Exercise-induced silent myocardial ischemia and coronary morbidity and mortality in middle-aged men.

OBJECTIVES: We investigated the prognostic significance of exercise-induced silent myocardial ischemia in both high and low risk men with no prior coronary heart disease (CHD). BACKGROUND: Silent ischemia predicts future coronary events in patients with CHD, but there is little evidence of its prognostic significance in subjects free of CHD. METHODS: We investigated the association of silent ischemia, as defined by ST depression during and after maximal symptom-limited exercise test, with coronary risk in a population-based sample of men with no prior CHD followed for 10 years on average. RESULTS: Silent ischemia during exercise was associated with a 5.9-fold (95% CI 2.3 to 11.8) CHD mortality in smokers, 3.8-fold (95% CI 1.9 to 7.9) in hypercholesterolemic men and 4.7-fold (95% CI 2.4 to 9.1) in hypertensive men adjusting for other risk factors. The respective relative risks (RRs) of any acute coronary event were 3.0 (95% CI 1.7 to 5.1), 1.9 (95% CI 1.2 to 3.1) and 2.2 (95% CI 1.4 to 3.5). These associations were weaker in men without these risk factors. Furthermore, silent ischemia after exercise was a stronger predictor for the risk of acute coronary events and CHD death in smokers and in hypercholesterolemic and hypertensive men than in men without risk factors. CONCLUSIONS: Exercise-induced silent myocardial ischemia was a strong predictor of CHD in men with any conventional risk factor, emphasizing the importance of exercise testing to identify asymptomatic high risk men who could benefit from risk reduction and preventive measures.     

Exercise workload, coronary risk evaluation and the risk of cardiovascular and all-cause death in middle-aged men.

BACKGROUND: No data exist on exercise workload combined with European Systematic Coronary Risk Evaluation (SCORE) with respect to death from cardiovascular diseases and other causes. We therefore investigated the prognostic significance of risk scores and exercise capacity with respect to cardiovascular diseases. DESIGN: A population-based follow-up study. METHODS: Exercise workload was measured by exercise test with an electrically braked cycle ergometer. The study is based on a random population-based sample of 1639 men (42-60 years) without history of type II diabetes or atherosclerotic cardiovascular disease including coronary heart disease, stroke or claudication. RESULTS: During an average follow-up of 16 years, a total of 304 overall deaths and 116 cardiovascular deaths occurred. Relative risk (RR) was 2.50 [95% confidence intervals (CI): 1.71-3.68, P<0.001] for all-cause death and 2.04 (95% CI: 1.14-3.65, P=0.016) for cardiovascular death among men with exercise capacity less than 162 W as compared with those with exercise capacity over 230 W, after adjustment for risk factors. Independent predictors for all-cause death were European SCORE (for 1% increment, RR: 1.15, 95% CI: 1.10-1.20, P<0.001), exercise workload (for 20 W increment, RR: 0.86, 95% CI: 0.82-0.91, P<0.001), C-reactive protein and alcohol consumption, when adjusted for serum high-density lipoprotein, body mass index, family history of coronary heart disease, exercise-induced ST changes and the use of medications for hypertension, dyslipidemia or aspirin. CONCLUSION: Low exercise workload predicts an especially high risk for death from cardiovascular and any other cause when combined with high risk SCORE.     

The value of NT-proBNP in early risk stratification of acute coronary syndromes.

