Neutrophil lymphocyte ratio significantly improves the Framingham risk score in prediction of coronary heart disease mortality: Insights from the National Health and Nutrition Examination Survey-III

Background

Neutrophil lymphocyte ratio (NLR) has been shown to predict cardiovascular events in several studies. We sought to study if NLR predicts coronary heart disease (CHD) in a healthy US cohort and if it reclassifies the traditional Framingham risk score (FRS) model.

Methods

We performed post hoc analysis of National Health and Nutrition Examination Survey-III (1998–94) including subjects aged 30–79 years free from CHD or CHD equivalent at baseline. Primary endpoint was death from ischemic heart disease. NLR was divided into four categories: < 1.5, ≥ 1.5 to < 3.0, 3.0–4.5 and > 4.5. Statistical analyses involved multivariate Cox proportional hazards models as well as discrimination, calibration and reclassification.

Results

We included 7363 subjects with a mean follow up of 14.1 years. There were 231 (3.1%) CHD deaths, more in those with NLR > 4.5 (11%) compared to NLR < 1.5 (2.4%), p < 0.001. Adjusted hazard ratio of NLR > 4.5 was 2.68 (95% CI 1.07–6.72, p = 0.035). There was no significant improvement in C-index (0.8709 to 0.8713) or area under curve (0.8520 to 0.8531) with addition of NLR to FRS model. Model with NLR was well calibrated with Hosmer–Lemeshow chi-square of 8.57 (p = 0.38). Overall net reclassification index (NRI) was 6.6% (p = 0.003) with intermediate NRI of 10.1% (p < 0.001) and net upward reclassification of 5.6%. Absolute integrated discrimination index (IDI) was 0.003 (p = 0.039) with relative IDI of 4.3%.

Conclusions

NLR can independently predict CHD mortality in an asymptomatic general population cohort. It reclassifies intermediate risk category of FRS, with significant upward reclassification. NLR should be considered as an inflammatory biomarker of CHD.     

Validation of contemporary stroke and bleeding risk stratification scores in non-anticoagulated Chinese patients with atrial fibrillation

Background

Risk stratification schemes assessing stroke and thromboembolism (stroke/TE) and bleeding relating to atrial fibrillation (AF) have largely been derived and validated in Western populations. We assessed risk factors that constitute scores for assessing stroke/TE (CHADS₂, CHA₂DS₂-VASc) and bleeding (HAS-BLED), and the predictive value of these scores in a large cohort of Chinese patients with AF.

Methods and results

We studied 1034 AF patients (27.1% female, median age 75; 85.6% non-anticoagulated) with mean follow-up of 1.9 years. On multivariate analysis, vascular disease was independently associated with stroke/TE in non-anticoagulated patients (p = 0.04). In patients with a CHADS₂ or CHA₂DS₂-VASc score = 1, the rate of stroke/TE was 2.9% and 0.9% respectively, but in patients at “high risk” (scores ≥ 2), this rate was 4.6% and 4.5%, respectively. The c-statistics for predicting stroke/TE with CHADS₂ and CHA₂DS₂-VASc were 0.58 (p = 0.109) and 0.72 (p < 0.001), respectively. Compared to CHADS₂, the use of CHA₂DS₂-VASc would result in a Net Reclassification Improvement (NRI) of 16.6% (p = 0.009) and an Integrated Discrimination Improvement (IDI) of 1.1% (p = 0.002). Cumulative survival of the patients with a CHA₂DS₂-VASc score ≥ 2 was decreased compared to those with a CHA₂DS₂-VASc score 0–1 (p < 0.001), but the CHADS₂ was not predictive of mortality. There was an increased risk of major bleeding with increasing HAS-BLED score (c-statistic 0.61, 95% CI: 0.51–0.71, p = 0.042).

Conclusions

Vascular disease was a strong independent predictor of stroke/TE in Chinese patients with AF. The CHA₂DS₂-VASc score performed better than CHADS₂ in predicting stroke/TE in this Chinese AF population. Cumulative survival of the patients at high risk with the CHA₂DS₂-VASc score (but not using CHADS₂) was significantly decreased.     

Serum albumin changes and multivariate dynamic risk modelling in chronic heart failure

Background

We examined the prognostic utility of rate of change in serum albumin over time in chronic heart failure (CHF), as well as the utility of multivariate dynamic risk modelling.

