Clot strength is negatively associated with ambulatory function in patients with peripheral artery disease and intermittent claudication.

Peripheral artery disease (PAD) is associated with exercise impairment and greater thrombotic risk. We investigated whether clot formation and platelet aggregation assessed by thromboelastography and light-transmission aggregometry correlate with the severity of symptomatic PAD assessed by ambulatory function measures. We studied 40 symptomatic patients with PAD in whom severity of disease was assessed using ankle-brachial index, peak walking time (PWT), claudication onset time, peak oxygen uptake, daily ambulatory activity, and walking impairment questionnaire (WIQ) scores. Clot strength correlated negatively with peak oxygen uptake, PWT, WIQ distance, and stair-climbing scores. Time to clot formation did not correlate with exercise parameters. Platelet aggregation was negatively correlated with WIQ distance score and was positively correlated with PWT and peak oxygen uptake. In conclusion, clot strength and platelet aggregation correlated with objective and self-perceived ambulatory measures. Patients with PAD having more severe walking impairment may be likely to form stronger clots.

Step-monitored home exercise improves ambulation, vascular function, and inflammation in symptomatic patients with peripheral artery disease: a randomized controlled trial.

BACKGROUND: This prospective, randomized, controlled clinical trial compared changes in primary outcome measures of claudication onset time (COT) and peak walking time (PWT), and secondary outcomes of submaximal exercise performance, daily ambulatory activity, vascular function, inflammation, and calf muscle hemoglobin oxygen saturation (StO2) in patients with symptomatic peripheral artery disease (PAD) following new exercise training using a step watch (NEXT Step) home-exercise program, a supervised exercise program, and an attention-control group. METHODS AND RESULTS: One hundred eighty patients were randomized. The NEXT Step program and the supervised exercise program consisted of intermittent walking to mild-to-moderate claudication pain for 12 weeks, whereas the controls performed light resistance training. Change scores for COT (P<0.001), PWT (P<0.001), 6-minute walk distance (P=0.028), daily average cadence (P=0.011), time to minimum calf muscle StO2 during exercise (P=0.025), large-artery elasticity index (LAEI) (P=0.012), and high-sensitivity C-reactive protein (hsCRP) (P=0.041) were significantly different among the 3 groups. Both the NEXT Step home program and the supervised exercise program demonstrated a significant increase from baseline in COT, PWT, 6-minute walk distance, daily average cadence, and time to minimum calf StO2. Only the NEXT Step home group had improvements from baseline in LAEI, and hsCRP (P<0.05). CONCLUSIONS: NEXT Step home exercise utilizing minimal staff supervision has low attrition, high adherence, and is efficacious in improving COT and PWT, as well as secondary outcomes of submaximal exercise performance, daily ambulatory activity, vascular function, inflammation, and calf muscle StO2 in symptomatic patients with PAD. CLINICAL TRIAL REGISTRATION URL: ClinicalTrials.gov. Unique Identifier: NCT00618670.

Monitored daily ambulatory activity, inflammation, and oxidative stress in patients with claudication.

We determined the association between daily ambulatory activity and markers of inflammation and oxidative stress in patients with peripheral artery disease (PAD) and claudication. Patients with PAD (n = 134) limited by claudication were studied. Patients took 3275 ± 1743 daily strides for 273 ± 112 minutes each day, and their average daily cadence was 11.7 ± 2.7 strides/min. High-sensitivity C-reactive protein was significantly and negatively associated with the total number of daily strides (P < .001), total daily ambulatory time (P < .01), peak activity index (P < .01), daily average cadence (P < .05), and the maximum cadences for 60 minutes (P < .05), 30 minutes (P < .05), 20 minutes (P < .05), and 5 minutes (P < .01). Oxidized low-density lipoprotein and soluble vascular cell adhesion molecule 1 were not significantly associated with any of the ambulatory measures (P > .05). We conclude that higher levels of community-based, daily ambulatory activity are associated with lower levels of inflammation but are not associated with markers of oxidative stress.

Diabetic women are poor responders to exercise rehabilitation in the treatment of claudication.