INTRODUCTION: The N-terminal portion of brain natriuretic peptide (NT-proBNP) has been identified as an indicator of prognosis in different cardiovascular diseases. Its role in risk stratification in patients with acute coronary syndromes (ACS) is still under evaluation. OBJECTIVE: We aimed to evaluate the prognostic value of NT-proBNP measured in the first 48 hours after admission due to an acute coronary syndrome. METHODS: Our study included 142 patients (aged 62.7 +/- 12.0 years, 70.4% males) admitted to a cardiology unit with an ACS. All laboratory evaluations were performed in the first 48 hours after admission. The mean follow-up was 200 days. Death from any cause or hospitalization because of a major acute cardiovascular event (whichever occurred first) was defined as the end-point. RESULTS: Cardiovascular risk factors were found in a significant proportion of our sample (hypertension in 56.3%, diabetes mellitus in 38.0%, current or previous smoking in 51.4%, dyslipidemia in 67.6%). Fifty-eight patients had left ventricular systolic dysfunction (LVSD). Serum levels of NT-proBNP were 2174 +/- 4801 pg/ml. Variables associated with event-free survival in univariate analysis were: NT-proBNP (HR 1.007, 95% CI 1.003-1.011, for each 100 pg/ml increment), serum glucose (hazard ratio [HR] 1.007, 95% CI 1.001-1.012, for each 1 mg/dl increment) and maximum cardiac troponin I (cTnI) level (HR 1.005, 95% CI 1.001-1.009, for each 1 ng/ml increment). The white blood count (WBC) was marginally associated with a poor prognosis (HR 1.152, 95% CI 0.994-1.335, for each 1000/mm3 increment). After adjustment for the above variables, age, sex, left ventricular systolic dysfunction, diabetes, coronary anatomy and coronary revascularization using a forward likelihood ratio Cox regression model, NT-proBNP remained the only variable with significant prognostic value (HR 1.007, 95% CI 1.003-1.011, for each 100 pg/ml increment). CONCLUSIONS: These data suggest that NT-proBNP is a strong clinical predictor of prognosis in acute coronary syndromes. Its early measurement should be included in the risk stratification strategy in this setting.     

A direct comparison of the natriuretic peptides and their relationship to survival in chronic heart failure of a presumed non-ischaemic origin

The natriuretic peptides have been validated as sensitive and specific markers of left ventricular dysfunction; brain natriuretic peptide (BNP), N-terminal atrial natriuretic peptide (NT-proANP) and N-terminal brain natriuretic peptide (NT-proBNP) elevations have been associated with New York Heart Association (NYHA) Class I-IV heart failure. We directly compared the association of each of these markers with 1-year survival in 173 patients with chronic heart failure of a presumed nonischaemic origin entering the PRAISE-2 Trial, a clinical study which assessed the therapeutic effect of Amlodipine in patients with NYHA Class III and IV heart failure and a left ventricular ejection fraction (LVEF) <30%. BNP, NT-proBNP, and NT-proANP levels were all correlated with 1-year mortality by univariate Cox proportional hazards analyses. With respect to multivariate Cox proportional hazards regression models containing variables deemed significant in univariate analyses, NT-proANP alone was identified as an independent predictor of 1-year mortality when log-transformed continuous covariates were utilized in the analysis. When the analysis was repeated using dichotomous covariates, NT-proANP remained the most significant predictor of 1-year mortality, followed by NT-proBNP, NYHA classification and BNP. We conclude that all three natriuretic peptides are significant predictors of short-term mortality in subjects with chronic congestive heart failure (CHF) of a presumed nonischaemic origin. Larger prospective studies are required to validate the clinical utility of NT-proANP as a discriminating marker of short-term survival, and to validate proposed cutoffs of approximately 2300 pmol/l for NT-proANP, 1500 pg/ml for NT-proBNP, and 50 pmol/l for BNP as prognostic indicators of adverse short-term outcome.     

N-端心房利钠肽与N-端脑利钠肽对预测左室收缩功能障碍的价值

目的比较N-端心房利钠肽(心钠素NT-proANP)和N-端脑钠肽(NT-proBNP)对左室收缩功能障碍(LVSD)预测效率,依据二者特性确定适用范围并界定最佳下限(cut-off)值。方法入选心血管病患者380例(病例组),依据左室射血分数(LVEF)将患者划分为LVSD组(LVEF≤40%,n=90)及非LVSD组(LVEF40%,n=290)。另选136名健康体检者作为对照组。超声心动图测定LVEF;ELISA法测定血浆NT-proANP和NT-proB-NP浓度。描记NT-proANP和NT-proBNP预测左室收缩功能障碍受试者工作特征(ROC)曲线。依据年龄(以65岁为分界)、性别及原发心血管疾病种类划分亚组,分别描记各组患者NT-proANP和NT-proBNP预测左室收缩功能障碍ROC曲线;确定最佳cut-off值。结果病例组血浆NT-proANP和NT-proBNP浓度均显著高于对照组log(NT-proANP):(3.30±0.41)vs(2.98±0.16),P0.01;log(NT-proBNP):(2.71±0.30)vs(2.49±0.13),P0.01。NT-proANP和NT-proBNP对不同程度LVSD(LVEF≤40%或LVEF≤30%)患者诊断ROC曲线下面积(AUC)均大于0.73(P0.01);对LVEF≤40%的患者,NT-proANPAUC大于NT-proBNP(0.820vs0.738);对LVEF≤30%的患者,NT-proANPAUC明显小于NT-proBNP(0.853vs0.877)。根据各亚组ROC曲线确定cut-off值,NT-proANP为1676.92pmol/L时对各组LVSD预测敏感度88.9%～100%;特异度14.0%～58.7%;阳性预测值9.04%～30.04%;阴性预测值96.96%～98.77%。NT-proBNP为417.37pmol/L时,敏感度77.8%～94.4%;特异度10.0%～55.8%;阳性预测值7.07%～48.88%;阴性预测值94.46%～98.87%。结论 NT-proBNP与NT-proANP均能够反映心力衰竭高危人群心脏功能状态,可作为LVSD的诊断指标,对于LVEF≤40%的预测,NT-proANP效果优于NT-proBNP,有助于早期发现LVSD患者。     

