Subclinical Peripheral Arterial Disease Research Articles

Cardiovascular Risk Factors and Signs of Subclinical Atherosclerosis in the Heinz Nixdorf Recall Study

Modern investigation modalities allow markers of atherosclerosis to be detected at a subclinical stage. The aim of the study was to analyze the prevalence of these markers in relation to traditional risk factors. The population based study included 4814 participants, aged 45 to 75 years, with a response rate of 55.8% of those contacted. The patients' history, psychosocial and environmental risk factors were assessed. The prevalence of obesity was 26.2% in men and 28.1% in women, 26% of men and 21% of women were smokers. Hypertension was found in 46% of men and 31% of women, diabetes in 9.3% of men and 6.3% of women. Markers of subclinical peripheral arterial disease were found in 6.4% of men and 5.1% of women, of subclinical carotid artery disease in 43.2% and 30.7%, and of subclinical coronary artery calcification in 82.3% and 55.2%, respectively. The prevalence of coronary calcification measured using an Agatston Score >100 was in 40% in men and 15% in women, using a score >400, 16.8% and 4.5%, respectively. A high prevalence of subclinical atherosclerosis was found in the older population. The follow-up period will demonstrate whether the detection of markers of subclinical atherosclerosis will improve risk stratification beyond that offered by traditional risk factors.

Accuracy of the screening physical examination to identify subclinical atherosclerosis and peripheral arterial disease in asymptomatic subjects

This study assessed the accuracy of the screening vascular physical examination for predicting asymptomatic peripheral arterial disease (PAD) or subclinical atherosclerosis in asymptomatic and apparently healthy subjects. A standardized physical examination and a carotid and femoral ultrasonography were administered to 2736 men and women aged 20 to 90 years old, with no personal history of cardiovascular disease (CVD) and no complaint of neurologic, coronary, or lower limb symptom. We assessed the accuracy of auscultation for bruits and pulse palpation for identifying the presence of significant carotid stenosis, carotid plaque, femoral plaque, and ankle-brachial index (ABI) <0.9 at ultrasonography. The presence of a femoral bruit provided information on the presence of both an ABI <0.9 (positive likelihood ratio [+LR], 2.90; 95% confidence interval [CI], 1.63 to 5.16) and a femoral plaque (+LR, 3.23; 95% CI, 2.22 to 4.71), and this information was independent from the cardiovascular risk factors. The absence of both pedal pulses also provided additional information, beyond risk factors, on the presence of an ABI <0.9 (+LR, 3.57; 95% CI, 1.93 to 6.60). The presence of a carotid bruit did not affect the likelihood of carotid stenosis, plaque, or intima-media thickness above the median. Unlike carotid auscultation, pulse palpation and auscultation for femoral bruits provided valuable information on the presence of asymptomatic PAD and underlying atherosclerosis in apparently healthy subjects.

Novel clinico-molecular insights in pseudoxanthoma elasticum provide an efficient molecular screening method and a comprehensive diagnostic flowchart

Pseudoxanthoma elasticum (PXE) is a heritable connective tissue disorder characterized by ocular, cutaneous and cardiovascular manifestations. It is caused by mutations in the ABCC6 gene (chr. 16p13.1), encoding a transmembrane transporter protein, the substrate and biological function of which are currently unknown. A comprehensive clinical and molecular study of 38 Belgian PXE probands and 21 relatives (4 affected and 17 carriers) was performed. An extensive clinical evaluation protocol was implemented with serial fundus, skin and cardiovascular evaluation. We report on 14 novel mutations in the ABCC6 gene. We observed extensive variability in severity of both cutaneous and ocular lesions. The type of skin lesion however usually remained identical throughout the evolution of the disorder, while ophthalmological progression was mainly due to functional decline. Peripheral artery disease (53%) and stroke (15%) were significantly more prevalent than in the general population (10-30% and 0.3-0.5% respectively). Interestingly, we also observed a relatively high incidence of subclinical peripheral artery disease (41%) in our carrier population. We highlight the significance of peripheral artery disease and stroke in PXE patients as well as the subclinical manifestations in carriers. Through follow-up data we gained insight into the natural history of PXE. We propose a cost- and time-efficient two-step method of ABCC6 analysis which can be used in different populations. Additionally, we created a diagnostic flowchart and attempted to define the role of molecular analysis of ABCC6 in the work-up of a PXE patient.