BACKGROUND: It is not clear whether subgroups of patients with peripheral artery disease (PAD) and claudication respond more favorably to exercise rehabilitation than others. We determined whether sex and diabetes were factors associated with the response to exercise rehabilitation in patients with claudication. METHODS: Eighty patients were randomized to home-based and supervised exercise programs, and 60 finished with complete exercise intervention data. Exercise consisted of intermittent walking to near maximal claudication pain for 3 months. Primary outcome measures included claudication onset time (COT) and peak walking time. Patients were partitioned into diabetic and nondiabetic groups and then further partitioned by sex to form four groups. RESULTS: Overall, exercise adherence was high (84%), and there was no significant difference (P > .05) in the amount of exercise completed among the four groups. All groups had significant improvements (P < .05) in COT and peak walking time after exercise rehabilitation, except for diabetic women (P > .05). Only 37% of women with diabetes had an increase in COT compared with 100% of men with diabetes (P < .01), and their risk ratio for nonresponse was 9.2 (P < .0001). CONCLUSIONS: Women with PAD and claudication, particularly those with diabetes, represent a vulnerable subgroup of patients who respond poorly to a program of exercise rehabilitation. Diabetic women with PAD and claudication may need a greater dose of exercise or another intervention separate from or in combination with exercise to elicit improvements in claudication measures that are similar to nondiabetic women and to diabetic and nondiabetic men.

Effects of fluid load on human urine characteristics related to workplace drug testing.

During workplace drug testing, urine is tested for dilution, substitution and adulteration. Donors argue that these findings are due to medical, health or working conditions or diet and genetic differences. There is a paucity of data correlating changes in urine characteristics after a fluid load to various body parameters. Therefore, five urine specimens (one in the morning, one prior to drinking 800 mL of a beverage, and three time intervals thereafter) from 12 males and 12 females were tested for four different beverages on separate occasions. Of the 480 samples, 376 were in sufficient amounts. Of these 376, 36 (10%) had creatinine <20 mg/dL but ≥2 mg/dL; 27 (75%) of 36 had specific gravity <1.0030 but >1.0010. Thus, these 27 samples can be considered to be dilute; 20 (74%) of 27 were from females. For males with at least one dilute sample, body fat was 11% less and resting metabolic rate (RMR) was 29% more than males with no dilute samples (p > 0.05); for females with at least one dilute sample, height was 8% less and weight 20% less than females with no dilute samples (p > 0.05). Individuals with a higher RMR appear to have a greater potential for producing dilute urine specimens than those with a lower RMR. Thus, a dilute sample does not necessarily indicate that it was intentionally diluted. Such samples must be carefully evaluated in consideration with recent consumption of liquid by donors to avoid false accusations.

Calf muscle hemoglobin oxygen saturation in patients with peripheral artery disease who have different types of exertional leg pain.

BACKGROUND: This study compared calf muscle hemoglobin oxygen saturation (Sto(2)) and exercise performance during standardized treadmill exercise in patients with peripheral artery disease (PAD) who describe different types of exertional leg pain and compared secondary outcomes consisting of daily ambulatory activity and exercise performance during a 6-minute walk test (6MWT). METHODS: Leg pain symptoms were evaluated in 114 patients with PAD using the San Diego Claudication Questionnaire, by which atypical exertional leg pain was defined in 31, claudication in 37, and leg pain on exertion and rest in 46. Patients were evaluated on a standardized, graded treadmill test during which calf muscle Sto(2) was continuously monitored. The 6MWT distance, Walking Impairment Questionnaire (WIQ), and ambulatory activity were monitored during 1 week. RESULTS: All patients experienced symptoms during the treadmill test consistent with claudication. The groups were not significantly different on the primary outcomes of time to reach the minimum calf muscle Sto(2) (P = .350) or peak walking time (P = .238) during treadmill exercise. Patients with atypical leg pain had the highest daily ambulatory activity for total strides per day (P = .032), average daily cadence (P = .010), maximum cadences for durations between 5 minutes (P = .035) and 60 minutes (P = .029), speed score on the WIQ (P = .006), and lowest rating of perceived exertion at the end of the 6MWT (P = .017). CONCLUSIONS: PAD patients with atypical leg pain have vascular-mediated limitations in exercise performance during standardized treadmill testing similar to patients with claudication and patients with leg pain on exertion and rest but have higher levels of daily ambulatory activity in the community setting and higher perceived ambulatory function.

