Association between urinary stone disease and peripheral arterial disease in a rural population in Pinggu district of Beijing city

Objective To explore the association between urinary stone disease (USD) and peripheral arterial disease (PAD). Methods The study was based on the cross-sectional chronic diseases survey performed in Pinggu district, Beijing from March to May, 2014. All subjects completed a questionnaire, physical examination, renal ultrasound examination to detect USD, ankle-brachial index (ABI) examination to detect PAD (defined as ABI＜0.9 on either side of the body), and brachial-ankle pulse wave velocity (baPWV) measurement to estimate arterial stiffness. Blood and first morning urine sample were detected for serum creatinine, blood glucose and so on. Results There were 10 281 participants included in this study. Among these participants, the prevalences of USD and PAD were 5.66% and 3.95%, respectively. Compared with non-stone participants, the persistent USD formers had a higher prevalence of PAD (8.26% vs 3.90%, P＜0.001) and baPWV [(16.3±3.5) m/s vs (15.5±3.2) m/s, P＜0.001]. Even after adjusting the confounding factors, the persistent USD formers also had a 2.066-fold increased risk of PAD (OR=2.066, 95%CI 1.276-3.343, P=0.003). In the subgroup analysis, persistent USD patients in older participants who were≥60 years old, women, chronic kidney disease, and central obesity had a significantly increased risk of PAD. Conclusions In the present population, persistent USD is positively associated with a high risk of PAD and increased arterial stiffness. Patients with persistent USD should be screened for vascular diseases.     

Platelet activation is increased in peripheral arterial disease

OBJECTIVE: Platelet activation was assessed in patients with peripheral arterial disease compared with healthy control subjects. METHODS: This prospective comparative study included 100 subjects: 40 consecutive patients with intermittent claudication, 20 consecutive patients with critical ischemia and tissue loss, and 40 healthy control subjects. Whole blood flow cytometric analysis was performed to determine resting and stimulated platelet P-selectin expression and resting and stimulated platelet fibrinogen binding. Results are presented as platelet percentage and also as mean fluorescence intensity. RESULTS: P-selectin expression was significantly increased in patients with intermittent claudication (median, 0.85%; range, 0.31%-4.77%; P =.023) and critical ischemia (median, 1.11%; range, 0.2%-3.26%; P =.028) compared with control subjects (median, 0.59%; range, 0.16%-4.58%). The percentage of platelets binding fibrinogen was also significantly higher in patients with intermittent claudication (median, 2.89%; range, 1.08%-9.59%; P <.001) compared with control subjects (median, 1.57%; range, 0.17%-10.7%). There was no significant difference in percentage of platelet fibrinogen binding between control subjects and patients with critical ischemia. Fibrinogen binding by stimulated platelets was significantly diminished in patients with critical limb ischemia compared with control subjects (67.2% vs 77.9%; P =.006). CONCLUSIONS: Platelet activation is increased in patients with peripheral arterial disease, suggesting an underlying prothrombotic state. Platelets from patients with critical limb ischemia are less responsive to in vitro stimulation.     

Propionyl-L-carnitine therapy: effects on endothelin-1 and homocysteine levels in patients with peripheral arterial disease and end-stage renal disease

BACKGROUND/AIMS: Recent data have addressed the issue of higher levels of homocysteine (Hcy) and endothelin-1 (ET-1) in end-stage renal disease (ESRD) that may be considered an independent predictor for cardiovascular disease. The prevalence of peripheral arterial disease (PAD) in patients with ESRD has been reported to be relevant, highlighting its clinical importance. We aimed to explore the therapeutic role of propionyl-L-carnitine (PLC) in hemodialysis patients with PAD by measuring ankle/brachial index (ABI), ET-1 and Hcy. DESIGN: Randomized, double-blind, placebo-controlled trial. METHODS: Sixty-four patients on hemodialysis with chronic renal insufficiency and PAD were assigned to receive either intravenous PLC (600 mg) or placebo 3 times weekly for 12 months. The ABI and plasma levels of ET-1 and Hcy were measured at baseline, 6 and 12 months. RESULTS: In the PLC-treated group, progressive increases in ABI were observed, while in the placebo group the reverse trend was seen. Highly significant and progressive reductions in plasma levels of ET-1 and Hcy, compared to baseline, were also seen in the PLC-treated group. CONCLUSIONS: Hemodynamic flow, endothelial profile and Hcy levels were ameliorated by the administration of PLC in hemodialysis patients with ESRD and PAD.     

Hyperlipidemia in peripheral atherosclerotic arterial disease.