Smoking and postprandial triglycerides are associated with vascular disease in patients with type 2 diabetes

Aims To determine whether postprandial lipid levels are markers of clinical and subclinical macrovascular disease in a select group of patients with type 2 diabetes. Methods We recruited 119 local patients with type 2 diabetes and moderate metabolic control (HbA1c <8%). The patients were being treated with dietary measures and/or oral antihyperglycemic therapy. No patient was receiving lipid-lowering therapy. A history of cardiovascular events was recorded and the ankle–arm index was measured to assess subclinical peripheral artery disease. The patients underwent a lipid analysis after a 12-h fast and 4 h after a mixed breakfast (50 g of fat, 40 g of carbohydrates). Results The patients with clinical and subclinical macrovascular disease had a greater history of smoking, a longer disease duration, and higher serum creatinine levels. The groups with macroangiopathy had lower postprandial concentrations of HDL cholesterol ( p < 0.05) and a trend towards lower fasting levels of HDL cholesterol ( p = 0.08) and higher fasting and postprandial levels of triglycerides ( p = 0.07). Multivariate analysis showed the presence of vascular (both clinical and subclinical) disease to be significantly associated with smoking (OR 3.06; 95% CI, 1.15–8.4), disease duration (for each year, OR 1.12; 95% CI, 1.03–1.22) and postprandial levels of triglycerides (for each 50 mg, OR 1.73; 95% CI, 1.13–2.65). Conclusions In our diabetic patients, the postprandial level of triglycerides 4 h after a fatty breakfast, though not fasting lipids, plus smoking and disease duration were independently associated to clinical and subclinical macrovascular disease.

Volumetric and Areal Bone Mineral Density Measures Are Associated with Cardiovascular Disease in Older Men and Women: The Health, Aging, and Body Composition Study

The associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with prevalent cardiovascular disease (CVD) and subclinical peripheral arterial disease (PAD) were investigated in a cohort of older men and women enrolled in the Health, Aging, and Body Composition Study. Participants were 3,075 well-functioning white and black men and women (42% black, 51% women), aged 68-80 years. Total hip, femoral neck, and trochanter aBMD were measured using dual-energy X-ray absorptiometry. Quantitative computed tomography was used to evaluate spine trabecular, integral, and cortical vBMD measures in a subgroup (n = 1,489). Logistic regression was performed to examine associations of BMD measures with CVD and PAD. The prevalence of CVD (defined by coronary heart disease, PAD, cerebrovascular disease, or congestive heart failure) was 29.8%. Among participants without CVD, 10% had subclinical PAD (defined as ankle-arm index <0.9). Spine vBMD measures were inversely associated with CVD in men (odds ratio of integral [OR(integral)] = 1.34, 95% confidence interval [CI] 1.10-1.63; OR(trabecular )= 1.25, 95% CI 1.02-1.53; OR(cortical )= 1.36, 95% CI 1.11-1.65). In women, for each standard deviation decrease in integral vBMD, cortical vBMD, or trochanter aBMD, the odds of CVD were significantly increased by 28%, 27%, and 22%, respectively. Total hip aBMD was associated with subclinical PAD in men (OR = 1.39, 95% CI 1.03-1.84) but not in women. All associations were independent of age and shared risk factors between BMD and CVD and were not influenced by inflammatory cytokines (interleukin-6 and tumor necrosis factors-alpha). In conclusion, our results provide further evidence for an inverse association between BMD and CVD in men and women. Future research should investigate common pathophysiological links for osteoporosis and CVD.

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Subclinical Peripheral Arterial Disease and Incompressible Ankle Arteries Are Both Long-Term Prognostic Factors in Patients Undergoing Coronary Artery Bypass Grafting

This study was designed to determine the prevalence of peripheral arterial disease (PAD) in candidates for coronary artery bypass grafting (CABG) and to assess the predictive value of different types of subclinical PAD (peripheral occlusive disease and medial arterial calcification [incompressible ankle arteries]). Observational studies report poor prognosis after CABG in the presence of clinical PAD, but data on subclinical PAD are scarce. We prospectively enrolled CABG candidates and measured ankle-brachial index (ABI) preoperatively. Patients were divided into four groups: clinical PAD, subclinical PAD (ABI <0.85), incompressible arteries (ABI >1.5), and no PAD. The primary end point was a composite combining death, acute coronary syndrome, stroke or transient ischemic attack (TIA), and coronary or peripheral revascularization. Secondary end points were overall and cardiovascular death, acute coronary syndrome, and stroke or TIA. Statistical analyses were performed using the Cox regression model. We consecutively enrolled 1,022 patients (mean age 66.9 +/- 9.2 years). In addition to the 14% with clinical PAD, we detected subclinical PAD in 13% and medial artery calcification in 12%. During an actuarial follow-up of 4.4 years, 81.2% of patients remained event-free. Adverse factors were (p < 0.05) supraventricular arrhythmia (odds ratio [OR] 2.5), ejection fraction <0.40 (OR 2.3), combined valvular surgery (OR 2.5), clinical PAD (OR 3.6), subclinical PAD (OR 3.3), and medial artery calcification (OR 1.9). The latter three factors were also independently predictive for overall and cardiovascular death. Beyond clinical PAD, the measurement of ABI before coronary surgery provides substantial information on long-term postoperative prognosis. To our knowledge, this is the first study highlighting the prognostic role of incompressible ankle arteries in secondary prevention.

