Mortality from infectious diseases in diabetes.

BACKGROUND AND AIMS: To investigate the risk of mortality from infections by comparing the underlying causes of death versus the multiple causes of death in known diabetic subjects living in the Veneto region of Northern Italy. METHODS AND RESULTS: A total of 185,341 subjects with diabetes aged 30-89 years were identified in the year 2010, and causes of death were assessed from 2010 to 2015. Standardized Mortality Ratios (SMRs) with 95% confidence intervals (CIs) were computed with regional mortality rates as reference. The underlying causes of death and all the diseases reported in the death certificates were scrutinized. At the end of the follow-up, 36,382 subjects had deceased. We observed an increased risk of death from infection-related causes in subjects with diabetes with a SMR of 1.83 (95% CI, 1.71-1.94). The SMR for death from septicemia was 1.91 (95% CI, 1.76-2.06) and from pneumonia was 1.47 (95% CI, 1.36-1.59). The use of the multiple causes of death approach emphasized the association of infectious diseases with mortality. CONCLUSION: The results of the present study demonstrate an excess mortality due to infection-related diseases in patients with diabetes; more interestingly, by routine mortality analyses, the results show a possible underestimation of the effect of these diseases on mortality.

Prevalence of chondrocalcinosis in Italian subjects from northeastern Italy. The Pro.V.A. (PROgetto Veneto Anziani) study.

OBJECTIVES: To undertake an epidemiological survey of the prevalence of radiological chondrocalcinosis (CC) of the lower limbs in the elderly Italian population of the Pro.V.A. study. METHODS: Knee and pelvic basin radiographs were performed on 3099 subjects aged 65 and older, residing in the Veneto Region of Italy (Rovigo and Camposampiero areas). Two readers independently analysed the knee, coxofemoral and pubic symphysis x-rays of a consecutive sample of 1629 subjects according to Altman. Some laboratory indexes, such as serum parathyroid hormone (PTH), vitamin D (vit D), bone alkaline phosphatase (bALP), deyidroepiandrosterone (DHEA), urinary CrossLaps (XL), and inflammatory biomarkers were evaluated. Quantitative variables were summarised as mean + or - standard deviation and qualitative ones as distributions. Unpaired t-test was used to compare mean values among groups for normally distributed variables, and non-parametric Mann-Whitney test for non normal variables. RESULTS: CC was found in 169 (mean age 78.2 + or - 8.0 yrs) out of the 1629 subjects studied (10.4%). After adjusting for the sex and age structure of the target population, the prevalence was 10.0%. CC was more often observed in women than in men (M: 7.0%; F: 12.8%, p=0.0002), and increased in occurrence with age, rising from 7.8% in subjects aged 65-74 yrs, to 9.4% in those aged 75-84 yrs, and to 21.1% in subjects older than 85 yrs. The knee was the most prevalent location since it was affected in 94.1% of all the subjects with CC, in particular the right limb. Knee CC was bilateral in 71.7% of the affected patients. The occurrence of rheumatic disorders did not differ significantly between the subjects with CC and those without (rheumatoid arthritis 0.59% vs. 0.48%, p=ns). CONCLUSIONS: Although the detection of CC was limited to few joints with the knee being the most affected location, our study confirms the frequent presence of CC at different sites, in keeping with the possible role of systemic factors. Articular CC is an age-related disorder, which could partly explain the prevalence discrepancies reported by various studies. The prevalence of CC found in our survey based on standardised x-ray reading was high, suggesting that CC could be an underdiagnosed disease in the absence of radiographic investigation.

Estimating the real burden of cardiovascular mortality in diabetes.

