Use of acetaminophen and nonsteroidal anti-inflammatory drugs: a prospective study and the risk of symptomatic diverticular disease in men.

OBJECTIVE: To examine prospectively the relationship between self-reported regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen and the risk of symptomatic diverticular disease. DESIGN: Prospective cohort study using a mailed baseline questionnaire in 1986, and follow-up every 2 years through 1992. SETTING: Male health professionals residing in 50 US states. PATIENTS: A total of 35 615 male health professionals (dentists, optometrists, veterinarians, physicians, pharmacists, osteopathic physicians, podiatrists) 40 to 75 years of age at baseline and free of diagnosed diverticular disease, colon or rectal polyp, ulcerative colitis, and cancer prior to 1988. MAIN OUTCOME MEASURES: Follow-up questionnaires in 1988, 1990, and 1992 about use of NSAIDs, acetaminophen, and other variables including the diagnosis of symptomatic diverticular disease. RESULTS: During 4 years of follow-up, we documented 310 newly diagnosed cases of symptomatic diverticular disease. After adjustment for age, physical activity, and energy-adjusted dietary fiber and total fat intake, regular and consistent use of NSAIDs and acetaminophen was positively associated with the overall risk of symptomatic diverticular disease (for users vs nonusers, relative risk [RR] for NSAIDs = 2.24, 95% confidence interval [CI], 1.28-3.91; RR for acetaminophen = 1.81, 95% CI, 0.79-4.11). Most of this positive association was attributable to cases associated with bleeding, particularly for acetaminophen (for users vs nonusers, RR for NSAIDs = 4.64, 95% CI, 0.99-21.74; RR for acetaminophen = 13.63, 95% CI, 3.53-52.60). CONCLUSIONS: These results suggest that regular and consistent use of NSAIDs in general and acetaminophen is associated with symptoms of severe diverticular disease, particularly bleeding. Further research is needed to investigate the potentially deleterious effect of NSAIDs and other medications on the lower gastrointestinal tract.

The relation of physical activity to risk for symptomatic gallstone disease in men.

BACKGROUND: Gallstone disease is a major source of morbidity in the United States. Gallstones are twice as common in women as in men, but severe biliary events leading to surgery occur with equal frequency in the two sexes. OBJECTIVE: To determine whether physical activity decreases risk for symptomatic gallstone disease in men. DESIGN: Prospective cohort study. SETTING: U.S. male health professionals. PATIENTS: 45,813 men 40 to 75 years of age were followed from 1986 to 1994. MEASUREMENTS: Questionnaires mailed in 1986, 1988, 1990, 1992, and 1994 asked about physical activity, incidence of gallstone disease, age, body weight, dietary and alcohol intake, smoking habits, use of medications, and occurrence of diagnosed medical conditions other than gallstone disease. RESULTS: 828 men reported having newly symptomatic gallstones (diagnosed by ultrasonography or radiography) or undergoing cholecystectomy for recent symptoms. After adjustment for multiple confounders, increased physical activity was inversely related to risk for symptomatic gallstone disease. When extreme quintiles were compared, men younger than 65 years of age had a stronger inverse association (multivariate relative risk, 0.58 [95% CI, 0.44 to 0.78]) with risk than did men 65 years of age or older (relative risk, 0.75 [CI, 0.52 to 1.09]). In contrast, sedentary behavior was positively related to risk for symptomatic gallstone disease. Men who watched television more than 40 hours per week had a higher risk for symptomatic gallstones than men who watched less than 6 hours per week (relative risk for older men, 3.32 [CI, 1.51 to 7.27]; relative risk for younger men, 1.58 [CI, 0.38 to 6.48]). CONCLUSIONS: Physical activity may play an important role in the prevention of symptomatic gallstone disease in men even beyond its benefit for control of body weight. The results of this study indicate that 34% of cases of symptomatic gallstone disease in men could be prevented by increasing exercise to 30 minutes of endurance-type training five times per week.

A prospective study of alcohol, smoking, caffeine, and the risk of duodenal ulcer in men.