Methods and results

The survival implication of ?albumin was analysed in 232 systolic CHF patients and validated in 212 patients. A multivariate dynamic risk score predicated on the rate of change in 6 simple indices including albumin was calculated and related to mortality. In derivation patients, 50 (22%) deaths occurred over 13 months. Greater rates of decline in albumin related to higher mortality (HR 0.55, 95% CI 0.41–0.73, P < 0.0001) independently, incrementally and more accurately than other covariates including baseline albumin. A rate of attenuation > 0.4 g/dL/month optimally forecasted death and was associated with a 5-fold escalated risk of mortality (HR 5.13, 95% CI 2.92–9.00, P < 0.0001). Similar results were seen in the validation cohort. On multivariate dynamic risk modelling, survival at 1-year worsened with higher scores—a score ≥ 3 was associated with a 12-fold greater risk of death than a score of 0, a 6-fold higher risk of death than a score of 1, and a 4-fold enhanced risk of mortality than a score of 2.

Conclusion

Attenuations in serum albumin over time relate to increased mortality in CHF, and a risk model predicated on the rate of change in 6 simple indices can identify patients at a 12-fold enhanced risk of death over the coming year.     

Prealbumin improves death risk prediction of BNP-added Seattle Heart Failure Model: Results from a pilot study in elderly chronic heart failure patients

Background

An accurate prognosis prediction represents a key element in chronic heart failure (CHF) management. Seattle Heart Failure Model (SHFM) prognostic power, a validated risk score for predicting mortality in CHF, is improved by adding B-type natriuretic peptide (BNP). We evaluated in a prospective study the incremental value of several biomarkers, linked to different biological domains, on death risk prediction of BNP-added SHFM.

Methods

Troponin I (cTnI), norepinephrine, plasma renin activity, aldosterone, high sensitivity-C reactive protein (hs-CRP), tumor necrosis factor-α ?(TNF-α), interleukin 6 (IL-6), interleukin 2 soluble receptor, leptin, prealbumin, free malondialdehyde, and 15-F_2t-isoprostane were measured in plasma from 142 consecutive ambulatory, non-diabetic stable CHF (mean NYHA-class 2.6) patients (mean age 75 ± 8 years). Calibration, discrimination, and risk reclassification of BNP-added SHFM were evaluated after individual biomarker addition.

Results

Individual addition of biomarkers to BNP-added SHFM did not improve death prediction, except for prealbumin (HR 0.49 CI: (0.31–0.76) p = 0.002) and cTnI (HR 2.03 CI: (1.20–3.45) p = 0.009). In fact, with respect to BNP-added SHFM (Harrell's C-statistic 0.702), prealbumin emerged as a stronger predictor of death showing the highest improvement in model discrimination (+ 0.021, p = 0.033) and only a trend was observed for cTn I (+ 0.023, p = 0.063). These biomarkers showed also the best reclassification statistic (Integrated Discrimination Improvement—IDI) at 1-year (IDI: cTnI, p = 0.002; prealbumin, p = 0.020), 2-years (IDI: cTnI, p = 0.018; prealbumin: p = 0.006) and 3-years of follow-up (IDI: cTnI p = 0.024; prealbumin: p = 0.012).

Conclusions

Individual addition of prealbumin allows a more accurate prediction of mortality of BNP enriched SHFM in ambulatory elderly CHF suggesting its potential use in identifying those at high-risk that need nutritional surveillance.     

Does residual aortic regurgitation after transcatheter aortic valve implantation increase mortality in all patients? The importance of baseline natriuretic peptides

Background

Aortic regurgitation (AR) is an important complication of transcatheter aortic valve implantation (TAVI) and even moderate AR is associated with increased mortality after TAVI. The association with decreased survival is unclear. We aimed to analyse the impact of AR after TAVI as a function of baseline NT-proBNP.

Methods

We included 236 consecutive patients implanted in our centre with the SAPIEN and SAPIEN XT valves, via the transfemoral route. AR was evaluated by transthoracic echocardiography. NT-proBNP was measured 24 h before implantation and patients were divided according to the median value.

Results

Median age was 85 years (80–89) and 137 (58.1%) were women. Patients with high NT-proBNP had lower left ventricular ejection fraction: 52% (35–65) vs. 63% (55–70), p < 0.001, larger telediastolic diameters: 56 mm (49–61) vs. 52 mm (46–56), p = 0.01, and more severe aortic stenosis: 0.62 ± 0.15 cm² vs. 0.70 ± 0.2 cm², p < 0.001. Pre-procedural moderate or severe AR (42% vs. 26%, p = 0.013) and mitral regurgitation (56% vs. 36%, p = 0.004) were more common in the high NT-proBNP group. After TAVI, moderate or severe AR occurred in 26% of patients and was associated with increased 2-year mortality only in the low NT-proBNP group, while patients in the high NT-proBNP group were not affected.

