Use of N-terminal pro-B-type natriuretic peptide to detect myocardial ischemia

Purpose

To evaluate the utility of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels to detect myocardial ischemia.

Methods

We conducted a prospective observational study in 260 consecutive patients with suspected myocardial ischemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography. Levels of NT-proBNP were determined before and immediately after symptom-limited bicycle ergometry.

Results

Inducible myocardial ischemia on perfusion images was detected in 129 patients (49.6%). Baseline NT-proBNP and exercise induced increase in NT-proBNP (ΔNT-proBNP) were significantly higher in patients with myocardial ischemia (median baseline NT-proBNP 155 pg/mL vs 91 pg/mL, P <.001; ΔNT-proBNP 15 pg/mL vs 7 pg/mL, P = .002). Compared with patients in the lowest ΔNT-proBNP quartile, those in the highest quartile of ΔNT-proBNP had three times the risk of inducible ischemia (relative risk, 2.9; 95% confidence interval, 1.4 to 6.0; P = .003). Overall, the accuracy of baseline NT-proBNP and ΔNT-proBNP in the detection of myocardial ischemia were similar to that of the exercise electrocardiogram (ECG). Combining exercise ECG and baseline NT-proBNP or ΔNT-proBNP slightly increased the accuracy of exercise ECG only.

Conclusion

The NT-proBNP level at rest as well as ΔNT-proBNP during exercise stress testing is associated with inducible myocardial ischemia. NT-proBNP levels may have incremental value in the diagnosis of myocardial ischemia.     

B-Type Natriuretic Peptides for the Evaluation of Exercise Intolerance

Background

Cardiopulmonary exercise testing is the method of choice for the differentiation of exercise intolerance. This study sought to assess the utility of B-type natriuretic peptide (BNP) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) for the identification of a cardiocirculatory exercise limitation.

Methods

In 162 patients undergoing cardiopulmonary exercise testing, rest and peak exercise BNP and NT-proBNP levels were measured. In 94 patients fulfilling criteria for appropriate effort and sufficient diagnostic certainty, the accuracy of BNP and NT-proBNP for the prediction of a cardiocirculatory limitation, as assessed based on clinical and exercise testing data, was determined.

Results

A cardiocirculatory limitation was identified in 27 (29%) patients. Median (interquartile range) resting BNP [162 (45-415) vs 39 (19-94) vs 24 (15-46) pg/mL; P <.001] and NT-proBNP [506 (129-1167) vs 77 (35-237) vs 34 (19-77) pg/mL; P <.001] were higher in patients with cardiocirculatory as compared with those with pulmonary limitation (n = 28) and those without cardiocirculatory or pulmonary limitation (n = 39). The area under the receiver operator characteristics curve for BNP and NT-proBNP to identify a cardiocirculatory limitation was 0.79 and 0.84, respectively (P = .15 for comparison of the curves). Sensitivity and specificity of the optimal BNP cutoff of 85 pg/mL were 63% and 84%, respectively. Sensitivity and specificity of the optimal NT-proBNP cutoff of 223 pg/mL were 74% and 85%, respectively. Peak exercise biomarkers were not more accurate than resting levels.

Conclusions

Among patients referred for cardiopulmonary exercise testing for evaluation of unexplained exercise intolerance, BNP and NT-proBNP were similarly useful to identify those with a cardiocirculatory limitation.     

The characteristics and prognostic importance of NT-ProBNP concentrations in critically ill patients

Background

There are limited data for prognostic and diagnostic use of natriuretic peptides in intensive care unit (ICU) patients. We evaluate amino-terminal brain natriuretic peptide (NT-proBNP) in the medical ICU, specifically its correlation with noncardiac admission diagnosis and prognosis of critically ill patients.

Methods

NT-proBNP (pg/mL) was measured in 179 ICU patients without acute decompensated heart failure or acute coronary syndrome. Death during hospitalization (mortality), APACHE II score, laboratory data, echocardiograms, medical history, and demographics were assessed. NT-proBNP concentrations were compared with established cutoffs for congestive heart failure (>450 pg/mL for patients <50 years of age, >900 pg/mL for patients 50-70 years of age, and >1800 pg/mL for patients >70 years of age). Predictors of mortality and of NT-proBNP were analyzed by regression analysis. Tertiles were compared by analysis of variance and chi-squared test.