Relationship of Monocyte Count and Peripheral Arterial Disease

Although white blood cell (WBC) count has been consistently associated with cardiovascular end points, little information is available on the independent contribution of specific white blood cell types. The objective of this study is to assess the independent association of WBC types and other inflammatory markers with the presence of reduced ankle-brachial blood pressure index (ABI), a marker of subclinical peripheral arterial disease (PAD). Cross-sectional study in 3949 individuals > or =40 years of age without known cardiovascular disease who participated in the 1999 to 2002 National Health and Nutrition Examination Survey (NHANES). PAD was defined as an ABI <0.9 in at least 1 leg. After adjustment for traditional cardiovascular risk factors, the odds ratios of PAD comparing the highest to the lowest quartiles were 2.24 (95% confidence interval 1.24 to 4.04) for monocytes, 1.74 (0.87 to 3.45) for neutrophils, 2.53 (1.62 to 3.96) for C-reactive protein, and 2.68 (1.03 to 6.94) for fibrinogen. When WBC types and inflammatory markers were simultaneously included in the full model, the corresponding odds ratios were 1.91 (95% confidence interval 1.06 to 3.42) for monocytes, 1.15 (0.49 to 2.69) for neutrophils, 1.37 (0.75 to 2.49) for C-reactive protein, and 2.21 (0.88 to 5.57) for fibrinogen. Monocytes were the only WBC type significantly and independently associated with PAD in a representative sample of the U.S. population after adjustment for other inflammatory markers. These findings reflect the potential role of circulating monocyte counts as markers of atherosclerosis.

High prevalence of subclinical peripheral artery disease in Greek hospitalized patients

Background Peripheral artery disease (PAD) represents a common manifestation of systemic atherosclerosis that is associated with an increased risk of cardiovascular death and ischemic events but one that may be underdiagnosed in clinical practice. The purpose of this study was to identify PAD using the ankle–brachial index (ABI) in hospitalized patients from a Department of Internal Medicine and to further investigate the association of this index with traditional cardiovascular risk factors. Methods We measured ABI in 990 consecutive patients (400 men and 590 women) aged 50 years or older (71.2 ± 9.1) without a history or symptoms suggestive of PAD. ABI values below 0.90 were considered abnormal. Results PAD was detected in 356 patients (36%), and men had a higher prevalence than women ( p < 0.001). Hypertension ( p < 0.001), smoking ( p < 0.001), diabetes ( p < 0.05), male sex ( p < 0.001), and dyslipidemia ( p < 0.05) were statistically more frequent in patients with PAD, whereas obesity had no significant relation to PAD in our series. In a stepwise, logistic regression analysis, hypertension, male sex, diabetes mellitus, smoking, and dyslipidemia were found to be independent risk factors with odds ratios (95% confidence intervals) of 2.46 (1.85–3.27), 2.25 (1.66–3.05), 1.80 (1.32–2.47), 1.78 (1.31–2.42), and 1.64 (1.22–2.19), respectively. Conclusions A simple ABI measurement revealed a large number of patients with unrecognized PAD. It is, therefore, recommended that ABI measurement should be included in the evaluation of cardiovascular risk in hospitalized patients aged 50 years or older.

