Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: A systematic review and meta-analysis.

Growing evidence suggests chronic low-grade inflammation (LGI) as a possible mechanism underlying the aging process. Some biological and pharmaceutical compounds may reduce systemic inflammation and potentially avert functional decline occurring with aging. The aim of the present meta-analysis was to examine the association of pre-selected interventions on two established biomarkers of inflammation, interleukin-6 (IL-6), and C-reactive protein (CRP) in middle-age and older adults with chronic LGI. We reviewed the literature on potential anti-inflammatory compounds, selecting them based on safety, tolerability, acceptability, innovation, affordability, and evidence from randomized controlled trials. Six compounds met all five inclusion criteria for our systematic review and meta-analysis: angiotensin II receptor blockers (ARBs), metformin, omega-3, probiotics, resveratrol and vitamin D. We searched in MEDLINE, PubMed and EMBASE database until January 2017. A total of 49 articles fulfilled the selection criteria. Effect size of each study and pooled effect size for each compound were measured by the standardized mean difference. I2 was computed to measure heterogeneity of effects across studies. The following compounds showed a significant small to large effect in reducing IL-6 levels: probiotics (-0.68 pg/ml), ARBs (-0.37 pg/ml) and omega-3 (-0.19 pg/ml). For CRP, a significant small to medium effect was observed with probiotics (-0.43 mg/L), ARBs (-0.2 mg/L), omega-3 (-0.17 mg/L) and metformin (-0.16 mg/L). Resveratrol and vitamin D were not associated with any significant reductions in either biomarker. These results suggest that nutritional and pharmaceutical compounds can significantly reduce established biomarkers of systemic inflammation in middle-age and older adults. The findings should be interpreted with caution, however, due to the evidence of heterogeneity across the studies.

Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events.

BACKGROUND: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS. DESIGN: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events. METHODS: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events. RESULTS: In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19% resulted in higher NRI of 15.9% (95% CI 6.1 to 20.6%, p < 0.001) in men and 23.3% (95% CI 13.8 to 62.5%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0% (95% CI 2.3 to 4.2%, p = 0.567) in men and 1.1% (95% CI 1.9 to 4.0%, p = 0.483) in women. CONCLUSIONS: An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest.

The relationship between sex hormones, sex hormone binding globulin and peripheral artery disease in older persons.

OBJECTIVE: The prevalence of peripheral artery disease (PAD) increases with aging and is higher in persons with metabolic syndrome and diabetes. PAD is associated with adverse outcomes, including frailty and disability. The protective effect of testosterone and sex hormone binding globulin (SHBG) for diabetes in men suggests that the biological activity of sex hormones may affect PAD, especially in older populations. METHODS: Nine hundred and twenty-one elderly subjects with data on SHBG, testosterone (T), estradiol (E2) were selected from InCHIANTI study. PAD was defined as an Ankle-Brachial Index (ABI) < 0.90. Logistic regression models adjusted for age (Model 1), age, BMI, insulin, interleukin-6, physical activity, smoking, chronic diseases including metabolic syndrome (Model 2), and a final model including also sex hormones (Model 3) were performed to test the relationship between SHBG, sex hormones and PAD. RESULTS: The mean age (±SD) of the 419 men and 502 women was 75.0 ± 6.8 years. Sixty two participants (41 men, 21 women) had ABI < 0.90. Men with PAD had SHBG levels lower than men without PAD (p = 0.03). SHBG was negatively and independently associated with PAD in men (p = 0.028) but not in women. The relationship was however attenuated after adjusting for sex hormones (p = 0.07). The E2 was not significantly associated with PAD in both men and women. In women, but not in men, T was positively associated with PAD, even after adjusting for multiple confounders, including E2 (p = 0.01). CONCLUSIONS: Low SHBG and high T levels are significantly and independently associated with the presence of PAD in older men and women, respectively.

Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.

CONTEXT: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment.