OBJECTIVE: To compare different methods assessing the burden of cardiovascular mortality in diabetes mellitus, which is usually underestimated by standard mortality statistics based on the underlying cause of death. PATIENTS AND METHODS: All residents in the Veneto Region (Italy) aged 30-89 years with co-payment exemption for diabetes in January 2010 (n=185,341) were identified and linked with mortality records (2010-2015). The underlying causes of death, as well as all the diseases mentioned in the death certificate (multiple causes), were extracted. The standardized mortality ratios (SMR) were computed with regional rates as a reference. RESULTS: After grouping diabetes and circulatory diseases as the underlying cause of death, the mortality rates were highly increased, especially among patients aged 30-54 years: SMR 4.24 (95% confidence interval 3.57-5.00) and 9.84 (7.47-12.72) in males and females, respectively. After re-assignment of the underlying cause in deaths from diabetes, the percentage of overall mortality caused by circulatory diseases increased from 33.8% to 41.7%. Based on multiple causes, the risk of death was increased for several cardiovascular diseases, including causes rarely emerging from standard mortality statistics such as atrial fibrillation/flutter. CONCLUSIONS: The re-assignment of the underlying cause and the analyses of the multiple causes of death allowed to estimate the whole burden of mortality associated with cardiovascular diseases.

Obesity, Muscular Strength, Muscle Composition and Physical Performance in an Elderly Population.

OBJECTIVE: To evaluate the association between BMI levels, muscular strength, muscle composition and physical performance in the elderly. DESIGN: Italians subjects from the Progetto Veneto Anziani (ProVA) study were analyzed. SETTING: The ProVa was a population study focused on chronic diseases and functional limitations in Italian subjects aged ≥65 years living in two Northeast Italian cities. PARTICIPANTS: The ProVa study included 3099 subjects. ProVa participants with unknown information on BMI or disability status were excluded. The final sample was thus represented by 1.188 men, and 1.723 women. MEASUREMENTS: Physical performance was measured with the Short Physical Performance Battery (SPPB) and leg muscular strength with dynamometry. Fat distribution and skeletal muscle composition were measured in an abdominal single-scan magnetic resonance (MRI) in a randomly selected sample of 348 subjects. Study population was stratified by BMI classes. RESULTS: An association between BMI levels and SPPB was observed. Normal weight subjects showed the best SPPB scores (8.29±0.03), with significant differences compared to underweight (7.50±0.15; p<0.001), overweight (8.12±0.02; p<0.001), class I (7.72±0.04; p<0.001), class II (6.67±0.09; p<0.001) and class III obesity (5.88±0.24; p<0.001). This pattern was not modified by adjustment for possible confounders. Compared to normal weight subjects (22.9±0.1 kg), leg muscular strength was higher in overweight (23.8±0.1; p<0.001) and in class I obesity (24.5±0.1; p<0.001), but it was reduced in class II (21.4±0.3; p<0.001) and class III (19.8±0.9; p<0.001). The association between BMI and impaired physical performance was not affected by adjustment for muscular strength. An inverse association between SPPB scores and fat infiltration in skeletal muscle was observed in patients with abdominal MRI. CONCLUSION: A poor physical performance was observed in overweight and obese elderly subjects. Leg strength was reduced only in subjects with severe obesity. Physical performance was negatively influenced by the degree of fat infiltration in skeletal muscle.

Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly.

PURPOSE: To investigate whether interleukin-6 and C-reactive protein levels predict all-cause and cause-specific mortality in a population-based sample of nondisabled older people. SUBJECTS AND METHODS: A sample of 1,293 healthy, nondisabled participants in the Iowa 65+ Rural Health Study was followed prospectively for a mean of 4.6 years. Plasma interleukin-6 and C-reactive protein levels were measured in specimens obtained from 1987 to 1989. RESULTS: Higher interleukin-6 levels were associated with a twofold greater risk of death [relative risk (RR) for the highest quartile (> or = 3.19 pg/mL) compared with the lowest quartile of 1.9 [95% confidence interval, CI, 1.2 to 3.1]). Higher C-reactive protein levels (> or = 2.78 mg/L) were also associated with increased risk (RR = 1.6; CI, 1.0 to 2.6). Subjects with elevation of both interleukin-6 and C-reactive protein levels were 2.6 times more likely (CI, 1.6 to 4.3) to die during follow-up than those with low levels of both measurements. Similar results were found for cardiovascular and noncardiovascular causes of death, as well as when subjects were stratified by sex, smoking status, and prior cardiovascular disease, and for both early (<2.3 years) and later follow-up. Results were independent of age, sex, body mass index, and history of smoking, diabetes, and cardiovascular disease, as well as known indicators of inflammation including fibrinogen and albumin levels and white blood cell count. CONCLUSIONS: Higher circulating levels of interleukin-6 and C-reactive protein were associated with mortality in this population-based sample of healthy older persons. These measures may be useful for identification of high-risk subgroups for anti-inflammatory interventions.

