Diagnostic accuracy of B type natriuretic peptide and amino terminal proBNP in the emergency diagnosis of heart failure.

OBJECTIVE: To compare head to head the diagnostic accuracy of B type natriuretic peptide (BNP) and the amino terminal fragment of its precursor hormone (NT-proBNP) for congestive heart failure (CHF) in an emergency setting. METHODS: 251 consecutive patients presenting to the emergency department with dyspnoea as a chief complaint were prospectively studied. Patients with acute coronary syndromes were excluded. The diagnosis of CHF was based on the Framingham score for CHF plus echocardiographic evidence of systolic or diastolic dysfunction. Blood concentrations of BNP and NT-proBNP were measured by two commercially available assays (Abbott and Roche methods). The diagnostic accuracies of BNP and NT-proBNP were assessed by receiver operating characteristic curve analysis. RESULTS: Areas under the curve for BNP and NT-proBNP in patients with dyspnoea caused by CHF (n = 137) and in patients with dyspnoea attributable to other reasons (n = 114) did not differ significantly (area under the curve 0.916 v 0.903, p = 0.277, statistical power 94%). Cut off concentrations with the highest diagnostic accuracy were 295 ng/l for BNP (sensitivity 80%, specificity 86%, diagnostic accuracy 83%) and 825 ng/l for NT-proBNP (sensitivity 87%, specificity 81%, diagnostic accuracy 84%). Evaluation of discordant false classifications at these cut off concentrations showed no advantage for either BNP nor NT-proBNP in the biochemical diagnosis of CHF (17 misclassifications by BNP and 14 by NT-proBNP, p = 0.720). In the population studied, age, sex, and renal function had no impact on the diagnostic utility of both tests when compared by logistic regression models. CONCLUSIONS: BNP and NT-proBNP may be equally useful as an aid in the diagnosis of CHF in short of breath patients presenting to the emergency department.

Serum total 8-iso-prostaglandin F2alpha: a new and independent predictor of peripheral arterial disease.

OBJECTIVE: Circulating 8-iso-prostaglandin F 2alpha (8-iso-PGF 2alpha ) has been proposed as new indicator of oxidative stress, which is involved in the pathophysiologic changes of atherosclerosis. We proposed to test the hypothesis that 8-iso-PGF 2alpha is an independent predictor of symptomatic peripheral arterial disease (PAD). METHODS: A case-control study in 100 patients with symptomatic PAD and 100 control subjects matched for age, sex, and diabetes mellitus was conducted. Smokers and subjects using lipid-lowering drugs were excluded. Serum total 8-iso-PGF 2alpha was quantified with an enzyme immunoassay. RESULTS: Median 8-iso-PGF 2alpha was higher in patients with PAD than in control subjects (63 vs 42 pg/mL; P = .001). Logistic regression with hypertension, body mass index, and creatinine, low-density lipoprotein (LDL) cholesterol, triglyceride, high-sensitivity C-reactive protein (hs-CRP), 8-iso-PGF 2alpha , and total homocysteine concentrations as independent variables and case-control status as dependent variable revealed significant odds ratios (OR) for hypertension (OR, 3.74; 95% confidence interval [CI], 1.85-7.53), low-density lipoprotein cholesterol (OR, 1.16, for an increment of 10 mg/dL; 95% CI, 1.07-1.27), high-sensitivity C-reactive protein (OR, 1.02, for an increment of 1 mg/L; 95% CI, 1.00-1.03), and 8-iso-PGF 2alpha (OR, 1.11, for an increment of 10 pg/mL; 95% CI, 1.03-1.20). CONCLUSIONS: Serum total 8-iso-PGF 2alpha was an independent predictor of PAD in the population studied. This finding supports the hypothesis that 8-iso-PGF 2alpha is a risk marker for PAD. Our results indicate increased systemic oxidative stress in patients with PAD.

Relation between homocysteine and non-fatal stroke in peripheral arterial disease.