Comparison of the impact of atrial fibrillation on the risk of stroke and cardiovascular death in women versus men (The Copenhagen City Heart Study)

The Copenhagen City Heart Study is a population-based cohort study. Using baseline data from 3 cohort examinations (1976 to 1978, 1981 to 1983, and 1991 to 1994), we analyzed the gender-specific effect of atrial fibrillation (AF) on the risk of stroke and cardiovascular death during 5 years of follow-up. Baseline data from 29,310 subjects were included. AF was documented in 276 subjects (110 women and 166 men). During a mean follow-up of 4.7 years, 635 strokes were identified, 35 of which occurred in subjects who had AF (22 women and 13 men). After adjustment for age and co-morbidity, the effect of AF on the risk of stroke was 4.6-fold greater in women (hazard ratio 7.8, 95% confidence interval 5.8 to 14.3) than in men (hazard ratio 1.7, 95% confidence interval 1.0 to 3.0). Cardiovascular death occurred in 1,122 subjects, 63 of whom had AF (28 in women and 35 in men). The independent effect of AF on cardiovascular mortality rate was 2.5-fold greater in women (hazard ratio 4.4, 95% confidence interval 2.9 to 6.5) than in men (hazard ratio 2.2, 95% confidence interval 1.6 to 3.1). Our results indicate that AF is a much more pronounced risk factor for stroke and cardiovascular death in women than in men.     

Risk of new-onset atrial fibrillation in relation to body mass index

BACKGROUND: Obesity is associated with increased risk of atrial fibrillation (AF), but it is unknown whether the association differs by duration or persistence of AF. It is also unknown to what extent cardiovascular risk factors may mediate this association. METHODS: This population-based case-control study included 425 subjects with new-onset AF and 707 controls. The AF cases were identified through International Classification of Diseases, Ninth Revision codes for inpatient and outpatient visits and verified by medical record review. Medical records provided data on height, weight, and cardiovascular risk factors. RESULTS: On average, AF risk was 3% higher (95% confidence interval [CI], 1%-5%) per unit increment in body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared). For sustained AF (duration > or =6 months), risk was higher by 7% (95% CI, 3%-11%) per unit BMI increment; for intermittent AF (duration > or =8 days or recurrent), 4% (95% CI, 1%-6%); and for transitory AF (duration <8 days), 1% (95% CI, -1% to +4%). Compared with those with normal BMI, the odds ratios for overweight and obese subjects were as follows: overweight, 0.97 (95% CI, 0.68-1.38); obese class 1, 1.18 (95% CI, 0.80-1.73); obese class 2, 1.34 (95% CI, 0.82-2.18); and obese class 3, 2.31 (95% CI, 1.36-3.91) (P = .002 for trend). When diabetes mellitus, a possible mediator, was added to the model, the odds ratio per unit increment of BMI decreased from 1.034 to 1.028. Adjustment for other cardiovascular risk factors including hyperlipidemia and blood pressure did not attenuate the BMI-AF association. CONCLUSIONS: The association with BMI was stronger for sustained AF than for transitory or intermittent AF. The obesity-AF association appears to be partially mediated by diabetes mellitus but minimally through other cardiovascular risk factors.     

