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W R Hiatt

Publications and source records attributed to W R Hiatt.

At least 19 recordsLinked to original sources
PubMed2004

Omega-3 fatty acids for intermittent claudication.

BACKGROUND: Omega-3 fatty acids are established as being effective in the treatment and prevention of coronary artery disease. It is possible that they may also benefit people with peripheral arterial disease, since the pathogenesis of the two conditions is similar. OBJECTIVES: To determine the effects of omega-3 supplementation in people with intermittent claudication. SEARCH STRATEGY: Trials were identified from the Cochrane Peripheral Vascular Diseases Group trials register (last searched April 2004), and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 1, 2004). In addition, literature from pharmaceutical companies (Roche Pharmaceuticals and Seven Seas), manufacturers of omega-3 rich foods (Columbus Eggs) and web sites of nutritional organisations dedicated to omega-3 fatty acids (Omega-3 information and the Fish Foundation) were searched. SELECTION CRITERIA: Randomised controlled trials of omega-3 fatty acids versus placebo or non-omega-3 fatty acids in people with intermittent claudication. DATA COLLECTION AND ANALYSIS: One reviewer (TS) identified potential trials, assessed study quality and extracted data. The other reviewer (WH) assessed study quality and checked data extraction. MAIN RESULTS: Four studies were included involving a total of 203 participants. The overall methodological quality of studies was good. All studies compared omega-3 fatty acid supplementation with placebo. Two studies used an omega-6 fatty acid as the placebo preparation, one used a monounsaturated fatty acid and one used a combination of omega-6 and monounsaturated fatty acids.Omega-3 fatty acid supplementation reduced triglyceride levels (weighted mean difference (WMD) -0.66 mmol/litre; 95% confidence interval (CI) -1.24 to -0.09) and diastolic blood pressure (WMD -1.94 mmHg; 95% CI -3.58 to -0.29) in the treatment group, but increased total cholesterol levels (WMD 0.41 mmol/litre; 95% CI 0.03 to 0.80) and LDL cholesterol levels (WMD 0.43 mmol/litre; 95% CI 0.12 to 0.74). Gastrointestinal side-effects were observed in one study. No significant changes were observed in pain-free walking distance (WMD -17 m; 95% CI -51 to 17 m), maximal walking distance (WMD -21 m; 95% CI -59 to 17 m) or ankle brachial pressure index (WMD -0.03; 95% CI -0.1 to 0.04). REVIEWERS' CONCLUSIONS: Omega-3 fatty acids appear to have some beneficial biochemical and haemodynamic effects in people with intermittent claudication but there is no evidence of improved clinical outcomes. It should be noted that no consistent effect on primary outcome measures was detected. Further research is needed in this area, to evaluate short- and long-term effects on more clinically relevant outcomes.

Dietary Supplements↗
PubMed2002

Preventing atherothrombotic events in peripheral arterial disease: the use of antiplatelet therapy.

Patients with peripheral arterial disease (PAD) are at increased risk of generalized atherothrombotic events. Epidemiologic data shows a high rate of co-prevalence of PAD and atherosclerosis in other vascular beds. Aggressive risk-factor modification and antiplatelet therapy has become the cornerstone of treatment to prevent ischaemic events associated with PAD. Recent clinical trials have confirmed the clinical benefit of clopidogrel and ticlopidine in patients with PAD, agents that irreversibly inhibit the binding of adenosine diphosphate to its platelet receptor. In the clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) trial, clopidogrel was associated with an overall risk reduction of 8.7% (compared with aspirin, P=0.043) in myocardial infarction (MI), ischaemic stroke and vascular death. These results demonstrated that long-term administration of clopidogrel was effective in preventing ischaemic events in patients with atherosclerotic vascular disease including PAD. Aspirin and/or clopidogrel are the antiplatelet agents of choice for the reduction of atherothrombotic events in patients with PAD.

Algorithms↗
PubMed2001

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.

Aged↗
PubMed2001

Design of the therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (TRAFFIC) trial.

The Therapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 for Intermittent Claudication (TRAFFIC) is a large, randomized, placebo-controlled, regimen-finding trial of intra-arterial recombinant fibroblast growth factor-2 in patients with intermittent claudication. This report describes the major design considerations and end points in TRAFFIC.

Double-Blind Method↗
PubMed2001

Propionyl-L-carnitine improves exercise performance and functional status in patients with claudication.

