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Glycemia and inflammatory markers in acute coronary syndrome: Association with late post-hospital outcomes
Abstract
Glycemia and inflammatory markers were associated with clinical outcomes in patients with acute coronary syndrome (ACS).
To evaluate the role of glycemia and inflammatory markers as predictors of late cardiovascular outcomes after ACS.
One hundred and ninety-nine ACS patients of a Coronary Care Unit were included, from March to November 2002. They were reassessed clinically after approximately 3 years. Clinical variables, glycemia, CRP and fibrinogen were evaluated as event and mortality predictors. Statistical analyses included Cox multivariate analysis and survival curves (Kaplan-Meier).
At admission, 16.7% had normal glycemia. After 3 years, this proportion increased to 55.2%; the 40.6% who belonged to the borderline category decreased to 27.1%; the 42.7% with elevated glycemia decreased to 17.7%. Glycemia was not associated with the development of major cardiovascular events (MACE) and mortality at follow-up ( approximately 3 years). Considering MACE, CRP (p<0.001), but not fibrinogen, was predictive in bivariate analysis. Regarding mortality, both fibrinogen (p=0.020) and CRP (p=0.008) were predictive in bivariate analysis.
Glycemia was not associated with late mortality after ACS, but inflammatory markers were, suggesting that these are more sensitive markers to predict events in long-term. Moreover, glucose intolerance prevalence is lower in the follow-up after the ACS episode.
... Outro estudo também mostrou que a GPJ foi um bom preditor de mortalidade de longo prazo em pacientes não-diabéticos com IAM 19 . Em alguns outros estudos, no entanto, nenhuma associação foi observada entre a GPJ na internação e eventos adversos após a SCA no seguimento de longo prazo 28,29 . ...
The fasting plasma glucose (FPG) test is a predictor of complications after Acute Coronary Syndrome (ACS). However, its prognostic value is not yet fully established in different age groups.
To evaluate the role of admission fasting plasma glucose (FPG) as a predictor of 30 days after ACS, and the association of hyperglycemia with major cardiovascular events (MACE): death, reinfarction and coronary artery bypass grafting, in two different age groups (<65 year and ≥65 year-old patients).
Contemporary cohort of patients hospitalized for ACS in the Institute of Cardiology of Rio Grande do Sul (Southern Brazil). In the first 24 hours of admission, patients answered a questionnaire with clinical information and had peripheral blood collected for measurement of FPG. Patients were followed up during hospitalization and for 30 days for the presence of MACE. Statistical analyses were performed using the SPSS 15.0 with the chi-square or Fisher Exact test (categorical variables) and the Student t test (numerical variables). Multivariate analysis was performed.
580 patients were included in the study. Mean age was 61.2 (±12.3) years, with 38.6% of the patients (224) ≥65 years old, and 67.7% (393) were male. Multivariable analysis showed that, after 30 days of follow-up, only FPG (OR= 1.01, 95% CI:1.00-1.01, P= 0.001) was associated with MACE in both age groups.
Admission FPG was an independent predictor for MACE in the early phase of ACS.
In patients with unstable coronary artery disease, there is a relation between the short-term risk of death and blood levels of troponin T (a marker of myocardial damage) and C-reactive protein and fibrinogen (markers of inflammation). Using information obtained during an extension of the follow-up period in the Fragmin during Instability in Coronary Artery Disease trial, we evaluated the usefulness of troponin T, C-reactive protein, and fibrinogen levels and other indicators of risk as predictors of the long-term risk of death from cardiac causes.
Levels of C-reactive protein and fibrinogen at enrollment and the maximal level of troponin T during the first 24 hours after enrollment were analyzed in 917 patients included in a clinical trial of low-molecular-weight heparin in unstable coronary artery disease. The patients were followed for a mean of 37.0 months (range, 1.6 to 50.6).
During follow-up, 1.2 percent of the 173 patients with maximal blood troponin T levels of less than 0.06 microg per liter died of cardiac causes, as compared with 8.7 percent of the 367 patients with levels of 0.06 to 0.59 microg per liter and 15.4 percent of the 377 patients with levels of at least 0.60 microg per liter (P=0.007 and P=0.001, respectively). The rates of death from cardiac causes were 5.7 percent among the 314 patients with blood C-reactive protein levels of less than 2 mg per liter, 7.8 percent among the 294 with levels of 2 to 10 mg per liter, and 16.5 percent among the 309 with levels of more than 10 mg per liter (P=0.29 and P=0.001, respectively). The rates of death from cardiac causes were 5.4 percent among the 314 patients with blood fibrinogen levels of less than 3.4 g per liter, 12.0 percent among the 300 with levels of 3.4 to 3.9 g per liter, and 12.9 percent among the 303 with levels of at least 4.0 g per liter (P=0.004 and P=0.69, respectively). In a multivariate analysis, levels of troponin T and C-reactive protein were independent predictors of the risk of death from cardiac causes.
