natriuretic-peptide--brain and Peripheral-Arterial-Disease

Supervised exercise training (walking) is recommended in patients with intermittent claudication, both as a means to improve symptoms (walking distance and quality of life [QoL]) and as a means to improve general cardiovascular health (including vascular function and heart rate variability [HRV]). Our aim was to compare two types of supervised training (moderate-pain and pain-free walking) with comparable intensity based on heart rate, in terms of walking capacity, QoL, vascular function, biomarkers, and HRV in patients with intermittent claudication.. Thirty-six adults with intermittent claudication were randomized to either moderate-pain or pain-free exercise training (36 sessions, two or three times a week) or usual care (no supervised exercise). Initial walking distance and absolute walking distance using treadmill testing, flow-mediated vasodilation and pulse wave velocity using ultrasound, N-terminal pro-B-type natriuretic peptide and fibrinogen levels, HRV, and QoL (36-Item Short Form Health Survey questionnaire) were determined at baseline and after the intervention period.. Twenty-nine patients (mean age, 64 ± 9 years; 72% male) completed the study. Both training programs similarly improved walking capacity. Initial walking distance and absolute walking distance significantly increased with either moderate-pain walking (median, 50 m to 107 m [P = .005] and 85 m to 194 m [P = .005], respectively) or pain-free walking (median, 53 m to 128 m [P = .003] and 92 m to 163 m [P = .003], respectively). QoL also similarly improved with both training modalities, whereas only moderate-pain walking was also associated with a statistically significant improvement in the vascular parameters flow-mediated vasodilation (4.4% to 8.0%; P = .002) and pulse wave velocity (6.6 m/s to 6.1 m/s; P = .013). Neither training program was associated with changes in biomarker levels and HRV.. Both moderate-pain and pain-free training modalities were safe and similarly improved walking capacity and health-related QoL. Conversely, vascular function improvements were associated with only moderate-pain walking.

Topics: Aged; Biomarkers; Exercise Therapy; Exercise Tolerance; Female; Fibrinogen; Health Status; Heart Rate; Hemodynamics; Humans; Intermittent Claudication; Male; Middle Aged; Natriuretic Peptide, Brain; Pain Measurement; Peptide Fragments; Peripheral Arterial Disease; Prospective Studies; Quality of Life; Recovery of Function; Slovenia; Time Factors; Treatment Outcome; Vascular Stiffness; Vasodilation; Walk Test; Walking

Patients with peripheral artery disease (PAD) are at high risk of excess mortality despite major improvements in multimodal pharmacotherapy for cardiovascular disease. However, little is known about co-prevalences and implications for the combination of heart failure (HF) and PAD. Thus, NT-proBNP as a suggested surrogate for HF was evaluated in symptomatic PAD regarding long-term mortality. After approval by the institutional ethics committee a total of 1028 patients with PAD, both with intermittent claudication or critical limb ischemia were included after admission for endovascular repair and were followed up for a median of 4.6 years. Survival information was obtained from central death database queries. During the observation period a total of 336 patients died (calculated annual death rate of 7.1%). NT-proBNP (per one standard deviation increase) was highly associated with outcome in the general cohort in crude (HR 1.86, 95%CI 1.73-2.01) and multivariable-adjusted Cox-regression analyses with all-cause mortality (HR 1.71, 95%CI 1.56-1.89) and CV mortality (HR 1.86, 95% CI 1.55-2.15). Similar HR's were found in patients with previously documented HF (HR 1.90, 95% CI 1.54-2.38) and without (HR 1.88, 95%CI 1.72-2.05). NT-proBNP levels were independently associated with below-the-knee lesions or multisite target lesions (OR 1.14, 95% CI 1.01-1.30). Our data indicate that increasing NT-proBNP levels are independently associated with long-term mortality in symptomatic PAD patients irrespective of a previously documented HF diagnosis. HF might thus be highly underreported in PAD, especially in patients with the need for below-the-knee revascularization.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Phenotype; Prognosis

NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T (hs-troponin T), and high-sensitivity cardiac troponin I (hs-troponin I) are increasingly being recommended for risk stratification for a variety of cardiovascular outcomes. The aims of our study were to establish the prevalence and associations of elevated NT-proBNP, hs-troponin T, and hs-troponin I with lower extremity disease, including peripheral artery disease (PAD) and peripheral neuropathy (PN), in the US general adult population without known cardiovascular disease. We also assessed whether the combination of PAD or PN and elevated cardiac biomarkers was associated with an increased risk of all-cause and cardiovascular mortality.. We conducted a cross-sectional analysis of the associations of NT-proBNP, hs-troponin T, and hs-troponin I with PAD (based on ankle-brachial index <0.90) and PN (diagnosed by monofilament testing) in adult participants aged ≥40 years of age without prevalent cardiovascular disease in NHANES (National Health and Nutrition Examination Survey) 1999 to 2004. We calculated the prevalence of elevated cardiac biomarkers among adults with PAD and PN and used multivariable logistic regression to assess the associations of each cardiac biomarker, modeled using clinical cut points, with PAD and PN separately. We used multivariable Cox proportional hazards models to assess the adjusted associations of cross categories of clinical categories of each cardiac biomarker and PAD or PN with all-cause and cardiovascular mortality.. In US adults aged ≥40 years, the prevalence (±SE) of PAD was 4.1±0.2% and the prevalence of PN was 12.0±0.5%. The prevalence of elevated NT-proBNP (≥125 ng/L), hs-troponin T (≥6 ng/L), and hs-troponin I (≥6 ng/L for men and ≥4 ng/L for women) was 54.0±3.4%, 73.9±3.5%, and 32.3±3.7%, respectively, among adults with PAD and 32.9±1.9%, 72.8±2.0%, and 22.7±1.9%, respectively, among adults with PN. There was a strong, graded association of higher clinical categories of NT-proBNP with PAD after adjusting for cardiovascular risk factors. Clinical categories of elevated hs-troponin T and hs-troponin I were strongly associated with PN in adjusted models. After a maximum follow-up of 21 years, elevated NT-proBNP, hs-troponin T, and hs-troponin I were each associated with all-cause and cardiovascular mortality, with higher risks of death observed among adults with elevated cardiac biomarkers plus PAD or PN compared with elevated biomarkers alone.. Our study establishes a high burden of subclinical cardiovascular disease defined by cardiac biomarkers in people with PAD or PN. Cardiac biomarkers provided prognostic information for mortality within and across PAD and PN status, supporting the use of these biomarkers for risk stratification among adults without prevalent cardiovascular disease.

Topics: Adult; Biomarkers; Cardiovascular Diseases; Cross-Sectional Studies; Female; Humans; Male; Natriuretic Peptide, Brain; Nutrition Surveys; Peptide Fragments; Peripheral Arterial Disease; Peripheral Nervous System Diseases; Prognosis; Risk Factors; Troponin I; Troponin T

We investigated the associations of high-sensitivity cardiac Troponin T (hs-cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels with risk of developing clinical peripheral artery disease (PAD) or a low ankle-brachial index (ABI).. Hs-cTnT and NT-proBNP were measured in 6692 and 5458 participants respectively without baseline PAD between 2000 and 2002 in the Multi-ethnic Study of Atherosclerosis. A significant number also had repeat biomarker measurement between 2004 and 2005. Incident clinical PAD was ascertained through 2017. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15 from baseline, was assessed among 5920 eligible individuals who had an ABI >0.9 at baseline and at least one follow-up ABI measurement 3-10 years later. Multivariable Cox proportional hazards and logistic regression modeling were used to determine the association of these biomarkers with clinical PAD and low ABI, respectively.. Overall, 121 clinical PAD and 118 low ABI events occurred. Adjusting for demographic and clinical characteristics, each log unit increment in hs-cTnT and NT-proBNP was associated with a 30% (adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI): 1.1, 1.6) and 50% (HR) 1.5, 95% CI: 1.2, 1.8) higher risk of clinical PAD respectively. No significant associations were observed for incident low ABI. Change in these biomarkers was not associated with either of the PAD outcomes.. NT-proBNP and hs-cTnT are independently associated with the development of clinical PAD. Further study should determine whether these biomarkers can help to better identify those at higher risk for PAD.