One hundred and ten patients with radiologically established peripheral atherosclerotic arterial disease were studied. None of them suffered from diabetes, endocrine disorders or renal disease. Their serum cholesterol and triglyceride values were compared with those of a reference group consisting of 548 individuals. When the 95th percentile of the reference values was used for cut-off, the frequency of hyperlipidemias in the patients with peripheral arterial atherosclerosis was about 52%. Combined hyperlipidemia was slightly more common (21%) than isolated increase of either cholesterol (17.9%) or triglycerides (12.6%). Using other cut-off limits for the definition of hyperlipidemia, a striking change in the distribution between these three types of hyperlipidemia occurred. In our patients, the frequencies of different blood groups were not significantly different from those of a comparable population. The serum lipids were at the same level in the different blood groups.     

Life-style modification in peripheral arterial disease.

OBJECTIVE: To review the published evidence supporting the use of life-style modification in peripheral arterial disease (PAD). DESIGN: A systematic search of the medical literature was performed for relevant studies. MATERIALS: The publications obtained were then searched for randomised clinical trials which reported end-points of mortality or major cardiovascular event rates with various life-style modifications. RESULTS: Only one randomised controlled trial was found reporting relevant end-points. Other trials were of other end-points such as walking distance or biochemical markers. CONCLUSIONS: There is a lack of randomised controlled data proving the benefit of life-style modification in improving mortality and reducing cardiovascular events in patients with PAD. Despite this there is sufficient evidence to recommend some life-style modification as part of the overall approach to risk reduction in these patients. There is compelling evidence to support smoking cessation, increased exercise and improved diet.     

Characteristics of peripheral arterial disease and its relevance to the diabetic population

Peripheral arterial disease (PAD) is very frequent in diabetics, and it increases with age. Foot examination contributes poorly to diagnosis of PAD. The ankle-brachial index (ABI) measurement is considered the most accurate noninvasive diagnostic method when evaluating PAD: ABI evaluation is recommended in all diabetics aged >50 years. Many diabetic patients with PAD have a concomitant sensitive neuropathy: as a consequence, perception of ischemic pain is remarkably reduced or completely blocked. The result is that the prevalence of claudication in the diabetic population with PAD is lower than the prevalence of critical limb ischemia (CLI) in this population. CLI is a major risk factor for lower extremity amputation without revascularization. Ankle and toe pressures and oxygen tension at the foot are the noninvasive diagnostic parameters of CLI though the medial artery calcification inhibits accurate determination of the ankle and toe pressures, especially when a forefoot ulcer is present. In diabetics, the anatomical localization is mainly distal; arterial wall calcification is frequently observed and occlusion occurs more frequently than stenosis. Such anatomical features, along with the difficulties in the diagnostic approach, account for the fundamental role of CLI as the main prognostic indicator for major amputation. PAD is an expression of systemic atherosclerotic disease. Prognosis of patients with PAD is related to the presence and extent of underlying coronary artery disease (CAD) but also to the severity of PAD: in particular, patients in whom revascularization is not feasible have the highest mortality rate.     

Validity of duplex scanning in the detection of peripheral arterial disease in the general population.

Duplex scanning has the potential to identify asymptomatic atherosclerosis of the lower limbs in the general population. The aim of this study was to assess the validity of scanning in a group of men and women aged 55-74, sampled from a population survey. Disease was measured using the WHO questionnaire on claudication, the ankle brachial pressure index, and a reactive hyperaemia test. In 73 cases of peripheral arterial disease and 91 controls, a duplex scan was conducted on both legs from the inguinal ligament to the lower popliteal region. The two radiologists performing the scans were blind to the arterial status of the subjects. Interpretation of the image, waveform and peak systolic velocity resulted in a sensitivity of 78%, specificity of 65% and positive predictive value of only 19%. The image alone had the best positive predictive value (62%) and specificity (97%). These results suggest that duplex scanning may currently be of limited use as a diagnostic screening test in the general population. Interpretation of the image alone, however, may be useful in some settings in identifying healthy subjects free of disease.     

Kidney function predicts the risk of asymptomatic peripheral arterial disease in a Chinese community-based population

Purpose

Lower-extremity peripheral arterial disease (PAD) can predict the risk of subsequent cardiovascular disease (CVD) and all-cause mortality. Chronic kidney disease (CKD) as a precursor of CVD has been proven to be independently associated with PAD. However, few data exist regarding the prediction value of kidney function for incident asymptomatic PAD in community-based populations. We aimed to investigate the predicting value of estimated glomerular filtration rate (eGFR) for incident asymptomatic PAD in a Chinese community-based population. A total of 3549 subjects without PAD and eGFR?>?30 ml/min/1.73 m² were included.

Methods

PAD was defined by an ankle-brachial index (ABI)?≤?0.9. Multivariate regression models were used to evaluate the associations.