The associations between smoking, caffeine, and alcohol intake and the risk of duodenal ulcer have rarely been investigated prospectively. We examined these associations in a prospective cohort of 47,806 men, 40-75 years of age, using a mailed baseline questionnaire in 1986, with follow-up every 2 years through 1992. During 6 years of follow-up, we documented 138 newly diagnosed cases of duodenal ulcer. After adjustment for age, energy-adjusted dietary fiber, body mass index, and use of aspirin or other nonsteroidal antiinflammatory drugs, current smoking was not associated with a substantial risk of duodenal ulcer [relative risk (RR) = 1.07; 95% confidence interval (CI) = 0.61-1.89]. Overall, past smokers were not at increased risk compared with never-smokers (RR = 0.99; 95% CI = 0.69-1.42). Adjusting for other risk factors, alcohol intake (comparing those who drink > 30 gm of alcohol per day to nondrinkers) was not associated with higher risk of duodenal ulcer (RR = 0.74; 95% CI = 0.42-1.29). We observed little association between caffeine, caffeine-containing beverages, and decaffeinated coffee and the risk of duodenal ulcer. These results indicate that smoking is not associated with a substantial increase in risk of duodenal ulcer, nor is high intake of alcohol and caffeine.

Dietary fiber, glycemic load, and risk of NIDDM in men.

OBJECTIVE: Intake of carbohydrates that provide a large glycemic response has been hypothesized to increase the risk of NIDDM, whereas dietary fiber is suspected to reduce incidence. These hypotheses have not been evaluated prospectively. RESEARCH DESIGN AND METHODS: We examined the relationship between diet and risk of NIDDM in a cohort of 42,759 men without NIDDM or cardiovascular disease, who were 40-75 years of age in 1986. Diet was assessed at baseline by a validated semiquantitative food frequency questionnaire. During 6-years of follow-up, 523 incident cases of NIDDM were documented. RESULTS: The dietary glycemic index (an indicator of carbohydrate's ability to raise blood glucose levels) was positively associated with risk of NIDDM after adjustment for age, BMI, smoking, physical activity, family history of diabetes, alcohol consumption, cereal fiber, and total energy intake. Comparing the highest and lowest quintiles, the relative risk (RR) of NIDDM was 1.37 (95% CI, 1.02-1.83, P trend = 0.03). Cereal fiber was inversely associated with risk of NIDDM (RR = 0.70; 95% CI, 0.51-0.96, P trend = 0.007; for > 8.1 g/day vs. < 3.2 g/day). The combination of a high glycemic load and a low cereal fiber intake further increased the risk of NIDDM (RR = 2.17, 95% CI, 1.04-4.54) when compared with a low glycemic load and high cereal fiber intake. CONCLUSIONS: These findings support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of NIDDM in men. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of NIDDM.

Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women.

OBJECTIVE: To examine prospectively the relationship between glycemic diets, low fiber intake, and risk of non-insulin-dependent diabetes mellitus. DESIGN: Cohort study. SETTING: In 1986, a total of 65173 US women 40 to 65 years of age and free from diagnosed cardiovascular disease, cancer, and diabetes completed a detailed dietary questionnaire from which we calculated usual intake of total and specific sources of dietary fiber, dietary glycemic index, and glycemic load. MAIN OUTCOME MEASURE: Non-insulin-dependent diabetes mellitus. RESULTS: During 6 years of follow-up, 915 incident cases of diabetes were documented. The dietary glycemic index was positively associated with risk of diabetes after adjustment for age, body mass index, smoking, physical activity, family history of diabetes, alcohol and cereal fiber intake, and total energy intake. Comparing the highest with the lowest quintile, the relative risk (RR) of diabetes was 1.37 (95% confidence interval [CI], 1.09-1.71, P trend=.005). The glycemic load (an indicator of a global dietary insulin demand) was also positively associated with diabetes (RR= 1.47; 95% CI, 1.16-1.86, P trend=.003). Cereal fiber intake was inversely associated with risk of diabetes when comparing the extreme quintiles (RR=0.72, 95% CI, 0.58-0.90, P trend=.001). The combination of a high glycemic load and a low cereal fiber intake further increased the risk of diabetes (RR=2.50, 95% CI, 1.14-5.51) when compared with a low glycemic load and high cereal fiber intake. CONCLUSIONS: Our results support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of diabetes in women. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of diabetes.

Prospective study of diet and the risk of duodenal ulcer in men.

