Elevated Cardiac Troponin T Levels in Critically Ill Patients with Sepsis

Background

It is known that troponin elevations have prognostic importance in critically ill patients. We examined whether cardiac troponin T elevations are independently associated with in-hospital, short-term (30 days), and long-term (3 years) mortality in intensive care unit (ICU) patients admitted with sepsis, severe sepsis, and septic shock after adjusting for the severity of disease with the Acute Physiology, Age and Chronic Health Evaluation III system.

Methods

We studied the Mayo Clinic's Acute Physiology, Age and Chronic Health Evaluation III database and cardiac troponin T levels from patients admitted consecutively to the medical ICU. Between January 2001 and December 2006, 926 patients with sepsis had cardiac troponin T measured at ICU admission. In-hospital, short-term, and long-term all-cause mortality were determined.

Results

Among study patients, 645 (69.7%) had elevated cardiac troponin T levels and 281 (30.3%) had undetectable cardiac troponin T. During hospitalization, 15% of the patients with troponin T <0.01 ng/mL died compared with 31.9% of those with troponin T ≥0.01 ng/mL (P < .0001). At 30 days, mortality was 31% and 17% in patients with and without elevations, respectively (P < .0001). The Kaplan-Meier probability of survival at 1-, 2-, and 3-year follow-ups was 68.1%, 56.3%, and 46.8% with troponin T ≥0.01 ng/mL, respectively, and 76.4%, 69.1%, and 62.0% with troponin T <0.01 μg/L, respectively (P < .0001). After adjustment for severity of disease and baseline characteristics, cardiac troponin T levels remained associated with in-hospital and short-term mortality but not with long-term mortality.

Conclusions

In patients with sepsis who are admitted to an ICU, cardiac troponin T elevations are independently associated with in-hospital and short-term mortality but not long-term mortality.     

Prognostic Value of Elevated Levels of Intestinal Microbe-Generated Metabolite Trimethylamine-N-Oxide in Patients With Heart Failure : Refining the Gut Hypothesis

Background

Altered intestinal function is prevalent in patients with heart failure (HF), but its role in adverse outcomes is unclear.

Objectives

This study investigated the potential pathophysiological contributions of intestinal microbiota in HF.

Methods

We examined the relationship between fasting plasma trimethylamine-N-oxide (TMAO) and all-cause mortality over a 5-year follow-up in 720 patients with stable HF.

Results

The median TMAO level was 5.0 μM, which was higher than in subjects without HF (3.5 μM; p < 0.001). There was modest but significant correlation between TMAO concentrations and B-type natriuretic peptide (BNP) levels (r = 0.23; p < 0.001). Higher plasma TMAO levels were associated with a 3.4-fold increased mortality risk. Following adjustments for traditional risk factors and BNP levels, elevated TMAO levels remained predictive of 5-year mortality risk (hazard ratio [HR]: 2.2; 95% CI: 1.42 to 3.43; p < 0.001), as well as following the addition of estimated glomerular filtration rate to the model (HR: 1.75; 95% CI: 1.07 to 2.86; p < 0.001).

Conclusions

High TMAO levels were observed in patients with HF, and elevated TMAO levels portended higher long-term mortality risk independent of traditional risk factors and cardiorenal indexes.     

Association of borderline ankle-brachial index with mortality and the incidence of peripheral artery disease in diabetic patients

Objective

Peripheral artery disease (PAD) and diabetes mellitus are significant risk factors for all-cause death or cardiovascular death. PAD occurs more frequently in diabetic than in non-diabetic patients. However, the association of ankle-brachial index (ABI), especially borderline ABI, with clinical outcomes has not been fully elucidated in diabetic patients. This study aimed to investigate the association of ABI with mortality and the incidence of PAD in Japanese diabetic patients.

Methods

This observational study included 3981 diabetic patients (61.0 ± 11.8 years of age, 59.4% men), registered in the Kyushu Prevention Study for Atherosclerosis. Patients were divided into 3 groups according to the value of ABI at baseline: ABI ≤0.90 (abnormal ABI:354 patients), 0.91 ≤ ABI ≤ 0.99 (borderline ABI:333 patients), and 1.00 ≤ ABI ≤ 1.40 (normal ABI:3294 patients).

