGALS2 gene variant was significantly associated with a decreased risk of CHD in women [odds ratio (95% confidence interval), 0.70 (0.50-0.97); P=0.03]. In addition, the LGALS2 polymorphism was directly associated with CRP (C-reactive protein) levels in cases from both studies (P<0.05). The LTA gene polymorphisms were directly associated with levels of sTNFRs (soluble tumour necrosis factor receptors) and VCAM-1 (vascular cell adhesion molecule-1) in both women and men with CHD (P<0.05). However, no overall effect was demonstrated between LTA gene polymorphisms and risk of CHD.

Age Factors↗

Use of oral conjugated estrogen alone and risk of breast cancer.

The authors conducted a prospective cohort analysis in the Women's Health Study (1992-2004), a completed randomized trial assessing aspirin and vitamin E in the primary prevention of cancer and cardiovascular disease, to evaluate use of oral conjugated estrogen alone (0.625 mg/day) and breast cancer risk in a time-varying fashion. Over an average of 10 years of follow-up, 305 incident cases of breast cancer (258 invasive and 47 in situ cancers) were documented among 12,718 women aged 45 years or more who were either consistent current users of oral conjugated estrogen alone (0.625 mg/day) or never users of any type of postmenopausal hormones at baseline and during follow-up. The multivariable hazard ratios comparing "consistent current users" with "never users" were 1.11 (95% confidence interval: 0.79, 1.56) for total breast cancer and 1.13 (95% confidence interval: 0.77, 1.64) for invasive cases. No significant associations were observed for use of less than 8 and 8 years or more. Restricting the analyses to women with prior hysterectomy somewhat strengthened the associations, albeit still not significantly. These data, like those from the Women's Health Initiative, show no significant increase in breast cancer risk with use of oral conjugated estrogen alone (0.625 mg/day), but a small increase or decrease in risk cannot be excluded.

Administration, Oral↗

Coffee consumption and coronary heart disease in men and women: a prospective cohort study.

BACKGROUND: We examined the association between long-term habitual coffee consumption and risk of coronary heart disease (CHD). METHODS AND RESULTS: We performed a prospective cohort study with 44,005 men and 84,488 women without history of cardiovascular disease or cancer. Coffee consumption was first assessed in 1986 for men and in 1980 for women and then repeatedly every 2 to 4 years; the follow-up continued through 2000. We documented 2173 incident cases of coronary heart disease (1449 nonfatal myocardial infarctions and 724 fatal cases of CHD) among men and 2254 cases (1561 nonfatal myocardial infarctions and 693 fatal cases of CHD) among women. Among men, after adjustment for age, smoking, and other CHD risk factors, the relative risks (RRs) of CHD across categories of cumulative coffee consumption (<1 cup/mo, 1 cup/mo to 4 cups/wk, 5 to 7 cups/wk, 2 to 3 cups/d, 4 to 5 cups/d, and > or =6 cups/d) were 1.0, 1.04 (95% confidence interval 0.91 to 1.17), 1.02 (0.91 to 1.15), 0.97 (0.86 to 1.11), 1.07 (0.88 to 1.31), and 0.72 (0.49 to 1.07; P for trend=0.41); among women, the RRs were 1.0, 0.97 (0.83 to 1.14), 1.02 (0.90 to 1.17), 0.84 (0.74 to 0.97), 0.99 (0.83 to 1.17), and 0.87 (0.68 to 1.11; P for trend=0.08). Stratification by smoking status, alcohol consumption, history of type 2 diabetes mellitus, and body mass index gave similar results. Similarly, we found no effect when the most recent coffee consumption was examined. RRs for quintiles of caffeine intake varied from 0.97 (0.84 to 1.10) in the second quintile to 0.97 (0.84 to 1.11) in the highest quintile (P for trend=0.82) in men and from 1.02 (0.90 to 1.16) to 0.97 (0.85 to 1.11; P for trend=0.37) in women. CONCLUSIONS: These data do not provide any evidence that coffee consumption increases the risk of CHD.

Caffeine↗

Physical exertion, exercise, and sudden cardiac death in women.

