US Male Health Professionals Research Articles

A Prospective Study of Periodontal Disease and Pancreatic Cancer in US Male Health Professionals

Two previous cohort studies reported positive associations between tooth loss or periodontitis and pancreatic cancer risk. Data on periodontal disease were obtained at baseline and every other year thereafter in a cohort of 51,529 male health professionals aged 40-75 years. A total of 216 patients were diagnosed with incident pancreatic cancer during 16 years of follow-up. Multivariable relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models controlling for potential confounders, including detailed smoking history. All statistical tests were two-sided. Compared with no periodontal disease, history of periodontal disease was associated with increased pancreatic cancer risk (overall, multivariable RR = 1.64, 95% CI = 1.19 to 2.26; P = .002; crude incidence rates: 61 versus 25 per 100,000 person-years; among never smokers, multivariable RR = 2.09, 95% CI = 1.18 to 3.71; P = .01; crude incidence rates: 61 versus 19 per 100,000 person-years). In contrast, baseline number of natural teeth and cumulative tooth loss during follow-up were not strongly associated with pancreatic cancer. The association between periodontal disease and increased risk of pancreatic cancer may occur through plausible biologic mechanisms, but confirmation of this association is necessary.

Statin Drugs and Risk of Advanced Prostate Cancer

Statins are commonly used cholesterol-lowering drugs that have proapoptotic and antimetastatic activities that could affect cancer risk or progression. Results from previous epidemiologic studies of the association between statin use and cancer have been inconsistent. We investigated the association of statin use with total and advanced prostate cancer, the latter being the most important endpoint to prevent. We analyzed data from an ongoing prospective cohort study of 34,989 US male health professionals who were cancer free in 1990 and were followed to 2002. Participants reported their use of cholesterol-lowering drugs on biennial questionnaires. Prostate cancer diagnosis was confirmed by medical record review. Multivariable-adjusted relative risks (RRs) were estimated from Cox proportional hazards regression models. Statistical tests were two-sided. During 376,939 person-years of follow-up, we ascertained 2579 prostate cancer cases, 316 of which were advanced (regionally invasive, metastatic, or fatal). The age-standardized incidence rates of advanced prostate cancer were 38 and 89 per 100,000 person-years in current statin users and in past or never users, respectively. The multivariable-adjusted relative risk of advanced disease was 0.51 (95% confidence interval [CI] = 0.30 to 0.86) and of metastatic or fatal disease was 0.39 (95% CI = 0.19 to 0.77) for current statin use compared with no current use. The associations remained after adjusting for prostate-specific antigen screening history (advanced disease: RR = 0.57, 95% CI = 0.30 to 1.11; metastatic or fatal disease: RR = 0.35, 95% CI = 0.14 to 0.92). Risk of advanced disease was lower with longer statin use (P(trend) = .003); compared with never use, the relative risk for less than 5 years of use was 0.60 (95% CI = 0.35 to 1.03) and for 5 or more years of use was 0.26 (95% CI = 0.08 to 0.83). We found no association between statin use and risk of total prostate cancer (RR = 0.96, 95% CI = 0.85 to 1.09). In this cohort of male health professionals, use of statin drugs was not associated with risk of prostate cancer overall but was associated with a reduced risk of advanced (especially metastatic or fatal) prostate cancer.

A retrospective study of the relationship between biomarkers of atherosclerosis and erectile dysfunction in 988 men