Conclusions

Moderate or severe AR after TAVI was not associated with increased 2-year mortality in patients with high baseline NT-proBNP. Our data suggest that the impact of AR after TAVI is absent in patients with significant pre-procedural AR or mitral regurgitation and more severe aortic stenosis.     

Role of euroSCORE II in predicting long-term outcome after percutaneous catheter intervention for coronary triple vessel disease or left main stenosis

Objectives

The SYNTAX score (Ssc) assessing the complexity of coronary anatomy predicts survival after percutaneous coronary intervention (PCI). We tested the hypothesis that the newly developed euroSCORE II (eSC2) can improve the prediction of outcome after complex PCI by the Ssc.

Methods and results

Our study comprised 1262 consecutive patients with triple vessel disease or left main stenosis, who were contacted 3 years after elective PCI with drug-eluting stents. We calculated eSC2, Ssc, logistic euroSCORE, and ACEF score. Prediction of 3-year all-cause mortality by these scores was assessed by Cox proportional hazard models. Models were compared by the Hosmer–Lemeshow test for calibration (HL), the C-statistics (AUC) for discrimination and by net reclassification indices (NRI). eSC2 and Ssc were significant predictors of 3-year mortality (unadjusted hazard ratios [95%-confidence limits], 1.050 [1.033–1.067], 1.180 [1.146–1.215], respectively, P < 0.001). The predictive value of eSC2 was improved by logarithmic transformation. Adding eSC2 to the model with Ssc improved calibration (HL 7.4 vs. 11.1) and discrimination (increase in AUC [95%-confidence limits] 0.12 [0.07 to 0.17]) and yielded a significant NRI of 0.38 (95%-confidence limits 0.28 to 0.47). The absolute difference in 3-year mortality between strata of Ssc (≤ 22, > 22–32, > 32) was smaller with eSC2 < 1% (1.4%, 3.4%, 9.7%, respectively), than with eSC2 > 1.6% (11.2%, 20.2%, 30.6%, respectively). The predictive ability of eSC2 was similar to that of the other clinical scores.

Conclusions

eSC2 predicts 3-year mortality after complex PCI and modifies the impact of angiographic complexity on outcome.     

Pre-discharge risk stratification in unselected STEMI: Is there a role for ST2 or its natural ligand IL-33 when compared with contemporary risk markers?

Background

Soluble ST2 is a marker of cellular stress and injury whose natural ligand is interleukin-33. We investigate, for the first time, the relationship of IL-33 and ST2 with death at 30-days, 1-year and beyond in unselected STEMI patients. We assess the incremental value they offer over GRACE score and NT-proBNP. Secondary endpoints were heart failure readmission and re-infarction.

Methods

ST2 and IL-33 were measured in 677 patients 3–5 days after admission. Median follow-up was 587 (134–2818) days during which 101 (15%) patients died.

Results

ST2 was higher in those who died when compared to event-free survivors (median [range] 1125 [123–15781] vs. 630 [59–11729] pg/ml, p < 0.001) as was IL-33 (75 [5.4-17893] vs. 5.4 [5.4-16466] pg/mL, p = 0.006). Multivariate Cox regression analysis reveals that elevated ST2 is associated with increased risk of mortality at 30-days (HR 9.34, p < 0.001) and 1-year (HR 3.15, p = 0.001). These relationships continued after further adjustment for GRACE-RS and NT-proBNP. Combining ST2 (c-statistic 0.82, p < 0.001), GRACE-RS (0.82, p < 0.001) and NT-proBNP (0.84, p < 0.001) leads to a significant improvement in the c-statistic for 30-day mortality to 0.90 (p = 0.01). IL-33 above 5.4 pg/ml was independently associated with increased mortality at 30-days (HR 4.16, p = 0.007) and 1-year (HR 2.29, p = 0.008) but, did not add incremental prognostic value over using GRACE-RS and NT-proBNP. The ratio IL-33/ST2 was not associated with events.

Conclusions

Elevated ST2 and IL-33 were both associated with increased mortality. ST2 demonstrated incremental value over contemporary risk markers but, IL-33 did not. ST2 has a potential role in risk stratification using a multi-marker approach.     

