Measures of arterial stiffness and wave reflection are associated with walking distance in patients with peripheral arterial disease

We hypothesized that measures of arterial stiffness and wave reflection influence functional capacity of patients with peripheral arterial disease (PAD). Consecutive patients (n=106, 69+/-10 years, 66% men) referred for lower extremity arterial evaluation were studied. Radial artery pulse waveforms were obtained by applanation tonometry and an ascending aortic pressure waveform derived by a transfer function. Aortic augmentation index (AIx) is the difference between the first and second systolic peak of the ascending aortic pressure waveform indexed to the pulse pressure (PP) and T(r) is the reflected wave arrival time. Ankle-brachial index (ABI) and walking distance were measured as per laboratory protocol after excluding patients with non-compressible vessels (ABI>1.5) and severe PAD (ABI<0.5). To account for right-censoring of walking distances in patients completing the 5 min walk (n=56), we used survival analysis to identify variables associated with walking distance. Mean (+/-S.D.) values were: AIx, 31.2+/-10.9%; T(r), 134+/-18 ms; PP, 66.5+/-17.1 mmHg; ABI, 0.87+/-0.22; walking distance, 177+/-75 m. In both multivariable accelerated failure time (AFT) and Cox proportional-hazards models, older age, female sex, greater body mass index, lower ABI, and a measure of arterial stiffness (higher AIx and PP, lower T(r)) were associated with a lower walking distance. Higher AIx and lower T(r) were associated with a lower walking distance even after adjustment for PP as well as in the subset of patients with PAD (ABI<0.9 at rest or post-exercise, n=82). In conclusion, measures of arterial stiffness and wave reflection are associated with walking distance in patients with PAD and may be a target of therapy in such patients.     

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.     

Limb hemodynamics are not predictive of functional capacity in patients with PAD

To the practicing clinician, it seems obvious that limb hemodynamics would be the primary determinant of walking distance. However, other determinants, such as skeletal muscle metabolism, may play a role. Accordingly, in the current study, we examined the relationship between measures of limb hemodynamics and walking capacity in patients with peripheral arterial disease (PAD). We measured toe and ankle pressures for calculation of toe- (TBI) and ankle (ABI)-brachial indices; basal and hyperemic calf blood flow (CBF; by plethysmography); and initial (ICT) and absolute (ACT) claudication time using the Skinner-Gardner protocol. As expected, PAD patients had impaired limb hemodynamics with reduced TBI, ABI and a reduction in ABI post-exercise. However, there was no relationship between any of the hemodynamic variables (including ABI, ABI reduction post-exercise, TBI, baseline or maximal CBF) and walking distance as assessed by ICT or ACT. A subset of PAD patients with an ACT >750s (n = 16; 'long claudicators') were compared with a subset of PAD patients with an ACT <260s (n = 16; 'short claudicators'). The average ACT in the long claudicants was over fivefold greater than the short claudicators. Surprisingly, there were no differences between the two groups in any of the hemodynamic variables. There was also no relationship between the initial ABI, TBI, toe pressure, baseline or hyperemic CBF, and the improvement in ACT over the 3-month course of the study. This study found little relationship between hemodynamic variables and functional capacity in PAD. Accordingly, to assess the response to therapeutic interventions, exercise performance and functional status need to be directly measured, and cannot be predicted from hemodynamic measurements.     

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.     

Statin use and functional decline in patients with and without peripheral arterial disease.