Topics: Ankle Brachial Index; Atherosclerosis; Biomarkers; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Risk Factors; Troponin T

N-terminal pro B-type natriuretic peptide (NT-proBNP), a cardiac disease biomarker, has been demonstrated to be a strong independent predictor of cardiovascular events in patients without heart failure. Patients with peripheral arterial disease (PAD) are at high risk of cardiovascular events and death. In this study, we investigated levels of NT-proBNP in patients with PAD compared to non-PAD controls. A total of 355 patients were recruited from outpatient clinics at a tertiary care hospital network. Plasma NT-proBNP levels were quantified using protein multiplex. There were 279 patients with both clinical and diagnostic features of PAD and 76 control patients without PAD (non-PAD cohort). Compared with non-PAD patients, median (IQR) NT-proBNP levels in PAD patients were significantly higher (225 ng/L (120-363) vs 285 ng/L (188-425), p- value = 0.001, respectively). Regression analysis demonstrated that NT-proBNP remained significantly higher in patients with PAD relative to non-PAD despite adjusting for age, sex, hypercholesterolemia, smoking and hypertension [odds ratio = 1.28 (1.07-1.54), p-value <0.05]. Subgroup analysis showed elevated NT-proBNP levels in patients with PAD regardless of prior history of CHF, CAD, diabetes and hypercholesteremia (p-value <0.05). Finally, spearmen's correlation analysis demonstrated a negative correlation between NT-proBNP and ABI (ρ = -0.242; p-value < 0.001). In conclusion, our data shows that patients with PAD in an ambulatory care setting have elevated levels of NT-proBNP compared to non-PAD patients in the absence of cardiac symptoms.

Topics: Aged; Comorbidity; Diabetes Mellitus; Female; Heart Diseases; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatient Clinics, Hospital; Outpatients; Peptide Fragments; Peripheral Arterial Disease; Smoking

Brain natriuretic peptide (BNP) is introduced as a predictor of the degree of ventricular dysfunction and is associated with mortality. There are limited reports on the relationship of BNP with long-term all-cause death (AD) and cardiovascular or limb events in peripheral artery disease (PAD). We examined the relationship between BNP level and these events in PAD patients.. We performed a prospective cohort study in 938 PAD patients. The patients were divided into four groups based on BNP levels with median (interquartile range): Q1: ≤20.4; Q2: 20.5-42.8; Q3: 42.9-103.4; and Q4: ≥103.5 pg/mL. The endpoints were AD, freedom from major adverse cardiovascular events (MACE), and MACE plus limb events (MALE).. The median follow-up time was 65 months. There were 383 deaths (40.8%) during follow-up period. AD depended on BNP levels (P<0.01), with 5-year freedom from AD rates of Q1: 94%, Q2: 84%, Q3: 69%, and Q4: 55%. The Kaplan-Meier estimates of freedom from AD, MACE, and MALE had significant differences among Q1- Q4 groups (P<0.001). In multiple regression analysis, BNP had significant negative correlations with eGFR, serum albumin, and BMI and positive correlations with diabetes (P<0.05). In Cox multivariate analysis, higher BNP, age, CRP, D-dimer, lower BMI, ABI, serum albumin, and eGFR were related to AD; and higher BNP, age, lower ABI, serum albumin, CAD, and DM were related to MACE and MALE (P<0.05). Statins improved AD, MACE, and MALE (P<0.01).. BNP was a promising biomarker for AD, MACE, and MALE in patients with PAD.

Topics: Biomarkers; Humans; Life Expectancy; Natriuretic Peptide, Brain; Peripheral Arterial Disease; Predictive Value of Tests; Prognosis; Prospective Studies

Among changes in demographics, aging is the most relevant cardiovascular risk factor. The prevalence of peripheral artery disease (PAD) is high in elderly patients and is associated with a worse prognosis. Despite optimal treatments, mortality in the high-risk population of octo- and nonagenarians with PAD remains excessive, and predictive factors need to be identified. The objective of this study was to investigate predictors of mortality in octo- and nonagenarians with PAD.. Cases of treated octo- and nonagenarians, including the clinical characteristics and markers of myocardial injury and heart failure, were studied retrospectively with respect to all-cause mortality. Hazard ratios [HR] were calculated and survival was analyzed by Kaplan-Meyer curves and receiver operating characteristic curved were assessed for troponin-ultra and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and chronic limb-threatening ischemia (CLTI).. A total of 123 octo- and nonagenarians admitted for PAD were eligible. The troponin level was the major predictor of all-cause mortality (HR: 4.6, 95% confidence interval [CI]: 1.4-15.3), followed by the NT-proBNP level (HR: 3.9, 95% CI 1.8-8.8) and CLTI (HR: 3.1, 95% CI 1.6-5.9). Multivariate regression revealed that each increment of 1 standard deviation in log troponin and log NT-proBNP was associated with a 2.7-fold (95% CI 1.8-4.1) and a 1.9-fold (95% CI 1.2-2.9) increased risk of all-cause death. Receiver operating characteristic curve analysis using a combination of all predictors yielded an improved area under the curve of 0.888. In a control group of an equal number of younger individuals, only NT-proBNP (HR: 4.2, 95% CI 1.2-14.1) and CLTI (HR: 6.1, 95% CI 1.6-23.4) were predictive of mortality.. Our study demonstrates that cardiovascular biomarkers and CLTI are the primary predictors of increased mortality in elderly PAD patients. Further risk stratification through biomarkers in this high-risk population of octo- and nonagenarians with PAD is necessary.

Topics: Age Factors; Aged; Aged, 80 and over; Aging; Biomarkers; Chronic Disease; Female; Humans; Ischemia; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Troponin

The cause of perioperative myocardial infarction (PMI) is postulated to involve hemodynamic stress or coronary plaque destabilization. We aimed to evaluate perioperative factors in patients with peripheral artery disease (PAD) undergoing major vascular surgery to determine the likely mechanisms and predictors of PMI.. This was a prospective cohort study of 133 patients undergoing major vascular surgery including open abdominal aortic aneurysm (AAA) repair (n = 40) and major suprainguinal or infrainguinal arterial bypasses (non-AAA; n = 93). Preoperative assessment with history, physical examination, and peripheral artery tonometry was performed in addition to plasma sampling of biomarkers associated with inflammation and coronary plaque instability. The primary outcome was occurrence of a 30-day cardiovascular event (CVE; composite of PMI [troponin I elevation >99th percentile reference of ≥0.1 μg/L], stroke, or death).. Of 133 patients, 36 patients (27%) developed a 30-day CVE after vascular surgery, and all were PMI. Patients with 30-day CVE were older (75 ± 8 years vs 69 ± 10 years, mean ± standard deviation; P = .001), had higher prevalence of hypertension (94% vs 79%; P = .01) and preoperative beta-blocker therapy (50% vs 29%; P = .02), and had longer duration of surgery (5.1 ± 1.8 hours vs 4.0 ± 1.1 hours; P < .0001). Significant elevations in cystatin C, N-terminal pro-B-type natriuretic peptide (NT-proBNP), troponin I, high-sensitivity troponin T, matrix metalloproteinase 3, and osteoprotegerin occurred in those who developed 30-day CVE (all P < .05). Multivariate binary logistic regression identified AAA surgery and log-transformed NT-proBNP to be independent preoperative predictors of 30-day CVE (area under the receiver operating characteristic curve = 0.81).. In patients with peripheral artery disease undergoing major vascular surgery, the likely mechanism of PMI appears to be the hemodynamic stress related to the type and duration of surgery. NT-proBNP was a useful independent predictor of CVE and thus may serve as an important biomarker of cardiovascular fitness for surgery.