CONTEXT: Exercise is associated with a lower risk of cardiovascular events but may transiently increase the risk of ventricular arrhythmias. Its short-term and long-term associations with risk of sudden cardiac death among women are unclear. OBJECTIVES: To compare the risk of sudden cardiac death in women during moderate to vigorous exertion with the risk of sudden cardiac death during lighter or no exertion; and to assess the long-term association between moderate to vigorous exercise and sudden cardiac death. DESIGN, SETTING, AND PARTICIPANTS: Prospective, nested case-crossover study of 288 cases of sudden cardiac death within the Nurses' Health Study (1980-2004); and a prospective cohort analysis of 69,693 participants without prior cardiovascular disease followed up from 1986-2004. MAIN OUTCOME MEASURE: Risk of sudden cardiac death associated with moderate to vigorous exertion. RESULTS: The absolute risk of sudden cardiac death associated with moderate to vigorous exertion was exceedingly low at 1 per 36.5 million hours of exertion. In case-crossover analyses, the risk of sudden cardiac death was transiently elevated during moderate to vigorous exertion (relative risk [RR], 2.38; 95% confidence interval [CI], 1.23-4.60; P = .01) compared with the risk during lesser or no exertion. Habitual moderate to vigorous exertion modified this transient risk (P = .005 for interaction) and the risk was no longer significantly elevated among those who exercised 2 or more hours per week. In the cohort analyses, an increasing amount of moderate to vigorous exercise was associated with a lower long-term risk of sudden cardiac death in age-adjusted and multivariable models that excluded biological intermediates (P = .006 for trend). This relationship was attenuated when biological intermediates were included (P = .06 for trend); however, the reduction in risk remained significant among women who exercised 4 or more hours per week (adjusted RR, 0.41; 95% CI, 0.20-0.83; P = .01) compared with women who did not exercise. CONCLUSIONS: These prospective data suggest that sudden cardiac death during exertion is an extremely rare event in women. Regular exercise may significantly minimize this small transient risk and may lower the overall long-term risk of sudden cardiac death.

Adult↗

Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events.

BACKGROUND: Although randomized trials of cyclooxygenase-2 (COX-2) inhibitors have shown increased cardiovascular risk, studies of nonselective, nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen have been inconsistent. METHODS AND RESULTS: We examined the influence of NSAIDs and acetaminophen on the risk of major cardiovascular events (nonfatal myocardial infarction, fatal coronary heart disease, nonfatal and fatal stroke) in a prospective cohort of 70,971 women, aged 44 to 69 years at baseline, free of known cardiovascular disease or cancer, who provided medication data biennially since 1990. During 12 years of follow-up, we confirmed 2041 major cardiovascular events. Women who reported occasional (1 to 21 d/mo) use of NSAIDs or acetaminophen did not experience a significant increase in the risk of cardiovascular events. However, after adjustment for cardiovascular risk factors, women who frequently (> or =22 d/mo) used NSAIDs had a relative risk (RR) for a cardiovascular event of 1.44 (95% CI, 1.27 to 1.65) compared with nonusers, whereas those who frequently consumed acetaminophen had a RR of 1.35 (95% CI, 1.14 to 1.59). The elevated risk associated with frequent NSAID use was particularly evident among current smokers (RR=1.82; 95% CI, 1.38 to 2.42) and was absent among never smokers (Pinteraction=0.02). Moreover, we observed significant dose-response relations: Compared with nonusers, the RRs for a cardiovascular event among women who used > or =15 tablets per week were 1.86 (95% CI, 1.27 to 2.73) for NSAIDs and 1.68 (95% CI, 1.10 to 2.58) for acetaminophen. CONCLUSIONS: Use of NSAIDs or acetaminophen at high frequency or dose is associated with a significantly increased risk for major cardiovascular events, although more moderate use did not confer substantial risk.

Acetaminophen↗

Obesity as compared with physical activity in predicting risk of coronary heart disease in women.