OBJECTIVES: We determined whether statin use (vs. non-use) is associated with less annual decline in lower-extremity functioning in patients with and without lower-extremity peripheral arterial disease (PAD) over three-year follow-up. BACKGROUND: It is unclear whether statin use is associated with less functional decline in patients with PAD. METHODS: Participants included 332 men and women with an ankle brachial index (ABI) <0.90 and 212 with ABI 0.90 to 1.50. Functional outcomes included 6-min walk distance and usual and rapid-pace 4-m walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for five repeated chair rises into an ordinal score ranging from 0 to 12 (12 = best). RESULTS: Adjusting for age, race, gender, comorbidities, education, health insurance, total cholesterol/high-density lipoprotein level, body mass index, pack-years of smoking, leg symptoms, immediately previous year functioning, statin use/non-use, ABI, and change in ABI, the PAD participants using statins had less annual decline in usual-pace walking velocity (0.002 vs. -0.024 m/s/year, p = 0.013), rapid-pace walking velocity (-0.006 vs. -0.042 m/s/year, p = 0.006), 6-min walk performance (-34.5 vs. -57.9 feet/year, p = 0.088), and the summary performance score (-0.152 vs. -0.376, p = 0.067) compared with non-users. These associations were attenuated slightly by additional adjustment for high-sensitivity C-reactive protein levels. Among non-PAD participants, there were no significant associations between statin use and functional decline. CONCLUSIONS: The PAD patients on statins have less annual decline in lower-extremity performance than PAD patients who are not taking statins.     

Poorer clock draw test scores are associated with greater functional impairment in peripheral artery disease: the Walking and Leg Circulation Study II

We hypothesized that, in the absence of clinically recognized dementia, cognitive dysfunction measured by the clock draw test (CDT) is associated with greater functional impairment in men and women with peripheral artery disease (PAD). Participants were men and women aged 60 years and older with Mini-Mental Status Examination scores ≥ 24 with PAD (n = 335) and without PAD (n = 234). We evaluated the 6-minute walk test, 4-meter walking velocity at usual and fastest pace, the Short Physical Performance Battery (SPPB), and accelerometer-measured physical activity. CDTs were scored using the Shulman system as follows: Category 1 (worst): CDT score 0-2; Category 2: CDT score 3; Category 3 (best): CDT score 4-5. Results were adjusted for age, sex, race, education, ankle-brachial index (ABI), and comorbidities. In individuals with PAD, lower CDT scores were associated with slower 4-meter usual-paced walking velocity (Category 1: 0.78 meters/second; Category 2: 0.83 meters/second; Category 3: 0.86 meters/second; p-trend = 0.025) and lower physical activity (Category 1: 420 activity units; Category 2: 677 activity units; Category 3: 701 activity units; p-trend = 0.045). Poorer CDT scores were also associated with worse functional performance in individuals without PAD (usual and fast-paced walking velocity and SPPB, p-trend = 0.022, 0.043, and 0.031, respectively). In conclusion, cognitive impairment identified with CDT is independently associated with greater functional impairment in older, dementia-free individuals with and without PAD. Longitudinal studies are necessary to explore whether baseline CDT scores and changes in CDT scores over time can predict long-term decline in functional performance in individuals with and without PAD.     

N-terminal pro-B-type natriuretic peptide as an indicator of disease severity in a heterogeneous group of patients with chronic precapillary pulmonary hypertension

N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) is well established as a predictor of prognosis in patients with left ventricular dysfunction. Although a similar prognostic significance has been suggested in 1 study of right ventricular failure and idiopathic pulmonary arterial hypertension, NT-pro-BNP has not been assessed as a marker of disease severity in a more heterogenous group of patients with chronic precapillary pulmonary hypertension (PH). Hence, this study assessed plasma NT-pro-BNP and other clinical variables in 61 consecutively recruited patients with various forms of chronic precapillary PH. Right-sided cardiac catheterization and cardiopulmonary exercise testing were performed at baseline, and the prognostic significance of NT-pro-BNP was investigated with a mean follow-up of 25 months. Compared with age-matched controls (n = 10), plasma NT-pro-BNP was significantly greater in those with idiopathic pulmonary arterial hypertension (n = 16), chronic precapillary PH associated with other diseases (n = 26), and chronic thromboembolic disease (n = 19) and was correlated with hemodynamic variables and functional capacity. In 17 medically treated patients, the significant decrease in NT-pro-BNP levels correlated with improved hemodynamics. During follow-up, 15 patients died from cardiopulmonary causes. Baseline NT-pro-BNP was an independent predictor of mortality. Kaplan-Meier survival analysis according to the median value of NT-pro-BNP (168 pmol/L) demonstrated a significantly higher mortality rate in those with supramedian values than in those with low plasma levels (p = 0.010). In conclusion, these findings suggest that in a heterogenous group of patients with chronic precapillary PH, plasma NT-pro-BNP can be used to determine the clinical severity of disease and is independently associated with long-term mortality.     