CONTEXT: Persons with lower-extremity peripheral arterial disease (PAD) are often asymptomatic or have leg symptoms other than intermittent claudication (IC). OBJECTIVE: To identify clinical characteristics and functional limitations associated with a broad range of leg symptoms identified among patients with PAD. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 460 men and women with PAD and 130 without PAD, who were identified consecutively, conducted between October 1998 and January 2000 at 3 Chicago-area medical centers. MAIN OUTCOME MEASURES: Ankle-brachial index score of less than 0.90; scores from 6-minute walk, accelerometer-measured physical activity over 7 days, repeated chair raises, standing balance (full tandem stand), 4-m walking velocity, San Diego claudication questionnaire, Geriatric Depression Score Short-Form, and the Walking Impairment Questionnaire. RESULTS: All groups with PAD had poorer functioning than participants without PAD. The following values are for patients without IC vs those with IC. Participants in the group with leg pain on exertion and rest (n = 88) had a higher (poorer) score for neuropathy (5.6 vs 3.5; P<.001), prevalence of diabetes mellitus (48.9% vs 26.7%; P<.001), and spinal stenosis (20.8% vs 7.2%; P =.002). The atypical exertional leg pain/carry on group (exertional leg pain other than IC associated with walking through leg pain [n = 41]) and the atypical exertional leg pain/stop group (exertional leg pain other than IC that causes one to stop walking [n = 90]) had better functioning than the IC group. The group without exertional leg pain/inactive (no exertional leg pain in individual who walks

Peripheral arterial disease detection, awareness, and treatment in primary care.

CONTEXT: Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis that is common and is associated with an increased risk of death and ischemic events, yet may be underdiagnosed in primary care practice. OBJECTIVE: To assess the feasibility of detecting PAD in primary care clinics, patient and physician awareness of PAD, and intensity of risk factor treatment and use of antiplatelet therapies in primary care clinics. DESIGN AND SETTING: The PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) program, a multicenter, cross-sectional study conducted at 27 sites in 25 cities and 350 primary care practices throughout the United States in June-October 1999. PATIENTS: A total of 6979 patients aged 70 years or older or aged 50 through 69 years with history of cigarette smoking or diabetes were evaluated by history and by measurement of the ankle-brachial index (ABI). PAD was considered present if the ABI was 0.90 or less, if it was documented in the medical record, or if there was a history of limb revascularization. Cardiovascular disease (CVD) was defined as a history of atherosclerotic coronary, cerebral, or abdominal aortic aneurysmal disease. MAIN OUTCOME MEASURES: Frequency of detection of PAD; physician and patient awareness of PAD diagnosis; treatment intensity in PAD patients compared with treatment of other forms of CVD and with patients without clinical evidence of atherosclerosis. RESULTS: PAD was detected in 1865 patients (29%); 825 of these (44%) had PAD only, without evidence of CVD. Overall, 13% had PAD only, 16% had PAD and CVD, 24% had CVD only, and 47% had neither PAD nor CVD (the reference group). There were 457 patients (55%) with newly diagnosed PAD only and 366 (35%) with PAD and CVD who were newly diagnosed during the survey. Eighty-three percent of patients with prior PAD were aware of their diagnosis, but only 49% of physicians were aware of this diagnosis. Among patients with PAD, classic claudication was distinctly uncommon (11%). Patients with PAD had similar atherosclerosis risk factor profiles compared with those who had CVD. Smoking behavior was more frequently treated in patients with new (53%) and prior PAD (51%) only than in those with CVD only (35%; P <.001). Hypertension was treated less frequently in new (84%) and prior PAD (88%) only vs CVD only (95%; P <.001) and hyperlipidemia was treated less frequently in new (44%) and prior PAD (56%) only vs CVD only (73%, P<.001). Antiplatelet medications were prescribed less often in patients with new (33%) and prior PAD (54%) only vs CVD only (71%, P<.001). Treatment intensity for diabetes and use of hormone replacement therapy in women were similar across all groups. CONCLUSIONS: Prevalence of PAD in primary care practices is high, yet physician awareness of the PAD diagnosis is relatively low. A simple ABI measurement identified a large number of patients with previously unrecognized PAD. Atherosclerosis risk factors were very prevalent in PAD patients, but these patients received less intensive treatment for lipid disorders and hypertension and were prescribed antiplatelet therapy less frequently than were patients with CVD. These results demonstrate that underdiagnosis of PAD in primary care practice may be a barrier to effective secondary prevention of the high ischemic cardiovascular risk associated with PAD.