BACKGROUND: The comparative importance of physical inactivity and obesity as predictors of coronary heart disease (CHD) risk remains unsettled. METHODS AND RESULTS: We followed 88 393 women, 34 to 59 years of age, in the Nurses' Health Study from 1980 to 2000. These participants did not have cardiovascular disease and cancer at baseline. We documented 2358 incident major CHD events (including nonfatal myocardial infarction and fatal CHD) during 20 years of follow-up, including 889 cases of fatal CHD and 1469 cases of nonfatal myocardial infarction. In a multivariate model adjusting for cardiovascular risk factors, overweight and obesity were significantly associated with increased risk of CHD, whereas increasing levels of physical activity were associated with a graded reduction in CHD risk (P<0.001). In joint analyses of body mass index (BMI) and physical activity in women who had a healthy weight (BMI, 18.5 to 24.9 kg/m2) and were physically active (exercise > or =3.5 h/wk) as the reference group, the relative risks of CHD were 3.44 (95% confidence interval [CI], 2.81 to 4.21) for women who were obese (BMI > or =30 kg/m2) and sedentary (exercise <1 h/wk), 2.48 (95% CI, 1.84 to 3.34) for women who were active but obese, and 1.48 (95% CI, 1.24 to 1.77) for women who had a healthy weight but were sedentary. In combined analyses of waist-hip ratio and physical activity, both waist-hip ratio and physical activity were significant predictors of CHD, and the highest risk was among women in the lowest category of physical activity and the highest tertile of waist-hip ratio (relative risk=3.03; 95% CI, 1.96 to 4.18). Even a modest weight gain (4 to 10 kg) during adulthood was associated with 27% (95% CI, 12% to 45%) increased risk of CHD compared with women with a stable weight after adjusting for physical activity and other cardiovascular risk factors. CONCLUSIONS: Obesity and physical inactivity independently contribute to the development of CHD in women. These data underscore the importance of both maintaining a healthy weight and regular physical activity in preventing CHD.

Adult↗

Low sex hormone-binding globulin is associated with the metabolic syndrome in postmenopausal women.

Although an association between the metabolic syndrome and hyperandrogenism has been suggested in women with polycystic ovarian syndrome, few studies have investigated this relationship in postmenopausal women. We measured estradiol, testosterone, and sex hormone-binding globulin (SHBG) and calculated the free androgen index (FAI) in 212 postmenopausal women not using hormone therapy in the Women's Health Study. A modified definition of the metabolic syndrome (3 or more of the following: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein, elevated blood pressure, and abnormal glucose metabolism) from the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults was used. Women with the metabolic syndrome had higher mean levels of estradiol, testosterone, and FAI values and lower SHBG levels. Higher FAI and lower SHBG were associated with all components of the metabolic syndrome. After adjustment for BMI and other factors, women in the highest tertile of FAI had an odds ratio of 12.6 (95% confidence interval, 3.8-41.6) for the metabolic syndrome, whereas those in the lowest SHBG tertile had an odds ratio of 7.3 (95% confidence interval, 2.7-19.8). When stratified by body mass index, the associations with high FAI and low SHBG remained significant even in women with body mass index less than 26.7 kg/m2. An androgenic hormone profile is associated with both the individual components of the metabolic syndrome and clustering of metabolic abnormalities in postmenopausal women.

Aged↗

Sex hormone-binding globulin and serum testosterone are inversely associated with C-reactive protein levels in postmenopausal women at high risk for cardiovascular disease.

PURPOSE: C-reactive protein (CRP), androgens, and menopausal loss of endogenous estrogens are associated with cardiovascular disease (CVD). We hypothesized that high androgens, low estradiol, and low sex hormone-binding globulin (SHBG) would be associated with high CRP in postmenopausal women. METHODS: CRP, SHBG, estradiol, and total testosterone were measured using baseline bloods of 221 hormone therapy (HT)-nonusers and 162 HT-users from a cross-sectional analysis in a nested case-control sample of the Women's Health Study. Hormones and CRP were ln-transformed and relationships were assessed with Spearman correlations and linear regression. RESULTS: ln-SHBG (beta=-0.40; p<0.01) and ln-testosterone (beta=-0.24; p=0.04) were the only independent hormonal predictors of ln-CRP among HT-nonusers after adjusting for age, hypertension, smoking, body mass index, diabetes, exercise, HDL cholesterol, alcohol intake, and CVD occurrence during follow-up. Upon stratification, the association between ln-SHBG and ln-CRP persisted among HT nonusers who subsequently developed CVD (beta=-0.55; p=0.01), but not among women who remained CVD-free (p=0.28). The inverse relationship between ln-SHBG and ln-CRP was strongest among the leanest women. None of the sex-hormones predicted ln-CRP among HT-users. CONCLUSIONS: SHBG and total testosterone were inversely associated with CRP among HT nonusers in this study. The relationship between SHBG and CRP was more strongly inverse among leaner women.