PURPOSE: We tested the hypothesis that propionyl-L-carnitine would improve peak walking time in patients with claudication. Secondary aims of the study were to evaluate the effects of propionyl-L-carnitine on claudication onset time, functional status, and safety. SUBJECTS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 155 patients with disabling claudication from the United States (n = 72) or Russia (n = 83) received either placebo or propionyl-L-carnitine (2g/day orally) for 6 months. Subjects were evaluated at baseline and 3 and 6 months after randomization with a graded treadmill protocol at a constant speed of 2 miles per hour, beginning at 0% grade, with increments in the grade of 2% every 2 minutes until maximal symptoms of claudication forced cessation of exercise. Questionnaires were used to determine changes in functional status. RESULTS: At baseline, peak walking time was 331 +/- 171 seconds in the placebo group and 331 +/- 187 seconds in the propionyl-L-carnitine group. After 6 months of treatment, subjects randomly assigned to propionyl-L-carnitine increased their peak walking time by 162 +/- 222 seconds (a 54% increase) as compared with an improvement of 75 +/- 191 seconds (a 25% increase) for those on placebo (P <0.001). Similar improvements were observed for claudication onset time. Propionyl-L-carnitine treatment significantly improved walking distance and walking speed (by the Walking Impairment Questionnaire), and enhanced physical role functioning, reduced bodily pain, and resulted in a better health transition score (by the Medical Outcome Study SF-36 Questionnaire). The incidence of adverse events and study discontinuations were similar in the two treatment groups. CONCLUSIONS: Propionyl-L-carnitine safely improved treadmill exercise performance and enhanced functional status in patients with claudication.

Adult↗
PubMed2001

Intravenous L-carnitine increases plasma carnitine, reduces fatigue, and may preserve exercise capacity in hemodialysis patients.

Exercise capacity in patients with end-stage renal disease (ESRD) remains impaired despite correction of anemia. Carnitine insufficiency may contribute to impaired exercise and functional capacities in patients with ESRD. Two randomized placebo-controlled trials were conducted to test whether intravenous L-carnitine improves exercise capacity (assessed by maximal rate of oxygen consumption [VO(2max)]) and quality of life (measured by the Kidney Disease Questionnaire [KDQ]) in patients with ESRD. In study A, patients were administered L-carnitine, 20 mg/kg (n = 28), or placebo (n = 28) intravenously at the conclusion of each thrice-weekly dialysis session for 24 weeks. In study B, a dose-ranging study, patients were administered intravenous L-carnitine, 10 mg/kg (n = 32), 20 mg/kg (n = 30), or 40 mg/kg (n = 32), or placebo (n = 33) as in study A. The prospective primary statistical analysis evaluated changes in VO(2max) in each study and specified that changes in the KDQ were assessed only in the combined populations. L-Carnitine supplementation increased plasma carnitine concentrations, but did not affect VO(2max) in either study. Because change in VO(2max) showed significant heterogeneity, a secondary analysis using a mixture of linear models approach on the combined study populations was performed. L-Carnitine therapy (combined all doses) was associated with a statistically significant smaller deterioration in VO(2max) (-0.88 +/- 0.26 versus -0.05 +/- 0.19 mL/kg/min, placebo versus L-carnitine, respectively; P = 0.009). L-Carnitine significantly improved the fatigue domain of the KDQ after 12 (P = 0.01) and 24 weeks (P = 0.03) of treatment compared with placebo using the primary analysis but did not significantly affect the total score (P = 0.10) or other domains of the instrument (P > 0.11). Carnitine was well tolerated, and no drug-related adverse effects were identified. Intravenous L-carnitine treatment increased plasma carnitine concentrations, improved patient-assessed fatigue, and may prevent the decline in peak exercise capacity in hemodialysis patients. VO(2max) in the primary analysis and other assessed end points were unaffected by carnitine therapy.

Adult↗
PubMed2001

Blood pressure reductions with exercise and sodium restriction in postmenopausal women with elevated systolic pressure: role of arterial stiffness.