Gait alterations associated with walking impairment in people with peripheral arterial disease with and without intermittent claudication.

OBJECTIVES: To describe gait alterations associated with impaired walking endurance in patients with and without lower-extremity peripheral arterial disease (PAD) and determine whether the Caltrac accelerometer provides a valid measure of physical activity in PAD. DESIGN: Cross-sectional. SETTING: Academic medical center. PARTICIPANTS: PAD (n = 40) and non-PAD patients (n = 22) from two Chicago hospitals. MEASUREMENTS: Participants underwent measurement of the ankle brachial index (ABI), leg length, and 6-minute walk. Steps per minute and step length were measured during the first and last 100 feet of the 6-minute walk. Participants wore a Caltrac accelerometer, sensitive to vertical acceleration, during the 6-minute walk and for 7 continuous days. RESULTS: Five PAD participants (13%) and one non-PAD participant (5%) ceased walking before the end of 6 minutes. Among the remaining participants, distance walked in 6 minutes was more highly related to walking velocity during the last 100 feet of the walk than walking velocity during the first 100 feet. ABI was associated significantly with cadence (20.77 steps/minute per unit ABI, P <.001) but not step length (10.12 centimeters/unit ABI, P =.08). ABI was associated significantly with 6-minute walk distance (493 feet/unit ABI, P =.018), but this association disappeared completely after adjustment for step length and cadence. We found no difference in accelerometer scores between PAD and non-PAD participants over a fixed distance of 800 feet (7.34 vs 7.17 activity units, P =.789). However, scores were significantly different after 7 days (730.8 vs 1,485.0 activity units, P =.003). CONCLUSION: Walking performance in PAD patients who completed 6 minutes of walking was largely determined by a decline in walking velocity rather than slower initial walking velocity. ABI was more closely associated with cadence than step length. Future studies should assess the effect of exercise programs and revascularization on cadence and step length in PAD.

Prevalence and significance of unrecognized lower extremity peripheral arterial disease in general medicine practice*.

OBJECTIVE: To determine the prevalence of unrecognized lower extremity peripheral arterial disease (PAD) among men and women aged 55 years and older in a general internal medicine (GIM) practice and to identify characteristics and functional performance associated with unrecognized PAD. DESIGN: Cross-sectional. SETTING: Academic medical center. PARTICIPANTS: We identified 143 patients with known PAD from the noninvasive vascular laboratory, and 239 men and women aged 55 and older with no prior PAD history from a GIM practice. Group 1 consisted of patients with PAD consecutively identified from the noninvasive vascular laboratory (n = 143). Group 2 included GIM practice patients found to have an ankle brachial index less than 0.90, consistent with PAD (n = 34). Group 3 consisted of GIM practice patients without PAD (n = 205). MEASUREMENTS AND MAIN RESULTS: Leg functioning was assessed with the 6-minute walk, 4-meter walking velocity, and Walking Impairment Questionnaire (WIQ). Of GIM practice patients, 14% had unrecognized PAD. Only 44% of patients in Group 2 had exertional leg symptoms. Distances achieved in the 6-minute walk were 1,130, 1,362, and 1,539 feet for Groups 1, 2, and 3, respectively, adjusting for age, gender, and race (P <.001). The degree of difficulty walking due to leg symptoms as reported on the WIQ was comparable between Groups 2 and 3 and significantly greater in Group 1 than Group 2. In multiple logistic regression analysis including Groups 2 and 3, current cigarette smoking was associated independently with unrecognized PAD (odds ratio [OR], 6.82; 95% confidence interval [95% CI], 1.55 to 29.93). Aspirin therapy was nearly independently associated with absence of PAD (OR, 0.37; 95% CI, 0.12 to 1.12). CONCLUSION: Unrecognized PAD is common among men and women aged 55 years and older in GIM practice and is associated with impaired lower extremity functioning. Ankle brachial index screening may be necessary to diagnose unrecognized PAD in a GIM practice.

Peripheral arterial disease and depressed mood in older men and women.

