Chronically depressed mood and cancer risk in older persons.

BACKGROUND: Depression has been proposed as a predisposing factor for cancer, but prospective studies have been inconclusive. We examined whether a high level of depressive symptoms, present for a long time, is associated with increased risk of cancer in the elderly. METHODS: Data were obtained and analyzed from persons who lived in three communities (Massachusetts, Iowa, and Connecticut) of the Established Populations for Epidemiologic Studies of the Elderly, a prospective cohort study with a mean follow-up of 3.8 years that included 4825 persons (1708 men and 3117 women) aged 71 years and older. Chronically depressed mood was defined as present when the number of depressive symptoms exceeded specific cut points on the Center for Epidemiologic Studies-Depression scale at baseline (1988) and 3 and 6 years before baseline. New cases of cancer were identified from Medicare hospitalization records and death certificates. RESULTS: Of the 4825 persons studied, 146 (3.0%) were chronically depressed. The incidence rate of cancer was 30.5 per 1000 person-years for the 146 persons with chronic depression and 21.9 per 1000 person-years for the 4679 nonchronically depressed persons. After adjustment for age, sex, race, disability, hospital admissions, alcohol intake, and smoking, the hazard ratio for cancer associated with chronically depressed mood was 1.88 (95% confidence interval = 1.13-3.14). The excess risk of cancer associated with chronic depression was consistent for most types of cancer and was not specific to cigarette smokers. CONCLUSION: When present for at least 6 years, depression was associated with a generally increased risk of cancer.

Metabolic cardiovascular syndrome and risk of dementia in Japanese-American elderly men. The Honolulu-Asia aging study.

Cardiovascular risk factors often cluster into a metabolic syndrome that may increase the risk of dementia. The objective of the present study was to assess the long-term association between clustered metabolic cardiovascular risk factors measured at middle age and the risk of dementia in old age. This prospective cohort study of cardiovascular disease was started in 1965 and was extended to a study of dementia in 1991. The subjects were Japanese-American men with an average age of 52.7+/-4.7 (mean+/-SD) years at baseline. Dementia was diagnosed in 215 men, according to international criteria, and was based on a clinical examination, neuropsychological testing, and an informant interview. The z scores were calculated for 7 risk factors (random postload glucose, diastolic and systolic blood pressures, body mass index, subscapular skinfold thickness, random triglycerides, and total cholesterol). The relative risk (RR [95% CI]) of dementia (subtypes) per 1 SD increase in the sum of the z scores was assessed after adjustment for age, education, occupation, alcohol consumption, cigarette smoking, and years of childhood lived in Japan. The z-score sum was higher in demented subjects than in nondemented subjects, indicating a higher risk factor burden (0.74 versus -0.06, respectively; P=0. 008). Per SD increase in the z-score sum, the risk of dementia was increased by 5% (RR 1.05, 95% CI 1.02 to 1.09). The z-score sum was specifically associated with vascular dementia (RR 1.11, 95% CI 1.05 to 1.18) but not with Alzheimer's disease (RR 1.00, 95% CI 0.94 to 1.05). Clustering of metabolic cardiovascular risk factors increases the risk of dementia (mainly, dementia of vascular origin).

Race and sex differentials in the impact of hypertension in the United States. The National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study.

Hypertension was evaluated longitudinally in a nationally representative sample of the US population. This study, based on the data from the National Health and Nutrition Examination Survey NHANES I Epidemiologic Follow-up Study, analyzed changes in blood pressure and frequency of treatment, hypertension incidence, and ten-year survival of the cohort relative to hypertension status at baseline. Higher prevalence rates for each older age group, especially in women, as previously reported on data from community studies were confirmed. However, this analysis found minimal differences in the incidence of hypertension between men and women for all age groups. Incidence rates for blacks were at least twice the rates for whites for almost every age-sex group. Decreased survival in older hypertensive men probably explained the higher prevalence in older women. Treatment and location of measurement in clinic or household must be major considerations in the calculation of incident cases.