Topics: Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Biomarkers; Female; Humans; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Operative Time; Peptide Fragments; Peripheral Arterial Disease; Postoperative Complications; Predictive Value of Tests; Preoperative Care; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Vascular Surgical Procedures

Peripheral artery disease (PAD) becomes more prevalent with advancing age and is associated with elevated risk of cardiovascular events and shortened life expectancy. We investigated the prognostic performance of cardiac and vascular biomarkers in a cohort of PAD patients.. A total of 95 PAD patients were enrolled (mean age 68 years, range 47 to 86 years, 73 males). Carotid intima-media thickness (cIMT), ankle brachial index (ABI), high sensitive cardiac troponin T, and N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) were measured.. During a median follow-up time of 9.5 years, 44 patients died and 51 patients survived. Upon Kaplan-Meier survival analysis hs-TnT (P < .001) or NT-proBNP levels (P < .001) above the median but not cIMT above the median (P = .488) or ABI below the median (P < .436)were associated with reduced survival rate. Upon univariate cox regression and after adjustment for age, gender, prior cerebral artery disease, and diabetes mellitus only the association between hs-cTnT and mortality remained significant (HR 1.93, 95% CI 1.33-2.79, P < .001). In receiver operating curve analysis hs-cTnT (area under the curve [AUC]: 0.77, 95% CI: 0.67-0.87, P < .001) NT-proBNP (AUC: 0.74, 95% CI: 0.64-0.84, P < .001) as well as hs-cTnT, and NT-proBNP combined (AUC: 0.79, 95% CI: 0.69-0.88, P < .001) were superior to cIMT (AUC: 0.64, 95%, CI: 0.53-0.76, P = .022) and ABI (AUC: 0.57, 95% CI: 0.44-0.68, P = .313) in discriminating risk for mortality.. hs-cTnT and NT-proBNP should be taken into account for prognosis of patients with PAD.

Topics: Aged; Aged, 80 and over; Ankle Brachial Index; Atherosclerosis; Biomarkers; Carotid Intima-Media Thickness; Female; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Prognosis

To analyze the incidence rates (IR) and spectrum of vascular events in people living with HIV (PLWH) in Spain from 2004 to 2015. Serial measurements of different plasma cardiovascular biomarkers were assessed in relation to disease development.. Longitudinal study in a nationwide contemporary multicenter cohort of PLWH. A nested case-control study was performed to evaluate the predictive value of cardiovascular biomarkers. Additive generalized and Cox mixed models were used for the analyses.. 9,712 PLWH and 48,341 person-years of follow-up were analysed. During 2004-2015, 147 persons developed 154 vascular events; 80 (54.42%) coronary-related; 65 (44.22%) cerebrovascular-related, and 9 (6.12%) peripheral arterial disease. The 2004-2015 IR (95% confidence interval) of vascular events was 3.17 (2.69-3.71) x1,000 person-years; 1.64 (1.30-2.05) for coronary events; 1.34 (1.03-1.70) for cerebrovascular events; and 0.19 (0.09-0.35) for peripheral arterial disease (p<0.001). IR of vascular events gradually increased from 0.37 (0.12-0.85) x1,000 patient-years in the stratum 25-34-years to 19.65 (6.38-45.85) x1,000 patient-years in the stratum 75-84-years. Compared to the general population, there was a higher incidence of acute myocardial infarction (AMI) in men (sIR ratio 1.29 [95% CI 1.16-1.42]), of cerebrovascular events in women (sIR ratio 2.44 [95% CI 1.68-3.19]), and of both types of events specifically among the younger age-strata. CD4 count (hazard ratio 0.80, [95% CI, 0.79-0.81]), age (1.86 [1.47-2.34] for 45-65 years and 3.44 [2.37-4.97] for >65 years) and vascular event (1.81 [1.12-2.94]) were associated with total mortality. Adjusted levels of intercellular-adhesion-molecule (sICAM), pro-b-type-natriuretic-peptide (pro-BNP) and marginally sCD14, were higher among patients who subsequently developed vascular events.. Vascular events in PLWH do preferentially occur in the older age-strata, they are associated with increased mortality and, compared to the general population, the excess risk occurs at younger ages. Peripheral arterial disease is unusual. Vascular events are preceded by increased levels of sICAM, pro-BNP and, marginally, sCD14.

Topics: Adult; Age Factors; Biomarkers; Case-Control Studies; Cerebrovascular Disorders; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Intercellular Adhesion Molecule-1; Lipopolysaccharide Receptors; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Predictive Value of Tests; Risk Assessment; Risk Factors; Sex Factors; Spain

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Cholesterol; Cystatin C; Diabetes Mellitus; Female; Glycopeptides; Humans; Hypertension; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Prospective Studies; Protein Precursors; Risk Factors; Sex Factors; Smoking; Sweden

Methods to identify patients at risk for incident HF would be welcome as such patients might benefit from earlier interventions.. From a registry of 1251 patients referred for coronary and/or peripheral angiography, we sought to identify independent predictors of incident HF during follow-up and develop a clinical and biomarker strategy to predict this outcome. There were 991 patients free of prevalent HF at baseline. Cox proportional hazard models were developed to predict adjudicated diagnosis of incident HF. Model discrimination and reclassification were evaluated. At follow-up, 177 (18%) developed new-onset HF. Independent predictors of new-onset HF included five clinical variables (age, male sex, heart rate, history of atrial fibrillation/flutter, and history of hypertension) and two biomarkers (amino-terminal pro-B type natriuretic peptide and ST2). The c-statistic for the model without biomarkers was 0.69; including biomarkers increased the c-statistic to 0.76 (P < 0.001). A score was developed from the model. Patients in the highest score quintile had shortest time to incident HF compared with lower quintiles (log-rank P < 0.001). Following 100 bootstrap iterations, internal validation was confirmed with Harrell's c-statistic of 0.77. Use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers at enrollment was associated with substantial attenuation of predictive value of the risk score.. Patients undergoing coronary/peripheral angiographic procedures are a population at high risk for incident HF. We describe an accurate clinical and biomarker strategy for predicting incident HF and possibly intervening in such patients (NCT00842868).

Topics: Aged; Angiography; Biomarkers; Catheterization; Coronary Artery Disease; Female; Follow-Up Studies; Heart Failure; Humans; Incidence; Male; Massachusetts; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Prognosis; Registries; Retrospective Studies; Risk Assessment; Time Factors

Cardiac troponin T (cTnT) is suggested as a predictor of amputation in patients with peripheral artery disease (PAD). However, cTnT-PAD association has not been systematically studied in a large study. This study evaluated the association of high-sensitivity cTnT (hs-cTnT) with PAD incidence and also explored whether natriuretic peptide (NT-proBNP), another representative cardiac marker, predicts PAD risk.. Among 12 288 middle-aged adults, the associations of hs-cTnT and NT-proBNP with incident PAD (hospitalizations with PAD diagnosis or leg revascularization [cases with rest pain or tissue loss considered as critical limb ischaemia (CLI)]) were quantified with multivariable Cox regression models. The risk discrimination was assessed by c-statistic. During a follow-up over 22 years, 454 participants developed PAD (164 CLI cases). In demographically adjusted models, the highest category of hs-cTnT (≥14 vs. <3 ng/L) and NT-proBNP (≥258.3 vs. <51.5 pg/mL) showed ∼8- and 10-20-fold higher risk of PAD and CLI, respectively. Even after adjusting for potential confounders and each other, hazard ratios were greater for CLI than for PAD (7.74 95% confidence interval [95% CI 4.43-13.55] vs. 2.84 [2.02-4.00] for the highest vs. reference hs-cTnT category and 4.63 [2.61-8.23] vs. 3.16 [2.23-4.49] for the highest vs. reference NT-proBNP category). The addition of these cardiac markers improved c-statistics for CLI.. High-sensitivity cTnT and NT-proBNP were independently associated with incident PAD, particularly its severe form, CLI. Although future studies are warranted to investigate pathophysiological mechanisms behind these associations, our study suggests the usefulness of cardiac markers to identify individuals at high risk of CLI.