Upper normal blood pressures predict incident atrial fibrillation in healthy middle-aged men: a 35-year follow-up study

Hypertension is the most prevalent risk factor for incident atrial fibrillation (AF). Recently, even high normal blood pressures (BPs) have been established as predictive of AF in women. We aimed to study the long-term impact of upper normal BP on incident AF in a population-based study of middle-aged men. From 1972 to 1975, 2014 healthy Norwegian men were included in a prospective cardiovascular survey and underwent a comprehensive clinical examination including standardized BP measurements. During up to 35 years of follow-up, 270 men were documented with AF by scrutinizing all hospital discharges. Risk estimations for incident AF were analyzed in quartiles of BP using multivariate adjusted Cox proportional hazards. Men with baseline systolic BP ≥140 mm Hg and upper normal BP 128 to 138 mm Hg had 1.60-fold (95% CI 1.15-2.21) and 1.50-fold (1.10-2.03) risk of AF, respectively, compared with men with BP <128 mm Hg. Baseline diastolic BP ≥80 mm Hg increased the risk of incident AF 1.79-fold (95% CI 1.28-2.59) compared with diastolic BP <80 mm Hg. When adjusting for the occurrence of diabetes mellitus or cardiovascular diseases before an AF event, the results still maintained significance. Additional analyses, on average 7 years after baseline, including men still healthy, showed that sustained upper normal systolic BP remained a significant predictor of subsequent AF. In conclusion, upper normal blood pressures are long-term predictors of incident AF in initially healthy middle-aged men.     

N-terminal pro-brain natriuretic peptide: a powerful predictor of mortality in hypertension

Natriuretic peptides are controregulatory hormones associated with cardiac remodeling, namely, left ventricular hypertrophy and systolic/diastolic dysfunction. We intended to address the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in hypertension. We prospectively studied the relationship between plasma NT-proBNP and all-cause mortality in 684 hypertensive patients with no history or symptoms of heart failure referred for hypertension workup in our institution from 1998 to 2008. After a mean duration of 5.7 years, we observed 40 deaths (1.04 deaths per 100 patients per year). After adjustment for traditional cardiovascular risk factors, including ambulatory blood pressure and serum creatinine, the risk for all-cause mortality more than doubled with each increment of 1 log NT-proBNP (hazard ratio: 2.33 [95% CI: 1.36 to 3.96]). The risk of death of patients with plasma NT-proBNP≥133 pg/mL (third tertile of the distribution) was 3.3 times that of patients with values<50.8 pg/mL (first tertile; hazard ratio: 3.30 [95% CI: 0.90 to 12.29]). This predictive value was independent of, and superior to, that of 2 ECG indexes of left ventricular hypertrophy, the Sokolov-Lyon index and the amplitude of the R wave in lead aVL. In addition, it persisted in patients without ECG left ventricular hypertrophy, which allowed refining risk stratification in this relatively low-risk patient category. In this large sample of hypertensive patients, plasma NT-proBNP appeared as a strong prognostic marker. This performance, together with the ease of measurement, low cost, and widespread availability of NT-proBNP test kits, should prompt a wide use of this marker for risk stratification in hypertension.     

Comparison of N-terminal pro-B-natriuretic peptide, C-reactive protein, and creatinine clearance for prognosis in patients with known coronary heart disease

BACKGROUND: The purpose of this study was to investigate the prognostic role of N-terminal pro-B-natriuretic peptide (NT-proBNP) serum level compared with C-reactive protein (CRP) level and creatinine clearance (CrCl) for the subsequent risk of cardiovascular events in a large cohort of patients with stable coronary heart disease (CHD). METHODS: Serum concentrations of NT-proBNP and CRP and CrCl were measured at baseline in a cohort of 1051 patients aged 30 to 70 years with CHD. The Cox proportional hazards model was used to determine the prognostic value of NT-proBNP, CRP, and CrCl on a combined cardiovascular disease (CVD) end point (fatal and nonfatal myocardial infarction and stroke). RESULTS: During follow-up (mean of 48.7 months), 95 patients (9.0%) experienced a secondary CVD event. Patients in the top quartile of the NT-proBNP distribution at baseline had a hazard ratio (HR) of 3.34 (95% confidence interval [CI], 1.74-6.45) for subsequent secondary CVD events compared with those in the bottom quartile (P for trend <.001) after controlling for age, sex, smoking status, history of diabetes mellitus, initial management of CHD, rehabilitation clinic, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and treatment with lipid-lowering drugs. For CRP, the corresponding HR was 1.76 (95% CI, 0.96-3.24) (P value for trend, .06). Patients with CrCl levels lower than 60 mL/min had an HR of 2.39 (95% CI, 1.06-5.40) compared with patients with a CrCl of 90 mL/min or higher (P for trend, .002). If all 3 markers were included simultaneously in 1 model, NT-proBNP still showed predictive ability for recurrent CVD events. CONCLUSION: N-terminal proBNP may be a clinically useful marker weeks after an acute coronary event and may provide complementary prognostic information to established risk determinants.     

