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This Viewpoint outlines the challenges posed by the COVID-19 pandemic in conducting clinical trials and offers some solutions to those barriers. [ABSTRACT FROM AUTHOR]

The article presents a study on subclinical hypothyroidism in older people. It tests older people by thyroid function in thyrotropin (TSH) levels including euthyroid, mid subclinical hypothyroid, and moderate subclinical hypothyroid. It states that mid subclinical hypothyroid shows better mobility to those with good cardiorespiratory fitness. It adds that older people with subclinical hypothyroidism do not show mobility problems and prove advantages to those with mild elevation in TSH level.

This Viewpoint discusses ways the coronavirus pandemic is threatening clinical trial conduct and enrollment, and suggests ways to adapt, including changes to how outcomes data are collected and how interventions are delivered and monitored, to minimize trial disruption, maximize trial benefit, and ensure patient health and safety during the pandemic. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the association of aerobic fitness in older people with several factors including mortality, cardiovascular disease, mobility limitation, and disability. The study, called the Health, Aging, and Body Composition study, selected a group of people between the ages of 70 and 79 and assessed their performance as they walked 400 meters in a corridor. The methods by which the participants were selected is described. A chart listing those who were excluded from the corridor walk and why is presented. Another chart lists the characteristics of the participants. Other charts list event rates and hazard ratios as well as cardiovascular response for the participants. Eight graphs depict percentages of mortality, incident cardiovascular disease, mobility limitation, and mobility disability in men and women.

Background The association of cystatin C, a novel marker of renal function, with risk for developing complications related to peripheral arterial disease (PAD) has not been examined. Methods We evaluated the hypothesis that a high cystatin C concentration is independently associated with future PAD events among 4025 participants in the Cardiovascular Health Study who underwent serum cystatin C measurement at the 1992-1993 visit and who did not have PAD at baseline. The association of cystatin C quintiles with time to first lower-extremity PAD procedure (bypass surgery, angioplasty, or amputation) was evaluated using multivariable proportional hazards models. Secondary analyses were conducted using quintiles of serum creatinine level and estimated glomerular filtration rate (eGFR). Results The annualized risk of undergoing a procedure for PAD was 0.43% per year among participants in the highest cystatin C quintile (>1.27 mg/L) compared with 0.21% per year or less in all other quintiles. After multivariable adjustment for known risk factors for PAD, elevated cystatin C levels remained associated with the outcome (hazard ratio, 2.5 for highest vs lowest quintile of cystatin C, 95% confidence interval, 1.2-5.1). The highest quintiles of serum creatinine level and eGFR were not associated with future PAD events in either unadjusted or adjusted analyses. Conclusion Elevated concentrations of cystatin C were independently predictive of incident PAD events among community-dwelling elderly patients. [ABSTRACT FROM AUTHOR]

Background Subclinical hypothyroidism has been associated with systolic and diastolic cardiac dysfunction and an elevated cholesterol level, but data on cardiovascular outcomes and death are limited. Methods We studied 2730 men and women, aged 70 to 79 years, with baseline thyrotropin (TSH) measurements and 4-year follow-up data to determine whether subclinical hypothyroidism was associated with congestive heart failure (CHF), coronary heart disease, stroke, peripheral arterial disease, and cardiovascular-related and total mortality. After the exclusion of participants with abnormal thyroxine levels, subclinical hypothyroidism was defined as a TSH level of 4.5 mIU/L or greater, and was further classified according to TSH levels (4.5-6.9, 7.0-9.9, and ≥10.0 mIU/L). Results Subclinical hypothyroidism was present in 338 (12.4%) of the participants. Compared with euthyroid participants, CHF events occurred more frequently among those with a TSH level of 7.0 mIU/L or greater (35.0 vs 16.5 per 1000 person-years; P = .006), but not among those with TSH levels between 4.5 and 6.9 mIU/L. In multivariate analyses, the risk of CHF was higher among those with high TSH levels (TSH of 7.0-9.9 mIU/L: hazard ratio, 2.58 [95% confidence interval, 1.19-5.60]; and TSH of ≥10.0 mIU/L: hazard ratio, 3.26 [95% confidence interval, 1.37-7.77]). Among the 2555 participants without CHF at baseline, the hazard ratio for incident CHF events was 2.33 (95% confidence interval, 1.10-4.96; P = .03) in those with a TSH of 7.0 mIU/L or greater. Subclinical hypothyroidism was not associated with increased risk for coronary heart disease, stroke, peripheral arterial disease, or cardiovascular-related or total mortality. Conclusions Subclinical hypothyroidism is associated with an increased risk of CHF among older adults with a TSH level of 7.0 mIU/L or greater, but not with other cardiovascular events and mortality. Further investigation is warranted to assess whether subclinical hypothyroidism causes or worsens preexisting heart failure. [ABSTRACT FROM AUTHOR]