Results

NT-proBNP was elevated in these ICU patients (median 2139 pg/mL, 25^th percentile 540 pg/mL, 75% percentile 7389 pg/mL). Severity of illness and renal dysfunction (APACHE II score and serum creatinine) increased with rising NT-proBNP. The incidence of acute respiratory distress syndrome, sepsis, death, history of coronary artery disease (CAD) or congestive heart failure (all P <.05) increased with each tertile. Independent predictors of increased NT-proBNP were creatinine (P <.001), CAD (P <.001), APACHE II score (P <.05), and sepsis (P ≤.001). Overall hospital mortality was 26%, and log NT-proBNP (P <.05), APACHE II (P ≤.001), and CAD (P <.05) were independent predictors of mortality.

Conclusions

For patients admitted to the ICU without decompensated heart failure or acute coronary syndrome, NT-proBNP concentrations are markedly elevated, especially in patients with sepsis. NT-proBNP strongly and independently predicts mortality. However, NT-proBNP should not be used to direct volume management in critically ill patients.     

血浆氨基末端脑钠肽前体水平评价冠心病严重程度的价值

目的观察冠心病患者血浆氨基末端脑钠肽前体(NT-proBNP)水平变化,探讨血浆NT-proBNP水平评价冠心病严重程度价值。方法选择住院治疗,并行冠状动脉造影的患者205例,LVEF 75%共182例,分为急性心肌梗死(AMI)组(41例),不稳定性心绞痛(UAP)组(85例),稳定性心绞痛(SAP)组(40例)和正常组(16例);又根据冠状动脉造影分为单支病变组(52例)、双支病变组(49例)、多支病变组(64例)和零支病变组(40例)。采用Gensini积分法评价冠状动脉病变的狭窄严重程度,测定血浆NT-proBNP水平以及LVEF。结果AMI组和UAP组血浆NT-proBNP水平明显高于SAP组和正常组(P<0.05)。单支病变组、双支病变组和多支病变组血浆NT-proBNP水平明显高于零支病变组(P<0.05)。血浆NT-proBNP水平与LVEF呈负相关,与Gensini积分呈正相关。结论AMI和UAP患者血浆NT-proBNP水平明显升高,可能是冠心病危险分层的有效指标。     

Activation of polymorphonuclear leukocytes and increased plasma vasoconstrictors in vasospastic and nonvasospastic angina

Background

The cause of coronary vasoconstriction in patients with angina at rest, nonsignificant coronary stenosis, and endothelial dysfunction remains unknown. Our objective was to investigate the association between enhanced coronary vasoconstriction and increased circulating levels of vasoconstrictor agents.

Methods

Plasma levels of big endothelin-1, serotonin, and superoxide produced by polymorphonuclear leukocytes were measured in 38 patients with stable angina at rest without significant coronary artery stenosis—23 with nonvasospastic angina and 15 with vasospastic angina—and were compared with 10 patients with stable coronary disease and 20 age-matched controls.

Results

Patients with angina at rest showed higher big endothelin-1 (1.28 vs 0.72 fmol/mL, P < 0.001), serotonin (18.0 vs 9.1 ng/mL, P = 0.002), and superoxide produced by polymorphonuclear leukocytes (177 vs 67 nmol/10 × E8 × minutes, P = 0.001) than did controls. Serotonin and superoxide produced by polymorphonuclear leukocytes were also higher than in coronary disease patients (5.4 ng/mL, P = 0.001, and 97 nmol/10 x E8 x minutes, P = 0.005), and big endothelin-1 levels tended to be higher (0.99 fmol/mL, P = 0.073). Moreover, there were no significant differences in these 3 parameters between patients with vasospastic and nonvasospastic angina, and among the latter, between patients with a positive and those with a negative exercise stress test.

Conclusion

Systemic plasma levels of agents with the potential to produce coronary vasoconstriction are increased in patients with stable vasospastic or nonvasospastic angina and, hence, may contribute to their angina, increased coronary tone, and impaired vasodilatory capacity. Furthermore, they may establish a mechanistic link between the 2 conditions.     

