Cumulative Incidence Of Cardiovascular Death Research Articles

Perioperative Medicine

Perioperative Medicine

A Sensitive Cardiac Troponin T Assay in Stable Coronary Artery Disease

In most patients with stable coronary artery disease, plasma cardiac troponin T levels are below the limit of detection for the conventional assay. The distribution and determinants of very low circulating troponin T levels, as well as their association with cardiovascular events, in such patients are unknown. We used a new, high-sensitivity assay to determine the concentration of cardiac troponin T in plasma samples from 3679 patients with stable coronary artery disease and preserved left ventricular function. Results of the assay were analyzed in relation to the incidence of cardiovascular events during a median follow-up period of 5.2 years. With the highly sensitive assay, concentrations of cardiac troponin T were at or above the limit of detection (0.001 microg per liter) in 3593 patients (97.7%) and at or above the 99th percentile for apparently healthy subjects (0.0133 microg per liter) in 407 patients (11.1%). After adjustment for other independent prognostic indicators, there was a strong and graded increase in the cumulative incidence of cardiovascular death (adjusted hazard ratio per unit increase in the natural logarithm of the troponin T level, 2.09; 95% confidence interval [CI], 1.60 to 2.74; P<0.001) and of heart failure (adjusted hazard ratio, 2.20; 95% CI, 1.66 to 2.90; P<0.001) in this study group. Increased risk associated with higher levels of troponin T was evident well below the limit of detection of conventional cardiac troponin T assays and below the 99th percentile of values in a healthy population. There was no association between troponin T levels as measured with the highly sensitive assay and the incidence of myocardial infarction (adjusted hazard ratio, 1.16; 95% CI, 0.97 to 1.40; P=0.11). After adjustment for other independent prognostic indicators, cardiac troponin T concentrations as measured with a highly sensitive assay were significantly associated with the incidence of cardiovascular death and heart failure but not with myocardial infarction in patients with stable coronary artery disease.

Endogenous Secretory Receptor for Advanced Glycation End-Products and Cardiovascular Disease in End-Stage Renal Disease

The receptor for advanced glycation end-products (RAGE) is involved in microvascular and macrovascular complications in diabetes. The expression of RAGE is up-regulated in atherosclerotic plaques of diabetic animals, and the augmentation of atherosclerosis in diabetic mice is inhibited by the competition of RAGE. An endogenous secretory RAGE (esRAGE) was identified as a novel splice variant carrying all of the extracellular domains, but devoid of the transmembrane and intracytoplasmic domains. The esRAGE is released from the cells, to bind advanced glycation end-products, and this is capable of neutralizing the actions of advanced glycation end-products on endothelial cells in culture. The adenoviral overexpression of esRAGE restores the impairment of vascular dysfunction in diabetes, suggesting that esRAGE may be an important inhibitor of RAGE signaling in vivo, and may be useful for the prevention of diabetic vascular complications. In 203 age-matched and sex-matched type 2 diabetic and 134 nondiabetic subjects, plasma esRAGE levels were inversely associated with carotid or femoral atherosclerosis. In patients with end-stage renal disease (ESRD), plasma esRAGE levels are higher than in those without ESRD. In a cohort of 206 patients (including 171 nondiabetic patients) with chronic renal failure who were followed for a median of 111 months, the cumulative incidence of cardiovascular death by Kaplan-Meier estimation was significantly higher in subjects in the lowest tertile of plasma esRAGE than in those in the middle or highest tertile. Compared with the lowest tertile of plasma esRAGE, the hazards ratios for the highest and middle tertile were 0.40 (95% confidence interval, 0.18 to 0.89) and 0.26 (95% confidence interval, 0.10 to 0.66), respectively. The higher risk at the lower level of esRAGE was still significant even after adjustment for body mass index, hypertension, dyslipidemia, and vascular complications, and was confounded only by age and diabetes. Thus, we postulate that plasma esRAGE is a potential protective factor and a novel biomarker against the occurrence of cardiovascular disease in ESRD.