Topics: Female; Humans; Incidence; Leg; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Predictive Value of Tests; Prospective Studies; Risk Assessment; Sensitivity and Specificity; Troponin T

The aim was to investigate whether cardiopulmonary exercise testing (CPET) variables derived from cycle and arm ergonometry correlate, and whether CPET variables and pre-operative N-terminal pro-brain natriuretic peptide (NT-proBNP) have prognostic significance and if the combination of the two has incremental value.. A prospective observational pilot study was conducted; 70 patients who underwent infra-inguinal bypass surgery were recruited. Pre-operatively subjects underwent CPET with both arm and leg ergonometry, to measure peak oxygen consumption, anaerobic threshold (AT), and ventilatory equivalents. In addition pre-operative serum samples of NT-proBNP were obtained. The primary endpoint was 1 year all-cause mortality; in addition, data were collected on complications, morbidity, length of stay, and major adverse cardiac events (MACE).. The measurement of pre-operative NT-proBNP in peripheral vascular disease patients undergoing infra-inguinal bypass can predict 1 year mortality and MACE. CPET variables from cycle ergonometry are predictors of post-operative complications in this patient group.

Topics: Aged; Anaerobic Threshold; Biomarkers; Chi-Square Distribution; Exercise Test; Female; Humans; Kaplan-Meier Estimate; Length of Stay; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Oxygen Consumption; Peptide Fragments; Peripheral Arterial Disease; Pilot Projects; Predictive Value of Tests; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vascular Grafting

Peripheral artery disease (PAD) is a risk factor for the development of heart failure and mortality. The serum levels of carboxy-terminal telopeptide of type I collagen (I-CTP), a marker for collagen degradation derived from the extracellular matrix of vascular and myocardial tissue, is reportedly a useful marker for cardiac events in patients with heart disease. However, it remains unclear whether I-CTP can predict poor clinical outcome in patients with PAD. Serum I-CTP was measured in 246 consecutive PAD patients who underwent endovascular therapy. Patients were prospectively followed during a median follow-up period of 887 days with the end points of major adverse cardiovascular events (MACE). I-CTP was significantly higher in patients with critical limb ischemia than those without. A multivariate Cox proportional hazard analysis revealed that I-CTP was an independent predictor of MACE after adjusting for confounding factors. Patients were stratified into three groups based on I-CTP level tertile, and those with third tertile had higher levels of brain natriuretic peptide levels and high-sensitivity C-reactive protein compared to the other two groups. Kaplan-Meier analysis demonstrated that patients in the highest tertile of I-CTP also had the greatest risk of MACE. The net reclassification index significantly improved with the addition of I-CTP to basic predictors. I-CTP is a reliable marker and indicator for MACE in patients with PAD.

Topics: Aged; Aged, 80 and over; Ankle Brachial Index; Biomarkers; Blood Pressure; C-Reactive Protein; Cause of Death; Collagen Type I; Computed Tomography Angiography; Endovascular Procedures; Female; Heart Failure; Humans; Japan; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Peptides; Peripheral Arterial Disease; Prospective Studies; Risk Assessment; Risk Factors; ROC Curve; Survival Analysis

The purpose of our study was to determine outcome differences as a function of baseline high-sensitivity C-reactive protein (hsCRP) and B-type natriuretic peptide (BNP) levels in patients receiving lower extremity open reconstructions for the treatment of peripheral arterial occlusive disease. We retrospectively examined patients who underwent surgical reconstructions performed by a single operator during a seven-year time span who received preoperative hsCRP and BNP testing and post-procedure imaging. Outcomes of interest included major adverse limb events, a composite end point of target vessel revascularization, limb amputation, and disease progression, and major adverse cardiovascular events comprised of stroke, myocardial infarction, and death. A total of 89 limbs in 82 patients were included in analysis. Multivariate analysis demonstrated that higher hsCRP levels (>3.0 mg/L) trended toward, but failed to significantly associate with major adverse limb events at 24 months (hazard ratio: 2.2 [1.0-5.2], p = 0.06), however the use of a vein bypass conduit (vs. prosthetic reconstruction) significantly predicted major adverse limb events (hazard ratio: 3.2 [1.5-6.9], p < 0.01). Elevated BNP levels (>100 pg/ml), but not hsCRP, associated with major adverse cardiovascular events (hazard ratio: 3.5 [1.2-10.3], p = 0.03). Preoperative biochemical markers may assist in clinical decision making and stratifying patients regarding adverse events following open reconstructions.

Topics: Aged; Amputation, Surgical; Biomarkers; C-Reactive Protein; Chi-Square Distribution; Decision Support Techniques; Disease Progression; Female; Humans; Kaplan-Meier Estimate; Limb Salvage; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Patient Selection; Peripheral Arterial Disease; Plastic Surgery Procedures; Predictive Value of Tests; Proportional Hazards Models; Reoperation; Retrospective Studies; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Up-Regulation; Vascular Surgical Procedures

Low ankle-brachial index (ABI) is associated with increased mortality and an increased incidence of cardiovascular events. The purpose of this study was to investigate the value of borderline ABI in predicting clinical outcomes.. The data were derived from the Shinken Database 2004-2012, from a single hospital-based cohort study (N = 19,994). ABI was measured in 5205 subjects; 4756 subjects whose ABI was 0.91-1.39 and having no history of peripheral artery disease were enrolled. The subjects were classified into two groups as follows: borderline ABI (0.91-1.00; n = 324) and normal ABI (1.01-1.39; n = 4432). Subjects in the borderline ABI group had more comorbidities, including diabetes mellitus, aortic disease, and stroke. Moreover, the borderline ABI group was associated with higher levels of hemoglobin A1c and brain natriuretic peptide, larger diameters of left atrium and left ventricle, and lower levels of estimated glomerular filtration rate and left ventricular ejection fraction. All-cause death and cardiovascular death occurred in 9.3% and 4.6% of subjects in the borderline ABI group, and in 2.0% and 0.8% of subjects in the normal ABI group, respectively. An adjusted Cox regression model showed that borderline ABI was associated with a higher incidence of all-cause death (hazard ratio [HR] 2.27, p = 0.005) and cardiovascular death (HR 3.47, p = 0.003).. A borderline ABI was independently associated with worse clinical outcomes in relatively high risk population. Our data should be confirmed in larger populations including those with low risk profiles.

Topics: Aged; Ankle Brachial Index; Databases, Factual; Diabetes Mellitus; Female; Follow-Up Studies; Glycated Hemoglobin; Heart Atria; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peripheral Arterial Disease; Predictive Value of Tests; Proportional Hazards Models; Registries; Treatment Outcome

Cardiovascular morbidity is high among patients with peripheral arterial occlusive disease (PAOD). The aim of this study was to evaluate the ability of ischemia-modified albumin (IMA), N-terminal proBNP (NT-proBNP), and high-sensitive cardiac Troponin T (hs-cTnT) to predict cardiovascular complications in male patients with Fontaine stage II PAOD.. 68 men with stage II PAOD underwent treadmill testing. NT-proBNP, IMA and hs-cTnT were measured before and after exercise. Patients were followed up prospectively and complete follow-up data were available for 66 individuals.. Median follow-up time was 43.0months. 12 (18.2%) patients had suffered from a major adverse cardiac event (MACE). IMA and NT-proBNP baseline concentrations were significantly higher in patients who developed MACE during follow-up: IMA: 110.6±2.4kU/L vs. 102.5±0.9kU/L (p<0.001); NT-proBNP: 270.5±295.9ng/L vs. 84.6±15.4ng/L (p=0.007). In multivariable regression models only IMA was significantly associated with the primary endpoint (HR=1.07, CI 1.01-1.13; p=0.029).. In the present study, a serum concentration of >103.9kU/L of IMA was a better independent predictor of MACE than NT-proBNP or hs-cTnT. IMA might be a valuable tool for risk stratification in PAOD patients.

