Search

Context: Clinicians and trialists have difficulty with identifying which patients are highest risk for cardiovascular events. Prior ischemic events, polyvascular disease, and diabetes mellitus have all been identified as predictors of ischemic events, but their comparative contributions to future risk remain unclear., Objective: To categorize the risk of cardiovascular events in stable outpatients with various initial manifestations of atherothrombosis using simple clinical descriptors., Design, Setting, and Patients: Outpatients with coronary artery disease, cerebrovascular disease, or peripheral arterial disease or with multiple risk factors for atherothrombosis were enrolled in the global Reduction of Atherothrombosis for Continued Health (REACH) Registry and were followed up for as long as 4 years. Patients from 3647 centers in 29 countries were enrolled between 2003 and 2004 and followed up until 2008. Final database lock was in April 2009., Main Outcome Measures: Rates of cardiovascular death, myocardial infarction, and stroke., Results: A total of 45,227 patients with baseline data were included in this 4-year analysis. During the follow-up period, a total of 5481 patients experienced at least 1 event, including 2315 with cardiovascular death, 1228 with myocardial infarction, 1898 with stroke, and 40 with both a myocardial infarction and stroke on the same day. Among patients with atherothrombosis, those with a prior history of ischemic events at baseline (n = 21,890) had the highest rate of subsequent ischemic events (18.3%; 95% confidence interval [CI], 17.4%-19.1%); patients with stable coronary, cerebrovascular, or peripheral artery disease (n = 15,264) had a lower risk (12.2%; 95% CI, 11.4%-12.9%); and patients without established atherothrombosis but with risk factors only (n = 8073) had the lowest risk (9.1%; 95% CI, 8.3%-9.9%) (P < .001 for all comparisons). In addition, in multivariable modeling, the presence of diabetes (hazard ratio [HR], 1.44; 95% CI, 1.36-1.53; P < .001), an ischemic event in the previous year (HR, 1.71; 95% CI, 1.57-1.85; P < .001), and polyvascular disease (HR, 1.99; 95% CI, 1.78-2.24; P < .001) each were associated with a significantly higher risk of the primary end point., Conclusion: Clinical descriptors can assist clinicians in identifying high-risk patients within the broad range of risk for outpatients with atherothrombosis.

To assess the effect of prior cardiovascular interventions on long-term clinical outcomes in patients with symptomatic atherothrombosis, the risk factor profiles, treatment patterns, and 24-month outcomes of patients in the United States with and without prior cardiovascular intervention (catheter-based, surgical, or lower-limb amputation) enrolled in the global REACH (REduction of Atherothrombosis for Continued Health) Registry were compared. Of the 17,521 US outpatients aged > or =45 years with established coronary artery disease, cerebrovascular disease, or peripheral artery disease enrolled in the REACH Registry between December 1, 2003 and June 1, 2004 who had > or =1 follow-up visit, 11,925 (68.1%) had a previous cardiovascular intervention. Prior intervention was most common in patients with coronary artery disease (76.7%) and least common in patients with cerebrovascular disease (14.6%) at baseline. Patients with prior cardiovascular intervention were significantly more likely to be taking antihypertensive, antithrombotic, or lipid-lowering therapies than those without prior intervention (P < 0.0001 for each therapy). However, 24-month Kaplan-Meier event rates for the composite outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke were similar between patients with and without prior intervention (9.10% vs. 9.00%; P = 0.49). Thus, in the US REACH Registry, prior cardiovascular intervention was not associated with an increased risk of subsequent cardiovascular ischemic events during follow-up. Patients without prior cardiovascular intervention had a lower intensity of risk factor modification at baseline and appear to represent an at-risk, undertreated population.

Objectives: To examine differences in risk factor (RF) management between peripheral artery disease (PAD) and coronary artery (CAD) or cerebrovascular disease (CVD), as well as the impact of RF control on major 1-year cardiovascular (CV) event rates., Methods: The REACH Registry recruited >68000 outpatients aged >or=45 years with established atherothrombotic disease or >or=3 RFs for atherothrombosis. The predictors of RF control that were evaluated included: (1) patient demographics, (2) mode of PAD diagnosis, and (3) concomitant CAD and/or CVD., Results: RF control was less frequent in patients with PAD (n=8322), compared with those with CAD or CVD (but no PAD, n=47492) [blood pressure; glycemia; total cholesterol; smoking cessation (each P<0.001)]. Factors independently associated with optimal RF control in patients with PAD were male gender (OR=1.9); residence in North America (OR=3.5), Japan (OR=2.5) or Latin America (OR=1.5); previous coronary revascularization (OR=1.3); and statin use (OR=1.4); whereas prior leg amputation was a negative predictor (OR=0.7) (P<0.001). Optimal RF control was associated with fewer 1-year CV ischemic symptoms or events., Conclusions: Patients with PAD do not achieve RF control as frequently as individuals with CAD or CVD. Improved RF control is associated with a positive impact on 1-year CV event rates.

