Large-vessel Peripheral Arterial Disease Research Articles

Risk of Cardiovascular Mortality in Relation to Increased Total Serum IgE Levels in Older Adults: A Population-Based Cohort Study.

Background: Despite a potential link between immunoglobulin E (IgE) levels and cardiovascular disease, the effect of elevated total IgE levels on long-term mortality risk remains unclear. We prospectively investigated the association between total serum IgE levels and all-cause and cardiovascular mortality in US adults. Methods: We analyzed data from the 2005–2006 National Health and Nutrition Examination Survey (NHANES) and the NHANES (2005–2006) Linked Mortality Public File. The 2005–2006 NHANES data of 1496 older adults aged ≥50 years and who underwent a serum total IgE antibody test in the initial survey were included. Results: After a median follow-up of 119 months, a significant association was observed between total serum IgE levels and cardiovascular mortality, with subjects with the highest total IgE exhibiting a 3.19-fold (HR = 3.19; 95% confidence interval: 1.71–5.96) increase in the risk of cardiovascular mortality compared with those with the lowest total IgE (≤16.80 kU/L). Furthermore, the mortality rate increased with an increase in total IgE levels, regardless of baseline history of cardiovascular diseases (e.g., myocardial infarction, stroke, and noninvasively diagnosed large-vessel peripheral arterial disease). Conclusions: This finding suggests that the elevation of IgE levels may be a risk factor for increased cardiovascular mortality.

Peripheral Arterial Disease and Cardiovascular Risk

Peripheral arterial disease (PAD) refers to the obstruction of large arteries of the body. The prevalence of PAD in the general population is estimated to be around 12% to 14% and increases up to 20% of those over 70 years old. It is of interest that 70% to 80% of affected individuals are asymptomatic and only a minority requires revascularization or amputation. Major risk factors for PAD are smoking, physical inactivity, dyslipidemias, hypertension, diabetes, and, consequently, the metabolic syndrome (MetS); PAD affects approximately 30% of people with diabetes mellitus. Since the early 1990s, studies revealed the association between PAD and mortality from cardiovascular disease (CVD). For example, Criqui et al evaluated the association of large-vessel PAD with mortality rates from CVD and reported that the relative risk of dying among patients with large-vessel PAD when compared to those with no largevessel disease was 3.1-fold higher (95% confidence interval [CI] 1.9-4.9) for all-cause mortality and 5.9-fold higher (95% CI 3.0-11.4) for CVD mortality. Diet has long been investigated in relation to CVD risk and its major risk factors, like dyslipidemia, hypertension, diabetes, and the MetS. A recent systematic search of the literature based on 15 relevant observational studies that evaluated the direct effect of diet on CVD risk reported that the attributable risk of an unhealthy dietary pattern varies from 9% to 37%; moreover, the authors observed that the inclusion of diet component in CVD risk scores may increase the accuracy of the models and better identify people at high risk. The Mediterranean diet is one of the most known and studied dietary patterns in relation to human health. It was described in the late 1960s by Ancel Keys in the Seven Countries Study. This traditional dietary pattern is characterized by daily consumption of olive oil, fruits and vegetables, nonrefined grains and dairy products as well as weekly consumption of fish and poultry, potatoes, olives, nuts and legumes, and monthly consumption of red meat. Another major characteristic of this dietary pattern is the moderate consumption of alcohol, mainly wine (1-2 glasses/d), usually with meals. However, it should be acknowledged that although the dietary patterns that prevail in the wider Mediterranean region share many common characteristics, the macronutrient distribution varies from area to area. Nevertheless, studies from the Mediterranean region as well as from other parts of the world strongly support the cardioprotective role of this dietary pattern, mainly through its beneficial role on cardiometabolic markers. At this point it is important to mention that the Mediterranean diet may exert its positive influence on human health and CVD particularly due to its antioxidant and anti-inflammatory effects. Despite the large body of evidence regarding Mediterranean diet and CVD mortality and morbidity, the role of this traditional dietary pattern on risk of PAD has been rarely studied. Very recently, Ruiz-Canela et al, in a randomized trial conducted from October 2003 and December 2010 in Spain, assessed the association between Mediterranean diet and the occurrence of symptomatic PAD in 7477 participants with type 2 diabetes mellitus or at least 3 cardiovascular risk factors, aged 55 to 80 years and without clinical PAD or baseline CVD. Participants were randomized to the following groups: a Mediterranean diet supplemented with extra virgin olive oil, a Mediterranean diet supplemented with nuts, or counseling on a low-fat diet (control group). All participants received a comprehensive dietary educational program on a quarterly basis. Both Mediterranean diet intervention groups were associated with lower risk of PAD compared to the control group. A mechanistic hypothesis of the beneficial effect of Mediterranean diet on PAD may be due its pleiotropic beneficial effects on endothelial function, arterial blood pressure, lipids, and glucose

Guest Editorial: are diabetes‐related wounds and amputations worse than cancer?