Comparative assessment of the HAS-BLED score with other published bleeding risk scoring schemes,for intracranial haemorrhage risk in a non-atrial fibrillation population: The Chin-Shan Community Cohort Study

Background

The HAS-BLED score is a validated bleeding risk model for predicting major bleeding events in anticoagulated individuals with atrial fibrillation (AF). It remains uncertain whether the HAS-BLED score could identify non-AF individuals at risk of developing intracranial haemorrhage (ICH), which is the most intractable and devastating major bleeding complication.

Methods

We assessed the predictive value of a modified HAS-BLED and other bleeding risk scoring models to predict the risk for ICH in the Chin-Shan Community Cohort, which followed 1899 women and 1703 men, aged > 35 years, for a median of 15.9 years. ICH events (including haemorrhagic strokes) were ascertained according to questionnaires and the national register database.

Results

Of 3524 individuals without baseline AF, 54 ICH events occurred during follow-up. The risk for ICH was raised with increasing HAS-BLED scores, and was significantly associated with uncontrolled hypertension and older age (Odds Ratios [95% confidence interval (CI)], 4.2[2.3–7.6] and 1.9[1.1–3.4], respectively). Among the five bleeding risk scoring schemes tested, HAS-BLED had highest general discrimination performance (c-statistic [95% CI], 0.72 [0.67–0.78]), and better ability to discriminate between those who were at risk for ICH and who were not (NRI, net reclassification improvement, all p < 0.05, compared to other four scoring schemes).

Conclusion

The HAS-BLED score had the highest general discrimination performance and best ability to discriminate risk for ICH. This score may be of clinical use in predicting the risk for occurrence of ICH among non-AF individuals.     

Cangrelor infusion is associated with an increased risk for bleeding: Meta-analysis of randomized trials

Context

Aggressive antiplatelet strategies unquestionably cause extra hemorrhagic risks. Bleeding episodes are associated with poor outcomes including increased mortality. However, lack of uniform reporting and adjudication of bleeding events might prevent objective evaluation of the efficacy/safety profile of antithrombotic agents.

Objective

We analyzed the bleeding rates by several previously used bleeding scales (TIMI, GUSTO, ACUITY, and BARC) after cangrelor in recent head-to-head randomized, controlled clinical trials (RCTs).

Results

Data for meta-analyses were pooled from 3 RCTs (CHAMPION-PLATFORM, CHAMPION-PCI and CHAMPION-PHOENIX) including 25,106 patients. In addition, the bleeding risks were also assessed from the small (n = 210) BRIDGE RCT. Cangrelor caused a significantly increased risk for major bleeding at 48 h according to the ACUITY scale (RR: 1.51, 95% CI: 1.32–1.72, p < 0.00001); however, this impact was less prominent according to less sensitive bleeding scales (GUSTO severe: RR: 1.21, 95% CI: 0.70–2.11, p = 0.49; TIMI major: RR: 1.00, 95% CI: 0.59–1.68, p = 0.99). There was also an obvious trend towards an increased risk for any transfusions (RR: 1.31, 95% CI: 0.97–1.77, p = 0.08) and TIMI major + minor bleeding events (RR: 1.30, 95% CI: 0.96–1.76, p = 0.09).

Conclusions

Cangrelor on top of aspirin or/and clopidogrel increases the risk for early bleeding events after PCI; however, it largely depends on the bleeding definition used, and how this excess risk of bleeding was captured. The bleeding hazard needs to be verified in the ongoing FDA secondary cangrelor review.     

Cardiovascular risk prediction in the general population with use of suPAR,CRP, and Framingham Risk Score

Background

The inflammatory biomarkers soluble urokinase plasminogen activator receptor (suPAR) and C-reactive protein (CRP) independently predict cardiovascular disease (CVD). The prognostic implications of suPAR and CRP combined with Framingham Risk Score (FRS) have not been determined.

Methods

From 1993 to 1994, baseline levels of suPAR and CRP were obtained from 2315 generally healthy Danish individuals (mean [SD] age: 53.9 [10.6] years) who were followed for the composite outcome of ischemic heart disease, stroke and CVD mortality.