Oxygen uptake before and after the onset of claudication during a 6-minute walk test.

OBJECTIVE: This study compared oxygen uptake before and after the onset of claudication in individuals with peripheral artery disease (PAD) during a 6-minute walk test, and identified predictors of the change in oxygen uptake after the onset of claudication pain. METHODS: The study included 50 individuals with PAD. During a 6-minute walk test, 33 experienced claudication (pain group), and 17 were pain-free (pain-free group). Oxygen uptake and ambulatory cadence were the primary outcomes evaluated during the 6-minute walk test. RESULTS: The pain group experienced onset of claudication pain at a mean (standard deviation) of 179 (45) meters and continued to walk to achieve a 6-minute walk distance of 393 (74) meters, which was similar to the 401 (76) meters walked in the pain-free group (P = .74). Oxygen uptake increased (P < .0001) after the onset of pain in the pain group, and this change was greater (P = .025) than the increase in oxygen uptake from the second to fifth minutes of walking in the pain-free group. Ambulatory cadence decreased after the onset of pain in the pain group (P = .0003). The change in oxygen uptake was associated with metabolic syndrome (P = .0023), 6-minute walk distance (P = .0037), age (P = .0041), and oxygen uptake during the second minute of the test (P = .012). CONCLUSION: Claudication increases oxygen uptake of self-paced, over-the-ground ambulation, despite a decrease in cadence. The pain-mediated increase in oxygen uptake was blunted in individuals with metabolic syndrome, suggesting that the ability to increase oxygen uptake during ambulation is impaired. The clinical significance is that claudication increases the metabolic cost of ambulation, thereby increasing the relative intensity of exercise and reducing the tolerance to sustain ambulation.

Gender differences in the prevalence and management of metabolic syndrome and its components in patients with peripheral artery disease.

We compared the prevalence and management of metabolic syndrome (MetS) and its components in men and women with peripheral artery disease (PAD). A total of 70 men and 70 women with PAD were evaluated for presence of MetS. There was no significant gender difference in presence of MetS (P = .399) and the number of MetS components (P = .411). Among PAD patients with each MetS component, there was no significant gender difference in the use (P = .617) and number (P = .716) of blood pressure medications, the use (P = .593) and number (P = .591) of lipid-lowering medications, and the number (P = .155) of diabetic medications. Significantly more women were treated with diabetic medications compared with men (85 vs 57%, P = .026). The prevalence and management of MetS and its components was similar between men and women with PAD, except that more women were treated for diabetes. Patients with PAD having MetS did not receive optimal medical management.

Efficacy of quantified home-based exercise and supervised exercise in patients with intermittent claudication: a randomized controlled trial.

BACKGROUND: This prospective, randomized, controlled clinical trial compared changes in exercise performance and daily ambulatory activity in peripheral artery disease patients with intermittent claudication after a home-based exercise program, a supervised exercise program, and usual-care control. METHODS AND RESULTS: Of the 119 patients randomized, 29 completed home-based exercise, 33 completed supervised exercise, and 30 completed usual-care control. Both exercise programs consisted of intermittent walking to nearly maximal claudication pain for 12 weeks. Patients wore a step activity monitor during each exercise session. Primary outcome measures included claudication onset time and peak walking time obtained from a treadmill exercise test; secondary outcome measures included daily ambulatory cadences measured during a 7-day monitoring period. Adherence to home-based and supervised exercise was similar (P=0.712) and exceeded 80%. Both exercise programs increased claudication onset time (P<0.001) and peak walking time (P<0.01), whereas only home-based exercise increased daily average cadence (P<0.01). No changes were seen in the control group (P>0.05). The changes in claudication onset time and peak walking time were similar between the 2 exercise groups (P>0.05), whereas the change in daily average cadence was greater with home-based exercise (P<0.05). CONCLUSIONS: A home-based exercise program, quantified with a step activity monitor, has high adherence and is efficacious in improving claudication measures similar to a standard supervised exercise program. Furthermore, home-based exercise appears more efficacious in increasing daily ambulatory activity in the community setting than supervised exercise.

Green tea minimally affects biomarkers of inflammation in obese subjects with metabolic syndrome.