Serum iron level, coronary artery disease, and all-cause mortality in older men and women.

The association between iron levels and coronary artery disease (CAD) mortality is controversial. Whereas most data show no association, some have raised the possibility of a causal role, while others have suggested a protective effect of iron on CAD. To address these possibilities, we examined the association between serum iron and CAD, cardiovascular disease, and all-cause mortality in a large cohort of 3,936 persons aged > or =71 years who completed an interview, had a serum iron determination, and survived at least 1 year after baseline. The median follow-up time was 4.4 years. Serum iron levels were categorized according to sex-specific quartiles. Relative risks (RR) and 95% confidence intervals (CI) were calculated from proportional-hazards regression models adjusted for age, race, education, creatinine, serum albumin, serum lipids, use of iron supplementation, smoking, use of alcohol, blood pressure, body mass index, and presence of chronic conditions. There was a gradual decrease in the RRs of CAD, cardiovascular disease, and all-cause mortality with increasing serum iron levels (all tests for trend, p <0.05). Men in the highest iron quartile were one fifth as likely to die of CAD as men in the lowest iron quartile (RR 0.22; 95% CI 0.11 to 0.48), and women in the highest quartile had half the risk of women in the lowest quartile (RR 0.48; 95% CI 0.27 to 0.87). When compared with the lowest quartile, risk of all-cause mortality was 38% lower in men in the highest iron quartile (RR 0.62; 95% CI 0.46 to 0.85) and 28% lower in women in the highest quartile (RR 0.72; 95% CI 0.53 to 0.96). Results of similar strength and magnitude were observed for cardiovascular disease mortality and in analyses that excluded the first 3 years of follow-up. In this large cohort of persons aged > or =71 years, there was consistent evidence of increasing risk of mortality at lower serum iron levels. In fact, lower serum iron levels were associated with an increased risk of CAD, cardiovascular disease, and all-cause mortality. The results are compatible with the possibility that in an older population, there is an inverse association between serum iron levels and risk of mortality.

Cardiovascular events and mortality in newly and chronically depressed persons > 70 years of age.

The role of duration of depressed mood in the prediction of cardiovascular disease (CVD) requires further study, as it has been suggested that emerging depressive symptoms may be a better predictor than persistent depressive symptoms. This prospective cohort study of 3,701 men and women aged > 70 years uses 3 measurement occasions of depressive symptomatology (Center for Epidemiologic Studies-Depression Scale) during a 6-year period to distinguish persons who were newly (depressed at baseline but not at 3 and 6 years before baseline) and chronically depressed (depressed at baseline and at 3 or 6 years before baseline). Their risk of subsequent CVD events and all-cause mortality was compared with that of subjects who were never depressed during the 6-year period. Outcome events were based on death certificates and Medicare hospitalization records. During a median follow-up of 4.0 years, there were 732 deaths (46.2/1,000 person-years) and 933 new CVD events (64.7/1,000 person-years). In men, but not in women, newly depressed mood was associated with an increased risk of CVD mortality (relative risk 1.75, 95% confidence interval [CI] 1.00 to 3.05), new CVD events (relative risk 2.07, 95% CI 1.44 to 2.96), and new coronary heart disease events (relative risk 2.03, 95% CI 1.28 to 3.24) after adjustment for traditional CVD risk factors. The association between newly depressed mood and all-cause mortality was smaller (relative risk 1.40, 95% CI 0.95 to 2.07). Chronic depressed mood was not associated with new CVD events or all-cause mortality. Our findings suggest that newly depressed older men, but not women, were approximately twice as likely to have a CVD event than those who were never depressed. In men, recent onset of depressed mood is a better predictor of CVD than long-term depressed mood.

Iron status and risk of cardiovascular disease.