The relationship between lower extremity functional strength and severity of peripheral arterial disease

The purposes of this study were to (1) determine if peripheral arterial disease (PAD) severity is related to deficits in lower extremity functional strength, (2) identify covariates that might affect the relationship between lower extremity functional strength and severity of PAD, and (3) determine if the relationship between lower extremity functional strength and severity of PAD still persists after statistically controlling for significant covariates. A total of 144 patients were grouped into tertiles according to disease severity. Patients having an ankle-brachial index (ABI) of 0.76 to 0.90 were classified as having mild PAD (high ABI group), 0.51 to 0.75 classified as having moderate PAD (moderate ABI group), and 0.36 to 0.50 as having severe PAD (low ABI group). Lower extremity functional strength was assessed using the chair-stand test where the time to complete 5 consecutive stand-to-sit transfers was recorded. Patients were also characterized on ambulatory function and clinical characteristics. The moderate ABI group took significantly (p < 0.05) less time (13.49 +/- 0.49 s) to complete the chair-stand test than the low ABI group (15.86 +/- 0.63 s). Both daily physical activity level and total 6-minute walk distance were identified as significant covariates (p < 0.05) of lower extremity functional strength. After controlling for daily physical activity level and total 6-minute walk distance, no significant differences (p > 0.05) in the time to complete the chair-stand test existed between the ABI groups. These findings indicate that the greater impairment in lower extremity functional strength in patients with severe PAD is explained by their lower physical activity level and poorer overall walking ability.     

Inflammatory and thrombotic blood markers and walking-related disability in men and women with and without peripheral arterial disease

OBJECTIVES: To determine whether higher circulating levels of thrombotic and inflammatory markers are associated with greater disability. DESIGN: Cross-sectional. SETTING: Academic medical center. PARTICIPANTS: A total of 346 men and women with peripheral arterial disease (PAD) and 203 without PAD. MEASUREMENTS: Disability measures were the Walking Impairment Questionnaire (WIQ) distance, speed, and stair-climbing scores and the 36-item Short-Form (SF-36) physical functioning score. The SF-36 and WIQ are scored on a 0 to 100 scale (100=best). RESULTS: In persons with PAD, higher D-dimer levels were associated with lower WIQ speed scores (P<.001), lower stair-climbing scores (P<.04), and poorer SF-36 physical functioning scores (P<.01), adjusting for known and potential confounders. In participants without PAD, higher D-dimer levels were associated with lower WIQ distance scores (P<.03), lower speed scores (P<.05), and poorer SF-36 physical functioning scores (P<.02). Higher high-sensitivity C-reactive protein (hsCRP) levels were associated with lower WIQ distance (P<.02) and speed scores (P<.001) in persons without PAD. Most of these associations were attenuated after additional adjustment for objectively measured functional limitations. CONCLUSION: Higher circulating D-dimer and hsCRP levels are associated with greater disability in walking and physical functioning in individuals with and without PAD. Physiological changes that result in walking disability may mediate these associations.     

Serum bilirubin level is negatively correlated with disease progression of peripheral arterial disease: an observational cohort study

We determined whether low bilirubin level is a risk factor for peripheral arterial disease (PAD). We recruited 318 patients with PAD and 100 healthy volunteers. Patients were divided into 4 groups by the Fontaine classification for PAD, namely, group 1 (grade 1, n = 4); group 2 (grade 2, n = 114), group 3 (grade 3, n = 164), and group 4 (grade 4, n = 36). Total bilirubin (T-BIL), direct bilirubin (D-BIL), and indirect bilirubin (I-BIL) levels were compared using stepwise multiple regressions adjusted for selected factors. After adjusting for gender, age, smoking, and diastolic blood pressure, serum levels of T-BIL, D-BIL, and I-BIL were significantly lower in the PAD group (P < .05). Patients with grade 4 PAD showed significantly (P < .05) lower levels of T-BIL when compared with grade 2 patients. We concluded that serum bilirubin levels are negatively correlated with the severity and progression of PAD.     