Results

Cumulative incidence of all-cause death was significantly higher in patients with abnormal and borderline ABI than in those with normal ABI (34.4% vs. 13.5%, P < 0.0001 and 26.1% vs. 13.5%, P < 0.0001, respectively). In multivariate analysis, the risks for all-cause death in patients with abnormal ABI (HR:2.16; 95%CI:1.46–3.14; P = 0.0002) and borderline ABI (HR:1.78; 95%CI:1.14–2.70; P = 0.01) were significantly higher than in those with normal ABI. The incidence of PAD was remarkably higher in patients with borderline ABI than in those with normal ABI (32.2% vs.9.6%, P < 0.0001). After adjustment, the risk for PAD was significantly higher in patients with borderline ABI than in those with normal ABI (HR:3.10; 95%CI:1.90–4.95; P < 0.0001).

Conclusions

Borderline ABI in diabetic patients was associated with significantly higher risks for mortality and PAD compared with normal ABI.     

Autologous Transplantation of Bone Marrow/Blood-Derived Cells for Chronic Ischemic Heart Disease: A Systematic Review and Meta-analysis

Background

Studies focused on cell therapy for chronic ischemic heart disease (CIHD) have been published with conflicting results. In this meta-analysis, we aimed to assess the effectiveness and safety of autologous bone marrow/blood-derived cell transplantation in patients with CIHD.

Methods

Randomized controlled trials (RCTs) were identified in PubMed, OVID, EMBASE, and Cochrane Library reviews and reference lists of relevant articles. Weighted mean difference was calculated for changes in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) using a random-effects model.

Results

Nineteen trials with a total of 886 patients were included. Compared with controls, patients who received transplantation of bone marrow/blood-derived cells had significantly improved LVEF (3.54%; 95% confidence interval [CI], 1.92%-5.17%; P < 0.001) and LVESV (−8.96 mL; 95% CI, −13.64 to −4.28 mL; P < 0.001). No significant improvement in LVEDV (−0.75 mL; 95% CI, −9.80-8.30 mL; P = 0.22) was detected. Subgroup analysis revealed that significant improvement in LVEDV was observed in patients with lower baseline LVEF. Moreover, there were trends in favor of a benefit for LV function and remodelling when intramyocardial cells were injected during coronary bypass surgery and the bone marrow mononuclear cell number was ≤1 × 10⁸. Furthermore, cell therapy was associated with a significant decrease in all-cause death (relative risk: 0.49; 95% CI, 0.29-0.84; P = 0.01).

Conclusions

Current evidence showed that cell therapy moderately improved left ventricle function and significantly decreased all-cause death in patients with CIHD and supports further RCTs with larger sample size and longer follow-up.     

Prognostic significance of mitral regurgitation in long-term all-cause mortality in patients aged ≥ 80 years with acute coronary syndrome

Background

Mitral regurgitation (MR) has been shown to be associated with a poor prognosis in the patients with acute myocardial infarction, whether or not percutaneous coronary intervention (PCI) is employed. However, the long-term prognostic significance of MR in octogenarian patients with acute coronary syndrome (ACS) remains unknown. We sought to determine the impact of MR on long-term all-cause mortality and to further reveal whether PCI could influence the prognosis in octogenarian MR patients with ACS.

Methods

In this study, we included a total of 353 consecutive hospitalized patients, aged ≥ 80 years, with ACS during the period of 5-year follow-up. Association between MR and long-term all-cause mortality was analyzed both in a overall cohort and in a matched cohort developed from a propensity score analysis.

Results

MR was independently associated with long-term all-cause mortality in the overall and matched cohorts (hazard ratio (HR) 1.58, 95% CI 1.01–2.47, P = 0.043; HR 1.90, 95% CI 1.15–3.13, P = 0.013). In the subgroup treated with PCI, MR also exhibited higher long-term all-cause mortality, PCI remained an independent determinant of improving long-term survival rate by reducing the mortality by 15.1% in ACS patients with MR aged ≥ 80 years.

Conclusions

Our study demonstrates that MR is independently associated with long-term all-cause mortality, and PCI is an independent determinant for improving the long-term survival rate in the octogenarian ACS patients with MR.     

Change in health-related quality of life in patients with coronary artery disease predicts 4-year mortality

Aims

Self-reported health-related quality of life (HRQL) and changes in HRQL have been shown to predict mortality and/or adverse events in patients with coronary artery disease. MacNew Heart Disease HRQL questionnaire scores were examined as predictors of 4-year all-cause mortality.

Methods

Following referral for angioplasty in 385 patients with coronary artery disease, data were analyzed for differences in all-cause mortality by MacNew Global and subscale baseline and 1- and 3-month change scores (deteriorated ≥ 0.50; unchanged (− 0.49 to + 0.49); and improved ≥ 0.50 points).

