Prognostic value of tissue inhibitor of metalloproteinase-1 for cardiovascular death among patients with cardiovascular disease: results from the AtheroGene study.

AIMS: Metalloproteinases are proteolytic enzymes, which decompose the extracellular matrix, influence cardiac remodelling, and are inhibited by tissue inhibitor of metalloproteinases (TIMPs). Little is known about the prognostic impact of the TIMP-1/matrix metalloproteinase complex in patients with future cardiovascular death. METHODS AND RESULTS: In 1979 patients with suspected coronary artery disease (CAD), TIMP-1 has been determined at baseline. Among 1945 (98.4%) patients with a mean follow-up period of 2.6+/-1.2 years, 75 patients died because of cardiovascular causes. Mean concentrations of TIMP-1 were higher among patients who experienced a fatal cardiovascular event than among those who did not (820 vs. 692 ng/mL; P<0.001). Age and sex adjusted hazard ratio of future cardiovascular death associated with one standard deviation of TIMP-1 level, was 1.37 (95% CI: 1.17-1.61; P<0.001). The hazard ratio remained nearly identical after adjustment for clinical and therapeutic confounders. B-type natriuretic peptide (2.75, 95% CI: 1.94-3.89; P<0.001), C-reactive protein (1.79, 95% CI: 1.43-2.24; P<0.001), and TIMP-1 (1.30, 95% CI: 1.07-1.58; P=0.008) were independently associated with future cardiovascular death. CONCLUSION: In patients with CAD, TIMP-1 proves as an independent predictor for future cardiovascular death.     

Preliminary data on the potential usefulness of B-type natriuretic peptide levels in predicting outcome after hospital discharge in patients with heart failure

PURPOSE: Among patients admitted for treatment of heart failure, we aimed to evaluate the value of B-type natriuretic peptide levels in predicting subsequent death or hospital readmission. SUBJECTS AND METHODS: We observed and followed 50 consecutive patients admitted with decompensated heart failure. B-type natriuretic peptide levels were measured using an immunofluorometric assay at admission and at discharge. We followed patients for 6 months and ascertained readmissions for cardiovascular causes and death. RESULTS: Forty-three patients were discharged. There were 20 events during follow-up (15 readmissions and 5 deaths). Mean (+/- SD) B-type natriuretic peptide levels decreased during the initial hospitalization, from 619 +/- 491 pg/mL to 328 +/- 314 pg/mL (P <0.001) among patients who were event free during follow-up, whereas declines were less marked among patients with hospital readmission or death (from 779 +/- 608 pg/mL to 643 +/- 465 pg/mL, P = 0.08). Among the 7 patients with in-hospital increases in B-type natriuretic peptide level, 6 had events, compared with 14 of the 36 patients whose levels declined (P = 0.04). An increase in B-type natriuretic peptide levels during hospital stay was associated with an increased event rate (hazard ratio [HR] = 3.3; 95% confidence interval [CI]: 1.3 to 8.8). Patients whose B-type natriuretic peptide level at discharge was above the median (321 pg/mL) had a somewhat higher rate of dying or being readmitted (HR = 2.3; 95% CI: 0.9 to 5.8). CONCLUSION: These preliminary results in a small number of patients suggest that changes in B-type natriuretic peptide levels, as well as predischarge levels, are related to hospital readmission and death within 6 months.     

NT-ProBNP and Troponin T and Risk of Rapid Kidney Function Decline and Incident CKD in Elderly Adults

Background and objectives

Elevations in N-terminal pro–B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated.

Design, setting, participants, & measurements

N-terminal pro–B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR≥30%, and incident CKD was defined as the onset of serum cystatin C eGFR<60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors.

Results

In total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro–B-type natriuretic peptide (>237 pg/ml) had an 67% higher risk of rapid decline and 38% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (>10.58 pg/ml) had 80% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.92 to 1.50).

Conclusions

Elevated N-terminal pro–B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association.     