Use of antihypertensive drugs and trends in blood pressure in the elderly.

BACKGROUND: During the 1980s data became available from randomized trials concerning the clear benefits of treating hypertension in the elderly. In three large communities, we examined the impact of these findings on rates of treatment, use of specific antihypertensive drugs, and rates of elevated blood pressure as well as distributions of levels. METHODS: In 1981 the National Institute on Aging initiated population-based cohort studies in the residents of three communities who were 65 years and older. East Boston, Mass; Washington and Iowa counties, Iowa; and New Haven, Conn. Participation rates ranged from 80% to 85% across sites with 10,294 community-dwelling participants in the combined cohorts. Baseline evaluation included inhome blood pressure assessment and medication inventory. Repeated in-home evaluations occurred 3 and 6 years after baseline and follow-up rates ranged from 71% to 88%. RESULTS: Use of antihypertensive drugs increased over time in all three communities: the age- and sex-adjusted rates of use were between 14% and 32% higher in 1988 and 1989 relative to 1982 and 1983. Parallel declines in the use of thiazide diuretics occurred in all three populations along with large increases in the use of angiotensin-converting enzyme inhibitors and calcium channel blockers. In East Boston and New Haven mean systolic blood pressure decreased substantially over time and the prevalence of elevated systolic pressure (> or = 160 mmHg) decreased overall as well as by age and sex. In Iowa the mean levels of systolic blood pressure were lowest at baseline and increased slightly. CONCLUSIONS: The reported evidence about the benefits of treatment for hypertension in the elderly was followed by substantial increases in treatment rates. The use of drugs with proven efficacy declined while the use of newer agents with theoretical advantages, not yet tested in clinical trials of mortality, increased. In the United States, the ongoing therapeutic efforts to lower elevated blood pressure in elderly populations may be contributing to the continuing decline in cardiovascular and stroke mortality.

Abnormal blood glucose and coronary heart disease: the Puerto Rico Heart Health Program.

The presence of abnormal blood glucose (ABG) was determined for participants in the Puerto Rico Heart Health Program, a prospective epidemiological study of cardiovascular disease. Subjects were considered to have ABG at baseline if they were receiving treatment for diabetes (diet, oral hypoglycemics, or insulin), or if the blood glucose level was 140 mg/dl or more. Urban-rural comparisons of the prevalence of ABG were made in this cohort of 2585 rural and 6208 urban men aged 45-64 yr. The prevalence of ABG in the urban population was more than double that in the rural. This population has been followed up for coronary heart disease (CHD) over an 8 1/4-yr period. ABG at baseline is significantly associated with CHD death in urban men. When the relationship is controlled for smoking, systolic blood pressure, cholesterol, and relative weight, the relationship remains significant. The association with total CHD is similar. Either by adjusting for diabetes (i.e., when treated diabetes was excluded from analysis) or by entering both blood glucose and diabetes under treatment into the model, blood glucose was no longer statistically significant. This suggests that ABG, rather than blood glucose alone, is the important variable associated with CHD.

Joint effect of the APOE gene and midlife systolic blood pressure on late-life cognitive impairment: the Honolulu-Asia aging study.

BACKGROUND AND PURPOSE: The aim of this study was to explore the joint effect of the APOE epsilon4 allele and midlife systolic blood pressure (SBP) on the risk for poor cognitive function in late life. METHODS: The study includes 3605 surviving members of the cohort of the Japanese-American men followed prospectively over 26 years (1965-1991) as a part of the Honolulu Heart Program. In 1965 men were aged 45 to 68 years and were living in the island of Oahu, Hawaii. For this study the sample was divided into 4 categories: normal SBP (<160 mm Hg)/No epsilon4, as the reference category; normal SBP/epsilon4; high SBP/no epsilon4; high SBP/epsilon4. The relative risk (RR) of late-life intermediate and poor cognitive function relative to good function was measured by the Cognitive Abilities Screening Instrument (CASI) test. RESULTS: After adjusting for age, education, smoking, alcohol use, and body mass index, the RR for poor cognitive function (CASI <74) compared with good cognitive function (CASI >/=82) in never-treated subjects was 1.3 (95% CI 0.9 to 1.9) for the normal SBP/epsilon4 category, 2.6 (0.7 to 10.0) for the high SBP/no epsilon4, and 13.0 (1.9 to 83.8) for the high SBP/epsilon4. Adjustment for diabetes, prevalent stroke, coronary disease, and ankle-brachial index reduced the RR of poor cognition by 25.5% (RR 13.0 to 10.8) in those with both risk factors. In the treated group, the RR was 1.9 (0.7 to 4.5) for those with both risk factors. CONCLUSIONS: The results suggest that midlife high SBP has a stronger adverse effect on cognitive function in persons with higher genetic susceptibility, but this effect may be modified by antihypertensive treatment.