The objective of this study was to determine whether lower extremity peripheral arterial disease (PAD) is associated with depressive symptoms and whether PAD-related disability mediates the association between PAD and depressive symptoms. The study used a cross-sectional design set in an academic medical center. A cohort of men and women aged 55 years and older with (n = 93) or without (n = 74) PAD was recruited. PAD subjects were identified from a blood flow laboratory and a general medicine practice. Non-PAD subjects were identified from the same general medicine practice. PAD was diagnosed and quantified using the ankle-brachial index (ABI). Depressive symptoms were assessed by the 15-item short version of the Geriatric Depression Scale (GDS-S; score range 0-15, 0 = no depressive symptoms). The six-minute walk test and the Walking Impairment Questionnaire (WIQ) distance score (score range 0-100, 100 = better walking ability) were measures of walking impairment. PAD subjects had depressive mood (DM) (defined by GDS-S score >5) twice as often as controls (24% vs 12%, p = 0.06). After adjustment for age, education, and number of comorbidities, the prevalence of depressive mood among PAD subjects was increased, but this association was not significant (OR = 1.8, 95% CI 0.7-4.4). The WIQ distance score weakened the association between PAD and DM, and higher distance scores were associated with a lower likelihood of DM (OR = 0.98 per one unit of the WIQ, 95% CI 0.96-0.99). Among PAD subjects, severe PAD (ABI <0.5) was not significantly associated with DM (OR = 1.4, 95% CI 0.5-4.1), but a greater 6-min walk distance was associated with a lower likelihood of DM (OR = 0.8 per 100 feet, 95% CI 0.70-0.97). Substituting the WIQ scores for six-min walk distance in the model showed that higher WIQ scores were associated with lower likelihood of DM among PAD subjects (OR= 0.98 per one unit of the WIQ, 95% CI 0.95-1.0), though the association did not achieve statistical significance. In conclusion, these data suggest that PAD may be associated with an increased risk of DM and that this relationship may be related to PAD-associated disability. An evaluation for depression may be appropriate in men and women with PAD. Findings should be evaluated in a larger study cohort.

Lower ankle/brachial index, as calculated by averaging the dorsalis pedis and posterior tibial arterial pressures, and association with leg functioning in peripheral arterial disease.

OBJECTIVE: We compared three commonly used methods of ankle/brachial index (ABI) calculation to determine their relative association with objective measures of leg functioning in peripheral arterial disease. METHOD: The study design was cross-sectional; the setting was an academic medical center. The participants were 244 men and women, aged 55 years and older, with and without peripheral arterial disease, from a noninvasive vascular laboratory and a general medicine practice. The main outcome measures were walking velocity and endurance, measured with the 4-m walk and the 6-minute walk, respectively. Three methods of ABI calculation were assessed: using the highest arterial pressure within each leg (method #1), using the lowest pressure in each leg (method #2), and averaging the dorsalis pedis and posterior tibial pressures within each leg (method #3). For each method, we established the prevalence of peripheral arterial disease. We then used regression analyses to identify the ABI calculation method most closely associated with leg functioning. The ABI with the greatest statistical significance and largest regression coefficient was considered most closely associated with leg functioning. RESULTS: Peripheral arterial disease prevalence ranged from 47% when method #1 was used to 59% when method #2 was used. When the right and left legs were compared, the leg with the lower ABI, as identified through use of method #3, was most associated with leg functioning. Within the leg with the lower ABI, method #3 was more closely associated with 6-minute walk distance (regression coefficient = 811.5 feet per 1 unit ABI; P<.001) and 4-m walking velocity (regression coefficient = 0.353 m/s per 1 unit ABI; P<.001) than method #1 or method #2. CONCLUSION: The lower ABI, determined by averaging the dorsalis pedis and posterior tibial arterial pressures in each leg, is most predictive of walking endurance and walking velocity in peripheral arterial disease.

Asymptomatic peripheral arterial disease is independently associated with impaired lower extremity functioning: the women's health and aging study.