Erectile dysfunction (ED) is associated with clinical atherosclerosis and several atherosclerotic risk factors including smoking, hypertension, dyslipidemia, diabetes mellitus, obesity and sedentary lifestyle. Clinical atherosclerosis is also associated with these same risk factors and with biomarkers of inflammation, thrombosis, endothelial cell activation. We evaluated the cross-sectional association between the degree of ED and levels of atherosclerotic biomarkers. A subcohort of 988 US male health professionals between the ages 46 and 81 years as part of an ongoing epidemiologic study had atherosclerotic biomarkers measured from blood collected in 1994-1995. These same men had in 2000, been retrospectively asked about erectile function in 1995 and in 2000. Biennial questionnaires since 1986 assessed medical conditions, medications, smoking, physical activity, body mass index, alcohol intake. The retrospective assessment of erectile function in 2000 for 1995 in these 988 men ranged from very good - 28.2%, good - 25.1%, fair - 19.2%, poor - 13.6%, to very poor - 13.9%. Men with poor to very poor erectile function compared to men with good and very good erectile function had 2.9 the odds of having elevated Factor VII levels (P=0.03), 1.9 times the odds of having elevated vascular cell adhesion molecule (P=0.13) and 2.0 times the odds of having elevated intracellular adhesion molecule (P=0.06) and 2.1 times the odds of having elevated total cholesterol/high-density lipoprotein ratio (P=0.02) comparing the top to bottom quintiles for each atherosclerotic biomarker after multivariate adjustment. Lipoprotein(a), homocysteine, interleukin-6 and tumor necrosis factor receptor, C-reactive protein and fibrinogen were not associated with the degree of erectile function after adjustment. We conclude that selected biomarkers for endothelial function, thrombosis and dyslipidemia but not inflammation are associated with the degree of ED in this cross-sectional analysis. Future studies evaluating the prospective association of ED, endothelial function and cardiovascular disease appear warranted.

A prospective study of physical activity and incident and fatal prostate cancer: Giovannucci EL, Liu Y, Leitzmann MF, Stampfer MJ, Willett WC, Department of Nutrition, Harvard School of Public Health, Boston, MA

Background Whether physical activity has benefits against prostate cancer incidence or progression is unclear. Therefore, we assessed physical activity in relation to prostate cancer incidence, mortality, and Gleason histologic grade. Methods We used data from the Health Professionals Follow-up Study, a prospective cohort study, to determine the number of cases of incident, advanced (seminal vesicle invasion, metastasis, or fatal), fatal, and high-grade prostate cancer in a cohort of 47,620 US male health professionals, followed up from February 1, 1986, to January 31, 2000. Results During 14 years of follow-up, we documented 2892 new cases of prostate cancer, including 482 advanced cases (280 of which were fatal). For total prostate cancer, no association was observed for total, vigorous, and nonvigorous physical activity. In men 65 years or older, we observed a lower risk in the highest category of vigorous activity for advanced (multivariable relative risk, 0.33; 95% confidence interval, 0.17–0.62, for more than 29 vs 0 metabolic equivalent hours) and for fatal (relative risk, 0.26; 95% confidence interval, 0.11–0.66) prostate cancer. No associations were observed in younger men. Differential screening by prostate-specific antigen or a reduction in physical activity due to undiagnosed prostate cancer did not appear to account for the results. Among cases, men with high levels of physical activity were less likely to be diagnosed with poorly differentiated cancers (Gleason grade ≥7). Conclusion Although the mechanisms are not yet understood, these findings suggest that regular vigorous activity could slow the progression of prostate cancer and might be recommended to reduce mortality from prostate cancer, particularly given the many other documented benefits of exercise.

A Prospective Study of Physical Activity and Incident and Fatal Prostate Cancer

Whether physical activity has benefits against prostate cancer incidence or progression is unclear. Therefore, we assessed physical activity in relation to prostate cancer incidence, mortality, and Gleason histologic grade. We used data from the Health Professionals Follow-up Study, a prospective cohort study, to determine the number of cases of incident, advanced (seminal vesicle invasion, metastasis, or fatal), fatal, and high-grade prostate cancer in a cohort of 47,620 US male health professionals, followed up from February 1, 1986, to January 31, 2000. During 14 years of follow-up, we documented 2892 new cases of prostate cancer, including 482 advanced cases (280 of which were fatal). For total prostate cancer, no association was observed for total, vigorous, and nonvigorous physical activity. In men 65 years or older, we observed a lower risk in the highest category of vigorous activity for advanced (multivariable relative risk, 0.33; 95% confidence interval, 0.17-0.62, for more than 29 vs 0 metabolic equivalent hours) and for fatal (relative risk, 0.26; 95% confidence interval, 0.11-0.66) prostate cancer. No associations were observed in younger men. Differential screening by prostate-specific antigen or a reduction in physical activity due to undiagnosed prostate cancer did not appear to account for the results. Among cases, men with high levels of physical activity were less likely to be diagnosed with poorly differentiated cancers (Gleason grade > or = 7). Although the mechanisms are not yet understood, these findings suggest that regular vigorous activity could slow the progression of prostate cancer and might be recommended to reduce mortality from prostate cancer, particularly given the many other documented benefits of exercise.