Background The relationship of weight changes to the incidence, progression, and remission of sleep-disordered breathing (SDB) is not well defined. This study aims to determine the relationship between change in weight and progression or remission of SDB by polysomnography. Methods We performed a longitudinal cohort study of the cardiovascular consequences of sleep apnea in diverse US communities. Sleep apnea and polysomnographic indicators of SDB were assessed 5 years apart. Results A total of 2968 men and women (mean age, 62 years) participated in the study. Men were more likely to have an increase in Respiratory Disturbance Index (RDI) with a given increase in weight than were women, and this was not explained by differences in starting weight, waist circumference, age, or ethnicity. In a linear regression analysis, both men and women had a greater increase in RDI with weight gain than a decrease in RDI with weight loss. In a categorical analysis of larger degrees of change, this sex difference was also evident. Associations were similar in diverse ethnic groups. However, SDB progressed over time, even in those with stable weight. Conclusion Modest changes in weight were related to an increase or decrease in SDB, and this association was stronger in men than in women. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases are the primary cause of death in older adults. Among those without clinical disease, high levels of subclinical disease are associated with poor survival. The effect of the extent of subclinical cardiovascular disease on the quality of the remaining years has not been defined. Methods: In a longitudinal cohort study, 2932 men and women aged 65 years and older were followed up for 8 years to determine the likelihood of maintaining intact health and functioning. Successful aging was defined as remaining free of cardiovascular disease, cancer, and chronic obstructive pulmonary disease and with intact physical and cognitive functioning. Results: Younger age at study entry and a lower extent of subclinical cardiovascular disease were independently associated with the likelihood of maintaining successful aging. In age-stratified summaries, those with subclinical disease had a trajectory of decline similar to subjects 5 years older without subclinical vascular disease. Regression analyses showed that the decline associated with subclinical disease was equivalent to 6.5 (95% confidence interval, 6.4-6.6) years of aging for women and 5.6 (95% confidence interval, 5.4-5.8) years of aging for men. Individual measures of the extent of cardiovascular disease, diabetes mellitus, smoking, and higher C-reactive protein level were also independently predictive of fewer years of successful aging, but none of these factors substantially attenuated the effect of age itself. Conclusions: There is a graded relationship between the extent of vascular disease measured noninvasively and the likelihood of maintaining intact health and function. Prevention of subclinical vascular disease may increase the quality and the quantity of years in late life. [ABSTRACT FROM AUTHOR]

Studies the relationship between ankle/arm blood pressure index (AAI) and cardiovascular morbidity and mortality in older adults with systolic hypertension. Systolic Hypertension in the Elderly Program; Coronary heart disease mortality; Cardiovascular disease mortality.

Background: Short-term prospective studies have shown physical activity to be related to functional status. To our knowledge, the association between physical activity levels and functional status over a longer period has not been established. Methods: Two hundred twenty-nine older women (mean age, 74.2 years) who were involved in a randomized controlled walking intervention from 1982 to 1985 were subsequently followed up until December 1999. Physical activity was assessed in 1985, 1995, and 1999 using a physical activity questionnaire and a physical activity monitor. In 1999, functional status was assessed by self-report and performance-based measures. Results: Subjective and objective measures of physical activity in 1985 independently predicted gait speed in 1999 after controlling for age, chronic conditions, and activity limitation (subjective model-adjusted R[sup 2] = 0.09 [P= .03]; and objective model-adjusted R[sup 2] = 0.13 [P= .008]). The consistency of physical activity participation from 1985 to 1995 was also related to functional status in 1999. Women who were always active had the best functional status and women who were always inactive had the worst functional status. For difficulty with activities of daily living: those always active, 17 (37.8%) of 45 women; those inconsistently active, 24 (40.0%) of 60 women; and those always inactive, 39 (59.1%) of 66 women (χ[sup 2] for trend P= .02). For score on the Physical Performance Test: those always active, 24.9; those inconsistently active, 24.5; and those always inactive, 23.8 (analysis of variance with linear contrasts P= .04). For gait speed: those always active, 1.17 m/s; those inconsistently active, 1.15 m/s; and those always inactive, 1.03 m/s (analysis of variance with linear contrasts P= .002). Conclusion: We demonstrated a significant relation between physical activity during a 14-year period and current functional status in older women, thus suggesting that physical activity plays a role in maintaining functional ability later in life. [ABSTRACT FROM AUTHOR]