OBJECTIVE: Green tea (Camellia sinensis) has shown to exert cardioprotective benefits in observational studies. The objective of this clinical trial was to assess the effects of green tea on features of metabolic syndrome and inflammation in obese subjects. METHODS: We conducted a randomized controlled trial in obese subjects with metabolic syndrome. Thirty-five subjects [(mean ± SE) age 42.5 ± 1.7 y, body mass index 36.1 ± 1.3 kg/m(2)] completed the 8-wk study and were randomly assigned to receive green tea (4 cups/d), green tea extract (2 capsules and 4 cups water/d), or no treatment (4 cups water/d). Both the beverage and extract groups had similar dosing of epigallocatechin-3-gallate, the active green tea polyphenol. Fasting blood samples were collected at screening, 4 and 8 wk of the study. RESULTS: Green tea beverage or extract supplementation did not significantly alter features of metabolic syndrome or biomarkers of inflammation including adiponectin, C-reactive protein, interleukin-6, interleukin-1ß, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, leptin, or leptin:adiponectin ratio. However, both green tea beverage and extracts significantly reduced plasma serum amyloid alpha versus no treatment (P < 0.005). CONCLUSION: This study suggests that the daily consumption of green tea beverage or extracts for 8 wk was well tolerated but did not affect the features of metabolic syndrome. However, green tea significantly reduced plasma serum amyloid alpha, an independent cardiovascular disease risk factor, in obese subjects with metabolic syndrome.

Gender differences in daily ambulatory activity patterns in patients with intermittent claudication.

OBJECTIVES: To compare the pattern of daily ambulatory activity in men and women with intermittent claudication, and to determine whether calf muscle hemoglobin oxygen saturation (StO2) is associated with daily ambulatory activity. METHODS: Forty men and 41 women with peripheral arterial disease limited by intermittent claudication were assessed on their community-based ambulatory activity patterns for 1 week with an ankle-mounted step activity monitor and on calf muscle StO2 during a treadmill test. RESULTS: Women had lower adjusted daily maximal cadence (mean±SE) for 5 continuous minutes of ambulation (26.2±1.2 strides/min vs 31.0±1.2 strides/min; P=.009), for 1 minute of ambulation (43.1±0.9 strides/min vs 47.2±0.9 strides/min; P=.004), and for intermittent ambulation determined by the peak activity index (26.3±1.2 strides/min vs 31.0±1.2 strides/min; P=.009). Women also had lower adjusted time to minimum calf muscle StO2 during exercise (P=.048), which was positively associated with maximal cadence for 5 continuous minutes (r=0.51; P<.01), maximal cadence for 1 minute (r=0.42; P<.05), and peak activity index (r=0.44; P<.05). These associations were not significant in men. CONCLUSION: Women with intermittent claudication ambulate slower in the community setting than men, particularly for short continuous durations of up to 5 minutes and during intermittent ambulation at peak cadences. Furthermore, the daily ambulatory cadences of women are correlated with their calf muscle StO2 during exercise, as women who walk slower in the community setting reach their minimum calf muscle StO2 sooner than those who walk at faster paces. Women with intermittent claudication should be encouraged to not only walk more on a daily basis, but to do so at a pace that is faster than their preferred speed.

Robert Koch and the 'golden age' of bacteriology.

Robert Koch's discovery of the anthrax bacillus in 1876 launched the field of medical bacteriology. A 'golden age' of scientific discovery ensued. A century after Koch's death, we remember his life and work.

Gender and ethnic differences in arterial compliance in patients with intermittent claudication.

