Nurses’ Health Study

GIOVANNUCCI E, STAMPFER M J, COLDITZ G A, HUNTER J, FUCHS C, ROSNER B A, SPEIZER F E and WILLETT w c (1998) Multivitamin use, folate, and colon cancer in women in the Nurses Health Study , Ann Intern Med, 129, 517-24. 

Karlson, E. W., Mandl, L. A., Hankinson, S. E., and Grodstein, E. (2004). Do breast-feeding and other reproductive factors influence future risk of rheumatoid arthritis Results from the nurses health study. Arthitis Rheum. 50,3458-3467. 

F. Laden et al., Plasma Organochlorine Levels and the Risk of Breast Cancer An Extended Follow-up in the Nurses Health Study, Int. J. Cancer 91 (2001) 568-74 K. J. Aronson et al., Breast Adipose Tissue Concentrations of Polychlorinated Biphenyls and Other Organochlorines and Breast Cancer Risk, Cancer Epidemiol. Biomarkers. Prev. 9 (2000) 55-65. 

Colditz GA, Stampfer MJ, Willett WC, Hunter DJ, Manson JE, Hennekens CK, Rosner BA, Speizer FE. Type of postmenopausal hormone use and risk of breast cancer. 12-year follow-up from the Nurses Health Study. Cancer Causes Control 1992 3 433-9. 

Data from the classic Nurses Health Study, followed up in 1994, reflected no difference in all-cause mortality between women who had ever used oral contraceptives and those who had never used them (7). There was also no increase in mortality associated with duration of use and no relation with time since first use or time since last use. Similarly, in the OFPA (Oxford) study, the overall 20-year mortality risk for oral contraceptive users compared with women using diaphragms or IUCDs was 0.9, suggesting no effect (8). Although the number of deaths from each cause was small, the pattern is consistent with the risks found in other studies. Oral contraceptive users had somewhat higher death rates from ischemic heart disease and cervical cancer, but lower rates of ovarian cancer mortality. Breast cancer mortality was similar for oral contraceptive users and non-users. 

Colditz GA. Oral contraceptive use and mortality during 12 years of follow-up the Nurses Health Study. Ann Intern Med 1994 120(10) 821-6. 

Stampfer MJ, Willett WC, Colditz GA, Speizer FE, Hennekens CH. Past use of oral contraceptives and cardiovascular disease a meta-analysis in the context of the Nurses Health Study. Am J Obstet Gynecol 1990 163(1 Pt 2) 285-91. 

A number of groups continue to stress the possibility, raised in the Nurses Health Study and elsewhere, that by reducing the dosages used in hormonal replacement one might eliminate the risks while retaining efficacy (17), but so long as this has not been shown to be true it will not provide a way ahead. 

Nonetheless, the inverse relationship between unsaturated fat and CVD is supported by the results from prospective cohort studies such as the Ireland-Boston Diet Heart Study (Kushi et al., 1985) and the Nurses Health Study (Hu et al., 1997) and long-term intervention studies such as the Los Angeles Veteran Study and the Finnish Mental Hospital Study (Dayton et al., 1965 Turpeinen et al., 1979). In the Indo-Mediterranean Diet Heart Study (Singh et al., 2002) and the Lyon Diet Heart Study (de Lorgeril et al., 1999), a diet high in unsaturated fat and complex carbohydrates were proven to be potent to reduce coronary events. It has been difficult to prove a clear relationship between saturated fat and future cardiovascular events in prospective cohort studies, and this is highlighted by the recent meta-analysis described below. 

In the Nurses Health Study (Hu et ah, 1997), the dietary intake of short- and medium-chained saturated fatty acids (4 0-10 0) was not significantly associated with CHD (but other saturated fatty acids were). In an intervention study a higher intake of medium-chained triglycerides was found to significantly decrease total adipose tissue, subcutaneous adipose tissue, and upper-body adipose tissue stores in men compared to longer chained triglyceride consumption (St-Onge, 2005). 

Inflammation is an important factor in the development of cardiovascular disease. Most clinical studies involving inflammation parameters have been relatively small. The Nurses Health Study involving 727 women was the largest study designed to determine the effects of n-3 fatty acids on biomarkers of inflammation and endothelium activation (Lopez-Garcia et al., 2004). They found an inverse association between ALA intake and plasma concentrations of C-reactive protein (a marker for inflammation), Interlukin-6, and E-selectin. Bemelmans et al. (2004) also found an inverse association between C-reactive protein and ALA intake in a randomized, double-blind placebo-controlled study involving 103 hypercholesterolemic subjects. 

Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA. Rotating night shifts and risk of breast cancer in women participating in the Nurses Health Study. J Natl Cancer Inst 2001 93(20) 1563-1568. 