A predictive model for screening cerebrovascular disease in patient undergoing coronary artery bypass grafting

The occurrence of stroke during coronary artery bypass grafting (CABG) is multifactorial but the coexistence of carotid disease is considered as one of the avoidable sources. Beyond the perioperative management, the detection of carotid disease in a coronary patient could be of prognostic significance. A systematic screening for all candidates for CABG could, however, be a non-efficient strategy. We aimed to optimize the Duplex screening of candidates for CABG by studying risk factors of significant concomitant carotid lesions. We prospectively studied 1043 consecutive candidates for CABG by Duplex scanning. A first subgroup of 825 patients permitted to establish the predictive model of >50% stenosis. A multivariate analysis provided independent predictive factors. The ability of the model to predict >50% and >70% stenosis of neck arteries has been prospectively assessed on the 218 consecutive patients. In the first group, 108 (13.1%) and 58 (7%) had respectively at least a >50% and >70% stenosis. The independent risk factors were: past history of stroke or transient ischemic attack, neck bruit, clinically apparent peripheral arterial disease (PAD) or subclinical PAD (ABI <0.85 or >1.5), and age >70 years (P<0.05). Among the subsequent 218 patients, the presence of at least one of these factors was able to detect 24 out of 26 patients (92.3%) with a >50% stenosis, and 100% of those with >70% stenosis, and could rule out 41% from a systematic Duplex screening. The excellent sensitivity of this risk assessment approach, makes an efficient screening of cerebrovascular disease possible in CABG patients.

Subclinical peripheral arterial disease in patients with chronic kidney disease: Prevalence and related risk factors

Atherosclerotic artery disease is a common condition in patients with chronic kidney disease (CKD); however, there are few published data on the prevalence of peripheral arterial disease (PAD) in nondialyzed patients with renal insufficiency. The ankle-brachial index (ABI) is a simple, noninvasive, and reliable method to assess PAD. Prevalence of PAD using ABI was investigated in 102 patients referred for the first time to a nephrology clinic with CKD in stages 3 to 5 of the K/DOQI classification, and with no previous diagnosis of PAD. Patients with ABI <0.9 were considered positive for PAD. A total of 64% of the patients were male. The mean age was 70 +/- 11 (range 58-84) years, and the estimated creatinine clearance (CrCl) was 35 +/- 12 (range 6-59) mL/min(-1). Of the total sample, 26% were diabetics, 10% active smokers, 48% ex-smokers, and 29% had a diagnosis of coronary heart disease (CHD), 15% had been previously diagnosed of stroke, and 17% had signs and symptoms compatible with intermittent claudication, which had passed unnoticed. Thirty-two percent of patients had an ABI <0.9 (mean 0.64 +/- 0.25). Of these patients with PAD, 84% were men (P < 0.005), and only 30% presented a clinical picture compatible with intermittent claudication. Absolute risk of CHD according to the Framingham 1998 score was higher in the PAD group (19.3% +/- 6 vs. 13.1% +/- 8; P= 0.01). Patients with PAD were older (75 +/- 6 vs. 66 +/- 11 years, P= 0.000), and had worse renal function (CrCl 30.8 +/- 12 vs. 37 +/- 10.7 mL.min(-1), P= 0.016) compared to patients without PAD, but no differences were found in cholesterol levels (total, HDL, LDL), calcium, phosphorus, or PTH. In the logistic regression analysis, independent indicators of PAD risk were male sex, age, and lower CrCl. Twelve percent of patients had an ABI > or =1.3, suggestive of parietal arterial calcifications. In these patients, systolic blood pressure and pulse pressure were lower (126 +/- 18 vs. 150 +/- 27, P= 0.005, and 52 +/- 13 vs. 68 +/- 25 mm Hg, P= 0.044), i-PTH levels were higher (228 +/- 267 vs. 117 +/- 63 pg/mL, P= 0.01), and a larger proportion of this group was treated with calcitriol (34% vs. 13%) compared to patients with a normal ABI. A high prevalence of PAD, considered as an ABI <0.9, was demonstrated in nondialyzed patients with CKD. This was related with age, male sex, and higher degree of renal insufficiency, while the presence of ABI > or =1.3 was associated with a greater degree of hyperparathyroidism. These data show the need to carry out routine ABI determinations in patients with CKD for early detection of peripheral arterial disease.

Impact of ramipril in patients with evidence of clinical or subclinical peripheral arterial disease

Impact of ramipril in patients with evidence of clinical or subclinical peripheral arterial disease

Family history is a major determinant of subclinical peripheral arterial disease in young adults.