Effect of peripheral arterial disease on functional and clinical outcomes in patients with heart failure (from HF-ACTION)

Patients with peripheral arterial disease (PAD) have lower functional capacity and worse clinical outcomes than age- and gender-matched patients. Few data exist on the relation of PAD to functional and clinical outcomes in patients with heart failure (HF). We sought to compare patients with HF with and without PAD for baseline functional capacity, response to exercise training, and clinical outcomes. HF-ACTION was a randomized controlled trial comparing usual care to structured exercise training plus usual care in patients with HF and an ejection fraction ≤35% and New York Heart Association class II to IV HF symptoms. Cardiopulmonary exercise testing occurred at enrollment, 3 months, and 1 year. Clinical follow-up occurred up to 4 years. Of the 2,331 HF-ACTION patients, 157 (6.8%) had PAD. At baseline, patients with HF and PAD had a shorter exercise duration (8.0 vs 9.8 minutes, p <0.001), lower peak oxygen consumption (12.5 vs 14.6 ml/kg/min, p <0.001), and shorter 6-minute walking distance (306 vs 371 m, p <0.001) compared to patients with HF without PAD. At 3 months patients with HF and PAD had less improvement on cardiopulmonary exercise testing (exercise duration 0.5 vs 1.1 minutes, p = 0.002; mean change in peak oxygen consumption 0.1 vs 0.6 ml/kg/min, p = 0.04) compared to patients with HF without PAD. PAD was an independent predictor of all-cause death or hospitalization (hazard ratio 1.31, 95% confidence interval 1.06 to 1.62, p = 0.011). Patients with PAD and HF had deceased baseline exercise capacity and decreased response to exercise training. In conclusion, PAD is an independent predictor of all-cause death or hospitalization in patients with HF.     

Effect of cilostazol on treadmill walking,community-based walking ability,and health-related quality of life in patients with intermittent claudication due to peripheral arterial disease: meta-analysis of six randomized controlled trials

OBJECTIVES: To assess whether cilostazol, a phosphodiesterase III inhibitor, improves treadmill and community-based walking ability and health-related quality of life (HQL) in patients with intermittent claudication resulting from peripheral arterial disease (PAD). DESIGN: Retrospective meta-analysis of data pooled from six Phase 3, multicenter, double-blind, placebo-controlled, parallel-group, randomized studies. SETTING: Patients were recruited from outpatient ambulatory medical care facilities. PARTICIPANTS: Patients' (n = 1,751) mean age +/- standard deviation was 65 +/- 9, and they had a history of PAD for 6 months or longer and an ankle brachial index (ABI) of 0.90 or less. INTERVENTION: Cilostazol 50 mg bid or 100 mg bid for 12, 16, or 24 weeks. MEASUREMENTS: ABI; maximal walking distance (MWD); pain-free walking distance on a graded and constant-load treadmill; and HQL, measured using the Walking Impairment Questionnaire (WIQ) and the Medical Outcomes Study Short Form-36 (SF-36). RESULTS: Maximal treadmill walking distance improved more in both cilostazol groups than in the placebo group (both P <.0001). WIQ and SF-36 physical summary scores improved significantly more with cilostazol than with placebo (for instance, WIQ distance score, P <.0001 and SF-36 physical summary score, P <.0001, comparing persons taking cilostazol with controls). Improved MWD correlated with improvements in WIQ (correlation with distance score, r = 0.34, P <.0001) and SF-36 physical summary scores (r = 0.29, P <.0001). CONCLUSIONS: Treatment with cilostazol was associated with greater improvements in community-based walking ability and HQL in patients with intermittent claudication than treatment with placebo. These improvements correlated with increased MWD. This analysis of effects of cilostazol on improving walking ability in persons with claudication is the first cilostazol study focused on community-based measures of functional status and HQL. Questionnaires assessing walking ability and HQL provide important patient-based information about clinical outcomes of claudication therapy.     