Free Iron, as well as other transition metals, can catalyze free radical formation. For this reason iron is tightly bound to transport and storage proteins to prevent their involvement in free radical formation. It has been hypothesized that increased iron intake or iron stores may promote atherogenesis by increasing free radical formation and oxidative stress. While a coherent, plausible hypothesis as to how transition metals, such as iron, might accelerate the progression of atherosclerosis has been generated from basic research, iron status, measured as dietary iron intake, serum iron, serum ferritin, and transferrin saturation, has been inconsistently associated with cardiovascular disease in human epidemiologic research. In addition, limited data suggest that iron overload states do not appear to be strongly associated with increased risk of atherosclerotic disease. One real limitation of the existing data is the lack of a generally agreed upon and logistically feasible means of assessing iron status in free living humans. Further research, including basic research and large-scale epidemiologic studies, is needed to fully assess the association between iron status and the risk of CVD and other adverse outcomes. At present the currently available data do not support radical changes in dietary recommendations or screening to detect high normal levels nor do they support the need for large-scale randomized trials of dietary restriction or phlebotomy as a means of lowering iron stores.

Serum albumin and physical function as predictors of coronary heart disease mortality and incidence in older persons.

The role of traditional risk factors in predicting coronary heart disease (CHD) among men and women aged 65 years and over has been extensively debated, but the search for risk factors that are distinctive in the elderly is still ongoing. The relation of serum albumin levels and physical disability to risk of CHD morality and incidence was prospectively assessed in a cohort of 4116 men and women, aged 71 years and over, who were evaluated in 1987-1989 and followed for a mean of 4.0 years. Outcome events were based on death certificates and Medicare hospitalization records. Analyses were adjusted for major CHD risk factors. There were 275 CHD deaths (16.8/1000 person-years) among all participants and 503 incident (fatal and nonfatal) CHD events (39.4 per 1000 person-years) among participants free of prevalent CHD during the observation period. The relative risk (RR) of CHD morality for women with an albumin concentration < 38 g/liter was 2.5 times higher than for women with albumin > 43 g/liter (RR 2.5; 95% confidence interval [CI], 1.4-4.6). There was a significant and graded increase in CHD incidence with decreasing albumin concentration in women but not in men. The presence of physical disability doubled the risk of CHD mortality among both men and women, an increase in risk that was comparable to that imposed by a previous myocardial infarction and was independent of other coronary risk factors. Disability had a lesser impact on CHD incidence, which was significant only in women. Low albumin concentration (< 38 g/liter) identifies a group of women at higher risk of CHD mortality and incidence. Physical disability is an independent predictor of CHD mortality in both men and women and for CHD incidence only in women.

Effect of age and severity of disability on short-term variation in walking speed: the Women's Health and Aging Study.

Standardized objective measures of human performance have been introduced in clinical and epidemiologic studies of older populations. Reliability of these measures has usually been estimated by comparing two measures obtained in the same person. However, no information is available on variability of multiple measures collected serially over short time intervals. This study uses data from the Weekly Disability Study, a component of the Women's Health and Aging Study, to describe fluctuations in physical performance over multiple, consecutive time intervals. Walking speed was measured weekly over a 6-month period in 99 older women affected by mild to severe disability. Overall, 2120 observations were explored using techniques developed for the analysis of repeated measures. Results showed that the correlations between observations in the same person were inversely related to their separation in time. The decay in the autocorrelation function was steeper in the least disabled. However, even with 20-week separations in assessments, correlations remained above 0.6 in all age and severity of disability subgroups. Changes over time in performance differed somewhat between disability subgroups, but the relative performance across subgroups remained stable over the entire course of the study. A clear learning effect was found only in those in the middle disability subgroup. Results support the utilization of repeated measures of physical performance in research that evaluates older persons over time.

Long-term survival and use of antihypertensive medications in older persons.

