George W. Comstock

Symptoms of depression in two communities

Histories of depression-related symptoms were obtained from 3845 randomly selected adult residents of Kansas City, Missouri, and Washington County, Maryland. Depressed persons were slightly more common in Kansas City than in Washington County but within the latter area no urban-rural differences were observed. More depressed persons were found among blacks than among whites. Slightly more white females than males were depressed; no significant differences were found between black females and males. After adjustment for the effects of other independent variables, the probability of having symptoms of depression was highest among persons who were young adults, unmarried, not employed outside the home, poorly paid, and not well educated.

Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study.

Blood samples taken in 1974 in Washington County, Maryland, from 25 620 volunteers were used to investigate the relation of serum 25-hydroxyvitamin D (25-OHD) with subsequent risk of getting colon cancer. 34 cases of colon cancer diagnosed between August, 1975, and January, 1983, were matched to 67 controls by age, race, sex, and month blood was taken. Risk of colon cancer was reduced by 75% in the third quintile (27-32 ng/ml) and by 80% in the fourth quintile (33-41 ng/ml) of serum 25-OHD. Risk of getting colon cancer decreased three-fold in people with a serum 25-OHD concentration of 20 ng/ml or more. The results are consistent with a protective effect of serum 25-OHD on colon cancer.

Serum beta-carotene, vitamins A and E, selenium, and the risk of lung cancer

We studied the relation of serum vitamin A (retinol), beta-carotene, vitamin E, and selenium to the risk of lung cancer, using serum that had been collected during a large blood-collection study performed in Washington County, Maryland, in 1974. Levels of the nutrients in serum samples from 99 persons who were subsequently found to have lung cancer (in 1975 to 1983) were compared with levels in 196 controls who were matched for age, sex, race, month of blood donation, and smoking history. A strong inverse association between serum beta-carotene and the risk of squamous-cell carcinoma of the lung was observed (relative odds, 4.30; 95 percent confidence limits, 1.38 and 13.41). Mean (+/- SD) levels of vitamin E were lower among the cases than the controls (10.5 +/- 3.2 vs. 11.9 +/- 4.90 mg per liter), when all histologic types of cancer were considered together. In addition, a linear trend in risk was found (P = 0.04), so that persons with serum levels of vitamin E in the lowest quintile had a 2.5 times higher risk of lung cancer than persons with levels in the highest quintile. These data support an association between low levels of serum vitamin E and the risk of any type of lung cancer and between low levels of serum beta-carotene and the risk of squamous-cell carcinoma of the lung.

Risk Factors for Chronic Kidney Disease: A Prospective Study of 23,534 Men and Women in Washington County, Maryland

Chronic kidney disease (CKD) is an increasing cause of morbidity and mortality in the United States. Prospective data on risk factors for CKD are limited to men, and few studies examine the importance of smoking. The authors performed a community-based, prospective observational study of 20-yr duration to examine the association between hypertension and smoking on the future risk of CKD in 23,534 men and women in Washington County, Maryland. CKD was identified as end-stage renal disease in the Health Care Financing Administration database or kidney disease listed on the death certificate. All cases were confirmed as CKD by medical chart review. Adjusted relative hazards of CKD were modeled using Cox proportional hazards regression including age as the time variable and baseline BP, cigarette smoking, gender, and diabetes status as risk factors. The adjusted hazard ratio (95% confidence interval) of developing CKD among women was 2.5 (0.05 to 12.0) for normal BP, 3.0 (0.6 to 14.4) for high-normal BP, 3.8 (0.8 to 17.2) for stage 1 hypertension, 6.3 (1.3 to 29.0) for stage 2 hypertension, and 8.8 (1.8 to 43.0) for stages 3 or 4 hypertension compared with individuals with optimal BP. In men, the relationship was similar but somewhat weaker than in women, with corresponding hazard ratios of 1.4 (0.2 to 12.1), 3.3 (0.4 to 25.6), 3.0 (0.4 to 22.2), 5.7 (0.8 to 43.0), and 9.7 (1.2 to 75.6), respectively. Current cigarette smoking was also significantly associated with risk of CKD in both men and women (hazard ratio in women 2.9 [1.7 to 5.0] and in men 2.4 [1.5 to 4.0]). A large proportion of the attributable risk of CKD in this population was associated with stage 1 hypertension (23%) and cigarette smoking (31%). In conclusion, CKD risk shows strong graded relationships to the sixth report of the Joint National Committee (JNC-VI) on Prevention, Detection Evaluation and Treatment of High BP criteria for BP, to diabetes, and to current cigarette smoking that are at least as strong in women as in men.

