The Effect of Magnesium Supplementation on Vascular Calcification in CKD: A Randomized Clinical Trial (MAGiCAL-CKD).

SIGNIFICANCE STATEMENT: Magnesium prevents vascular calcification in animals with CKD. In addition, lower serum magnesium is associated with higher risk of cardiovascular events in CKD. In a randomized, double-blinded, placebo-controlled trial, the authors investigated the effects of magnesium supplementation versus placebo on vascular calcification in patients with predialysis CKD. Despite significant increases in plasma magnesium among study participants who received magnesium compared with those who received placebo, magnesium supplementation did not slow the progression of vascular calcification in study participants. In addition, the findings showed a higher incidence of serious adverse events in the group treated with magnesium. Magnesium supplementation alone was not sufficient to delay progression of vascular calcification, and other therapeutic strategies might be necessary to reduce the risk of cardiovascular disease in CKD. BACKGROUND: Elevated levels of serum magnesium are associated with lower risk of cardiovascular events in patients with CKD. Magnesium also prevents vascular calcification in animal models of CKD. METHODS: To investigate whether oral magnesium supplementation would slow the progression of vascular calcification in CKD, we conducted a randomized, double-blinded, placebo-controlled, parallel-group, clinical trial. We enrolled 148 subjects with an eGFR between 15 and 45 ml/min and randomly assigned them to receive oral magnesium hydroxide 15 mmol twice daily or matching placebo for 12 months. The primary end point was the between-groups difference in coronary artery calcification (CAC) score after 12 months adjusted for baseline CAC score, age, and diabetes mellitus. RESULTS: A total of 75 subjects received magnesium and 73 received placebo. Median eGFR was 25 ml/min at baseline, and median baseline CAC scores were 413 and 274 in the magnesium and placebo groups, respectively. Despite plasma magnesium increasing significantly during the trial in the magnesium group, the baseline-adjusted CAC scores did not differ significantly between the two groups after 12 months. Prespecified subgroup analyses according to CAC>0 at baseline, diabetes mellitus, or tertiles of serum calcification propensity did not significantly alter the main results. Among subjects who experienced gastrointestinal adverse effects, 35 were in the group receiving magnesium treatment versus nine in the placebo group. Five deaths and six cardiovascular events occurred in the magnesium group compared with two deaths and no cardiovascular events in the placebo group. CONCLUSIONS: Magnesium supplementation for 12 months did not slow the progression of vascular calcification in CKD, despite a significant increase in plasma magnesium. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov ( NCT02542319 ).

Prognostic Value of Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). OBJECTIVES: This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non-high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure. RESULTS: Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non-high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07). CONCLUSIONS: Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891).

Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: In patients with non-ST-segment elevation acute coronary syndrome (NSTEACS), coronary pathology may range from structurally normal vessels to severe coronary artery disease. OBJECTIVES: The purpose of this study was to test if coronary computed tomography angiography (CTA) may be used to exclude coronary artery stenosis ≥50% in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial (NCT02061891) evaluated the outcome of patients with confirmed NSTEACS randomized 1:1 to very early (within 12 h) or standard (48 to 72 h) invasive coronary angiography (ICA). As an observational component of the trial, a clinically blinded coronary CTA was conducted prior to ICA in both groups. The primary endpoint was the ability of coronary CTA to rule out coronary artery stenosis (≥50% stenosis) in the entire population, expressed as the negative predictive value (NPV), using ICA as the reference standard. RESULTS: Coronary CTA was conducted in 1,023 patients-very early, 2.5 h (interquartile range [IQR]: 1.8 to 4.2 h), n = 583; and standard, 59.9 h (IQR: 38.9 to 86.7 h); n = 440 after the diagnosis of NSTEACS was made. A coronary stenosis ≥50% was found by coronary CTA in 68.9% and by ICA in 67.4% of the patients. Per-patient NPV of coronary CTA was 90.9% (95% confidence interval [CI]: 86.8% to 94.1%) and the positive predictive value, sensitivity, and specificity were 87.9% (95% CI: 85.3% to 90.1%), 96.5% (95% CI: 94.9% to 97.8%) and 72.4% (95% CI: 67.2% to 77.1%), respectively. NPV was not influenced by patient characteristics or clinical risk profile and was similar in the very early and the standard strategy group. CONCLUSIONS: Coronary CTA has a high diagnostic accuracy to rule out clinically significant coronary artery disease in patients with NSTEACS.

Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. METHODS: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure. RESULTS: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1-4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78-1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67-1.01; P value for interaction=0.023). CONCLUSIONS: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.

Value of Myocardial Perfusion Assessment With Coronary Computed Tomography Angiography in Patients With Recent Acute-Onset Chest Pain.

OBJECTIVES: The authors sought to perform a randomized controlled trial to evaluate the clinical efficacy of combined examination with coronary computed tomography angiography (CTA) and computed tomography perfusion imaging (CTP) compared to coronary CTA alone. BACKGROUND: Stress myocardial CTP may increase diagnostic specificity when added to coronary CTA in patients suspected of having ischemic heart disease. METHODS: Patients recently hospitalized for acute-onset chest pain, who had acute coronary syndrome had been ruled out by normal electrocardiograms, normal troponin levels, and relief of symptoms, and who had a clinical indication for outpatient noninvasive testing, were screened for inclusion in the CATCH-2 (CArdiac cT in the treatment of acute CHest pain 2) trial (NCT02014311). Patients were randomized 1:1 to examination with coronary CTA or coronary CTA+CTP. The primary endpoint was the frequency of coronary revascularization among patients referred for invasive coronary angiography (ICA) based on index computed tomography evaluation. Secondary endpoints were invasive procedural complications at index-related ICA, post-index cardiac death, hospital admittance because of recurrence of chest pain, unstable angina pectoris, or acute myocardial infarction, ICA, and revascularization. RESULTS: Among 300 patients allocated to the coronary CTA+CTP group, 41 (14%) were referred for ICA compared with 89 (30%) allocated to coronary CTA (p < 0.0001). The primary endpoint occurred in 50% of coronary CTA+CTP patients versus 48% of invasively examined patients (p = 0.85). The total number of revascularizations was significantly lower in the coronary CTA+CTP group compared to the coronary CTA group (n = 20 [7%] vs. n = 42 [14%]; p = 0.0045). At median follow-up of 1.5 years, the occurrence of secondary endpoints was similar in the 2 groups. CONCLUSIONS: A post-discharge diagnostic strategy of coronary CTA+CTP safely reduces the need for invasive examination and treatment in patients suspected of having ischemic heart disease. (CArdiac cT in the treatment of acute CHest pain 2-Myocardial CT Perfusion [CATCH2]; NCT02014311).

Rationale and Design of the First Double-Blind, Placebo-Controlled Trial with Allogeneic Adipose Tissue-Derived Stromal Cell Therapy in Patients with Ischemic Heart Failure: A Phase II Danish Multicentre Study.

BACKGROUND: Ischemic heart failure (IHF) has a poor prognosis in spite of optimal therapy. We have established a new allogeneic Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors. It is produced without animal products, in closed bioreactor systems and cryopreserved as an off-the-shelf product ready to use. STUDY DESIGN: A multicentre, double-blind, placebo-controlled phase II study with direct intramyocardial injections of allogeneic CSCC_ASC in patients with chronic IHF. A total of 81 patients will be randomised at 2 : 1 to CSCC_ASC or placebo. There is no HLA tissue type matching needed between the patients and the donors. METHODS: The treatment will be delivered by direct injections into the myocardium. The primary endpoint is change in the left ventricle endsystolic volume at 6-month follow-up. Secondary endpoints are safety and changes in left ventricle ejection fraction, myocardial mass, stroke volume, and cardiac output. Other secondary endpoints are change in clinical symptoms, 6-minute walking test, and the quality of life after 6 and 12 months. CONCLUSION: The aim of the present study is to demonstrate safety and the regenerative efficacy of the allogeneic CSCC_ASC product from healthy donors in a double-blind, placebo-controlled, multicentre study in patients with IHF.

The effect of magnesium supplementation on vascular calcification in chronic kidney disease-a randomised clinical trial (MAGiCAL-CKD): essential study design and rationale.