Prospective study of phobic anxiety and risk of Parkinson's disease.

Anxiety disorders are common in Parkinson's disease (PD). However, the risk of PD among people with anxiety has not been examined in a prospective cohort study. We examined this relation prospectively within the Health Professionals Follow-Up Study, a cohort of US male health professionals. In 1988, anxiety was assessed using the Crown-Crisp phobic anxiety index in 35,815 men without PD, stroke, or cancer at baseline. There were 189 incident cases of PD during 12 years of follow-up. After adjusting for age, smoking, and caffeine intake, the relative risk of PD among men with the highest level of anxiety (Crown-Crisp index scores of 4 and above) was 1.5 (95% CI = 1.0-2.1; P-trend = 0.01) compared to men with the lowest level of anxiety. This positive association persisted after excluding cases of PD with onset in the first 2 years of follow-up. Use of anxiolytic medication was also associated with an elevated risk of PD (RR= 1.6; 95% CI = 0.9-3.1), but adjusting for this potential confounder did not materially affect the association between anxiety and risk of PD. Our results suggest that anxiety is a risk factor for PD. Whether this association is causal or the result of shared underlying biology remains a question.

Social ties and change in social ties in relation to subsequent total and cause-specific mortality and coronary heart disease incidence in men.

The authors prospectively examined the effects of social ties and change in social ties, as measured by a well-known social network index, on total and cause-specific mortality and on coronary heart disease incidence in 28,369 US male health professionals aged 42-77 years in 1988. Over 10 years, the relative risk of total mortality for men in the lower two levels of social integration compared with more socially integrated men was 1.19 (95% confidence interval: 1.06, 1.34) after controlling for age, occupation, health behaviors, general physical condition, coronary risk factors, and dietary habits. In multivariate analysis, deaths from accidents and suicide and from other noncancer, noncardiovascular causes were significantly increased among less socially connected men. Socially isolated men also had an increased risk of fatal coronary heart disease (multivariate relative risk = 1.82, 95% confidence interval: 1.02, 3.23). An increase in the overall social network index between 1988 and 1996 was not significantly associated with subsequent 2-year mortality. In analyses of change in social network components restricted to older men, each categorical unit increase in number of close friends was significantly associated with a 29% decrease in risk of death. Increase in religious service attendance over time was also significantly predictive of decreased mortality.

Adherence to the Dietary Guidelines for Americans and risk of major chronic disease in men

The Dietary Guidelines for Americans and the food guide pyramid aim to reduce the risk of major chronic disease in the United States, but data supporting their overall effectiveness are sparse. The healthy eating index (HEI) measures the concordance of dietary patterns with these guidelines. We tested whether a high HEI score (range: 0-100; 100 is best) calculated from a validated food-frequency questionnaire (HEI-f) could predict lower risk of major chronic disease in men. A cohort of US male health professionals without major disease completed detailed questionnaires on food intake and other risk factors for heart disease and cancer in 1986 and repeatedly during the 8-y follow-up. Major chronic disease outcome was defined as incident major cardiovascular disease (stroke or myocardial infarction, n = 1092), cancer (n = 1661), or other non-trauma-related deaths (n = 366). The HEI-f was weakly inversely associated with risk of major chronic disease [comparing highest with lowest quintile of the HEI-f, relative risk (RR) = 0.89; 95% CI: 0.79, 1.00; P: < 0.001 for trend]. The HEI-f was associated with moderately lower risk of cardiovascular disease (RR = 0.72; 95% CI: 0.60, 0.88; P: < 0.001) but was not associated with lower cancer risk. The HEI-f was only weakly associated with risk of major chronic disease, suggesting that improvements to the HEI may be warranted. Further research on the HEI could have implications for refinements to the Dietary Guidelines for Americans and the food guide pyramid.