OBJECTIVE: To determine whether older persons with hypertension who use specific calcium antagonists and ACE inhibitors have a different risk of mortality than those using beta-blockers. DESIGN: A prospective cohort study continuing from 1988 through 1992. SETTING: Three communities of the Established Populations for Epidemiologic Studies of the Elderly. PARTICIPANTS: Hypertensive participants aged > or = 71 years (n = 906) who had no evidence of congestive heart failure and who were using either beta-blockers (n = 515), verapamil (n = 77), diltiazem (n = 92), nifedipine (n = 74), or ACE inhibitors (n = 148). Nifedipine was of the short acting variety. MEASUREMENTS: The main outcome measure was all-cause mortality. Age, gender, smoking, HDL-cholesterol, blood pressure, intake of digoxin and diuretics, physical disability, self-perceived health, and comorbid conditions were examined as confounders. RESULTS: During 3538 person-years of follow-up, 188 participants died (53 deaths per 1000 person-years). Compared with beta-blockers, after adjusting for age, gender, comorbid conditions and other health-related factors, the relative risks (95% confidence interval) for mortality associated with use of verapamil, diltiazem, nifedipine, and ACE inhibitors were 0.8 (0.4-1.4), 1.3 (0.8-2.1), 1.7 (1.1-2.7), and 0.9 (0.6-1.4), respectively. The results were unchanged after excluding participants with other potential contraindications to beta-blockers and after stratifying on coronary heart disease and use of diuretics. Higher doses of nifedipine were associated with higher mortality. CONCLUSION: Compared with beta-blockers, use of short acting nifedipine was associated with decreased survival in older hypertensive persons. However, selective factors influencing the use of specific drugs in higher risk patients could not be completely discounted, and final conclusions will depend on clinical trials.

The value of serum albumin and high-density lipoprotein cholesterol in defining mortality risk in older persons with low serum cholesterol.

OBJECTIVES: To investigate the relationship between low cholesterol and mortality in older persons to identify, using information collected at a single point in time, subgroups of persons with low and high mortality risk. DESIGN: Prospective cohort study with a median follow-up period of 4.9 years. SETTINGS: East Boston, Massachusetts; New Haven, Connecticut; and Iowa and Washington counties, Iowa. PARTICIPANTS: Four thousand one hundred twenty-eight participants (64% women) age 70 and older at baseline (mean 78.7 years, range 70-103); 393 (9.5%) had low cholesterol, defined as < or =160 mg/dl. MEASUREMENTS: All-cause mortality and mortality not related to coronary heart disease and ischemic stroke. RESULTS: During the follow-up period there were 1,117 deaths. After adjustment for age and gender, persons with low cholesterol had significantly higher mortality than those with normal and high cholesterol. Among subjects with low cholesterol, those with albumin> 38 g/L had a significant risk reduction compared with those with albumin < or =38 g/L (relative risk (RR) = 0.57; 95% confidence interval (CI) = 0.41-0.79). Within the higher albumin group, high-density lipoprotein cholesterol (HDL-C) level further identified two subgroups of subjects with different risks; participants with HDL-C <47 mg/dl had a 32% risk reduction (RR = 0.68; 95% CI = 0.47-0.99) and those with HDL-C > or =47 mg/dl had a 62% risk reduction (RR = 0.38; 95% CI = 0.20-0.68), compared with the reference category; those with albumin < or =38 g/L and HDL-C <47 mg/dl. CONCLUSIONS: Older persons with low cholesterol constitute a heterogeneous group with regard to health characteristics and mortality risk. Serum albumin and HDL-C can be routinely used in older patients with low cholesterol to distinguish three subgroups with different prognoses: (1) high risk (low albumin), (2) intermediate risk (high albumin and low HDL-C), and (3) low risk (high albumin and high HDL-C).

Occult caffeine as a source of sleep problems in an older population.