Context: Multiple factors contribute to mortality in older adults, but the extent to which subclinical disease and other factors contribute independently to mortality risk is not known.Objective: To determine the disease, functional, and personal characteristics that jointly predict mortality in community-dwelling men and women aged 65 years or older.Design: Prospective population-based cohort study with 5 years of follow-up and a validation cohort of African Americans with 4.25-year follow-up.Setting: Four US communities.Participants: A total of 5201 and 685 men and women aged 65 years or older in the original and African American cohorts, respectively.Main Outcome Measures: Five-year mortality.Results: In the main cohort, 646 deaths (12%) occurred within 5 years. Using Cox proportional hazards models, 20 characteristics (of 78 assessed) were each significantly (P<.05) and independently associated with mortality: increasing age, male sex, income less than $50000 per year, low weight, lack of moderate or vigorous exercise, smoking for more than 50 pack-years, high brachial (>169 mm Hg) and low tibial (< or = 127 mm Hg) systolic blood pressure, diuretic use by those without hypertension or congestive heart failure, elevated fasting glucose level (>7.2 mmol/L [130 mg/dL]), low albumin level (< or = 37 g/L), elevated creatinine level (> or = 106 micromol/L [1.2 mg/dL]), low forced vital capacity (< or = 2.06 mL), aortic stenosis (moderate or severe) and abnormal left ventricular ejection fraction (by echocardiography), major electrocardiographic abnormality, stenosis of internal carotid artery (by ultrasound), congestive heart failure, difficulty in any instrumental activity of daily living, and low cognitive function by Digit Symbol Substitution test score. Neither high-density lipoprotein cholesterol nor low-density lipoprotein cholesterol was associated with mortality. After adjustment for other factors, the association between age and mortality diminished, but the reduction in mortality with female sex persisted. Finally, the risk of mortality was validated in the second cohort; quintiles of risk ranged from 2% to 39% and 0% to 26% for the 2 cohorts.Conclusions: Objective measures of subclinical disease and disease severity were independent and joint predictors of 5-year mortality in older adults, along with male sex, relative poverty, physical activity, smoking, indicators of frailty, and disability. Except for history of congestive heart failure, objective, quantitative measures of disease were better predictors of mortality than was clinical history of disease. [ABSTRACT FROM AUTHOR]

IMPORTANCE In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining whether physical activity prevents or delays mobility disability. OBJECTIVE To test the hypothesis that a long-term structured physical activity program is more effective than a health education program(also referred to as a successful aging program) in reducing the risk of major mobility disability. DESIGN, SETTING, AND PARTICIPANTS The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial that enrolled participants between February 2010 and December 2011, who participated for an average of 2.6 years. Follow-up ended in December 2013. Outcome assessors were blinded to the intervention assignment. Participants were recruited from urban, suburban, and rural communities at 8 centers throughout the United States. We randomized a volunteer sample of 1635 sedentary men and women aged 70 to 89 years who had physical limitations, defined as a score on the Short Physical Performance Battery of 9 or below, but were able to walk 400m. INTERVENTIONS Participants were randomized to a structured, moderate-intensity physical activity program(n = 818) conducted in a center (twice/wk) and at home (3-4 times/wk) that included aerobic, resistance, and flexibility training activities or to a health education program (n = 817) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises. MAIN OUTCOMES ANDMEASURES The primary outcome was major mobility disability objectively defined by loss of ability to walk 400m. RESULTS Incident major mobility disability occurred in 30.1% (246 participants) of the physical activity group and 35.5% (290 participants) of the health education group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98], P = .03). Persistent mobility disability was experienced by 120 participants (14.7%) in the physical activity group and 162 participants (19.8%) in the health education group (HR, 0.72 [95% CI, 0.57-0.91]; P = .006). Serious adverse events were reported by 404 participants (49.4%) in the physical activity group and 373 participants (45.7%) in the health education group (risk ratio, 1.08 [95% CI, 0.98-1.20]). CONCLUSIONS AND RELEVANCE A structured, moderate-intensity physical activity program compared with a health education program reduced major mobility disability over 2.6 years among older adults at risk for disability. These findings suggest mobility benefit from such a program in vulnerable older adults. [ABSTRACT FROM AUTHOR]

Importance: In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining whether physical activity prevents or delays mobility disability.Objective: To test the hypothesis that a long-term structured physical activity program is more effective than a health education program (also referred to as a successful aging program) in reducing the risk of major mobility disability.Design, Setting, and Participants: The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial that enrolled participants between February 2010 and December 2011, who participated for an average of 2.6 years. Follow-up ended in December 2013. Outcome assessors were blinded to the intervention assignment. Participants were recruited from urban, suburban, and rural communities at 8 centers throughout the United States. We randomized a volunteer sample of 1635 sedentary men and women aged 70 to 89 years who had physical limitations, defined as a score on the Short Physical Performance Battery of 9 or below, but were able to walk 400 m.Interventions: Participants were randomized to a structured, moderate-intensity physical activity program (n = 818) conducted in a center (twice/wk) and at home (3-4 times/wk) that included aerobic, resistance, and flexibility training activities or to a health education program (n = 817) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises.Main Outcomes and Measures: The primary outcome was major mobility disability objectively defined by loss of ability to walk 400 m.Results: Incident major mobility disability occurred in 30.1% (246 participants) of the physical activity group and 35.5% (290 participants) of the health education group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98], P = .03).Persistent mobility disability was experienced by 120 participants (14.7%) in the physical activity group and 162 participants (19.8%) in the health education group (HR, 0.72 [95% CI, 0.57-0.91]; P = .006). Serious adverse events were reported by 404 participants (49.4%) in the physical activity group and 373 participants (45.7%) in the health education group (risk ratio, 1.08 [95% CI, 0.98-1.20]).Conclusions and Relevance: A structured, moderate-intensity physical activity program compared with a health education program reduced major mobility disability over 2.6 years among older adults at risk for disability. These findings suggest mobility benefit from such a program in vulnerable older adults.Trial Registration: clinicaltrials.gov Identifier: NCT01072500. [ABSTRACT FROM AUTHOR]