In unstable coronary artery disease, elevated levels of troponin T and C-reactive protein are strongly related to the long-term risk of death from cardiac causes. These markers are independent risk factors, and their effects are additive with respect to each other and other clinical indicators of risk.
Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known.
We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter [4.4 and 6.1 mmol per liter]) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter [11.9 mmol per liter] and maintenance of glucose at a level between 180 and 200 mg per deciliter [10.0 and 11.1 mmol per liter]).
At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P<0.04, with adjustment for sequential analyses). The benefit of intensive insulin therapy was attributable to its effect on mortality among patients who remained in the intensive care unit for more than five days (20.2 percent with conventional treatment, as compared with 10.6 percent with intensive insulin therapy, P=0.005). The greatest reduction in mortality involved deaths due to multiple-organ failure with a proven septic focus. Intensive insulin therapy also reduced overall in-hospital mortality by 34 percent, bloodstream infections by 46 percent, acute renal failure requiring dialysis or hemofiltration by 41 percent, the median number of red-cell transfusions by 50 percent, and critical-illness polyneuropathy by 44 percent, and patients receiving intensive therapy were less likely to require prolonged mechanical ventilation and intensive care.
Intensive insulin therapy to maintain blood glucose at or below 110 mg per deciliter reduces morbidity and mortality among critically ill patients in the surgical intensive care unit.
To analyse the relation between serum glucose concentration and hospital outcome across the whole spectrum of acute coronary syndromes.
This was a prospective cohort study of 2127 patients presenting with acute coronary syndromes. The patients were stratified into quartile groups (Q1 to Q4) defined by serum glucose concentrations of 5.8, 7.2, and 10.0 mmol/l. The relation between quartile group and major in-hospital complications was analysed.
The proportion of patients with acute myocardial infarction increased incrementally across the quartile groups, from 21.4% in Q1 to 47.9% in Q4 (p < 0.0001). The trend for frequency of in-hospital major complications was similar, particularly left ventricular failure (LVF) (Q1 6.4%, Q4 25.2%, p < 0.0001) and cardiac death (Q1 0.7%, Q4 6.1%, p < 0.0001). The relations were linear, each glucose quartile increment being associated with an odds ratio of 1.46 (95% confidence interval (CI) 1.27 to 1.70) for LVF and 1.52 (95% CI 1.17 to 1.97) for cardiac death. Although complication rates were higher for a discharge diagnosis of acute myocardial infarction than for unstable angina, there was no evidence that the effects of serum glucose concentration were different for the two groups, there being no significant interaction with discharge diagnosis in the associations between glucose quartile and LVF (p = 0.69) or cardiac death (p = 0.17). Similarly there was no significant interaction with diabetic status in the associations between glucose quartile and LVF (p = 0.08) or cardiac death (p = 0.09).
Admission glycaemia stratified patients with acute coronary syndromes according to their risk of in-hospital LVF and cardiac mortality. There was no detectable glycaemic threshold for these adverse effects. The prognostic correlates of admission glycaemia were unaffected by diabetic status and did not differ significantly between patients with acute myocardial infarction and those with unstable angina.
There are limited data describing the presenting characteristics, management, and outcomes of diabetic and nondiabetic patients with an acute coronary syndrome (ACS).
To examine differences in these factors, patients with ST-segment elevation acute myocardial infarction, non-ST-segment elevation acute myocardial infarction, and unstable angina were enrolled in a large multinational coronary disease registry.
The Global Registry of Acute Coronary Events is a prospective observational study of patients hospitalized with an ACS at 94 hospitals in 14 countries. The study sample consisted of 5403 patients with ST-segment elevation acute myocardial infarction, 4725 with non-ST-segment elevation acute myocardial infarction, and 5988 with unstable angina.