OBJECTIVE: To evaluate the impact of caffeine in medication on sleep complaints in a community population of persons aged 67 or older. DESIGN: Cross-sectional analysis. SETTING: Iowa 65+ Rural Health Study. PARTICIPANTS: Those who completed their own interview, including a section on the use of medications, during the third annual in-person follow-up in 1984-1985. MAIN OUTCOMES: trouble falling asleep or other sleep complaints. Covariates: use of caffeine-containing medication, spasmolytic, or sympathomimetic drug; number of drugs used; depressive symptoms; self-perceived health; comorbidity, hip fracture, arthritis, ulcer of stomach or intestines; and consumption of caffeinated beverages. RESULTS: The prevalence of caffeinated medication use by participants was 5.4%. Those reporting the use of any caffeine-containing medication were at an increased risk of having trouble falling asleep (Odds Ratio [OR] = 1.79, 95% confidence interval [CI] = 1.19-2.68). There was no significant risk of other reported nighttime or daytime sleep problems associated with use of caffeine-containing drugs. Even after adjusting for other factors that could interfere with initiation of sleep, such as painful disease, depressive symptoms, polypharmacy, use of specific medications known to interfere with sleep, and coffee consumption, the use of caffeine-containing medication still presented a significantly increased risk of having trouble falling asleep (OR = 1.60, CI = 1.04-2.46). Although those participants using over-the-counter analgesic medication containing caffeine had an increased risk of trouble falling asleep (OR = 1.88, CI = 1.22-2.90), there was no significant risk of trouble falling asleep for those who took similar noncaffeinated OTC analgesic drugs (OR = 1.26, CI = 0.87-1.83). CONCLUSIONS: The use of caffeine-containing medication is associated with sleep problems. Healthcare providers should be aware of potential problems associated with over-the-counter medications containing caffeine and should counsel patients about the potential of sleep problems. Older patients should be encouraged to read the label on medications and to select drugs that are caffeine-free when that is possible.

Alcohol consumption and risk of deep venous thrombosis and pulmonary embolism in older persons.

OBJECTIVES: To assess whether low to moderate alcohol consumption decreases the risk of deep venous thrombosis and pulmonary embolism. DESIGN: Prospective cohort study. SETTING: Three communities of the Established Populations for Epidemiologic Studies of the Elderly. PARTICIPANTS: A total of 7959 persons aged 68 years or older. MEASUREMENTS: The incidence of deep venous thrombosis and pulmonary embolism was assessed by surveying hospital discharge diagnoses and deaths from 1985 through 1992. Those participants who estimated they used alcohol less than 1 time, on average, in the past month, less than 1 ounce per day, and 1 ounce or more per day were compared with those who reported no alcohol intake in the past year. Age, gender, race, body mass index, smoking, education, income, disability, cognitive function, arterial pressure, medication use, baseline chronic conditions, number of hospital admissions in past year, and occurrence of disease during follow-up were examined as possible confounders. RESULTS: During 48,038 person-years of follow-up, 155 events were observed (35 deep venous thromboses and 123 pulmonary emboli). Compared with non-drinkers, after adjusting for potential confounding variables, the relative risks (95% confidence interval) for deep venous thrombosis and pulmonary embolism associated with increasing alcohol consumption levels were 0.7 (0.4-1.1), 0.6 (0.4-0.9), and 0.5 (0.2-1.1), respectively (P for trend = .004). The results were unchanged after stratifying on health status and disability. CONCLUSIONS: Low to moderate alcohol consumption is associated with a decreased risk of deep venous thrombosis and pulmonary embolism in older persons.

The prognostic value of serum albumin in healthy older persons with low and high serum interleukin-6 (IL-6) levels.

OBJECTIVE: We sought to determine the prognostic value of serum albumin for 4-year mortality among high-functioning persons who did or did not have evidence of inflammation as indicated by high interleukin-6 (IL-6) levels. DESIGN: We used a case-cohort design of healthy, nondisabled older persons who had serum albumin and plasma IL-6 measured at baseline. Crude and multiply adjusted (for sociodemographics and chronic diseases) proportional hazards models were used to identify the effect of baseline levels of serum albumin level on 4-year mortality among those with higher and lower levels of IL-6. RESULTS: Among subjects without evidence of IL-6-mediated inflammation (IL-6 < 3.20 pg/mL), having a lower (< or = 4.4 g/dL) albumin level was associated with a multiply adjusted relative risk of 2.1 for 4-year mortality compared with those with higher albumin. In the presence of inflammation (IL-6 > or = 3.20 pg/mL), higher and lower serum albumin levels had similar risks (adjusted relative risks 4.0 and 3.8, respectively) compared with the referent group (higher albumin and low IL-6). CONCLUSIONS: High serum albumin has a protective effect in healthy older persons who do not have evidence of cytokine-mediated inflammation. This protective effect is not conferred in presence of inflammation. The mechanisms by which inflammation eliminates the protective effect of high albumin remain to be determined.

Blood pressure and mortality risk in older people: comparison between African Americans and whites.