Association of N-terminal pro-brain natriuretic peptide level with adverse outcomes in patients with acute myocardial infarction: A meta-analysis

BackgroundStudies evaluating the association of blood level of N-terminal pro-brain natriuretic peptide (NT-proBNP) with adverse prognosis have yielded conflicting results in patients with acute myocardial infarction (AMI). This meta-analysis sought to evaluate the prognostic value of blood level of NT-proBNP in patients with AMI.MethodsTwo authors independently searched articles in PubMed and Embase databases up to June 13, 2021. Studies evaluating the association of baseline NT-proBNP level with all-cause mortality or major adverse cardiovascular events (MACEs, including death, new or worsening heart failure, recurrent myocardial infarction, revascularization, stroke, etc.) among AMI patients were selected. Multivariable-adjusted risk ratio (RR) with 95% confidence interval (CI) was pooled by the highest vs. lowest category of NT-proBNP level.ResultsA total of 19 studies enrolling 12,158 AMI patients were identified. When compared highest with the lowest category of NT-proBNP level, the pooled RR was 5.28 (95% CI 2.87–9.73) for in-hospital/30-day death, 2.62 (95% CI 2.04–3.37) for follow-up all-cause mortality, and 2.50 (95% CI 1.91–3.28) for follow-up MACEs, respectively. Subgroup analysis further confirmed the value of NT-proBNP in predicting all-cause mortality and MACEs.ConclusionsElevated NT-proBNP level is independently associated with an increased risk of all-cause mortality and MACEs. Determination of blood NT-proBNP level can improve risk stratification of AMI patients.     

Usefulness of clinical and NT-proBNP monitoring for prognostic guidance in destabilized heart failure outpatients.

AIMS: To study the relative prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) monitoring in addition to clinical disease severity scores (CDSSs) in outpatients with destabilized heart failure (HF). METHODS AND RESULTS: Seventy-one outpatients with recently destabilized HF were recruited. At baseline, and at all following visits, a CDSS based on Framingham criteria was obtained, and NT-proBNP levels were measured in a blind fashion. CDSS did not correlate with NT-proBNP levels at any time (P > 0.1), although their relative changes correlated during follow-up (P < 0.001). Forty patients (56%) had clinical events (cardiovascular death and/or HF hospitalization) within 1 year of follow-up. Changes in CDSS from baseline were not predictive of subsequent events (P > 0.1 for all visits), whereas changes in NT-proBNP levels were predictive at several time points: week 2 (P = 0.005), week 3 (P = 0.037), week 4 (P = 0.015), and 6 months (P = 0.026). A change in NT-proBNP levels at follow-up week 2 (%) added independent prognostic information (P < 0.001, HR 0.982, 95% CI 0.972-0.992) to baseline CDSS (P = 0.002, HR 2.05, 95% CI 1.290-3.266), age (P = 0.007, HR 1.034, 95% CI 1.009-1.059), and left ventricular ejection fraction (P = 0.013, HR 0.942, 95% CI 0.898-0.987). CONCLUSION: Serial monitoring for per cent change in NT-proBNP concentrations offers superior prognostic information to clinical assessment among outpatients with recent destabilized HF.     

The predictive value of cardiorespiratory fitness combined with coronary risk evaluation and the risk of cardiovascular and all-cause death

BACKGROUND: There are no data on directly measured cardiorespiratory fitness combined coronary risk evaluation with respect to death from cardiovascular diseases and all-causes. We investigated the prognostic significance of risk scores and cardiorespiratory fitness with respect to cardiovascular disease and all-cause mortality. METHODS: Cardiorespiratory fitness (maximal oxygen uptake, VO2peak) was measured by exercise test with an electrically braked cycle ergometer. The study is based on a random population-based sample of 1639 men (42-60 years) without history of type 2 diabetes or atherosclerotic cardiovascular diseases. RESULTS: During an average follow-up of 16 years, a total of 304 deaths occurred. Independent predictors for all-cause death were European Score (for 1% increment, RR 1.15, 95% CI 1.10-1.20), VO2peak (for 1 MET increment, RR 0.84, 95% CI 0.78-0.89), when adjusted for C-reactive protein, alcohol consumption, serum high-density lipoprotein, waist-to-hip ratio, family history of coronary heart disease, exercise-induced ST changes and the use of medications for hypertension, dyslipidaemia or aspirin. Also, Framingham risk score was related to the risk of death (RR 1.05, 95% CI 1.03-1.07, P < 0.001). Subjects with high European or Framingham score and low VO2peak represent the highest risk group. CONCLUSION: An important finding is that the risk scores can be used to identify men for whom low cardiorespiratory fitness predicts an especially high risk for death from cardiovascular and any other cause.     