OBJECTIVES: This study determined the relative efficacy of aerobic exercise (daily walking) and moderate dietary sodium restriction (sodium intake <100 mmol/day) for reducing systolic blood pressure (SBP) and pulse pressure (PP) in postmenopausal women with elevated initial levels, and the potential role of reductions in large artery stiffness in these changes. BACKGROUND: Lifestyle behaviors are recommended for lowering blood pressure (BP) in adults with elevated baseline levels, but there is little information as to the relative efficacy of different interventions or the mechanisms underlying their potential beneficial effects. METHODS: After baseline measurements and random assignment, 35 nonmedicated healthy postmenopausal women with SBP between 130 and 159 mm Hg completed three months of either aerobic (walking) exercise (n = 18; 62 +/- 9 years, mean +/- SD) or moderate dietary sodium restriction (SR) (n = 17; 65 +/- 10 years, mean +/- SD). RESULTS: Body mass and composition, plasma volume, and fasting concentrations of metabolic coronary risk factors did not differ between the groups at baseline or change with intervention. Systolic BP and PP at rest decreased with both exercise and SR (p < 0.05); however, the reductions were three- to fourfold greater with SR (p < 0.05). Sodium restriction, but not exercise, also reduced 24-h SBP and PP (p < 0.05). Aortic pulse wave velocity (PWV) and carotid augmentation index were reduced only with SR (p < 0.05). Changes in SBP and PP at rest and over 24 h correlated with the corresponding changes in aortic PWV (r = 0.53 to 0.61, p < 0.01). CONCLUSIONS: Moderate SR lowers SBP and PP in postmenopausal women with elevated baseline levels more than does daily walking. The greater blood pressure reductions with SR may be mediated in part by a decrease in the stiffness of the large elastic arteries.

Aged↗
PubMed2001

Decreased NADH dehydrogenase and ubiquinol-cytochrome c oxidoreductase in peripheral arterial disease.

Peripheral arterial disease (PAD) is associated with muscle metabolic changes that may contribute to the disability in these patients. However, the biochemical defects in PAD have not been identified. The present study was undertaken to test the hypothesis that PAD is associated with specific defects in skeletal muscle electron transport chain activity. Seventeen patients with PAD and nine age-matched controls underwent gastrocnemius muscle biopsies. There were no differences in the mitochondrial content per gram of skeletal muscle as assessed by citrate synthase activity between the PAD patients and the control subjects. Skeletal muscle NADH dehydrogenase activity was decreased by 27% compared with controls when expressed per unit of citrate synthase activity. Expression of enzyme activities normalized to cytochrome c-oxygen oxidoreductase activity confirmed a 26% decrease in NADH dehydrogenase activity and also demonstrated a 38% decrease in ubiquinol-cytochrome c oxidoreductase activity. Thus PAD is associated with specific changes in muscle mitochondrial electron transport chain activities characterized by relative decreases in NADH dehydrogenase and ubiquinol-cytochrome c oxidoreductase activities, which may contribute to the metabolic abnormalities and decreased exercise performance in these patients.

Aged↗
PubMed2001

Proteinuria in a placebo-controlled study of basic fibroblast growth factor for intermittent claudication.

Intermittent claudication is the most common symptom of peripheral arterial disease (PAD), in part due to an inadequate rise in limb blood flow with exercise. Claudication causes a severe impairment in functional capacity and quality of life in over 3 million Americans. Basic fibroblast growth factor (bFGF) stimulates angiogenesis in vivo and improves limb blood flow in several animal models of hindlimb ischemia. However, the relative safety and efficacy of angiogenic molecules in the treatment of claudication has not been fully evaluated in prospective, blinded clinical trials. In this study, a randomized, double-blind, placebo-controlled, phase II trial of recombinant human bFGF for the treatment of intermittent claudication was performed. bFGF was administered weekly by intravenous infusions of 2 microg/kg for 6 sequential weeks (total dose 12 microg/kg). The primary efficacy endpoint was change in peak walking time (PWT) on a graded exercise treadmill protocol. Secondary efficacy endpoints included changes in functional status as measured by validated questionnaires. The study was stopped prematurely after treatment of the first 24 subjects due to proteinuria in five of the 16 subjects who received systemic bFGF, which exceeded 1000 mg/24 h in four of these five subjects. The small sample size limited evaluation of the predefined efficacy endpoints; however, there was no significant difference between the treatment and control groups for any of the measures of efficacy. In conclusion, intravenous administration of bFGF delivered at low doses weekly for 6 weeks was associated with a high rate of severe proteinuria. It is speculated that bFGF-related proteinuria in this study was primarily related to the systemic route of administration and the frequent dosing schedule. Future clinical trials of bFGF protein should carefully monitor renal function and consider alternative dosing schedules and drug administration routes.

Aged↗
PubMed2001

PAD awareness, risk, and treatment: new resources for survival--the USA PARTNERS program.