Results

Mean baseline, 1-month, and 3-month MacNew Global and subscale scores were similar in survivors and non-survivors. Mean 1- and 3-month Global and emotional subscale and mean 1-month social subscale change scores decreased more in non-survivors than survivors. Compared with patients whose Global MacNew HRQL scores improved at one month, 4-year all-cause mortality hazard ratio (HR) was higher in patients whose HRQL deteriorated (HR, 1.70, 95% CI, 1.09, 2.65; p = 0.021). Compared with patients whose Global MacNew HRQL improved at three months, 4-year all-cause mortality was higher in both patients whose HRQL had deteriorated (HR, 2.07, 95% CI, 1.29, 3.32; p = 0.003) and patients with unchanged HRQL (HR, 2.62, 95% CI, 1.11, 6.17; p = 0.028).

Conclusions

A deterioration of ≥ 0.50 points in MacNew HRQL Global scores at both one and three months is predictive of 4-year all-cause mortality. Serial HRQL information may be useful to identify patients at higher risk for adverse cardiac events and mortality and may have implications for determining follow-up frequency and treatment in individual patients.     

Providing Rapid Out of Hospital Acute Cardiovascular Treatment 3 (PROACT-3)

Background

The outcomes of acute cardiovascular symptom presentations are potentially modifiable with the use of biomarkers to accelerate accurate diagnosis. This randomized trial tested troponin and B-type natriuretic peptide before hospital guidance in patients with acute cardiovascular symptoms.

Methods

Patients with either chest pain or shortness of breath were randomized to usual care or biomarkers analyzed using a point-of-care device in the ambulance. The primary end point was time to final disposition (discharge from the emergency department or admission to hospital). The trial was stopped prematurely because of less than expected enrollment of patients of interest and no difference in the primary end point.

Results

We randomized 491 patients; 480 formed the final cohort. Patients were 49% male; median age 70 years; 42% had previous acute coronary syndrome; and 28% diabetes. The B-type natriuretic peptide level before hospital arrival was ≥ 100 pg/mL in 36.4%. Troponin was > 0.03 ng/mL in 13.4%; 3.6% had troponin > 0.1 ng/mL. After adjudication, 16% had acute coronary syndrome, 6.5% acute heart failure, 3.3% angina, and 74.2% another diagnosis. The primary end point was 9.2 (interquartile range, 7.3-11.1) hours in the biomarker group and 8.8 (interquartile range, 6.3-12.1) hours in the usual care group (P = 0.6). None died in the ambulance or in the emergency department: all-cause 30-day mortality was 2.1% (usual care) and 1.7% (biomarker).

Conclusions

To our knowledge, this is the first randomized trial of biomarkers before hospital arrival to guide emergency management of suspected acute cardiovascular disease which showed no benefit and was terminated early because of futility. The results have important implications for the use of biomarkers in emergency management of heart disease and for the design of future randomized trials on this important topic.     

Low exercise blood pressure and risk of cardiovascular events and all-cause mortality: Systematic review and meta-analysis

Objective

The independent prognostic significance of abnormally low systolic blood pressure (SBP) during exercise stress testing (LowExBP) across different clinical and exercise conditions is unknown. We sought by systematic review and meta-analysis to determine the association between cardiovascular/all-cause outcomes and LowExBP across different patient clinical presentations, exercise modes, exercise intensities and categories of LowExBP.

Methods

Seven online databases were searched for longitudinal studies reporting the association of LowExBP with risk of fatal and non-fatal cardiovascular events and/or all-cause mortality. LowExBP was defined as either: SBP drop below baseline; failure to increase >10 mmHg from baseline or; lowest SBP quantile among reporting studies.

Results

After review of 13,257 studies, 19 that adjusted for resting SBP were included in the meta-analysis, with a total of 45,895 participants (average follow-up, 4.4 ± 3.0 years). For the whole population, LowExBP was associated with increased risk for fatal and non-fatal cardiovascular events and all-cause mortality (hazard ratio [HR]: 2.01, 95% confidence interval [CI]: 1.59–2.53, p < 0.001). In continuous analyses, a 10 mmHg decrease in exercise SBP was associated with higher risk (n = 9 HR: 1.13, 95% CI: 1.06–1.20, p < 0.001). LowExBP was associated with increased risk regardless of clinical presentation (coronary artery disease, heart failure, hypertrophic cardiomyopathy or peripheral artery disease), exercise mode (treadmill or bike), exercise intensity (moderate or maximal), or LowExBP category (all p < 0.05). However, bias toward positive results was apparent (Eggers test p < 0.001 and p = 0.009).