OBJECTIVES: To determine the risk from hypertension for all-cause mortality in a racially mixed sample of community-dwelling older adults. DESIGN: Baseline blood pressure was assessed between 1985 and 1986 in a sample of persons 65 years of age and older from five counties of the Piedmont of North Carolina (N = 4,162). All-cause mortality was monitored annually over the subsequent 6 years as part of the Established Populations for Epidemiologic Studies of the Elderly (EPESE) sponsored by the National Institute on Aging. SETTING: Eighteen percent of all respondents in the sample had a systolic blood pressure of > 160 (17% for whites and 18% for African Americans) and 16% had a diastolic blood pressure of >90 (14% for whites and 20% for African Americans). During the 6 years of follow-up, 29% of the sample died (with no difference in mortality rates between whites and African Americans). PARTICIPANTS: 4,000 community-dwelling people age 65 years and older; 1,846 were white and 2,154 were African American. MEASUREMENTS: Systolic and diastolic blood pressure and all-cause mortality. RESULTS: Systolic blood pressure positively related to mortality during the 6 years of follow-up (relative risk = 1.05). Among whites the relationship of diastolic pressure to mortality was nonlinear, with those at the upper and lower ends of the distribution at increased risk. Among African Americans, diastolic pressure was unrelated to mortality. The analyses were controlled for age; gender; education; body mass index (BMI); smoking history; taking a medication to manage blood pressure; a history of cancer, diabetes mellitus, heart attack, or stroke; poor subjective health; impaired functional status; and cognitive impairment. CONCLUSIONS: The findings confirm that among older adults there is a significant relationship overall between systolic blood pressure and mortality over 6 years of follow-up in both whites and African Americans. Diastolic pressure was a risk factor for whites only.

Characteristics of nondisabled older persons who perform poorly in objective tests of lower extremity function.

OBJECTIVES: It has been suggested that nondisabled older persons with poor performance of lower extremity function are ideal targets for interventions of disability prevention. However, health-related factors associated with poor performance are largely unknown. Using data from a representative sample of nondisabled older persons, this study identifies the diseases and biological markers that characterize this group of the population. DESIGN AND PARTICIPANTS: A total of 3,381 persons aged 71 or older, interviewed and administered a battery of physical performance tests at the sixth annual follow-up of the Established Populations for Epidemiologic Studies of the Elderly (EPESE), who reported no need for help in walking 1/4 mile or climbing stairs. MEASUREMENTS: Lower extremity performance was measured using a short battery of tests including assessment of standing balance, a timed 2.4-m walk, and timed test of rising 5 times from a chair. Chronic conditions were ascertained as self-report of a physician diagnosis. Data on previous hospitalizations were obtained from the Medicare database. Nonfasting blood samples were obtained and processed with standard methods. RESULTS: In a multivariate analysis, older age, female gender, higher BMI, history of hip fracture and diabetes, one or more hospital admissions for acute infection in the last 3 years, lower levels of hemoglobin and albumin, and higher leukocytes and gamma-glutamyl transferase were all associated independently with poor performance. CONCLUSIONS: Screening for older patients who are not disabled but have poor lower extremity performance selects a subgroup of the population with a high percentage of women, high prevalence of diabetes and hip fracture, and high levels of biological markers of inflammation. This group represents about 10% of the US population 70 to 90 years old. These findings should be considered in planning specifically tailored interventions for disability prevention in this subgroup.

Cognitive impairment and risk of stroke in the older population.

