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Kathryn M Rexrode

Publications and source records attributed to Kathryn M Rexrode.

32 records · Page 2Linked to original sources

Folate intake and risk of stroke among women.

BACKGROUND AND PURPOSE: Few studies have examined the association between folate intake and risk of stroke, although numerous studies have suggested that high levels of homocysteine are positively related to stroke. We aim to assess the relation between folate intake and stroke incidence among women participating in the Nurses' Health Study. METHODS: 83,272 female nurses aged 34 to 59 years in 1980 and residing in 11 US states were followed-up for 18 years. Follow-up questionnaires were sent biennially to update information on diet and to identify newly diagnosed cases of stroke and other illnesses. RESULTS: During 1,379614 person-years of follow-up from 1980 to 1998, we identified 1140 incident cases of stroke. Using age-adjusted and multivariable-adjusted models, no appreciable association between the intake of folate and total incidence of stroke was observed [relative risk in the multivariable-adjusted model for the highest quintile of folate intake (median=696 microg/d) compared with the lowest quintile (median=158 microg/d) was 1.01 (95% confidence interval [CI]: 0.79 to 1.29), P for trend=0.8]. Similar null results were found in secondary analyses on stroke subtypes (ischemic, thrombotic, embolic, subarachnoid hemorrhage, intraparenchymal hemorrhage) and in analyses that separately assessed dietary folate (excluding supplement users) and folate supplement intake. CONCLUSIONS: Folate intake was not associated with incident stroke among women participating in the Nurses' Health Study.

Adult↗

Body mass index and risk of colorectal cancer in women (United States).

OBJECTIVE: Epidemiologic data relating obesity to risk of colorectal cancer in women have been inconclusive. Two recent studies have suggested that the association may be modified by estrogen status; BMI was positively associated with colorectal cancer risk among women with high estrogen exposures [premenopausal women, and postmenopausal women who currently received postmenopausal hormone therapy (PMH)]. We prospectively investigated the role of BMI in colorectal cancer risk along with the modifying effects of estrogen in a large cohort from the Women's Health Study. METHODS: Among 39,876 apparently healthy women aged > or = 45 years at baseline (54% of them were postmenopausal), 37,671 were eligible for the present study. During an average of 8.7 years of follow-up, 202 women had a confirmed diagnosis of colorectal cancer. Baseline BMI was calculated by dividing self-reported weight in kilograms by height in meters squared. RESULTS: The multivariate relative risks (RRs) and 95% confidence interval (CI) of colorectal cancer were 1.72 (1.12-2.66) for 27-29.9 kg/m2, and 1.67 (1.08-2.59) for > or = 30 kg/m2, as compared with BMI < 23 kg/m2 ( p for trend = 0.02). This positive association was seen primarily in the proximal colon ( p for trend = 0.004). When the association was further examined according to PMH use among postmenopausal women, we found that both current and never users with higher BMI were at a greater risk of colorectal cancer ( p for interaction between BMI and PMH use = 0.33). As compared with BMI < 23 kg/m2, the multivariate RRs and 95% CI for 27-29.9 and > or = 30 kg/m2 were 1.98 (0.98-3.99) and 1.41 (0.65-3.06) among current users, and 1.05 (0.42-2.65) and 2.91 (1.40-6.06) among never users. CONCLUSIONS: These data suggest that higher BMI was associated with an elevated risk of colorectal cancer, and the positive relationship was not altered by estrogen exposure among postmenopausal women.

Aged↗

Kidney dysfunction, inflammation, and coronary events: a prospective study.