OBJECTIVE: To assess the gender and ethnic differences in arterial compliance in patients with intermittent claudication. METHODS: A total of 114 patients participated, including 38 Caucasian men, 32 Caucasian women, 16 African American men, and 28 African American women. Patients were assessed on large artery elasticity index (LAEI), small artery elasticity index (SAEI), age, weight, body mass index, ankle-brachial index (ABI), smoking status, and metabolic syndrome components. RESULTS: Group differences were found for LAEI (P = .042), SAEI (P = .019), body mass index (P = .020), prevalence of elevated fasting glucose (P = .001), and prevalence of abdominal obesity (P = .025). Significant covariates for LAEI included age (P = .0002) and elevated triglycerides (P = .0719). LAEI (units = 10 mL x mm Hg) adjusted for age and triglycerides was 39% lower (P = .0005) in African Americans (11.4 +/- .90; mean +/- SE) than in Caucasians (15.8 +/- 0.72), whereas no significant difference (P = .7904) existed between men (13.8 +/- 0.81) and women (13.5 +/- 0.79). Significant covariates for SAEI included age (P = .0001), abdominal obesity (P = .0030), and elevated blood pressure (P = .0067). SAEI (units = 100 mL x mm Hg) adjusted for age, abdominal obesity, and elevated blood pressure was 32% lower (P = .0007) in African-Americans (2.8 +/- 0.3) than in Caucasians 4.1 +/- 0.2), and was 18% lower (P = .0442) in women (3.1 +/- 0.2) than in men (3.8 +/- 0.2). CONCLUSION: African American patients with intermittent claudication have more impaired macrovascular and microvascular function than Caucasian patients, and women have more impaired microvascular function than men. These ethnic and gender differences in arterial compliance are evident even though ABI was similar among groups, suggesting that arterial compliance provides unique information to quantify vascular impairment in patients with intermittent claudication.

Walking economy before and after the onset of claudication pain in patients with peripheral arterial disease.

PURPOSE: To determine the walking economy before and after the onset of claudication pain in patients with peripheral arterial disease (PAD), and to identify predictors of the change in walking economy following the onset of claudication pain. METHODS: A total of 39 patients with PAD were studied, in which 29 experienced claudication (Pain group) during a constant load, walking economy treadmill test (speed = 2.0 mph, grade = 0%) and 10 were pain-free during this test (Pain-Free group). Patients were characterized on walking economy (ie, oxygen uptake during ambulation), as well as on demographic characteristics, cardiovascular risk factors, baseline exercise performance measures, and the ischemic window calculated from the decrease in ankle systolic blood pressure following exercise. RESULTS: During the constant load treadmill test, the Pain group experienced onset of claudication pain at 323 +/- 195 seconds (mean +/- standard deviation) and continued to walk until maximal pain was attained at 759 +/- 332 seconds. Walking economy during pain-free ambulation (9.54 +/- 1.42 ml x kg(-1) x min(-1)) changed (P < .001) after the onset of pain (10.18 +/- 1.56 ml x kg(-1) x min(-1)). The change in walking economy after the onset of pain was associated with ischemic window (P < .001), hypertension (P < .001), diabetes (P = .002), and height (P = .003). In contrast, the Pain-Free group walked pain-free for the entire 20-minute test duration without a change in walking economy (P = .36) from the second minute of exercise (9.20 +/- 1.62 ml x kg(-1) x min(-1)) to the nineteenth minute of exercise (9.07 +/- 1.54 ml x kg(-1) x min(-1)). CONCLUSION: Painful ambulation at a constant speed is associated with impaired walking economy, as measured by an increase in oxygen uptake in patients limited by intermittent claudication, and the change in walking economy is explained, in part, by severity of PAD, diabetes, and hypertension.

Electrocardiogram abnormalities with atazanavir and lopinavir/ritonavir.

PURPOSE: Concurrent atazanavir (ATV) and lopinavir/ritonavir (LPV/r) may be useful for patients with extensive antiretroviral resistance; however, limited information exists concerning the pharmacokinetics and safety of this combination. METHOD: A parallel-arm pharmacokinetic study was conducted in HIV-infected patients (n = 10) using contemporary formulations of each agent. Intensive pharmacokinetics were conducted at Day 6 (ATV/r), Day 16 (ATV qd + LPV/r bid), and Day 20 (ATV + LPV/r qd) in Arm A and Day 6 (LPV/r) and Day 12 (LPV/r bid + ATV qd) in Arm B. Plasma ATV, LPV, and ritonavir concentrations were measured by HPLC-UV. Electrocardiograms (12-lead) and safety labs were conducted at each visit. RESULTS: Prolonged PR and QRS intervals occurred in the majority of patients (mean increase: 16 ms and 5 ms, respectively; p < or = .01). Two patients developed new-onset arrhythmias (bundle branch block, atrioventricular block), resulting in premature termination of the study. No change in ATV or LPV pharmacokinetics was evident. CONCLUSION: Concurrent ATV and LPV/r was associated with PR and QRS interval changes in this small study population. Electrocardiogram monitoring should be considered for patients receiving concurrent ATV and LPV/r shortly after their initiation, especially if other risk factors for altered conduction are present.