Certainly one of the most feared complications of diabetes is the lower extremity amputation 1. This fear is not unwarranted. Diabetes-related ulcer and amputation may be associated with surprisingly high 5-year mortality. Moulik et al.2 reported a 5-year mortality of 45%, 18% and 55% for neuropathic, neuroischaemic and ischaemic ulcers, respectively. As expected, mortality was higher in ischaemic ulcers than neuropathic ulcers. However, it is fairly evident based on these data that all types of diabetic foot ulcers are associated with high morbidity and mortality. Similarly, approximately half the persons receiving a diabetes-related amputation will not be alive in 5 years. Certainly, peripheral vascular disease may be implicated as a significant factor associated with shorter life span. Criqui reported the 10-year mortality in patients with peripheral arterial disease and found a substantially higher risk of mortality among patients with large vessel peripheral arterial disease – a factor that may be even more profound today than when it was reported in the early 1990s 3, 4. Faglia et al. related this high mortality with the absence of revascularisation, citing a 1.7-fold greater risk for death in ischaemic subjects who might have benefited from intervention 5. How do these data compare with other serious medical conditions, such as cancer? If one reviews Figure 1, one might conclude that persons with lower extremity complications of diabetes have 5-year mortality rates similar or worse than many common types of cancer 6-10. In fact, some high-risk subgroups such as persons with renal disease requiring distal bypass may have 5-year mortality rates approaching 95% 10. Five-year mortality (%). Perhaps now is the time to change our discussion with health-care administrators, policy makers and especially ourselves. The disease state that many of us treat routinely is, quite literally, killing our patients at a rate comparable to cancer. Addressing this issue aggressively may alter this and make a difference for millions of people worldwide.

Risk Factors for Progression of Peripheral Arterial Disease in Large and Small Vessels

Data on the natural history of peripheral arterial disease (PAD) are scarce and are focused primarily on clinical symptoms. Using noninvasive tests, we assessed the role of traditional and novel risk factors on PAD progression. We hypothesized that the risk factors for large-vessel PAD (LV-PAD) progression might differ from small-vessel PAD (SV-PAD). Between 1990 and 1994, patients seen during the prior 10 years in our vascular laboratories were invited for a new vascular examination. The first assessment provided baseline data, with follow-up data obtained at this study. The highest decile of decline was considered major progression, which was a -0.30 ankle brachial index decrease for LV-PAD and a -0.27 toe brachial index decrease for SV-PAD progression. In addition to traditional risk factors, the roles of high-sensitivity C-reactive protein, serum amyloid-A, lipoprotein(a), and homocysteine were assessed. Over the average follow-up interval of 4.6+/-2.5 years, the 403 patients showed a significant ankle brachial index and toe brachial index deterioration. In multivariable analysis, current smoking, ratio of total to HDL cholesterol, lipoprotein(a), and high-sensitivity C-reactive protein were related to LV-PAD progression, whereas only diabetes was associated with SV-PAD progression. Risk factors contribute differentially to the progression of LV-PAD and SV-PAD. Cigarette smoking, lipids, and inflammation contribute to LV-PAD progression, whereas diabetes was the only significant predictor of SV-PAD progression.