Serum parathyroid hormone levels predict coronary heart disease: the Troms? Study.

BACKGROUND: Primary hyperparathyroidism (PHPT) is associated with hypertension, coronary atherosclerosis and other cardiovascular diseases. We aimed to evaluate serum parathyroid hormone (PTH) levels as an independent risk factor for coronary heart disease (CHD) in subjects with serum calcium within the reference range. DESIGN: Population-based cross-sectional study. METHODS: The Troms? Study was attended by 27159 subjects aged 25-79 years. Serum PTH was measured in 3570 subjects. They all completed a questionnaire on medical history, including questions on angina pectoris and myocardial infarction along with a food-frequency questionnaire. A total of 1459 men and 1753 women with serum calcium 2.20-2.60 mmol/l, serum creatinine<121 micromol/l and who did not use diuretics were included in the present study. Linear regression was used to reveal associations between PTH, age, body mass index, serum calcium, calcium intake, cholesterol, blood pressure, glycosylated haemoglobin (HbA1c) and smoking status. A logistic regression model was used to find the independent predictors of CHD. RESULTS: When stratified for age the rate of CHD was higher in the subjects with serum PTH > 6.8 pmol/l than in those with normal or low serum PTH levels [relative risk 1.67, 95% confidence interval (CI) 1.26-2.23 in men and 1.78, 95% CI 1.22-2.57 in women]. The highest PTH quartile (> 3.50 pmol/l in men and > 3.30 pmol/l in women) predicted CHD, with odds ratios of 1.70 (95% CI 1.08-2.70) for men and 1.73 (95% CI 1.04-2.88) for women, versus the lowest PTH quartile (< 1.90 pmol/l for men and <1.80 pmol/l for women). CONCLUSIONS: Serum PTH predicts CHD in subjects with calcium levels within the reference range. This may indicate a role for PTH in the development of CHD.     

Elevated NT-ProBNP as a Cardiovascular Disease Risk Equivalent: Evidence from the Atherosclerosis Risk in Communities (ARIC) Study

BackgroundIt remains unclear whether elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) can serve as a “risk equivalent” for cardiovascular disease to adults at high cardiovascular risk.MethodsWe included 9789 participants (mean age 63.2 years, 55% women, 19.4% Black, 13% with a history of cardiovascular disease) who attended Atherosclerosis Risk in Communities Study Visit 4 (1996-1998). We classified participants as having a history of cardiovascular disease at baseline and, among those without cardiovascular disease, we defined categories of NT-proBNP (<125, 125-449, ≥450 pg/mL). We used Cox regression to estimate associations of NT-proBNP with incident cardiovascular disease and mortality.ResultsOver a median 20.5 years of follow-up, there were 4562 deaths (917 cardiovascular deaths). There were 2817 first events and 806 recurrent events (in those with a history of cardiovascular disease at baseline). Among individuals without a history of cardiovascular disease, those adults with NT-proBNP ≥450 pg/mL had significantly higher risks of all-cause death (hazard ratio [HR] 2.12; 95% confidence interval [CI], 1.78-2.53), cardiovascular mortality (HR 2.92; 95% CI, 2.15-3.97), incident total cardiovascular disease (HR 2.59; 95% CI, 2.13-3.16), atherosclerotic cardiovascular disease (HR 2.20; 95% CI, 1.72-2.80), and heart failure (HR 3.81; 95% CI, 3.01-4.81), compared with individuals with NT-proBNP <125 pg/mL. The elevated cardiovascular risk in persons with high NT-proBNP and no history of cardiovascular disease was similar to, or higher than, the risk conferred by a history of cardiovascular disease.ConclusionsOur findings suggest that it might be appropriate to manage adults with NT-proBNP ≥450 pg/mL as if they had a history of clinical cardiovascular disease.     