Usefulness of serial N-terminal pro-B-type natriuretic peptide measurements for determining prognosis in patients with pulmonary arterial hypertension

Previous studies have shown the prognostic benefit of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in pulmonary arterial hypertension (PAH) at time of diagnosis. However, there are only limited data on the clinical utility of serial measurements of the inactive peptide NT-pro-BNP in PAH. This study examined the value of serial NT-pro-BNP measurements in predicting prognosis PAH. We retrospectively analyzed all available NT-pro-BNP plasma samples in 198 patients who were diagnosed with World Health Organization group I PAH from January 2002 through January 2009. At time of diagnosis median NT-pro-BNP levels were significantly different between survivors (610 pg/ml, range 6 to 8,714) and nonsurvivors (2,609 pg/ml, range 28 to 9,828, p <0.001). In addition, NT-pro-BNP was significantly associated (p <0.001) with other parameters of disease severity (6-minute walking distance, functional class). Receiver operating curve analysis identified ≥1,256 pg/ml as the optimal NT-pro-BNP cutoff for predicting mortality at time of diagnosis. Serial measurements allowed calculation of baseline NT-pro-BNP (i.e., intercept obtained by back-extrapolation of concentration-time graph), providing a better discrimination between survivors and nonsurvivors than NT-pro-BNP at time of diagnosis alone (p = 0.010). Furthermore, a decrease of NT-pro-BNP of >15%/year was associated with survival. In conclusion, a serum NT-pro-BNP level ≥1,256 pg/ml at time of diagnosis identifies poor outcome in patients with PAH. In addition, a decrease in NT-pro-BNP of >15%/year is associated with survival in PAH.     

Short-term change in distance walked in 6 min is an indicator of outcome in patients with chronic heart failure in clinical practice.

OBJECTIVES: The purpose of this study was to investigate the prognostic value of change in distance walked in 6 min in chronic heart failure (CHF). BACKGROUND: The strongest indication for the 6-min walking test (6MWT) is for measuring the response to therapeutic interventions in patients with CHF. Whether the increase in distance walked after a therapeutic intervention translates into improved clinical outcome is largely unknwon. METHODS: We studied 476 CHF patients with left ventricular systolic dysfunction who were referred to our institution for adjustment of heart failure therapy because of persisting or worsening symptoms. Adjustment of therapy involved four classes of drugs: angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, beta-blockers, loop diuretics, and aldosterone antagonists. A standardized 6MWT was performed at baseline and at discharge. RESULTS: After 15.2 +/- 8 days, the distance walked increased from 326 +/- 107 m to 408 +/- 109 m (+25%; p = 0.001). During a mean follow-up of 23.9 months, 94 patients died and 12 patients underwent cardiac transplantation. Among a set of variables, New York Heart Association functional class (p = 0.02), serum creatinine concentration (p = 0.01), left ventricular ejection fraction (p = 0.002), distance walked at baseline (p = 0.0002), and change in distance walked (p = 0.002) were significant independent predictors of survival. When the patients were divided into two subgroups according to the median value of the distance walked at baseline, the increase in walking distance was significantly associated with survival only in the subgroup of patients who walked <340 m at baseline. CONCLUSIONS: Our data indicate that repeating a 6MWT after drug intervention provides independent prognostic information in CHF patients with more compromised exercise capacity.     

Utility of plasma N-terminal brain natriuretic peptide as a marker of functional capacity in patients with chronic severe mitral regurgitation