Background: Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis and is associated with a high risk of stroke, myocardial infarction and cardiovascular death. PAD also fosters major morbidity by causing claudication, functional impairment, disability and amputation. PAD is largely unrecognized and under-treated compared with other cardiovascular diseases. The public health impact of PAD, as a contributor to Canadian national rates of heart attack, stroke, amputation, death and disability, will be challenging to address if the public is unaware of this common cardiovascular disease., Objective: To assess public knowledge of PAD in Canada., Methods: A cross-sectional, population-based telephone survey of 501 adults 50 years of age and older (mean age 64.4 years) was conducted using random digit dialing. The survey assessed demographics and risk factors of the study population and knowledge of PAD causes and consequences., Results: Survey respondents reported a high prevalence of atherosclerotic risk factors including high blood pressure (43%), high blood cholesterol (37%), diabetes (12%) and smoking history (18% current and 49% former smokers). Only 36% of respondents reported familiarity with PAD, which was significantly lower than other cardiovascular diseases or risk factors. Knowledge of perceived consequences of PAD was low and knowledge gaps were more pronounced in older, less educated and lower income respondents., Conclusions: The Canadian public is largely unaware of PAD as a prevalent systemic manifestation of atherosclerosis and its associated morbidity and mortality. National PAD awareness programs should be instituted to increase PAD knowledge to levels comparable with other cardiovascular diseases and risk factors.

Background: Atrial fibrillation (AF) is a major risk factor (RF) for ischemic stroke. Its prevalence and prognostic impact in patients with atherothrombosis are unclear., Methods: Risk factors, drug usage, and 1-year cardiovascular (CV) outcomes (CV death, myocardial infarction [MI], and stroke) were compared in AF and non-AF patients from the REduction of Atherothrombosis for Continued Health (REACH) Registry, an international, prospective cohort of 68,236 stable outpatients with established atherothrombosis or>or=3 atherothrombotic RFs., Results: Atrial fibrillation and 1-year follow-up data are available for 63,589 patients. The prevalence of AF was, 12.5%, 13.7%, 11.5%, and 6.2% among coronary artery disease, CV disease, peripheral artery disease, and RF-only patients, respectively. Of the 6,814 patients with AF, 6.7% experienced CV death, nonfatal MI, or nonfatal stroke within a year. The annual incidence of nonfatal stroke (2.4% vs 1.6%, P<.0001) and unstable angina (6.0% vs 4.0%, P<.00001) was higher, and CV death was more than double (3.2% vs 1.4%, P<.0001), in AF versus non-AF patients. In these patients with or at high risk of atherothrombosis, most patients with AF received antiplatelet agents, but only 53.1% were treated with oral anticoagulants. Even with high CHADS2 (congestive heart failure, hypertension, aging, diabetes mellitus, and stroke) scores, anticoagulant use did not exceed (59%). The rate of bleeding requiring hospitalization was higher in AF versus non-AF patients (1.5% vs 0.8%, P<.0001), possibly related to the more frequent use of anticoagulants (53.1% vs 7.1%)., Conclusions: Atrial fibrillation is common in patients with atherothrombosis, associated with more frequent fatal and nonfatal CV outcomes, and underuse of oral anticoagulants.

Objective: Datasets regarding patients with abdominal aortic aneurysm (AAA) have almost universally been restricted to single geographic regions. We aimed to obtain data on the risk factor profile and cardiovascular (CV) co-morbidity among multi-ethnic patients with known AAA in the global REACH (REduction of Atherothrombosis for Continued Health) Registry., Methods: The REACH Registry is an international, prospective, observational out-patient registry enrolling out-patients >/=45 years of age with established coronary artery disease (CAD), cerebrovascular disease (CVD) or peripheral arterial disease (PAD) or with at least three atherothrombotic risk factors. This report includes observations pertaining to 68,236 out-patients enrolled in 44 countries., Main Outcome Measures: Gender, ethnic origin, CV risk factors, established atherosclerotic disease (CAD, CVD and PAD) at baseline, and CV outcome events at 1-year were compared in patients with and without AAA., Results: An AAA was reported in 1722 (2.5%) of 68,236 out-patients enrolled in the REACH Registry. Older age (73 +/- 8 vs 68 +/- 10, P < .0001), male gender (81% vs 63%, P < .0001), White ethnicity (79% vs 67%, P < .0001) and a history of smoking (81% vs 55%, P < .0001) were independently related to the diagnosis of AAA. There was a weaker association with hypertension or hypercholesterolemia, and an inverse relation with diabetes. Fatal and non-fatal coronary and cerebrovascular event rates were not different between the AAA and non-AAA cohorts, but individuals with AAA suffered increased rates of other cardiovascular deaths (1.39% vs 0.94%, P = .0135), hospitalizations for atherothrombotic events (14.1% vs 9.3%, P < .0001) due to increased rates of revascularization procedures, and new or worsening PAD (3.7% vs 1.3%, P < .0001) at 1-year follow-up., Conclusion: This study, the largest published to date, presents the CV risk profile and outcome of patients with an established diagnosis of AAA from a cohort of patients with either overt manifestations of CV disease or multiple risk factors, and further defines these patients in a multi-ethnic, global context.

