AIMS :To assess the prognostic value of anti-apolipoprotein A-1 (anti-apoA-1) IgG after myocardial infarction (MI) and its association with major cardiovascular events (MACEs) at 12 months and to determine their association with resting heart rate (RHR), a well-established prognostic feature after MI. Anti-apoA-1 IgG have been reported in MI without autoimmune disease, but their clinical significance remains undetermined.
METHODS AND RESULTS: A total of 221 consecutive patients with MI were prospectively included, and all completed a 12-month follow-up. Major cardiovascular events consisted in death, MI, stroke, or hospitalization either for an acute coronary syndrome or heart failure. Resting heart rate was obtained on Holter the day before discharge under the same medical treatment. Neonate rat ventricular cardiomyocytes (NRVC) were used in vitro to assess the direct anti-apoA-1 IgG effect on RHR. During follow-up, 13% of patients presented a MACE. Anti-apoA-1 IgG positivity was 9% and was associated with a higher RHR (P = 0.0005) and higher MACE rate (adjusted OR, 4.3; 95% CI, 1.46–12.6; P = 0.007). Survival models confirmed the significant nature of this association. Patients with MACE had higher median anti-apoA-1 IgG values at admission than patients without (P = 0.007). On NRVC, plasma from MI patients and monoclonal anti-apoA-1 IgG induced an aldosterone and dose-dependent positive chronotropic effect, abrogated by apoA-1 and therapeutic immunoglobulin (IVIG) pre-incubation.
CONCLUSIONS: In MI patients, anti-apoA-1 IgG is independently associated with MACE at 1-year, interfering with a currently unknown aldosterone-dependent RHR determinant. Knowing whether anti-apoA-1 IgG assessment could be of interest to identify an MI patient subset susceptible to benefit from apoA-1/IVIG therapy remains to be demonstrated.
Nicolas Vuilleumier1,*, Michel F. Rossier1,2, Sabrina Pagano1, Magaly Python2, Emmanuel Charbonney3, René Nkoulou4, Richard James2, Guido Reber5, François Mach4 and Pascale Roux-Lombard6
Sunday
Thursday
Evaluation of erectile dysfunction and associated cardiovascular risk using structured questionnaires in Chinese type 2 diabetic men
ABSTRACT
Erectile dysfunction (ED) is not uncommon, but frequently underdiagnosed in type 2 diabetic men. In this study, we aimed to explore the frequency and severity of ED in Chinese type 2 diabetic men using a structured questionnaire. We furthermore sought to investigate the associations of ED with diabetes-related complications and metabolic indices.
A consecutive cohort of 313 Chinese type 2 diabetic men aged between 25 and 76 years attending a diabetic centre were recruited between October 2006 and June 2007. Of the study population, the frequency of ED was 39.3% according to the National Institutes of Health (NIH) Consensus Conference criteria, compared with 84.3% (41.7% of them having moderate to severe ED) as diagnosed by International Index of Erectile Function (IIEF-5) questionnaire.
After adjusting for potential confounding factors by multivariable logistic regression, ED defined by NIH criterion was associated with advanced age [OR = 1.05 (95% CI 1.01–1.09), p = 0.012], the presence of diabetic retinopathy [OR = 2.43 (95% CI 1.27–4.66), p = 0.008] and coronary heart disease [OR = 2.63 (95% CI 1.21–5.70), p = 0.015]. ED defined by IIEF-5 was associated with advanced age [OR = 1.12 (95% CI 1.06–1.17), p < 0.0001], use of insulin therapy [OR = 2.94 (95% CI 1.12–7.73), p = 0.029] and urinary albumin-creatinine ratio [OR = 2.29 (95% CI 1.05–5.01), p = 0.037].