Conclusion

Our data show that irrespective of clinical or exercise conditions, LowExBP independently predicts fatal and non-fatal cardiovascular events and all-cause mortality.     

Leisure-Time Running Reduces All-Cause and Cardiovascular Mortality Risk

Background

Although running is a popular leisure-time physical activity, little is known about the long-term effects of running on mortality. The dose-response relations between running, as well as the change in running behaviors over time, and mortality remain uncertain.

Objectives

We examined the associations of running with all-cause and cardiovascular mortality risks in 55,137 adults, 18 to 100 years of age (mean age 44 years).

Methods

Running was assessed on a medical history questionnaire by leisure-time activity.

Results

During a mean follow-up of 15 years, 3,413 all-cause and 1,217 cardiovascular deaths occurred. Approximately 24% of adults participated in running in this population. Compared with nonrunners, runners had 30% and 45% lower adjusted risks of all-cause and cardiovascular mortality, respectively, with a 3-year life expectancy benefit. In dose-response analyses, the mortality benefits in runners were similar across quintiles of running time, distance, frequency, amount, and speed, compared with nonrunners. Weekly running even <51 min, <6 miles, 1 to 2 times, <506 metabolic equivalent-minutes, or <6 miles/h was sufficient to reduce risk of mortality, compared with not running. In the analyses of change in running behaviors and mortality, persistent runners had the most significant benefits, with 29% and 50% lower risks of all-cause and cardiovascular mortality, respectively, compared with never-runners.

Conclusions

Running, even 5 to 10 min/day and at slow speeds <6 miles/h, is associated with markedly reduced risks of death from all causes and cardiovascular disease. This study may motivate healthy but sedentary individuals to begin and continue running for substantial and attainable mortality benefits.     

Impact of Estimated Glomerular Filtration Rate on Vascular Disease Extent and Adverse Cardiovascular Events in Patients Without Chronic Kidney Disease

Background

Estimated glomerular filtration rate (eGFR) predicts major adverse cardiovascular events (MACE) in patients with chronic kidney disease (CKD), though the effect of eGFR on MACE and vascular disease extent among individuals with normal or mildly impaired renal function requires definition. Our aim was to examine the prognostic implications of eGFR and its effect on atherosclerosis burden in individuals without CKD undergoing vascular imaging studies.

Methods

The study enrolled 2746 consecutive patients undergoing clinically-driven coronary angiography who had an eGFR > 60 mL/min/1.73 m² and no history of CKD. Same-day carotid duplex results were available for 317 patients. Patients were followed for up to 3 years for the occurrence of all-cause mortality, myocardial infarction, and stroke.

Results

After adjustment for potential clinical and biochemical confounders, eGFR was found to be independently associated with coronary artery disease extent in the entire study population and among patients with normal renal function (n = 1170; eGFR > 90 mL/min/1.73 m²): odds ratio (OR) = 1.16 (95% confidence interval [CI], 1.09-1.24) and OR = 1.25 (95% CI, 1.11-1.4) per 10 mL/min decrements in eGFR, respectively. Similarly, eGFR was independently associated with carotid artery stenosis in the entire cohort (OR, 1.86 [95% CI, 1.12-3.1]). By Cox regression analysis, eGFR was an independent predictor of the composite MACE end point (hazard ratio, 1.16 [95% CI, 1.04-1.28]), and all-cause mortality (hazard ratio, 1.38 [95% CI, 1.19-1.60]).

Conclusions

eGFR is an independent predictor of atherosclerotic vascular disease extent and MACE rates in patients with normal or mildly impaired renal function.     

The Effect of Intravenous Vitamin C Infusion on Periprocedural Myocardial Injury for Patients Undergoing Elective Percutaneous Coronary Intervention

Background

This small study has determined the effect of vitamin C on myocardial reperfusion in patients undergoing elective percutaneous coronary intervention (PCI). This study was to explore whether antioxidant vitamin C infusion before the procedure is able to affect the incidence of periprocedural myocardial injury (PMI) in patients undergoing PCI.

Methods

In this prospective single-centre randomized study, 532 patients were randomized into 2 groups: the vitamin C group, which received a 3-g vitamin C infusion within 6 hours before PCI, and a control group, which received normal saline. The primary end point was the troponin I–defined PMI, and the second end point was the creatine kinase (CK)-MB–defined PMI. Separate analyses using both end points were performed. PMI was defined as an elevation of cardiac biomarker values (CK-MB or troponin I) > 5 times the upper limit of normal (ULN), alone or associated with chest pain or ST-segment or T-wave changes.