Hodgkin's disease and Epstein-Barr virus. Altered antibody pattern before diagnosis.

In patients with Hodgkins disease, titers of IgG antibody against viral capsid antigen of Epstein-Barr virus and the prevalence of antibodies against early antigen are higher than expected. To evaluate whether this condition antedates diagnosis, we identified 43 persons with Hodgkins disease, from whom blood had been drawn and stored for an average of 50.5 months before diagnosis, and 96 controls from the same populations, from whom blood had been drawn at the same time. The relative risks of Hodgkins disease associated with elevated levels of IgG and IgA antibodies against capsid antigen were 2.6 (90 percent confidence interval, 1.1 to 6.1) and 3.7 (1.4 to 9.3), respectively. For Epstein-Barr nuclear antigen, the relative risk was 4.0 (1.4 to 11.4), and for early antigen D it was 2.6 (1.1 to 6.1). However, the prevalence of IgM antibody against capsid antigen was substantially lower in patients with Hodgkins disease (0.22 [0.04 to 1.3]). These associations were stronger in serum samples obtained at least three years before diagnosis than in serum samples obtained closer to diagnosis. We conclude that the development of Hodgkins disease may in some patients be preceded by enhanced activation of Epstein-Barr virus. Whether Epstein-Barr virus has a direct role in the pathogenesis of the disease or is simply a marker for a more fundamental factor affecting the immune control of latent infections is unknown.

Uric acid and serum antioxidant capacity: a reaction to atherosclerosis?

BACKGROUND the evidence of a potential beneficial role of antioxidants in preventing atherosclerotic disease is not entirely consistent. OBJECTIVE to assess the longitudinal association of serum total antioxidant capacity and serum antioxidants with the presence of subclinical carotid atherosclerosis. METHODS Prospective case-control study nested within an historical cohort. Cases were 150 individuals with elevated carotid intimal-medial thickness measured by B-mode ultrasound at the first two examinations of the Atherosclerosis Risk in Communities Study (1987-92). Controls were 150 age-gender-matched individuals with low carotid intimal-medial thickness. Serum antioxidant vitamins, uric acid, and serum total antioxidant capacity were measured in frozen serum samples collected from the same individuals in 1974 (13-15 years prior to the determination of case-control status). RESULTS Compared to controls, atherosclerosis cases had significantly higher levels of serum total antioxidant capacity in 1974 than controls. This difference was almost entirely explained by increased serum concentration of uric acid in cases. In contrast with cross-sectional results, uric acid serum concentration in 1974, was significantly higher in cases than in controls, even after adjusting for the main cardiovascular risk factors. Cases had significantly lower levels of alpha-carotene in the 1974 sera than controls, but no other differences in serum antioxidant vitamin concentrations were observed. CONCLUSIONS The higher serum uric acid concentration seemed associated with elevated total serum antioxidant capacity among individuals with atherosclerosis. This finding is consistent with experimental evidence suggesting that hyperuricemia may be a compensatory mechanism to counteract oxidative damage related to atherosclerosis and aging in humans.

Cohort Study of Cytomegalovirus Infection as a Risk Factor for Carotid Intimal-Medial Thickening, a Measure of Subclinical Atherosclerosis

BACKGROUND Animal studies as well as clinical and cross-sectional epidemiological studies in humans have suggested a possible role of cytomegalovirus (CMV) and other herpesvirus infections in the development of cardiovascular disease. METHODS AND RESULTS The present report is based on a case-control study nested within a historical cohort. The case group comprised 150 individuals with elevated carotid intimal-medial thickness (IMT) measured by B-mode ultrasound at the first two examinations of the Atherosclerosis Risk in Communities (ARIC) Study (1987 through 1992). The control group comprised 150 age- and sex-matched individuals with low IMT. Antibody titers for CMV and herpesvirus 1 and 2 were determined in sera obtained in 1974 as part of a community-wide survey conducted in Washington County, Maryland. Case subjects had higher mean CMV antibody titers in 1974 sera than control subjects, although the difference was not statistically significant when adjusted for other cardiovascular risk factors. There was evidence of a graded relation between the odds of intimal-medial thickening and the levels of CMV antibodies that remained significant after adjustment for the main cardiovascular risk factors (P = .013). The adjusted odds ratio for a high CMV antibody titer (a positive/negative value > or = 20) compared with a positive/negative value < 4 was 5.3 (95% confidence interval, 1.5 to 18.0). CONCLUSIONS The results from this first population-based cohort study of CMV infection and carotid IMT are compatible with the hypothesis of a causal role of CMV in atherosclerosis.