OBJECTIVE: Recent studies have suggested that vascular dementia in older persons is more common than previously hypothesized. A substantial proportion of dementia in old age may be an early manifestation of cerebrovascular disease (CVD), that eventually becomes clinically evident as an acute cerebrovascular accident. This study was aimed at assessing whether cognitive impairment and cognitive decline in older persons free of stroke are associated with higher risk of future stroke, independently of other risk factors. DESIGN: Population-based prospective study. PARTICIPANTS: A total of 5024 subjects from the Established Populations for Epidemiologic Studies of the Elderly, who were alive and had no history of previous stroke at the sixth follow-up visit. Subjects who had reported a stroke in a previous interview or with a diagnosis of cerebrovascular disease in a hospitalization record during the previous 3 years were excluded. MEASUREMENTS: Cognitive function was assessed by the Short Portable Mental Status Questionnaire (SPMSQ). Occurrence of a stroke was prospectively assessed by examining hospital discharge diagnoses and death certificates. RESULTS: During 19,533 person-years of follow-up, 259 strokes were recorded (13.3/1000 person-years). Stroke incidence was lowest in those with normal SPMSQ score (12.1/1000 person-years), intermediate in those with moderate impairment (16.3/1000 person-years), and highest in those with severe impairment (30.9/1000 person-years). Adjusting for age, education, smoking, history of hypertension, blood pressure, heart attack, diabetes, and disability, the relative risks of stroke for moderate and severe cognitive impairment were 1.2 (0.9-1.6) and 2.2 (1.2-3.8), respectively. The association between cognitive impairment and incident stroke was not mediated by hypertension or diabetes. Compared with subjects with stable or improved SPMSQ score in the previous 3 years, those who declined had higher risk of stroke. CONCLUSIONS: The elevated risk of subsequent strokes in older persons with cognitive impairment suggests that CVD may play larger role in causing cognitive impairment then previously suspected. It remains to be demonstrated whether reducing modifiable risk factors for CVD decreases the burden of cognitive impairment in older persons without stroke.

Serum IL-6 level and the development of disability in older persons.

BACKGROUND: The serum concentration of interleukin 6 (IL-6), a cytokine that plays a central role in inflammation, increases with age. Because inflammation is a component of many age-associated chronic diseases, which often cause disability, high circulating levels of IL-6 may contribute to functional decline in old age. We tested the hypothesis that high levels of IL-6 predict future disability in older persons who are not disabled. METHODS: Participants at the sixth annual follow-up of the Iowa site of the Established Populations for Epidemiologic Studies of the Elderly aged 71 years or older were considered eligible for this study if they had no disability in regard to mobility or in selected activities of daily living (ADL), and they were re-interviewed 4 years later. Incident cases of mobility-disability and of ADL-disability were identified based on responses at the follow-up interview. Measures of IL-6 were obtained from specimens collected at baseline from the 283 participants who developed any disability and from 350 participants selected randomly (46.9%) from those who continued to be non-disabled. FINDINGS: Participants in the highest IL-6 tertile were 1.76 (95% CI, 1.17-2.64) times more likely to develop at least mobility-disability and 1.62 (95% CI, 1.02-2.60) times more likely to develop mobility plus ADL-disability compared with to the lowest IL-6 tertile. The strength of this association was almost unchanged after adjusting for multiple confounders. The increased risk of mobility-disability over the full spectrum of IL-6 concentration was nonlinear, with the risk rising rapidly beyond plasma levels of 2.5 pg/mL. INTERPRETATION: Higher circulating levels of IL-6 predict disability onset in older persons. This may be attributable to a direct effect of IL-6 on muscle atrophy and/or to the pathophysiologic role played by IL-6 in specific diseases.

Do calcium channel blockers increase the risk of cancer?

Calcium channel blockers can block calcium signals that trigger cell differentiation and apoptosis, which are important mechanisms of cancer growth regulation. To ascertain whether calcium channel blocker use was associated with an increased risk of cancer, 750 hypertensive persons age > or = 71 years, with no history of cancer at baseline, were followed from 1988 through 1992. The patients were using either beta-blockers, angiotensin converting enzyme inhibitors or calcium channel blockers (verapamil, nifedipine, and diltiazem; mainly of the short-acting variety). Compared to beta-blockers (n = 424, 28 events), after adjusting for age, gender, race, smoking, body mass index, and number of hospital admissions not related with cancer, the relative risks of cancer (95% confidence interval) for angiotensin converting enzyme inhibitors (n = 124, 6 events) and calcium channel blockers (n = 202, 27 events) were 0.73 (0.30 to 1.78) and 2.02 (1.16 to 3.54), respectively. These findings indicate that calcium channel blocker therapy might increase the risk of cancer. New data are needed in patients using modern calcium channel blocker agents with more gradual absorption. This report should encourage further study of cancer outcomes in elderly patients who are vulnerable to cancer and who are receiving calcium channel blockers.