There are currently no data on whether high total serum homocysteine (tHcy) is predictive for cerebrovascular events in patients with symptomatic peripheral arterial disease (PAD). Therefore, the purpose of this study was to determine whether high tHcy levels were related to the evidence of non-fatal stroke in PAD. Evidence of non-fatal atherothrombotic stroke events was verified in 450 consecutive male patients, admitted for inpatient treatment of symptomatic PAD. The extent of carotid stenosis was evaluated by colour duplex Doppler measurement and fasting tHcy was determined by high-performance liquid chromatography. Within the population of 450 PAD patients a documented history of ischaemic stroke was evident in 50 subjects. The median tHcy values were significantly higher in PAD patients with stroke (18.6 micromol/l) than in PAD patients without stroke (15.1 micromol/l, P < 0.001). Logistic regression analysis revealed that tHcy was an independent and significant predictor (P=0.001) with an odds ratio (OR) of 1.37 for an increment of 5 micromol/l. In this multivariate model, diabetes mellitus (OR=2.34, P=0.011) and carotid stenosis > or =50% (OR=2.59, P=0.005) were also independently related to clinical cerebrovascular disease in PAD. In conclusion, the present study demonstrates an association of tHcy and evidence of non-fatal atherothrombotic stroke in patients with symptomatic PAD. This could be important, as a reduction of elevated tHcy concentrations by vitamin supplement might decrease the high frequency of cerebrovascular complications in PAD patients.

Erythrocyte mean corpuscular volume associated with the anatomical distribution in peripheral arterial disease.

BACKGROUND: Elevated erythrocyte mean corpuscular volume (MCV) has been suggested to be a risk factor for peripheral arterial disease (PAD). The aim of the present study was to evaluate whether MCV was associated with a distinct pattern of severe atherosclerosis (lumen reductions > or = 75%) in patients with symptomatic PAD, as measured by angiography. PATIENTS AND METHODS: 100 consecutively admitted male PAD patients with iliac, femoral-popliteal and crural disease manifestation were compared with 100 male age-matched control subjects without PAD on the basis of angiographically determined lumen reductions > or = 75%. RESULTS: The pattern of severe atherosclerosis was as follows: 41 PAD patients displayed stenoses/occlusions in the iliac segment, 68 in the femoral-popliteal and 15 in the crural segment. When comparing the PAD patients with the controls by multivariate conditional logistic regression analysis, MCV was an independent predictor of severe atherosclerosis in the iliac (OR = 2.72 for an increment of 5 fl, 95% CI = 1.15-6.40) and the femoral-popliteal segment (OR = 3.13 for an increment of 5 fl, 95% CI = 1.51-6.49) but not in the crural site. This pattern was similar to the impact of smoking. CONCLUSION: Higher MCV values contributed to lumen reductions > or = 75% of the proximal segments in patients with symptomatic PAD. This observation could be clinically important since revascularisation procedures are done predominantly in these segments. As a consequence, observance of elevated MCV values should be considered in PAD patients.

Erythrocyte mean cellular volume and its relation to serum homocysteine, vitamin B12 and folate.

Cobalamin (B12) and folate deficiency is related to both increased erythrocyte mean cellular volume (MCV) and raised serum total homocysteine (tHcy) values. Furthermore, there are indications that B12 and folate serum values do not represent the tissue status of the two vitamins exactly. Therefore, a direct relationship between MCV and tHcy, if demonstrated, could support the hypothesis that tHcy is a better indicator for the cited vitamin status than the serum levels of B12 and folate. We studied MCV, gamma glutamyl transferase (GGT), serum B12, folate and tHcy values in 200 hospitalized patients. There was a significant correlation of MCV with GGT (r = 0.266, P < 0.001) and with tHcy (r = 0.248, P < 0.001), but not with serum B12 and folate. Stepwise multiple linear regression with MCV as dependent and GGT, B12, folate and tHcy as independent variables, respectively, revealed significant associations of MCV with GGT (B = 2.18, 95% CI 0.95-3.42, P = 0.001) and tHcy (B = 3.33, 95% CI 1.26-5.39, P = 0.002). By removing tHcy from this model, serum B12 became a significant predictor of MCV (B = -1.70, 95% CI -3.25 to -0.15, P = 0.032). Serum folate was not significantly associated with MCV in multivariate analysis. In conclusion, the present study confirms indications that serum B12 and folate values lack clinical sensitivity and specificity in diagnosing vitamin deficiency states by showing MCV was better associated to tHcy, than to B12 or folate serum levels. This observation demonstrates that tHcy may be useful in diagnosing patients with B12 and/or folate deficiency.

Impact of atherosclerotic risk factors on the anatomical distribution of peripheral arterial disease.