Epidemiology and genetics of hypertension.

The major decline in cardiovascular mortality during the last 20 years may be related to improved hypertension control, but a causal relationship has not been proven. Fundamental epidemiologic associations between age, sex, race, socioecomonic class, and blood pressure (BP) have been well characterized. Risk of coronary heart disease and stroke mortality and morbidity is linearly related to BP or to categorically defined hypertension. Weight is a major correlate of BP at all ages and in most populations. The relationships between hypertension and other nutritionally related factors are not so well defined. The Framingham Study (both cohort and offspring components) provides information about other BP correlates such as heart rate and clinical chemistry values as well as evidence suggesting a genetic influence on BP variability in families. Combined with observations from other studies, it appears that heredity plays a very important role in human hypertension.

Antihypertensive drug therapy and survival by treatment status in a national survey.

The National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study, an investigation of a cohort originally examined during the period 1971-1975, provided an opportunity to assess the frequency of antihypertensive drug therapy in the United States during the period 1982-1984. For most age-sex-race subgroups, the frequency of medication use during 1982-1984 was higher than that observed during 1976-1980 based on the NHANES II. In the interval 1982-1984, diuretic agents were the most frequent medications prescribed (47% of drugs prescribed), and beta-blockers were second (17%). At the time of the initial survey in 1971-1975, participants had their blood pressures measured and a history of diagnosis and treatment of hypertension ascertained. Follow-up for vital status was 93% complete by 1984 (average length of follow-up, 9 years). In white men and women aged 50 years and older, the relative risk of death increased steadily, from those with elevated blood pressure (systolic blood pressure greater than or equal to 160 mm Hg or diastolic blood pressure greater than or equal to 95 mm Hg) but no history of hypertension to those treated for hypertension but whose blood pressure was still elevated. Regardless of history or treatment, those with an elevated blood pressure had about a 25-30% excess risk of death. Evidence from these national studies shows a high frequency of antihypertensive drug therapy in 1982-1984 and suggests the importance of adequate blood pressure control for optimal survival.

Milk consumption, calcium intake, and decreased hypertension in Puerto Rico. Puerto Rico Heart Health Program study.

The baseline observations in the Puerto Rico Heart Health Program during 1965-1968 involved blood pressure determinations, other measurements, and a 24-hour dietary recall in 7932 men aged 45-64 years. This extensive data base provided an opportunity to test the hypothesis that low calcium intake is related to increased blood pressure level. Among men without baseline coronary heart disease and not taking antihypertensive medication, there was an inverse relationship between milk consumption and definite hypertension in urban Puerto Rican men and older rural men. When data from all age and area groups had been averaged, a twofold increase in hypertension was found in subgroups who drank no milk compared to those who consumed over 1 quart of milk a day. Similar trends were found when an estimate of total calcium intake from food, principally from milk, was used. With multivariate analysis while known correlates of blood pressure were simultaneously considered, an independent effect persisted between milk consumption and blood pressure. These results appeared to confirm an inverse association between calcium and hypertension. It was still not possible to ascribe a causal relationship between calcium and blood pressure, however, due to the intricate network of covarying food intakes, the factors related to absorption or lack of absorption of calcium, and the possible role that unmeasured social and cultural factors may play in the observed relations.