A prospective study of carotenoid intake and risk of cataract extraction in US men

Dietary antioxidants, including carotenoids, are hypothesized to decrease the risk of age-related cataracts by preventing oxidation of proteins or lipids within the lens. However, prospective epidemiologic data concerning this phenomenon are limited. Our objective was to examine prospectively the association between carotenoid and vitamin A intakes and cataract extraction in men. US male health professionals (n = 36644) who were 45-75 y of age in 1986 were included in this prospective cohort study. Others were subsequently included as they became 45 y of age. A detailed dietary questionnaire was used to assess intake of carotenoids and other nutrients. During 8 y of follow-up, 840 cases of senile cataract extraction were documented. We observed a modestly lower risk of cataract extraction in men with higher intakes of lutein and zeaxanthin but not of other carotenoids (alpha-carotene, beta-carotene, lycopene, and beta-cryptoxanthin) or vitamin A after other potential risk factors, including age and smoking, were controlled for. Men in the highest fifth of lutein and zeaxanthin intake had a 19% lower risk of cataract relative to men in the lowest fifth (relative risk: 0.81; 95% CI: 0.65, 1.01; P for trend = 0.03). Among specific foods high in carotenoids, broccoli and spinach were most consistently associated with a lower risk of cataract. Lutein and zeaxanthin may decrease the risk of cataracts severe enough to require extraction, although this relation appears modest in magnitude. The present findings add support for recommendations to consume vegetables and fruit high in carotenoids daily.

Risk factors for basal cell carcinoma of the skin in men: results from the health professionals follow-up study.

The authors examined the relation of constitutional factors and sun exposure to risk of basal cell carcinoma of the skin (BCC) in a prospective cohort of 44,591 predominantly Caucasian US male health professionals, 40-75 years of age and free of cancer at enrollment in 1986. During 8 years of follow-up, 3,273 cases of self-reported BCC were documented. The following variables were each associated with an elevated risk of BCC: having red hair; green, hazel, or blue eyes; a tendency to sunburn; and north European ancestry. The lifetime number of blistering sunburns was also positively associated with BCC risk (p trend < 0.0001). Compared with men who as teenagers had been outside less than once a week, men who had been outside weekly (relative risk (RR) = 1.30; 95% confidence interval (CI): 1.14, 1.47) and daily (RR = 1.42; 95% CI: 1.24, 1.63) had an elevated risk of BCC. Living in a region of residence with high solar radiation as an adult was also associated with an increased risk of BCC (RR = 1.48; 95% CI: 1.36, 1.60), whereas living in such a region only in childhood did not increase BCC risk. These results confirm the role of constitutional factors and suggest that adult sun exposure increases BCC risk.

A prospective study of coffee consumption and the risk of symptomatic gallstone disease in men.

Coffee has several metabolic effects that could reduce the risk of gallstone formation. To examine the association between coffee consumption and the risk of symptomatic gallstone disease in men. The Health Professionals Follow-up Study, a prospective cohort study, in which the consumption of coffee and other caffeinated drinks was assessed starting in 1986 as part of the 131-item food frequency questionnaire given to US male health professionals with follow-up through 1996. A total of 46008 men, aged 40 to 75 years in 1986, without history of gallstone disease. Newly symptomatic gallstone disease (diagnosed by ultrasonography or x-ray) or a cholecystectomy. During 404 166 person-years of follow-up, 1081 subjects reported symptomatic gallstone disease, of whom 885 required cholecystectomy. After adjusting for other known or suspected risk factors, compared with men who did not consume regular coffee in 1986 and 1990, the adjusted relative risk (RR) for those who consistently drank 2 to 3 cups of regular coffee per day was 0.60 (95% confidence interval [CI], 0.42-0.86) and for those who drank 4 or more cups per day the RR was 0.55 (95% CI, 0.33-0.92). All coffee brewing methods showed a decreased risk. The risk of symptomatic gallstone disease also declined with increasing caffeine intake (P for trend = .005). After controlling for known or suspected risk factors, the RR for men in the highest category of caffeine intake (>800 mg/d) compared with men in the lowest category (< or =25 mg/d) was 0.55 (95% CI, 0.35-0.87). In contrast, decaffeinated coffee was not associated with a decreased risk. In this cohort of US men, coffee consumption may have helped to prevent symptomatic gallstone disease.