Serum Ig E Concentration In Acute Pulmonary Thromboembolism

Background : Events mediated by immunoglobulin E (IgE) may be related to platelet activation and aggregation, and serum IgE concentrations may increase in various vascular diseases such as previous myocardial infarction, previous stroke and current large-vessel peripheral arterial disease. There may be an association between serum IgE and acute pulmonary thromboembolism (PTE). Objectives : The aim of the study was to evaluate serum IgE concentrations in patients with acute PTE. Methods : Twenty-two patients with a diagnosis of acute PTE were included in the study. Serum IgE concentrations were measured by an automated microparticle enzyme immunoassay at the time of diagnosis and 5th, 15th, and 30th days after the diagnosis. Because serum IgE concentrations follow a log-normal distribution, all subsequent analysis were performed on a log transformed scale and geometric mean values were used. The Wilcoxon matched-pairs signed-ranks test was applied for paired analysis. Results : Serum IgE concentrations (geometric mean ± SEM) were 1.90 ± 0.15, 1.91 ± 0.16, 1.82 ± 0.15, and 1.76 ± 0.15 at the time of diagnosis and 5th , 15th, and 30th days after the diagnosis, respectively. Serum IgE concentrations were not significantly different between at the time of diagnosis and 5th day after the diagnosis. However, serum IgE concentrations were significantly lesser at the 15th and 30th days after the diagnosis than serum IgE concentrations at the time of diagnosis and at 5th days after the diagnosis (p < 0.001). Conclusions : The data evaluating serum IgE concentrations in patients with acute PTE is limited and, to our knowledge, until now there has been only one study. Our study showed that serum IgE concentrations that were detected at the time of diagnosis of acute PTE significantly lessen with treatment at the 15th and 30th days after the diagnosis.

The generalized nature of atherosclerosis: how peripheral arterial disease may predict adverse events from coronary artery disease

Non-invasive measurements, especially segmental pressure ratios and flow measurements, are useful for gauging the severity of peripheral arterial disease (PAD). Although the incidence of PAD is similar for men and women, men are more likely to have severe disease, while women usually have more moderate or asymptomatic disease. Published reports confirm the clinical impression that patients with PAD are more likely to have both coronary artery disease and cerebrovascular disease than those without PAD. However, the degree of overlap is a function of the sensitivity of the diagnostic assessments for the three conditions. A San Diego population study found that the incidence of PAD may be underestimated, with many patients being asymptomatic. Based on blood flow measurements, the study found that 11.9% of the study population had large vessel PAD. Morbidity from both coronary heart disease and stroke was increased in people with PAD, who were 2.5 times more likely to present with morbidity from cardiovascular disease (CVD) than those who did not have PAD. Several studies have now confirmed the strong predictive value of PAD for subsequent CVD mortality and that the risk of CVD mortality increases with the severity of PAD.

Screening for Peripheral Arterial Disease: The Sensitivity, Specificity, and Predictive Value of Noninvasive Tests in a Defined Population

Large vessel peripheral arterial disease (LV-PAD) is a common condition that causes significant morbidity and disability. The authors evaluated the individual components of a comprehensive noninvasive vascular examination to identify the most sensitive and specific measurements for diagnosing LV-PAD. This cohort, initially screened between 1979 and 1981 in Rancho Bernardo, California, included 421 normal subjects and 63 subjects with LV-PAD. Segmental blood pressure ratios and flow velocities by Doppler ultrasound were used to define cases of LV-PAD. The sensitivity, specificity, positive predictive value, and negative predictive value of each individual component of the diagnostic algorithm were determined. Overall, measurements of posterior tibial flow showed the highest sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy. In addition, an absent or non-recordable posterior tibial peak forward flow, occurring in 96% of all limbs with isolated posterior tibial disease, or an ankle ratio < or = 0.8 considered in parallel yielded a test with sensitivity of 89%, specificity of 99%, positive predictive value of 90%, negative predictive value of 99%, and overall accuracy of 98%. These results indicate that the vast majority of LV-PAD cases can be detected with a single measurement using a handheld Doppler flowmeter employed at the ankle.