Serum antioxidants and myocardial infarction. Are low levels of carotenoids and alpha-tocopherol risk factors for myocardial infarction?

BackgroundIn vitro, animal and epidemiological studies suggest that lipoprotein oxidation may play an important role in atherosclerosis. Antioxidants may protect against lipoprotein oxidation and in that way inhibit atherosclerosis and its clinical sequelae. To investigate this possibility, we examined the association between levels of several antioxidants and myocardial infarction using serum specimens collected 7 to 14 years before the onset of myocardial infarction. Methods and ResultsA nested case-control design was used. Cases and control subjects were selected from the 25 802 persons who had donated 15 mL of blood in 1974 for a serum bank. Cases comprised 123 persons with a subsequent first diagnosis of myocardial infarction who ranged from 23 through 58 years of age in 1974 and who had had their first diagnosis of myocardial infarction during 1981 to 1988. Two groups of control subjects matched to the cases for sex and age were selected from donors to the serum bank, one from those with hospital admissions during the same period and the other from the total group of donors. Sera were assayed for four carot-A enoids (β-carotene, lycopene, lutein, and zeaxanthin), α-to-copherol, and cholesterol. Because associations with these serum nutrients showed similar trends whether based on hospital or community controls, the two control groups were combined. There was a significantly increasing risk for subse-quent myocardial infarction with decreasing levels of (β-caro-tene in 1974 (P value for trend,.02) and a suggestive trend with decreasing levels of lutein (P=.09). When the results were stratified by smoking status, the excess risk of myocardial infarction associated with low serum levels of carotenoids was limited to smokers. A protective association with higher levels of α-tocopherol was suggested only among persons with high levels of serum cholesterol. ConclusionsLow serum levels of carotenoids were associ-ated with an increased risk of subsequent myocardial infarc-tion among smokers.

Factors associated with mortality after widowhood.

A non-concurrent prospective study in Washington County, Maryland identified 4,032 (1,204 male, 2,828 female) White persons aged 18 and over who were enumerated in a 1963 non-official census and who became widowed between 1963 and 1974, and an equal number of married persons, each matched to a widowed as to race, sex, year of birth and geography of residence. All were followed to 1975, the date of a second census. Mortality rates based on person-years at risk were about the same for widowed as for married females, but significantly higher for male widowed than male married, even after adjustment for a number of demographic, socioeconomic, and behavioral variables. Mortality rates among widowed males who remarried were very much lower than among those who did not remarry, but no significant difference was observable among widowed females who did nor did not remarry. Multiple regression analysis also showed that, for both sexes and independently of other factors, moving into a nursing home or other chronic care facility was associated with higher mortality than any other residential change or no change, and living alone was associated with higher mortality than living with someone else in the household.

Dietary n-3 polyunsaturated fatty acids and smoking-related chronic obstructive pulmonary disease

BACKGROUND Fish contain n-3 polyunsaturated fatty acids, principally eicosapentaenoic acid and docosahexaenoic acid, which are known to interfere with the bodys inflammatory response and may be of benefit in chronic inflammatory conditions. METHODS We studied the relation between the dietary intake of n-3 fatty acids and chronic obstructive pulmonary disease (COPD) in 8960 current or former smokers participating in a population-based study of atherosclerosis. Intake of fatty acids was estimated with a dietary questionnaire. The presence of COPD was assessed by a questionnaire on respiratory symptoms and by spirometry. Three case definitions of COPD were used: symptoms of chronic bronchitis (667 subjects), physician-diagnosed emphysema reported by the subject (185 subjects), and spirometrically detected COPD (197 subjects). RESULTS After control for pack-years of smoking, age, sex, race, height, weight, energy intake, and educational level, the combined intake of eicosapentaenoic acid and docosahexaenoic acid was inversely related to the risk of COPD in a quantity-dependent fashion. The adjusted odds ratio for the highest quartile of intake as compared with the lowest quartile was 0.66 for chronic bronchitis (95 percent confidence interval, 0.52 to 0.85; P < 0.001 for linear trend across the range of intake values), 0.31 for physician-diagnosed emphysema (95 percent confidence interval, 0.18 to 0.52; P for linear trend, 0.003), and 0.50 for spirometrically detected COPD (95 percent confidence interval, 0.32 to 0.79; P for linear trend, 0.007). CONCLUSIONS A high dietary intake of n-3 fatty acids may protect cigarette smokers against COPD.