BACKGROUND: We report the implications of asymptomatic lower extremity peripheral arterial disease (PAD) for lower extremity functioning among participants in the Women's Health and Aging Study, an observational study of disabled women > or = 65 years of age living in and around Baltimore. METHODS AND RESULTS: The ankle brachial index (ABI) and measures of upper and lower extremity functioning were measured among study participants. Of 933 women with ABI < or =1. 50, 328 (31%) [corrected] had an ABI <0.90, consistent with PAD. Sixty-three percent of PAD participants had no exertional leg pain. Among participants without exertional leg pain, lower ABI levels were associated with slower walking velocity, poorer standing balance score, slower time to arise 5 times consecutively from a seated position, and fewer blocks walked per week, adjusting for age, sex, race, cigarette smoking, and comorbidities. ABI was not associated independently with measures of upper extremity functioning. CONCLUSIONS: Asymptomatic PAD is common and is independently associated with impaired lower extremity functioning. In addition to preventing cardiovascular morbidity and death, further study is warranted to identify effective interventions to improve functioning among the growing number of men and women with asymptomatic PAD.

Measuring physical activity in peripheral arterial disease: a comparison of two physical activity questionnaires with an accelerometer.

Peripheral arterial disease (PAD)-related exertional leg pain may limit physical activity, thereby contributing to mobility loss and increasing cardiovascular morbidity and mortality in men and women with PAD. The objectives of this study were: (1) to compare objectively measured physical activity levels between patients with and without PAD, (2) to assess the validity of two physical activity questionnaires in patients with PAD. Twenty PAD patients from a noninvasive vascular laboratory and 21 patients without PAD from a general medicine practice wore an accelerometer continuously for 7 days to measure physical activity objectively. After 7 days, participants completed the leisure time physical activity questionnaire (LTPAQ), derived from the Health Interview Survey, (continued on next page)and the Stanford 7-day physical activity recall questionnaire (PARQ). PAD participants had markedly lower physical activity levels than non-PAD participants as measured by accelerometer (803 kcal/week +/-364 (range=284-2,000, median=708) vs 1,750 kcal/week +/-1,296 (range=882-6,586, median=1,278), p<0.001). For the LTPAQ, physical activity levels in PAD and non-PAD participants were 609 kcal/week +/-576 (range=0-2,085, median=529) vs 832 kcal/week +/-784 (range=53-2,820, median= 623), p=0.128. For the PARQ, physical activity levels in PAD and non-PAD participants were 234 METS/week +/-21 (range=214-301, median=229) vs 238 METS/week +/- 11 (range=225-268, median=234), p=0.454, respectively. Pearson's correlation coefficient for the association between the accelerometer and the log-transformed LTPAQ measure was 0.419 (p=0.006). Pearson's correlation coefficient was 0.348 for the association between the accelerometer and the log-transformed PARQ measure of physical activity (p=0.026). In conclusion, PAD patients have significantly lower physical activity levels than non-PAD patients. Two commonly used physical activity questionnaires were less sensitive than objective measurement to the association between PAD and inactivity.

Use of learning contracts in an office-based primary care clerkship.

OBJECTIVES: This paper describes implementation of the learner-centred learning goal within the primary care clerkship at a Midwestern, United States medical school. DESIGN: The learner-centred learning goal exercise was developed to tailor students' educational activities to their personal level of development and to enhance their commitment to life-long learning in medicine. In the learner-centred learning goal exercise, each student records three specific learning goals early in the primary care clerkship. Students record the methods by which they will pursue and document achievement of each goal. Attainment of the learner-centred learning goal is evaluated based on an oral presentation at the end of the clerkship. We compiled presented learning goals along with the corresponding grade. Students' ratings of the learner-centred learning goal exercise were also compiled. Evaluations and ratings were made on a 1-5 Likert scale, where 1 is the best rating and 5 is worst. SETTING: Department of Medicine, Northwestern University Medical School, Chicago, USA. SUBJECTS: One hundred and seventy-seven third- and fourth-year medical students who presented learner-centred learning goals between 1 July 1995 and 30 June 1996. RESULTS: Students rated pursuing their individual learning goals more worthwhile than most clerkship lectures but less worthwhile than the office experience. Several learning goals were chosen by a disproportionate number of students, potentially indicative of some perceived deficiencies elsewhere in the curriculum. Third-year students ranked the learner-centred learning goal exercise more favourably than fourth-year students (2.14 vs. 2. 51, P = 0.03). CONCLUSIONS: The learner-centred learning goal exercise is a feasible and well-received method within our primary care clerkship. Further study is required to determine whether the exercise promotes independent learning after formal medical school education is completed.