Effect of Beta-blockade and ACE Inhibition on B-type Natriuretic Peptides in Stable Patients with Systolic Heart Failure

INTRODUCTION: The long-term effect of beta-blockade on the plasma levels of natriuretic peptides BNP and its N-terminal counterpart, NT-proBNP, as risk markers in heart failure (HF) is obscure. METHODS: Stable systolic HF patients from the CARMEN study were divided in groups matching their randomised treatment allocation: Carvedilol, enalapril or carvedilol+enalapril. Changes in BNP and NT-proBNP from baseline to 6 months maintenance visit were evaluated in each treatment arm. Furthermore, the prognostic value of BNP and NT-proBNP during monotherapy with carvedilol was assessed with univariate Cox proportional hazards models using a combined endpoint of all cause mortality and cardiovascular hospitalisation. RESULTS: NT-proBNP and BNP were significantly reduced after six months treatment with enalapril (NT-proBNP 1,303 to 857 pg/ml (P < 0.001), BNP 119 to 85 pg/ml (P < 0.001)) or carvedilol+enalapril (NT-proBNP 1,223 to 953 pg/ml (P = 0.003), BNP 117 to 93 pg/ml (P = 0.01)). In contrast, no change was observed in the carvedilol group (NT-proBNP 907 to 1,082 pg/ml (P = 0.06), BNP 114 to 130 pg/ml (P = 0.15). The prognostic value of NT-proBNP and BNP was maintained in the carvedilol group (NT-proBNP HR 1.018 95% CI (1.005-1.032), BNP 1.171 (1.088-1.260)). CONCLUSION: Treatment of HF patients with carvedilol alone does not reduce levels of natriuretic peptides, but treatment with enalapril does. Both BNP and NT-proBNP predict death and hospitalisation in HF patients treated with carvedilol for six months. The clinical implication of our results is that NT-proBNP and BNP can be used as risk markers of death and cardiovascular hospitalisations in systolic HF patients receiving carvedilol without ACE inhibition.     

The routine electrocardiogram for cardiovascular risk stratification in old age: the Leiden 85-plus study

OBJECTIVES: To explore the prognostic value of signs of prior myocardial infarction (MI) and atrial fibrillation (AF) on routine electrocardiograms (ECGs) at the age of 85 with respect to mortality and changes in functional status. DESIGN: Observational, prospective cohort study with complete 6-year follow-up. SETTING: General population. PARTICIPANTS: A population-based sample of 566 85-year-old participants (377 women, 189 men), without exclusion criteria. MEASUREMENTS: Annual ECG recording and evaluation using automated Minnesota Coding; annual assessment of functional status using validated questionnaires and tests; complete mortality data from civic and national registries. RESULTS: Participants with prior MI at the age of 85 (prevalence 9%) showed greater all-cause mortality (relative risk (RR)=1.7, 95% confidence interval (CI)=1.2-2.2) and cardiovascular mortality (RR=2.5, 95% CI=1.6-3.8) but no accelerated decline in functional status during follow-up. Participants with AF at the age of 85 (prevalence 10%) showed greater all-cause (RR=1.5, 95% CI=1.2-2.0) and cardiovascular (RR=2.0, 95% CI=1.3-3.0) mortality, as well as an accelerated decline in functional status during follow-up. CONCLUSION: Very elderly people with prior MI or AF on a routine ECG have markedly greater (cardiovascular) mortality risks. In addition, AF, but not prior MI, is associated with accelerated decline in functional status. These findings suggest that older patients with occasional findings of prior MI or AF on a routine ECG should receive optimal secondary preventive therapy. Furthermore, programmatic ECG recording could be of significant value for cardiovascular risk stratification in old age and needs further exploration.     

Sex differences in risk for coronary heart disease mortality associated with diabetes and established coronary heart disease