Effects of lesion complexity on baseline and postprocedural B-type natriuretic peptide levels in patients undergoing percutaneous coronary interventions

The time-related alteration of plasma B-type natriuretic peptide levels after percutaneous coronary interventions has been investigated chiefly in patients with acute coronary syndromes; very few data are available in patients with stable coronary artery disease. Therefore, we aimed to evaluate the alterations of plasma B-type natriuretic peptide levels, and the effects of lesion complexity on these levels, after elective percutaneous coronary interventions in stable coronary artery disease patients. We enrolled 103 of these patients and used modified American College of Cardiology/American Heart Association lesion morphology criteria to qualitatively evaluate the angiograms: type A and B1 lesions were categorized as simple, and type B2 and C lesions were designated as complex. Plasma B-type natriuretic peptide levels were determined before intervention and 1 and 24 hours afterwards. Median baseline B-type natriuretic peptide levels were significantly higher in patients who had complex lesions (n=53) (108 pg/mL) compared with those who had simple lesions (n=50) (33 pg/mL) (P <0.001), and this difference was maintained 1 and 24 hours after intervention (P = 0.003 and P = 0.001, respectively). However, for both lesion types, percutaneous coronary intervention procedures did not significantly alter plasma B-type natriuretic peptide levels (all P >0.05). On binary logistic regression analysis, age and lesion complexity were found to be independently associated with B-type natriuretic peptide levels. We conclude that, in stable coronary artery disease patients, elective percutaneous coronary intervention does not cause any significant alteration in plasma B-type natriuretic peptide levels. However, elevated levels are significantly associated with more complex lesions and with advanced age.     

B-type natriuretic peptide and the risk of cardiovascular events and death in patients with stable angina: results from the AtheroGene study.

OBJECTIVES: The aim of this study was to assess the predictive value of the cardiac hormone B-type natriuretic peptide (BNP) for long-term outcome in a large cohort of stable angina patients. BACKGROUND: Recent data suggest a role of BNP in stable ischemic heart disease beyond its known value in heart failure and acute coronary syndromes. METHODS: In 1,085 patients with coronary artery disease (CAD) baseline levels of BNP were prospectively associated with cardiovascular (CV) events during a mean follow-up of 2.5 years. RESULTS: BNP concentrations were significantly elevated in patients with future CV events (median [25th/75th interquartile range] 119.2 [43.6/300.4] pg/ml vs. 36.2 [11.3/94.6] pg/ml; p < 0.001). Kaplan-Meier survival analysis showed a stepwise decrease in event-free survival across quartiles of BNP baseline concentration (p(log rank) < 0.001). Patients in the highest quartile revealed a 6.1-fold increased risk (p = 0.001) compared to patients in the lowest quartile after adjustment for potential confounders. For a cut-off value of 100 pg/ml, an independently increased risk of adverse outcome (hazard ratio [HR] 4.4; p < 0.001) could be demonstrated. One standard deviation (SD) decrease in ejection fraction implied the most prominent increase in risk of future CV events (HR 1.69; p < 0.001) followed by one SD increase in BNP (HR 1.53; p < 0.001). The highest prognostic accuracy could be demonstrated for BNP (area under the curve 0.671). CONCLUSIONS: The data of this large group of CAD patients provide independent evidence that BNP is a strong predictor of cardiovascular risk in patients with stable angina independent of left ventricular systolic performance and known risk factors.     

Higher prevalence of cardiovascular events among patients with abnormal atrial depolarization and coronary artery disease at 18 months' post-exercise tolerance testing

Abnormal atrial depolarization, denoted as interatrial block (IAB; P wave >110 ms), is associated with myocardial ischemia during exercise. The authors conducted an 18-month follow-up for cardiovascular events in 31 consecutive patients with IAB and 60 controls without IAB at rest; participants had coronary artery disease and hypertension and had undergone coronary angiography following positive exercise tolerance test (ETT) results. Atrial fibrillation and need for repeat ETT and coronary artery revascularization were significant with IAB (77.4% vs 20%; P<.001). In patients with such events, IAB, left atrial dilatation, left ventricular hypertrophy, increased left ventricular end-diastolic volume, poorer Duke prognostic treadmill (DPT) scores, and significant coronary artery stenoses were predominant. IAB (hazard ratio [HR], 4.9; 95% confidence interval [CI], 1.3-19.7; P=.02) and DPT scores (HR, 0.84; 95% CI, 0.72-0.98; P=.03) were independently associated with these events. At 18 months' follow-up, IAB at rest was associated with cardiovascular events among those with known coronary artery disease and hypertension.     