Aged↗

Polymorphisms in the CC-chemokine receptor-2 (CCR2) and -5 (CCR5) genes and risk of coronary heart disease among US women.

OBJECTIVE: Genetic variation in CC-chemokine receptor-2 (CCR2) and -5 (CCR5), and their common haplotypes, acting through inflammatory responses, may affect atherosclerosis and risk of coronary heart disease (CHD). METHOD AND RESULTS: We examined seven common variants in the CCR2 and CCR5 loci and risk of CHD among women in the Nurses' Health Study. During 8 years of follow-up, we documented 248 incident cases of nonfatal myocardial infarction and fatal CHD, and matched controls 2:1 based on age and smoking. The distribution of alleles was similar between cases and controls. The haplotype-specific odds ratios (ORs) were not statistically significant nor was the globally-adjusted p-value (p=0.61). However, there was a statistically significant association for CCR5-Delta32 and A58755G (rs2856758) between cases and controls comparing age of onset <55 and >or=55 years. For Delta32, the OR for having the variant was 0.12 (0.02-0.76) for age <55, and 1.14 (0.69-1.88) for age >or=55 years (p, interaction=0.04). The CCR5-Delta32 was in linkage disequilibrium with 58755G, and a similar association was observed for having the 58755G. CONCLUSIONS: In this population, CCR2-CCR5 haplotypes were not associated with risk of CHD. However, our data suggest a strong inverse association for certain CCR5 variants and early age of CHD onset.

Adult↗

Peroxisome proliferator-activated receptor-gamma2 P12A polymorphism and risk of coronary heart disease in US men and women.

OBJECTIVE: Activation of the peroxisome proliferator-activated receptor-gamma (PPARgamma) improves insulin sensitivity and exerts antiatherogenic effects. A common alanine for proline substitution at codon 12 in the PPARG2 gene is related to lower receptor activity. Studies suggest that the A12 allele is associated with reduced risk of type 2 diabetes; however, data on the risk of coronary heart disease (CHD) are scarce and controversial. METHODS AND RESULTS: We examined the relationship between PPARG2 P12A and CHD risk in women (Nurses' Health Study) and men (Health Professionals Follow-Up Study) in nested case control settings. Among participants free of cardiovascular disease at baseline, 249 women and 266 men developed nonfatal myocardial infarction (MI) or fatal CHD during 8 and 6 years of follow-up, respectively. Using risk-set sampling, controls were selected 2:1 matched on age, smoking, and date of blood draw. The relative risk (RR) of nonfatal MI or fatal CHD of carriers compared with noncarriers of the A12 allele was 1.17 (95% CI, 0.82 to 1.68) among women and 1.44 (95% CI, 1.00 to 2.07) among men (pooled RR, 1.30 [95% CI, 1.00 to 1.67]). We found a significantly increased risk associated with the A12 allele among individuals with a body mass index > or =25 kg/m2 (women: RR, 1.88; 95% CI, 1.01 to 3.50; men: RR, 1.55; 95% CI, 0.92 to 2.60; pooled: RR, 1.68; 95% CI, 1.13 to 2.50) but not among those <25 kg/m2 (pooled RR, 0.86; 95% CI, 0.37 to 1.97; P heterogeneity overweight versus nonoverweight 0.16). CONCLUSIONS: These data do not support the hypothesis that the A12 allele is associated with a decreased risk of CHD. The potential interaction between PPARG2 P12A, overweight, and increased CHD risk needs further evaluation.

Adult↗

Longitudinal study of birth weight and adult body mass index in predicting risk of coronary heart disease and stroke in women.

