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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

Smoking, physical activity, and active life expectancy.

The effect of smoking and physical activity on active and disabled life expectancy was estimated using data from the Established Populations for Epidemiologic Studies of the Elderly (EPESE). Population-based samples of persons aged > or = 65 years from the East Boston, Massachusetts, New Haven, Connecticut, and Iowa sites of the EPESE were assessed at baseline between 1981 and 1983 and followed for mortality and disability over six annual follow-ups. A total of 8,604 persons without disability at baseline were classified as "ever" or "never" smokers and doing "low," "moderate," or "high" level physical activity. Active and disabled life expectancies were estimated using a Markov chain model. Compared with smokers, men and women nonsmokers survived 1.6-3.9 and 1.6-3.6 years longer, respectively, depending on level of physical activity. When smokers were disabled and close to death, most nonsmokers were still nondisabled. Physical activity, from low to moderate to high, was significantly associated with more years of life expectancy in both smokers (9.5, 10.5, 12.9 years in men and 11.1, 12.6, 15.3 years in women at age 65) and nonsmokers (11.0, 14.4, 16.2 years in men and 12.7, 16.2, 18.4 years in women at age 65). Higher physical activity was associated with fewer years of disability prior to death. These findings provide strong and explicit evidence that refraining from smoking and doing regular physical activity predict a long and healthy life.

Evidence for a black-white crossover in all-cause and coronary heart disease mortality in an older population: the North Carolina EPESE.

OBJECTIVES: This cohort study evaluated racial differences in mortality among Blacks and Whites 65 years and older. METHODS: A total of 4136 men and women (1875 Whites and 2261 Blacks) living in North Carolina were interviewed in 1986 and followed up for mortality until 1994. Hazard ratios (HRs) for all-cause and cause-specific mortality were calculated, with adjustment for sociodemographic and coronary heart disease (CHD) risk factors. RESULTS: Black persons had higher mortality rates than Whites at young-old age (65-80 years) but had significantly lower mortality rates after age 80. Black persons age 80 or older had a significantly lower risk of all-cause mortality (HR of Blacks vs Whites, 0.75; 95% confidence interval [CI] = 0.62, 0.90) and of CHD mortality (HR 0.44: 95% CI = 0.30, 0.66). These differences were not observed for other causes of death. CONCLUSIONS: Racial differences in mortality are modified by age. This mortality crossover could be attributed to selective survival of the healthiest oldest Blacks or to other biomedical factors affecting longevity after age 80. Because the crossover was observed for CHD deaths only, age overreporting by Black older persons seems an unlikely explanation of the mortality differences.

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.

Black/white differences in the relationship between MMSE scores and disability: the Women's Health and Aging Study.

The purpose of this article is to examine Black/White differences among older women in the relationship between physical functional difficulties and variations in cognitive status, measured within the low to high normal range of the Mini-Mental State Examination (MMSE). We studied 3,585 women with MMSE scores of 18 and above from a population-based random sample of 3,841 community-dwelling women aged 65 and older living in East Baltimore, Maryland. Trained interviewers administered the MMSE and obtained information on demographics, medical conditions, and functional difficulties. Prevalence of any functional difficulty was 43.3% in Whites and 48.5% in Blacks, who were 25% of the study sample. After adjusting for age and education, a significant trend for increasing functional difficulty with decreasing MMSE scores was found in White women but not in Black women. Since no explanation for these racial differences could be identified, these findings suggest that the MMSE may not be a valid predictor of functional difficulty in Black women who score > or = 18 on the instrument.

Apolipoprotein E epsilon 2 allele and risk of stroke in the older population.