Kidney dysfunction and high C-reactive protein (CRP) levels are independently associated with coronary events. However, it is unclear whether the risk of coronary events associated with decreased kidney function is at least partially mediated by inflammation and whether the association between inflammatory biomarkers and coronary events is influenced by level of kidney function. With the use of a prospective, nested, case-control study design, the association among kidney function, inflammatory biomarker levels, and coronary events was studied. A total of 244 women who were participants in the Nurses' Health Study and had no history of cardiovascular disease received a diagnosis of an incident coronary event (defined as nonfatal myocardial infarction or death as a result of coronary disease) during the follow-up period from 1990 to 1998 and were matched to 486 control subjects. Serum creatinine and inflammatory biomarker levels were measured in blood samples collected in 1989. Creatinine clearance (CrCl) was estimated using creatinine, age, weight, and height. In multivariate analyses, the odds ratio (OR) for a coronary event in women with an estimated CrCl <60 ml/min was 2.33 (95% confidence interval [CI], 1.01 to 5.38) compared with those with a CrCl > or =90 ml/min. When soluble tumor necrosis factor receptor (sTNFR) I and II levels were added into this model individually, the observed OR for women with CrCl <60 ml/min was attenuated. In analyses stratified by estimated CrCl, higher high-sensitivity CRP (hs-CRP), IL-6, and sTNFR I and II levels each were significantly associated with an increased odds of coronary events in women with an estimated CrCl < or =74 ml/min but not in women with an estimated CrCl > or =75 ml/min. The OR per 5-mg/L unit increase in hs-CRP was 1.68 (95% CI, 1.13 to 2.52) for women with an estimated CrCl < or =74 ml/min, compared with 1.23 (95% CI, 0.86 to 1.76) and 0.99 (95% CI, 0.76 to 1.29) for women with an estimated CrCl 75 to 89 and > or =90 ml/min, respectively (P = 0.004 for interaction). In conclusion, kidney dysfunction is associated with an increased odds of coronary events, and inflammation, as assessed by higher sTNFR I and II levels, may mediate some of this risk. Higher inflammatory biomarkers levels, specifically, hs-CRP, IL-6, and sTNFR I and II, were significantly associated with coronary events only in women with reduced kidney function. These findings warrant further investigation in other populations.

Adult↗

Sex hormone levels and risk of cardiovascular events in postmenopausal women.

BACKGROUND: Despite diffuse effects of sex hormones on the cardiovascular system, few prospective studies have examined the relationship of plasma androgens and estrogens with risk of cardiovascular disease (CVD) in postmenopausal women. METHODS AND RESULTS: A nested case-control study was performed among women in the Women's Health Study. Two hundred women who developed CVD were matched 1:1 by age, smoking, and postmenopausal hormone therapy (HT) to controls who remained free of CVD. We measured testosterone, estradiol, and sex hormone binding globulin (SHBG) levels and calculated free androgen index (FAI), free estradiol index, and the FAI/free estradiol index ratio. Results were stratified by HT use. Among HT nonusers, cases had significantly higher androgen profiles (higher median FAI and lower SHBG levels) than controls. After adjustment for age, smoking, use of aspirin, vitamin E, and alcohol, family history of myocardial infarction, and physical activity, nonusers in the lowest SHBG quartile had an OR of 2.25 (95% CI, 1.03 to 4.91) for CVD, and there were significant trends across FAI quartiles (P for trend=0.03). Additional adjustment for body mass index, hypertension, diabetes, and elevated cholesterol eliminated associations with SHBG and FAI. Among women using HT, no significant differences in hormones or SHBG were observed among women who developed CVD and controls. CONCLUSIONS: Among HT nonusers, lower SHBG and higher FAI levels were noted among postmenopausal women who developed CVD events, but this was not independent of body mass index and other cardiovascular risk factors. Estradiol levels were not associated with risk of CVD in HT users or nonusers.

Cardiovascular Diseases↗

Prospective study of sudden cardiac death among women in the United States.

BACKGROUND: There are few data regarding the determinants of sudden cardiac death (SCD) in women, primarily because of their markedly lower rate of SCD compared with men. Nonetheless, existing data, although sparse, suggest possible gender differences in risk factors for SCD. METHODS AND RESULTS: In this prospective cohort of 121 701 women aged 30 to 55 years at baseline, SCD was defined as death within 1 hour of symptom onset. From 1976 to 1998, 244 SCDs were identified. Although the risk of SCD increased markedly with age, the percentage of cardiac deaths that were sudden decreased. Most (69%) women who suffered a SCD had no history of cardiac disease before their death. However, almost all of the women who died suddenly (94%) had reported at least 1 coronary heart disease risk factor. Smoking, hypertension, and diabetes conferred markedly elevated (2.5- to 4.0-fold) risk of SCD, similar to that conferred by a history of nonfatal myocardial infarction (relative risk, 4.1; 95% confidence interval, 2.9 to 6.7). Family history of myocardial infarction before age 60 years and obesity were associated with moderate (1.6-fold) elevations in risk. With regard to mechanism, 88% of SCDs were classified as arrhythmic. In 76% of these, the first rhythm documented was ventricular tachycardia or ventricular fibrillation. CONCLUSIONS: These prospective data suggest that, as in men, coronary heart disease risk factors predict risk of SCD in women and that SCD is usually an arrhythmic death. Therefore, prevention of atherosclerosis or ventricular arrhythmias may reduce the incidence of SCD in women.

Adult↗

Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women.