Topics: Aged; Biomarkers; Exercise Test; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Peripheral Arterial Disease; Prognosis; Prospective Studies; Risk Factors; Serum Albumin; Serum Albumin, Human; Troponin T

Individuals with an impaired ventricular function have a poor prognosis due to underlying heart failure and higher mortality rates. Patients with peripheral arterial disease (PAD) represent a high-risk population for left ventricular systolic dysfunction (LVSD).. The left ventricular ejection fraction (LVEF) was measured in a subset of the CAVASIC Study, consisting of 180 male patients with intermittent claudication and 226 controls. The patients were prospectively followed for a median time of 7 years. The association of LVEF with PAD and prevalent cardiovascular disease (CVD) as well as with incident CVD and survival rates during follow-up was analyzed.. The prevalence of LVSD (LVEF<55%) was 30% among PAD patients and 7% among controls (p < 0.001). The adjusted logistic regression analysis showed that a decrease of LVEF by one standard deviation (SD) and an LVEF below 55% was associated with PAD (OR = 1.72, 95%CI 1.30-2.28 and OR = 5.71, 95%CI 2.52-12.95, both p < 0.001). Similar results were found for prevalent CVD (n = 50) in PAD patients: LVEF per SD: OR 1.60; LVEF <55%: OR 2.81, both p ≤ 0.008. The adjustment for ln-NT-proBNP or hs-cTnT resulted in a borderline significant association. In the adjusted Cox regression analysis a decrease of LVEF by one SD showed a trend for association with all-cause mortality (n = 32) (HR 1.27, p = 0.08). An impaired LVEF significantly increased the risk for incident major CVD events (n = 52): HR 1.56, p < 0.01.. Patients with PAD have significantly lower LVEF values compared to controls. The LVEF can serve as a risk predictor for subsequent cardiovascular disease among this high-risk population.

Topics: Aged; Austria; Biomarkers; Case-Control Studies; Chi-Square Distribution; Follow-Up Studies; Humans; Incidence; Intermittent Claudication; Linear Models; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Peripheral Arterial Disease; Prevalence; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Troponin T; Ventricular Dysfunction, Left; Ventricular Function, Left

Blood flow in lower extremity arteries is frequently impaired in diabetic patients even though they have a normal ankle-brachial index (ABI 1.0-1.4). Risk factors contributing to this lower extremity arterial disease have not been fully elucidated. We enrolled 52 type 2 diabetic patients with normal ABI and 30 age-matched nondiabetic subjects consecutively admitted to our hospital. Plasma B-type natriuretic peptide (BNP) concentrations were measured. Distensibility in ascending thoracic and abdominal aortas as well as total flow volume and resistive index at popliteal artery were evaluated by gated magnetic resonance imaging. An automatic device was used to measure ABI and brachial-ankle pulse-wave velocity (baPWV). Diabetic patients showed lower distensibility in ascending thoracic aorta (p<0.001) and total flow volume (p<0.001) and higher baPWV (p<0.001) and resistive index (p=0.005) and similar BNP and distensibility in abdominal aorta compared to nondiabetic subjects. Simple linear regression analyses revealed that distensibility in ascending thoracic (p=0.019) and abdominal (p=0.030) aortas positively as well as baPWV (p=0.020), resistive index (p<0.001) and BNP (p<0.001) negatively correlated with total flow volume. Stepwise multiple regression analysis demonstrated that increased BNP and resistive index were independent risk factors for total flow volume in diabetic patients (r(2)=0.639, p<0.001). These results indicate that increased plasma BNP levels and peripheral vascular resistance, but not decreased aortic distensibility, associate with impaired blood flow in lower extremity arteries in diabetic patients.

Topics: Aged; Ankle Brachial Index; Aorta; Aortography; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Elasticity; Female; Humans; Japan; Magnetic Resonance Angiography; Male; Middle Aged; Natriuretic Peptide, Brain; Peripheral Arterial Disease; Popliteal Artery; Pulse Wave Analysis; Regional Blood Flow; Risk Factors; Up-Regulation; Vascular Resistance

Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, has recently emerged as a predictor of survival and cardiovascular risk. Along with others, we have shown an independent association between PlGF and cardiovascular events in CKD patients, but not much is known about patients receiving dialysis.. We studied 205 dialysis patients undergoing cardiac catheterization at the Nara Medical University between April 1, 2004, and December 31, 2012. Serum levels of PlGF and VEGF were measured with ELISA in all the patients.. During a median follow-up of 20 months, 121 participants died from any cause or experienced a cardiovascular event. In the fully adjusted analysis, having an above-median PlGF or VEGF level was associated with a hazards ratio for adverse outcomes of 2.55 (1.72-3.83) and 1.39 (0.95-2.04), respectively. Using a multimarker strategy in a model with age, serum albumin, history of coronary artery disease, brain natriuretic peptide and PlGF, patients with 2, 3 and 4 positive markers had a 3.82-, 5.77- and 6.59-fold higher risk of mortality or a cardiovascular event, respectively, compared to those with no positive markers. The model with PlGF had a significantly higher c-statistic, integrated discrimination improvement index and category-free net reclassification improvement index than the model without PlGF.. PlGF is independently associated with mortality and cardiovascular events, but the association between VEGF and adverse events was attenuated with covariate adjustment. The addition of PlGF to models with established clinical predictors provides additional useful prognostic information in patients receiving dialysis.

Topics: Aged; Aortic Aneurysm; Aortic Diseases; Aortic Dissection; Aortic Rupture; Cardiovascular Diseases; Coronary Artery Disease; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Peripheral Arterial Disease; Placenta Growth Factor; Pregnancy Proteins; Prognosis; Proportional Hazards Models; Renal Dialysis; Stroke; Vascular Endothelial Growth Factor A

Atherosclerotic peripheral arterial disease (PAD) is one of the most prevalent, morbid, and mortal diseases. The aim of this study was to evaluate mortality rates of patients with atherosclerotic PAD stratified according to age and diabetes and to determine predictors of death.. We studied 487 patients with symptomatic PAD consecutively admitted to the hospital. This cohort included the following four patient subgroups: (1) 216 patients with PAD <75 years of age without diabetes mellitus; (2) 115 patients with PAD < 75 years of age with diabetes mellitus; (3) 102 patients with PAD ≥ 75 years of age without diabetes mellitus; and (4) 54 patients with PAD ≥ 75 years of age with diabetes mellitus. Control subjects without atherosclerotic disease were matched to the patients with PAD in a 1:1 design by sex, age (± 2 years), and diabetes mellitus status. Outcome measure was all-cause mortality at 5 years.. Mortality rates at 5 years were 10% in nondiabetic patients with PAD < 75 years of age (vs 5% in control subjects; risk ratio [RR], 2.15; 95% confidence interval [CI], 1.60-4.34); 23% in diabetic patients with PAD < 75 years of age (vs 7% in control subjects; RR, 3.53; 95% CI, 1.80-6.91); 38% in nondiabetic patients with PAD ≥ 75 years of age (vs 22% in control subjects; RR, 2.08; 95% CI, 1.26-3.44); and 52% in diabetic patients with PAD ≥ 75 years of age. Applying multivariate Cox proportional hazards regression analyses (with cardiovascular risk factors, coexisting atherosclerotic disease, clinical stage of PAD, and several biochemical markers as predictor variables), we found the following independent predictors of outcome: in the 216 nondiabetic patients with PAD < 75 years of age, high-sensitivity C-reactive protein (hs-CRP) (RR, 3.04; 95% CI, 1.48-6.26); in the 115 diabetic patients with PAD < 75 years of age, amino-terminal pro-B-type natriuretic peptide (NT-proBNP) (RR, 2.63; 95% CI, 1.65-4.19); in the 102 nondiabetic patients with PAD ≥ 75 years of age, critical limb ischemia (RR, 3.70; 95% CI, 1.82-7.52) and NT-proBNP (RR, 1.93; 95% CI, 1.32-2.82); and in the 54 diabetic patients with PAD ≥ 75 years of age, hs-CRP (RR, 2.61; 95% CI, 1.45-4.67) and NT-proBNP (RR, 3.31; 95% CI, 1.96-5.60).. Mortality rates at 5 years varied considerably among patients with PAD stratified according to age and diabetes. Predictors of death differed among the four patient subgroups in this study and included critical limb ischemia, hs-CRP, and NT-proBNP. Our results might help to develop future strategies for optimized treatment of hospitalized patients with symptomatic PAD.