The article details a study which examined the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism. Of the 52,674 study subjects, 4.2 percent were found to have clinical hyperthyroidism. Study authors concluded that endogenous subclinical hyperthyroidism is associated with increased risks of total and CHD mortality, and AF development.

Context: In populations of older adults, prediction of coronary heart disease (CHD) events through traditional risk factors is less accurate than in middle-aged adults. Electrocardiographic (ECG) abnormalities are common in older adults and might be of value for CHD prediction.Objective: To determine whether baseline ECG abnormalities or development of new and persistent ECG abnormalities are associated with increased CHD events.Design, Setting, and Participants: A population-based study of 2192 white and black older adults aged 70 to 79 years from the Health, Aging, and Body Composition Study (Health ABC Study) without known cardiovascular disease. Adjudicated CHD events were collected over 8 years between 1997-1998 and 2006-2007. Baseline and 4-year ECG abnormalities were classified according to the Minnesota Code as major and minor. Using Cox proportional hazards regression models, the addition of ECG abnormalities to traditional risk factors were examined to predict CHD events.Main Outcome Measure: Adjudicated CHD events (acute myocardial infarction [MI], CHD death, and hospitalization for angina or coronary revascularization).Results: At baseline, 276 participants (13%) had minor and 506 (23%) had major ECG abnormalities. During follow-up, 351 participants had CHD events (96 CHD deaths, 101 acute MIs, and 154 hospitalizations for angina or coronary revascularizations). Both baseline minor and major ECG abnormalities were associated with an increased risk of CHD after adjustment for traditional risk factors (17.2 per 1000 person-years among those with no abnormalities; 29.3 per 1000 person-years; hazard ratio [HR], 1.35; 95% CI, 1.02-1.81; for minor abnormalities; and 31.6 per 1000 person-years; HR, 1.51; 95% CI, 1.20-1.90; for major abnormalities). When ECG abnormalities were added to a model containing traditional risk factors alone, 13.6% of intermediate-risk participants with both major and minor ECG abnormalities were correctly reclassified (overall net reclassification improvement [NRI], 7.4%; 95% CI, 3.1%-19.0%; integrated discrimination improvement, 0.99%; 95% CI, 0.32%-2.15%). After 4 years, 208 participants had new and 416 had persistent abnormalities. Both new and persistent ECG abnormalities were associated with an increased risk of subsequent CHD events (HR, 2.01; 95% CI, 1.33-3.02; and HR, 1.66; 95% CI, 1.18-2.34; respectively). When added to the Framingham Risk Score, the NRI was not significant (5.7%; 95% CI, -0.4% to 11.8%).Conclusions: Major and minor ECG abnormalities among older adults were associated with an increased risk of CHD events. Depending on the model, adding ECG abnormalities was associated with improved risk prediction beyond traditional risk factors. [ABSTRACT FROM AUTHOR]

The article provides information on a study which determined whether baseline electrocardiographic (ECG) abnormalities or development of new and persistent ECG abnormalities are associated with increased coronary heart disease (CHD) events. The population-based study enrolled 2,192 white and African American older adults aged 70 to 79 years from health, Aging and Body Composition Study without known cardiovascular disease (CVD). The study then assessed incident CHD events among participants without preexisting CVD at baseline.

The article discusses a study which evaluated the relationship between gait speed and survival in geriatric patients, as well as determined the degree to which gait speed explains variability in survival after accounting for age and sex. The study's design, setting and participants are described. Main outcome measures include survival rates and life expectancy. The study found that survival increased across the full range of gait speeds based on the pooled analysis of individual data from 9 selected cohorts.

A response by Elsa S. Strotmeyer, Ann V. Schwartz, Anne B. Newman to a letter to the editor about their article published in the previous issue is presented.