Background: Atherothrombosis is the underlying cause of cardiovascular, cerebrovascular, and peripheral arterial disease and is the leading cause of death in the industrialized world. The objectives of the present study are (1) to examine the annual costs associated with vascular events and interventions that require hospitalization, as well as long-term medication use for the management of associated risk factors, in a US population of outpatients with multiple atherothrombotic risk factors or a history of symptomatic disease and (2) to compare costs across patient subgroups defined according to specific arterial bed(s) affected and the number of affected arterial beds., Methods and Results: The international REduction of Atherothrombosis for Continued Health (REACH) Registry enrolled outpatients > or =45 years of age who had established coronary artery, cerebrovascular, or peripheral artery disease or > or =3 atherothrombotic risk factors. Data on risk factors, associated medications, and vascular hospitalizations and interventions were collected. Of the total 68 236-patient REACH cohort, 25 763 were enrolled from US sites. Complete 1-year data were available for 23 974 (93%) of the US patients. Annualized medication costs ranged from $2401 to $3481. Mean annual hospitalization costs per patient were $1344, $2864, $4824, and $8155 for patients with 0 (n=6145), 1 (n=14 353), 2 (n=3106), and 3 (n=370) affected arterial beds at baseline (P<0.0001 for trend). Among patients with 1 affected arterial bed, mean hospitalization costs were $2999, $2010, and $3911 for patients with coronary artery disease (n=11 063), cerebrovascular disease (n=2613), and peripheral arterial disease (n=677), respectively. Annualized medication costs ranged from $2401 to $3481., Conclusions: These results reveal the high economic burden of atherothrombosis-related clinical events and procedures and the especially high economic burden associated with polyvascular disease.

To determine whether elevated levels of hemostatic and inflammatory markers [von Willebrand factor (vWF), fibrinogen, D-dimer, factor VII, factor VIII, PAI-1, tPA, beta-thromboglobulin (beta-TG), CRP, and WBC count] are associated with increased peripheral arterial disease (PAD) prevalence, measured by low ABI, we studied 13,778 participants from the ARIC study in a cross-sectional analysis after adjustment for major cardiovascular risk factors. PAD was positively associated with fibrinogen, vWF, factor VIII, WBC count, D-dimer, beta-TG, and CRP (p for trend <0.05) but not with the other markers. Adjusted odds ratios for the highest versus the lowest quartile of fibrinogen in men and women, respectively, were 3.49 (95% CI 1.68-7.26) and 2.44 (95% CI 1.58-3.77); for vWF 2.36 (95% CI 1.36-4.07) and 1.45 (95% CI 1.00-2.10); for factor VIII 2.31 (95% CI 1.36-3.94) and 1.68 (95% CI 1.14-2.48). In a smaller subset, the sex and risk factor adjusted odds ratio for the highest versus the lowest quartile of D-dimer was 2.70 (95% CI 1.56-4.65), for beta-TG was 1.80 (95% CI 1.12-2.88), and for CRP was 1.57 (95% CI 0.84-2.95). Plasma levels of hemostatic and inflammatory markers are elevated in PAD, suggesting these processes are involved in the pathophysiology of PAD.

Context: Few data document current cardiovascular (CV) event rates in stable patients with atherothrombosis in a community setting. Differential event rates for patients with documented coronary artery disease (CAD), cerebrovascular disease (CVD), or peripheral arterial disease (PAD) or those at risk of these diseases have not been previously evaluated in a single international cohort., Objective: To establish contemporary, international, 1-year CV event rates in outpatients with established arterial disease or with multiple risk factors for atherothrombosis., Design, Setting, and Participants: The Reduction of Atherothrombosis for Continued Health (REACH) Registry is an international, prospective cohort of 68 236 patients with either established atherosclerotic arterial disease (CAD, PAD, CVD; n = 55 814) or at least 3 risk factors for atherothrombosis (n = 12 422), who were enrolled from 5587 physician practices in 44 countries in 2003-2004., Main Outcome Measures: Rates of CV death, myocardial infarction (MI), and stroke., Results: As of July 2006, 1-year outcomes were available for 95.22% (n = 64 977) of participants. Cardiovascular death, MI, or stroke rates were 4.24% overall: 4.69% for those with established atherosclerotic arterial disease vs 2.15% for patients with multiple risk factors only. Among patients with established disease, CV death, MI, or stroke rates were 4.52% for patients with CAD, 6.47% for patients with CVD, and 5.35% for patients with PAD. The incidences of the end point of CV death, MI, or stroke or of hospitalization for atherothrombotic event(s) were 15.20% for CAD, 14.53% for CVD, and 21.14% for PAD patients with established disease. These event rates increased with the number of symptomatic arterial disease locations, ranging from 5.31% for patients with risk factors only to 12.58% for patients with 1, 21.14% for patients with 2, and 26.27% for patients with 3 symptomatic arterial disease locations (P<.001 for trend)., Conclusions: In this large, contemporary, international study, outpatients with established atherosclerotic arterial disease, or at risk of atherothrombosis, experienced relatively high annual CV event rates. Multiple disease locations increased the 1-year risk of CV events.