Results

After PCI, the incidence of PMI was reduced, whether defined by troponin or by CK-MB, compared with the control group (troponin I, 10.9% vs 18.4%; P = 0.016; CK-MB, 4.2% vs 8.6%; P = 0.035). Logistic multivariate analysis showed that preprocedure use of vitamin C is an independent predictor of PMI either defined by troponin I (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.33-0.97; P = 0.037) or by CK-MB (OR, 0.37; 95% CI, 0.14-0.99; P = 0.048).

Conclusions

In patients undergoing elective PCI, preprocedure intravenous treatment with vitamin C is associated with less myocardial injury.     

Clinical usefulness and prognostic value of elevated cardiac troponin I levels in acute pulmonary embolism

Background

Right ventricular myocardial ischemia and injury contribute to right ventricular dysfunction and failure during acute pulmonary embolism. The objective of this study was to evaluate the clinical usefulness of cardiac troponin I (cTnI) in the assessment of right ventricular involvement and short-term prognosis in acute pulmonary embolism

Methods

Thirty-eight patients with acute pulmonary embolism were included in the study. Clinical characteristics, right ventricular involvement, and clinical outcome were compared in patients with elevated levels of serum cTnI versus patients with normal levels of serum cTnI.

Results

Among the study population (n = 38 patients), 18 patients (47%) had elevated cTnI levels (mean ± SD 1.6 ± 0.7 ng/mL, range 0.7-3.7 ng/mL, median, 1.4 ng/mL), and comprised the cTnI-positive group. In the other 20 patients, the serum cTnI levels were normal (≤0.4 ng/mL), and they comprised the cTnI-negative group. In the cTnI-positive group (n = 18 patients), 12 patients (67%) had right ventricular dilatation/hypokinesia, compared with 3 patients (15%) in the cTnI-negative group (n = 20 patients, P = .004). Right ventricular systolic pressure was significantly higher in the cTnI-positive group (51 ± 8 mm Hg vs 40 ± 9 mm Hg, P = .002). Cardiogenic shock developed in a significantly higher number of patients with elevated serum cTnI levels (33% vs 5%, P = .01). In patients with elevated cTnI levels, the odds ratio for development of cardiogenic shock was 8.8 (95% CI 2.5-21).

Conclusions

Patients with acute pulmonary embolism with elevated serum cTnI levels are at a higher risk for the development of right ventricular dysfunction and cardiogenic shock. Serum cTnI has a role in risk stratification and short-term prognostication in patients with acute pulmonary embolism.     

Prognostic Significance of LGE by CMR in Aortic Stenosis Patients Undergoing Valve Replacement

Background

Prior studies have shown that late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) can detect focal fibrosis in aortic stenosis (AS), suggesting that it might predict higher mortality risk.

Objectives

This study was conducted to evaluate whether LGE-CMR can predict post-operative survival in patients with severe AS undergoing aortic valve replacement (AVR).

Methods

We prospectively evaluated survival (all-cause and cardiovascular disease related) according to LGE-CMR status in 154 consecutive AS patients (96 men; mean age: 74 ± 6 years) without a history of myocardial infarction undergoing surgical AVR and in 40 AS patients undergoing transcatheter aortic valve replacement (TAVR).

Results

LGE was present in 29% of patients undergoing surgical AVR and in 50% undergoing TAVR. During a median follow-up of 2.9 years, 21 patients undergoing surgical AVR and 20 undergoing TAVR died. In surgical AVR, the presence of LGE predicted higher post-operative mortality (odds ratio: 10.9; 95% confidence interval [CI]: 1.2 to 100.0; p = 0.02) and worse all-cause survival (73% vs. 88%; p = 0.02 by log-rank test) and cardiovascular disease related survival (85% vs. 95%; p = 0.03 by log-rank test) on 5-year Kaplan-Meier estimates of survival after surgical AVR. Multivariate Cox analysis identified the presence of LGE (hazard ratio: 2.8; 95% CI: 1.3 to 6.9; p = 0.025) and New York Heart Association functional class III/IV (hazard ratio: 3.2; 95% CI: 1.1 to 8.1; p < 0.01) as the sole independent predictors of all-cause mortality after surgical AVR. The presence of LGE also predicted higher all-cause mortality (p = 0.05) and cardiovascular disease related mortality (p = 0.03) in the subgroup of patients without angiographic coronary artery disease (n = 110) and higher cardiovascular disease related mortality in 25 patients undergoing transfemoral TAVR.