Androgen Deprivation Therapy for Localized Prostate Cancer and the Risk of Cardiovascular Mortality

We investigated whether androgen deprivation therapy (ADT) use is associated with an increased risk of death from cardiovascular causes in patients treated for localized prostate cancer. From the Cancer of the Prostate Strategic Urologic Research Endeavor database, data on 3262 patients treated with radical prostatectomy and 1630 patients treated with external beam radiation therapy, brachytherapy, or cryotherapy for localized prostate cancer were included in this analysis. Competing risks regression analyses were performed to assess whether use of ADT was associated with a shorter time to death from cardiovascular causes after controlling for age (as a continuous variable) and the presence of baseline cardiovascular disease risk factors. All tests for statistical significance were two-sided. The median follow-up time was 3.8 years (range = 0.1-11.3 years). Among the 1015 patients who received ADT, the median duration of ADT use was 4.1 months (range = 1.0-32.9 months). In a competing risks regression analysis that controlled for age and risk factors for cardiovascular disease, both ADT use (adjusted hazard ratio [HR] = 2.6; 95% confidence interval [CI] = 1.4 to 4.7; P = .002) and age (adjusted HR = 1.07; 95% CI = 1.02 to 1.1; P = .003) were associated with statistically significantly increased risks of death from cardiovascular causes in patients treated with radical prostatectomy. Among patients 65 years or older treated with radical prostatectomy, the 5-year cumulative incidence of cardiovascular death was 5.5% (95% CI = 1.2% to 9.8%) in those who received ADT and 2.0% (95% CI = 1.1% to 3.0%) in those who did not. Among patients 65 years or older treated with external beam radiation therapy, brachytherapy, or cryotherapy, ADT use was associated with a higher cumulative incidence of death from cardiovascular causes, but the difference did not reach statistical significance. The use of ADT appears to be associated with an increased risk of death from cardiovascular causes in patients undergoing radical prostatectomy for localized prostate cancer.

Relationship between QRS duration and prognosis in non-ST-segment elevation acute coronary syndrome

Background Previous studies have shown that prolonged QRS duration increases the risk of death in patients with heart failure and after an ST-segment elevation acute myocardial infarction. Very little data exist about the prognostic implications of QRS duration in the non-ST-segment elevation acute coronary syndrome (NST-ACS): unstable angina and non-ST elevation acute myocardial infarction (non-STEMI). Methods This is a prospective and observational study in which we included 502 patients (age 71 ± 10 years, 68% males, 29% diabetes) consecutively admitted for NST-ACS. QRS duration was manually measured from the 12-lead electrocardiogram. Our aim is to assess the relation between the QRS duration on admission (QRSd) and the risk of cardiovascular death (CvD) in the long-term. Results Mean QRSd was: 93 ± 19 ms. After a median follow-up of 450 days, the cumulative incidence of CvD was: 17.8%. QRSd correlated with the incidence of CvD during the follow-up period: c = 0.72 ( p < 0.001). The best cut-off point was 90 ms (sensitivity, specificity and negative predictive value of QRSd ≥ 90 ms for CvD: 82, 68 and 93%). According to the Kaplan–Meier analysis, QRSd ≥ 90 ms was associated with an increase in the risk of CvD: 26.6% versus 7.2% (log rank: 28.6; p < 0.001). Cumulative incidence of CvD was higher in QRSd ≥ 90 ms in patients with unstable angina: 15.5% versus 4% ( p = 0.02), and in those with non-STEMI: 30.5% versus 8.9% ( p < 0.001). After adjusting for other significant variables (Cox-regression analysis), QRSd ≥ 90 ms persisted as an independent predictor for overall CvD (Hazard Ratio: 2.62; 95% Confidence Interval: 1.44–4.74; p < 0.001). Conclusion In NST-ACS, the QRSd, even in the normal range, has prognostic implications. QRSd ≥ 90 ms is independently associated with an increased risk of CvD in the long-term.