Topics: Age Factors; Aged; Aged, 80 and over; Austria; Biomarkers; C-Reactive Protein; Case-Control Studies; Comorbidity; Critical Illness; Diabetes Mellitus; Female; Humans; Ischemia; Kaplan-Meier Estimate; Male; Middle Aged; Mortality; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Patient Admission; Peptide Fragments; Peripheral Arterial Disease; Proportional Hazards Models; Prospective Studies; Risk Factors; Time Factors

Patients with peripheral arterial disease (PAD) are at high risk for cardiovascular (CV) events. We have previously shown that ambulatory pulse pressure (APP) predicts CV events in PAD patients. The biomarkers amino-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and cystatin C are related to a worse outcome in patients with CV disease, but their predictive values have not been studied in relation to APP.. Blood samples and 24-hour measurements of ambulatory blood pressure were examined in 98 men referred for PAD evaluation during 1998-2001. Patients were followed for a median of 71 months. The outcome variable was CV events defined as either CV mortality or any hospitalization for myocardial infarction, stroke, or coronary revascularization. The predictive values of log(NT-proBNP), log(hs-CRP), and log(cystatin C) alone and together with APP were assessed by multivariable Cox regression. Area under the curve (AUC) and net reclassification improvement (NRI) were calculated compared with a model containing other significant risk factors.. During follow-up, 36 patients had at least 1 CV event. APP, log(NT-proBNP), and log(hs-CRP) all predicted CV events in univariable analysis, whereas log(cystatin C) did not. In multivariable analysis log(NT-proBNP) (hazard ratio (HR) = 1.62; 95% confidence interval (CI) = 1.05-2.51) and log(hs-CRP) (HR = 1.63; 95% CI = 1.19-2.24) predicted events independently of 24-hour PP. The combination of log(NT-proBNP), log(hs-CRP), and average day PP improved risk discrimination (AUC = 0.833 vs. 0.736; P < 0.05) and NRI (37%; P < 0.01) when added to other significant risk factors.. NT-proBNP and hs-CRP predict CV events independently of APP and the combination of hs-CRP, NT-proBNP, and day PP improves risk discrimination in PAD patients.

Topics: Aged; Area Under Curve; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; C-Reactive Protein; Chi-Square Distribution; Cystatin C; Disease Progression; Disease-Free Survival; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Revascularization; Natriuretic Peptide, Brain; Patient Admission; Peptide Fragments; Peripheral Arterial Disease; Predictive Value of Tests; Proportional Hazards Models; Risk Assessment; Risk Factors; ROC Curve; Sex Factors; Stroke; Sweden; Time Factors

High-sensitivity C-reactive protein (hsCRP) and brain natriuretic peptide (BNP) have been shown to be independent predictors of adverse cardiovascular outcomes and increased risk of secondary interventions or limb loss in patients with peripheral arterial disease (PAD). To assist clinicians in decision-making about treatment approaches and predicting postprocedure mortality and morbidity, we retrospectively examined patients with preprocedure hsCRP and BNP levels who underwent elective angioplasty or stent placement for lower extremity PAD.. The study period was from January 1, 2007, to December 31, 2012, and patients were included who had angioplasty or stenting for PAD. Minimal required follow-up for study inclusion was at least one postoperative ankle-brachial index, contrast angiography, or duplex imaging of the treated limb. Events of interest included major adverse limb events (MALE), defined as target vessel revascularization, amputation, or disease progression by 1 year, and major adverse cardiovascular events (MACE; stroke, myocardial infarction, or death) by 2 years. Elevated/abnormal values for our biomarkers of interest were established by the upper limits of our institution's clinical laboratory reference range (hsCRP, >0.80 mg/dL; BNP, >100 pg/mL).. A total of 159 limbs in 118 patients were included in analysis (42% men; median age [range], 64 [42-87] years). All limbs were symptomatic (Rutherford classification: 1-6). Iliac artery revascularization without other adjunct lower extremity intervention was performed in 60% of the limbs. High hsCRP levels (>0.80 mg/dL) were present in 32 patients (27%) and high BNP values (>100 pg/mL) in 24 patients (20%). Kaplan-Meier analysis with log-rank comparison demonstrated that elevated hsCRP levels were associated with MALE but only in limbs receiving interventions distal to the iliac arteries (P = .005). High BNP levels did not affect MALE rates (P = .821). Conversely, both elevated BNP levels (hazard ratio, 5.6; 95% confidence interval [CI], 2.0-5.8; P = .001) and hsCRP levels (hazard ratio, 2.9; 95% CI, 1.1-7.6; P = .034) predicted MACE at 2 years in the presence of confounders in Cox proportional hazards multivariate analysis. Patients with high preintervention values of hsCRP and BNP were 10.6 times (95% CI, 2.6-42.9; P = .001) more likely to experience MACE than were patients with normal hsCRP and BNP values.. After lower extremity endovascular interventions, elevated preprocedural hsCRP levels are associated with MALE (femoral-popliteal interventions), and elevated levels of hsCRP and BNP are associated with late cardiovascular events.

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty; Ankle Brachial Index; Biomarkers; C-Reactive Protein; Chi-Square Distribution; Disease Progression; Female; Humans; Kaplan-Meier Estimate; Limb Salvage; Lower Extremity; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peripheral Arterial Disease; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Stents; Stroke; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Up-Regulation

Serum concentrations of high-sensitivity cardiac troponin T (hs-cTnT) are elevated in various diseases. The role of this marker in peripheral arterial disease (PAD) has not been fully investigated.. Hs-cTnT was measured in the CAVASIC Study, a male cohort of 235 patients diagnosed with intermittent claudication and 249 age- and diabetes-matched controls. Patients with symptomatic PAD were prospectively followed for a median time of 7 years. The association of hs-cTnT with PAD, cardiovascular disease (CVD) at baseline as well as incident CVD and all-cause mortality during follow-up was analyzed.. Detectable hs-cTnT was associated with an 84% higher probability for symptomatic PAD at baseline: OR = 1.84, 95%CI 1.05-3.21, p = 0.03. Inclusion of ln-NT-proBNP or prevalent CVD abolished this association (both OR = 1.22, p = 0.52). However, detectable hs-cTnT was associated with prevalent CVD (n = 69) in PAD patients independent from ln-NT-proBNP: OR = 3.42, p = 0.001. In the adjusted Cox regression analysis detectable (HR = 2.15, p = 0.05) and especially hs-cTnT ≥ 14 ng/L (HR = 5.06, p < 0.001) were predictive for all-cause mortality (n = 39) independent from ln-NT-proBNP. Furthermore, hs-cTnT ≥ 14 ng/L was significantly associated with incident CVD (n = 66): HR = 3.15, 95%CI 1.26-7.89, p = 0.01.. This study in male patients with intermittent claudication and age- and diabetes-matched controls revealed hs-cTnT to be associated with PAD and prevalent CVD. The latter association was even significant after considering NT-proBNP. Prospectively, in PAD patients hs-cTnT was predictive for incident cardiovascular diseases and all-cause mortality. Thus, hs-cTnT could be a surrogate marker for cardiomyocyte damage also in symptomatic PAD patients.