Influence of diabetes mellitus on long-term (five-year) outcomes of drug-eluting stents and coronary artery bypass grafting for multivessel coronary revascularization

Diabetes mellitus is a major risk factor for coronary artery disease (CAD) and for diffuse and progressive atherosclerosis. We evaluated the outcomes of drug-eluting stent (DES) placement and coronary artery bypass grafting (CABG) in 891 diabetic patients (489 for DES implantation and 402 for CABG) and 2,151 nondiabetic patients (1,058 for DES implantation and 1,093 for CABG) with multivessel CAD treated from January 2003 through December 2005 and followed up for a median 5.6 years. Outcomes of interest included death; the composite outcome of death, myocardial infarction (MI), or stroke; and repeat revascularization. In diabetic patients, after adjusting for baseline covariates, 5-year risk of death (hazard ratio 1.01, 95% confidence interval 0.77 to 1.33, p = 0.96) and the composite of death, MI, or stroke (hazard ratio 1.03, 95% confidence interval 0.80 to 1.31, p = 0.91) were similar in patients undergoing DES or CABG. However, rate of repeat revascularization was significantly higher in the DES group (hazard ratio 3.69, 95% confidence interval 2.64 to 5.17, p <0.001). These trends were consistent in nondiabetic patients (hazard ratio 0.80, 95% confidence interval 0.55 to 1.16, p = 0.23 for death; hazard ratio 0.77, 95% confidence interval 0.56 to 1.05, p = 0.10 for composite of death, MI, or stroke; hazard ratio 2.77, 95% CI 1.95 to 3.91, p <0.001 for repeat revascularization). There was no significant interaction between diabetic status and treatment strategy on clinical outcomes (p for interaction = 0.36 for death; 0.20 for the composite of death, MI, or stroke; and 0.40 for repeat revascularization). In conclusion, there was no significant prognostic influence of diabetes on long-term treatment with DES or CABG in patients with multivessel CAD.     

Prognostic usefulness of anemia and N-terminal pro-brain natriuretic peptide in outpatients with systolic heart failure

N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and anemia are predictors of outcome in systolic heart failure. It is currently unclear how these 2 markers interact in particular with regard to the prognostic information carried by each risk marker. We therefore tested the hypothesis that anemia (World Health Organization criteria, hemoglobin levels <7.5 mmol/L for women and <8.0 mmol/L for men) and NT-pro-BNP are associated and evaluated how a possible association affects the prognostic value of each risk marker. Clinical data from 345 patients with systolic heart failure were obtained prospectively at the baseline visit to our heart failure clinic (inclusion criterion left ventricular ejection fraction <0.45, no exclusion criteria). Follow-up was 30 months (median), and 70 events (mortality) occurred. Prevalence of anemia was 27%. In a multivariate logistic regression model, anemia (p = 0.041) was closely associated with NT-pro-BNP levels above the median (1,381 pg/ml) after adjustment for traditional confounders (left ventricular ejection fraction, age, body mass index, atrial fibrillation, chronic kidney disease). In an adjusted Cox proportional hazard model, the 2 parameters were associated with mortality after adjustment for traditional confounders (hazard ratio for anemia 1.73, 95% confidence interval 1.06 to 2.83, p = 0.029; hazard ratio for NT-pro-BNP >1,381 pg/ml 2.68, 95% confidence interval 1.58 to 4.66, p <0.001). Patients with anemia and high NT-pro-BNP levels had a fivefold increased risk for mortality (hazard ratio 4.77, 95% confidence interval 2.47 to 9.18, p <0.001). In conclusion, anemia is closely associated with NT-pro-BNP in patients with systolic heart failure, and anemia and NT-pro-BNP carry independent prognostic information. Patients with anemia and high levels of NT-pro-BNP have a markedly increased mortality risk.     