Cambridge Heart Antioxidant Study DATATOR Deprenyl and Tocopherol Antioxidative Therapy of Rarkinsonism FMC, Finnish Mobile Clinic Health Examination Survey GISSI, Gruppo Italiano Studio Soprawivenza Infarto HOPE, Heart Outcome Prevention Evaluation HPFS, Health Professional Follow-up Study NHS, Nurses Health Study PPR Primary Prevention Project SPACE, Secondary Prevention with Antioxidants of Cardiovascular disease in End-stage renal disease VEAPS, Vitamin E Atherosclerosis Prevention Study VECAT Vitamin E Cataract Age-related maculopathy Trial. 

The 14-year follow-up of the Nurses Health Study, the largest of the prospective studies with 2,956 cases, also found no evidence of association between total or type of fat and breast cancer risk (Holmes et al., 1999a). Further, no survival advantage was found for a low-fat diet or diets containing a particular fat type after diagnosis of breast cancer in this cohort of nurses (Holmes et al., 1999b). 

Ravnskov (1998) presented data for 28 cohorts from 21 prospective studies. In only three of these cohorts did the evidence show that saturated fat was associated with a statistically significant increased risk of CHD. CHD patients in three cohort studies had consumed significantly more polyunsaturated fat, and in only one cohort had CHD patients eaten less polyunsaturated fat than CHD-free participants. The cohorts included the Framingham Study and the large well-conducted Health Professionals Follow-up Study and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Since then, Hu et al. (1997) presented the 14-year follow-up data from the Nurses Health Study. After adjustment for confounding variables in multivariate analyses, no statistically significant associations were found between intake of total fat, animal fat, or saturated fat and the risk of CHD. 

Kritchevsky and Kritchevsky (2000) provided a summary of the evidence linking dietary cholesterol to the risk of CHD in 10 cohorts from eight large, well-conducted prospective studies that were reported since 1980, which included the Nurses Health Study, the Health Professionals Followup Study and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. In eight of the cohorts there was no statistical association between cholesterol intake and the risk of CHD. In one of the positive studies the association was established by simple univariate analysis and was not adjusted for other dietary variables. The other study adjusted only for fat intake. There is no compelling evidence from these epidemiological studies that dietary cholesterol is associated with the risk of CHD. 

Early studies of the relation between intake of TFAs and the occurrence of CHD also produced conflicting results. However, the large, well-conducted prospective studies showed positive associations between TFA intake and risk of CHD. The Nurses Health Study and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study produced statistically significant positive associations, whereas in the Health Professionals Followup Study the positive association did not attain statistical significance (Ascherio et al., 1999). There was also a significant positive association between TFA intake and CHD risk in the smaller Zutphen Elderly Study (Oomen et al., 2001). 

A case-control study (Ascherio et al., 1994), a cross-sectional study (Bolton-Smith et al., 1996) and three prospective studies the Nurses Health Study (Willett et al., 1993), the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (Pietinen et al., 1997), and the Zutphen Elderly Study (Oomen et al., 2001), separately assessed the effect of TFAs from hydrogenated vegetable oil and animal fat on the risk of CHD. With the exception of the small Zutpen Elderly Study (Oomen et al., 2001), the studies found that the positive association with the risk of CHD was explained entirely by the intake of TFAs from hydrogenated vegetable oil. 

A study on diet and colon cancer was reported by W. Willett s group (Willett et at., 1990) (Table 11.3). The study examined various components of the diet, such as fiber, fat, and meat. The fiber component was divid into cereal fiber and fruit fiber. The fat component was divided into meat fat, dairy fat, saturated fat, and unsaturated fat. The meat component was divided into beef, pork, and lamb, and into rare versus well-done Styles of cooking. The body mass index, as defined in the Obesity chapter, was also recorded. The study was part of the Nurses Health Study Cohort, which was inibated in 1976 and involved 121,700 female nurses. Every 2 years, the nurses filled in a questionnaire that asked about various risk factors for disease. The questionnaire asked, for example, about 61 foods and their frequency In the diet. The foods were chosen to allow epidemiologists to make broad statements regarding the component nutrients. 

Despite the high prevalence of the use of minor analgesics (aspirin and paracetamol) there is little information available on the association between the use of these analgesics and the risk of hypertension. A prospective cohort study in 80 020 women aged 31-50 years has provided some useful information (5). The women had participated in the Nurses Health Study II and had no previous history of hypertension. The frequency of use of paracetamol, aspirin, and NSAIDs was collected by mailed questionnaires and cases of physician-diagnosed hypertension were identified by self-report. During 164 000 person-years of follow-up, 1650 incident cases of hypertension were identified. Overall, 73% of the cohort had used paracetamol at least 1-4 days/month, 51% had used aspirin, and 77% had used an NS AID. Compared with non-users of paracetamol the age-adjusted relative risk... 

It is of interest that several recent studies confirm that smoking increases not only the risk to develop diabetic nephropathy, but also the risk to develop type 2 diabetes as found in the nurses health study [34] and recently confirmed by other studies [35]. 

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