The authors examined the associations between dietary factors and the risk of duodenal ulcer in a prospective cohort of 47,806 men, aged 40-75 years, who were free of diagnosed gastric or duodenal ulcer or cancer. During 6 years of follow-up, they documented 138 newly diagnosed cases of duodenal ulcer. They found little evidence for an important effect of fat, type of fat, or protein intake. Higher consumption of fruits and vegetables was associated with lower risk of duodenal ulcer (relative risk (RR) = 0.67, 95% confidence interval (CI) 0.39-1.15 for > or = 7 servings per day vs. < 3 servings per day) after adjustment for age, body mass index, smoking, and use of aspirin or other nonsteroidal anti-inflammatory drugs. Total dietary fiber intake was inversely associated with the risk of duodenal ulcer (RR = 0.55, 95% CI 0.31-0.96 for men in the highest vs. the lowest quintile of dietary fiber). The soluble component of fiber was strongly associated with a decreased risk of duodenal ulcer (RR = 0.40, 95% CI 0.22-0.74 for the highest quintile). Several age- and energy-adjusted nutrients correlated with dietary fiber were also inversely related to the risk of duodenal ulcer, but vitamin A from all sources combined (including supplements and multivitamins) was the only nutrient that was statistically significant after adjustment for other risk factors (RR = 0.46, 95% CI 0.23-0.91 for men in the highest vs. the lowest quintile of vitamin A intake). These findings provide evidence that vitamin A from all sources, as well as diets high in fruits and vegetables, may reduce the development of duodenal ulcer, possibly due to their fiber content. Although the associations appeared stronger for dietary fiber and vitamin A, the authors can not exclude the possibility that other closely correlated dietary factors may be the true protective factors.

A prospective study of alcohol, smoking, caffeine, and the risk of symptomatic diverticular disease in men.

The relationship between smoking, caffeine, and alcohol intake and the risk of symptomatic diverticular disease has not been investigated directly. We examined these associations in a prospective cohort of 47,678 US men, 40 to 75 years old. During 4 years of follow-up (1988 to 1992), we documented 382 newly diagnosed cases of symptomatic diverticular disease. After adjustments for age, physical activity, and energy-adjusted intake of dietary fiber and total fat, alcohol intake (comparing those who drink > 30 g of alcohol/d to nondrinkers) was only weakly and nonsignificantly associated with risk of symptomatic diverticular disease (relative risk (RR) = 1.36; 95 percent confidence interval (CI), 0.94 to 1.97; P for trend = 0.37). We observed no association between caffeine, specific caffeinated beverages, and decaffeinated coffee and the risk of symptomatic diverticular disease. Current smoking was not appreciably associated with risk of symptomatic diverticular disease compared to nonsmokers (RR = 1.25; 95 percent CI, 0.75 to 2.09) after adjustment for age, physical activity, and energy-adjusted intake of dietary fiber and total fat. In a subset analysis restricted to men who had undergone sigmoidoscopy or colonoscopy, a modest positive association was seen between smoking and risk of symptomatic diverticular disease. These results suggest that smoking, caffeine, and alcohol intake are not associated with any substantially increased risk of symptomatic diverticular disease.

Prospective study of physical activity and the risk of symptomatic diverticular disease in men.

The relationship between physical activity and risk of symptomatic diverticular disease has not been investigated directly. This association was examined in a prospective cohort of 47,678 American men, 40 to 75 years of age, and free of diagnosed diverticular disease, colon or rectal polyp, ulcerative colitis, and cancer before 1988. During four years of follow up, 382 newly diagnosed cases of symptomatic diverticular disease were documented. After adjustment for age, energy adjusted dietary fibre, and energy adjusted total fat, overall physical activity was inversely associated with the risk of symptomatic diverticular disease (for highest versus lowest extremes, relative risk (RR) = 0.63 (95% confidence interval (CI) 0.45, 0.88). Most of the inverse association was attributable to vigorous activity, for extreme categories RR = 0.60 (95% CI 0.41, 0.87). For activity that was not vigorous the RR was 0.93 (95% CI 0.67, 1.69). Several specific activities were inversely associated with the risk of diverticular disease, but jogging and running combined was the only individual activity that was statistically significant (p for trend = 0.03). For men in the lowest quintile for dietary fibre intake and total physical activity (compared with those in the opposite extreme), the RR was 2.56 (95% CI 1.36, 4.82). Physical activity, along with a high fibre diet, may be an important factor in the prevention of symptomatic diverticular disease.

A prospective study of diet and the risk of symptomatic diverticular disease in men.