Mortality over a Period of 10 Years in Patients with Peripheral Arterial Disease

Previous investigators have observed a doubling of the mortality rate among patients with intermittent claudication, and we have reported a fourfold increase in the overall mortality rate among subjects with large-vessel peripheral arterial disease, as diagnosed by noninvasive testing. In this study, we investigated the association of large-vessel peripheral arterial disease with rates of mortality from all cardiovascular diseases and from coronary heart disease. We examined 565 men and women (average age, 66 years) for the presence of large-vessel peripheral arterial disease by means of two noninvasive techniques--measurement of segmental blood pressure and determination of flow velocity by Doppler ultrasound. We identified 67 subjects with the disease (11.9 percent), whom we followed prospectively for 10 years. Twenty-one of the 34 men (61.8 percent) and 11 of the 33 women (33.3 percent) with large-vessel peripheral arterial disease died during follow-up, as compared with 31 of the 183 men (16.9 percent) and 26 of the 225 women (11.6 percent) without evidence of peripheral arterial disease. After multivariate adjustment for age, sex, and other risk factors for cardiovascular disease, the relative risk of dying among subjects with large-vessel peripheral arterial disease as compared with those with no evidence of such disease was 3.1 (95 percent confidence interval, 1.9 to 4.9) for deaths from all causes, 5.9 (95 percent confidence interval, 3.0 to 11.4) for all deaths from cardiovascular disease, and 6.6 (95 percent confidence interval, 2.9 to 14.9) for deaths from coronary heart disease. The relative risk of death from causes other than cardiovascular disease was not significantly increased among the subjects with large-vessel peripheral arterial disease. After the exclusion of subjects who had a history of cardiovascular disease at base line, the relative risks among those with large-vessel peripheral arterial disease remained significantly elevated. Additional analyses revealed a 15-fold increase in rates of mortality due to cardiovascular disease and coronary heart disease among subjects with large-vessel peripheral arterial disease that was both severe and symptomatic. Patients with large-vessel peripheral arterial disease have a high risk of death from cardiovascular causes.

Coronary Disease and Stroke in Patients with Large-Vessel Peripheral Arterial Disease

Previous reports have indicated an excess of mortality from coronary heart disease (CHD), cardiovascular disease (CVD), and all causes in subjects with large-vessel peripheral arterial disease (LV-PAD). However, there is little information available concerning the risk of nonfatal events (morbidity) in this patient group. In a population-based study of 67 patients with LV-PAD and 408 control subjects without this condition, nonfatal CHD and stroke, and total CVD events, morbidity and mortality were evaluated in both men and women. Those with LV-PAD had a 3-fold excess of CVD morbidity at baseline compared with control subjects of the same sex. However, the absolute CVD rates were greater in men than women. During the 10 years of follow-up, women with LV-PAD had more nonfatal CVD events than men, resulting in comparable overall morbidity rates. In logistic regression models adjusted for other CVD risk factors, total CVD morbidity and mortality combined with 2.5 times as great in men and 5 times as great in women with LV-PAD as in those without peripheral arterial disease. These results suggest that the total morbidity and mortality burden are dramatically increased in both men and women with LV-PAD.

Peripheral arterial disease in large vessels is epidemiologically distinct from small vessel disease. An analysis of risk factors.

The authors used noninvasive techniques, including flow velocity by Doppler ultrasound, to accurately assess and distinguish between large and small vessel peripheral arterial disease in a population study in southern California, 1978-1981. In 565 men and women aged 38-82 years, there were 69 cases of large vessel peripheral arterial disease, 19 of which were severe, and 90 cases of isolated small vessel peripheral arterial disease. In cross-sectional multivariate analysis in men, large vessel peripheral arterial disease was significantly associated with age, pack-years of cigarettes smoked, systolic blood pressure, fasting plasma glucose, and marginally with obesity. Similar analysis in women revealed significant associations only for age and systolic blood pressure, although the associations for pack-years of cigarettes, obesity, and low density lipoprotein cholesterol were suggestive. By contrast, isolated small vessel peripheral arterial disease was not significantly associated with any of the major cardiovascular disease risk factors, including two measures of carbohydrate metabolism, fasting plasma glucose and glycosylated hemoglobin. These findings, coupled with our earlier report that large vessel peripheral arterial disease but not isolated small vessel peripheral arterial disease was independently predictive of subsequent mortality, suggest that large vessel peripheral arterial disease and isolated small vessel peripheral arterial disease are epidemiologically, as well as pathophysiologically, distinct entities.

Ige and cardiovascular disease: Results from a population-based study

Because previous reports have suggested that IgE-mediated events may lead to both platelet activation and arterial spasm, a population-based study of 262 men and 315 women, aged 38 to 82, was conducted to investigate the association of serum IgE levels with myocardial infarction, stroke, and noninvasively diagnosed large-vessel peripheral arterial disease. In men with previous myocardial infarction, previous stroke, or current large-vessel peripheral arterial disease, geometric mean serum IgE levels were increased 119 percent, 164 percent, and 78 percent, respectively. These associations were statistically significant (p <0.05). Because IgE was positively or inversely correlated with several traditional cardiovascular disease risk factors, logistic regression was used to evaluate the independent association of IgE with any cardiovascular disease (myocardial infarction, stroke, or large-vessel peripheral arterial disease). In a model including age, cigarette smoking, fasting plasma glucose level, diastolic blood pressure, and low-density lipoprotein cholesterol level as covariates, IgE was positively and independently associated with any cardiovascular disease (p = 0.03). Similar evaluations in women revealed no correlation between IgE and cardiovascular disease by either univariate or multivariable analysis. These data indicate that IgE may be an independent marker for cardiovascular disease in men, and thus suggest IgE-mediated events may play a role in the pathogenesis of cardiovascular disease.