Sex differences in calf muscle hemoglobin oxygen saturation in patients with intermittent claudication.

PURPOSES: We tested the hypotheses that women have greater impairment in calf muscle hemoglobin oxygen saturation (StO(2)) in response to exercise than men, and that the sex-related difference in calf muscle StO(2) would partially explain the shorter claudication distances of women. METHODS: The study comprised 27 men and 24 women with peripheral arterial disease limited by intermittent claudication. Patients were characterized on calf muscle StO(2) before, during, and after a graded treadmill test, as well as on demographic and cardiovascular risk factors, ankle-brachial index (ABI), ischemic window, initial claudication distance (ICD), and absolute claudication distance (ACD). RESULTS: Women had a 45% lower ACD than men (296 +/- 268 m vs 539 +/- 288 m; P = .001) during the treadmill test. Calf muscle StO(2) declined more rapidly during exercise in women than in men; the time to reach minimum StO(2) occurred 54% sooner in women (226 +/- 241 vs 491 +/- 426 seconds; P = .010). The recovery time for calf muscle StO(2) to reach the resting value after treadmill exercise was prolonged in women (383 +/- 365 vs 201 +/- 206 seconds; P = .036). Predictors of ACD included the time from start of exercise to minimum calf muscle StO(2), the average rate of decline in StO(2) from rest to minimum StO(2) value, the recovery half-time of StO(2), and ABI (R(2) = 0.70; P < .001). The ACD of women remained lower after adjusting for ABI (mean difference, 209 m; P = .003), but was no longer significantly lower (mean difference, 72 m; P = .132) after further adjustment for the StO(2) variables for the three calf muscles. CONCLUSION: In patients limited by intermittent claudication, women have lower ACD and greater impairment in calf muscle StO(2) during and after exercise than men, the exercise-mediated changes in calf muscle StO(2) are predictive of ACD, and women have similar ACD as men after adjusting for calf StO(2) and ABI measures.

Association between daily ambulatory activity patterns and exercise performance in patients with intermittent claudication.

PURPOSE: To determine the association between daily ambulatory activity patterns and exercise performance in patients with intermittent claudication. METHODS: One hundred thirty-three patients limited by intermittent claudication participated in this study. Patients were assessed on their ambulatory activity patterns for 1 week with a small, lightweight step activity monitor attached to the ankle using elastic velcro straps above the lateral malleolus of the right leg. The step activity monitor recorded the number of strides taken on a minute-to-minute basis and the time spent ambulating. Patients also were characterized on ankle-brachial index (ABI), ischemic window (IW) after a treadmill test, as well as initial claudication distance (ICD), and absolute claudication distance (ACD) during treadmill exercise. RESULTS: The patient characteristics (mean +/- SD) were as follows: ABI = 0.71 +/- 0.23, IW = 0.54 +/- 0.72 mm Hg.min.meter(-1), ICD = 236 +/- 198 meters, and ACD = 424 +/- 285 meters. The patients took 3366 +/- 1694 strides/day, and were active for 272 +/- 103 min/day. The cadence for the 30 highest, consecutive minutes of each day (15.1 +/- 7.2 strides/min) was correlated with ICD (r = 0.316, P < .001) and ACD (r = 0.471, P < 0.001), and the cadence for the 60 highest, consecutive minutes of each day (11.1 +/- 5.4 strides/min) was correlated with ICD (r = 0.290, P < .01) and ACD (r = 0.453, P < .001). Similarly, the cadences for the highest 1, 5, and 20 consecutive minutes, and the cadence for the 30 highest, nonconsecutive minutes all were correlated with ICD and ACD (P < .05). None of the ambulatory cadences were correlated with ABI (P > .05) or with ischemic window (P > .05). CONCLUSION: Daily ambulatory cadences are associated with severity of intermittent claudication, as measured by ACD and ICD, but not with peripheral hemodynamic measures.