Conclusions

The presence of LGE indicating focal fibrosis or unrecognized infarct by CMR is an independent predictor of mortality in patients with AS undergoing AVR and could provide additional information in the pre-operative evaluation of risk in these patients.     

Desphospho-uncarboxylated matrix Gla-protein is associated with mortality risk in patients with chronic stable vascular disease

Background

Vitamin K is the essential co-factor for activation of matrix Gla-protein (MGP), the natural inhibitor of tissue calcification. Biologically inactive, desphospho-uncarboxylated MGP (dp-ucMGP) is a marker of vascular vitamin K status and is described to predict mortality in patients with heart failure and aortic stenosis. We hypothesized that increased dp-ucMGP might be associated with mortality risk in clinically stable patients with chronic vascular disease.

Materials and methods

We examined 799 patients (mean age 65.1 ± 9.3 years) who suffered from myocardial infarction, coronary revascularization or first ischemic stroke (pooled Czech samples of EUROASPIRE III and EUROASPIRE-stroke surveys), and followed them in a prospective cohort study. To estimate the 5-year all-cause and cardiovascular mortality we ascertained vital status and declared cause of death. Circulating dp-ucMGP and desphospho–carboxylated MGP (dp-cMGP) were measured by ELISA methods (IDS and VitaK).

Results

During a median follow-up of 2050 days (5.6 years) 159 patients died. In the fully adjusted multivariate Cox proportional hazard model, the patients in the highest quartile of dp-ucMGP (≥977 pmol/L) had higher risk of all-cause and cardiovascular 5-year mortality [HRR 1.89 (95% CI, 1.32–2.72) and 1.88 (95% CI, 1.22–2.90)], respectively. Corresponding HRR for dp-cMGP were 1.76 (95% CI, 1.18–2.61) and 1.79 (95% CI, 1.12–2.57).

Conclusions

In patients with overt vascular disease, circulating dp-ucMGP and dp-cMGP were independently associated with the risk of all-cause and cardiovascular mortality. Since published results are conflicting regarding the dp-cMGP, we propose only circulating dp-ucMGP as a potential biomarker for assessment of additive cardiovascular risk.     

Haemostatic factors,lipoproteins and long-term mortality in a multi-ethnic population of Gujarati,African-Caribbean and European origin

Objectives

To examine the relations between haemostatic factors and lipoproteins with mortality in British Europeans, African-Caribbeans (AfC) and Gujarati Indians.

Methods

A prospective cohort study of 331 subjects (40–79 years), followed-up over 26 years for mortality. Apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B), factor VII coagulant activity (FVIIc), fibrinogen and von Willebrand Factor (vWF) were measured at baseline in 118 Europeans, 100 AfC and 113 Gujaratis. Aortic pulse wave velocity (aPWV) was measured in 174 participants.

Results

147 (44.4%) subjects died during a median of 24 years follow-up with 69 cardiovascular deaths. Women at baseline had higher, and AfC males the lowest FVIIc and Apo-A1 levels. Baseline age-sex and ethnicity adjusted FVIIc levels were higher in those who died (131.0 vs. 117.4%; P = 0.048). In similarly adjusted partial correlations, Apo-A1 was inversely related to arterial stiffness (ρ = −0.23, P = 0.04).Over the 26 years follow-up, participants below the median (i.e. with lower concentration) of FVIIc, Fibrinogen, Apo-B and vWF had better survival rates than those with higher concentrations; those with higher concentrations of Apo-A1 had better survival. In Cox multivariable regression analyses including sex, ethnicity and aPWV, independently increased risk of all-cause mortality came only from SBP (per 5 mmHg); P = 0.011), age (per year); P < 0.0001 and FVIIc at 7% (per 10-unit; HR 1.07 (1.02, 1.12); P = 0.008. Separately, Apo-A1 (HR 0.12 (0.02, 0.75; P = 0.029) was independently associated with a very significant 88% reduction in all-cause mortality.

Conclusions

Despite a relatively small sample size, long-term follow-up suggests an independent effect of the prothrombotic state (via FVIIc) and apo-A1 (a constituent of HDL) on mortality.     