Noninvasively diagnosed peripheral arterial disease as a predictor of mortality: results from a prospective study.

Intermittent claudication has been reported in previous studies to approximately double the risk of subsequent mortality. However, a history of claudication is often present in the absence of significant peripheral arterial disease (PAD) and absent in the presence of PAD. For this reason we evaluated the association between large-vessel and small-vessel PAD, measured by highly reliable and valid noninvasive tests, and mortality in 567 older subjects from a defined population followed-up for an average of 4 years. Large-vessel PAD was strongly and significantly predictive of all-cause mortality in both men and women with a relative risk of 4 to 5, and this finding was independent of other cardiovascular disease risk factors in multivariable analysis. In addition, this finding persisted after exclusion of subjects with extant cardiovascular disease at baseline. The associations of both claudication and abnormal peripheral pulses with mortality were weaker than the large-vessel PAD association. Isolated small-vessel PAD was unrelated to subsequent mortality. These findings suggest older subjects of both sexes at a high risk of impending mortality can be identified through noninvasive testing for large-vessel PAD.

The sensitivity, specificity, and predictive value of traditional clinical evaluation of peripheral arterial disease: results from noninvasive testing in a defined population.

In a companion article we have reported the prevalence, in an older, defined population, of traditional assessments (intermittent claudication and abnormal pulse examination) of peripheral arterial disease (PAD) as compared with the results of highly accurate noninvasive testing. In this article we report the sensitivity, specificity, and positive and negative predictive values for claudication and abnormal pulses for the diagnosis of large-vessel and small-vessel PAD as determined by noninvasive testing. Claudication and abnormal pulses were completely unrelated to isolated small-vessel PAD. In contrast, both claudication and abnormal pulses were significantly correlated with large-vessel PAD. Claudication and an abnormal femoral pulse showed a high specificity and positive predictive value but a low sensitivity for large-vessel PAD. Conversely, an abnormal dorsalis pedis pulse showed a good sensitivity but low specificity and positive predictive value. The best single discriminator was an abnormal posterior tibial pulse, which had high sensitivity, specificity, and positive predictive value. Various combinations of claudication and pulse abnormalities revealed a good sensitivity for broader criteria but at the expense of specificity, whereas stricter criteria had a good specificity and positive predictive value but a poor sensitivity. No combination was superior to an abnormal posterior tibial pulse alone.(ABSTRACT TRUNCATED AT 250 WORDS)

The prevalence of peripheral arterial disease in a defined population.

Because patients with peripheral arterial disease (PAD) may be asymptomatic or may present with atypical symptoms or findings, the true population prevalence of PAD is essentially unknown. We used four highly reliable, sophisticated noninvasive tests (segmental blood pressure, flow velocity by Doppler ultrasound, postocclusive reactive hyperemia, and pulse reappearance half-time) to assess the prevalence of large-vessel PAD and small-vessel PAD in an older (average age 66 years) defined population of 613 men and women. A total of 11.7% of the population had large-vessel PAD on noninvasive testing, and nearly half of those with large-vessel PAD also had small-vessel PAD (5.2%). An additional 16.0% of the population had isolated small-vessel PAD. Large-vessel PAD increased dramatically with age and was slightly more common in men and in subjects with hyperlipidemia. Isolated small-vessel PAD, by contrast, was essentially unrelated to sex, hyperlipidemia, or age, although it was somewhat less common before age 60. Intermittent claudication rates in this population were 2.2% in men and 1.7% in women, and abnormalities in femoral or posterior tibial pulse were present in 20.3% of men and 22.1% of women compared with the noninvasively assessed large-vessel PAD rate of 11.7%. Thus assessment of large-vessel PAD prevalence by intermittent claudication dramatically underestimated the true large-vessel PAD prevalence and assessment by peripheral pulse examination dramatically overestimated the true prevalence.