INTRODUCTION: Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease and mortality, which is thought to be caused by increased propensity towards vascular calcification (VC). Magnesium (Mg) inhibits phosphate-induced VC in vitro and in animal models and serum Mg is inversely associated with cardiovascular mortality in predialysis CKD and in end-stage renal disease. This paper will describe the design and rationale of a randomised double-blinded placebo-controlled multicentre clinical trial, which will investigate whether oral Mg supplementation can prevent the progression of coronary artery calcification (CAC) in subjects with predialysis CKD. METHODS AND ANALYSIS: We will randomise 250 subjects with estimated glomerular filtration rate of 15 to 45 mL/min/1.73 m2 to 12 months treatment with either slow-release Mg hydroxide 30 mmol/day or matching placebo in a 1:1 ratio. The primary end point is change in CAC score as measured by CT at baseline and after 12 months treatment. Secondary end points include change in pulse wave velocity, bone mineral density, measures of mineral metabolism and clinical end points related to cardiovascular and renal events. ETHICS AND DISSEMINATION: This trial has been approved by the local biomedical research ethics committees and data protection agencies and will be performed in accordance with the latest revision of the Helsinki Declaration. The trial will examine for the first time the effect of increasing the uptake of a putative VC inhibitor (ie, Mg) on progression of CAC in subjects with predialysis CKD. TRIAL REGISTRATION NUMBER: NCT02542319, pre-results.

Myocardial perfusion 320-row multidetector computed tomography-guided treatment strategy for the clinical management of patients with recent acute-onset chest pain: Design of the CArdiac cT in the treatment of acute CHest pain (CATCH)-2 randomized controlled trial.

AIMS: Patients admitted with chest pain are a diagnostic challenge because the majority does not have coronary artery disease (CAD). Assessment of CAD with coronary computed tomography angiography (CCTA) is safe, cost-effective, and accurate, albeit with a modest specificity. Stress myocardial computed tomography perfusion (CTP) has been shown to increase the specificity when added to CCTA, without lowering the sensitivity. This article describes the design of a randomized controlled trial, CATCH-2, comparing a clinical diagnostic management strategy of CCTA alone against CCTA in combination with CTP. METHODS: Patients with acute-onset chest pain older than 50 years and with at least one cardiovascular risk factor for CAD are being prospectively enrolled to this study from 6 different clinical sites since October 2013. A total of 600 patients will be included. Patients are randomized 1:1 to clinical management based on CCTA or on CCTA in combination with CTP, determining the need for further testing with invasive coronary angiography including measurement of the fractional flow reserve in vessels with coronary artery lesions. Patients are scanned with a 320-row multidetector computed tomography scanner. Decisions to revascularize the patients are taken by the invasive cardiologist independently of the study allocation. The primary end point is the frequency of revascularization. Secondary end points of clinical outcome are also recorded. DISCUSSION: The CATCH-2 will determine whether CCTA in combination with CTP is diagnostically superior to CCTA alone in the management of patients with acute-onset chest pain.

Normal-Weight Central Obesity and Mortality Risk in Older Adults With Coronary Artery Disease.

OBJECTIVE: To study the relationship between body mass index (BMI) and central obesity and mortality in elderly patients with coronary artery disease (CAD). PATIENTS AND METHODS: We identified 7057 patients 65 years or older from 5 cohort studies assessing mortality risk using either waist circumference (WC) or waist-hip ratio (WHR) in patients with CAD from January 1, 1980, to December 31, 2008. Normal weight, overweight, and obesity were defined using standard BMI cutoffs. High WHR was defined as 0.85 or more for women and 0.90 or more for men. High WC was defined as 88 cm or more for women and 102 cm or more for men. Separate models examined WC or WHR in combination with BMI (6 categories each) as the primary predictor (referent = normal BMI and normal WC or WHR). Cox proportional hazards models investigated the relationship between these obesity categories and mortality. RESULTS: Patients' mean age was 73.0±6.0 years (3741 [53%] women). The median censor time was 7.1 years. A normal BMI with central obesity (high WHR or high WC) demonstrated highest mortality risk (hazard ratio [HR], 1.29; 95% CI, 1.14-1.46; HR, 1.29; 95% CI, 1.12-1.50, respectively). High WHR was also predictive of mortality in the overall (HR, 2.14; 95% CI, 1.93-2.38) as well as in the sex-specific cohort. In the overall cohort, high WC was not predictive of mortality (HR, 1.04; 95% CI, 0.97-1.12); however, it predicted higher risk in men (HR, 1.12; 95% CI, 1.01-1.24). CONCLUSION: In older adults with CAD, normal-weight central obesity defined using either WHR or WC is associated with high mortality risk, highlighting a need to combine measures in adiposity-related risk assessment.