Plasma levels of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) are elevated in severe mitral regurgitation, but their relation to functional capacity and cardiac remodeling is not well defined. We evaluated the role of NT-pro-BNP as a marker of functional capacity, symptoms, and cardiac remodeling in 38 patients with severe degenerative mitral regurgitation and preserved left ventricular ejection fraction. The NT-pro-BNP levels increased progressively with New York Heart Association (NYHA) functional class: NYHA class I (geometric mean [GM] 97.1 pg/ml), NYHA class II (GM 169.8 pg/ml), and NYHA III (GM 457.6 pg/ml; p = 0.015). The end-systolic volume index (r = 0.52, p = 0.001), end-diastolic volume index (r = 0.46, p = 0.003), left atrial volume index (r = 0.4, p = 0.01), regurgitant volume index (r = 0.38, p = 0.02), regurgitant fraction (r = 0.46, p = 0.003), and end-diastolic sphericity index (r = 0.56, p <0.001) all correlated significantly with NT-pro-BNP. The NT-pro-BNP levels correlated significantly with the exercise parameters: maximum oxygen uptake (r = -0.6, p <0.001), exercise time (r = -0.52, p <0.001), and oxygen pulse (r = -0.57, p <0.001). In contrast, only weak correlations were obtained between the exercise and echocardiographic variables. NT-pro-BNP was a strong independent predictor of maximum oxygen uptake (p = 0.001). In conclusion, the results of this study have demonstrated that NT-pro-BNP increases progressively with worsening symptoms, is linked to the extent of LV remodeling, and is an independent predictor of functional capacity. NT-pro-BNP may have a role in the optimal treatment of patients with severe mitral regurgitation.     

Depressive symptoms and lower extremity functioning in men and women with peripheral arterial disease

OBJECTIVE: Factors associated with impaired functioning in patients with lower extremity peripheral arterial disease (PAD) are not fully understood. The purpose of this study was to determine the relationship between depressive symptoms and objective measures of lower extremity functioning in persons with PAD. DESIGN: Cross-sectional. PATIENTS/PARTICIPANTS: Four hundred twenty-three men and women with PAD identified from 3 Chicago area medical centers. MEASUREMENTS AND MAIN RESULTS: PAD was defined as ankle brachial index (ABI) <0.90. The Geriatric Depression Scale short form (GDS-S) (0-15 scale, 15 = worst) was completed by all participants. A clinically significant number of depressive symptoms was defined as a GDS-S score >or=6. Six-minute walk distance and usual-and fast-pace walking velocity were determined for all participants. A GDS-S score >or=6 was present in 21.7% of participants with PAD. Adjusting for age, increasing numbers of depressive symptoms were associated with an increasing prevalence of leg pain on exertion and rest (P =.004). Adjusting for age, sex, race, ABI, number of comorbidities, current smoking, and antidepressant medications, increasing numbers of depressive symptoms were associated with shorter 6-minute walk distance (P <.001), slower usual-pace walking velocity (P =.005), and slower fast-pace walking velocity (P =.005). These relationships were attenuated slightly after additional adjustment for presence versus absence of leg pain on exertion and rest and severity of exertional leg symptoms. CONCLUSIONS: Among men and women with PAD, the prevalence of a clinically significant number of depressive symptoms is high. Greater numbers of depressive symptoms are associated with greater impairment in lower extremity functioning. Further study is needed to determine whether identifying and treating depressive symptoms in PAD is associated with improved lower extremity functioning.     

Functional status measured by walking impairment questionnaire and cardiovascular risk prediction in peripheral arterial disease: results of the Peripheral Arteriopathy and Cardiovascular Events (PACE) study

The prognostic impact of the functional status of patients with intermittent claudication is still obscure. From the lists of seven general practitioners, we identified all subjects aged 40-80 years (n = 4352). Of those reporting leg symptoms while walking on the Rose questionnaire (n = 760), 60 had a qualifying diagnosis of peripheral arterial disease (PAD). All of them received the Walking Impairment Questionnaire (WIQ). For each patient affected by PAD, three sex- and age-matched controls were selected randomly. After a 24-month follow-up, survival curves showed that PAD patients with WIQ scores > median had a higher cardiovascular risk than controls, and patients with WIQ scores < median had an even poorer prognosis (p < 0.001 for all WIQ domains). In PAD, after adjustment for age, sex, ankle-brachial index and comorbidity, two WIQ domains (ie walking speed and stair-climbing) were associated with cardiovascular events. The cardiovascular risk of claudicants who had a score > median for at least three WIQ domains was intermediate versus the risk of controls and PAD patients with a WIQ score < median, also when adjusted for the covariates indicated above (RR = 3.26, p = 0.019). In intermittent claudication, a worse functional status entails a greater risk of ischemic events versus low functional impairment.     