To examine the association between dietary fiber, sources of fiber, other nutrients, and the diagnosis of symptomatic diverticular disease, we analyzed data from a prospective cohort of 47,888 US men. During 4 y of follow-up we documented 385 new cases of symptomatic diverticular disease. Total dietary fiber intake was inversely associated with the risk of diverticular disease after adjustment for age, energy-adjusted total fat intake, and physical activity [relative risk (RR) 0.58; 95% CI 0.41, 0.83; P for trend = 0.01 for men in the highest as compared with the lowest quintile of dietary fiber]. This inverse association was primarily due to fruit and vegetable fiber. For men on a high-total-fat, low-fiber diet, the RR was 2.35 (95% CI 1.38, 3.98) compared with those on a low-total-fat, high-fiber diet, and for men on a high-red-meat, low-fiber diet the RR was 3.32 (95% CI 1.46, 7.53) compared with those on a low-red-meat, high-fiber diet. These prospective data support the hypothesis that a diet low in total dietary fiber increases the incidence of symptomatic diverticular disease. They also provide evidence that the combination of high intake of total fat or red meat and a diet low in total dietary fiber particularly augments the risk.

Changes in physical activity and other lifeway patterns influencing longevity.

We studied the adoption or maintenance of physical activity and other optional lifeway patterns for their influence on mortality rates of Harvard College alumni. Men aged 45-84 in 1977, surveyed by questionnaire in 1962 or 1966 and again in 1977, were followed from 1977 through 1988 or to age 90. Of 14,786 alumni, 2,343 died in 165,402 man-years of follow-up. Relative risks of death, standardized for potential confounding influences, for men who between questionnaires increased their physical activity through walking, stair climbing, and sports or recreational activities to 1,500 kcal or more per wk were 0.72 (95% confidence interval 0.64-0.82), compared with 1.00 for men who remained less active. Corresponding relative risks for men who adopted moderately vigorous sports play (> or = 4.5 METs) were 0.73 (0.65-0.81) vs 1.00 for men not adopting such sports; and for cigarette smokers who quit, 0.74 (0.65-0.84) vs 1.00 for persistent smokers. Men with recently diagnosed hypertension had a lower death risk than long-term hypertensives (0.80; 0.70-0.92), as did men with consistent normotension (0.52; 0.47-0.58). Changes in body-mass index had little influence on mortality during follow-up. These findings fit the hypothesis that adopting a physically active lifeway, quitting cigarette smoking, and remaining normotensive independently delay all-cause mortality and extend longevity.

The association of changes in physical-activity level and other lifestyle characteristics with mortality among men.

BACKGROUND: Recent trends toward increasing physical exercise, stopping cigarette smoking, and avoiding obesity may increase longevity. We analyzed changes in the lifestyles of Harvard College alumni and the associations of these changes with mortality. METHODS: Men who were 45 to 84 years of age in 1977 and who had reported no life-threatening disease on questionnaires completed in 1962 or 1966 and again in 1977 were classified according to changes in lifestyle characteristics between the first and second questionnaires. We analyzed changes in their level of physical activity, cigarette smoking, blood pressure, and body weight, and the relation of these factors to mortality between 1977 and 1985. RESULTS: Of the 10,269 men, 476 died during this period (which totaled 90,650 man-years of observation). Beginning moderately vigorous sports activity (at an intensity of 4.5 or more metabolic equivalents) was associated with a 23 percent lower risk of death (95 percent confidence interval, 4 to 42 percent; P = 0.015) than not taking up moderately vigorous sports. Quitting cigarette smoking was associated with a 41 percent lower risk (95 percent confidence interval, 20 to 57 percent; P = 0.001) than continuing smoking, but with a 23 percent higher risk than constant nonsmoking. Men with recently diagnosed hypertension had a lower risk of death than those with long-term hypertension (relative risk, 0.75; 95 percent confidence interval, 0.55 to 1.02; P = 0.057), as did men with consistently normal blood pressure (relative risk, 0.52; 95 percent confidence interval, 0.40 to 0.68; P < 0.001). Maintenance of lean body mass was associated with a lower mortality rate than long-term, recent, or previous obesity. The associations between changes in lifestyle and mortality were independent and were largely undiminished by age. Our findings on death from coronary heart disease mirrored those on death from all causes. CONCLUSIONS: Beginning moderately vigorous sports activity, quitting cigarette smoking, maintaining normal blood pressure, and avoiding obesity were separately associated with lower rates of death from all causes and from coronary heart disease among middle-aged and older men.

The role of physical exercise in the occurrence of Parkinson's disease.