Cardiovascular disease is prevalent in first-degree relatives of young adults with premature-onset peripheral arterial occlusive disease (premature PAD), but it is not known whether the genetic influence is independent of other risk factors, the most prevalent of which is smoking. This study was performed to determine the relative contributions of family history and smoking to the development of occult PAD in siblings of patients with premature PAD. The prevalence of occult PAD was determined with carotid, abdominal, and lower extremity duplex ultrasound scanning in 50 asymptomatic siblings (25 men, 25 women) of patients with premature PAD (onset <or=49 years). Thirty of the siblings (60%) were active smokers, and 20 had never smoked. Age-matched and sex-matched reference groups included 50 asymptomatic heavy smokers (>20 cigarettes/day) and 50 nonsmokers. Duplex ultrasound scans demonstrated raised arterial lesions in 20 asymptomatic siblings (40%), 20 heavy smokers (40%), and 2 nonsmoking control subjects (4%), resulting in 42 affected and 108 unaffected subjects. As expected, smokers were far more likely to have arterial lesions than were nonsmokers (odds ratio [OR], 11.19; 95% confidence interval [CI], 4.1-30.7; P <.0001). Individuals with a family history of premature PAD were almost three times more likely to have arterial lesions than those with no family history of cardiovascular disease (OR, 2.76; 95% CI, 1.3-5.8; P =.006). Stratified and multivariable logistic regression indicated no interaction between smoking and family history, indicating simple additive effects on PAD. Family history is a major determinant of occult PAD in young adults, and is at least as important as standard atherosclerotic risk factors. A high proportion of heavy smokers have clearly detectable lesions even though asymptomatic. Smoking and family history act additively to increase the risk for premature PAD.

High prevalence of peripheral arterial disease in persons with renal insufficiency: results from the National Health and Nutrition Examination Survey 1999-2000.

Although renal insufficiency is a recognized risk factor for coronary artery disease, little is known about the epidemiology of lower-extremity peripheral arterial disease (PAD) in persons with renal insufficiency. We examined the cross-sectional association of PAD, defined as an ankle-brachial index (ABI) <0.9, and renal insufficiency, defined as an estimated creatinine clearance (CRCL) <60 mL. min(-1). 1.73 m(-2), among 2229 eligible participants in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2000. An estimated 1.2+/-0.3 million persons >/=40 years old with CRCL <60 mL. min(-1). 1.73 m(-2) (24%) have PAD defined as an ABI <0.9 (versus 3.7% of persons with CRCL >/=60 mL. min(-1). 1.73 m(-2)). The association of ABI <0.9 with renal insufficiency was independent of potential confounders such as age, diabetes, hypertension, coronary artery disease, stroke history, and hypercholesterolemia (OR 2.5, 95% CI 1.2 to 5.1, P=0.011, referent category ABI 1.0 to 1.3). Clinicians should be aware of the remarkably high prevalence of PAD among patients with renal insufficiency. In the clinical setting, accurate identification of patients with renal insufficiency combined with routine ABI measurement in this group would greatly enhance efforts to detect subclinical PAD.

Prevention Conference VI: Diabetes and Cardiovascular Disease: executive summary: conference proceeding for healthcare professionals from a special writing group of the American Heart Association.

The American Heart Association (AHA) sponsored a scientific conference entitled “Prevention VI: Diabetes and Cardiovascular Disease” on January 18 to 20, 2001, in Orlando, Fla. The purpose of this conference was to create a report that would assist the AHA in the development of an agenda to reduce cardiovascular diseases (CVDs) that are associated with diabetes. The report has been developed by working group sections. The topics to be covered by each working group were introduced by a series of presentations, and this was followed by an extensive discussion of a team of working group members. The primary objectives of this meeting were as follows: The key findings of each working group are presented in this Executive Summary of the conference. The full conference report with references is available online at http://www.circulationaha.org in the May 7, 2002, issue of Circulation . The prevalence of diabetes in the United States is increasing rapidly, and individuals with diabetes are at high risk for cardiovascular disorders that affect the heart, brain, and peripheral vessels. Although CVD accompanying diabetes is on the rise, many unanswered questions remain concerning the temporal relations between diabetes and CVD, the contributions of conventional risk factors, and the role of diabetes-specific risk factors. Almost 35 million Americans—20% …

THE INCIDENCE OF UNSUSPECTED PERIPHERAL ARTERIAL DISEASE AMONGST SURGICAL PATIENTS IN HONG KONG

A survey of surgical in-patients in Hong Kong has shown that subclinical peripheral arterial disease caused by atherosclerosis and detected by palpation is not uncommon and is similar in incidence to that reported in European populations. However, only a small proportion of affected patients had any associated symptoms. Reduced or absent ankle and ulnar pulses occurred with the same frequency in our patients as in those in Europe. Cigarette smoking does not appear to be associated with symptomatic arterial disease in the local population in Hong Kong.