The article focuses on a study which examined the risks of coronary heart disease (CHD) and total mortality among adults with subclinical hypothyroidism. The study included 55,287 adults in the U.S., Europe, Australia, Brazil and Japan, who were followed up from 1972 to 2007. Of the total study participants, 3,450 developed subclinical hypothyroidism, while 51,837 had euthyroidism. Study authors found that increased thyroid-stimulating hormone (TSH) concentration increased the risk of CHD and CHD-related mortality. They concluded that patients with subclinical hypothyroidism have higher risk of CHD.

The article provides information on a prospective cohort study which investigated the association between adiposity, changes in adiposity and risk of incident type 2 diabetes in adults 65 years of age and older. Participants were men and women in the Cardiovascular Health Study, conducted between 1989 and 2007. Measures of adiposity were based from anthropometry and bioelectrical impedance data at baseline and anthropometry measured three years after. Main outcome measure was incident diabetes determined based on use of antidiabetic drug or a fasting glucose level of 126 milligram/deciliter or greater. A detailed discussion on the research findings is offered.

The article discusses the study which aims to assess the effects of weight loss on obstructive sleep apnea (OSA). In the study, researchers examined the respondents' body mass index calculated in kilograms and divided by height in meters squared along with the apnea-hypopnea index per hour. The study found that physicians and their patients can expect weigh loss which with relevant improvements in OSA among obese patients with type 2 diabetes.

The article presents a study which examines the race- and sex-specific epidemiology of incident heart failure (HF) in a contemporary elderly cohort. The researchers investigate the incidence of HF, the population-attributable risk (PAR) for HF, and outcomes of incident HF among 2,934 participant with HF who enrolled in the Health, Aging, and Body Composition Study. The study shows that incident HF is common in old persons in which a large proportion of risk is attributed to modifiable risk factors.

The article reports on the study that examines the slop of annual decline in estimated glomerular filtration rate (eGFR) using both serum creatinine and cystatin rates in the American older people. The study, conducted by Internal Medicine Dena E. Rifkin and colleagues, reveals that the association of rapid decline in eGFR with elevated mortality risk did not differ across subgroups based on baseline kidney function, age, sex, and prevalent coronary heart disease. It also suggests that rapid decline in eGFR is associated with an increased risk of cardiovascular and all-acute cause mortality in older adults.

The article discusses the effect of Cystatin C on successful aging. A study was conducted to determine the relation between kidney function and aging success for a six-year follow-upcardiovascular health study in the United States. The level of Cystatin C of the Two thousand one hundred forty participants have been observed. The result of the study showed that even if the patient possess a relatively normal kidney function, the presence of cystatin C in a higher level, the greater unsuccessful aging it entails.

The article investigates the relationship of alcohol intake with all-cause mortality and cardiac events. The overall survival benefit of alcohol consumption and the mechanisms underlying the cardioprotective effect of light to moderate alcohol intake is discussed. Findings suggest that the protective effect of moderate alcohol consumption on health-related outcomes may be mediated through anti-inflammatory effect.

The article explores whether there is a difference of the association of chronic kidney disease with incident heart failure between blacks and whites. Results of the study showed that the association of kidney dysfunction with heart failure seems to be stronger in blacks than for whites, especially when cystatin C is used to measure kidney function. More information could be found in the article.

Background Anemia is viewed as a negative prognostic factor in the elderly population; its independent impact on survival is unclear. Methods Baseline hemoglobin quintiles and anemia, as defined by the World Health Organization criteria, were assessed in relation to mortality in the Cardiovascular Health Study, a prospective cohort study with 11.2 years of follow-up of 5888 community-dwelling men and women 65 years or older, enrolled in 1989-1990 or 1992-1993 in 4 US communities. Results A total of 1205 participants were in the lowest hemoglobin quintile (<13.7 g/dL for men; <12.6 g/dL for women), and 498 (8.5%) were anemic (<13 g/dL for men; <12 g/dL for women). A reverse J-shaped relationship with mortality was observed; age-, sex-, and race-adjusted hazard ratios (95% confidence interval [CI]) in the first and fifth quintiles, compared with the fourth quintile, were 1.42 (95% CI, 1.25-1.62) and 1.24 (95% CI, 1.09-1.42). After multivariate adjustment, these hazard ratios were 1.33 (95% CI, 1.15-1.54) and 1.17 (95% CI, 1.01-1.36). The demographic- and fully-adjusted hazard ratios of anemia for mortality were 1.57 (95% CI, 1.38-1.78) and 1.38 (95% CI, 1.19-1.54). Adjustment for causes and consequences of anemia (renal function, inflammation, or frailty) did not reduce associations. Conclusions Lower and higher hemoglobin concentrations and anemia by World Health Organization criteria were independently associated with increased mortality. The World Health Organization criteria did not identify risk as well as a lower hemoglobin value. Additional study is needed on the clinically valid definition for and causes of anemia in the elderly and on the increased mortality at the extremes of hemoglobin concentrations. [ABSTRACT FROM AUTHOR]