Myocardial endothelin-1 release and indices of inflammation during angioplasty for acute myocardial infarction and stable coronary artery disease

Background

Elevations in endothelin-1 (ET-1) and inflammatory cytokines may impair myocardial reperfusion through the induction of microvascular constriction or obstruction; however, the generation of these factors close to the site of lesion rupture is unknown.

Methods and results

Coronary sinus (CS) and aortic blood was sampled during angioplasty for acute myocardial infarction (AMI) or stable angina to assess the local release of ET-1, interleukin-1β, interleukin-6, tumor necrosis factor-α and C-reactive protein following atherosclerotic plaque rupture. Transthoracic echocardiography documented left ventricular function in AMI. ET-1 levels were higher in CS than in aortic blood in AMI (3.0 ± 0.3 pmol/L vs 2.6 ± 0.3 pmol/L, P = .04), but not in stable angina (1.7 ± 0.2 pmol/L vs 1.5 ± 0.3 pmol/L, P = NS). CS ET-1 levels were also higher in AMI than in stable angina (3.0 ± 0.3 pmol/L vs 1.7 ± 0.2 pmol/L, P = .002), and correlated with left ventricular dysfunction (R² = 0.51, P = .02). In contrast, C-reactive protein levels were higher in CS than in aortic blood only in stable angina (2.3 ± 0.4 mg/L vs 1.8 ± 0.3 mg/L, P = .01). Similarly, CS tumor necrosis factor-α was higher in stable angina than in AMI (6.0 ± 1.4 pg/mL vs 2.5 ± 0.9 pg/mL, P = .02).

Conclusions

Local myocardial release of ET-1 is highest in AMI, where it relates to the extent of myocardial dysfunction. Although local inflammation is a component of stable coronary artery disease, it does not appear acutely enhanced in AMI.     

Response of B-type natriuretic peptide to exercise in hypertensive patients with suspected diastolic heart failure: correlation with cardiac function, hemodynamics, and workload

Background

Diastolic heart failure (DHF) is characterized by dyspnea due to increased left ventricular (LV) filling pressures during stress. We sought the relationship of exercise-induced increases in B-type natriuretic peptide (BNP) to LV filling pressures and parameters of cardiovascular performance in suspected DHF.

Methods

Twenty-six treated hypertensive patients with suspected DHF (exertional dyspnea, LV ejection fraction >50%, and diastolic dysfunction) underwent maximal exercise echocardiography using the Bruce protocol. BNP, transmitral Doppler, and tissue Doppler for systolic (Sa) and early (Ea) and late (Aa) diastolic mitral annular velocities were obtained at rest and peak stress. LV filling pressures were estimated with E/Ea ratios.

Results

Resting BNP correlated with resting pulse pressure (r=0.45, P=0.02). Maximal exercise performance (4.6 ± 2.5min) was limited by dyspnea. Blood pressure increased with exercise (from 143 ± 19/88 ± 8 to 191 ± 22/ 90 ± 10 mm Hg); 13 patients (50%) had a hypertensive response. Peak exercise BNP correlated with peak transmitral E velocity (r = 0.41, P < .05) and peak heart rate (r = −0.40, P < .05). BNP increased with exercise (from 48 ± 57 to 74 ± 97 pg/mL, P = .007), and the increment of BNP with exercise was associated with maximal workload and peak exercise Sa, Ea, and Aa (P < .01 for all). Filling pressures, approximated by lateral E/Ea ratio, increased with exercise (7.7 ± 2.0 to 10.0 ± 4.8, P < .01). BNP was higher in patients with possibly elevated filling pressures at peak exercise (E/Ea >10) compared to those with normal pressures (123 ± 124 vs 45 ± 71 pg/mL, P = .027).

Conclusions

Augmentation of BNP with exercise in hypertensive patients with suspected DHF is associated with better exercise capacity, LV systolic and diastolic function, and left atrial function. Peak exercise BNP levels may identify exercise-induced elevation of filling pressures in DHF.     

The relationship of serum erythropoietin level with coronary collateral grade

Background

Erythropoietin has been shown to induce neovascularization and protect against ischemic vascular injury. We investigated whether a higher serum erythropoietin (EPO) level is related to better coronary collateral vessel grade.

