Coronary artery calcium and cardiovascular disease prediction by scanner type: the multi-ethnic study of atherosclerosis.

AIM: To evaluate the predictive value of coronary artery calcium (CAC) scoring methods across cardiac computed tomography (CT) scanner types. MATERIALS AND METHODS: CAC was measured in participants from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of participants free of baseline cardiovascular disease (CVD), using either EBCT (electron beam CT) or MDCT (multidetector CT). The risks for incident coronary heart disease (CHD) and CVD events were compared for CAC scores per SD using Cox proportional hazards models with multivariable adjustment in 3,362 MESA participants with detectable CAC. RESULTS: Using the Agatston score, the hazard ratio (HR) and 95% confidence interval (CI) for CHD was 1.50 (1.27,1.78) for EBCT and 1.60 (1.37,1.87) for MDCT. Using volume and density scores, the HR for CHD was 2.14 (1.71,2.68) for volume and 0.61 (0.48,0.76) for density on EBCT and 1.73 (1.42,2.11) for volume and 0.88 (0.71,1.10) for density on MDCT. Similar results were seen for CVD risk and in analyses stratified by sex, body mass index (BMI), and age. The volume and density score model demonstrated higher areas under the curve (AUC) for CHD than the Agatston score with EBCT (0.702, 95% CI: 0.666,0.738 versus 0.677, 95% CI: 0.638,0.715, p<0.001) and MDCT (0.669, 95% CI: 0.632,0.705 versus 0.660, 95% CI: 0.622,0.697, p=0.216). CONCLUSION: The CAC volume and density scores provide better risk prediction than the Agatston score for CHD and CVD events, regardless of CT scanner type. CAC density was strongly and inversely associated with CHD risk. Both density and volume score prediction were stronger for EBCT than MDCT.

Adiponectin is independently associated with NT-proBNP: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: To investigate the associations between selected adipokines and the N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). METHODS AND RESULTS: As many as 1489 individuals enrolled in the Multi-Ethnic Study of Atherosclerosis were evaluated at 4 clinic visits about every 2 years. The evaluation included fasting venous blood, which was analyzed for NT-proBNP (at visits 1 and 3) and the adipokines adiponectin and leptin (at visits 2 and 3). The mean age was 64.8 ± 9.6 years and 48% were female. After multivariable adjustment, a 1-SD increment in adiponectin was associated with a 14 pg/ml higher NT-proBNP level (p < 0.01), while, compared to the 1st quartile of adiponectin, the 2nd, 3rd and 4th quartiles had 28, 45 and 67% higher NT-proBNP levels (p < 0.01 for all). For changes in NT-proBNP over the follow-up period, and after multivariable adjustment including baseline NT-proBNP, a 1-SD increment in adiponectin was associated with a 25 pg/ml absolute increase in NT-proBNP (p < 0.01), while those in the 2nd, 3rd and 4th quartiles of adiponectin were associated with increases of 5, 28 and 65 pg/ml (p = 0.74, 0.09 and <0.01, respectively). There was a significant interaction between adiponectin and sex for visit 3 NT-proBNP (p-interaction < 0.01), with significantly stronger associations in men. Leptin was not associated with NT-proBNP. CONCLUSION: Higher adiponectin, but not leptin, is significantly associated with higher levels of NT-proBNP, as well as with greater longitudinal increases in NT-proBNP. The associations were stronger in men.

Inflammation and peripheral venous disease. The San Diego Population Study.