OBJECTIVES: To determine whether birth weight and adult body size interact to predict coronary heart disease in women, as has been observed for men. To determine whether birth weight and adult body size interact to predict risk of stroke. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: 66,111 female nurses followed since 1976 who were born of singleton, term pregnancies and reported their birth weight in 1992. MAIN OUTCOME MEASURES: 1504 events of coronary heart disease (myocardial infarction or sudden cardiac death) and 1164 strokes. RESULTS: For each kilogram of higher birth weight, age adjusted hazard ratios from prospective analysis were 0.77 (95% confidence interval 0.69 to 0.87) for coronary heart disease and 0.89 (0.78 to 1.01) for total stroke. In combined prospective and retrospective analysis, hazard ratios were 0.84 (0.76 to 0.93) for total stroke, 0.83 (0.71 to 0.96) for ischaemic stroke, and 0.86 (0.66 to 1.11) for haemorrhagic stroke. Exclusion of macrosomic infants (> 4536 g) yielded stronger estimates. Risk of coronary heart disease was especially high for women who crossed from a low centile of weight at birth to a high centile of body mass index in adulthood. The association of lower birth weight with increased risk of stroke was apparent across categories of body mass index in adults and was not especially strong among heavier women. CONCLUSIONS: Higher body mass index in adulthood is an especially strong risk factor for coronary heart disease among women who were small at birth. In this large cohort of women, size at birth and adiposity in adulthood interacted to predict events of coronary heart disease but not stroke events.

Adolescent↗

Prospective study of body mass index and risk of stroke in apparently healthy women.

BACKGROUND: Obesity is an escalating pandemic in the United States, and its association with coronary heart disease is well understood. Several studies have found positive associations between body mass index (BMI) and stroke in men, but the association with stroke and its subtypes is less clear in women. METHODS AND RESULTS: This was a prospective cohort study among 39 053 women participating in the Women's Health Study. BMI was measured as self-reported weight (in kilograms) divided by height (in meters) squared. Incident stroke was self-reported and confirmed by medical record review. We used the Cox proportional hazards model to evaluate the association between BMI and stroke. After a mean follow-up of 10 years, a total of 432 strokes (347 ischemic, 81 hemorrhagic, and 4 undefined) occurred. We found a statistically significant trend for increased risk of total and ischemic stroke across 7 BMI categories. With World Health Organization criteria, women who were obese (BMI > or =30 kg/m2) had hazard ratios of 1.50 (95% CI 1.16 to 1.94) for total stroke, 1.72 (95% CI 1.30 to 2.28) for ischemic stroke, and 0.82 (95% CI 0.43 to 1.58) for hemorrhagic stroke compared with women with BMI <25 kg/m2. Additional control for history of hypertension, diabetes, and elevated cholesterol substantially attenuated the hazard ratios for total and ischemic stroke. There was no effect modification for age, exercise, or smoking. CONCLUSIONS: In this large prospective cohort study among women, BMI was a strong risk factor for total and ischemic stroke but not for hemorrhagic stroke. The association was highly mediated by hypertension, diabetes, and elevated cholesterol.

Body Mass Index↗

Phobic anxiety and risk of coronary heart disease and sudden cardiac death among women.

BACKGROUND: High levels of phobic anxiety have been associated with elevated risks of coronary heart disease (CHD) death and sudden cardiac death (SCD) among men. To the best of our knowledge, no studies have looked at this association among women. Anxiety may influence CHD mortality by increasing the risk of ventricular arrhythmia and SCD. METHODS AND RESULTS: We prospectively examined the relationship between phobic anxiety, as measured by the Crown-Crisp index (CCI), and CHD among women participating in the Nurses' Health Study. Among 72,359 women with no history of cardiovascular disease or cancer in 1988, 97 SCDs, 267 CHD deaths, and 930 nonfatal myocardial infarctions (MI) were documented over 12 years of follow-up. A higher score on the CCI was associated with an increased risk of SCD and fatal CHD but not of nonfatal MI in age-adjusted (P, trend < or =0.008) and in multivariable models excluding possible biological intermediaries (P, trend < or =0.03). Multivariable adjustment appeared to attenuate the relations; women who scored 4 or greater on the CCI were at a 1.59-fold (95% CI, 0.97 to 2.60) marginally increased risk of SCD and a 1.31-fold (95% CI, 0.97 to 1.75) marginally increased risk of fatal CHD compared with those who scored 0 or 1. After control for possible intermediaries (hypertension, diabetes, and elevated cholesterol), a trend toward an increased risk persisted for SCD (P=0.06). CONCLUSIONS: These prospective data suggest that high levels of phobic anxiety are associated with an increased risk of fatal CHD, particularly from SCD. Some but not all of this risk can be accounted for by CHD risk factors associated with phobic anxiety.