Combining body mass index with measures of central obesity in the assessment of mortality in subjects with coronary disease: role of "normal weight central obesity".

OBJECTIVES: This study sought to assess the mortality risk of patients with coronary artery disease (CAD) based ona combination of body mass index (BMI) with measures of central obesity. BACKGROUND: In CAD patients, mortality has been reported to vary inversely with BMI ("obesity paradox"). In contrast,central obesity is directly associated with mortality. Because of this bidirectionality, we hypothesized that CAD patients with normal BMI but central obesity would have worse survival compared to individuals with other combinations of BMI and central adiposity. METHODS: We included 15,547 participants with CAD who were part of 5 studies from 3 continents. Multivariate stratifiedCox-proportional hazard models adjusted for potential confounders were used to assess mortality risk according to different patterns of adiposity that combined BMI with measures of central obesity. RESULTS: Mean age was 66 years, 60% were men. There were 5,507 deaths over a median follow-up of 2.4 years (IQR: 0.5 to 7.4 years). Individuals with normal weight central obesity had the worst long-term survival: a person with BMI of 22 kg/m2 and waist circumference (WC) of 101 cm had higher mortality than a person with similar BMI but WC of 85 cm (HR: 1.10[95% CI: 1.05 to 1.17]), than a person with BMI of 26 kg/m2 and WC of 85 cm (HR: 1.20 [95% CI: 1.09 to 1.31]), than a person with BMI of 30 kg/m2 and WC of 85 cm (HR: 1.61 [95% CI: 1.39 to 1.86]) and than a person with BMI of 30kg/m2 and WC of 101 cm (HR: 1.27 [95% CI: 1.18 to 1.39), p < 0.0001 for all). CONCLUSIONS: In patients with CAD, normal weight with central obesity is associated with the highest risk of mortality [corrected].

Central obesity and survival in subjects with coronary artery disease: a systematic review of the literature and collaborative analysis with individual subject data.

OBJECTIVES: The aim of this study was to examine the association of central (waist circumference [WC] and waist-hip ratio [WHR]) and total obesity (body mass index [BMI]) measures with mortality in coronary artery disease (CAD) patients. BACKGROUND: The question of which measure of obesity better predicts survival in patients with CAD is controversial. METHODS: We searched OVID/Medline, EMBASE, CENTRAL, and Web of Science from 1980 to 2008 and asked experts in the field for unpublished data meeting inclusion criteria, in which all subjects had: 1) CAD at baseline; 2) measures of WC or WHR; 3) mortality data; and 4) a minimum follow-up of 6 months. RESULTS: From 2,188 studies found, 6 met inclusion criteria. We obtained individual subject data from 4, adding unpublished data from a cardiac rehabilitation cohort. A variable called "central obesity" was created on the basis of tertiles of WHR or WC. Cox-proportional hazards were adjusted for age, sex, and confounders. The final sample consisted of 15,923 subjects. There were 5,696 deaths after a median follow-up of 2.3 (interquartile range 0.5 to 7.4) years. Central obesity was associated with mortality (hazard ratio [HR]: 1.70, 95% confidence interval [CI]: 1.58 to 1.83), whereas BMI was inversely associated with mortality (HR: 0.64, 95% CI: 0.59 to 0.69). Central obesity was also associated with higher mortality in the subset of subjects with normal BMI (HR: 1.70, 95% CI: 1.52 to 1.89) and BMI ≥30 kg/m(2) (HR: 1.93, 95% CI: 1.61 to 2.32). CONCLUSIONS: In subjects with CAD, including those with normal and high BMI, central obesity but not BMI is directly associated with mortality.