BACKGROUND: Although several prospective cohort studies have found an inverse association between fish consumption and risk of coronary heart disease (CHD) or sudden cardiac death in the general population, limited data are available among diabetic patients. METHODS AND RESULTS: We examined prospectively the association between intake of fish and omega-3 fatty acids and risk of CHD and total mortality among 5103 female nurses with diagnosed type 2 diabetes but free of cardiovascular disease or cancer at baseline. Between 1980 and 1996 (45 845 person-years of follow-up), we documented 362 incident cases of CHD (141 CHD deaths and 221 nonfatal myocardial infarctions) and 468 deaths from all causes. Compared with women who seldom consumed fish (<1 serving/mo), the relative risks (RRs) (95% CI) of CHD adjusted for age, smoking, and other established coronary risk factors were 0.70 (0.48 to 1.03) for fish consumption 1 to 3 times per month, 0.60 (0.42 to 0.85) for once per week, 0.64 (0.42 to 0.99) for 2 to 4 times per week, and 0.36 (0.20 to 0.66) for 5 or more times per week (P for trend=0.002). Higher consumption of fish was also associated with a significantly lower total mortality (multivariate RR=0.48 [0.29 to 0.80] for > or =5 times per week [P for trend=0.005]). Higher consumption of long-chain omega-3 fatty acids was associated with a trend toward lower incidence of CHD (RR=0.69 [95% CI 0.47 to 1.03], P for trend=0.10) and total mortality (RR=0.63 [95% CI, 0.45 to 0.88], P for trend=0.02). CONCLUSIONS: A higher consumption of fish and long-chain omega-3 fatty acids was associated with a lower CHD incidence and total mortality among diabetic women.

Adult↗

Analgesic use and change in kidney function in apparently healthy men.

BACKGROUND: Studies using a single creatinine measurement have yielded inconsistent results regarding analgesic use and kidney function. METHODS: This is a prospective cohort study of 4,494 US male physicians who provided blood samples in both 1982 and 1996. Outcomes measured were increase in plasma creatinine level of 0.3 mg/dL or greater (> or =26.5 micromol/L) and decline in glomerular filtration rate (GFR) of 29.0 mL/min/1.73 m2 or greater during this 14-year period. Self-reported use of aspirin, acetaminophen, and other nonsteroidal anti-inflammatory drugs (NSAIDs) was classified as never (<12 pills during the study period), 12 to 1,499 pills, 1,500 to 2,499 pills, and 2,500 or greater pills during the study period. RESULTS: Blood measurements made 14 years apart showed increased creatinine levels in 242 participants and decreased GFRs in 224 participants. Compared with never use, multivariable-adjusted odds ratios (ORs) of increased creatinine levels were 0.98 (95% confidence interval [CI], 0.43 to 2.23) for 2,500 or greater pills of aspirin, 1.02 (95% CI, 0.55 to 1.90) for 2,500 or greater pills of acetaminophen, and 1.12 (95% CI, 0.67 to 1.87) for 2,500 or greater pills of other NSAIDs. For decreased GFRs, ORs for intake of 2,500 or greater pills were 0.75 (95% CI, 0.35 to 1.57) for aspirin, 1.22 (95% CI, 0.66 to 2.26) for acetaminophen, and 1.11 (95% CI, 0.65 to 1.90) for other NSAIDs. Use of aspirin, but not acetaminophen or other NSAIDs, was associated with a reduced risk for change in kidney function in participants without cardiovascular risk factors and a possible but nonsignificant increase in those with cardiovascular risk factors. CONCLUSION: Occasional to moderate analgesic intake of aspirin, acetaminophen, or NSAIDs does not appear to increase the risk for decline in kidney function during a period of 14 years.

Acetaminophen↗

Relationship of total and abdominal adiposity with CRP and IL-6 in women.

PURPOSE: To examine the relationship between different measures of adiposity as predictors of C-reactive protein (CRP) and interleukin-6 (IL-6) levels. METHODS: A cross-sectional study of 733 women free from preexisting cardiovascular disease or cancer at baseline. MEASUREMENTS: Total adiposity, as measured by body mass index (BMI). Abdominal adiposity, as measured by waist circumference (WC) and waist/hip ratio (WHR). High sensitivity CRP levels and IL-6 levels. RESULTS: BMI, WHR, and WC were all significantly correlated with CRP and IL-6, throughout the anthropometric spectrum. After adjustment for risk factors, the odds ratios (ORs) were 12.2 (95% CI, 6.44-23.0) for elevated CRP (>/=75th percentile) and 4.13 (95% CI, 2.37-7.18) for elevated IL-6 (>/=75th percentile) in comparisons of extreme BMI quartiles. Among women in the highest WC quartile, the OR for elevated CRP and IL-6 were 8.57 (95% CI, 4.59-16.0) and 4.40 (95%CI, 2.46-7.89), while ORs for the highest WHR quartile were 2.88 (95% CI, 1.60-5.19) and 1.76 (95% CI, 1.03-3.01), respectively. Compared with lean nonusers, women in the highest BMI quartile who did not use hormone therapy (HT) had an OR for elevated CRP of 7.79 (95% CI, 2.08-29.2) vs. 31.6 (95% CI, 7.97-125.6) for current hormone users. CONCLUSIONS: Indices of both total and abdominal adiposity were strongly associated with significant increased levels of CRP and IL-6. This association was evident across the entire spectrum of BMI.