Approximately 1 in 4 patients presented to participating hospitals with a history of diabetes. Patients with diabetes were older, more often women, with a greater prevalence of comorbidities, and they were less likely to be treated with effective cardiac therapies than nondiabetic patients. Patients with diabetes who developed an ACS were at increased risk for each hospital outcome examined including heart failure, renal failure, cardiogenic shock, and death. These differences remained after adjustment for potentially confounding prognostic factors.
A considerable proportion of patients with an ACS has diabetes and is at increased risk for adverse outcomes compared with patients without diabetes. There are certain proven therapeutic strategies that remain underused in the diabetic population. A more widespread awareness of this increased risk and a more diligent use of proven cardiac treatment approaches are indicated for patients with diabetes who develop an ACS.
Patients with diabetes have an unfavourable prognosis after an acute myocardial infarction. In the first DIGAMI study, an insulin-based glucose management improved survival. In DIGAMI 2, three treatment strategies were compared: group 1, acute insulin-glucose infusion followed by insulin-based long-term glucose control; group 2, insulin-glucose infusion followed by standard glucose control; and group 3, routine metabolic management according to local practice.
DIGAMI 2 recruited 1253 patients (mean age 68 years; 67% males) with type 2 diabetes and suspected acute myocardial infarction randomly assigned to groups 1 (n=474), 2 (n=473), and 3 (n=306). The primary endpoint was all-cause mortality between groups 1 and 2, and a difference was hypothesized as the primary objective. The secondary objective was to compare total mortality between groups 2 and 3, whereas morbidity differences served as tertiary objectives. The median study duration was 2.1 (interquartile range 1.03-3.00) years. At randomization, HbA1c was 7.2, 7.3, and 7.3% in groups 1, 2, and 3, respectively, whereas blood glucose was 12.8, 12.5, and 12.9 mmol/L, respectively. Blood glucose was significantly reduced after 24 h in all groups, more in groups 1 and 2 (9.1 and 9.1 mmol/L) receiving insulin-glucose infusion than in group 3 (10.0 mmol/L). Long-term glucose-lowering treatment differed between groups with multidose insulin (> or =3 doses/day) given to 15 and 13% of patients in groups 2 and 3, respectively compared with 42% in group 1 at hospital discharge. By the end of follow-up, HbA1c did not differ significantly among groups 1-3 ( approximately 6.8%). The corresponding values for fasting blood glucose were 8.0, 8.3, and 8.6 mmol/L. Hence, the target fasting blood glucose for patients in group 1 of 5-7 mmol/L was never reached. The study mortality (groups 1-3 combined) was 18.4%. Mortality between groups 1 (23.4%) and 2 (22.6%; primary endpoint) did not differ significantly (HR 1.03; 95% CI 0.79-1.34; P=0.831), nor did mortality between groups 2 (22.6%) and 3 (19.3%; secondary endpoint) (HR 1.23; CI 0.89-1.69; P=0.203). There were no significant differences in morbidity expressed as non-fatal reinfarctions and strokes among the three groups.
DIGAMI 2 did not support the fact that an acutely introduced, long-term insulin treatment improves survival in type 2 diabetic patients following myocardial infarction when compared with a conventional management at similar levels of glucose control or that insulin-based treatment lowers the number of non-fatal myocardial reinfarctions and strokes. However, an epidemiological analysis confirms that the glucose level is a strong, independent predictor of long-term mortality in this patient category, underlining that glucose control seems to be an important part of their management.
The study evaluated the associations between glycometabolic parameters at admission and during hospitalization and 2 year all-cause mortality risk in an unselected cohort of consecutive patients with diabetes admitted for unstable angina or non-Q-wave myocardial infarction to a university hospital during 1988-98.
A total of 713 consecutive patients with diabetes were included. During 2 years of follow-up, 242 (34%) patients died. All analyses were retrospective using prospectively collected clinical data. The primary study endpoint was 2 year all-cause mortality collected from the Swedish cause-specific mortality register. In unadjusted analyses, high admission blood glucose (highest vs. lowest quartile: hazard ratio (HR) 2.66; 95% confidence interval (CI) 1.83, 3.86) and hypoglycaemia recorded during hospitalization (hypoglycaemia vs. normal: HR 1.77; 95% CI 1.09, 2.86) were both significantly associated with increased 2 year all-cause mortality risk. These associations remained significant after multivariable adjustment.