A case-control study of Parkinson's disease and physical exercise was conducted in a cohort of 50,002 men who attended Harvard College (Cambridge, Mass) or the University of Pennsylvania (Philadelphia) between 1916 and 1950 and were followed up in adulthood for morbidity and mortality data. Cases of Parkinson's disease were identified from responses to mailed questionnaires and death certificates through 1978. Four controls from the same population were selected for each case. The association between physical activity at the time of college and subsequent risk of Parkinson's disease was evaluated for 137 cases and 548 controls, whereas the data on physical activity in adulthood before the disease occurrence was available only for 94 of these cases. Having belonged to a varsity team or having done regular physical exercise in college was associated with a lower nonsignificant risk of Parkinson's disease. In adulthood, practice of moderate or heavy sports was linked to a reduced risk, although more precise analysis revealed that there was only a modest nonsignificant reduction in risk for subjects who do a moderate amount of physical exercise, but this negative association disappears at higher levels of physical expenditure. These results, which require further confirmation, are compatible with a slight protective effect of physical exercise on the risk of Parkinson's disease, although the lack of association cannot be refuted.

Physical activity, all-cause mortality, and longevity of college alumni.

We examined the physical activity and other life-style characteristics of 16,936 Harvard alumni, aged 35 to 74, for relations to rates of mortality from all causes and for influences on length of life. A total of 1413 alumni died during 12 to 16 years of follow-up (1962 to 1978). Exercise reported as walking, stair climbing, and sports play related inversely to total mortality, primarily to death due to cardiovascular or respiratory causes. Death rates declined steadily as energy expended on such activity increased from less than 500 to 3500 kcal per week, beyond which rates increased slightly. Rates were one quarter to one third lower among alumni expending 2000 or more kcal during exercise per week than among less active men. With or without consideration of hypertension, cigarette smoking, extremes or gains in body weight, or early parental death, alumni mortality rates were significantly lower among the physically active. Relative risks of death for individuals were highest among cigarette smokers and men with hypertension, and attributable risks in the community were highest among smokers and sedentary men. By the age of 80, the amount of additional life attributable to adequate exercise, as compared with sedentariness, was one to more than two years.

Physical activity, other life-style patterns, cardiovascular disease and longevity.

Longitudinal study of 16,936 Harvard alumni, followed for life-style experiences as related to cardiovascular disease (CVD) and longevity, identified 572 first coronary heart disease (CHD) attacks, 1962-1972, and 1,413 all-cause deaths, 1962-1978. Men expending 8.4+ MJ (2,000+ kcal) per week in walking, stair-climbing, and sports play were at 39% lower risk of developing CHD than less active classmates. Attributable risk estimates suggested: there might have been 16% fewer CVD deaths in the alumni population if every man had exercised 8.4+ MJ per week; 25% fewer from total cigarette abstinence; 9% fewer from abolition of hypertension; 6% fewer with less obesity; and 11% fewer CVD deaths in the absence of parental CHD. Discounting the influence of blood pressure status, cigarette habit, net weight gain since college, and parental history of early death, the more active alumni (39% of the population) are estimated to have lived on average one and one-quarter years longer than less active men.

Cigarette smoking and cardiovascular diseases.

That cigarette smoking is causally associated with development of cardiovascular disease is recognized unequivocally. Epidemiological studies worldwide have documented the many pathways of influence and synergism by which this ubiquitous but artificial habit exerts its ill effects on cardiorespiratory and other body systems, leading not only to cardiovascular disease but to cancer and other ailments. Current investigations among college alumni, women, elderly, and other subgroups provide data on how various independent influences combine with smoking to establish risk and promote pathogenesis of cardiovascular disease. Their findings also confirm that cigarette smoking is one of the strongest instigators. All of this knowledge has implications for the design and implementation of effective intervention programmes.

A natural history of athleticism and cardiovascular health.

Epidemiologic studies in Olympic year 1984 suggest that personal athleticism alters trends in life-style and coronary heart disease. Analysis of 572 first attacks among 16,936 Harvard alumni, 1962 to 1972, and 1,413 total deaths, 1962 to 1978, shows that habitual postcollege exercise, not student sports play, predicts low coronary heart disease risk. Sedentary alumni, even ex-varsity athletes, have high risk. Sedentary students becoming physically active alumni acquire low risk. Exercise benefit is independent of contrary life-style elements--smoking, obesity, weight gain, hypertension, and adverse parental disease history--in affecting coronary heart disease incidence. Hypertension is clinically the strongest predictor of coronary attack, but inadequate exercise is strongest on a community basis. Exercise level is inversely related to total, cardiovascular, and respiratory mortality but less related to cancer or unnatural deaths. The current exercise revolution may improve life-style, cardiovascular health, and longevity.

Epidemiology of exercise and coronary heart disease.

Several studies are reviewed that examine the role of exercise in men at work and in men at leisure activity and sports play. All show that adequate exercise reduces the risk of coronary heart disease. Many recent investigations have undertaken the study of the various mechanisms by which physical activity produces these effects.