Methods

Ninety-nine patients with stable angina pectoris who have at least 1 coronary stenosis of equal to or greater than 70% at coronary angiography were prospectively enrolled. Serum EPO and vascular endothelial growth factor (VEGF) levels were studied. Coronary collateral degree was graded according to the Rentrop method. Patients with grade 2-3 collateral degree were included in the good collateral group and formed Group I. The patients with grade 0-1 collateral degree were included in the poor collateral group and formed Group II.

Results

The serum EPO level was significantly higher in the good collateral group (17.3 ± 9.3 mU/mL vs 11.7 ± 5.0 mU/mL; P < 0.001). There was also a positive correlation between serum EPO level and Rentrop score (r = 0.39; P < 0.001). In multivariate analysis, serum EPO level (odds ratio [OR] 1.336; 95% confidence interval [CI], 1.120-1.593; P = 0.001), oxygen saturation (OR 0.638; 95% CI, 0.422-0.963; P = 0.033) and presence of chronic total occlusion (CTO) (OR 26.7; 95% CI, 3.874-184.6; P = 0.001) were independently related to well-developed coronary collaterals.

Conclusions

Higher serum EPO level is related to better coronary collateral development. Erythropoietin may have a positive effect on the development of collaterals and may provide a new agent for the treatment strategies to enhance coronary collateral vessel development.     

Oxidized low-density lipoprotein levels circulating in plasma and deposited in the tissues: comparison between Helicobacter pylori-associated gastritis and acute myocardial infarction

Background

Oxidized low-density lipoprotein (ox-LDL) is a key factor in the progression of atherosclerosis. We developed a sensitive method for measuring plasma ox-LDL levels using a novel anti-ox-LDL antibody. Recently, several studies have shown positive associations between Helicobacter pylori (H pylori) infection and coronary heart disease. Thus the question arises whether an increase in the plasma levels of ox-LDL occurs in patients with H pylori gastritis.

Methods

We measured plasma ox-LDL levels in patients with H pylori gastritis (n = 27) and compared them with those in patients with acute myocardial infarction (AMI) (n = 62) and stable angina pectoris (SAP; n = 63) and those in control subjects (n = 64). In addition, ox-LDL localization and the presence of macrophages and neutrophils were studied immunohistochemically in gastritis specimens and in coronary culprit lesions obtained from patients with AMI.

Results

Plasma ox-LDL levels in patients with AMI were significantly higher than those in patients with SAP (P <.0001), patients with H pylori gastritis (P <.0001), or in control subjects (P <.0001; AMI, 1.34 ± 0.95; SAP, 0.61 ± 0.29; Gastritis, 0.53 ± 0.17; control, 0.57 ± 0.23 ng/5μg LDL protein). Immunohistochemically, H pylori gastritis specimens showed distinct infiltration of macrophages and myeloperoxidase-positive neutrophils; however, ox-LDL localization was not detected. In contrast, coronary culprit plaques revealed strong positivity for ox-LDL in ruptured lipid cores with abundant macrophage-derived foam cells, and these plaques also contained myeloperoxidase-positive neutrophils.

Conclusion

Our results suggest that plasma ox-LDL levels do not seem to be associated with H pylori infection, but do relate to coronary plaque instability in AMI.     

Plasma levels of stromal cell-derived factor-1 in patients with coronary artery disease: effect of clinical presentation and cardiovascular risk factors

Objective

To investigate the possible association of plasma levels of stromal cell-derived factor-1 (SDF-1; CXCL12) with clinical presentation of symptomatic coronary artery disease (CAD) and with cardiovascular risk factors.

Methods

A cath lab cohort of 492 consecutive patients with symptomatic CAD were recruited. Blood for plasma-SDF-1 determination was taken at the time of heart catheterization before percutaneous coronary intervention.

Results

Plasma-SDF-1 was significantly decreased in ST-elevation myocardial infarction (STEMI) compared to stable angina pectoris (SAP) or to non-ST-elevation myocardial infarction (NSTEMI) (SAP vs. NSTEMI vs. STEMI: [pg/ml]: mean ± SD: 2110 ± 562 vs. 2127 ± 467 vs. 1834 ± 377; P < 0.001) independent of cardiovascular therapy. A weak correlation was observed between cholesterol levels and plasma SDF-1 in the whole study population. Left ventricular function and diabetes mellitus associated with plasma SDF-1 levels in patients with NSTEMI, while among STEMI patients, those with hyperlipidemia presented with even further decreased SDF-1 levels.