BACKGROUND: The sex-specific independent effect of diabetes mellitus and established coronary heart disease (CHD) on subsequent CHD mortality is not known. METHODS: This is an analysis of pooled data (n = 5243) from the Framingham Heart Study and the Framingham Offspring Study with follow-up of 20 years. At baseline (1971-1975), 134 men and 95 women had diabetes, while 222 men and 129 women had CHD. Risk for CHD death was analyzed by proportional hazards models, adjusting for age, hypertension, serum cholesterol levels, smoking, and body mass index. The comparative effect of established CHD vs diabetes on the risk of CHD mortality was tested by testing the difference in log hazards. RESULTS: The adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for death from CHD were 2.1 (95% CI, 1.3-3.3) in men with diabetes only, and 4.2 (95% CI, 3.2-5.6) in men with CHD only compared with men without diabetes or CHD. The HR for CHD death was 3.8 (95% CI, 2.2-6.6) in women with diabetes, and 1.9 (95% CI, 1.1-3.4) in women with CHD. The difference between the CHD and the diabetes log hazards was +0.73 (95% CI, 0.72-0.75) in men and -0.65 (95% CI, -0.68 to -0.63) in women. CONCLUSIONS: In men, established CHD signifies a higher risk for CHD mortality than diabetes. This is reversed in women, with diabetes being associated with greater risk for CHD mortality. Current treatment recommendations for women with diabetes may need to be more aggressive to match CHD mortality risk.     

Cardiac effects within 3 months of BEAC high-dose therapy in non-Hodgkin's lymphoma patients undergoing autologous stem cell transplantation

OBJECTIVES: Limited data are available on the cardiac effects of high-dose cyclophosphamide (CY) in patients with non-Hodgkin's lymphoma (NHL). We prospectively assessed the cardiac effects of high-dose CY in 30 adult NHL patients receiving CY 6 g/m(2) as part of BEAC high-dose therapy (HDT). METHODS: Radionuclide ventriculography (RVG) and plasma natriuretic peptide (NT-proANP, NT-proBNP) measurements were performed simultaneously prior to BEAC at baseline (d - 7), 12 days (d + 12) and 3 months (m + 3) after stem cell infusion (D0). In addition to these time points, natriuretic peptides were measured 2 days before (d - 2) and 1 week (d + 7) after stem cell infusion. RESULTS: Left ventricular ejection fraction (LVEF) decreased from d - 7 (53% +/- 2%) to d + 12 (49% +/- 2%, P = 0.009). However, no significant change in cardiac diastolic function was observed. The LVEF returned towards baseline by m + 3. Plasma NT-proANP and NT-proBNP increased significantly from baseline (445 +/- 65 pmol/L and 129 +/- 33 pmol/L) to d - 2 (1,127 +/- 142 pmol/L, P < 0.001 and 624 +/- 148 pmol/L, P < 0.001, respectively). Thereafter, they started to decrease, but on d + 7 NT-proANP (404 +/- 157 pmol/L, P = 0.048) and NT-proBNP (648 +/- 125 pmol/L, P = 0.015) were still significantly higher than at baseline. On d + 12 and m + 3 they no longer differed from baseline. CONCLUSIONS: Our findings suggest that high-dose CY results in acute, subclinical systolic dysfunction in NHL patients previously treated with anthracyclines. Natriuretic peptides seem to be more sensitive than LVEF to reflect this transient cardiac effect. Serial measurements of natriuretic peptides might be a useful tool to assess cardiac effects of high-dose CY.     

Left atrium size and the risk of cardiovascular death in middle-aged men

BACKGROUND: The echocardiographic identification of subclinical risk markers may enhance risk stratification for the development of cardiovascular outcomes in the general population. Although echocardiography is widely used in the evaluation of cardiac structures and function, the prognostic value of echocardiographic assessment of left atrium (LA) size for risk stratification of cardiovascular death is unknown. METHODS: Left ventricular (LV) mass and LA size were measured by using M-mode echocardiography in a representative population-based sample of 830 men (age, 42-61 years) from eastern Finland. There were 54 deaths due to cardiovascular disease during an average follow-up of 13 years. RESULTS: The strongest risk factors for cardiovascular death were smoking, family history of coronary heart disease, low exercise capacity, elevated blood pressure, exercise-induced myocardial ischemia, and large LA diameter. Men in the highest tertile of LA diameter (>43 mm) had a 2.3-fold (95% confidence interval, 1.1-5.0) risk of cardiovascular death compared with men in the lowest tertile of LA diameter (<39 mm), after adjusting for other risk factors and the use of antihypertensive medications. The excess risk for cardiovascular mortality appeared to reside largely in the highest tertile of LA size. After additional adjustment for LV mass, the relation between LA size and mortality did not remain statistically significant (relative risk, 1.5; 95% confidence interval, 0.8-4.1; P = .15) in this group. CONCLUSIONS: This prospective population-based study shows that echocardiographically defined LA diameter was directly related to the risk of cardiovascular death. The association of LA enlargement to cardiovascular death appears to be partially related to LV hypertrophy.