Results

Subjects were 56.69?±?8.56 years old and 35.9% were males. After 2.36 years of follow-up, the incidence of asymptomatic PAD was 3.1%. The risk of incident PAD was graded related to the categories of eGFR. Compared to participants with normal kidney function, the multivariate adjusted OR [95% CI] for new PAD was 1.31 (0.81–2.12) for those with mildly decreased kidney function, 4.13 (1.73–9.89) for those with grades 3 CKD (P for trend: 0.014). Baseline eGFR was significantly and linearly associated with incident PAD (OR [95% CI] for each 5 mL/min/1.73 m² decrease of eGFR: 1.23 [1.09–1.38]) in participants with baseline eGFR?<?90 mL/min/1.73 m² but not in those with baseline eGFR?≥?90 mL/min/1.73 m² after adjustment for covariates.

Conclusion

Kidney function was an independent risk factor for development of incident PAD in community-based population with baseline eGFR?≤?90 mL/min/1.73 m².

     

Prospective blinded study of the relationship between plasma homocysteine and progression of symptomatic peripheral arterial disease

Purpose: An elevated plasma homocysteine level is an established risk factor for atherosclerotic coronary heart disease (CHD), cerebrovascular disease (CVD), and lower extremity occlusive disease (LED). An elevated plasma homocysteine level can be reduced by therapy with folate and vitamins B6 and B12. An accurate evaluation of the role of vitamin therapy requires knowledge of the influence of plasma homocysteine levels on the progression of CHD, CVD, and LED. Methods: The Homocysteine and Progression of Atherosclerosis Study is a blinded prospective study of the influence of homocysteine and of other atherosclerotic risk factors on the progression of disease in patients with symptomatic CVD, LED, or both. This study is set in a university hospital vascular surgery clinic and the General Clinical Research Center. Consecutive patients with stable symptomatic CVD or LED underwent baseline clinical, laboratory, and vascular laboratory testing for homocysteine and other risk factors and were examined every 6 months. The primary endpoints were ankle brachial pressure index, duplex scan–determined carotid stenosis, and death. The secondary endpoints were the clinical progressions of CHD, LED, and CVD. The hypothesis that was tested was whether the progression of symptomatic CVD or LED was more frequent or more rapid in patients with elevated plasma homocysteine levels. Results: After a mean follow-up period of 37 months (range, 1 to 78 months) for deaths from all causes (>14 μmol/L; elevated, 18.6%; normal, 9.4%; P = .022), deaths from cardiovascular disease (elevated, 12.5%; normal, 6.3%; P = .05) and the clinical progression of CHD (highest 20% of homocysteine levels, 80%; lowest 20% of homocysteine levels, 39%; P = .007) were significantly more frequent or more rapid by life-table analysis when the homocysteine levels were elevated. Multivariate Cox proportional hazards regression model showed a significant independent and increasing relationship between the plasma homocysteine levels and the time to death (relative risk for highest one third of homocysteine values, 1.6; 95% confidence interval [CI], 1.04 to 2.56; P = .029; and relative risk for highest one fifth of homocysteine values, 3.13; 95% CI, 1.69 to 6.64; P = .0001). After an adjustment for age, smoking, hypertension, diabetes, cholesterol, and the vascular laboratory progression of CVD or LED, each 1.0 μmol/L increase in the plasma homocysteine levels resulted in a 3.6% increase (95% CI, 0.0% to 6.6%; P = .06) in the risk of death (all causes) at 3 years and a 5.6% increase (95% CI, 2.2% to 8.5%; P = .003) in the risk of death from cardiovascular disease. Conclusion: We conclude that elevated plasma homocysteine levels are associated significantly with death, with death from cardiovascular disease, and with the progression of CHD in patients with symptomatic CVD or LED. These results strongly mandate clinical trials of homocysteine-lowering vitamin therapy in such patients. (J Vasc Surg 1999;29:8-21.)     

Increased platelet aggregation and activation in peripheral arterial disease.

OBJECTIVES: patients with peripheral arterial disease (PAD) have a threefold increase in cardiovascular mortality. Standard antiplatelet treatment may not confer uniform benefit in different patient groups. This study aimed to compare platelet function in patients with lower limb PAD, carotid disease and abdominal aortic aneurysm (AAA) with age- and sex-matched healthy controls. METHODS: patients with lower limb PAD (n = 20), carotid disease (n = 40), AAA (n = 13) and age/sex matched healthy controls (n= 20) were studied. Whole blood methods to detect spontaneous platelet aggregation (SPA), and adenosine diphosphate (ADP) and collagen-induced aggregation were used. The detection of platelet P-selectin and the PAC-1 antigen by flow cytometry were also used as markers of platelet activation and aggregation. RESULTS: patients with lower limb PAD or AAA had higher baseline SPA compared to normal controls (p < 0.01). There was significantly higher collagen-induced aggregation in IC patients compared to normal controls (p < 0.01). However, there was no difference in ADP-induced aggregation between lower limb PAD and control patients. There was no difference in PAC-1 binding between control patients and the patients with lower limb PAD, carotid disease or AAA. Patients with carotid disease had a higher expression of P-selectin compared to normal controls (p < 0.05). CONCLUSIONS: this study provides further evidence that platelet hyperactivity is present in patients with PAD despite the use of antiplatelet therapy. Further antiplatelet strategies may be indicated to protect these patients.     