Midlife blood pressure and dementia: the Honolulu-Asia aging study.

We studied the association of mid-life blood pressure to late age dementia, specifically Alzheimer's disease and vascular dementia. Data are from the cohort of 3703 Japanese-American men who were followed in the Honolulu Heart Program (HHP;1965-1971), and subsequently re-examined in 1991 for dementia. We assessed the risk (odds ratio (95% CI)) for dementia associated with categories of systolic (SBP) and diastolic blood pressure (DBP), stratified by never/ever treatment with anti-hypertensive medications, and adjusting for age, education, apolipoprotein epsilon allele, smoking and alcohol intake. Among those never treated (57% sample), the risk for dementia was OR 95% CI 3.8 (1.6-8.7) for DBP of 90-94 mm Hg, and 4. 3 (1.7-10.8) for DBP of 95 mmHg and over compared to those with DBP of 80 to 89 mm Hg. Compared to those with SBP of 110 to 139 mm Hg, the risk for dementia was 4.8 (2.0-11.0) in those with SBP 160 mm Hg and higher. Blood pressure was not associated with the risk for dementia in treated men. These results were consistent for Alzheimer's disease and vascular dementia. This study suggests elevated levels of blood pressure in middle age can increase the risk for late age dementia in men never treated with anti-hypertensive medication.

Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS. Honolulu-Asia aging Study.

Midlife hypertension is associated with later development of cognitive impairment, vascular dementia (VsD), and possibly Alzheimer's disease (AD). Neuropathic cerebrovascular lesions and brain atrophy have been associated with elevated blood pressure (BP), however, to our knowledge there have been no prospective investigations of an association of blood pressure levels measured in midlife with the microscopic lesions of AD. We investigated the relationship of BP level in midlife to development of neurofibrillary tangles (NFT), neuritic plaques (NP), and low brain weight at autopsy among Japanese-American men who were members of the Honolulu Heart Program/Honolulu-Asia aging Study (HHP/HAAS) cohort. The HHP/HAAS is a population-based, longitudinal study of cognitive function and dementia with 36 years of follow-up. Neocortical and hippocampal NFT and NP were counted per mm(2), and fixed brain weight was measured for 243 decedents. Elevated systolic BP, (> or =160 mm Hg) in midlife was associated with low brain weight and greater numbers of NP in both neocortex and hippocampus. Diastolic BP elevation, (> or =95 mm Hg) was associated with greater numbers of NFT in hippocampus. Results indicate that in addition to the accepted association of high BP with neuropathic cerebrovascular lesions, there is a direct relationship with brain atrophy, NP and NFT.

Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly.

We examined vitamin E and vitamin C supplement use in relation to mortality risk and whether vitamin C enhanced the effects of vitamin E in 11,178 persons aged 67-105 y who participated in the Established Populations for Epidemiologic Studies of the Elderly in 1984-1993. Participants were asked to report all nonprescription drugs currently used, including vitamin supplements. Persons were defined as users of these supplements if they reported individual vitamin E and/or vitamin C use, not part of a multivitamin. During the follow-up period there were 3490 deaths. Use of vitamin E reduced the risk of all-cause mortality [relative risk (RR) = 0.66; 95% CI: 0.53, 0.83] and risk of coronary disease mortality (RR = 0.53; 95% CI: 0.34, 0.84). Use of vitamin E at two points in time was also associated with reduced risk of total mortality compared with that in persons who did not use any vitamin supplements. Effects were strongest for coronary heart disease mortality (RR = 0.37; 95% CI: 0.15, 0.90). The RR for cancer mortality was 0.41 (95% CI: 0.15, 1.08). Simultaneous use of vitamins E and C was associated with a lower risk of total mortality (RR = 0.58; 95% CI: 0.42, 0.79) and coronary mortality (RR = 0.47; 95% CI: 0.25, 0.87). Adjustment for alcohol use, smoking history, aspirin use, and medical conditions did not substantially alter these findings. These findings are consistent with those for younger persons and suggest protective effects of vitamin E supplements in the elderly.