Background: The clinical significance of a high ankle-brachial index (ABI), defined by the associated risk factor burden and ischemic risk, is largely unknown., Methods: Using data from the Atherosclerosis Risk in Communities Study, we categorized 14,777 participants into normal (ABI between 0.9 and 1.3) and high ABI groups (ABI>1.3, >1.4, and >1.5) and compared the risk factor profile and CVD event rates of the normal ABI group to each high ABI group., Results: The prevalence of high ABI was 5.5% for ABI>1.3, 1.2% for ABI>1.4, and 0.37% for ABI>1.5. Compared with participants with a normal ABI, those with ABI>1.3 had a lower prevalence of hypertension and current smoking. The ABI>1.3 group had a greater mean body mass index, but was characterized by fewer pack years of smoking and lower systolic and diastolic blood pressures than the normal ABI group. The prevalence of diabetes, left ventricular hypertrophy, claudication, and coronary heart disease and mean values of fibrinogen, factor VIII activity, von Willebrand factor, lipoprotein (a), and carotid and popliteal intimal-medial thickness were similar between the two ABI groups. The risk factor profiles of the ABI>1.4 and >1.5 groups were also not statistically significantly different from that of the normal ABI group. Over a mean follow-up time of 12.2 years, the age, sex, and race-adjusted CVD event rates per 1000 person years were 8.1 in the normal ABI group, 7.6 in the ABI>1.3 group, 7.6 in the ABI>1.4 group, and 7.4 in the ABI>1.5 group. The CVD event rates of the high ABI groups were similar to that of the normal ABI group., Conclusion: Individuals with a high ABI are not characterized by a more adverse atherosclerosis risk factor profile and do not suffer greater CVD event rates than those with a normal ABI.

Chronic kidney disease (CKD) is associated with an increased risk for cardiovascular disease, but its association with peripheral arterial disease (PAD) is unclear. With the use of data from the Atherosclerosis Risk in Communities (ARIC) Study, 14,280 middle-aged adults were categorized on the basis of estimated GFR >/=90, 60 to 89, and 15 to 59 ml/min per 1.73 m(2) for normal kidney function, mildly decreased kidney function, and stages 3 to 4 CKD, respectively. Incident PAD was defined as a new onset of ankle-brachial index <0.9 assessed at regular examinations, new intermittent claudication assessed by annual surveillance, or PAD-related hospital discharges. Incidence rates and relative risks (RR) for PAD were compared across these categories. During a mean follow-up time of 13.1 yr (186,616 person-years), 1016 participants developed PAD. The incidence rates per 1000 person-years were 4.7, 4.9, and 8.6 for the normal kidney function, mildly decreased kidney function, and CKD groups, respectively. Compared with participants with normal kidney function, the age-, gender-, race-, and ARIC field center-adjusted RR for PAD was 1.04 (95% confidence interval [CI] 0.91 to 1.18) for those with mildly decreased kidney function and 1.82 (95% CI 1.34 to 2.47) for those with CKD. After additional adjustment for cardiovascular disease risk factors, an increase in risk for incident PAD still was observed in participants with CKD, with a multivariable adjusted RR of 1.56 (95% CI 1.13 to 2.14). Patients with CKD are at increased risk for incident PAD. Development of strategies for screening and prevention of PAD in this high-risk population seems warranted.

Context: Atherothrombosis is the leading cause of cardiovascular morbidity and mortality around the globe. To date, no single international database has characterized the atherosclerosis risk factor profile or treatment intensity of individuals with atherothrombosis., Objective: To determine whether atherosclerosis risk factor prevalence and treatment would demonstrate comparable patterns in many countries around the world., Design, Setting, and Participants: The Reduction of Atherothrombosis for Continued Health (REACH) Registry collected data on atherosclerosis risk factors and treatment. A total of 67,888 patients aged 45 years or older from 5473 physician practices in 44 countries had either established arterial disease (coronary artery disease [CAD], n = 40,258; cerebrovascular disease, n = 18,843; peripheral arterial disease, n = 8273) or 3 or more risk factors for atherothrombosis (n = 12,389) between 2003 and 2004., Main Outcome Measures: Baseline prevalence of atherosclerosis risk factors, medication use, and degree of risk factor control., Results: Atherothrombotic patients throughout the world had similar risk factor profiles: a high proportion with hypertension (81.8%), hypercholesterolemia (72.4%), and diabetes (44.3%). The prevalence of overweight (39.8%), obesity (26.6%), and morbid obesity (3.6%) were similar in most geographic locales, but was highest in North America (overweight: 37.1%, obese: 36.5%, and morbidly obese: 5.8%; P<.001 vs other regions). Patients were generally undertreated with statins (69.4% overall; range: 56.4% for cerebrovascular disease to 76.2% for CAD), antiplatelet agents (78.6% overall; range: 53.9% for > or =3 risk factors to 85.6% for CAD), and other evidence-based risk reduction therapies. Current tobacco use in patients with established vascular disease was substantial (14.4%). Undertreated hypertension (50.0% with elevated blood pressure at baseline), undiagnosed hyperglycemia (4.9%), and impaired fasting glucose (36.5% in those not known to be diabetic) were common. Among those with symptomatic atherothrombosis, 15.9% had symptomatic polyvascular disease., Conclusion: This large, international, contemporary database shows that classic cardiovascular risk factors are consistent and common but are largely undertreated and undercontrolled in many regions of the world.