Elevated thioredoxin after angioplasty in peripheral arterial disease.

OBJECTIVE: Oxidative stress and inflammation in the vessel wall may play important roles in the development of restenosis after angioplasty. Reactive oxygen species have been suggested to mediate the proliferative phenotype in smooth muscle cells. The role of the redox-active proteins, thioredoxin and glutaredoxin, after angioplasty in patients with peripheral arterial disease has never been assessed before. Circulating thioredoxin impairs the chemotactic response to local sites of inflammation and administration of human recombinant Trx has been shown to attenuate ischemic reperfusion injury. METHODS AND RESULTS: Patients with peripheral arterial disease undergoing angioplasty were included in this observational study. Plasma levels of thioredoxin and glutaredoxin were analysed before and 1, 4 and 24 h, and 1 week after angioplasty. Plasma levels of thioredoxin were significantly elevated 4 h after angioplasty [2.3 ng/ml (0.5-14), p=0.02] and returned to baseline within 24 h [1.1 ng/ml (0.5-3.1), p=0.02]. There may also exist an association between patients with elevated levels of thioredoxin after angioplasty and decreased rate of restenosis at follow-up angiography after 6 months. There were no changes in plasma levels of glutaredoxin after angioplasty. CONCLUSION: These findings provide a new insight to the role of thioredoxin in the complex process of vascular injury and restenosis in patients with peripheral arterial disease, suggesting thioredoxin both as a marker of oxidative stress and as a therapeutic agent.     

Homocysteine levels and peripheral arterial occlusive disease: a prospective cohort study and review of the literature

AIM: The aim of this study was to determine the prevalence of hyperhomocysteinemia in a population with peripheral vascular occlusive disease in Kuwait. METHODS: From November 2000 to May 2002, total serum homocysteine levels were measured in 172 consecutive patients admitted to the vascular surgery unit because of peripheral vascular arterial disease. A fluorescence polarization immunoassay was used for measuring total serum homocysteine levels. Serum homocysteine levels over 15 mol/L were considered as high. RESULTS: The mean ankle-brachial index was 0.59+/-0.2 and 0.55+/-0.2 for right and left legs, respectively. The mean serum homocysteine level was 14.9+/-4.7 mol/L (range, 4.2-50.0). High homocysteine levels were found in 70 out of 172 patients (40.7%). The prevalence of hyperhomocysteinemia was significant in patients with hypertension (P=0.03) and ischaemic heart disease (P=0.04). Binary logistic regression model showed that male gender, diabetes mellitus and hypertension were significant independent predictors for high levels of homocystinemia in peripheral vascular occlusive disease [adjusted odds ratio (OR) 2.90; 95% confidence interval (CI); 1.18-7.12; P=0.02]; [0.35 OR; 95% CI; 0.15-0.79; P=0.01] and [2.12 OR; 95% CI; 0.98-4.59; P=0.05], respectively. Diabetes was significant but appeared to protect for peripheral vascular occlusive disease in patients with high levels of serum homocysteine. CONCLUSION: Elevated homocysteinemia was found in 40.7% of patients suffering from peripheral vascular disease. In this cohort, male gender, diabetes and hypertension were found to be risk factors along with elevated homocysteine levels.     

Mitochondriopathy of peripheral arterial disease

The signs and symptoms of peripheral arterial occlusive disease (PAD), including claudication, rest pain, and tissue loss, are consequences of compromised bioenergetics and oxidative tissue injury within the affected lower extremities. Compromised bioenergetics is the result of a combination of low blood flow through diseased arteries and diminished adenosine triphosphate production by dysfunctional mitochondria. The tissue injury appears to be secondary to increased production of reactive oxygen species by dysfunctional mitochondria and by inflammation, in association with ischemia and ischemia/reperfusion. In this review, we present the current histomorphologic, physiologic, and biochemical evidence defining the nature of this mitochondriopathy and discuss its contribution to the pathogenesis and clinical manifestations of PAD.     

Association of arterial calcification with chronic limb ischemia in patients with peripheral artery disease

Objective

Arterial calcification is associated with an increased risk of limb events, including amputation. The association between calcification in lower extremity arteries and the severity of ischemia, however, has not been assessed. We thus sought to determine whether the extent of peripheral artery calcification (PAC) was correlated with Rutherford chronic ischemia categories and hypothesized that it could independently contribute to worsening limb status.