Endogenous Secretory RAGE as a Novel Biomarker for Metabolic Syndrome and Cardiovascular Diseases

Receptor for advanced glycation end-products (RAGE) is known to be involved in both micro- and macrovascular complications in diabetes. Among numerous truncated forms of RAGE recently described, the C-terminally truncated form of RAGE has received much attention. This form of RAGE, carrying all of the extracellular domains but devoid of the trans-membrane and intracytoplasmic domains, is released outside from cells, binds ligands including AGEs, and is capable of neutralizing RAGE signaling on endothelial cells in culture. This form of RAGE is generated as a splice variant and is named endogenous secretory RAGE (esRAGE). Adenoviral overexpression of esRAGE reverses diabetic impairment of vascular dysfunction, suggesting that esRAGE may be an important inhibitor of RAGE signaling in vivo and potentially be useful for prevention of diabetic vascular complications. An ELISA system to measure plasma esRAGE was recently developed, and the pathophysiological roles of esRAGE have begun to be unveiled clinically. Plasma esRAGE levels are decreased in patients with several metabolic diseases including type 1 and type 2 diabetes, metabolic syndrome and hypertension. In cross-sectional analysis, plasma esRAGE levels are inversely correlated with carotid or femoral atherosclerosis. In an observational cohort of patients with end-stage renal disease, cumulative incidence of cardiovascular death was significantly higher in subjects with lower plasma esRAGE levels. These findings suggest that plasma esRAGE may act as a protective factor against and a novel biomarker for the occurrence of metabolic syndrome and cardiovascular diseases.

Low Circulating Endogenous Secretory Receptor for AGEs Predicts Cardiovascular Mortality in Patients With End-Stage Renal Disease

Receptor for advanced glycation end-products (RAGE) is involved in diabetic vascular complications. We have recently shown that plasma endogenously secretory RAGE (esRAGE), an alternatively spliced form of RAGE, is closely associated with metabolic syndrome and atherosclerosis. Here, we evaluated if plasma esRAGE is a predictor of cardiovascular mortality in a cohort of 206 (171 nondiabetic) patients with end-stage renal diseases (ESRD). The cohort was followed for a median of 111 months, and 74 deaths including 34 cardiovascular deaths were recorded. Plasma esRAGE was measured at baseline. Cumulative incidence of cardiovascular death by Kaplan-Meier estimation was significantly higher in subjects in the lowest tertile of plasma esRAGE than those in the middle or the highest tertile both in all and nondiabetic subjects alone. In all subjects, as compared with the lowest tertile of plasma esRAGE, the hazards ratios for the highest and middle tertile were 0.40 (95% CI, 0.18 to 0.89) and 0.26 (0.10 to 0.66), respectively. The higher risk for lower esRAGE was still significant even after adjusted either with body mass index, hypertension, dyslipidemia and vascular complications, but was confounded by age and diabetes. Low circulating esRAGE is a predictor for cardiovascular mortality in ESRD patients.

Insulin resistance as an independent predictor of cardiovascular mortality in patients with end-stage renal disease.

Insulin resistance is closely associated with atherosclerosis and cardiovascular mortality in the general population. Patients with end-stage renal disease (ESRD) are known to have insulin resistance, advanced atherosclerosis, and a high cardiovascular mortality rate. We evaluated whether insulin resistance is a predictor of cardiovascular death in a cohort of ESRD. A prospective observational cohort study was performed in 183 nondiabetic patients with ESRD treated with maintenance hemodialysis. Insulin resistance was evaluated by the homeostasis model assessment method (HOMA-IR) using fasting glucose and insulin levels at baseline, and the cohort was followed for a mean period of 67 mo. Forty-nine deaths were recorded, including 22 cardiovascular deaths. Cumulative incidence of cardiovascular death by Kaplan-Meier estimation was significantly different between subjects in the top tertile of HOMA-IR (1.40 to 4.59) and those in the lower tertiles of HOMA-IR (0.28 to 1.39), and the hazard ratio (HR) was 2.60 (95% confidence interval [CI], 1.12 to 6.01; P = 0.026) in the univariate Cox proportional hazards model. In multivariate Cox models, the positive association between HOMA-IR and cardiovascular mortality remained significant (HR, 4.60; 95% CI, 1.83 to 11.55; P = 0.001) and independent of age, C-reactive protein, and presence of preexisting vascular complications. Further analyses showed that the effect of HOMA-IR on cardiovascular mortality was independent of body mass index, hypertension, and dyslipidemia. In contrast, HOMA-IR did not show such a significant association with noncardiovascular mortality. These results indicate that insulin resistance is an independent predictor of cardiovascular mortality in ESRD.