BACKGROUND: The aim of the study was to determine predictors of hemodynamically relevant atherosclerosis (HRA) in different segments of lower limb arteries in patients with peripheral arterial disease (PAD). METHODS: In a retrospective case-control study 106 hospitalized consecutive patients with symptomatic PAD and 52 asymptomatic control subjects were studied. All patients underwent distal aortofemoral angiography. The arteries of the lower limbs were divided into three sections: in the aorto-iliac and femoro-popliteal segments HRA was defined as one or more stenosis of over 50%. In the crural segment it was considered if at least two arteries of one lower leg had occlusions/stenoses of over 50%. RESULTS: In 106 patients, there were 132 cases of hemodynamically relevant lesions, and in 26 patients in two segments. We separately compared 23 cases with aorto-iliac, 82 with femoro-popliteal and 27 with crural manifestation to the 52 control subjects. Calculating age- and sex-adjusted odds ratios, we found that current smoking status and plasminogen levels were significantly associated with HRA in the aorto-iliac and femoro-popliteal segments, whereas in diabetes mellitus the association was found to be in the crural and femoro-popliteal segments. However, there was no such association for lipid profiles and fibrinogen. CONCLUSIONS: We conclude that the anatomic distribution of HRA in patients with PAD is different according to the risk factor profile. The aorto-iliac and crural segments show specific risk profiles while the femoro-popliteal segment seems to be a transition zone. Smoking and high plasminogen levels may be related to atherosclerosis of proximal segments, diabetes to that of the distal segments.

Association between erythrocyte mean corpuscular volume and peripheral arterial disease in male subjects: a case control study.

Elevated serum total homocysteine, an established risk factor for peripheral arterial disease, is influenced by the vitamin B12 and folate status. Since these vitamins are inversely correlated with erythrocyte mean corpuscular volume, an investigation of whether mean corpuscular volume is higher in patients with symptomatic peripheral arterial disease than in healthy subjects was performed. Furthermore, a determination of predictors of increased mean corpuscular volume levels in this population free of symptomatic coronary artery disease, cerebrovascular disease, and diabetes mellitus was carried out. From 469 consecutive patients with symptomatic peripheral arterial disease, 100 fulfilled study inclusion criteria. Peripheral arterial disease was confirmed by angiography. One hundred age-matched subjects without peripheral arterial disease as verified by ankle-brachial index measurements >0.9 served as control subjects. Patients with PAD displayed a significantly higher mean corpuscular volume level (94.5 fl) than control subjects (90.9 fl, p<0.001). Logistic regression analysis showed that current smoking status (p<0.001) and mean corpuscular volume (p=0.009), but not total homocysteine or lipid parameters discriminated case control status. In addition, logistic regression analysis revealed a relationship of mean corpuscular volume with smoking (p=0.001), gamma-glutamyltransferase (p<0.001), and total homocysteine (p=0.012). This model predicted mean corpuscular volume values with an accuracy of 83%. Elevated mean corpuscular volume is a predictor of symptomatic peripheral arterial disease in the sample studied. A deficiency of folate and/or vitamin B12 may be responsible for this observation, as indicated by the correlation of mean corpuscular volume with total homocysteine. Due to the additional association of mean corpuscular volume with smoking and gamma-glutamyltransferase, an unhealthy lifestyle with low vitamin intake may cause elevated mean corpuscular volume values in patients with PAD.

Total serum homocysteine--a predictor of extracranial carotid artery stenosis in male patients with symptomatic peripheral arterial disease.

High total serum homocysteine (tHcy) concentrations are associated with an increased risk of carotid artery disease in the general population. Since patients with peripheral arterial disease (PAD) have a threefold risk of cerebrovascular morbidity compared to individuals free of PAD, and since the total neurological event rate is associated with a > or = 50% lumen reduction in extracranial carotid arteries, it was tested whether tHcy is a predictor of internal carotid artery stenosis in patients with symptomatic PAD. A total of 443 consecutive male PAD patients without previous carotid surgery/stenting were studied. In all, 100 patients with PAD had an internal carotid artery stenosis > or = 50%. Of the remaining 343 patients, 100 individuals matched for age (+/- 2 years) and diabetes served as controls. The extent of carotid stenosis was evaluated with color duplex measurement; tHcy was determined by high-performance liquid chromatography. Cases displayed a significantly higher median fasting tHcy level (17.0 micromol/l) than controls (13.7 micromol/l, p=0.001). Multivariate analysis showed that tHcy (p=0.036) was an independent predictor of internal carotid artery stenosis > or = 50% in PAD patients, representing an odds ratio of 1.32 (95% CI, 1.02-1.72) for an increment of 5 micromol/l. In the present study, high tHcy was an independent risk factor for an internal carotid artery stenosis > or = 50% in patients with PAD. Since PAD patients suffer a threefold risk of stroke compared to healthy individuals, a simple vitamin substitution in PAD patients may reduce the occurrence of internal carotid artery stenosis and therefore diminish the relatively high rate of cerebrovascular events in this population.