In conclusion, ED was highly prevalent in Chinese type 2 diabetic men and was associated with multiple cardiovascular risk factors and complications. Advanced age, use of insulin therapy, the existence of microvascular complications such as retinopathy, albuminuria and coronary heart disease were associated with ED. NIH criteria diagnosed a much lower rate of ED compared with IIEF-5. Overall, structured questionnaires are useful and objective tools to detect ED, which should prompt a comprehensive risk assessment in these subjects
L. W. Yu*, A. P. Kong*†, P. C. Tong*, C. Tam*, G. T. Ko*, C.-S. Ho‡, W.-Y. So*, R. C. Ma*, C.-C. Chow* and J. C. Chan*
*Department of Medicine and Therapeutics , †Li Ka Shing Institute of Health Science , and ‡Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
Erectile dysfunction (ED) is not uncommon, but frequently underdiagnosed in type 2 diabetic men. In this study, we aimed to explore the frequency and severity of ED in Chinese type 2 diabetic men using a structured questionnaire. We furthermore sought to investigate the associations of ED with diabetes-related complications and metabolic indices.
A consecutive cohort of 313 Chinese type 2 diabetic men aged between 25 and 76 years attending a diabetic centre were recruited between October 2006 and June 2007. Of the study population, the frequency of ED was 39.3% according to the National Institutes of Health (NIH) Consensus Conference criteria, compared with 84.3% (41.7% of them having moderate to severe ED) as diagnosed by International Index of Erectile Function (IIEF-5) questionnaire.
After adjusting for potential confounding factors by multivariable logistic regression, ED defined by NIH criterion was associated with advanced age [OR = 1.05 (95% CI 1.01–1.09), p = 0.012], the presence of diabetic retinopathy [OR = 2.43 (95% CI 1.27–4.66), p = 0.008] and coronary heart disease [OR = 2.63 (95% CI 1.21–5.70), p = 0.015]. ED defined by IIEF-5 was associated with advanced age [OR = 1.12 (95% CI 1.06–1.17), p < 0.0001], use of insulin therapy [OR = 2.94 (95% CI 1.12–7.73), p = 0.029] and urinary albumin-creatinine ratio [OR = 2.29 (95% CI 1.05–5.01), p = 0.037].
In conclusion, ED was highly prevalent in Chinese type 2 diabetic men and was associated with multiple cardiovascular risk factors and complications. Advanced age, use of insulin therapy, the existence of microvascular complications such as retinopathy, albuminuria and coronary heart disease were associated with ED. NIH criteria diagnosed a much lower rate of ED compared with IIEF-5. Overall, structured questionnaires are useful and objective tools to detect ED, which should prompt a comprehensive risk assessment in these subjects
L. W. Yu*, A. P. Kong*†, P. C. Tong*, C. Tam*, G. T. Ko*, C.-S. Ho‡, W.-Y. So*, R. C. Ma*, C.-C. Chow* and J. C. Chan*
*Department of Medicine and Therapeutics , †Li Ka Shing Institute of Health Science , and ‡Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
Tuesday
Myeloperoxidase: A Useful Biomarker for Cardiovascular Disease Risk Stratification?
Clinical Chemistry. 2009;55:1462-1470
Abstract
Background: Inflammation and oxidative stress are associated with atherosclerosis. Myeloperoxidase (MPO) is linked to both inflammation and oxidative stress by its location in leukocytes and its role in catalyzing the formation of oxidizing agents. Recent evidence suggests that MPO activity precipitates atherogenesis. Measurement of MPO in plasma may therefore contribute to cardiovascular disease (CVD) risk stratification.
Content: Cross-sectional studies, case-control studies, and prospective-cohort studies investigating the relation between MPO and CVD have been evaluated. Differences in study populations, sample materials, sample handling, and assays were ascertained. Potential causal mechanisms linking MPO to accelerated atherosclerosis are discussed here. A majority of studies indicate that measurement of MPO in plasma was associated with improved CVD risk stratification above and beyond risk stratification results obtained with markers used in routine clinical practice. However, comparison of these epidemiological studies with regard to MPO and outcome is hampered because the reported MPO concentration depends on the assay method, sampling material, and preanalytical and analytical procedures. The link between MPO and CVD can, at least partly, be explained by MPO-dependent oxidation of LDL and HDL, subsequently leading to cholesterol accumulation in the arterial wall. Furthermore, MPO may reduce the bioavailability of nitric oxide, resulting in endothelial dysfunction. Finally, MPO destabilizes atherosclerotic plaques.