Background Oxidative damage plays an important role in leading to major health-related events. The aim of this study was to assess the predictive value of a lipoprotein peroxidation marker, oxidized low-density lipoprotein (oxLDL) for incident mobility limitation (ML). Methods Data are from 2985 well-functioning elders enrolled in the Health ABC study (median follow-up, 4.1 years). All oxLDL levels were measured at the baseline assessment. The oxLDL/LDL cholesterol (LDL-C) ratio (log value) was used as a measure of lipoprotein peroxidation. Mobility limitation was defined by 2 consecutive semiannual reports of any difficulty either walking 1/4 mile or climbing up 10 steps without resting. Severe ML was defined by 2 consecutive reports of great difficulty or inability to do the same tasks. Cox proportional hazards models were performed to assess hazard ratios (HRs) and 95% confidence intervals (CIs). Results The mean (SD) age of the sample was 74.2 (2.9) years. After adjustment for potential confounders (sociodemographic factors, smoking, physical activity, body mass index, clinical conditions, biological markers, and medications), the relationship between the oxLDL/LDL-C ratio and disability events was statistically significant (per log-unit difference in the oxLDL/LDL-C ratio) (for ML: HR, 1.22; 95% CI, 1.06-1.41; for severe ML: HR, 1.43; 95% CI, 1.15-1.79). Consistent results were found when interleukin 6 level was included as a covariate in the adjusted models (ML: HR, 1.13; 95% CI, 0.98-1.31; severe ML: HR, 1.31; 95% CI, 1.05-1.64). No significant sex, race, interleukin 6 level, or clinical conditions interaction was found with the oxLDL/LDL-C ratio and mobility disability. Conclusions Lipoprotein peroxidation predicts the onset of ML in older persons. The oxLDL predictive value for ML is partly explained by interleukin 6 levels. [ABSTRACT FROM AUTHOR]

Background An ankle-brachial index (ABI) of less than 0.9 is a noninvasive measure of lower extremity arterial disease and a predictor of cardiovascular events. Little information is available on longitudinal change in ABI or on risk factors for declining ABI in a community-based population. Methods To assess risk factors for ABI decline, we studied 5888 participants in the Cardiovascular Health Study cohort (men and women 65 years or older). We measured ABI in 1992-1993 and again in 1998-1999. At baseline, we excluded individuals with an ABI less than 0.9, ABI greater than 1.4, or confirmed symptomatic lower extremity arterial disease (n = 823). The group with ABI decline included 218 participants with decline greater than 0.15 and to 0.9 or less. The comparison group comprised the remaining 2071 participants with follow-up ABI. Results The percentage of participants with ABI decline was 9.5% over 6 years of follow-up. The mean ± SD decline was 0.33 ± 0.12 in cases of ABI decline and 0.02 ± 0.13 in noncases. Independent predictors of ABI decline, reported as odds ratios, were age, 1.96 (95% confidence interval [CI], 1.42-2.71) for 75 to 84 years and 3.79 (95% CI, 1.36-10.5) for those older than 85 years compared with those younger than 75 years; current cigarette use, 1.74 (95% CI, 1.02-2.96); hypertension, 1.64 (95% CI, 1.18-2.28); diabetes, 1.77 (95% CI, 1.14-2.76); higher low-density lipoprotein cholesterol level, 1.60 (95% CI, 1.03-2.51), and lipid-lowering drug use 1.74 (95% CI, 1.05-2.89). Conclusion Worsening lower extremity arterial disease, assessed as ABI decline, occurred in 9.5% of this elderly cohort over 6 years and was associated with modifiable vascular disease risk factors. [ABSTRACT FROM AUTHOR]

Context Physical performance in response to exercise appears to be influenced by the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) genotype in young adults, but whether this relationship could help explain variation in older individuals’ response to exercise has not been well studied. Objective To determine whether the ACE genotype interacts with significant physical activity to affect the incidence of mobility limitation in well-functioning older adults. Design, Setting, and Participants The Health Aging and Body Composition (Health ABC) Cohort Study, conducted in the metropolitan areas of Memphis, Tenn, and Pittsburgh, Pa. A total of 3075 well-functioning community-dwelling adults aged 70 through 79 years were enrolled from 1997 to 1998 and had a mean of 4.1 years of follow-up. Main Outcome Measure Incident mobility limitation defined as the report of difficulty walking a quarter of a mile (0.4 km) or walking up 10 steps on 2 consecutive semiannual interviews (n = 1204). Results Physically active participants (those reporting expending ≥1000 kcal/wk in exercise, walking, and stair climbing) were less likely to develop mobility limitation regardless of genotype. However, activity level interacted significantly with the ACE genotype (P = .002). In the inactive group, the ACE genotype was not associated with limitation (P = .46). In the active group, those with the II genotype were more likely to develop mobility limitation after adjusting for potential confounders compared with those with ID/DD genotypes (adjusted rate ratio, 1.45, 95% confidence interval, 1.08-1.94). The gene association was especially strong among participants reporting weightlifting. Exploration of possible physiological correlates revealed that among active participants, those with the II genotype had higher percentage of body fat (P = .02) and more intermuscular thigh fat (P = .02) but had similar quadriceps strength as those with ID/DD. Conclusions Among older individuals who exercised, those with the ACE DD or ID genotypes were less likely to develop mobility limitation than those with the II genotype. Regardless of genotype, individuals who exercised were less likely to develop mobility limitation than those who did not exercise. [ABSTRACT FROM AUTHOR]