APOE-epsilon4 predicts incident AD in Japanese-American men: the honolulu-asia aging study.

The authors assessed the 3-year incidence of dementia, including subtypes, in 2,603 Japanese-American men 71 to 93 years of age who were dementia free at baseline. There were 137 new cases of dementia according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised, including 51 with a primary diagnosis of AD. The rates for all subtypes increased with age. Men with an APOE4 allele had a significantly increased risk of AD of 2.39 (95% CI, 1.07, 5.31), after adjusting for age and education. There was no significant relationship of APOE4 with other subtypes of dementia.

Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias.

BACKGROUND: The association between antecedent head injury and AD is inconsistent. OBJECTIVE: To examine the association between early adult head injury, as documented by military hospital records, and dementia in late life; and to evaluate the interaction between head injury and APOE epsilon4 as risk factors for dementia. METHODS: The study had a population-based prospective historical cohort design. It included men who were World War II Navy and Marine veterans, and were hospitalized during their military service with a diagnosis of either a nonpenetrating head injury or another unrelated condition. In 1996 to 1997, military medical records were abstracted to document the occurrence and details of closed head injury. The entire sample was then evaluated for dementia and AD using a multistage procedure. There were 548 veterans with head injury and 1228 without head injury who completed all assigned stages of the study. The authors estimated risk of dementia, specifically AD, using proportional hazards models. RESULTS: Both moderate head injury (hazard ratio [HR] = 2.32; CI = 1.04 to 5.17) and severe head injury (HR = 4.51; CI = 1.77 to 11.47) were associated with increased risk of AD. Results were similar for dementia in general. The results for mild head injury were inconclusive. When the authors stratified by the number of APOE epsilon4 alleles, they observed a nonsignificant trend toward a stronger association between AD and head injury in men with more epsilon4 alleles. CONCLUSIONS: Moderate and severe head injuries in young men may be associated with increased risk of AD and other dementias in late life. However, the authors cannot exclude the possibility that other unmeasured factors may be influencing this association.

ABO blood group and cardiovacular disease: the Framingham study.

Following determination of ABO blood type at the sixth biennial examination, the Framingham Heart Study cohort was followed for the occurrence of cardiovascular events for a period of 10 years. A significant association was found between blood type and intermittent claudication, with blood group O showing the lowest rates. Slight but non-significant excesses for certain other CHD events were also found in non-O individuals. Serum cholesterol showed marginally significant but consistent elevations in non-O subjects but the increased risk in non-O individuals was found to occur independently of the known intermittent claudication risk factors. Since the observed relationship between blood type and intermittent claudication occurs independently of the usual atherosclerotic risk factors, blood type, possibily through an effect on clotting, should be considered in the pathogenesis of intermittent claudication.

Calcium channel blockers and cancer.

PURPOSE: We sought to explore the relation that has been previously reported between calcium channel blockers and an increased risk of cancer. SUBJECTS AND METHODS: We followed 3,511 participants, age 65 years or older, in the Duke Established Populations for Epidemiologic Studies of the Elderly for up to 10 years. Information about use of medications was obtained at baseline and 3 and 6 years later. Information about hospitalization for cancer, or death from cancer, was obtained from Health Care Financing Administration data and death certificates. RESULTS: Of the 133 users of calcium channel blockers, 16 (12%) developed cancer, compared with 548 (16%) of 3,378 nonusers (hazard ratio = 0.9; 95% confidence interval, 0.5 to 1.5). Adjusting for baseline and time-dependent covariates, such as race, diabetes, or blood pressure, for dose or class of calcium channel blockers, or for length of follow-up, had no effect. CONCLUSIONS: Use of calcium channel blockers does not appear to be related to cancer risk. Earlier reports showing such a relation may have been the result of chance.

Increased physical activity: a protective factor against heart attacks in Puerto Rico.