Abdomen↗

Postmenopausal hormone therapy and migraine headache.

BACKGROUND: Estrogen withdrawal has been described as a trigger for migraine headache, and some studies suggest that estrogen and progestin may exacerbate migraine. No population-based studies have examined the association between hormone therapy (HT) and migraine among postmenopausal women. METHODS: To examine the association between HT and migraine headache in postmenopausal women, we used self-report of HT use, HT characteristics, and migraine headache within the past year among 17,107 postmenopausal female health professionals enrolled in the Women's Health Study. RESULTS: Analyses were restricted to the 17,107 of 21,788 postmenopausal women who were postmenopausal at baseline and who were never (38.5%) or current (61.5%) users of HT. Of these, 1,909 (11.2%) experienced migraine headache within the last year. Women with migraine headache were significantly younger, had a younger age at menopause, were more likely to have had a surgical menopause, and were more likely to be current users of HT. After adjusting for age, race, smoking, alcohol use, ever use of oral contraception, age at menopause, and menopause type, the odds ratio (OR) for migraine headache was 1.42 (95% CI 1.24-1.62) for women who were current users of HT compared with never users. ORs were similar for users of estrogen alone (OR 1.39, 95% CI 1.14-1.69) and users of both estrogen and progestin (OR 1.41, 95% CI 1.22-1.63). CONCLUSIONS: In this cross-sectional study, current HT use was associated with higher rates of migraine headache than nonuse. Clinical trials are needed to determine if HT increases the incidence of migraine in postmenopausal women.

Aged↗

Cholesterol and the risk of renal dysfunction in apparently healthy men.

Despite extensive knowledge about abnormal lipid patterns in patients with end-stage renal disease, the association between cholesterol and the development of renal dysfunction is unclear. We evaluated this association in a prospective cohort study among 4,483 initially healthy men participating in the Physicians' Health Study who provided blood samples in 1982 and 1996. Main outcome measures were elevated creatinine, defined as >/= 1.5 mg/dl (133 micromol/L), and reduced estimated creatinine clearance, defined as </=55 ml/min. Cholesterol parameters included total cholesterol (<200, 200 to 239, and >/= 240 mg/dl), HDL (<40 or >/= 40 mg/dl), total non-HDL cholesterol, and the ratio of total cholesterol to HDL. We used logistic regression to calculate age- and multivariable adjusted odds ratios as a measure for the relative risk. After 14 yr, 134 men (3.0%) had elevated creatinine and 244 (5.4%) had reduced creatinine clearance. The multivariable relative risk for elevated creatinine was 1.77 (95% confidence interval [CI], 1.10 to 2.86) for total cholesterol >/= 240 mg/dl, 2.16 (95% CI, 1.42 to 3.27) for HDL <40 mg/dl, 2.34 (95% CI, 1.34 to 4.07) for the highest quartile of total cholesterol/HDL ratio (>/= >6.8), and 2.16 (95% CI, 1.22 to 3.80) for the highest quartile of non-HDL cholesterol (>/= 196.1). Similar although smaller associations were observed between cholesterol parameters and reduced creatinine clearance. Elevated total cholesterol, high non-HDL cholesterol, a high ratio of total cholesterol/HDL, and low HDL in particular were significantly associated with an increased risk of developing renal dysfunction in men with an initial creatinine <1.5 mg/dl.

Cholesterol↗

Fish and omega-3 fatty acid intake and risk of coronary heart disease in women.