The inflammatory response to healing in venous thrombosis might cause vein damage and post-thrombotic syndrome. Inflammation may also be involved in venous insufficiency apart from deep-vein thrombosis. We studied the association of inflammation markers with venous insufficiency in a general population sample. We characterised 2,404 men and women in a general population cohort for peripheral venous disease and its severity using physical exam, symptom assessment, and venous ultrasound. Inflammation markers, C-reactive protein (CRP), fibrinogen, interleukin 1-beta (IL-1-beta), IL-8, IL-10, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, monocyte chemoattractant-1 (MCP-1) and vascular endothelial cell growth factor (VEGF) were compared in 352 case participants with peripheral venous disease and 352 controls with no venous abnormalities frequency matched to cases by age, sex and race. Associations were also evaluated including a subset of 108 cases of severe venous disease, as previously defined. Odds ratios (95% CI), for peripheral venous disease for biomarkers in the top quartile (adjusting for age, race, sex, body mass index and history of venous thrombosis) were 1.8 (1.1-3.0), 1.6 (1.0-2.5) and 1.5 (0.9-2.3) for CRP, fibrinogen and IL-10, respectively. Associations were larger considering cases of severe venous disease, with odds ratios for these three analytes of 2.6 (1.2-5.9), 3.1 (1.3-7.3) and 2.2 (1.1-4.4), and for IL-8: 2.4 (1.1-5.2). There was no association of IL-1-beta, ICAM-1, VCAM-1, E-selectin, MCP-1 or VEGF with overall cases or severe venous disease. In conclusion, a subset of inflammation markers were associated with increased risk of peripheral venous disease, suggesting potential therapeutic targets for treatment.

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

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

Higher leptin is associated with hypertension: the Multi-Ethnic Study of Atherosclerosis.

Adipokines are secreted from adipose tissue, influence energy homeostasis and may contribute to the association between obesity and hypertension. Among 1897 participants enrolled in the Multi-Ethnic Study of Atherosclerosis, we examined associations between blood pressure and leptin, tumor necrosis factor-α (TNFα), resistin and total adiponectin. The mean age and body mass index (BMI) was 64.7 years and 28.1, respectively, and 50% were female. After adjustment for risk factors, a 1-s.d.-increment higher leptin level was significantly associated with higher systolic (5.0 mm Hg), diastolic (1.9), mean arterial (2.8) and pulse pressures (3.6), as well as a 34% higher odds for being hypertensive (P<0.01 for all). These associations were not materially different when the other adipokines, as well as BMI, waist circumference or waist-to-hip ratio, were additionally added to the model. Notably, the associations between leptin and hypertension were stronger in men, but were not different by race/ethnic group, BMI or smoking status. Adiponectin, resistin and TNFα were not independently associated with blood pressure or hypertension. Higher serum leptin, but not adiponectin, resistin or TNFα, is associated with higher levels of all measures of blood pressure, as well as a higher odds of hypertension, independent of risk factors, anthropometric measures and other selected adipokines.

Abdominal aortic diameter and vascular atherosclerosis: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVES: To gain insight into early mechanisms of aortic widening, we examined associations between the diameter of the abdominal aorta (AD) and cardiovascular disease (CVD) risk factors and biomarkers, as well as measures of subclinical atherosclerosis, in a multi-ethnic population. DESIGN: Cross-sectional cohort. METHODS: A total of 1926 participants (mean age 62, 50% women) underwent chest and abdomen scanning by computed tomography, ultrasound of the carotid arteries, and CVD risk factor assessment. AD was measured 5 cm above and at the bifurcation. RESULTS: In a model containing traditional CVD risk factors, biomarkers and ethnicity, only age (standardized ß = 0.97), male sex (ß = 1.88), body surface area (standardized ß = 0.92), current smoking (ß = 0.42), D-dimer levels (ß = 0.19) and hypertension (ß = 0.53) were independently and significantly associated with increasing AD (in mm) at the bifurcation; use of cholesterol-lowering medications predicted smaller AD (ß = -0.70) (P < 0.01 for all). These findings were similar for AD 5 cm above the bifurcation with one exception: compared to Caucasian-Americans, Americans of Chinese, African and Hispanic descent had significantly smaller AD 5 cm above the bifurcation (ß's = -0.59, -0.49, and -0.52, respectively, all P < 0.01), whereas AD at the bifurcation did not differ by ethnicity. Physical activity, alcohol consumption, diabetes and levels of IL-6, CRP and homocysteine were not independently associated with AD. Higher aortic and coronary artery calcium burden, but not common carotid artery intima-media thickness, were independently, but modestly (ß = 0.11 to 0.19), associated with larger AD. CONCLUSIONS: Incremental widening of the aortic diameter shared some, but not all, risk factors for occlusive vascular disease.