Leg symptoms, the ankle-brachial index, and walking ability in patients with peripheral arterial disease.

OBJECTIVE: To determine how functional status and walking ability are related to both severity of lower extremity peripheral arterial disease (PAD) and PAD-related leg symptoms. DESIGN: Cross-sectional study. SETTING: Academic medical center. PARTICIPANTS: Patients aged 55 years and older diagnosed with PAD in a blood flow laboratory or general medicine practice (n = 147). Randomly selected control patients without PAD were identified in a general medicine practice (n = 67). MEASUREMENTS: Severity of PAD was measured with the ankle-brachial index (ABI). All patients were categorized according to whether they had (1) no exertional leg symptoms; (2) classic intermittent claudication; (3) exertional leg symptoms that also begin at rest (pain at rest), or (4) exertional leg symptoms other than intermittent claudication or pain at rest (atypical exertional leg symptoms). Participants completed the 36-Item Short-Form Health Survey (SF-36) and the Walking Impairment Questionnaire (WIQ). The WIQ quantifies patient-reported walking speed, walking distance, and stair-climbing ability, respectively, on a scale of 0 to 100 (100 = best). MAIN RESULTS: In multivariate analyses patients with atypical exertional leg symptoms, intermittent claudication, and pain at rest, respectively, had progressively poorer scores for walking distance, walking speed, and stair climbing. The ABI was measurably and independently associated with walking distance (regression coefficient = 2.87/0.1 ABI unit, p =.002) and walking speed (regression coefficient = 2.09/0.1 ABI unit, p =.015) scores. Among PAD patients only, pain at rest was associated independently with all WIQ scores and six SF-36 domains, while ABI was an independent predictor of WIQ distance score. CONCLUSIONS: Both PAD-related leg symptoms and ABI predict patient-perceived walking ability in PAD.

Impact of same-day screening mammography availability: results of a controlled clinical trial.

BACKGROUND: We conducted a prospective controlled clinical trial in an urban academic general medicine practice to test the effect of same-day mammography availability on adherence to physicians' screening mammography recommendations. PATIENTS AND METHODS: Participants were a consecutive sample of 920 female patients aged 50 years or older who had received a physician's recommendation for screening mammography at an office visit and had no active breast symptoms, history of breast cancer, or a mammogram within the previous 12 months. Women were assigned to same-day screening mammography availability (intervention group) or usual screening mammography scheduling (control group). MAIN OUTCOME MEASURES: Three-, 6-, and 12-month rates of adherence to physicians' recommendations for screening mammography. RESULT: Twenty-six percent of women in the intervention group obtained a same-day screening mammogram. At 3 months, 58% of the women in the intervention group underwent the recommended screening mammography compared with 43% of the women in the control group (P<.001), increasing to 61% and 49% at 6 months (P<.001), and 268 (66%) of 408 vs 287 (56%) of 512 at 12 months (P = .003). The difference between the intervention and control groups 3-month adherence rates was most marked among women aged 65 years or older (58% vs 34%; P<.001), women who were not employed (54% vs 36%; P<.001), and women with a history of having had either no mammograms (39% vs 20%; P = .02) or only 1 to 2 mammograms (57% vs 38%; P<.001) within the last 5 years. CONCLUSIONS: Same-day mammography availability increased 3-, 6-, and 12-month screening mammography adherence rates in this urban academic general medicine practice. The effect was most marked among women aged 65 years or older, women who were not employed, and those who had had fewer than 3 mammograms in the last 5 years. The efficacy of this intervention in other settings still needs to be demonstrated.

Exertional leg symptoms other than intermittent claudication are common in peripheral arterial disease.