Conclusion

Plasma SDF-1 is significantly decreased in patients with STEMI, a fact which may reflect the importance of SDF-1 regulation in patients with acute myocardial infarction.     

Prevalence of carotid artery stenosis in Chinese patients with angina pectoris

Background

The prevalence of carotid artery stenosis (CAS) in Chinese patients with angina pectoris is unknown.

Methods

The study population consisted of 989 consecutive patients who were scheduled to undergo nonemergent coronary angiography for suspicion of coronary artery disease (CAD) because of angina pectoris between January 2013 and December 2014. All patients underwent carotid ultrasonography to screen for CAS within one month before or after coronary angiography. We defined cases with 0–50%, 50%–70%, and >70% stenosis as mild, moderate, and severe stenosis, respectively.

Results

CAD was presented in 853 patients (86.2%) of whom 191 patients (19.3%) had 1-vessel disease, 246 patients (24.9%) had 2-vessel disease and 416 patients (42.1%) had 3-vessel disease; left main trunk stenosis present in 137 patients (13.9%). In carotid ultrasonography, the prevalence of mild, moderate, and severe stenosis as well as that of total occlusion of the carotid artery was 54.5%, 13%, 4.7% and 0.8%, respectively. Significant CAS (>50% stenosis and total occlusion) was present in 10.3%, 13.9%, 19.9% and 22.8% of patients with 0-vessel, 1-vessel, 2-vessel and 3-vessel CAD. The severity of CAS was directly correlated (r=0.194, P<0.001) with the extent of CAD. The independent predictors of severe CAS and total carotid artery occlusion were increased age, male sex, hypertension, diabetes mellitus, hyperhomocysteinemia, a previous history of stroke and 3-vessel CAD.

Conclusions

The prevalence of CAS was not rare in China when compared with that in western countries, and the presence of CAS was weakly correlated with the extent of CAD. Screening for CAS should be recommended in Chinese patients with CAD, especially in those with one or more CAS-associated risk factors.     

Serum B-type natriuretic peptide levels on admission predict not only short-term death but also angiographic success of procedure in patients with acute ST-elevation myocardial infarction treated with primary angioplasty

Background

B-type natriuretic peptide (BNP) levels are predictive of short-term death in patients with acute coronary syndromes. Few data are available for BNP levels obtained on admission in patients with acute ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI).

Methods

Blood samples for BNP estimation, obtained on admission in 126 consecutive patients (mean age, 58.8 ± 10.7 years) with STEMI, were measured at the bedside by using a simple point-of-care test in a 15-minute period before PCI. Follow-up up to 42 days was performed.

Results

A baseline BNP value of 331 pg/mL had a sensitivity of 87.9% and a specificity of 90% for predicting death in a follow-up study. There was no difference in subgroups by median BNP (100 pg/mL) in Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 before PCI, although higher BNP levels were observed among patients with TIMI <3 after PCI than among those with TIMI 3 (356.7 ± 350.8 vs 144.9 ± 191.2 pg/mL; P < .0001). In multivariate logistic regression analysis, admission BNP was the independent predictor for the following: death (odds ratio [OR], 16.3; 95% confidence interval [CI], 1.4 to 186.7; P = .03), TIMI grade <3 after PCI (OR, 3.4; 95% CI, 1.2 to 9.6; P = .02), and the no-reflow phenomenon (OR, 6.2; 95% CI, 1.7 to 23; P = .007) after adjusting for other variables.

Conclusions

BNP levels obtained on admission are a powerful, independent predictor of short-term death and angiographic success after PCI in patients with STEMI. The no-reflow phenomenon may be predicted in STEMI on the basis of high serum BNP values on admission.     

N-terminal Pro brain natriuretic peptide is a reliable biomarker of reduced myocardial contractility in patients with lamin A/C gene mutations

Background

Recently, concerns have been raised about a possible lack of sensitivity of biomarkers to detect left ventricular (LV) dysfunction in patients with myopathies. We examined the ability of the N-terminal brain natriuretic peptide (NT-proBNP) to detect LV or right ventricular (RV) dysfunction in patients with lamin A/C (LMNA) gene mutations.

Methods

We prospectively measured plasma NT-proBNP in consecutive patients with documented LMNA mutations and age-sex matched controls. All patients underwent standard echocardiography implemented by pulsed tissue-Doppler echocardiography (TDE).