Adipokines are associated with lower extremity venous disease: the San Diego population study.

BACKGROUND: Obesity is a risk factor for venous disease. We tested the associations between adipokines and the presence and severity of venous disease. METHODS: Participants for this analysis were drawn from a cohort of 2408 employees and retirees of a university in San Diego who were examined for venous disease using duplex ultrasonography. From this cohort, a case-control study sample of all 352 subjects with venous disease and 352 age-, sex- and race-matched subjects without venous disease were included in this analysis. All subjects completed health history questionnaires, had a physical examination with anthropometric measurements and had venous blood analyzed for adipokines. RESULTS: After adjustment for age, sex and race, those with venous disease had significantly higher levels of body mass index (BMI), leptin and interleukin-6. Levels of resistin and tumor necrosis factor-alpha were also higher but of borderline significance (0.05 < P < 0.10). Compared with the lowest tertile and with adjustment for age, sex, race and BMI, the 2nd and 3rd tertiles of resistin (odds ratios, 1.9 and 1.7, respectively), leptin (1.7 and 1.7) and tumor necrosis factor-alpha (1.4 and 1.7) were associated with increasing severity of venous disease. Conversely, a 5 kg m⁻² increment in BMI was associated with a higher odds ratio (1.5) for venous disease, which was independent of the adipokines included in this study. CONCLUSIONS: Both obesity and adipokines are significantly associated with venous disease. These associations appear to be independent of each other, suggesting potentially different pathways to venous disease.

Risk factors for peripheral venous disease resemble those for venous thrombosis: the San Diego Population Study.

BACKGROUND: Clinically silent deep vein thrombosis (DVT) is common and may cause chronic venous disease that resembles post-thrombotic syndrome. OBJECTIVE: We evaluated whether peripheral venous disease in a general population shares risk factors with DVT. METHODS: In an established cohort of 2404 men and women, the San Diego Population Study, peripheral venous disease was evaluated using physical examination, symptom assessment and venous ultrasound. We performed a case-control study including 308 cases in four hierarchical groups by severity and 346 controls without venous abnormalities, frequency matched to cases by 10-year age group, race and gender. Cases and controls had no prior history of venous thrombosis. Hemostatic risk factors were measured in cases and controls. RESULTS: Accounting for age, obesity and family history of leg ulcer, odds ratios (ORs) of venous disease for elevated factor VIII, von Willebrand factor (VWF), D-dimer and for factor V Leiden were 1.4 (95% CI 0.9-2.1), 1.5 (CI 1.0-2.3), 1.7 (CI 1.1-2.8) and 1.1 (CI 0.5-2.4), respectively. These associations were larger for the two most severe case groups; ORs 2.0 (CI 1.0-3.8), 1.7 (CI 0.9-3.3), 2.7 (CI 1.2-6.1) and 2.3 (CI 0.8-7.1). Each hemostatic factor was also associated with severity of venous disease, for example elevated D-dimer was associated with a 2.2-fold increased odds of being in one higher severity case group. Prothrombin 20210A was not associated with venous disease. CONCLUSIONS: DVT risk factors are associated with presence and severity of peripheral venous disease. Results support a hypothesis that peripheral venous disease may sometimes be post-thrombotic syndrome as a result of a previous unrecognized DVT.

Vascular protection in peripheral artery disease: systematic review and modelling study.

AIMS: To ascertain the effectiveness of medical therapy for reducing risk in peripheral artery disease (PAD) and to model the potential impact of combining multiple efficacious approaches. METHODS AND RESULTS: 17 electronic databases, reference lists of primary studies, clinical practice guidelines, review articles, trial registries and conference proceedings from cardiology, vascular surgery and atherosclerosis meetings were screened. Eligible studies were randomized trials or meta-analyses of randomized trials of medical therapy for PAD which reported major cardiovascular events (myocardial infarction, stroke and cardiovascular death). Baseline event rates for modelling analyses were derived from published natural history cohorts. Overall, three strategies had persuasive evidence for reducing risk in PAD: antiplatelet agents (pooled RRR 26%, 95% CI 10 to 42), statins (pooled RRR 26%, 95% CI 18 to 33) and angiotensin-converting enzyme inhibitors (individual trial RRR 25%, 95% CI 8 to 39). The estimated cumulative relative risk reduction for all three strategies was 59% (CI 32 to 76). Given a 5-year major cardiovascular event rate of 25%, the corresponding absolute risk reduction and number needed to treat to prevent one event were 15% (CI 8 to 19) and 7 (CI 5 to 12), respectively. Population level analyses suggest that increased uptake of these modalities could prevent more than 200 000 events in patients with PAD each year. CONCLUSION: The use of multiple efficacious strategies has the potential to substantially reduce the cardiovascular burden of PAD. However, these data should be regarded as hypothetical, since they are based on mathematical modelling rather than factorial randomized trials.