BACKGROUND: Epidemiological data show that most community-dwelling men and women with lower-extremity peripheral arterial disease (PAD) do not have typical symptoms of intermittent claudication. We compared the prevalence of intermittent claudication, leg symptoms other than intermittent claudication, and absence of exertional leg symptoms between patients with PAD identified from a blood flow laboratory (group 1), patients with PAD in a general medicine practice (group 2), and control patients without PAD (group 3). METHODS: Numbers of participants in groups 1, 2, and 3 were 137, 26, and 105, respectively. Patients with previously diagnosed PAD were excluded from groups 2 and 3. All participants underwent ankle-brachial index measurement and were administered the San Diego claudication questionnaire to assess leg symptoms. RESULTS: Within groups 1, 2, and 3, prevalences of intermittent claudication were 28.5% (n = 39), 3.8% (n = 1), and 3.8% (n= 4), respectively. Prevalences of exertional leg symptoms other than intermittent claudication were 56.2% (n= 77), 42.3% (n= 11), and 19.0% (n = 20), respectively. Absence of exertional leg symptoms was reported by 15.3% (n= 21), 53.8% (n= 14), and 77.1% (n=81), respectively. Among patients with PAD, older age, male sex, diabetes mellitus, and group 2 vs group 1 status were associated independently with absence of exertional leg symptoms in multivariable regression analysis. Lower ankle-brachial index levels and group 1 vs group 2 status were associated with intermittent claudication. CONCLUSIONS: Clinical manifestations of PAD are diverse, particularly among patients identified by ankle-brachial index screening. Exertional leg symptoms other than intermittent claudication are common in PAD. Patients with PAD who are older, male, diabetic, or identified with ankle-brachial index screening in a primary care setting are more likely to have asymptomatic PAD.

Measurement of walking endurance and walking velocity with questionnaire: validation of the walking impairment questionnaire in men and women with peripheral arterial disease.

OBJECTIVES: The Walking Impairment Questionnaire (WIQ) was designed to measure community walking ability in patients with peripheral arterial disease (PAD) and intermittent claudication. We compared the WIQ scores to objective measures of walking in a heterogeneous group of patients with and without PAD. METHODS: The study was designed as a cross-sectional study, with the setting in an academic medical center. The subjects were patients with PAD (n = 145) who were identified from a noninvasive vascular laboratory at an academic medical center. The patients without PAD (n = 65) were identified from a general medicine practice. The average number of comorbidities was 2.03 for patients with PAD and 1.52 for patients without PAD. Among the patients with PAD, 28% had classical intermittent claudication symptoms and 55% had exertional leg symptoms other than claudication. The main outcome measures were the WIQ estimates of the patient-reported walking distance and walking speed on a scale of 0 to 100. Walking endurance was measured objectively with the 6-minute walk. Walking velocity was measured with a 4-m walk. PAD and PAD severity were defined with the ankle brachial index. RESULTS: The Spearman rank correlation coefficients (rho) between the WIQ distance score and the 6-minute walk score were 0.557 among patients with PAD (P <.001) and 0.484 among patients without PAD (P <.001). The correlation coefficients between the WIQ speed score and the usual-paced 4-m walk score were 0.528 among patients with PAD (P <.001) and 0.524 among patients without PAD (P <.001). The correlations were not affected by the presence versus the absence of intermittent claudication, by PAD severity, or by the presence of 2 or more versus less than 2 comorbid illnesses. The WIQ scores in the highest and lowest quartiles were the most closely associated with the objective measures of function. CONCLUSION: The WIQ is a valid measure of community walking ability in a heterogeneous group of patients with and without PAD. The WIQ discriminates best among patients in the highest and the lowest quartiles of walking speed and endurance.

The ankle brachial index independently predicts walking velocity and walking endurance in peripheral arterial disease.