Results

Twenty-three patients were included (10 males, mean age 39.2 ± 18.9 years);10 had previous atrial arrhythmias, 8 had been implanted with cardioverter defibrillator for primary prevention of sudden death, 5 patients were of NYHA class II and 18 of NHYA class I. Sinus rhythm was recorded in all. NT-proBNP was increased in LMNA patients versus controls (123 ± 229 versus 26 ± 78 pg/ml, p = 0.0004); 7 patients had depressed LV and/or RV contractility. Patients with reduced LV or RV contractility had increased mean NT-proBNP (341 ± 1032 pg/ml versus 80 ± 79 pg/ml in patients with normal myocardial contractility, p = 0.004). Receiver-operating-characteristics analysis shows that NT-proBNP reliably detected depressed contractility (area under the curve 0.889 [0.697-1.000]). Sensitivity and specificity were 88% and 83% respectively, applying manufacturer's recommended cut-off concentration of 125 pg/ml.

Conclusion

NT-proBNP reliably detected the presence of reduced LV/RV contractility in LMNA patients.     

Diagnostic coronary angiography induces a systemic inflammatory response in patients with stable angina

Background

Systemic markers of inflammation increase after percutaneous coronary intervention (PCI). The rise in inflammatory markers after PCI is frequently attributed to the inflammatory stimulus associated with coronary artery injury during balloon inflation and coronary stent implantation. The aim of this study was the determine whether diagnostic coronary angiography performed in patients with stable angina triggers a systemic inflammatory response.

Methods

We prospectively studied patients with chronic stable angina undergoing either coronary angiography (n = 13) or coronary angiography followed by PCI (n = 13). Peripheral blood samples were obtained before and 24 hours, 48 hours, and 4 weeks after the procedure and analyzed for C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Patients with periprocedural myocardial necrosis were excluded.

Results

There was a significant increase in CRP levels at 24 and 48 hours in both the coronary angiography (P <.05) and PCI (P <.01) groups. IL-6 levels peaked at 24 hours in both the coronary angiography (median, 2.5-9.5 pg/mL; P = .01) and PCI (median, 3.0-8.2 pg/mL; P <.005) groups. At 4 weeks, both CRP and IL-6 returned to baseline levels. TNF-α levels were unchanged with either coronary angiography or PCI. The magnitude of the rise of CRP and IL-6 levels was not significantly different between the groups. There was a fair correlation between baseline and peak postprocedural levels of CRP (r = 0.67, P = .008) and IL-6 (r = 0.48, P = .016).

Conclusion

Uncomplicated diagnostic coronary angiography triggers a systemic inflammatory response in patients with stable angina. The contribution of coronary angiography should be considered in interpreting the significance of the systemic inflammatory response observed after PCI.     

Low testosterone level in middle-aged male patients with coronary artery disease

Background

Endogenous testosterone has been shown to provide a protective role in the development of cardiovascular diseases in men. This study investigated the changes of testosterone level and its relationship to the severity of coronary artery stenosis in middle-aged men with coronary artery disease (CAD).

Methods

Serum testosterone concentration was measured in 87 middle-aged men patients with CAD including stable angina pectoris (SAP), unstable angina pectoris (USAP) and acute myocardial infarction (AMI). All patients underwent coronary angiography and the severity of coronary stenosis was estimated by the Gensini coronary score. The patients with the severity of coronary artery stenosis of less than 50% served as control group.

Results

The levels of testosterone in SAP group (488.2 ± 96.8 ng/dl), USAP group (411.6 ± 128.6 ng/dl) and AMI group (365.3 ± 116.6 ng/dl) were significantly lower than that in control group (562.8 ± 110.2 ng/dl) (all p < 0.05). When compared with another group among SAP, USAP and AMI groups, the level of testosterone in the AMI group was the lowest, the USAP group was the median while the SAP group was the highest (all p < 0.05). There was a significant correlation between angiographic Gensini score and testosterone level (n = 87, r = − 0.513, p < 0.05). Multiple regression analysis found that testosterone and BMI were independent predictors for CAD (testosterone: odds ratio 0.311, 95% confidence interval 0.174-0.512; BMI: odds ratio 1.905, 95% confidence interval 1.116-2.973).