European multicenter study on propionyl-L-carnitine in intermittent claudication.

OBJECTIVES: This study was performed to identify a target population of claudicants for propionyl-L-carnitine treatment. BACKGROUND: Previous studies suggest that the efficacy of propionyl-L-carnitine in intermittent claudication is greater in patients with severe functional impairment than in those with mild walking disability. METHODS: After run-in, 485 claudicant patients were randomized to placebo or propionyl-L-carnitine (1 g bid, p.o.) and then stratified on the basis of maximal walking distance (cutoff point 250 m) and maximal walking distance variability (cutoff point 25%). Treatment lasted 12 months. Walking capacity was assessed by treadmill and quality of life by a questionnaire exploring various aspects of daily life. RESULTS: In the target population, that is, patients who at baseline walked < or = 250 m and showed a maximal walking distance variability < or = 25%, per-protocol analysis showed that the effect of propinyl-L-carnitine was significantly greater than that with placebo for both maximal walking distance and initial claudication distance (ICD). In the intention-to-treat population, maximal walking distance increased by 62 +/- 14% on propionyl-L-carnitine and by 46 +/- 9% (p < 0.05) on placebo, while no difference between treatments was observed for ICD. The beneficial effect of propionyl-L-carnitine was confirmed when data of the target population were pooled with those of patients who at baseline walked < or = 250 m and showed a > 25% maximal walking distance < 50% variability. Actually, maximal walking distance increased by 98 +/- 16% in the propionyl-L-carnitine group and by only 54 +/- 10% in the placebo group (p < 0.01). The corresponding values for ICD were 99 +/- 21% and 51 +/- 8% (p < 0.05). For patients with baseline maximal walking distance > 250 m, no difference between treatments was observed. CONCLUSIONS: Claudicants with maximal walking distance < or = 250 m benefited from the use of propionyl-L-carnitine, with improvement in walking distance and quality of life. However, patients with mild functional impairment (i.e., walking distance > 250 m) showed no response to propionyl-L-carnitine.     

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.     

Reduction of N terminal-pro-brain (B-type) natriuretic peptide levels with exercise-based cardiac rehabilitation in patients with left ventricular dysfunction after myocardial infarction.

INTRODUCTION: N-terminal-pro-brain (B-type) natriuretic peptide (NT-pro-BNP) is a peptide hormone released from ventricles in response to myocyte stretch. The aim of the study was to investigate the influence of exercise training on plasma NT-pro-BNP to verify if this parameter could be used as a biological marker of left ventricular remodelling in myocardial infarction patients undergoing an exercise training programme. METHODS: Forty-four patients after myocardial infarction were enrolled into a cardiac rehabilitation programme, and were randomized in two groups of 22 patients each. Group A patients followed a 3-month exercise training programme, while group B patients received only routine recommendations. All patients underwent NT-pro-BNP assay, and cardiopulmonary exercise test before hospital discharge and after 3 months. RESULTS: In Group A, exercise training reduced NT-pro-BNP levels (from 1498+/-438 to 470+/-375 pg/ml, P=0.0026), increased maximal (VO2peak+4.3+/-2.9 ml/kg per min, P<0.001; Powermax+38+/-7, P<0.001) exercise parameters and work efficiency (Powermax/VO2peak+1.3+/-0.4 Power/ml per kg per min, P<0.001); there was also an inverse correlation between changes in NT-pro-BNP levels and in VO2peak (r=-0.72, P<0.001), E-wave (r=-0.51, P<0.001) and E/A ratio (r=0.59, P<0.001). In group B, at 3 months, no changes were observed in NT-pro-BNP levels, exercise and echocardiographic parameters. CONCLUSION: Three months exercise training in patients with moderate left ventricular systolic dysfunction after myocardial infarction induced a reduction in NT-pro-BNP levels, an improvement of exercise capacity and early left ventricular diastolic filling, without negative left ventricular remodelling. Whether the reduction of NT-pro-BNP levels could be useful as a surrogate marker of favourable left ventricular remodelling at a later follow-up remains to be further explored.