Peripheral arterial disease (PAD) is a very common manifestation of atherosclerosis and is associated with a high risk of cardiovascular morbidity and mortality. Despite the magnitude of the problem, PAD is often under-recognized in clinical practice until its limb manifestations are severe or heart attack or stroke supervene. The PAD Awareness, Risk and Treatment: New Resources for Survival (PARTNERS) program, recently completed in the USA, had five aims: (1) creation of a method for detection of PAD in primary care practice; (2) assessment of the awareness of the PAD diagnosis in both patients and physicians; (3) assessment of the magnitude of the atherosclerotic risk factor burden and intensity of treatment of atherosclerotic risk factors in PAD patients; (4) assessment of the disease-specific and general quality of life of PAD patients in their communities; and (5) provision of an educational intervention to foster improved community-prescribed medical interventions for patients with PAD. Lack of public and physician interest in PAD contrasts with the high prevalence and poor medical prognosis of PAD. The intention of PARTNERS was to create a community-based program to measure current rates of PAD awareness, physician recognition and treatment intensity. Data obtained will form the basis of future clinical investigations to improve clinical care for PAD patients in the USA.

Awareness↗
PubMed2001

Russian immigrant cardiovascular risk assessment.

Immigration from the former Soviet Union has been increasing. In 1990, there were 454,000 Russian immigrants living in the United States. Lifestyle habits prevalent in Russia, including smoking, alcoholism, and little preventive health, are compelling medical and economic reasons to understand the health status of this population. This study identified a cohort of Russian-born subjects living in Denver to characterize their cardiovascular risk profile. Using a risk assessment questionnaire, 204 Russian immigrants were screened. Seventy-one percent had Medicaid insurance; 14 percent were medically indigent. Those aged 55 to 64 years had a higher prevalence of hyperlipidemia (p < 0.04) and hypertension (p < 0.03) than U.S. counterparts; those age 20 to 34 and 65 to 74 years had a higher prevalence of hypertension (p < 0.00001). Almost half of the participants had two or more cardiac risk factors. Cardiac risk factor identification and intervention programs may help to reduce the health care costs for these patients.

Adult↗
PubMed2001

New treatment options in intermittent claudication: the US experience.

The goals of treatment in intermittent claudication are to modify cardiovascular risk factors and to reduce claudication pain, increase walking distance and improve quality of life. Walking distance in intermittent claudication can be improved both by exercise rehabilitation and by pharmacological treatments. At present, the only two drugs licensed in the US for the treatment of claudication symptoms are oxpentifylline and cilostazol. Although oxpentifylline has been shown to increase maximal and pain-free walking distance in a number of trials, other studies call its efficacy into question. Eight double-blind, placebo-controlled trials have established that cilostazol improves both maximal and pain-free walking distance in patients with moderate to severe intermittent claudication, with highly statistically significant differences compared with placebo. Cilostazol has also been shown to improve the physical dimensions of quality of life. Naftidrofuryl is licensed for the treatment of intermittent claudication in Europe, but not in the US. Some clinical trials have shown it to be effective in treating intermittent claudication. Promising new agents in the treatment of intermittent claudication include L-arginine, propionyl-L-carnitine, prostaglandins, and angiogenic growth factors such as vascular endothelial growth factor and basic fibroblast growth factor.

Arginine↗
PubMed2000

A comparison of cilostazol and pentoxifylline for treating intermittent claudication.

PURPOSE: We performed a randomized, double-blind, placebo-controlled, multicenter trial to evaluate the relative efficacy and safety of cilostazol and pentoxifylline. PATIENTS AND METHODS: We enrolled patients with moderate-to-severe claudication from 54 outpatient vascular clinics, including sites at Air Force, Veterans Affairs, tertiary care, and university medical centers in the United States. Of 922 consenting patients, 698 met the inclusion criteria and were randomly assigned to blinded treatment with either cilostazol (100 mg orally twice a day), pentoxifylline (400 mg orally 3 times a day), or placebo. We measured maximal walking distance with constant-speed, variable-grade treadmill testing at baseline and at 4, 8, 12, 16, 20, and 24 weeks. RESULTS: Mean maximal walking distance of cilostazol-treated patients (n = 227) was significantly greater at every postbaseline visit compared with patients who received pentoxifylline (n = 232) or placebo (n = 239). After 24 weeks of treatment, mean maximal walking distance increased by a mean of 107 m (a mean percent increase of 54% from baseline) in the cilostazol group, significantly more than the 64-m improvement (a 30% mean percent increase) with pentoxifylline (P <0.001). The improvement with pentoxifylline was similar (P = 0.82) to that in the placebo group (65 m, a 34% mean percent increase). Deaths and serious adverse event rates were similar in each group. Side effects (including headache, palpitations, and diarrhea) were more common in the cilostazol-treated patients, but withdrawal rates were similar in the cilostazol (16%) and pentoxifylline (19%) groups. CONCLUSION: Cilostazol was significantly better than pentoxifylline or placebo for increasing walking distances in patients with intermittent claudication, but was associated with a greater frequency of minor side effects. Pentoxifylline and placebo had similar effects.

Aged↗