Conclusion

The present study showed that middle-aged male patients with CAD present a lower level of serum testosterone and the testosterone level was negatively correlated with the severity of coronary artery stenosis.     

Aspirin resistance and adverse clinical events in patients with coronary artery disease

Purpose

We sought to determine the clinical significance of aspirin resistance measured by a point-of-care assay in stable patients with coronary artery disease (CAD).

Methods

We used the VerifyNow Aspirin (Accumetrics Inc, San Diego, Calif) to determine aspirin responsiveness of 468 stable CAD patients on aspirin 80 to 325 mg daily for ≥4 weeks. Aspirin resistance was defined as an Aspirin Reaction Unit ≥550. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), unstable angina requiring hospitalization, stroke, and transient ischemic attack.

Results

Aspirin resistance was noted in 128 (27.4%) patients. After a mean follow-up of 379 ± 200 days, patients with aspirin resistance were at increased risk of the composite outcome compared to patients who were aspirin-sensitive (15.6% vs 5.3%, hazard ratio [HR] 3.12, 95% confidence intervals [CI], 1.65-5.91, P < .001). Cox proportional hazard regression modeling identified aspirin resistance, diabetes, prior MI, and a low hemoglobin to be independently associated with major adverse long-term outcomes (HR for aspirin resistance 2.46, 95% CI, 1.27-4.76, P = .007).

Conclusions

Aspirin resistance, defined by an aggregation-based rapid platelet function assay, is associated with an increased risk of adverse clinical outcomes in stable patients with CAD.     

Short- and long-term beneficial effects of trimetazidine in patients with diabetes and ischemic cardiomyopathy

Background

Trimetazidine (TMZ) has been shown to partially inhibit free fatty acid oxidation by shifting substrate utilization from fatty acid to glucose. The aim of this study was to assess the effects of TMZ in patients with diabetes and ischemic cardiomyopathy.

Methods

Sixteen patients with diabetes and ischemic hypokinetic cardiomyopathy (all males) on conventional therapy were randomized to receive either placebo or TMZ (20 mg 3 times per day), each arm lasting 15 days, and then again to receive either placebo or TMZ for 2 additional 6-month periods, according to a double-blind, crossover design. At the end of each period, all patients underwent exercise testing, 2-dimensional echocardiography, and hyperinsulinemic/euglycemic clamp. Among the others, New York Heart Association class, ejection fraction, exercise time, fasting blood glucose, end-clamp M value (index of total body glucose disposal) and endothelin-1 levels were evaluated.

Results

Both in the short and long term (completed by 13 patients), on TMZ compared to placebo, ejection fraction (47 ± 7 vs 41 ± 9 and 45 ± 8 vs 36 ± 8%, P < .001 for both) and M value (4.0 ± 1.8 vs 3.3 ± 1.6, P = .003, and 3.5 ± 1.5 vs 2.7 ± 1.6 mg/kg body weight/min, P < .01) increased, while fasting blood glucose (121 ± 30 vs 136 ± 40, P = .02 and 125 ± 36 vs 140 ± 43, P = .19) and endothelin-1 (8.8 ± 3.8 vs 10.9 ± 3.8, P < .001 and 6.2 ± 2.4 vs 9.2 ± 4.3 pg/mL, P = .03) decreased. In the short term, 10 patients decreased 1 class on the NYHA scale during treatment with TMZ (P = .019 vs placebo). Eight patients decreased 1 NYHA class while on long-term TMZ treatment, while on placebo 1 patient increased 1 NYHA class and none improved (P = .018 vs placebo).

Conclusions

In a short series of patients with diabetes and ischemic cardiomyopathy, TMZ improved left ventricular function, symptoms, glucose metabolism, and endothelial function. Shifting energy substrate preference away from fatty acid metabolism and toward glucose metabolism by TMZ appears an effective adjunctive treatment in patients with diabetes with postischemic cardiomyopathy.     

Are exercise stress tests appropriate for assessing myocardial ischemia in patients with major depressive disorder?