Topics: Age Factors; Aged; Case-Control Studies; Diabetes Mellitus; Follow-Up Studies; Humans; Intermittent Claudication; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Peripheral Arterial Disease; Prevalence; Proportional Hazards Models; Prospective Studies; Regression Analysis; Risk Factors; Treatment Outcome; Troponin T

The use of multiple biomarkers representing various etiologic pathways of atherosclerosis may improve the prediction of interindividual variation in the ankle-brachial index (ABI). To this end, we investigated associations of 47 candidate biomarkers with the ABI and presence of peripheral arterial disease (PAD) in African-Americans (AAs) and non-Hispanic whites (NHWs).. Study participants included 1,291 AAs (71.1% women, mean age, 63.4±9.3 years) and 1,152 NHWs (57.5% women, mean age 58.5±10.1 years) belonging to hypertensive sibships. Peripheral arterial disease was defined as an ABI ≤ 0.90. Circulating levels of 47 candidate biomarkers were log-transformed before analysis because of skewed distribution. Multivariate regression analyses were used to identify biomarkers associated with ABI or PAD independently of age, sex, conventional risk factors, and medication use.. After adjustment for covariates, higher levels of nine biomarkers were associated with a lower ABI in AAs (all P ≤ 0.005); these biomarkers were C-reactive protein (CRP), interleukin-6, tumor necrosis factor receptor-II (TNF-R II), lipoprotein(a), N-terminal pro-brain natriuretic peptide (NT-proBNP), pro-atrial natriuretic peptide, C-terminal pro-arginine vasopressin, osteoprotegerin, and fibrinogen. Three biomarkers - myeloperoxidase, NT-proBNP, and D-dimer - were associated with ABI in NHWs (all P ≤ 0.01). C-reactive protein, interleukin-6, TNF-R II, lipoprotein(a), NT-proBNP, pro-atrial natriuretic peptide, D-dimer, and fibrinogen were associated with PAD (all P ≤ 0.005) in AAs after adjustment for covariates. None of the biomarkers were independently associated with PAD in NHWs.. A multimarker approach improved the prediction of interindividual variation in the ABI in AAs and NHWs, and improved prediction of the presence of PAD in AAs.

Topics: Aged; Ankle Brachial Index; Biomarkers; Black or African American; C-Reactive Protein; Cross-Sectional Studies; Female; Fibrin Fibrinogen Degradation Products; Humans; Interleukin-6; Linear Models; Lipoprotein(a); Male; Middle Aged; Natriuretic Peptide, Brain; Osteoprotegerin; Peptide Fragments; Peripheral Arterial Disease; Risk Factors; White People

Topics: Female; Heart Failure; Heart Ventricles; Humans; Male; Natriuretic Peptide, Brain; Peripheral Arterial Disease; Ventricular Dysfunction, Left

The goal of this study was to analyze differences in risk factors, including the level of brain natriuretic peptide (BNP) and the distribution of lesions, between cases of critical limb ischemia (CLI) and intermittent claudication (IC) among patients with peripheral arterial disease.. Risk factors and clinical characteristics were prospectively investigated in 817 consecutive patients, including 185 patients with CLI and 632 patients with IC.. The patients in the CLI group were older than those in the IC group (p＜0.001). The prevalence of diabetes and cerebral infarction and the proportion of women were higher in the CLI group (p＜0.05). The plasma BNP levels in the CLI group were higher than those observed in the IC group (333±538 vs. 136±354 pg/mL, p＜0.001). In contrast, the levels of homocysteine and fibrinogen were higher and the levels of albumin and the estimated glomerular filtration rate were lower in the CLI group (p＜0.05). According to a multiple logistic analysis, the BNP level, diabetes, female gender, the albumin level, body mass index (BMI) and ankle-brachial pressure index (ABI) were associated with CLI (p＜0.05). Aortoiliac artery lesions were less common, whereas femoropopliteal and below-the-knee (BK) lesions were more common, in the CLI group (p＜0.05). The number of affected BK arteries was also higher in the CLI group (p＜0.001). Correlations were found between the presence of aortoiliac lesions and smoking and a low HDL cholesterol level, while femoropopliteal lesions were found to correlate with age, BMI and hypertension and BK lesions were found to correlate with diabetes, age, female gender and BMI (p＜0.05). The plasma BNP level correlated with the number of affected BK arteries (p＜0.05).. A high BNP level, diabetes, female gender, a low albumin level, ABI and BMI are risk factors for CLI. In this study, differences in the levels of anatomical lesions and correlated risk factors were found between the CLI and IC groups.

Topics: Adult; Aged; Aged, 80 and over; Albumins; Angiography; Ankle Brachial Index; Asian People; Body Mass Index; Cholesterol; Female; Fibrinogen; Glomerular Filtration Rate; Homocysteine; Humans; Intermittent Claudication; Ischemia; Japan; Leg; Male; Middle Aged; Natriuretic Peptide, Brain; Peripheral Arterial Disease; Prevalence; Risk Factors; Sex Factors; Smoking

Recent studies have demonstrated that the natriuretic pepetides induce endothelial regeneration and angiogenesis after vascular injury through the autocrine or paracrine action, and might have an inhibitory effect on atherosclerosis. We therefore systematically investigated single nucleotide polymorphisms (SNPs) in the natriuretic peptide system in relation to ankle-brachial index (ABI) in a Chinese population.. The study population was recruited from a mountainous area 500 km south of Shanghai from 2003 to 2009. Using the SNapShot method, we first genotyped 951 subjects enrolled in 2005 for 16 SNPs and then the remaining 1355 subjects as validation for 5 SNPs selected from the primary study. ABI and plasma proBNP were measured using the Omron VP-2000/1000 device and the Elecsys proBNP immunoassay, respectively.. Overall, the genetic associations were not significant (P ≥ 0.07). However, in the primary study, there was significant (Pint ≤ 0.045) interaction between 3 SNPs (rs6668352, rs198388, and rs198389) at the NPPA-NPPB locus and urinary sodium excretion in relation to ABI, and the rs6668352 polymorphism had the strongest association (Pint = 0.018). In the primary combined with the validation study populations, the interaction between the rs6668352 polymorphism and urinary sodium excretion in relation to ABI remained statistically significant (Pint = 0.0036). After adjustment for covariates, the rs6668352 A allele carriers, compared with GG homozygotes, had a higher ABI (mean ± standard error, 1.103 ± 0.006 vs. 1.084 ± 0.004, P = 0.009) and lower risk of peripheral arterial disease (PAD, defined as an ABI < 0.90, odds ratio 0.37, 95% confidence interval: 0.14-0.98, P = 0.04) in the subjects of high sodium intake.. The minor alleles of 3 SNPs at the NPPA-NPPB locus are associated with a lower risk of PAD, especially in the subjects of high sodium intake.