Low plasma DHEA-S increases mortality risk among male hemodialysis patients

Objective

The incidence of chronic kidney disease (CKD) is on the rise. CKD patients are at high risk of cardiovascular (CVD) and all-cause mortality. CKD patients have several endocrine disorders, including low levels of dehydroepiandrosterone sulfate (DHEA-S). In the general population, low levels of DHEA-S are associated with high CVD and all-cause mortality. The aim of this study was to analyze the prognostic value of plasma DHEA-S on the survival of CKD patients on hemodialysis.

Method

This was a single-center prospective cohort study on two hundred CKD patients on hemodialysis, which assessed the prognostic value of plasma DHEA-S on their survival.

Result

We found that plasma DHEA-S levels were negatively associated with age, and positively associated with dialysis duration and plasma creatinine, albumin, and phosphate levels in hemodialysis men. Elderly patients with co-morbidities (i.e. diabetes mellitus, congestive heart failure, and chronic obstructive pulmonary disease), poorer fluid control which was evaluated by higher cardiothoracic ratio, and low plasma creatinine and albumin levels seemed to have poor prognosis in hemodialysis men. Furthermore, low plasma DHEA-S levels were significantly associated with CVD-related [hazard ratio (HR) = 3.877; P = 0.021], non-CVD-related (HR = 3.522; P = 0.016), and all-cause mortality (HR = 3.667; P = 0.001) in hemodialysis men. But low plasma DHEA-S levels were not significantly associated with CVD-related, non-CVD-related, and all-cause mortality in hemodialysis women. Multivariate Cox regression analysis suggested that low plasma DHEA-S levels are significantly and independently associated with all-cause mortality in hemodialysis men (HR = 2.933; P = 0.033).

Conclusion

The study suggested that low plasma DHEA-S was independently and significantly associated with all-cause mortality in CKD hemodialysis men.     

Contrast Volume Use in Manual vs Automated Contrast Injection Systems for Diagnostic Coronary Angiography and Percutaneous Coronary Interventions

Background

Contrast-induced nephropathy (CIN) is an important cause of iatrogenic morbidity and mortality. The amount of contrast delivered has a major effect on CIN and is operator-dependent. A few studies suggested that the use of automated contrast injection systems is associated with reduced contrast volume. It is unknown whether this is true when smaller amounts of contrast are used and how this is affected by training.

Methods

Volume of contrast media was measured in 1358 consecutive patients undergoing diagnostic catheterization and percutaneous coronary intervention (PCI) from January 31 to May 31, 2011. Patients were allocated to manual stopcock-manifold contrast injection (1052 patients) or automated contrast injection (306 patients).

Results

No significant difference in contrast volume use was found between manual and automated contrast injection systems, respectively: diagnostic catheterization, 72 ± 40 mL vs 96 ± 63 mL (P = 0.08); diagnostic catheterization with left ventricular angiography, 98 ± 40 mL vs 95 ± 35 mL (P = 0.51); PCI, 206 ± 82 mL vs 205 ± 90 mL (P = 0.84); diagnostic catheterization and PCI, 264 ± 83 mL vs 253 ± 93 mL (P = 0.51). No significant difference in CIN incidence, according to contrast injection systems, was found among patients receiving PCI (manual 9.8% vs automated 7.4%, P = 0.43). Using smaller sized catheters during diagnostic procedures was associated with injection of smaller amounts of contrast (P < 0.0001).

Conclusions

The use of automated contrast injection for diagnostic catheterization and PCI is not associated with reduced contrast volume as compared with manual injection. The use of smaller calibre catheters might reduce contrast volume.     

Lower Blood Vitamin D Levels Are Associated With an Increased Incidence of Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography

Background

Vitamin D deficiency may be associated with an increased risk of renovascular disease. We assessed the correlation between vitamin D levels and contrast-induced nephropathy (CIN) in patients undergoing coronary angiography (CAG).

Methods

Vitamin D and parathyroid hormone (PTH) levels were assessed before CAG in 403 patients. Estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation. Patients with eGFR < 60 mL/min/1.73 m² were hydrated with 0.9%-saline at 1 mL/kg/h for 12 hours before and after CAG. CIN was defined as serum creatinine increase of > 0.5 mg/dL or > 25% within 48-72 hours after CAG.