Summary: Increasing evidence suggests that MPO is causally linked to atherosclerosis and its measurement may improve CVD risk estimation. Before MPO can be used in routine clinical practice, however, standardization of sampling and laboratory procedures is needed
Abstract
Background: Inflammation and oxidative stress are associated with atherosclerosis. Myeloperoxidase (MPO) is linked to both inflammation and oxidative stress by its location in leukocytes and its role in catalyzing the formation of oxidizing agents. Recent evidence suggests that MPO activity precipitates atherogenesis. Measurement of MPO in plasma may therefore contribute to cardiovascular disease (CVD) risk stratification.
Content: Cross-sectional studies, case-control studies, and prospective-cohort studies investigating the relation between MPO and CVD have been evaluated. Differences in study populations, sample materials, sample handling, and assays were ascertained. Potential causal mechanisms linking MPO to accelerated atherosclerosis are discussed here. A majority of studies indicate that measurement of MPO in plasma was associated with improved CVD risk stratification above and beyond risk stratification results obtained with markers used in routine clinical practice. However, comparison of these epidemiological studies with regard to MPO and outcome is hampered because the reported MPO concentration depends on the assay method, sampling material, and preanalytical and analytical procedures. The link between MPO and CVD can, at least partly, be explained by MPO-dependent oxidation of LDL and HDL, subsequently leading to cholesterol accumulation in the arterial wall. Furthermore, MPO may reduce the bioavailability of nitric oxide, resulting in endothelial dysfunction. Finally, MPO destabilizes atherosclerotic plaques.
Summary: Increasing evidence suggests that MPO is causally linked to atherosclerosis and its measurement may improve CVD risk estimation. Before MPO can be used in routine clinical practice, however, standardization of sampling and laboratory procedures is needed
Thursday
Calcium and Vitamin D Status in Heart Failure Patients in Isfahan, Iran
Both calcium and vitamin D play important roles in cardiac muscle contraction and performance. In this cross-sectional study, we evaluated the status of serum calcium, PTH and 25(OH)D(3) and their correlation with left ventricular Function and NYHA Functional class in 95 heart failure patients referred to Shahid Chamran Hospital, Isfahan, Iran, by colorimetric, immunoradiometric, and Immunochemiluminescent assays, echocardiography and interview respectively. The study was performed between Oct 2007 and Feb 2008. Twenty eight women and 67 men of functional classes 1, 2, or 3 participated in the study.
Mean (SD) of age of the participants was 62(11) years. Mean (SD) serum calcium and 25(OH)D(3) were 2.41(0.16) mmol/L and 56.78(51.33) nmol/L, respectively. The overall prevalence of low vitamin D status was 84.2%. There was no correlation between serum calcium and 25(OH)D(3) with LVEF. Interestingly, patients with hyperparathyroidism (serum PTH>65 ng/L) had lower LVEF (27% versus 32.5% p = 0.03). NYHA functional class was worse in patients with hyperparathyroidism (p = 0.08). Hypovitaminosis D is very prevalent in heart failure patients. Hyperparathyroidism in these patients may adversely affect cardiac function. Vitamin D3 might serve as an adjunctive treatment for heart failure patients.
Garakyaraghi M, Kerdegari M, Siavash M.
Isfahan University of Medical Sciences, Isfahan Cardiovascular Research Center, Isfahan, Iran
Mean (SD) of age of the participants was 62(11) years. Mean (SD) serum calcium and 25(OH)D(3) were 2.41(0.16) mmol/L and 56.78(51.33) nmol/L, respectively. The overall prevalence of low vitamin D status was 84.2%. There was no correlation between serum calcium and 25(OH)D(3) with LVEF. Interestingly, patients with hyperparathyroidism (serum PTH>65 ng/L) had lower LVEF (27% versus 32.5% p = 0.03). NYHA functional class was worse in patients with hyperparathyroidism (p = 0.08). Hypovitaminosis D is very prevalent in heart failure patients. Hyperparathyroidism in these patients may adversely affect cardiac function. Vitamin D3 might serve as an adjunctive treatment for heart failure patients.