Is it possible to increase the diagnostic value of exercise electrocardiography by post-exercise B-type natriuretic peptide levels?

OBJECTIVE: Exercise electrocardiography is commonly available and a cost-effective test and therefore is widely used for the diagnosis of coronary artery disease. However, false positivity remains an important problem resulting in many unnecessary coronary angiographic examinations. In this study, we aimed to test the hypothesis that post-exercise B-type natriuretic peptides secreted in response to transient myocardial ischaemia induced by exercise, add any further information on positive test results. METHODS: Patients who underwent exercise electrocardiography with the suspicion of coronary artery disease were screened and those with positive test results based on standard electrocardiography criteria were selected. Blood samples for B-type natriuretic peptides were obtained within 5 minutes after exercise test. Patients included in the study had preserved left ventricular function on echocardiography. At least 70% stenosis of one epicardial coronary artery on coronary angiography was diagnosed as significant coronary artery disease. RESULTS: Of the 55 patients (age 59.8 +/- 7.6 y; 48 men) included in the study 29 had (52.7%) coronary artery disease requiring revascularization (CAD+) and 26 (47.3%) did not have significant coronary artery disease (CAD-). The cardiovascular risk factor profile of CAD+ and CAD- patients were similar (all p > 0.05).The median post-exercise B-type natriuretic peptide level was significantly higher in CAD+ (47.20 pg/ml) than CAD- patients (18.90 pg/ml) (P = 0.001). The sensitivity and specificity of a post-exercise B-type natriuretic peptide level > 30 pg/ml for the diagnosis of coronary artery disease in exercise test positive patients were calculated as 72% and 69%, respectively. CONCLUSION: The measurement of post-exercise B-type natriuretic peptide levels may increase the diagnostic value of positive exercise electrocardiography.     

Serial measurement of monocyte chemoattractant protein-1 after acute coronary syndromes: results from the A to Z trial.

OBJECTIVES: This study sought to determine whether the novel biomarker monocyte chemoattractant protein (MCP)-1 adds prognostic value to standard risk assessment tools and biomarkers after acute coronary syndromes (ACS). BACKGROUND: Monocyte chemoattractant protein-1 is a chemokine recruiting signal for monocytes that may function as both a mediator and biomarker of ACS. METHODS: Monocyte chemoattractant protein-1 was measured at baseline (n = 4,244), 4 months (n = 3,603), and 12 months (n = 2,950), and correlated with clinical events in the Z phase of the A to Z (Aggrastat to Zocor) trial, which compared early intensive versus delayed and less intensive statin therapy after ACS. RESULTS: Rates of death and the composite end points of death or myocardial infarction (MI); death, MI, or heart failure; and cardiovascular death, MI, readmission for ACS, or stroke increased across baseline quartiles of MCP-1 and among patients with MCP-1 greater than versus less than or equal to the pre-specified threshold of 238 pg/ml (p < 0.01 for each). After adjustment for standard risk predictors and levels of C-reactive protein and B-type natriuretic peptide, MCP-1 >238 pg/ml remained independently associated with mortality (hazard ratio 2.16; 95% confidence interval 1.54 to 3.02) and with each composite end point, and increased the C-statistic of the fully adjusted mortality model from 0.76 to 0.78 (p < 0.0001). A value of MCP-1 >238 pg/ml at the 4-month follow-up visit was also independently associated with mortality after 4 months (hazard ratio 1.76; 95% confidence interval 1.12 to 2.76). Elevated MCP-1 levels did not identify patients who derived incremental benefit from intensive statin therapy. CONCLUSIONS: Monocyte chemoattractant protein-1 provides independent prognostic value in the acute and chronic phases after ACS and merits further evaluation as a prognostic marker and potential therapeutic target.     

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.     