Metabolic syndrome and mortality in stable coronary heart disease: relation to gender.

BACKGROUND: Metabolic syndrome (MS) is associated with subsequent development of type 2 diabetes and cardiovascular disease in the general population. The impact of MS on mortality in patients with stable coronary heart disease is less well defined, and the association of prognosis to gender is unknown. METHODS: 1041 patients with stable coronary heart disease, referred for elective coronary angiography were included in this study. At baseline, history of hypertension, body mass index, lipids, fasting plasma glucose, and insulin were recorded. All-cause mortality was determined after a median follow-up of 9.2 years. RESULTS: At follow-up 296 (28%) patients had died. 315 (30%) patients had MS based on the definition by the World Health Organization. Patients with MS more frequently had diabetes and three-vessel disease of the coronary arteries. Men had a more severe risk profile than women. In a multivariable Cox regression analysis, MS was not associated with excess mortality risk in the overall population [adjusted HR=1.3 (95% CI: 0.7-2.3), p=0.43]. In gender specific analyses MS increased risk of all-cause mortality in women [adjusted HR=2.2 (95% CI: 1.1-4.3), p=0.02], but not in men [adjusted HR=1.0 (95% CI: 0.5-1.9), p=0.93]. CONCLUSIONS: MS provides prognostic information in women, but not in men. This association was independent of conventional cardiovascular risk factors including previously unrecognised diabetes, and angiographic coronary artery disease.

Is N-terminal pro B-type natriuretic peptide (NT-proBNP) a useful screening test for angiographic findings in patients with stable coronary disease?

BACKGROUND: Whether N-terminal pro B-type natriuretic peptide (NT-proBNP) is a useful screening tool for angiographic coronary artery disease in patients with angina is not known. Therefore, the purpose of this study was to assess the diagnostic test performance of NT-proBNP in detecting coronary atherosclerotic lesions, as assessed by coronary angiography. METHODS: We examined 1034 patients referred for diagnostic angiography because of symptoms or signs of coronary artery disease. The diagnostic value of NT-proBNP in predicting clinically significant coronary disease was assessed. RESULTS: In a multiple logistic regression model, NT-proBNP above the upper normal limit (125 pg/mL) predicted clinically significant coronary disease at angiography independently of traditional cardiovascular risk factors and invasive measurements of left ventricular function (odds ratio 2.1, 95% CI 1.3-3.2, P = .001). The ability of NT-proBNP in detecting clinically significant coronary disease at angiography was modest, however, with sensitivity of 0.61, specificity 0.60, accuracy 61 (95% CI 58-64), positive likelihood ratio 1.5 (95% CI 1.3-1.8), negative likelihood ratio 0.7 (95% CI 0.6-0.8), and area under the ROC curve 0.61 (95% CI 0.58-0.64). CONCLUSIONS: NT-proBNP is associated with clinically significant coronary disease at angiography, independently of left ventricular dysfunction. However, NT-proBNP is not a useful screening test for diagnosing significant angiographic lesions in patients with stable coronary disease.

[Prognostic value of N-terminal pro-BNP-type natriuretic peptide in patients with stable coronary heart disease--secondary publication]. / Prognostisk vaerdi af N-terminal pro B-type natriuretisk peptid hos patienter med stabil iskaemisk hjertesygdom--sekundaerpublikation.

We assessed the relationship between NT-proBNP levels and all-cause mortality in patients with stable coronary heart disease. NT-proBNP was measured in 1,034 patients referred for elective coronary angiography. In a multivariable Cox regression analysis, the hazard ratio for death from any cause for patients with NT-proBNP levels in the fourth quartile as compared with those in the first quartile was 2.4 (95% CI 1.5-4.0). NT-proBNP provides prognostic information on all-cause mortality independent of conventional cardiovascular risk factors and left ventricular dysfunction.

Biochemical cardiac risk markers in the general population, hypertension and coronary artery disease.