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

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

Diagnosis of peripheral arterial disease in general practice: can the ankle-brachial index be measured either by pulse palpation or an automatic blood pressure device?

BACKGROUND: Despite its validity as a screening test for peripheral arterial disease (PAD), and its prognostic value, the ankle-brachial index (ABI) is infrequently used in primary care, probably because a Doppler device is required, along with the requisite skill for its use. We hypothesized that ABI could be accurately measured either by pulse palpation (pABI) or automatic blood pressure devices (autoABI) instead of Doppler method (dABI). DESIGN AND METHODS: In 54 subjects, we compared the results and the intra-observer reproducibility of pABI to dABI, as well as the inter-observer reproducibility of both pABI and autoABI to dABI. Arm and ankle systolic pressures were measured by the three methods by two observers. The first observer repeated pABI and dABI measurements. The results were compared by the Student paired t-test. Reproducibility was assessed by the intra-class correlation coefficient of agreement (R) and the Bland and Altman method. RESULTS: The mean dABI obtained by the first observers was 1.03 +/- 0.26 vs. a pABI of 0.85 +/- 0.44 (p < 0.0001) and an autoABI of 1.09 +/- 0.31 (p < 0.05). The intra-observer R-coefficient was at 0.89 for dABI vs. 0.60 for pABI (p < 0.05). The inter-observer R-coefficients were 0.79 for dABI vs. 0.40 for pABI (p < 0.05) and 0.44 for autoABI (p < 0.05). CONCLUSION: Neither pulse palpation nor automatic oscillometric devices can be recommended as reliable methods for ABI measurement.

Albuminuria and peripheral arterial disease: results from the multi-ethnic study of atherosclerosis (MESA).

BACKGROUND: The association of albuminuria with cardiovascular disease (CVD) is increasingly recognized, but its association with peripheral arterial disease (PAD) is not well characterized in subjects with or without diabetes. METHODS: Using data from the Multi-Ethnic Study of Atherosclerosis, a cohort free of clinical vascular disease, we analyzed the cross-sectional association between albuminuria and PAD in diabetic and nondiabetic subjects. A spot urine albumin-creatinine ratio (ACR) was used to define albuminuria in two ways: presence or absence of albuminuria and the degree of albuminuria (no albuminuria defined as urine ACR<17 mg/g for men and <25mg/g for women, microalbuminuria as urine ACR 17 to 249 mg/g for men and 25 to 334 mg/g for women, and macroalbuminuria as urine ACR> or =250 mg/g for men and > or =355 mg/g for women). PAD was defined by ankle-brachial index (ABI)<0.9. RESULTS: Among the 6760 subjects, aged 45-84 years, 326 (4.8%) had prevalent PAD. Eight hundred and thirteen (12.0%) subjects had microalbuminuria and 100 (1.5%) had macroalbuminuria. Among diabetic subjects, those with albuminuria (micro- and macroalbuminuria combined) were 1.90 times more likely to have PAD (95% CI: 1.19-3.04) than those with no albuminuria. After adjusting for CVD risk factors, the odds ratio modestly attenuated to 1.65 (95% CI: 1.00-2.74). For nondiabetic subjects, there were no statistically significant associations observed in the univariable and multivariable analyses. The degree of albuminuria was not associated with PAD in either diabetic or nondiabetic subjects. CONCLUSIONS: The presence, but not magnitude of albuminuria, is an important risk factor for PAD in diabetic but not in nondiabetic subjects.