Peripheral arterial disease (PAD) is a group of syndromes characterized by chronic and progressive atherosclerosis with a high burden of physical disability and cardiovascular morbidity and mortality. Recruiting patients for clinical research is therefore challenging. In this article, we describe and evaluate our methods for recruiting participants for a cross-sectional feasibility study of PAD, nutritional status, and body composition. We used convenience and purposive sampling approaches to identify potential participants. Between May 2012 and April 2013, 1,446 patients were identified, and 165 patients (11.4%) responded to recruitment requests. The final enrollment was 64 participants (64/1,446; 4.4%), and four subjects (6.3%) subsequently withdrew from the study. Recruiting PAD patients presents a variety of challenges, due largely to the burdens of living with coexistent illnesses, and patients' reluctance or inability to travel for research. In this article, we delineate suggestions for improving the efficacy of recruitment methods in future PAD studies. [ABSTRACT FROM AUTHOR]

Background Advanced lower extremity peripheral artery disease (PAD), whether presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI), is associated with high rates of cardiovascular ischemic events, amputation, and death. Past research has focused on strategies of revascularization, but few data are available that prospectively evaluate the impact of key process of care factors (spanning pre-admission, acute hospitalization, and post-discharge) that might contribute to improving short and long-term health outcomes. Methods/Design The FRIENDS registry is designed to prospectively evaluate a range of patient and health system care delivery factors that might serve as future targets for efforts to improve limb and systemic outcomes for patients with ALI or CLI. This hypothesis-driven registry was designed to evaluate the contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of leg revascularization strategies, and (iii) use of risk-reduction pharmacotherapies, as pre-specified factors that may affect amputation-free survival. Sequential patients would be included at an index "vascular specialist-defined" ALI or CLI episode, and patients excluded only for non-vascular etiologies of limb threat. Data including baseline demographics, functional status, co-morbidities, pre-hospital time segments, and use of medical therapies; hospital-based use of revascularization strategies, time segments, and pharmacotherapies; and rates of systemic ischemic events (e.g., myocardial infarction, stroke, hospitalization, and death) and limb ischemic events (e.g., hospitalization for revascularization or amputation) will be recorded during a minimum of one year follow-up. Discussion The FRIENDS registry is designed to evaluate the potential impact of key factors that may contribute to adverse outcomes for patients with ALI or CLI. Definition of new "health system-based" therapeutic targets could then become the focus of future interventional clinical trials for individuals with advanced PAD. [ABSTRACT FROM AUTHOR]

We aimed to evaluate whether carotid intima-media thickness (CIMT) or the presence of plaque can confer additional predictive value of future cardiovascular (CV) ischemic events in patients with pre-existing atherosclerotic vascular disease. We identified 2317 patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry who had atherosclerotic vascular disease and baseline CIMT measurements. The entire range of CIMT was divided into quartiles and the fourth quartile (≥ 1.5 mm) was defined as carotid plaque. Mean ± standard deviation baseline CIMT was 1.31 ± 0.65 mm. Associated CV ischemic events and vascular-related hospitalizations were evaluated over a 2-year follow-up. There was a positive increase in adjusted hazard ratios (HRs) for all-cause mortality (p = 0.04 for trend) and the quadruple endpoint (CV death, myocardial infarction (MI), stroke, hospitalization for CV events) with increasing quartiles of CIMT (p = 0.0008 for trend), which was mainly driven by the fourth quartile (carotid plaque). HRs for all-cause mortality, CV death, CV death/MI/stroke and the quadruple endpoint comparing the highest (carotid plaque) with the lowest CIMT quartile were 2.09 (95% CI, 1.07–4.10; p = 0.03); 2.49 (1.10–5.67; p = 0.03); 1.71 (1.10–2.67; p = 0.02); and 1.73 (1.31–2.27; p = 0.0001). In conclusion, our analyses suggest that the presence of carotid plaque, rather than the thickness of intima-media, appears to be associated with increased risk of CV morbidity and mortality, but confirmation of these findings in other population and prospective studies is required. [ABSTRACT FROM AUTHOR]