OBJECTIVES: Maintaining function among older men and women is an important public health goal as the population lives longer with chronic disease. We report the relationships between lower extremity peripheral arterial disease (PAD), PAD severity, and PAD-related symptoms with walking velocity and endurance among men and women aged 55 and older. DESIGN: A cross-sectional design. SETTING: An academic medical center. PARTICIPANTS: Participants with PAD were men and women aged 55 and older identified from a blood flow laboratory or a general medicine practice (n = 158). Randomly selected controls without PAD were identified from the general medicine practice (n = 70). MEASUREMENTS: PAD was diagnosed and quantified using the ankle brachial index (ABI). Subjects were categorized according to whether they had severe PAD (ABI <0.40), mild to moderate PAD (ABI 0.40 to <0.90), or no PAD (ABI 0.90 to <1.50). Walking endurance was assessed with the 6-minute walk. Usual walking velocity and maximal walking velocity were assessed with "usual" and "maximal" paced 4-meter walks, respectively. RESULTS: Average distances achieved in the 6-minute walk were 1569+/-390 feet for subjects with ABI 0.90-1.50, 1192+/-368 feet for subjects with ABI 0.40 to <0.90, and 942+/-334 feet for subjects with ABI < 0.40 (trend P value < .001). Walking velocities for both the usual and maximal paced 4-meter walks were slowest among subjects with ABI < 0.40 and fastest among subjects with ABI 0.90 to <1.50. Subjects with PAD who had pain at rest had slower walking velocity and poorer walking endurance than other subjects with PAD. In multiple linear regression analyses that included subjects with PAD only, ABI level was an independent predictor of 6-minute walk performance (regression coefficient = 159 ft/0.40 ABI units, P = .011), usual paced 4-meter walk (regression coefficient = .095 meters/sec/0.40 ABI units, P = .031), and maximal paced 4-meter walk (regression coefficient = .120 meters/sec/0.40 ABI units, P = .050) adjusting for age, sex, race, leg symptoms, and comorbid diseases known to affect functioning. Pain at rest was associated independently with the maximally paced 4-meter walk (-0.201 meters/sec, P = .024), but not with the other walks. CONCLUSION: ABI level has a measurable and independent association with walking endurance and both usual and maximal walking velocity. These data suggest that PAD may impair lower extremity function by diminishing function of both Type I ("slow twitch") and Type II ("fast twitch") muscle fibers. Because walking velocity has important prognostic implications for functioning, these data also suggest that ABI may be used to identify patients at increased risk of mobility loss.

Patterns of angiotensin-converting enzyme inhibitor prescriptions, educational interventions, and outcomes among hospitalized patients with heart failure.

BACKGROUND: Among hospitalized patients with heart failure, we describe characteristics associated with prescription of angiotensin-converting enzyme (ACE) inhibitors in the doses recommended by clinical practice guidelines. We also describe the impact of ACE inhibitor prescriptions, increases in ACE inhibitor dose, and nonpharmacologic educational interventions on readmission-free survival rates. HYPOTHESIS: We hypothesize that care by a cardiologist physician and higher mean arterial blood pressure on admission are associated with receipt of optimal ACE inhibitor doses. We hypothesize that receipt of an ACE inhibitor at discharge and an increase in ACE inhibitor dose during hospitalization are associated with superior readmission-free survival. METHODS: Between January 1, 1992, and December 31, 1993, medical records were reviewed for consecutively hospitalized patients with a principal diagnosis of heart failure at an academic medical center. Documented instructions and medications prescribed at discharge were abstracted. Deaths and readmissions through December 31, 1994, were identified with the National Death Index and the study institution's administrative data base, respectively. RESULTS: During 1992 and 1993, 387 patients were discharged alive from hospitalization for heart failure. Among patients discharged on enalapril or captopril, 18% received doses recommended by heart failure clinical practice guidelines. Patients discharged on a recommended ACE inhibitor dose were more likely to be African-American and had lower sodium levels and higher mean arterial pressures than patients discharged on lower ACE inhibitor doses. In survival analyses, an increase in ACE inhibitor dose was associated with improved readmission-free survival, independent of left ventricular systolic function type. Receipt of an ACE inhibitor at discharge was also associated with superior readmission-free survival, while nonpharmacologic educational instructions were not associated with improved outcomes. CONCLUSION: Interventions are needed to improve the frequency with which ACE inhibitors are prescribed at recommended doses to hospitalized patients with heart failure. We conclude that among these patients, receipt of an ACE inhibitor at discharge and an increase in ACE inhibitor dose during hospitalization are each associated with measurable effects on readmission-free survival, while provision of educational instructions as currently practiced is not associated with better outcomes.