Association between systemic calcified atherosclerosis and bone density.

Both atherosclerosis and osteoporosis are responsible for significant morbidity and mortality, are independent predictors of cardiovascular disease (CVD) events, and may share common regulatory mechanisms as well as histopathology. Multiple reports of weak or null relationships between traditional CVD risk factors and calcified atherosclerosis have heightened interest in novel predictors of arterial calcium. One such hypothesis is for an inverse relationship between bone mineral density (BMD) and calcified coronary atherosclerosis. Although contrary findings have been reported, the majority of cross-sectional and all prospective studies have demonstrated a significant inverse association between arterial calcium deposits and BMD. The few studies that include men are equivocal, and, to date, no study has investigated the relationship between BMD and systemic arterial calcium. The aim of this study was to test the hypothesis that lumbar BMD is significantly associated with the presence of arterial atherosclerotic calcium in the carotid, coronary, and iliac vascular beds as well as the aorta.

Type-2 diabetes and carotid stenosis: a proposal for a screening strategy in asymptomatic patients.

The objective of this prospective observational study was to establish the prevalence of carotid atherosclerosis in an asymptomatic diabetic population and to determine predictive factors for a screening optimization. A total of 300 consecutive type-2 diabetic subjects (166 males, 134 females) underwent a physical examination and duplex carotid scanning. Patients with a recent cerebrovascular event (< or = 6 weeks) or previous carotid surgery were excluded. The prevalence of carotid stenosis > or = 60% or occlusion was 4.7%; the prevalence of carotid atherosclerosis was 68.3%. Risk factors for stenosis > or = 60% or occlusion were the presence of diabetic retinopathy (OR: 3.62; 95% CI: 1.12-11.73), ankle-brachial index (ABI) <0.85 (OR: 3.94; 95% CI: 1.21-12.84) and a personal history of neurological disorders (OR: 4.54; 95% CI: 1.16-17.81). Being female was a protective factor (OR: 0.09; 95% CI: 0.01-0.78). The two factors in the analysis limited to the male population were an ABI < 0.85 (OR: 3.66; 95% CI: 1.04-12.84) and a personal history of coronary heart disease (OR: 3.34; 95% CI: 1.01-11.01). If male diabetics without either of these two factors are excluded, the negative predictive value for carotid stenosis is 96.6%. In conclusion, the prevalence of atherosclerotic carotid disease in diabetic patients is high. In these patients, the probability of finding >60% stenosis is highest among men with a history of coronary heart disease or an ABI <0.85.

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

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

Systemic atherosclerosis risk and the mandate for intervention in atherosclerotic peripheral arterial disease.

Peripheral arterial disease (PAD), characterized by obstruction of the arteries in the lower limbs, is an important manifestation of atherosclerosis. There are >10 million individuals with PAD in the United States alone, and as the overall population in developed countries ages, PAD will become increasingly prevalent. Many individuals with PAD are asymptomatic and therefore remain undiagnosed and untreated. Most patients with PAD are at high risk for having a serious coronary or cerebrovascular event. Even for patients in whom symptoms, such as leg pain, are clearly evident, current treatment strategies tend to ignore the systemic nature of the disease and do not reduce overall atherosclerotic risk. Proven medical treatment options for patients with intermittent claudication include smoking cessation, exercise, and cilostazol. Pentoxifylline appears marginally effective. Several novel therapies for PAD are currently under investigation. Of particular interest are the observations from some studies that show that lipid-lowering therapy might be of benefit to PAD patients. The results of 2 ongoing prospective trials of dyslipidemic therapy in claudicants should further clarify the benefits of reducing serum lipid levels in patients with established PAD.

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.

Common femoral vein dimensions and hemodynamics including Valsalva response as a function of sex, age, and ethnicity in a population study.