Garakyaraghi M, Kerdegari M, Siavash M.
Isfahan University of Medical Sciences, Isfahan Cardiovascular Research Center, Isfahan, Iran
Monday
Neutrophil activation precedes myocardial injury in patients with acute myocardial infarction.
Department of Cardiology and Cardiovascular Research Center, University Heart Center, D-20246 Hamburg, Germany.
Myeloperoxidase (MPO), a heme protein abundantly expressed and secreted by polymorphonuclear neutrophils (PMN), has emerged as a critical mediator in coronary atherosclerosis. Retrospective analyses have suggested that free plasma levels of Myeloperoxidase predict adverse outcome in patients with low troponin T (TnT) levels who subsequently experience myocardial injury.
The aim of this study was to evaluate the time course of Myeloperoxidase plasma levels in the early stages of acute myocardial infarction (AMI). Of 155 consecutive patients hospitalized for acute coronary syndromes, 38 presenting within 2 h of the onset of symptoms and subsequently diagnosed for AMI were included in the study. Serial blood samples taken between 1 and 24 h after the onset of chest pain were analyzed for Myeloperoxidase, TnT, creatine kinase MB, myoglobin, and high sensitive C-reactive protein. Fifty patients with angiographically proven but stable coronary artery disease (CAD) served as controls.
In contrast to all other investigated markers, Myeloperoxidase was markedly elevated within 2 h of symptom onset in patients with AMI. Heparin, which is known to increase MPO plasma levels in patients with stable CAD, had no effect on MPO plasma levels in AMI patients. High levels of MPO plasma levels at the time of admission and the rapid peak of free plasma Myeloperoxidase levels after the onset of symptoms suggests that PMN activation is an early event in AMI and potentially precedes myocardial injury.
Myeloperoxidase (MPO), a heme protein abundantly expressed and secreted by polymorphonuclear neutrophils (PMN), has emerged as a critical mediator in coronary atherosclerosis. Retrospective analyses have suggested that free plasma levels of Myeloperoxidase predict adverse outcome in patients with low troponin T (TnT) levels who subsequently experience myocardial injury.
The aim of this study was to evaluate the time course of Myeloperoxidase plasma levels in the early stages of acute myocardial infarction (AMI). Of 155 consecutive patients hospitalized for acute coronary syndromes, 38 presenting within 2 h of the onset of symptoms and subsequently diagnosed for AMI were included in the study. Serial blood samples taken between 1 and 24 h after the onset of chest pain were analyzed for Myeloperoxidase, TnT, creatine kinase MB, myoglobin, and high sensitive C-reactive protein. Fifty patients with angiographically proven but stable coronary artery disease (CAD) served as controls.
In contrast to all other investigated markers, Myeloperoxidase was markedly elevated within 2 h of symptom onset in patients with AMI. Heparin, which is known to increase MPO plasma levels in patients with stable CAD, had no effect on MPO plasma levels in AMI patients. High levels of MPO plasma levels at the time of admission and the rapid peak of free plasma Myeloperoxidase levels after the onset of symptoms suggests that PMN activation is an early event in AMI and potentially precedes myocardial injury.
Tuesday
Prognostic Value of Troponin I Levels for Predicting Adverse Cardiovascular Outcomes in Postmenopausal Women Undergoing Cardiac Surgery
Abstract
BACKGROUND: Adverse cardiac events that follow cardiac surgery are an important source of perioperative morbidity and mortality for women. Troponin I provides a sensitive measure of cardiac injury, but the levels after cardiac surgery may vary between sexes. Our purpose in this study was to evaluate the prognostic value of troponin I levels for predicting cardiovascular complications in postmenopausal women undergoing cardiac surgery.