Asymmetric dimethylarginine and coronary collateral vessel development

INTRODUCTION: Nitric oxide (NO) plays a major role in collateral vessel development. Asymmetric dimethylarginine (ADMA) that is an endogenous inhibitor of NO synthesis may impair the effective coronary collateral vessel development. The aim of this study was to evaluate the relationship between plasma ADMA level and coronary collateral vessel development. METHODS: The patients with a greater than or equal to 95% obstruction in at least one epicardial coronary artery were included in the study. Degree of coronary collateral development was determined according to Rentrop method. Patients with grade 2-3 collateral development were regarded as good collateral group and formed group I. The patients with grade 0-1 collateral development were regarded as poor collateral group and were included in group II. Group III that had been formed as a control group included the patients with a normal coronary angiogram. We compared the plasma ADMA, symmetric dimethylarginine, L-arginine/ADMA ratio among three groups. RESULTS: Seventy-four patients have been included in the study. Patients with good collateral development had lower plasma ADMA level in comparison with patients with poor collateral development (0.41+/-0.25 micromol/l vs. 0.70+/-0.23 micromol/l, P=0.001) and had similar plasma ADMA levels with the patients who have normal coronary arteries. When we compared L-arginine/ADMA ratio between good and poor collateral groups, we found that the patients with higher L-arginine/ADMA ratio have significantly better collateral development (270.8+/-168.0 vs. 120.9+/-92.1, P<0.001). In the analyses comparing Rentrop score with ADMA level and L-arginine/ADMA ratio, there were significant correlations (r=-0.444, P=0.008 and r=0.553, P=0.001, respectively). In multivariate analysis, ADMA level (odds ratio, 0.009; 95% confidence interval, 0.000-0.466, P=0.020) and L-arginine/ADMA ratio (odds ratio, 1.010; 95% confidence interval, 1.001-1.020, P=0.032) were independent predictors of collateral development. CONCLUSION: Increased plasma ADMA levels are related with poor coronary collateral development. ADMA may be responsible for the difference in coronary collateral vessel development among different patients with coronary artery disease. NO inhibitors that have a determinative relation with endothelial cell functions may be integral prerequisite in all steps of collateral development.     

Subclinical thyroid dysfunction as a risk factor for cardiovascular disease

BACKGROUND: There have been few large epidemiological studies examining the association between thyroid dysfunction and cardiovascular disease. In particular, it is uncertain if subclinical hypothyroidism is a risk factor for cardiovascular disease. METHODS: Serum thyrotropin and free thyroxine concentrations were measured in 2108 archived serum samples from a 1981 community health survey in Busselton, Western Australia (Busselton Health Study). In a cross-sectional study, we examined the prevalence of coronary heart disease in subjects with and without subclinical thyroid dysfunction. In a longitudinal study, we examined the risk of cardiovascular mortality and coronary heart disease events (fatal and nonfatal combined) to the end of 2001 (excluding subjects who had coronary heart disease at baseline). RESULTS: In the cross-sectional analysis, subjects with subclinical hypothyroidism (n = 119) had a significantly higher prevalence of coronary heart disease than euthyroid subjects (n = 1906) (age- and sex-adjusted prevalence odds ratio, 1.8; 95% confidence interval, 1.0-3.1; P = .04). In the longitudinal analysis of subjects with subclinical hypothyroidism (n = 101), there were 21 cardiovascular deaths observed compared with 9.5 expected (age- and sex-adjusted hazard ratio, 1.5; 95% confidence interval, 1.0-2.4; P = .08) and 33 coronary heart disease events observed compared with 14.7 expected (age- and sex-adjusted hazard ratio, 1.7; 95% confidence interval, 1.2-2.4; P < .01). The increased risk of coronary heart disease events remained significant after further adjustment for standard cardiovascular risk factors. Subjects with subclinical hyperthyroidism (n = 39) had no adverse outcomes. CONCLUSION: Subclinical hypothyroidism may be an independent risk factor for coronary heart disease.     

Mild renal dysfunction associated with incident coronary artery disease in young males.