Results

During a median follow-up of 12.7 years, 302 events were recorded. After adjusting for FRS, women with suPAR levels in the highest tertile had a 1.74-fold (95% confidence interval [CI]: 1.08–2.81, p = 0.027) and men a 2.09-fold (95% CI: 1.37–3.18, p < 0.001) increase in risk compared to the lowest tertile. Including suPAR and CRP together resulted in stronger risk prediction with a 3.30-fold (95% CI: 1.36–7.99, p < 0.01) increase for women and a 3.53-fold (1.78–7.02, p < 0.001) increase for men when both biomarkers were in the highest compared to the lowest tertile. The combined extreme tertiles of suPAR and CRP reallocated individuals predicted to an intermediate 10-year risk of CVD of 10–20% based on FRS, to low (< 10%) or high (> 20%) risk categories, respectively. This was reflected in a significant improvement of C statistics for men (p = 0.034) and borderline significant for women (p = 0.054), while the integrated discrimination improvement was highly significant (P ≤ 0.001) for both genders.

Conclusions

suPAR provides prognostic information of CVD risk beyond FRS and improves risk prediction substantially when combined with CRP in this setting.     

Aggressive and diffuse coronary calcification in South Asian angina patients compared to Caucasians with similar risk factors

Background

Ethnic differences in prevalence and severity of coronary artery disease are well established and are usually attributed to risk factors variation. This study investigates the differences in coronary artery narrowing and coronary calcification between two age- and gender-matched cohorts of South Asian and Caucasian symptomatic angina patients.

Methods

We identified 101 symptomatic angina patients of South Asian origin who had undergone CT angiography and calcium scoring, and compared them with 101 age and gender matched Caucasian patients.

Results

South Asians had a greater mean number of arterial segments with both obstructive and non-obstructive plaque than Caucasians (p = 0.006 and p = 0.0003, respectively) and higher prevalence of triple-vessel disease (p = 0.0004). Similarly, South Asians had a higher mean CAC score (p < 0.0001) and the percentage of South Asians with CAC > 0 and in all categories of CAC score 100–1000 were also higher, as was the number of arterial segments with calcified and non-calcified plaque. These results were more marked in patients aged > 50 but in those ≤ 50, Caucasians showed a higher mean number of diseased segments (p = 0.019), with non-obstructive plaque (p = 0.02), possibly suggesting that Caucasians are likely to have more diffuse atherosclerosis at an earlier age. CAC prevalence and severity in this age-group were not significantly different between South Asians and Caucasians.

Conclusion

Despite similar conventional risk factors for CAD, symptomatic South Asians seem to have more aggressive and diffuse arterial calcification compared to Caucasians. These differences are more profound above the age of 50, suggesting potential genetic or other risk factors yet to be determined.     

The predictive value of CHADS2 risk score in post myocardial infarction arrhythmias — A Cardiac Arrhythmias and RIsk Stratification after Myocardial infArction (CARISMA) substudy

Background

Previous studies have shown substantially increased risk of cardiac arrhythmias and sudden cardiac death in post-myocardial infarction (MI) patients. However it remains difficult to identify the patients who are at highest risk of arrhythmias in the post-MI setting. The purpose of this study was to investigate if CHADS₂ score (congestive heart failure, hypertension, age ≥ 75 years, diabetes and previous stroke/TCI [doubled]) can be used as a risk tool for predicting cardiac arrhythmias after MI.

Methods

The study included 297 post-MI patients from the CARISMA study with left ventricular ejection fraction (LVEF) ≤ 40%. All patients were implanted with an implantable cardiac monitor (ICM) within 5 to 21 days post-MI and followed every three months for two years. Atrial fibrillation, bradyarrhythmias and ventricular tachycardias were diagnosed using the ICM, pacemaker or ICD. Patients were stratified according to CHADS₂ score at enrollment. Congestive heart failure was defined as LVEF ≤ 40% and NYHA class II, III or IV.

Results

We found significantly increased risk of an arrhythmic event with increasing CHADS₂ score (CHADS₂ score = 1–2: HR = 2.1 [1.1–3.9], p = 0.021, CHADS₂ score ≥ 3: HR = 3.7 [1.9–7.1], p < 0.001). This pattern was identical when dividing the arrhythmias into subgroups of atrial fibrillation, ventricular tachycardias and bradyarrhythmias. CHADS₂ score was similarly associated with the development of major cardiovascular events defined as reinfarction, stroke, and hospitalization for heart failure or cardiovascular death.

Conclusion

In the post-MI setting, CHADS₂ score efficiently identifies populations at high risk for cardiac arrhythmias.     

Prognostic implications of quantitative evaluation of baseline Q-wave width in ST-segment elevation myocardial infarction

Objectives

To evaluate quantitative relationships between baseline Q-wave width and 90-day outcomes in ST-segment elevation myocardial infarction (STEMI).