Topics: Adolescent; Adult; Aged; Ankle Brachial Index; Asian People; Atrial Natriuretic Factor; Child; China; Female; Genetic Predisposition to Disease; Genotype; Homozygote; Humans; Immunoassay; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Peripheral Arterial Disease; Phenotype; Polymorphism, Single Nucleotide; Risk; Sodium; Young Adult

Peripheral artery disease (PAD) and heart failure (HF) share many risk factors; however, the prevalence and characteristics of HF in patients with PAD have not been fully examined. We investigated 120 consecutive patients with PAD, defined by an ankle-brachial index ≤ 0.9. In all, 36 (30%) patients had brain natriuretic peptide (BNP) levels ≥ 100 pg/mL (high BNP group), and 84 (70%) patients had BNP levels < 100 pg/mL (low BNP group). Univariate analysis showed that high BNP was associated with age, estimated glomerular filtration rate, hypertension, and transmitral E-wave/early diastolic mitral annular velocity (E/e') ratio. Multivariate logistic regression analysis established that a high BNP was strongly and independently associated with the highest quartile of E/e', highlighting these patients' diastolic dysfunction. The prevalence of high BNP levels in patients with PAD suggests that routine BNP measurements might be useful to detect HF.

Topics: Aged; Aged, 80 and over; Ankle Brachial Index; Diastole; Echocardiography; Female; Heart Failure; Heart Ventricles; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peripheral Arterial Disease; Retrospective Studies; Risk Factors; Ventricular Dysfunction, Left

We hypothesized that higher serum levels of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) are associated with lower functional capacity in patients with peripheral arterial disease ([PAD] n = 481, mean age 67, 68% men). Functional capacity was quantified as distance walked on a treadmill for 5 minutes. Patients were divided into 3 groups according to the distance walked: >144 yards (group 1, n = 254); 60 to 144 yards (group 2, n = 80); <60 yards or did not walk (group 3, n = 147). The association between NT-pro-BNP levels and the ordinal 3-level walking distance was assessed using multivariable ordinal logistic regression analyses that adjusted for several possible confounding variables. Higher levels of NT-pro-BNP were associated with a lower ordinal walking category independent of possible confounders (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.28-1.77; P < .001). In conclusion, higher levels of NT-pro-BNP are independently associated with lower functional capacity in patients with PAD and may be a marker of hemodynamic stress in these patients.

Topics: Aged; Biomarkers; Exercise Test; Exercise Tolerance; Female; Follow-Up Studies; Humans; Leg; Male; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Prognosis; Protein Precursors; Retrospective Studies; Walking

Topics: Aged; Cross-Sectional Studies; Female; Humans; Kidney Failure, Chronic; Male; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease

To investigate the relationship of aortic augmentation index (AIx) with N-terminal pro B-type natriuretic peptide (NTproBNP) plasma levels in patients with peripheral arterial disease (PAD) with normal left ventricular (LV) function.. Totally, 31 patients (23 males, mean age 65 ± 7.4) with a confirmed diagnosis of PAD of the lower limbs (ankle-brachial pressure index [ABPI] <0.90 in at least 1 leg) were enrolled in this study. All patients underwent pulse wave analysis by applanation tonometry of the radial artery using the SphygmoCor system and had a measurement of plasma NTproBNP levels.. Patients had a mean resting ABPI of 0.62 ± 0.19 and a mean AIx 32.6% ± 6.9. Median (interquartile range) NTproBNP plasma level was 75 (44-210) pg/mL. In a univariate analysis which included age, brachial systolic blood pressure (BSBP), brachial diastolic blood pressure (BDBP), ejection duration index (ED%), heart rate (HR), and NTproBNP, aortic AIx was significantly associated (Spearman rho) with NTproBNP, HR, and ED% (r = .49, P = .006; r = -.72, P = .000, and r = -.42, P = .02, respectively). Multivariate linear regression analysis showed that AIx was associated with NTproBNP (β = 0.38, P = .02) independent of gender, HR, ED%, and use of β-blockers. N-terminal pro B-type natriuretic peptide explained 8% of the variance in aortic AIx, whereas HR explained 15% of the variance.. In patients with PAD with normal LV systolic function, AIx is independently associated with NTproBNP. Structural changes in the myocardium might occur due to increased LV afterload as a result of increased wave reflections and arterial stiffness due to atherosclerosis leading to an increase in NTproBNP plasma levels.

Topics: Aged; Ankle Brachial Index; Aorta; Arterial Pressure; Biomarkers; Female; Humans; Linear Models; Lower Extremity; Male; Manometry; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Predictive Value of Tests; Prospective Studies; Pulse Wave Analysis; Systole; Up-Regulation; Vascular Stiffness; Ventricular Function, Left; Ventricular Remodeling

To determine whether serum levels of N-terminal (NT) pro-B-type natriuretic peptide (pro-BNP) are higher in patients with poorly compressible arteries (PCA) than in patients with peripheral artery disease (PAD) and control subjects without PCA or PAD.. Medial arterial calcification in the lower extremities results in PCA and may be associated with increased arterial stiffness and hemodynamic/myocardial stress. PCA was defined as having an ankle-brachial index >1.4 or an ankle blood pressure >255 mm Hg, whereas PAD was defined as having an ankle-brachial index ≤0.9. Study participants with PCA (n=100; aged 71±10 years; 70% men) and age- and sex-matched patients with PAD (n=300) were recruited from the noninvasive vascular laboratory. Age- and sex-matched controls (n=300) were identified from a community-based cohort and had no history of PAD. NT pro-BNP levels were approximately 2.5-fold higher in patients with PCA than in patients with PAD and approximately 4-fold higher than in age- and sex-matched controls. In multivariable regression analyses that adjusted for age, sex, smoking, hypertension, history of coronary heart disease/stroke, systolic blood pressure, and serum creatinine, NT pro-BNP levels remained significantly higher in patients with PCA than in patients with PAD and controls (P<0.001).. Patients with medial arterial calcification and PCA have higher serum levels of NT pro-BNP than patients with PAD and controls, which is suggestive of an adverse hemodynamic milieu and increased risk for adverse cardiovascular outcomes.

Topics: Aged; Aged, 80 and over; Ankle Brachial Index; Arteries; Biomarkers; Blood Pressure; Calcinosis; Case-Control Studies; Cross-Sectional Studies; Elasticity; Female; Humans; Linear Models; Lower Extremity; Male; Middle Aged; Minnesota; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Risk Assessment; Risk Factors; Ultrasonography, Doppler, Duplex; Up-Regulation

Plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels improve preoperative cardiac risk stratification in vascular surgery patients. However, single preoperative measurements of NT-pro-BNP cannot take into account the hemodynamic stress caused by anesthesia and surgery. Therefore, the aim of the present study was to assess the incremental predictive value of changes in NT-pro-BNP during the perioperative period for long-term cardiac mortality. Detailed cardiac histories, rest left ventricular echocardiography, and NT-pro-BNP levels were obtained in 144 patients before vascular surgery and before discharge. The study end point was the occurrence of cardiovascular death during a median follow-up period of 13 months (interquartile range 5 to 20). Preoperatively, the median NT-pro-BNP level in the study population was 314 pg/ml (interquartile range 136 to 1,351), which increased to a median level of 1,505 pg/ml (interquartile range 404 to 6,453) before discharge. During the follow-up period, 29 patients (20%) died, 27 (93%) from cardiovascular causes. The median difference in NT-pro-BNP in the survivors was 665 pg/ml, compared to 5,336 pg/ml in the patients who died (p = 0.01). Multivariate Cox regression analyses, adjusted for cardiac history and cardiovascular risk factors (age, angina pectoris, myocardial infarction, stroke, diabetes mellitus, renal dysfunction, body mass index, type of surgery and the left ventricular ejection fraction), demonstrated that the difference in NT-pro-BNP level between pre- and postoperative measurement was the strongest independent predictor of cardiac outcome (hazard ratio 3.06, 95% confidence interval 1.36 to 6.91). In conclusion, the change in NT-pro-BNP, indicated by repeated measurements before surgery and before discharge is the strongest predictor of cardiac outcomes in patients who undergo vascular surgery.

Topics: Aged; Biomarkers; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Postoperative Period; Predictive Value of Tests; Preoperative Period; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Sensitivity and Specificity; Survival Analysis