METHODS: The cohort of this study were women enrolled in a previously reported clinical trial evaluating the neuroprotective potential of 17β-estradiol in elderly women. In that study, 175 postmenopausal women not receiving estrogen replacement therapy and scheduled to undergo coronary artery bypass graft (with or without valve surgery) were prospectively randomized to receive 17β-estradiol or placebo in a double-blind manner beginning the day before surgery and continuing for 5 days postoperatively. Serial 12-lead electrocardiograms were performed and serum troponin I concentrations were measured before surgery, after surgery on arrival in the intensive care unit, and for the first four postoperative days. The primary end-point of the present study was major adverse cardiovascular events (MACE) defined as a Q-wave myocardial infarction, low cardiac output state or death within 30 days of surgery. The diagnosis of Q-wave myocardial infarction was made independently by two physicians blinded to treatment and patient outcomes with the final diagnosis requiring consensus. Low cardiac output state was defined as cardiac index <2.0 L · min–1 · m–2 for >8 h regardless of treatment.
RESULTS: Troponin I levels on postoperative day 1 were predictive of MACE (area under the receiver operator curve = 0.862). A cutoff point for troponin I of >7.6 ng/mL (95% confidence interval, 6.4–10.8) provided the optimal sensitivity and specificity for identifying patients at risk for MACE. The negative predictive value of a Troponin I level for identifying a patient with a composite cardiovascular outcome was high (96%) and the positive predictive value moderate (40%). Postoperative troponin I levels were not different between women receiving perioperative 17β-estradiol treatment compared with placebo and the frequency of MACE was not influenced by 17β-estradiol treatment.
CONCLUSIONS: In postmenopausal women, elevated troponin I levels on postoperative day 1 are predictive of MACE. Monitoring of perioperative troponin I levels might provide a means for stratifying patients at risk for adverse cardiovascular events.
BACKGROUND: Adverse cardiac events that follow cardiac surgery are an important source of perioperative morbidity and mortality for women. Troponin I provides a sensitive measure of cardiac injury, but the levels after cardiac surgery may vary between sexes. Our purpose in this study was to evaluate the prognostic value of troponin I levels for predicting cardiovascular complications in postmenopausal women undergoing cardiac surgery.
METHODS: The cohort of this study were women enrolled in a previously reported clinical trial evaluating the neuroprotective potential of 17β-estradiol in elderly women. In that study, 175 postmenopausal women not receiving estrogen replacement therapy and scheduled to undergo coronary artery bypass graft (with or without valve surgery) were prospectively randomized to receive 17β-estradiol or placebo in a double-blind manner beginning the day before surgery and continuing for 5 days postoperatively. Serial 12-lead electrocardiograms were performed and serum troponin I concentrations were measured before surgery, after surgery on arrival in the intensive care unit, and for the first four postoperative days. The primary end-point of the present study was major adverse cardiovascular events (MACE) defined as a Q-wave myocardial infarction, low cardiac output state or death within 30 days of surgery. The diagnosis of Q-wave myocardial infarction was made independently by two physicians blinded to treatment and patient outcomes with the final diagnosis requiring consensus. Low cardiac output state was defined as cardiac index <2.0 L · min–1 · m–2 for >8 h regardless of treatment.
RESULTS: Troponin I levels on postoperative day 1 were predictive of MACE (area under the receiver operator curve = 0.862). A cutoff point for troponin I of >7.6 ng/mL (95% confidence interval, 6.4–10.8) provided the optimal sensitivity and specificity for identifying patients at risk for MACE. The negative predictive value of a Troponin I level for identifying a patient with a composite cardiovascular outcome was high (96%) and the positive predictive value moderate (40%). Postoperative troponin I levels were not different between women receiving perioperative 17β-estradiol treatment compared with placebo and the frequency of MACE was not influenced by 17β-estradiol treatment.
CONCLUSIONS: In postmenopausal women, elevated troponin I levels on postoperative day 1 are predictive of MACE. Monitoring of perioperative troponin I levels might provide a means for stratifying patients at risk for adverse cardiovascular events.
Monday
Value of Cardiac Troponin I Cutoff Concentrations below the 99th Percentile for Clinical Decision-Making
Proteomics and Protein Markers
Value of Cardiac Troponin I Cutoff Concentrations below the 99th Percentile for Clinical Decision-Making
Background: The aim of this study was to evaluate factors influencing the 99th percentile for cardiac Troponin I (cTnI) when this cutoff value is established on a highly sensitive assay, and to compare the value of this cutoff to that of lower cutoffs in the prognostic assessment of patients with coronary artery disease.