In patients with peripheral artery disease (PAD), statins may improve the symptoms of claudication. The Intermittent Claudication Proof of Principle (ICPOP) study tested the hypothesis that the combination of extended release niacin plus lovastatin would improve exercise performance in patients with PAD and claudication compared with a diet intervention. A phase 3 double-blind, parallel-group, multi-center, 28-week multi-national study evaluated subjects with a history of claudication who had an ankle-brachial index (ABI) ≤ 0.90, a reproducible peak treadmill walking time (PWT) of 1-20 minutes, and a low-density lipoprotein (LDL)-cholesterol level < 160 mg/dl (< 4.1 mmol/l). Subjects were randomly assigned to low-dose niacin 1000 mg plus lovastatin 40 mg (low niacin-statin), high-dose niacin 2000 mg plus lovastatin 40 mg (high niacin-statin), or diet intervention (diet). The co-primary efficacy endpoint of percent change in PWT and claudication onset time (COT) at 28 weeks was assessed using a graded treadmill protocol. At completion, 385 subjects were analyzed for safety and 370 subjects were analyzed for efficacy. The primary efficacy analysis showed no statistical significance for overall treatment effect at week 28 for the co-primary endpoint of PWT and COT. The PWT component of the primary endpoint increased 26.5% on diet, 37.8% on high niacin-statin (p = 0.137) and 38.6% on low niacin-statin (p = 0.096). Flushing as the most common event leading to discontinuation and treatment was associated with increases in liver enzymes, fasting blood glucose concentration and a decrease in platelet count. [ABSTRACT FROM AUTHOR]

Lower extremity peripheral arterial disease (PAD) is prevalent in the Medicare population and is associated with high rates of myocardial infarction, stroke, amputation, and death. Nevertheless, national health expenditures for PAD are not known. We hypothesized that PAD-related costs are high, increase with age, and that treatment rates would be less than known PAD prevalence. The objective was to determine national health care expenditures for PAD in the United States. PAD-related treatment costs were calculated in the elderly, non-disabled Medicare population. The cost analysis relied on the 5% control population for the linked SEER- Medicare data and Medicare claims for the calendar year 2001, identifying PAD cases based on diagnosis and procedure codes. Costs were aggregated separately for inpatient and outpatient treatment and estimates adjusted to reflect the Medicare population. A total of $4.37 billion was spent on PAD-related treatment and 88% of expenditures were for inpatient care. Medicare program outlays totaled $3.87 billion, while enrollees (or their supplemental insurance) spent the remaining $500 million. In total, 6.8% of the elderly Medicare population received treatment for PAD. Treatment increased with age at rates of 4.5%, 7.5%, and 11.8% for individuals aged 65-74, 75-84, and >85 years, respectively. PAD-related costs accounted for approximately 13% of all Medicare Part A and B expenditures for the PAD-treated cohort, and 2.3% of total Medicare Part A and B expenditures. In conclusion, US national PAD-related costs are high, associated with inpatient care, and increase with age. PAD is treated at rates lower than the known PAD prevalence as only approximately one-third of the population with known PAD had detectable PAD-related health care costs in our analysis. The potential impact of earlier PAD detection and use of outpatient preventive strategies on total national PAD health care costs is unknown. [ABSTRACT FROM AUTHOR]

There is mounting evidence to suggest that psychosocial factors, including anger proneness, depression and social isolation, are risk factors for cardiovascular disease. Nevertheless, evidence relating these factors to peripheral arterial disease (PAD) and intermittent claudication remains sparse. Using data from the Atherosclerosis Risk in Communities Study, we analyzed the relationship of psychosocial variables (Spielberger anger score, depression score from the Maastricht questionnaire, and a perceived social support scale) at study visit 2 with incident PAD (ankle-brachial index ≤0.9; a hospital discharge diagnosis of PAD, leg amputation, or leg revascularization procedures; or intermittent claudication). In 12 965 middle-aged adults with no prior history of PAD, 854 developed PAD over a mean follow-up time of 9.7 years, yielding an incidence rate of 6.8 per 1000 person years. A modest, monotonic dose–response, positive association between anger proneness and incident PAD was observed in a multivariable model: relative risk (RR) = 1.15 (95% confidence interval (CI) 0.99–1.38) in the moderate anger group and RR = 1.38 (95% CI 1.08–1.76) in the high anger group, compared with the low anger group. When compared with a low level of depressive symptoms, moderate and high levels of depressive symptoms were also associated with greater incident PAD, with multivariable RRs of 1.20 (95% CI 0.99–1.45) and 1.44 (95% CI 1.19–1.74) respectively. There was no association of perceived level of social support with the occurrence of PAD. Anger proneness and depressive symptoms may be associated with the occurrence of PAD, as for other atherosclerotic syndromes. These findings may warrant confirmation in further studies and, if causal, could serve as a unique target for a PAD prevention trial. [ABSTRACT FROM AUTHOR]