Background

Baseline Q-waves are useful in predicting clinical outcomes after MI.

Methods

3589 STEMI patients were assessed from a multi-centre study.

Results

1156 patients of the overall cohort had pathologic Q-waves. The 90-day mortality and the composite of mortality, congestive heart failure (CHF), or cardiogenic shock (p < 0.001 for both outcomes) rose as Q-wave width increased. After adapting a threshold ≥ 40 ms for inferior and ≥ 20 ms for lateral/apical MI in all patients (n = 3065) with any measureable Q-wave we found hazard ratios (HR) for mortality (HR: 2.44, 95% confidence interval (CI) (1.54–3.85), p < 0.001) and the composite (HR: 2.32, 95% CI (1.70–3.16), p < 0.001). This improved reclassification of patients experiencing the composite endpoint versus the conventional definition (net reclassification index (NRI): 0.23, 95% CI (0.09-0.36), p < 0.001) and universal MI definition (NRI: 0.15, 95% CI (0.02–0.29), p = 0.027).

Conclusions

The width of the baseline Q-wave in STEMI adds prognostic value in predicting 90-day clinical outcomes. A threshold of ≥ 40 ms in inferior and ≥ 20 ms for lateral/apical MI enhances prognostic insight beyond current criteria.     

Cardiometabolic risk and disease in Indigenous Australians: The heart of the heart study

Objectives

This study assessed the burden and determinants of cardiovascular and metabolic risk in a community sample of high risk Indigenous Australians.

Background

Indigenous Australians are over-represented in the most disadvantaged strata of Australian society. The role of psychosocial and socioeconomic factors in patterning cardiometabolic disease in this population is unclear.

Methods

The Heart of the Heart Study was a cross sectional study of 436 Aboriginal adults from remote, urban and peri-urban communities around Alice Springs (Northern Territory, Australia). Participants underwent detailed assessments of socio-demographic, psychosocial, cardiovascular and metabolic status.

Results

Individuals with depression were twice as likely to have cardiovascular disease (OR 2.03; 1.07–3.88; p < 0.05). Chronic kidney disease (39.7%, 37.2% and 18.2%) and diabetes (28.4%, 34.0% and 19.2%) were more common in peri-urban and remote compared to urban communities. Cardiovascular disease did not vary across locations (p = 0.069), but coronary artery disease did (p = 0.035 for trend). Unemployed individuals were more likely to have cardiovascular disease (OR 2.32; 1.33–4.06; p < 0.001). Socioeconomic gradients in coronary artery disease, all cardiovascular disease and diabetes, as measured by income, operated differentially across locations (p for location/socioeconomic status interactions 0.002; 0.01 and 0.04 respectively).

Conclusion

Participants had high rates of pre-existing cardiovascular disease, diabetes and chronic kidney disease. Cardiovascular risk in these communities was associated with psychosocial factors and socioeconomic indicators. However, gradients operated differentially across location. These data provide a strong foundation for better understanding key drivers of increased levels of cardiovascular and other common forms of non-communicable disease in Indigenous people.     

NT-proB natriuretic peptide,risk factors and asymptomatic left ventricular dysfunction: Results of the SCReening Evaluation of the Evolution of New Heart Failure Study (SCREEN-HF)

Background

We assessed left ventricular dysfunction in a population at high risk for heart failure (HF), and explored associations between ventricular function, HF risk factors and NT-proB natriuretic peptide (NT-proBNP).

Methods and results

3550 subjects at high risk for incident HF (≥ 60 years plus ≥ 1 HF risk factor), but without pre-existing HF or left ventricular dysfunction, were recruited. Anthropomorphic data, medical history and blood for NT-proBNP were collected. Participants at highest risk (n = 664) (NT-proBNP highest quintile; > 30.0 pmol/L) and a sample (n = 51) from the lowest NT-proBNP quintile underwent echocardiography.Participants in the highest NT-proBNP quintile, compared to the lowest, were older (74 years vs. 67 years; p < 0.001) and more likely to have coronary artery disease, stroke or renal impairment. In the top NT-proBNP quintile (n = 664), left ventricular systolic impairment was observed in 6.6% (95% CI: 4 to 8%) of participants and was associated with male gender, coronary artery disease, hypertension and NT-proBNP. At least moderate diastolic dysfunction was observed in 24% (95% CI 20 to 27%) of participants and was associated with diabetes and NT-proBNP. In this high risk population, NT-proBNP was associated with left ventricular systolic impairment (p < 0.001) and moderate to severe diastolic dysfunction (p < 0.001) after adjustment for age, gender, coronary artery disease, diabetes, hypertension and obesity.