Methods: We used the recently refined Access AccuTnI assay (Beckman-Coulter) to assess the distribution of cTnI results in a community population of elderly individuals [PIVUS (Prospective Study of the Vasculature in Uppsala Seniors) study; n = 1005]. The utility of predefined Troponin I cutoffs for risk stratification was then evaluated in 952 patients from the FRISC II (FRagmin and Fast Revascularization during InStability in Coronary artery disease) study at 6 months after these patients had suffered acute coronary syndrome .
Results: Selection of assay results from a subcohort of PIVUS participants without cardiovascular disease resulted in a decrease of the 99th percentile from 0.044 µg/L to 0.028 µg/L. Men had higher rates of cTnI elevation with respect to the tested thresholds. Whereas the 99th percentile cutoff was not found to be a useful prognostic indicator for 5-year mortality, both the 90th percentile (hazard ratio 3.1; 95% CI 1.9–5.1) and the 75th percentile (hazard ratio 2.8; 95% CI 1.7–4.7) provided useful prognostic information. Sex-specific cutoffs did not improve risk prediction.
Conclusions: The 99th percentile of cTnI depends highly on the characteristics of the reference population from which it is determined. This dependence on the reference population may affect the appropriateness of clinical conclusions based on this threshold. However, cTnI cutoffs below the 99th percentile seem to provide better prognostic discrimination in stabilized acute coronary syndrome patients and therefore may be preferable for risk stratification.
Kai M. Eggers1,a, Allan S. Jaffe4, Lars Lind2, Per Venge3 and Bertil Lindahl1
Departments of1 Medical Sciences, Cardiology,2 Medicine, and 3 Clinical Chemistry, Uppsala University Hospital, Sweden, and4 Mayo Medical School, Rochester, MN.
Value of Cardiac Troponin I Cutoff Concentrations below the 99th Percentile for Clinical Decision-Making
Background: The aim of this study was to evaluate factors influencing the 99th percentile for cardiac Troponin I (cTnI) when this cutoff value is established on a highly sensitive assay, and to compare the value of this cutoff to that of lower cutoffs in the prognostic assessment of patients with coronary artery disease.
Methods: We used the recently refined Access AccuTnI assay (Beckman-Coulter) to assess the distribution of cTnI results in a community population of elderly individuals [PIVUS (Prospective Study of the Vasculature in Uppsala Seniors) study; n = 1005]. The utility of predefined Troponin I cutoffs for risk stratification was then evaluated in 952 patients from the FRISC II (FRagmin and Fast Revascularization during InStability in Coronary artery disease) study at 6 months after these patients had suffered acute coronary syndrome .
Results: Selection of assay results from a subcohort of PIVUS participants without cardiovascular disease resulted in a decrease of the 99th percentile from 0.044 µg/L to 0.028 µg/L. Men had higher rates of cTnI elevation with respect to the tested thresholds. Whereas the 99th percentile cutoff was not found to be a useful prognostic indicator for 5-year mortality, both the 90th percentile (hazard ratio 3.1; 95% CI 1.9–5.1) and the 75th percentile (hazard ratio 2.8; 95% CI 1.7–4.7) provided useful prognostic information. Sex-specific cutoffs did not improve risk prediction.
Conclusions: The 99th percentile of cTnI depends highly on the characteristics of the reference population from which it is determined. This dependence on the reference population may affect the appropriateness of clinical conclusions based on this threshold. However, cTnI cutoffs below the 99th percentile seem to provide better prognostic discrimination in stabilized acute coronary syndrome patients and therefore may be preferable for risk stratification.
Kai M. Eggers1,a, Allan S. Jaffe4, Lars Lind2, Per Venge3 and Bertil Lindahl1
Departments of1 Medical Sciences, Cardiology,2 Medicine, and 3 Clinical Chemistry, Uppsala University Hospital, Sweden, and4 Mayo Medical School, Rochester, MN.
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