Body size and fat distribution as predictors of stroke among US men.

Evidence for an association between general obesity and risk of stroke is weak. However, abdominal obesity may be more closely related to stroke risk. The association of body mass index and abdominal obesity (waist/hip ratio) with stroke incidence was examined in 28,643 US male health professionals, aged 40-75 years in 1986, who had no history of cardiovascular disease or stroke. In 5 years of follow-up, there were 118 cases of stroke, of which 80 were ischemic. Compared with men in the lowest quintile of body mass index, men in the highest quintile had an age-adjusted relative risk of stroke of 1.29 (95% confidence interval 0.73-2.27). In contrast, the age-adjusted relative risk for extreme quintiles of waist/hip ratio was 2.33 (95% confidence interval 1.25-4.37). This relative risk was not substantially altered in a multivariate model including body mass index, height, and other potential risk factors. There was a weaker relation with waist circumference alone, with men in the highest quintile (> 40.2 inches) having a relative risk of 1.52 (95% confidence interval 0.82-2.82) compared with men in the lowest quintile (< or = 34.5 inches) (1 inch = 2.54 cm). The results suggest that abdominal obesity, but not elevated body mass index, predicts risk of stroke in men.

A prospective study of social networks in relation to total mortality and cardiovascular disease in men in the USA.

Previous studies have established a relationship between low levels of social networks and total mortality, but few have examined cause specific mortality or disease incidence. This study aimed to examine prospectively the relationships between social networks and total and cause specific mortality, as well as cardiovascular disease incidence. This was a four year follow up study in an ongoing cohort of men, for whom information on social networks was collected at baseline. The main outcome measures were total mortality, further categorised into deaths from cardiovascular disease (stroke and coronary heart disease), total cancer, accidents/suicides, and all other causes; as well as stroke and coronary heart disease incidence. Altogether 32,624 US male health professionals aged 42 to 77 years in 1988, who were free of coronary heart disease, stroke, and cancer at baseline. A total of 511 deaths occurred during 122,911 person years of follow up. Compared with men with the highest level of social networks, socially isolated men (not married, fewer than six friends or relatives, no membership in church or community groups) were at increased risk for cardiovascular disease mortality (age adjusted relative risk, 1.90; 95% CI 1.07, 3.37) and deaths from accidents and suicides (age adjusted relative risk 2.22; 95% CI 0.76, 6.47). No excess risks were found for other causes of death. Socially isolated men were also at increased risk of stroke incidence (relative risk, 2.21; 95% CI, 1.12, 4.35), but not incidence of non-fatal myocardial infarction. Social networks were associated with lower total mortality by reducing deaths from cardiovascular disease and accidents/suicides. Strong social networks were associated with reduced incidence of stroke, though not of coronary heart disease. However, social networks may assist in prolonging the survival of men with established coronary heart disease.

Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men.