The incidence and potential risk factors of coronary heart disease were assessed in 2,585 rural and 6,208 urban men, aged 45 to 64 years, participating in the Puerto Rico Heart Health Program, a prospective epidemiologic study of coronary heart disease initiated in 1965. An index of daily physical activity and a metabolic equivalent of heaviest activity were estimated from each individual history. Rural men had higher mean levels of overall activity as well as higher levels of heavy activity than urban men. An 8 1/4 year follow-up study for coronary heart disease other than angina pectoris was analyzed for relationships with physical activity. Significant inverse associations were found for both urban and rural men. Metabolic equivalent of heaviest activity showed similar results. Although the physical activity index was inversely associated with most known coronary risk factors, multivariate analyses indicated that a significant independent inverse relationship existed with the incidence of coronary heart disease. In Puerto Rico, increased physical activity appears to be a separate protective factor against heart attacks.

High-density lipoprotein cholesterol and vascular stiffness at baseline in the activity counseling trial.

In a middle-aged patient population, age was associated with stiffer vessels and high-density lipoprotein cholesterol with more elastic vessels. High-density lipoprotein cholesterol may be an indirect indicator of aerobic capacity or of less atherosclerosis, suggesting mechanisms for preserving vascular integrity.

Cancer and comorbidity in older patients: a descriptive profile.

In 1992, the National Institute on Aging (NIA) and the National Cancer Institute (NCI) initiated a study to assess the prevalence of comorbid conditions in elderly patients with cancer. Seven cancer sites were selected for the study: breast, cervix, ovary, prostate, colon, stomach, and urinary bladder. This report on approximately 7600 patients in the study sample describes the NIA/NCI approach to developing information on comorbidity in elderly patients and addresses the chronic disease burden (i.e., comorbidity) and severity for six particular conditions: arthritis, chronic obstructive pulmonary disease (COPD), diabetes, gastrointestinal problems, heart-related conditions, and hypertension. Data on comorbidity were collected by abstracting information from hospital medical records. Patients were registered in six geographic areas of the NCI Surveillance, Epidemiology, and End Results (SEER) Program. A stratified random sample of patients aged 55 to 64, 65 to 74, and 75 years or older-with the index cancers were selected. Comorbidity data were matched with data from the conventional SEER monitoring system. Analyses showed that hypertension is the most prevalent condition and is also much more common as a current management problem rather than as history for the NIA/NCI SEER Study patients. Heart conditions varied slightly in the percentage of severity reported, but percentages for all tumors remained within a range of 13 to 26% for current and past categories. A similar range was observed for arthritis, with the higher percentage seen in the current problem category. For episodic complaints (e.g., gastrointestinal problems), a medical history was more common, except for cancers that involve complaints associated with the malignancy (e.g., colon and stomach cancers and, to a lesser extent, ovarian cancer). COPD and diabetes were less prevalent. Analyses currently under way will determine the impact of a patient's comorbidity burden on the cancer care continuum of diagnosis, treatment, and survival. The broad and independent effects of chronic conditions, singly and in combination, are being examined.

Urban-rural differences in 12 year coronary heart disease mortality: the Puerto Rico Heart Health Program.

Preliminary observations of the Puerto Rican population in 1965 indicated that the coronary heart disease mortality rate was lower than in the U.S., and that the rate in rural areas might be less than urban ones because of lower levels of cardiovascular risk factors. This prompted a prospective investigation of 8793 urban and rural men, aged 45-64 years. A 12-year mortality study has been completed with almost total follow-up. After excluding those with known coronary heart disease at baseline, age-adjusted rates for coronary heart disease, sudden, and stroke death are 19-37% higher in urban than rural men. Urban men had higher average blood pressure, cholesterol, glucose, and heart rate and were less physically active than rural men. When urban-rural differences for the known risk factors, including education and alcohol intake, are adjusted for by multivariate logistic regression analysis, no remaining significant urban-rural coronary heart disease mortality differential is present. Thus, it appears that variation in identified risk factors could explain the difference in mortality within Puerto Rico. The presence of unidentified protective factors cannot be excluded.