Conclusion

A high burden of ventricular dysfunction was observed in this high risk group. Combining NT-proBNP and HF risk factors may identify those with ventricular dysfunction. This would allow resources to be focused on those at greatest risk of progression to overt HF.     

Lack of difference in T wave variability between patients at risk of sudden cardiac death and healthy subjects

Background

T wave variability (Tvar) is a proposed method to predict sudden cardiac death (SCD). The purpose of this trial was to evaluate the reproducibility of Tvar measurements over time and demonstrate a difference in Tvar between patient populations at risk for ventricular arrhythmias and healthy subjects.

Methods

Sixty subjects were enrolled in into 3 groups: healthy subjects (Population I), patients at high risk of SCD (Population II), and patients with a recent ventricular tachyarrhythmia event (Population III). Recording and analysis of T wave amplitude variance (TAV) as a measure of Tvar was performed at baseline and 3 months.

Results

TAV could not be interpreted in 12 of 43 patients in Populations II and III due to PVCs or noise. No subject had a TAV value suggestive of high risk of SCD as per a previously defined cutoff of > 59 μV. Median (range) values of TAV in μV at baseline for Populations I, II and III were 26 (15–39), 21 (13–43), and 24 (18–41), respectively (p = 0.39). TAV was reproducible within population's from baseline to 3 months (p = 0.27, 0.53, 0.17 for Populations I, II and III, respectively). There was no significant difference between TAV values of high risk patients and healthy subjects.

Conclusion

Tvar was reproducible primarily in patients with left ventricular dysfunction. However, the role of Tvar as a risk stratifying tool remains inconclusive.     

Prospective risk stratification of sudden cardiac death in Marfan's syndrome

Background

Marfan syndrome (MFS) is a variable, autosomal-dominant disorder of the connective tissue. In MFS serious ventricular arrhythmias and sudden cardiac death (SCD) can occur. The aim of this prospective study was to reveal underlying risk factors and to prospectively investigate the association between MFS and SCD in a long-term follow-up.

Methods

77 patients with MFS were included. At baseline serum N-terminal pro-brain natriuretic peptide (NT-proBNP), transthoracic echocardiogram, 12-lead resting ECG, signal-averaged ECG (SAECG) and a 24-h Holter ECG with time- and frequency domain analyses were performed. The primary composite endpoint was defined as SCD, ventricular tachycardia (VT), ventricular fibrillation (VF) or arrhythmogenic syncope.

Results

The median follow-up (FU) time was 868 days. Among all risk stratification parameters, NT-proBNP remained the exclusive predictor (hazard ratio [HR]: 2.34, 95% confidence interval [CI]: 1.1 to 4.62, p = 0.01) for the composite endpoint. With an optimal cut‐off point at 214.3 pg/ml NT-proBNP predicted the composite primary endpoint accurately (AUC 0.936, p = 0.00046, sensitivity 100%, specificity 79.0%). During FU, seven patients of Group 2 (NT-proBNP ≥ 214.3 pg/ml) reached the composite endpoint and 2 of these patients died due to SCD. In five patients, sustained VT was documented. All patients with a NT-proBNP < 214.3 pg/ml (Group 1) experienced no events. Group 2 patients had a significantly higher risk of experiencing the composite endpoint (logrank-test, p < 0.001).

Conclusions

In contrast to non-invasive electrocardiographic parameter, NT-proBNP independently predicts adverse arrhythmogenic events in patients with MFS.     

Red cell distribution width is associated with physical inactivity and heart failure,independent of established risk factors,inflammation or iron metabolism; the EPIC—Norfolk study

Aims

Red cell distribution width (RDW) is associated with increased risk of heart failure (HF). We examined in a healthy population (1) whether this association is independent of cardiovascular risk factors and iron metabolism and (2) whether RDW associates with physical activity.

Methods and results

Hazard ratios (HRs, highest quartile versus lowest quartile of RDW) for the risk of HF were calculated in 17,533 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)—Norfolk cohort. During a follow-up of 11.2 ± 2.2 years 640 participants developed a HF event. The HR for HF events was 1.44 (95%CI 1.15–1.80, p < 0.001). There was a non-linear increase in HF risk across RDW quartiles. Adjustment for established risk factors (sex, age, diabetes, smoking, systolic blood pressure, total and high-density lipoprotein cholesterol) attenuated the HR for HF to 1.40 (95%CI 1.11–1.77, p = 0.001). Adjustment for CRP, iron and ferritin levels did not affect the HR for HF. RDW levels are inversely associated with physical activity (per category β = − 0.37, 95%CI − 0.053 to − 0.021, p < 0.0001), independent of iron metabolism. However, the association between HF and RDW levels was not changed by physical activity.