Adult↗

Carbohydrate intake, glycemic index, glycemic load, and dietary fiber in relation to risk of stroke in women.

The associations of dietary carbohydrate, glycemic index, and glycemic load with stroke risk were examined among 78,779 US women who were free of cardiovascular disease and diabetes in 1980 and completed a food frequency questionnaire. During an 18-year follow-up, 1,020 stroke cases were documented (including 515 ischemic and 279 hemorrhagic). In analyses adjusting for nondietary risk factors and cereal fiber, carbohydrate intake was associated with elevated risk of hemorrhagic stroke when the extreme quintiles were compared (relative risk = 2.05, 95% confidence interval: 1.10, 3.83; p(trend) = 0.02), but not with ischemic stroke. The positive association between carbohydrate intake and stroke risk was most evident among women with a body mass index of > or =25 kg/m(2). Likewise, dietary glycemic load was positively associated with total stroke among only those women whose body mass index was > or =25 kg/m(2). Cereal fiber intake was inversely associated with total and hemorrhagic stroke risk; for total stroke, relative risk = 0.66 (95% confidence interval: 0.52, 0.83; p(trend) = 0.001) and for hemorrhagic stroke, relative risk = 0.51 (95% confidence interval: 0.33, 0.78; p(trend) = 0.01). Findings suggest that high intake of refined carbohydrate is associated with hemorrhagic stroke risk, particularly among overweight or obese women. In addition, high consumption of cereal fiber was associated with lower risk of total and hemorrhagic stroke.

Adult↗

Dietary intakes of fruit, vegetables, and fiber, and risk of colorectal cancer in a prospective cohort of women (United States).

OBJECTIVE: Although animal studies suggest an inverse association between consumption of plant foods and risk of colorectal cancer, many observational data have failed to support such an association. We prospectively examined the association between dietary intakes of fruit, vegetables, and fiber and colorectal cancer risk in a large female cohort from the Women's Health Study. METHODS: Among 39,876 healthy women aged >/=45 years at baseline, 36,976 with baseline self-reported information on dietary intakes and other risk factors for colorectal cancer were included in the analyses. During an average follow-up of 10 years, 223 women were diagnosed with colorectal cancer. Intakes of fruit, vegetables, and fiber were assessed by a baseline food-frequency questionnaire. The analyses were carried out using the Cox proportional hazards regression and all tests were two-sided. RESULTS: Intakes of fruit, vegetables, and the specific subgroups were not found to be associated with colorectal cancer risk. Multivariate relative risks (RRs) comparing the highest with lowest quintile were 0.79 (95% CI=0.49-1.27,p for trend =0.30) for fruit intake, and 0.88 (95% CI=0.56-1.38,p for trend=0.30) for vegetables intake. Similarly, intake of total fiber was not associated with colorectal cancer risk; the RR for the highest relative to lowest quintile was 0.75 (95% CI=0.48-1.17,p for trend=0.12). However, higher intake of legume fiber was associated with a lower risk of colorectal cancer; the RR for the highest versus slowest quintile was 0.60 (95% CI=0.40-0.91,p for trend=0.02). CONCLUSIONS: Our data offer little support for associations between intakes of fruit, vegetables, and fiber, and colorectal cancer risk. However, our data suggest that legume fiber and/or other related sources may reduce risk of colorectal cancer.