CONTEXT: Higher consumption of fish and omega-3 fatty acids has been associated with a lower risk of coronary heart disease (CHD) in men, but limited data are available regarding women. OBJECTIVE: To examine the association between fish and long-chain omega-3 fatty acid consumption and risk of CHD in women. DESIGN, SETTING, AND PARTICIPANTS: Dietary consumption and follow-up data from 84 688 female nurses enrolled in the Nurses' Health Study, aged 34 to 59 years and free from cardiovascular disease and cancer at baseline in 1980, were compared from validated questionnaires completed in 1980, 1984, 1986, 1990, and 1994. MAIN OUTCOME MEASURES: Incident nonfatal myocardial infarction and CHD deaths. RESULTS: During 16 years of follow-up, there were 1513 incident cases of CHD (484 CHD deaths and 1029 nonfatal myocardial infarctions). Compared with women who rarely ate fish (<1 per month), those with a higher intake of fish had a lower risk of CHD. After adjustment for age, smoking, and other cardiovascular risk factors, the multivariable relative risks (RRs) of CHD were 0.79 (95% confidence interval [CI], 0.64-0.97) for fish consumption 1 to 3 times per month, 0.71 (95% CI, 0.58-0.87) for once per week, 0.69 (95% CI, 0.55-0.88) for 2 to 4 times per week, and 0.66 (95% CI, 0.50-0.89) for 5 or more times per week (P for trend =.001). Similarly, women with a higher intake of omega-3 fatty acids had a lower risk of CHD, with multivariable RRs of 1.0, 0.93, 0.78, 0.68, and 0.67 (P<.001 for trend) across quintiles of intake. For fish intake and omega-3 fatty acids, the inverse association appeared to be stronger for CHD deaths (multivariate RR for fish consumption 5 times per week, 0.55 [95% CI, 0.33-0.90] for CHD deaths vs 0.73 [0.51-1.04]) than for nonfatal myocardial infarction. CONCLUSION: Among women, higher consumption of fish and omega-3 fatty acids is associated with a lower risk of CHD, particularly CHD deaths.

Adult↗

Estrogen-progestin replacement therapy and breast cancer risk: the Women's Health Study (United States).

OBJECTIVE: While there is substantial evidence that unopposed estrogen use increases the risk of breast cancer, there are limited data from epidemiologic studies on the impact of estrogen-progestin combinations. We therefore examined estrogen-progestin replacement therapy and breast cancer risk in the Women's Health Study. METHODS: We investigated postmenopausal hormone (PMH) use among 17,835 apparently healthy postmenopausal women aged > or =45 years, and followed them prospectively for an average of 5.9 years. Breast cancer occurred in 411 women. RESULTS: The multivariate relative risks of all breast cancer associated with never use of PMH, use of estrogen replacement therapy (ERT), and use of estrogen-progestin replacement therapy (HRT) were 1.00 (referent), 0.96 (95% CI 0.65-1.42), and 1.37 (95% CI 1.05-1.78). The increase in risk among users of HRT was largely limited to those women who had used estrogen-progestin replacement therapy for five years or more, and to those women who were on continuous rather than cyclic progestin combinations. Higher doses of estrogen, but not progestin, were associated with increased breast cancer risk, compared with lower doses. CONCLUSIONS: These prospective data suggest that use of estrogen-progestin replacement therapy imparts an increased risk of breast cancer in comparison with never use of PMH.

Breast Neoplasms↗

Body mass index and the risk of stroke in men.

BACKGROUND: Although obesity is an established risk factor for coronary heart disease, its role as a risk factor for stroke remains controversial. METHODS: Prospective cohort study among 21 414 US male physicians participating in the Physicians' Health Study. Incidence of total, ischemic, and hemorrhagic stroke was measured by self-report and confirmed by medical record review. We used Cox proportional hazards models to evaluate the association of body mass index (BMI), calculated as self-reported weight in kilograms divided by the square of the height in meters, with risk of total, ischemic, and hemorrhagic stroke. RESULTS: During 12.5 years of follow-up, 747 strokes (631 ischemic, 104 hemorrhagic, and 12 undefined) occurred. Compared with participants with BMIs less than 23, those with BMIs of 30 or greater had an adjusted relative risk of 2.00 (95% confidence interval [CI], 1.48-2.71) for total stroke, 1.95 (95% CI, 1.39-2.72) for ischemic stroke, and 2.25 (95% CI, 1.01-5.01) for hemorrhagic stroke. When BMI was evaluated as a continuous variable, each unit increase of BMI was associated with a significant 6% increase in the adjusted relative risks of total (95% CI, 4%-8%), ischemic (95% CI, 3%-8%), and hemorrhagic stroke (95% CI, 1%-12%). Additional adjustment for hypertension, diabetes mellitus, and hypercholesterolemia slightly attenuated the risks for total and ischemic (relative risk, 4%; 95% CI, 2%-7%), but not hemorrhagic, stroke. CONCLUSIONS: These prospective data indicate a significant increase in the relative risk of total stroke and its 2 major subtypes with each unit increase of BMI that is independent of the effects of hypertension, diabetes, and cholesterol. Because BMI is a modifiable risk factor, the prevention of stroke may be another benefit associated with preventing obesity in adults.

Age Factors↗