AIMS: Although impaired renal function is associated with adverse cardiovascular outcomes, it is unknown whether this association exists in young, healthy adults with normal or mildly impaired renal dysfunction. METHODS AND RESULTS We calculated the baseline creatinine clearance of young males without antecedent diabetes mellitus, coronary artery disease (CAD), or renal dysfunction, and examined their subsequent diagnosis of CAD, defined as coronary artery diameter stenosis of at least 50% and/or myocardial infarction. The 23 964 males, 32.5 +/- 5.9 years old, had a baseline estimated creatinine clearance of 107.9 +/- 0.6 mL min(-1) per 1.73 m(2) (60-150 mL min(-1) per 1.73 m(2)). During a mean follow-up of 3.5 +/- 1.9 years, 77 subjects were diagnosed with CAD. After age adjustment, there was a progressive increase in the risk for CAD as the estimated creatinine clearance decreased [hazard ratio (HR) 4.77, 95% confidence interval 3.22-7.06, P < 0.001 for comparison between the fifth and first quintiles]. This association also persisted after further adjustments for conventional and ancillary risk factors for CAD (HR 2.10, 95% confidence interval 1.40-3.14, P < 0.001). Conclusion Reduced renal function in the normal to mildly impaired range is independently associated with increased risk for CAD among young, healthy males.     

Comparative value of coronary artery calcium and multiple blood biomarkers for prognostication of cardiovascular events

The value of coronary artery calcium (CAC) scoring versus multiple biomarkers in increasing risk prediction for cardiovascular disease (CVD) remains unknown. The study group consisted of 1,286 asymptomatic participants (mean ± SD 59 ± 8 years old) with no known coronary heart disease. Mean follow-up time was 4.1 ± 0.4 years with the primary outcome of combined CVD (cardiac death, myocardial infarction, stroke, and late target vessel revascularization). CAC was calculated by the method of Agatston. Biomarkers measured were C-reactive protein, interleukin-6, myeloperoxidase, B-type natriuretic peptide, and plasminogen activator-1. During follow-up 35 participants developed CVD events including cardiac deaths (6%), myocardial infarction (23%), strokes (17%), and late revascularizations (54%). In Cox proportional-hazards models adjusted for Framingham Risk Score (FRS), presence of log CAC beyond FRS was associated with increased hazards for CVD events (hazard ratio 1.7, 95% confidence interval [CI] 1.4 to 2.0, p <0.001). Multiple biomarkers score was also associated with increased risk beyond FRS (hazard ratio 2.1, p = 0.02) per 1-U increase in score; however, the c-statistic did not increase significantly (0.75, 95% CI 0.68 to 0.84, p = 0.32). The c-statistic increased when log CAC was incorporated into FRS without or with multiple biomarkers score (c-statistic 0.84, p = 0.003 and p = 0.008 respectively). Addition of CAC to risk factors showed significant reclassification (net reclassification improvement 0.35 (95% CI 0.11 to 0.58, p = 0.007; integrated discrimination index 0.076, p = 0.0001), whereas addition of multiple biomarkers score did not show significant reclassification. In conclusion, in this study of asymptomatic subjects without known CVD, addition of CAC but not biomarkers substantially improved risk reclassification for future CVD events beyond traditional risk factors.     

Usefulness of noninvasive estimate of pulmonary vascular resistance to predict mortality, heart failure, and adverse cardiovascular events in Patients With stable coronary artery disease (from the Heart and Soul Study)

Pulmonary vascular resistance (PVR) is an important hemodynamic variable that affects prognosis and therapy in a wide range of cardiovascular and pulmonary conditions. We sought to determine whether a noninvasive estimate of PVR predicts adverse outcomes in patients with stable coronary artery disease. Using Doppler echocardiography we measured the estimated PVR (defined as the ratio of the tricuspid regurgitant velocity [TRV] to the velocity-time integral [VTI] of the right ventricular outflow tract [RVOT]) in 795 ambulatory patients with stable coronary artery disease. Participants were categorized by quartiles of the TRV/VTI RVOT ratio. Hazard ratios (HRs) and 95% confidence intervals were calculated for all-cause mortality, heart failure hospitalization, and adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or stroke). After 4.3 years of follow-up there were 161 deaths, 44 deaths from cardiovascular causes, 103 heart failure hospitalizations, and 120 adverse cardiovascular events. Compared with patients in the lowest TRV/VTI RVOT quartile, those in the highest quartile were at increased risk of all-cause mortality (unadjusted HR 1.8, 95% confidence interval 1.3 to 2.5), heart failure hospitalization (unadjusted HR 2.9, 95% confidence interval 2.0 to 4.3), and adverse cardiovascular events (unadjusted HR 2.0, 95% confidence interval 1.4 to 2.9). After multivariate adjustment, patients in the highest quartile were at increased risk of heart failure hospitalizations (adjusted HR 2.5, 95% confidence interval 1.3 to 4.7). In conclusion, a noninvasive estimate of PVR (TRV/VTI RVOT ratio) predicts mortality, heart failure hospitalization, and adverse cardiovascular events in patients with stable coronary artery disease.     