Recently there has been a growing interest in risk assessment of individuals, using biochemical markers of cardiac risk, with an increasing focus on a multi-marker strategy. Natriuretic peptides (BNP and NT-proBNP) are well-established markers of increased risk in the general population and in high-risk groups with hypertension, and coronary heart disease. However, there is at present no indication for routine measurements of natriuretic peptides in the risk assessment of individuals or patients, as there is no evidence for subsequent therapeutic initiatives. Natriuretic peptides are useful when screening for heart failure in symptomatic individuals. However, the use of NT-proBNP screening for risk or left ventricular systolic dysfunction in the general population is still a matter of debate.

N-terminal pro-B-type natriuretic peptide and long-term mortality in stable coronary heart disease.

BACKGROUND: The level of the inactive N-terminal fragment of pro-brain (B-type) natriuretic peptide (BNP) is a strong predictor of mortality among patients with acute coronary syndromes and may be a strong prognostic marker in patients with chronic coronary heart disease as well. We assessed the relationship between N-terminal pro-BNP (NT-pro-BNP) levels and long-term mortality from all causes in a large cohort of patients with stable coronary heart disease. METHODS: NT-pro-BNP was measured in baseline serum samples from 1034 patients referred for angiography because of symptoms or signs of coronary heart disease. The rate of death from all causes was determined after a median follow-up of nine years. RESULTS: At follow-up, 288 patients had died. The median NT-pro-BNP level was significantly lower among patients who survived than among those who died (120 pg per milliliter [interquartile range, 50 to 318] vs. 386 pg per milliliter [interquartile range, 146 to 897], P<0.001). Patients with NT-pro-BNP levels in the highest quartile were older, had a lower left ventricular ejection fraction (LVEF) and a lower creatinine clearance rate, and were more likely to have a history of myocardial infarction, clinically significant coronary artery disease, and diabetes than patients with NT-pro-BNP levels in the lowest quartile. In a multivariable Cox regression model, the hazard ratio for death from any cause for the patients with NT-pro-BNP levels in the fourth quartile as compared with those in the first quartile was 2.4 (95 percent confidence interval, 1.5 to 4.0; P<0.001); the NT-pro-BNP level added prognostic information beyond that provided by conventional risk factors, including the patient's age; sex; family history with respect to ischemic heart disease; the presence or absence of a history of myocardial infarction, angina, hypertension, diabetes, or chronic heart failure; creatinine clearance rate; body-mass index; smoking status; plasma lipid levels; LVEF; and the presence or absence of clinically significant coronary artery disease on angiography. CONCLUSIONS: NT-pro-BNP is a marker of long-term mortality in patients with stable coronary disease and provides prognostic information above and beyond that provided by conventional cardiovascular risk factors and the degree of left ventricular systolic dysfunction.

Impact of obesity on long-term prognosis following acute myocardial infarction.

OBJECTIVE: To evaluate the impact of obesity on mortality in patients with acute myocardial infarction. METHODS: This study comprises 6676 consecutive patients with acute myocardial infarction screened for entry into the Danish Trandolapril Cardiac Evaluation (TRACE) study. At baseline, body mass index (BMI) and waist to hip ratio (WHR) were measured. Survival status was determined after 8-10 years. RESULTS: BMI was used to divide patients into 4 groups: underweight, normal weight, overweight and obese. The normal weight group was used as reference for the other groups. WHR was divided in quartiles and the lowest quartile was used as reference for the three other quartiles. The prevalence of overweight (BMI 25-29.9 kg/m(2)) and obesity (BMI>30 kg/m(2)) were 48% and 13% in males and 31% and 13% in females. Obese patients were younger, less often smokers and more frequently suffered from diabetes and hypertension. In both men and women, there was no association between obesity assessed as BMI and mortality [men: adjusted RR=0.99 (0.85-1.14, p=0.3); women: adjusted RR=0.90 (0.74-1.10, p=0.2)]. Men with WHR in the upper quartile had an increased mortality [adjusted RR=1.21 (1.07-1.37, p<0.01)]. Increasing WHR in women showed a trend of increased mortality, although this was not significant [adjusted RR=1.13 (0.95-1.34, p=0.2)]. CONCLUSION: In patients with acute myocardial infarction overall obesity as assessed by body mass index is inversely related to mortality. However, abdominal obesity appears to be an independent predictor of all-cause mortality in men and perhaps also in women.