Background Diabetes mellitus (DM) and related complications may increase clinical fracture risk in older adults. Methods Our objectives were to determine if type 2 diabetes mellitus or impaired fasting glucose was associated with higher fracture rates in older adults and to evaluate how diabetic individuals with fractures differed from those without fractures. The Health, Aging, and Body Composition Study participants were well-functioning, community-dwelling men and women aged 70 to 79 years (N = 2979; 42% black), of whom 19% had DM and 6% had impaired fasting glucose at baseline. Incident nontraumatic clinical fractures were verified by radiology reports for a mean ± SD of 4.5 ± 1.1 years. Cox proportional hazards regression models determined how DM and impaired fasting glucose affected subsequent risk of fracture. Results Diabetes mellitus was associated with elevated fracture risk (relative risk, 1.64; 95% confidence interval, 1.07-2.51) after adjustment for a hip bone mineral density (BMD) and fracture risk factors. Impaired fasting glucose was not significantly associated with fractures (relative risk, 1.34; 95% confidence interval, 0.67-2.67). Diabetic participants with fractures had lower hip BMD (0.818 g/cm2 vs 0.967 g/cm2; P<.001) and lean mass (44.3 kg vs 51.7 kg) and were more likely to have reduced peripheral sensation (35% vs 14%), transient ischemic attack/stroke (20% vs 8%), a lower physical performance battery score (5.0 vs 7.0), and falls (37% vs 21%) compared with diabetic participants without fractures (P<.05). Conclusions These results indicate that older white and black adults with DM are at higher fracture risk compared with nondiabetic adults with a similar BMD since a higher risk of nontraumatic fractures was found after adjustment for hip BMD. Fracture prevention needs to target specific risk factors found in older adults with DM. [ABSTRACT FROM AUTHOR]

Background The metabolic syndrome is a disorder that includes dyslipidemia, insulin resistance, and hypertension and is associated with an increased risk of diabetes and cardiovascular disease. We determined whether patterns of regional fat deposition are associated with metabolic syndrome in older adults. Methods A cross-sectional study was performed that included a random, population-based, volunteer sample of Medicare-eligible adults within the general communities of Pittsburgh, Pa, and Memphis, Tenn. The subjects consisted of 3035 men and women aged 70 to 79 years, of whom 41.7% were black. Metabolic syndrome was defined by Adult Treatment Panel III criteria, including serum triglyceride level, high-density lipoprotein cholesterol level, glucose level, blood pressure, and waist circumference. Visceral, subcutaneous abdominal, intermuscular, and subcutaneous thigh adipose tissue was measured by computed tomography. Results Visceral adipose tissue was associated with the metabolic syndrome in men who were of normal weight (odds ratio, 95% confidence interval: 2.1, 1.6-2.9), overweight (1.8, 1.5-2.1), and obese (1.2, 1.0-1.5), and in women who were of normal weight (3.3, 2.4-4.6), overweight (2.4, 2.0-3.0), and obese (1.7, 1.4-2.1), adjusting for race. Subcutaneous abdominal adipose tissue was associated with the metabolic syndrome only in normal-weight men (1.3, 1.1-1.7). Intermuscular adipose tissue was associated with the metabolic syndrome in normal-weight (2.3, 1.6-3.5) and overweight (1.2, 1.1-1.4) men. In contrast, subcutaneous thigh adipose tissue was inversely associated with the metabolic syndrome in obese men (0.9, 0.8-1.0) and women (0.9, 0.9-1.0). Conclusion In addition to general obesity, the distribution of body fat is independently associated with the metabolic syndrome in older men and women, particularly among those of normal body weight. [ABSTRACT FROM AUTHOR]