Impact of Multivascular Disease on Cardiovascular Mortality and Morbidity in Patients Receiving Hemodialysis: Ten-Year Outcomes of the Q-Cohort Study

Aim: Multivascular disease, indicating concurrent arteriosclerotic lesions in a number of different vascular beds, is an independent risk factor for recurrent ischemic events in the general population. However, the impact of multivascular disease on the risk of developing cardiovascular disease has not been fully evaluated in patients receiving hemodialysis.Methods: A total of 3,504 hemodialysis patients were prospectively followed for 10 years. In this study, multivascular disease was defined as the coexistence of coronary artery disease and stroke. We examined the relationship between multivascular disease and the occurrence of composite cardiovascular endpoint, consisting of cardiovascular death, nonfatal coronary artery disease, nonfatal stroke, and peripheral artery disease.Results: The proportion of participants with multivascular disease was 5.7% (n = 200) at baseline. During follow-up (median, 106.6 months; interquartile range, 50.1–121.8 months), 1,311 patients experienced the composite endpoint, which was defined as at least one of the following: cardiovascular death (n = 620), nonfatal coronary artery disease (n = 318), nonfatal stroke (n = 340), and peripheral artery disease (n = 257). Compared with the group with no history of cardiovascular disease, the risk of experiencing the composite endpoint increased significantly with higher numbers of injured vascular beds in patients with single vascular disease (hazard ratio, 1.68; 95% confidence interval, 1.49–1.89) and in those with multivascular disease (hazard ratio, 2.11; 95% confidence interval, 1.71–2.60). In a multivariable analysis, multivascular disease was an independent predictor of cardiovascular events, in addition to diabetes, aging, and hypertension.Conclusions: This study clearly demonstrated that multivascular disease was a powerful predictor for cardiovascular mortality and morbidity in patients receiving hemodialysis.     

Cardiovascular risk prediction by N-terminal pro brain natriuretic peptide and high sensitivity C-reactive protein is affected by age and sex

BACKGROUND: Previous studies have shown that the urine albumin/creatinine ratio (UACR), high sensitivity C-reactive protein (hsCRP) and N-terminal pro brain natriuretic peptide (Nt-proBNP) predict cardiovascular events in a general population aged 41, 51, 61 or 71 years. This study investigated the impact of age and sex on their prognostic performance in a subgroup of 1994 apparently healthy individuals without diabetes, previous stroke or myocardial infarction, who did not receive any cardiovascular, antidiabetic or lipid-lowering medication. METHODS: In 1993-1994 we recorded cardiovascular risk factors, UACR, hsCRP and Nt-proBNP. The composite cardiovascular endpoint (CEP) of cardiovascular death and non-fatal stroke or myocardial infarction was assessed after 9.5 years. RESULTS: In Cox regression analyses predicting CEP, the effects of log(hsCRP) and log(Nt-proBNP) were modulated by sex (P < 0.05) and age (P < 0.05), respectively. The effect of logUACR was not significantly modulated by age or sex. Log(hsCRP)/SD did not predict CEP in women, but did predict CEP in 41 plus 51-year-old men [hazard ratio (HR) 1.71; 95% confidence interval, 1.1-2.6; P < 0.05] and 61 plus 71-year-old men (HR 1.64; 1.3-2.2; P < 0.001). Log(Nt-proBNP)/SD predicted CEP in 61 plus 71-year-old women (HR 1.74; 1.2-2.5; P < 0.01) and in 61 plus 71-year-old men (HR 1.58; 1.3-2.0; P < 0.001). CONCLUSION: Elevated hsCRP, reflecting early atherosclerosis, predicted CEP even in 41 plus 51-year-old men. Elevated Nt-proBNP, reflecting subclinical cardiovascular damage, predicted CEP in 61 plus 71-year-old subjects. Elevated UACR, reflecting endothelial dysfunction as well as microvascular damage, predicted events independently of age and sex, but primarily in 61 plus 71-year-old subjects.     