To examine prospectively the relationship between dietary fiber and risk of coronary heart disease. Cohort study. In 1986, a total of 43,757 US male health professionals 40 to 75 years of age and free from diagnosed cardiovascular disease and diabetes completed a detailed 131-item dietary questionnaire used to measure usual intake of total dietary fiber and specific food sources of fiber. Fatal and nonfatal myocardial infarction (MI). During 6 years of follow-up, we documented 734 cases of MI (229 were fatal coronary heart disease). The age-adjusted relative risk (RR) for total MI was 0.59 (95% confidence interval [CI], 0.46 to 0.76) among men in the highest quintile of total dietary fiber intake (median, 28.9 g/d) compared with men in the lowest quartile (median, 12.4 g/d). The inverse association was strongest for fatal coronary disease (RR, 0.45; 95% CI, 0.28 to 0.72). After controlling for smoking, physical activity and other known nondietary cardiovascular risk factors, dietary saturated fat, vitamin E, total energy intake, and alcohol intake, the RRs were only modestly attenuated. A 10-g increase in total dietary fiber corresponded to an RR for total MI of 0.81 (95% CI, 0.70 to 0.93). Within the three main food contributors to total fiber intake (vegetable, fruit, and cereal), cereal fiber was most strongly associated with a reduced risk of total MI (RR, 0.71; 95% CI, 0.55 to 0.91 for each 10-g increase in cereal fiber per day). Our results suggest an inverse association between fiber intake and MI. These results support current national dietary guidelines to increase dietary fiber intake and suggest that fiber, independent of fat intake, is an important dietary component for the prevention of coronary disease.

Prospective study of phobic anxiety and risk of coronary heart disease in men.

To examine prospectively the association between self-reported symptoms of phobic anxiety and subsequent risk of coronary heart disease, a 2-year follow-up study was conducted of a cohort of 33,999 US male health professionals, aged 42 to 77 years in 1988, who were free of diagnosed cardiovascular disease at baseline. Levels of phobic anxiety were assessed using the Crown-Crisp index, a short, diagnostic self-rating scale used for common phobias. Main outcomes were incidents of coronary heart disease consisting of nonfatal myocardial infarction (MI) and fatal coronary heart disease (CHD). One hundred sixty-eight incident cases of CHD occurred during 2 years of follow-up (128 cases of nonfatal MI and 40 cases of fatal CHD). The age-adjusted relative risk of fatal CHD among men with highest levels of phobic anxiety (scoring 4 or higher on the Crown-Crisp index) was 3.01 (95% confidence interval, 1.31 to 6.90) compared with men with the lowest levels of anxiety (scoring 0 or 1 on the phobia index). Risk of fatal CHD increased with levels of phobic anxiety (P trend = .002). When fatal CHD was further categorized into sudden and nonsudden coronary death, the excess risk was confined to sudden death (relative risk among men scoring 3 or higher on the phobia index was 6.08; 95% confidence interval, 2.35 to 15.73). No association was found between phobic anxiety and risk of nonfatal MI. These findings remained essentially unchanged after adjusting for a broad range of cardiovascular risk factors. The specificity, strength, and dose-response gradient of the association, together with the consistency and biological plausibility of the experimental and epidemiologic evidence, support a strong causal association between phobic anxiety and fatal CHD.

A prospective study of nutritional factors and hypertension among US men.

An effect of diet in determining blood pressure is suggested by epidemiological studies, but the role of specific nutrients is still unsettled. The relation of various nutritional factors with hypertension was examined prospectively among 30,681 predominantly white US male health professionals, 40-75 years old, without diagnosed hypertension. During 4 years of follow-up, 1,248 men reported a diagnosis of hypertension. Age, relative weight, and alcohol consumption were the strongest predictors for the development of hypertension. Dietary fiber, potassium, and magnesium were each significantly associated with lower risk of hypertension when considered individually and after adjustment for age, relative weight, alcohol consumption, and energy intake. When these nutrients were considered simultaneously, only dietary fiber had an independent inverse association with hypertension. For men with a fiber intake of < 12 g/day, the relative risk of hypertension was 1.57 (95% confidence interval, 1.20-2.05) compared with an intake of > 24 g/day. Calcium was significantly associated with lower risk of hypertension only in lean men. Dietary fiber, potassium, and magnesium were also inversely related to baseline systolic and diastolic blood pressure and to change in blood pressure during the follow-up among men who did not develop hypertension. Calcium was inversely associated with baseline blood pressure but not with change in blood pressure. No significant associations with hypertension were observed for sodium, total fat, or saturated, transunsaturated, and polyunsaturated fatty acids. Fruit fiber but not vegetable or cereal fiber was inversely associated with incidence of hypertension. These results support hypotheses that an increased intake of fiber and magnesium may contribute to the prevention of hypertension.