BACKGROUND AND PURPOSE: There is evidence for a role of apolipoprotein E (apoE) in atherosclerosis. Coronary heart disease morbidity is higher in persons carrying an epsilon 4 allele and lower in those carrying an epsilon 2 allele, but the effect on cerebrovascular disease is controversial. We estimated the risk of stroke associated with different apoE genotypes in older persons. METHODS: At the sixth annual follow-up of the Iowa cohort of the Established Populations for Epidemiologic Studies of the Elderly, 1664 persons aged > or = 71 years and free of stroke were genotyped for apo E. Occurrence of ischemic strokes was prospectively assessed from subsequent hospital discharge records and death certificates. RESULTS: One hundred fifty persons had an ischemic stroke over the subsequent 5 years (21.2 per 1000 person-years). The presence of epsilon 3 and epsilon 4 did not influence stroke risk. Among persons aged < 80 years at the time of genotyping, epsilon 2 carriers had lower risk of incident stroke, while no effect was detected in the older group. Compared with epsilon 2 carriers aged 70 to 79 years (reference group), those in the same age group and not carrying an epsilon 2 had 2.6-fold higher risk of incident stroke, and those aged > or = 80 years had even higher risk of stroke but without any difference according to presence/absence of epsilon 2 (relative risks 3.6 and 3.3). Results remained substantially unchanged when adjusted for potential confounders and in models estimating the effect of apoE polymorphism on the risk of developing a stroke at ages between 70 and 79 years (56 events) and separately at ages > or = 80 years (94 events). CONCLUSIONS: The conditioning influence of age on the protection conferred by the apoE epsilon 2 allele on stroke risk may account for previous controversies. This hypothesis should be verified in a population with a wider age range.

Departures from linearity in the relationship between measures of muscular strength and physical performance of the lower extremities: the Women's Health and Aging Study.

BACKGROUND: Sarcopenia, an age-related reduction in muscular mass and strength, may cause a decline in physical functioning and subsequent loss of autonomy. It has been suggested that strength is associated with lower extremity function mainly in the lower portion of the range of strength. Identifying the threshold under which strength is most critical to function may help in targeting groups who may benefit most from exercise interventions. METHODS: The study uses data from the Women's Health and Aging Study. The study population, recruited by screening a population-based sample aged 65 years and older, comprised 1,002 women who represent the one-third most disabled women without severe cognitive impairment living in the community. Knee extensor and hip flexor strength were assessed using a hand-held dynamometer. Lower extremity performance was evaluated using tests of walking, standing balance, and rising from a chair. RESULTS: Among women tested for strength (n = 892), those who could walk (97%), do the side-by-side stand (87%), or complete 5 chair stands (74%) had significantly greater strength. Walking speed was linearly associated with knee extensor strength over the entire range of strength, but its association with hip strength was limited to values below 15 kg. Time for five chair stands was associated with knee extensor and hip flexor strength below 10 and 15 kg, respectively, and no significant association was detected above these values. Stronger women were more likely to hold balance for 10 sec in the side-by-side, semi-tandem, and tandem positions. The percentage of the variance in performance explained by strength alone was always lower than 20%. CONCLUSIONS: In this population, which does not include the strongest older women, there is a departure from linearity in the relationship between muscular strength and some measures of lower extremity performance.

Lipoprotein alterations and atherosclerosis in the elderly.

Lipoproteins play a key role in the pathogenesis of atherosclerotic diseases. With increasing age, modifications in the metabolism, distribution and correlates of lipoprotein lipids have been described. Age associated changes in lipoproteins are determined by several genetic and environmental factors, but in elderly populations, an important role is also played by the presence of comorbid diseases and poor health. In older populations, the ability of lipoprotein levels to predict cardiovascular risk is controversial. When lipoprotein levels are measured at old age, secondary changes in total and high density lipoprotein-cholesterol levels may lead to misclassification and to underestimation of associations. When analyzing associations in older populations, it is therefore important to consider measures of disease burden and comorbidity. When these caveats are taken into account, evidence from observational studies in older persons confirms the association between lipoprotein lipids, cardiovascular and cerebrovascular disease. Among older patients with cardiovascular disease, intervention trials have demonstrated that lipid lowering drugs can significantly reduce total and coronary heart disease mortality. Unequivocal evidence that lipid-lowering drugs are beneficial in old and very old persons without pre-existing cardiovascular disease is still lacking. Results from primary and secondary intervention trials in older men and women are needed to provide conclusive guidelines.

Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons.

BACKGROUND: The importance of total cholesterol level as a risk factor for coronary heart disease in older adults is controversial. OBJECTIVE: To determine whether findings showing that total cholesterol level is not an important risk factor for coronary heart disease in older adults are the result of inadequate adjustment for co-occurring diseases and frailty. DESIGN: Multicenter, longitudinal study with 5-year follow-up for death. PARTICIPANTS: 4066 men and women from East Boston, Massachusetts; Iowa and Washington counties, Iowa; and New Haven, Connecticut. MEASUREMENTS: In 1988, participants were interviewed about their health status and had blood samples taken. Mortality follow-up was through 1992. RESULTS: In analyses that included all fatal coronary heart disease events (252 deaths) and did not adjust for risk factors for coronary heart disease and measures of frailty, persons with the lowest total cholesterol levels (< or = 4.15 mmol/L [< or = 160 mg/dL]) had the highest rate of death from coronary heart disease, whereas those with elevated total cholesterol levels (> or = 6.20 mmol/L [> or = 240 mg/dL]) seemed to have a lower risk for death from coronary heart disease (P for trend = 0.04). After adjustment for established risk factors for coronary heart disease and markers of poor health (including chronic conditions, low serum iron and albumin levels) and exclusion of 44 deaths from coronary heart disease that occurred within the first year, elevated total cholesterol levels predicted increased risk for death from coronary heart disease, and the risk for death from coronary heart disease decreased as cholesterol levels decreased (P for trend = 0.005). CONCLUSIONS: Elevated total cholesterol level is a risk factor for death from coronary heart disease in older adults, and the apparent adverse effects associated with low cholesterol levels are secondary to comorbidity and frailty. This suggests that excluding older persons from cholesterol screening is inappropriate, but interpretation of screening results in older persons requires clinical judgment. Results from controlled clinical trials are needed to clarify this issue.

Hospital diagnoses, Medicare charges, and nursing home admissions in the year when older persons become severely disabled.

OBJECTIVE: To characterize hospital diagnoses, procedures and charges, and nursing home admissions in the year when older persons become severely disabled, comparing those in whom severe disability develops rapidly with those in whom disability develops gradually. DESIGN: A prospective, population-based cohort study with at least 6 annual interviews beginning in 1982. SETTING: A total of 3 communities: East Boston, Mass, New Haven, Conn, and Iowa and Washington counties in Iowa. SUBJECTS: A total of 6070 persons at least 70 years old with at least 1 interview after the fourth annual follow-up and without evidence of previous severe disability, defined as disability in 3 or more activities of daily living (ADLs). MAIN OUTCOME MEASURES: Characteristics associated with development of severe disability after the fourth annual follow-up, in which the disability is classified as catastrophic disability if the individual did not report any ADL disability in the 2 interviews prior to severe disability onset or as progressive disability if the individual had previous disability in 1 or 2 ADLs. RESULTS: In the year during which severe disability developed, hospitalizations were documented for 72.1% of those developing catastrophic disability and for 48.6% of those developing progressive disability. In the corresponding year, only 14.7% of those who were stable with no disability and 22.3% of those with some disability were hospitalized. The 6 most frequent principal discharge diagnoses included stroke, hip fracture, congestive heart failure, and pneumonia in both severe disability subsets; coronary heart disease and cancer in catastrophic disability; and diabetes and dehydration in progressive disability. These diagnoses occurred in 49% of those with catastrophic disability and 25% of those with progressive disability. In both severe disability subsets, the oldest patients received less intensive hospital care as indicated by charges for surgery, diagnostics, and rehabilitation and by the percentage who received major diagnostic procedures; they were also more often admitted to nursing homes. CONCLUSIONS: In the year when they become severely disabled, a large proportion of older persons are hospitalized for a small group of diseases. Hospital-based interventions aimed at reducing the severity and functional consequences of these diseases could have a large impact on reduction of severe disability.

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.