PURPOSE: In this study we assessed the normal common femoral vein (CFV) dimensions and related hemodynamics in a cohort assembled to permit contrasts by means of sex, age, and ethnicity. METHODS: The CFV diameter and the flow velocity were analyzed by means of duplex ultrasonography at rest and with a standardized Valsalva maneuver, with the subject in a 15% reverse Trendelenberg position. Mean levels of each of the CFV measurements were analyzed with age category, sex, and ethnicity, each adjusted for the other two. Multiple linear regression was used as a means of assessing the independent associations of age, sex, ethnicity, body mass index (BMI), and height to the CFV measurements. RESULTS: The average CFV diameter at rest was 11.84 mm, increasing to 14.27 mm during the Valsalva maneuver. There was a significant (P <.0001) decline in both diameter measures beginning in patients 60 years old. The CFV diameter was larger in men (12.90 mm) than in women (11.22 mm; P <.0001). The average CFV diameter in Hispanics, Africian Americans, and Asians was significantly smaller (P <.001) than in the non-Hispanic whites in multivarate analysis. The independence of these associations was confirmed by means of multivariate analysis, and positive associations of CFV diameter with height and BMI were documented. The Valsalva response was higher in men than in women (2.67 mm vs 2.29 mm), but the percentage change was similar. CFV velocity at rest decreased significantly (P <.0001) in patients older than 50 years. The mean CFV velocity was 13.87 cm/s, and the values were significantly (P <.0001) higher in women (14.58 cm/s) than in men (12.67 cm/s). In multivariate analysis CFV velocity was higher in African Americans than in the other ethnic groups. We also documented an independent inverse association of CFV with BMI. The CFV velocity response (peak expiration post-Valsalva) increased significantly at all ages, from 52% to 83%. The percentage increase in women (68%) was slightly higher than that in men (58%). African American subjects had a somewhat higher percentage increase (74%) than the other three ethnic groups (63% to 64%). Because the flow rate is determined more by the diameter than the velocity, CFV flow associations were similar to those for diameter. Because an older age predicted both decreased diameter and velocity, the flow reduction with age was pronounced. CONCLUSION: Quantitative normative data that are age-, sex-, and ethnic group-specific are reported on CFV diameter, velocity, and total flow rate, both at rest and with the Valsalva maneuver. CFV diameter, velocity, and flow rate varied significantly as a function of age, sex, ethnicity, height, and BMI. The data also provide a baseline assessment for subsequent evaluations of changes with time in this cohort.

Six-month patient outcomes in a preventive cardiology center.

More effective ways to improve lifestyle behaviors need to be developed. Two hundred forty adult patients at a preventive cardiology clinic were randomly assigned to receive either one or five sessions of behavioral instruction to improve cardiovascular risk behaviors. Results for 102 patients from 6-month follow-up data revealed few significant differences between the two groups. However, in the two groups combined, there were significant reductions in total calories, percent of calories from total fat, percent of calories from saturated and monounsaturated fat, and dietary cholesterol. Reductions were also found in systolic blood pressure, triglycerides, body mass index, and weight. In multiple regression analyses, changes in physiologic variables were primarily associated with baseline and demographic characteristics. Changes in total calories, percent of calories from polyunsaturated fat, and walking were predicted by changes in social support or knowledge. Although most patients improved, the intensity of behavior change instruction was not related to the amount of change in cardiovascular risk factors. (c) 2001 by CHF, Inc.

Peripheral arterial disease--epidemiological aspects.

As many as 10 million people in the USA have peripheral arterial disease (PAD) with a prevalence over 10% in people aged more than 60 years old. Generally, men have a higher prevalence of PAD than women. The risk factors for PAD are similar to those for coronary artery disease (CAD) and cerebrovascular disease (CBVD), but diabetes and cigarette smoking have a particularly strong association with PAD. Patients with PAD also have CAD and CBVD as co-morbidities, although the extent of co-morbidity depends on the sensitivity of assessment. The risk of mortality is proportional to the severity of PAD, and the relative risk of all-cause mortality due to PAD is unaltered by the presence of CAD or CBVD. PAD is under-recognized and under-treated, even though it should be regarded as a severe disease leading to significant death and disability from stroke and myocardial infarction (MI). Thus, accurate diagnosis of PAD could provide an early indication of the need for intervention and help prevent future morbidity and mortality.