Relationship of depression to death or hospitalization in patients with heart failure

BACKGROUND: Depression is widely recognized as a risk factor in patients with coronary heart disease. However, patients with heart failure (HF) have been less frequently studied, and the effect of depression on prognosis, independent of disease severity, is uncertain. METHODS: Two hundred four outpatients having a diagnosis of HF, with a ventricular ejection fraction of 40% or less, underwent baseline assessments including evaluation of depressive symptoms using the Beck Depression Inventory and of HF severity determined by plasma N-terminal pro-B-type natriuretic peptide. Cox proportional hazards regression analyses were used to examine the effects of depressive symptoms on a combined primary end point of death and hospitalizations because of cardiovascular disease (hereafter referred to as cardiovascular hospitalization) during a median follow-up of 3 years. RESULTS: Symptoms of depression (Beck Depression Inventory score) were associated with risk of death or cardiovascular hospitalization (P<.001) after controlling for established risk factors including HF disease severity, ejection fraction, HF etiology, age, and medications. Clinically significant symptoms of depression (Beck Depression Inventory score >/=10) were associated with a hazard ratio of 1.56 (95% confidence interval, 1.07-2.29) for the combined end point of death or cardiovascular hospitalization. Contrary to our expectation, antidepressant medication use was associated with increased likelihood of death or cardiovascular hospitalization (hazard ratio, 1.75; 95% confidence interval,1.14-2.68, P =.01) after controlling for severity of depressive symptoms and for established risk factors. CONCLUSIONS: Symptoms of depression were associated with an adverse prognosis in patients with HF after controlling for HF severity. The unexpected association of antidepressant medications with worse clinical outcome suggests that patients with HF requiring an antidepressant medication may need to be monitored more closely.     

Evaluation of B-type natriuretic peptide for risk assessment in unstable angina/non-ST-elevation myocardial infarction: B-type natriuretic peptide and prognosis in TACTICS-TIMI 18

OBJECTIVES: This study was designed to evaluate B-type natriuretic peptide (BNP) for risk assessment and clinical decision making over a range of cut points, alone and with cardiac troponin I (cTnI), in patients with non-ST-elevation acute coronary syndromes (ACS). BACKGROUND: B-type natriuretic peptide holds promise for risk stratification. Additional evidence regarding optimal decision limits, use in combination with troponin, and use in targeting therapy is needed before acceptance into clinical use for ACS. METHODS: We evaluated BNP at baseline in 1,676 patients with non-ST-elevation ACS randomized to early invasive versus conservative management. RESULTS: Patients with elevated BNP (>80 pg/ml; n = 320) were at higher risk of death at seven days (2.5% vs. 0.7%, p = 0.006) and six months (8.4% vs. 1.8%, p < 0.0001). The association between BNP and mortality at six months (adjusted odds ratio [OR] 3.3; 95% confidence interval [CI] 1.7 to 6.3) was independent of important clinical predictors, including cTnI and congestive heart failure (CHF). Patients with elevated BNP had a fivefold higher risk of developing new CHF by 30 days (5.9% vs. 1.0%, p < 0.0001). B-type natriuretic peptide added prognostic information to cTnI, discriminating patients at higher mortality risk among those with negative (OR 6.9; 95% CI 1.9 to 25.8) and positive (OR 4.1; 95% CI 1.9 to 9.0) baseline cTnI results. No difference was observed in the effect of invasive versus conservative management when stratified by baseline levels of BNP (p(interaction) > or = 0.6). CONCLUSIONS: Elevated BNP (>80 pg/ml) at presentation identifies patients with non-ST-elevation ACS who are at higher risk of death and CHF and adds incremental information to cTnI. Additional work is needed to identify therapies that may reduce the risk associated with increased BNP.