Background

Major depressive disorder (MDD) disproportionately affects patients with coronary artery disease (CAD). Evidence of myocardial ischemia with electrocardiography (ECG) or single-photon-emission-computed-tomography (SPECT) assessments during exercise testing is an important determinant of CAD prognosis. However, many key symptoms of MDD, such as reduced interest in daily activities, lack of energy, and fatigue, may affect exercise performance and the detection of ischemia in patients with MDD. This study evaluated the extent to which MDD and depressive symptomatology moderate exercise test performance and compared the ability of ECG versus SPECT for detecting ischemia in 1367 consecutive patients who underwent exercise testing.

Methods

All patients underwent a brief, structured psychiatric interview (PRIME-MD) and completed the Beck Depression Inventory (BDI) on the day of their exercise (treadmill) test.

Results

A total of 183 patients (13%) met diagnostic criteria for MDD. Patients with MDD achieved a significantly lower percent of maximal predicted heart rate (%MPHR), exhibited lower peak exercise mets, and spent less time exercising compared with patients without MDD (all P values <.05). BDI scores were also negatively correlated with all 3 indices of exercise performance (all P values <.01). There were no differences in rates of SPECT ischemia in patients with MDD (40%) versus patients without MDD (45%; P = .23); however, rates of ECG ischemia were significantly lower (30%) in patients with MDD than in patients without MDD (48%; P <.0001).

Conclusions

Results suggest that patients with CAD who have MDD, depressive symptomatology, or both exhibit poor exercise tolerance and performance and that ECG, as compared with SPECT, may not be as reliable in detecting ischemia in patients who are depressed.     

Analysis of N-terminal-pro-brain natriuretic peptide and C-reactive protein for risk stratification in stable and unstable coronary artery disease: results from the AtheroGene study.

AIMS: N-terminal-pro-brain natriuretic peptide (Nt-proBNP) is a reliable risk predictor in acute coronary artery disease (CAD). Little is known about patients with stable angina pectoris (SAP). We aimed to investigate the prognostic impact of Nt-proBNP in a population with CAD especially focussing on patients with SAP. METHODS AND RESULTS: We obtained baseline samples from a prospective cohort of 904 consecutive patients with CAD. Cardiovascular events were registered during follow-up (median 2 years; maximum 3.7 years). Baseline Nt-proBNP was significantly higher among individuals with cardiovascular events compared with those without (711.5 vs. 238.8 pg/mL; P<0.0001). A similar association was found if the analysis was performed in patients who presented with stable angina (330 vs. 166.5 pg/mL; P=0.006) or acute coronary syndrome (990.9 vs. 527.7 pg/mL; P=0.03). In the SAP group, patients within the top quartile (>487.9 pg/mL) had a 3.7-fold (95% CI 1.2-9.1; P=0.01) increase in cardiovascular risk. After adjustment for most potential confounders including left ventricular ejection fraction, Nt-proBNP remained predictive for patients with serum concentrations in the upper quartile in comparison with patients in the lowest quartile (hazard ratio highest vs. lowest quartile: 4.0; P=0.03) (n=417). CONCLUSION: Baseline concentration of Nt-proBNP is independently related to future cardiovascular events in patients with stable angina.     

Change in circulating cytokines after 2 forms of exercise training in chronic stable heart failure

Background

A proinflammatory state is recognized in chronic heart failure and the degree of immune activation corresponds to disease severity and prognosis. Training is known to improve symptoms in heart failure but less is known about the effects of specific forms of training on the proinflammatory state.

Methods

Forty-six patients with stable chronic heart failure underwent a home-based program of exercise training for 30 minutes a day, 5 days per week over a 6-week period. Twenty-four used a bicycle ergometer and 22 used an electrical muscle stimulator applied to quadriceps and gastrocnemius muscles. Tumour necrosis factor-α (TNF-α), TNF-α soluble receptors 1 and 2, interleukin 6, and C-reactive protein were measured before and after the training period.

Results

Significant improvements in markers of exercise performance were seen in both training groups. Soluble TNF-α receptor 2 levels decreased after training in the bike group only (2900 ± 1069 pg/mL to 2625 ± 821 pg/mL, P = .013). Trends towards a decrease in levels of TNF-α and soluble receptor 1 were also seen in the bike group only. No change in circulating inflammatory markers was observed after stimulator training.

Conclusions

Physical training improves exercise capacity for patients with chronic heart failure but degree of attenuation of the proinflammatory response may depend on the mode of training despite similar improvements in exercise capacity.