Context Several studies have reported an association between the metabolic syndrome and cardiovascular disease. Despite an increasing awareness that cardiovascular risk factors increase risk of cognitive decline and dementia, there are few data on the metabolic syndrome and cognition. Objective To determine if the metabolic syndrome is a risk factor for cognitive decline and if this association is modified by inflammation. Design and Setting A 5-year prospective observational study conducted from 1997 to 2002 at community clinics at 2 sites. Participants A total of 2632 black and white elders (mean age, 74 years). Main Outcome Measures Association of the metabolic syndrome (measured using National Cholesterol Education Program guidelines) and high inflammation (defined as above median serum level of interleukin 6 and C-reactive protein) with change in cognition (Modified Mini-Mental State Examination [3MS]) at 3 and 5 years. Cognitive impairment was defined as at least a 5-point decline. Results Compared with those without the metabolic syndrome (n = 1616), elders with the metabolic syndrome (n = 1016) were more likely to have cognitive impairment (26% vs 21%, multivariate adjusted relative risk [RR], 1.20; 95% confidence interval [CI], 1.02-1.41). There was a statistically significant interaction with inflammation and the metabolic syndrome (P = .03) on cognitive impairment. After stratifying for inflammation, those with the metabolic syndrome and high inflammation (n = 348) had an increased likelihood of cognitive impairment compared with those without the metabolic syndrome (multivariate adjusted RR, 1.66; 95% CI, 1.19-2.32). Those with the metabolic syndrome and low inflammation (n = 668) did not exhibit an increased likelihood of impairment (multivariate adjusted RR, 1.08; 95% CI, 0.89-1.30). Stratified multivariate random-effects models demonstrated that participants with the metabolic syndrome and high inflammation had greater 4-year decline on 3MS (P = .0... [ABSTRACT FROM AUTHOR]

Background: Recommendations to treat older adults with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) for the primary prevention of coronary heart disease events are supported by a single clinical trial restricted to adults 73 years or younger with low levels of high-density lipoprotein cholesterol. Methods: We investigated the association of statin use with incident cardiovascular disease and all-cause mortality during up to 7.3 years' follow-up of 1250 women and 664 men from the Cardiovascular Health Study. Study participants were 65 years and older and free of cardiovascular disease at baseline. They received drug therapy to lower cholesterol levels at baseline or no treatment with a recommendation for therapy according to the National Cholesterol Education Program guidelines. Use of these drugs was assessed annually. We used proportional-hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for confounding variables. Results: We found 382 incident cardiovascular events (159 myocardial infarctions, 159 strokes, and 64 deaths due to coronary heart disease) and 362 total deaths from June 1, 1989, to May 31, 1997. Compared with no use of drugs to lower cholesterol levels, statin use was associated with decreased risk of cardiovascular events (multivariate HR, 0.44; 95% CI, 0.27-0.71) and all-cause mortality (HR, 0.56; 95% CI, 0.36-0.88). Similar associations were observed among participants 74 years or older at baseline. Conclusions: Use of statins was associated with decreased risk of incident cardiovascular events among elderly adults. These findings lend support to the National Cholesterol Education Program guidelines, which recommend therapy for the lowering of cholesterol levels for older adults with hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Background: Sleep-disordered breathing (SDB) is common, but largely undiagnosed in the general population. Information on demographic patterns of SDB occurrence and its predictive factors in the general population is needed to target high-risk groups that may benefit from diagnosis. Methods: The sample comprised 5615 communitydwelling men and women aged between 40 and 98 years who were enrolled in the Sleep Heart Health Study. Data were collected by questionnaire, clinical examinations, and in-home polysomnography. Sleep-disordered breathing status was based on the average number of apnea and hypopnea episodes per hour of sleep (apnea-hypopnea index [AHI]). We used multiple logistic regression modeling to estimate cross-sectional associations of selected participant characteristics with SDB defined by an AHI of 15 or greater. Results: Male sex, age, body mass index, neck girth, snoring, and repeated breathing pause frequency were independent, significant correlates of an AHI of 15 or greater. People reporting habitual snoring, loud snoring, and frequent breathing pauses were 3 to 4 times more likely to have an AHI of 15 or greater vs an AHI less than 15, but there were weaker associations for other factors with an AHI of 15 or greater. The odds ratios (95% confidence interval) for an AHI of 15 or greater vs an AHI less than 15 were 1.6 and 1.5, respectively, for 1-SD increments in body mass index and neck girth. As age increased, the magnitude of associations for SDB and body habitus, snoring, and breathing pauses decreased. Conclusions: A significant proportion of occult SDB in the general population would be missed if screening or case finding were based solely on increased body habitus or male sex. Breathing pauses and obesity may be particularly insensitive for identifying SDB in older people. A better understanding of predictive factors for SDB, particularly in older adults, is needed. [ABSTRACT FROM AUTHOR]

Presents a study of how sleep-disordered breathing and sleep apnea affect hypertension. Design and setting; Participants; Main outcome measures; Results; Conclusions.

Presents a letter to the editor in reply to Drs. O'Rourke and Safar and focuses on the role of systolic blood pressure and pulse pressure in predicting mortality in chronic kidney disease.