Peripheral arterial disease (PAD) is associated with significant morbidity and mortality, and yet remains under-recognized and under-treated. Atherosclerosis is the most common cause of lower extremity PAD and pharmacological interventions that alter this central patho- genic role of atherosclerosis may alter the natural history of PAD. There is growing evidence that the renin-angiotensin system (RAS) is a signi cant mediator of this disease process and that treatment with angiotensin-converting enzyme (ACE) inhibitors is associated with vasculopro- tective effects that are independent of the antihypertensive properties of these agents. Numerous lines of evidence suggest that ACE inhibitors directly inhibit the atherosclerotic process and improve vascular endothelial function. In patients with PAD, ACE inhibitors have been shown to improve peripheral circulation as measured by peripheral arterial blood pressure and by increases in peripheral blood flow. Preliminary evidence suggests that ACE inhibitors might improve clinical symptoms in patients with PAD. Recent evidence has confirmed that ACE inhibition is associated with a decrease in morbidity and mortality in patients with arterial disease without left ventricular dysfunction; this benefit was at least as great for the subset of patients with PAD. Overall, these data support a significant role for the RAS in the pathogenesis of all atherosclerotic diseases (including PAD) and suggest that the benefit is independent of the blood pressure lowering properties of these agents. These studies suggest that ACE inhibitor therapy should be considered in the routine management of individuals with PAD, regardless of whether they have hypertension or left ventricular dysfunction. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Individuals with peripheral arterial disease (PAD) have a 3- to 6-fold increased risk of coronary heart disease and stroke compared to those without PAD. We documented physician-reported practice behavior, knowledge, and attitudes regarding atherosclerotic risk factor reduction in patients with PAD. DESIGN: National physician survey. PATIENTS/PARTICIPANTS: General internists (N = 406), family practitioners (N = 435), cardiologists (N = 473), and vascular surgeons (N = 264) randomly identified using the American Medical Association's physician database. MEASUREMENTS AND MAIN RESULTS: Physicians were randomized to 1 of 3 questionnaires describing a) a 55- to 65-year-old patient with PAD; b) a 55- to 65-year-old patient with coronary artery disease (CAD), or c) a 55- to 65-year-old patient without clinically evident atherosclerosis (no disease). A mailed questionnaire was used to compare physician behavior, knowledge, and attitude regarding risk factor reduction for each patient. Rates of prescribed antiplatelet therapy were significantly lower for the patient with PAD than for the patient with CAD. Average low-density lipoprotein levels at which physicians “almost always” initiated lipid-lowering drugs were 121.6 ± 23.5 mg/dL, 136.3 ± 28.9 mg/dL, and 149.7 ± 24.4 mg/dL for the CAD, PAD, and no-disease patients, respectively (P < .001). Physicians stated that antiplatelet therapy (P < .001) and cholesterol-lowering therapy (P < .001) were extremely important significantly more often for the CAD than for the PAD patient. Perceived importance of risk factor interventions was highly correlated with practice behavior. Compared to other specialties, cardiologists had lowest thresholds, whereas vascular surgeons had the highest thresholds for initiating cholesterol-lowering interventions for the patient with PAD. Cardiologists were significantly more likely to report “almost always” prescribing antiplatelet therapy... [ABSTRACT FROM AUTHOR]

Atherosclerosis is a form of arterial disease that manifests in the coronary circulation as coronary artery disease (CAD), in the carotid arteries as cerebrovascular disease, and in the aorta and lower extremity arteries as peripheral arterial disease (PAD). The systemic nature of the disease is reflected in the fact that individuals with PAD or carotid artery disease are more likely to have CAD than those without. Since individuals with PAD are at markedly increased risk of cardiovascular ischemic events, early identification of this population and more aggressive medical interventions could substantially improve both morbidity and survival. The incidence of PAD in the general population is high, and currently affects 8–10 million Americans. The risk of developing PAD is predicted by both age and common atherosclerosis risk factors (e.g., smoking and diabetes). Efficient office-based PAD detection depends on the application of objective techniques to establish this diagnosis. Objective noninvasive tests, such as measurement of the ankle–brachial index (ABI), are known to be more sensitive than traditional clinical assessments. Since the major threat to patients with PAD is from secondary cardiovascular ischemic events, a primary therapeutic goal is to modify atherosclerotic risk factors. While national recommendations mandate aggressive lowering of serum low-density lipoprotein cholesterol (LDL-C) levels as a primary treatment goal in all patients with overt atherosclerosis, as 'coronary heart disease risk equivalent' syndromes, individuals with PAD are less intensively treated than those with CAD. Statins are the most effective of current treatments in lowering LDL-C, and have proven efficacy in secondary prevention among patients with established CAD. The use of statin medications in high-risk groups such as PAD patients could prove particularly beneficial in reducing cardiovascular morbidity and mortality and therefore merits prospective clinical investigation. [ABSTRACT FROM AUTHOR]

Presents a study to assess the feasibility of detecting peripheral arterial disease (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; Patients; Main outcome measures; Results; Conclusions.