Conclusions

This study confirms that RDW is associated with HF events in an apparently healthy middle-aged population. More importantly, we show that the underlying pathophysiology linking HF with anisocytosis is not reflected by conventional risk factors, nor it is explained by iron metabolism or inflammation. Furthermore, RDW levels were associated with physical inactivity, but this did not influence the RDW-associated-risk of heart failure.     

Prevention of heart failure in older adults may require higher levels of physical activity than needed for other cardiovascular events

Background

Little is known if the levels of physical activity required for the prevention of incident heart failure (HF) and other cardiovascular events vary in community-dwelling older adults.

Methods

We studied 5503 Cardiovascular Health Study (CHS) participants, age ≥ 65 years, free of baseline HF. Weekly metabolic equivalent task-minutes (MET-minutes), estimated using baseline total leisure-time energy expenditure, were used to categorize participants into four physical activity groups: inactive (0 MET-minutes; n = 489; reference), low (1–499; n = 1458), medium (500–999; n = 1086) and high (≥ 1000; n = 2470).

Results

Participants had a mean (± SD) age of 73 (± 6) years, 58% were women, and 15% African American. During 13 years of follow-up, centrally-adjudicated incident HF occurred in 26%, 23%, 20%, and 19% of participants with no, low, medium and high physical activity, respectively (trend p < 0.001). Compared with inactive older adults, age–sex–race-adjusted hazard ratios (95% confidence intervals) for incident HF associated with low, medium and high physical activity were 0.87 (0.71–1.06; p = 0.170), 0.68 (0.54–0.85; p = 0.001) and 0.60 (0.49–0.74; p < 0.001), respectively (trend p < 0.001). Only high physical activity had significant independent association with lower risk of incident HF (HR, 0.79; 95% CI, 0.64–0.97; p = 0.026). All levels of physical activity had significant independent association with lower risk of incident acute myocardial infarction (AMI), stroke and cardiovascular mortality.

Conclusion

In community-dwelling older adults, high level of physical activity was associated with lower risk of incident HF, but all levels of physical activity were associated with lower risk of incident AMI, stroke, and cardiovascular mortality.     

Prediabetes is not an independent risk factor for incident heart failure,other cardiovascular events or mortality in older adults: Findings from a population-based cohort study

Background

Whether prediabetes is an independent risk factor for incident heart failure (HF) in non-diabetic older adults remains unclear.

Methods

Of the 4602 Cardiovascular Health Study participants, age ≥ 65 years, without baseline HF and diabetes, 2157 had prediabetes, defined as fasting plasma glucose (FPG) 100–125 mg/dL. Propensity scores for prediabetes, estimated for each of the 4602 participants, were used to assemble a cohort of 1421 pairs of individuals with and without prediabetes, balanced on 44 baseline characteristics.

Results

Participants had a mean age of 73 years, 57% were women, and 13% African American. Incident HF occurred in 18% and 20% of matched participants with and without prediabetes, respectively (hazard ratio {HR} associated with prediabetes, 0.90; 95% confidence interval {CI}, 0.76–1.07; p = 0.239). Unadjusted and multivariable-adjusted HRs (95% CIs) for incident HF associated with prediabetes among 4602 pre-match participants were 1.22 (95% CI, 1.07–1.40; p = 0.003) and 0.98 (95% CI, 0.85–1.14; p = 0.826), respectively. Among matched individuals, prediabetes had no independent association with incident acute myocardial infarction (HR, 1.02; 95% CI, 0.81–1.28; p = 0.875), angina pectoris (HR, 0.93; 95% CI, 0.77–1.12; p = 0.451), stroke (HR, 0.86; 95% CI, 0.70–1.06; p = 0.151) or all-cause mortality (HR, 0.99; 95% CI, 0.88–1.11; p = 0.840).

Conclusions

We found no evidence that prediabetes is an independent risk factor for incident HF, other cardiovascular events or mortality in community-dwelling older adults. These findings question the wisdom of routine screening for prediabetes in older adults and targeted interventions to prevent adverse outcomes in older adults with prediabetes.