Colorectal Neoplasms↗

A prospective study of soluble tumor necrosis factor-alpha receptor II (sTNF-RII) and risk of coronary heart disease among women with type 2 diabetes.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha), a cytokine secreted by adipose tissue and other cells, might play a role in insulin resistance. RESEARCH DESIGN AND METHODS: Of 32,826 women from the Nurses' Health Study who provided blood at baseline, we followed 929 women with type 2 diabetes. During 10 years of follow-up, we documented 124 incident cases of coronary heart disease (CHD). RESULTS: After adjustment for age, smoking, BMI, and other cardiovascular risk factors, the relative risks (RRs) comparing extreme quartiles of soluble TNF-alpha receptor II (sTNF-RII) were 2.48 (95% CI 1.08-5.69; P = 0.034) for myocardial infarction (MI) and 2.02 (1.17-3.48; P = 0.003) for total CHD. The probability of developing CHD over 10 years was higher among diabetic subjects with substantially higher levels of both sTNF-RII (>75th percentile) and HbA(1c) (>7%), compared with diabetic subjects with lower levels (25% vs. 7%, P < 0.0001). Diabetic subjects with only higher sTNF-RII or HbA(1c) had similar (16-17%) risk. In a multivariate model, diabetic subjects with higher levels of both sTNF-RII and HbA(1c) had an RR of 3.66 (1.85-7.22) for MI and 3.03 (1.82-5.05) for total CHD, compared with those with lower levels of both biomarkers. CONCLUSIONS: Increased levels of sTNF-RII were strongly associated with risk of CHD among diabetic women, independent of hyperglycemia.

Biomarkers↗

Body mass index and total and cardiovascular mortality in men with a history of cardiovascular disease.

BACKGROUND: Previous studies designed to identify an association between body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) and cardiovascular or total mortality in populations with known atherosclerotic disease have shown conflicting results. In this study, we used the Physicians' Health Study enrollment cohort to examine the risk of total and cardiovascular mortality among men reporting a history of myocardial infarction or stroke, excluding those who reported a history of cancer. METHODS: Cause-specific death was ascertained for 5010 men during a mean follow-up of 5.0 years. End points were classified as total deaths and deaths due to cardiovascular causes. Four BMI categories (<22.0, 22.0-24.9 [referent], 25.0-27.9, and > or =28.0) were created a priori. We used proportional hazards models to calculate age and multivariate-adjusted relative risks (RRs) for each BMI category for each end point. RESULTS: Compared with men with a BMI of 22.0 to 24.9, men with a BMI of 28.0 or greater had an age-adjusted RR of 1.11 (95% confidence interval [CI], 0.91-1.36), a multivariate RR of 1.04 (95% CI, 0.84-1.28) in a model that did not include biological mediators of obesity, and a multivariate RR of 1.06 (95% CI, 0.78-1.44) in a model that included these mediators. The RRs for cardiovascular mortality were similar, at 1.07 (95% CI, 0.85-1.35), 1.01 (95% CI, 0.79-1.29), and 1.01 (95% CI, 0.71-1.43), respectively. A BMI of less than 22.0 was associated with a small increased risk of total mortality and cardiovascular mortality. CONCLUSION: These findings indicate that elevated BMI may not be strongly associated with total or cardiovascular mortality among men with previously manifested coronary artery disease.

Aged↗

Prospective study of major dietary patterns and stroke risk in women.

BACKGROUND AND PURPOSE: Many foods have been suggested to influence the risk of stroke. However, no previous studies have examined the relationship between overall dietary patterns and risk of stroke. METHODS: Using dietary information collected in 1984 from 71,768 women aged 38 to 63 years without a history of cardiovascular disease or diabetes in 1984, we conducted factor analysis and identified 2 major dietary patterns: "prudent" and "Western." We calculated scores for each participant for each pattern and prospectively examined their associations with stroke risk using a proportional hazard model, adjusting for other stroke risk factors. RESULTS: The prudent pattern was characterized by higher intakes of fruits, vegetables, legumes, fish, and whole grains, whereas the Western pattern by higher intakes of red and processed meats, refined grains, and sweets and desserts. During 14 years of follow-up, we identified 791 incidents of stroke, with 476 ischemic and 189 hemorrhagic strokes. After adjusting for potential confounders, we observed a relative risk (RR) of 1.58 (95% CI, 1.15 to 2.15; P=0.0002 for trend) for total strokes and 1.56 (95% CI, 1.05 to 2.33; P=0.02 for trend) for ischemic stroke when comparing the highest with lowest quintiles of the Western pattern. For the prudent pattern, the RRs comparing extreme quintiles were 0.78 (95% CI, 0.61 to 1.01) for total stroke and 0.74 (95% CI, 0.54 to 1.02) for ischemic stroke. CONCLUSIONS: These data suggest that a dietary pattern typified by higher intakes of red and processed meats, refined grains, and sweets and desserts may increase stroke risk, whereas a diet higher in fruits and vegetables, fish, and whole grains may protect against stroke.

Adult↗