Results

CIN developed in 74 participants. Baseline eGFR, blood urea and creatinine in CIN (+) and (−) groups were not significantly different (P = 0.14, P = 0.07, and P = 0.61, respectively). Total volume of contrast medium (CM) was higher in the CIN (+) group (132 ± 64 mL vs 90 ± 41 mL; P = 0.01). Vitamin D levels were lower (median 8.5 [range, 0.5-26.6] ng/mL vs 14.9 [range, 1.9-93.5] ng/mL; P = 0.01) and PTH levels were higher (median 73.9 [range, 22-530] pg/mL vs 44.2 [range, 5-361] pg/mL; P = 0.01) in the CIN (+) group. Multivariate logistic regression analysis revealed that lower vitamin D levels (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.11-1.26; P = 0.01) and increased CM volume (OR, 1.01; 95% CI, 1.008-1.017; P = 0.01) were independently correlated with CIN. In patients who had undergone percutaneous coronary intervention, lower levels of vitamin D were independently associated with CIN development.

Conclusions

Lower vitamin D levels, implying possible vitamin D deficiency, are associated with a higher incidence of CIN.     

Higher Neutrophil/Lymphocyte Ratio Is Related to Lower Ejection Fraction and Higher Long-term All-Cause Mortality in ST-Elevation Myocardial Infarction Patients

Background

Neutrophil/lymphocyte ratio (NLR) is a novel biomarker that can single out individuals at risk for vascular events. We assessed whether NLR provides additive prognostic value in patients with ST-elevation myocardial infarction (STEMI).

Methods

NLR was computed from the absolute values of neutrophils and lymphocytes from the complete blood count of patients who underwent primary coronary angioplasty for STEMI. The cohort was divided into 2 groups according to NLR (NLR ≥ 6.5%, NLR < 6.5%) using χ² automatic interaction detection. The association between NLR and in-hospital clinical complications and left ventricular ejection fraction (EF) was assessed using logistic regression. The association between NLR, 30-day and 5-year all-cause mortality were analyzed using Cox regression models, adjusting for potential clinical, metabolic, and inflammatory confounders.

Results

In a group of 538 consecutive STEMI patients, high NLR (NLR ≥ 6.5%) was independently associated with increased 30-day and 5-years mortality rates (odds ratio, 15.8; 95% confidence interval, 1.6-154; P = 0.018; and hazard ratio, 2.2; 95% confidence interval, 1.04-4.8; P = 0.039, respectively). High NLR was also independently associated with lower EF (49 ± 8 vs 46 ± 8; P < 0.001) and fewer hospital complications.

Conclusions

In patients presenting with STEMI, high NLR was independently associated with lower EF, fewer hospital complications, and higher mortality rates up to 5 years. NLR value appears additive to conventional risk factors and commonly used biomarkers.     

Fibroblast growth factor 23 (FGF23) and mortality: The Ludwigshafen Risk and Cardiovascular Health Study

Background

Fibroblast growth factor 23 (FGF23) is an important regulatory hormone in phosphate and vitamin D metabolism. Here, we investigated the associations of FGF23 with traditional cardiovascular risk factors and with bone metabolism parameters as well as the impact of FGF23 upon long-term mortality in a large cohort of patients referred for coronary angiography.

Methods

We examined whether c-term FGF23 concentrations at baseline were associated with cardiovascular and total mortality in 2974 patients from the Ludwigshafen Risk and Cardiovascular Health Study (LURIC). We investigated if these associations were independent from established cardiovascular risk factors as well as from other mineral regulating factors and bone biomarkers such as calcium, parathyroid hormone (PTH), alkaline phosphatase (AP), vitamin D, and serum phosphate.

Results

Mean age of participants was 63 ± 10 years; median c-term FGF23 serum levels were 54 (40–78) RU/ml. During a median follow-up of 9.9 years, 884 deaths (30%) occurred, 545 (18%) of which were cardiovascular. FGF23 significantly and inversely correlated with eGFR. AP, phosphate, and PTH increased in parallel with quartiles of FGF23. Age- and sex-adjusted hazard ratios (HRs) in the fourth quartile compared to the first quartile of FGF23 were 2.54 (95%CI, 2.09–3.09; p < 0.001) for all cause and 2.56 (95% CI, 1.99–3.28; p < 0.001) for cardiovascular mortality. These associations remained significant after additional adjustments for cardiovascular risk factors and bone biomarkers (calcium, PTH, AP, vitamin D, and phosphate): Adjusted HRs were 1.38 (95%CI, 1.26–1.52; p < 0.001) for all-cause and 1.35 (95%CI, 1.20–1.52; p < 0.001) for cardiovascular mortality for each increase by one standard deviation of c-term FGF23.

Conclusions

In patients undergoing coronary angiography baseline c-term FGF23 levels predict the risk for all-cause and cardiovascular mortality over 9.9 years of follow-up. These associations were independent of established cardiovascular risk factors and serum phosphate.