Background: Advanced lower extremity peripheral artery disease (PAD), whether presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI), is associated with high rates of cardiovascular ischemic events, amputation, and death. Past research has focused on strategies of revascularization, but few data are available that prospectively evaluate the impact of key process of care factors (spanning pre-admission, acute hospitalization, and post-discharge) that might contribute to improving short and long-term health outcomes. Methods/Design The FRIENDS registry is designed to prospectively evaluate a range of patient and health system care delivery factors that might serve as future targets for efforts to improve limb and systemic outcomes for patients with ALI or CLI. This hypothesis-driven registry was designed to evaluate the contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of leg revascularization strategies, and (iii) use of risk-reduction pharmacotherapies, as pre-specified factors that may affect amputation-free survival. Sequential patients would be included at an index “vascular specialist-defined” ALI or CLI episode, and patients excluded only for non-vascular etiologies of limb threat. Data including baseline demographics, functional status, co-morbidities, pre-hospital time segments, and use of medical therapies; hospital-based use of revascularization strategies, time segments, and pharmacotherapies; and rates of systemic ischemic events (e.g., myocardial infarction, stroke, hospitalization, and death) and limb ischemic events (e.g., hospitalization for revascularization or amputation) will be recorded during a minimum of one year follow-up. Discussion The FRIENDS registry is designed to evaluate the potential impact of key factors that may contribute to adverse outcomes for patients with ALI or CLI. Definition of new “health system-based” therapeutic targets could then become the focus of future interventional clinical trials for individuals with advanced PAD.

Background and aims Traditional glycemic markers, fasting glucose and hemoglobin A1c (HbA1c), predict incident peripheral artery disease (PAD). However, it is unknown whether nontraditional glycemic markers, fructosamine, glycated albumin, and 1,5-anhydroglucitol, are associated with PAD and whether these glycemic markers demonstrate particularly strong associations with severe PAD, critical limb ischemia (CLI). Methods We quantified the associations of these five glycemic markers with incident PAD (hospitalizations with PAD diagnosis or leg revascularization) in 11,634 ARIC participants using Cox regression models. Participants were categorized according to diabetes diagnosis and clinical cut-points of glycemic markers (nontraditional glycemic markers were categorized according to percentiles corresponding to the HbA1c cut-points). Results Over a median follow-up of 20.7 years, there were 392 cases of PAD (133 were CLI with tissue loss). HbA1c was more strongly associated with incident PAD than fasting glucose, with adjusted hazard ratios (HR) 6.00 (95% CI, 3.73–9.66) for diagnosed diabetes with HbA1c ≥ 7% and 3.53 (2.39–5.22) for no diagnosed diabetes with HbA1c ≥ 6.5% compared to no diagnosed diabetes with HbA1c <5.7%. Three nontraditional glycemic markers demonstrated risk gradients intermediate between HbA1c and fasting glucose and their risk gradients were substantially attenuated after adjusting for HbA1c. All glycemic markers consistently demonstrated stronger associations with CLI than PAD without CLI ( p for difference <0.02 for all glycemic markers). Conclusions Nontraditional glycemic markers were associated with incident PAD independent of fasting glucose but not necessarily HbA1c. Our results also support the importance of glucose metabolism in the progression to CLI. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate systemic and limb ischemic event rates of PAD patients with prior leg amputation and determine predictors of adverse outcomes. Methods: The REduction of Atherothrombosis for Continued Health (REACH) Registry provided a prospective multinational cohort of 7996 outpatients with PAD enrolled from primary medical clinics in 44 countries in 2003–2004. 1160 patients (14.5%) had a prior leg amputation at any level. Systemic (myocardial infarction [MI], stroke, cardiovascular death) and limb (angioplasty, surgery, amputation) ischemic event rates were determined in a 3-year follow-up. Results: PAD patients with leg amputations on entry had a 5-fold higher rate of a subsequent amputation (12.4% vs. 2.4%, P <.001), lower rate of peripheral angioplasty (8.3% vs. 10.7%, P =.005), and similar rates of surgical revascularization procedures compared with PAD patients without amputation. A nearly 2-fold increase in rates of cardiovascular death (14.5% vs. 7.7%, P <.001) and all-cause mortality (21.8% vs. 12.6%, P <.001) and an increase in the composite outcome of MI, stroke, cardiovascular death, or hospitalization (48.7% vs. 40.0%, P <.001) were noted. Recent (≤1 year) amputation was associated with higher rates of worsening PAD, subsequent lower extremity surgical revascularization procedures, re-amputation, non-fatal MI, and the composite outcome, including hospitalization. Adverse systemic and limb ischemic outcomes were similar regardless of amputation level. Conclusions: Individuals with a history of leg amputations have markedly elevated rates of systemic and limb-related outcomes. PAD patients with recent ischemic amputation have the highest risk of adverse events. A history of “minor” ischemic amputation may confer an identical systemic risk as “major” leg amputation. [Copyright &y& Elsevier]