In the setting of acute coronary syndromes (ACS) among patients with diabetes, hyperglycaemia on arrival and hypoglycaemia during hospitalization are both independently associated with worse adjusted all-cause 2 year mortality risk. These observations suggest that the avoidance of both hyper- and hypoglycaemia during ACS events may be of similar importance, and glucose modulation remains an important objective to address in future randomized trials.
Admission hyperglycaemia is associated with poorer prognosis in patients with an acute coronary syndrome (ACS). Whether hyperglycaemia is more important than prior long-term glucose metabolism, is unknown.
To investigate the prognostic value of admission glucose and HbA(1c) levels in patients with ACS.
We measured glucose and HbA(1c) at admission in 521 consecutive patients with suspected ACS. Glucose was categorized as <7.8 (n = 305), 7.8-11.0 (n = 138) or > or =11.1 mmol/l (n = 78); HbA(1c) as <6.2% (n = 420) or > or =6.2% (n = 101). Mean follow-up was 1.6 +/- 0.5 years.
The diagnosis of ACS was confirmed in 332 patients (64%), leaving 189 (36%) with atypical chest pain. In ACS patients, mortality by glucose category (<7.8, 7.8-11.0 or > or =11.1 mmol) was 9%, 8% and 25%, respectively (p = 0.001); mortality by HbA(1c) category (<6.2% vs. > or =6.2%) was 10% vs. 17%, respectively (p = 0.14). On multivariate analysis, glucose category was significantly associated with mortality (HR 3.0, 95% CI 1.1-8.3), but HbA(1c) category was not (HR 1.5, 95%CI 0.6-4.2).
Elevated admission glucose appears more important than prior long-term abnormal glucose metabolism in predicting mortality in patients with suspected ACS.
There is conflicting evidence regarding the benefit of intravenous insulin therapy on mortality following acute myocardial infarction (AMI). The goal of the current study was to determine whether improved glycemic control, achieved through an insulin/dextrose infusion with a variable rate of insulin, reduces mortality among hyperglycemic patients with AMI.
Subjects suffering AMI with either known diabetes or without diabetes but blood glucose level (BGL) > or =7.8 mmol/l were randomized to receive insulin/dextrose infusion therapy for at least 24 h to maintain a BGL <10 mmol/l or conventional therapy.
A total of 240 subjects were recruited. Insulin/dextrose infusion did not reduce mortality at the inpatient stage (4.8 vs. conventional 3.5%, P = 0.75), 3 months (7.1 vs 4.4%, P = 0.42), or 6 months (7.9 vs. 6.1%, P = 0.62). There was, however, a lower incidence of cardiac failure (12.7 vs. 22.8%, P = 0.04) and reinfarction within 3 months (2.4 vs. 6.1%, P = 0.05). When analyzed by mean BGL achieved during the first 24 h, mortality was lower among subjects with a mean BGL < or =8 mmol/l, compared with subjects with a mean BGL >8 mmol/l (2 vs. 11% at 6 months, P = 0.02).
We did not find a reduction in mortality among patients who received insulin/dextrose infusion therapy. However, it remains possible that tight glycemic control with insulin therapy following AMI improves outcomes.
The significance of admission blood glucose level in nondiabetic patients with heart failure (HF) is unknown. We examined the possible association between admission glucose levels and outcome in a large cohort of hospitalized patients with HF.
We analyzed the data of 4102 patients with HF, who were hospitalized during a prospective national survey. The present study focuses on a subgroup of 1122 nondiabetic patients with acute HF who were admitted because of acute HF or exacerbation of chronic HF.
In-hospital mortality was twice as high in patients with admission blood glucose levels in the third tertile (7.2%) compared with the first (3%) and second (4%) tertiles (P = .02). Furthermore, mortality risk was correlated with admission glucose levels; each 18-mg/dL (1-mmol/L) increase in glucose level was associated with a 31% increased risk of in-hospital mortality (adjusted odds ratio, 1.31; 95% confidence interval, 1.10-1.57; P = .003) and a 12% increase in 60-day mortality (adjusted hazard ratio, 1.12; 95% confidence interval, 1.01-1.25; P = .04). Admission blood glucose levels remained an independent predictor of in-hospital and 60-day mortality even after the exclusion of 315 patients (28%) with acute myocardial infarction and HF. The 6- and 12-month mortality rates were similar in patients with and without abnormal admission blood glucose levels.
Elevated admission blood glucose levels are associated with increased in-hospital and 60-day mortality, but not 6-month or 1-year mortality, in nondiabetic patients hospitalized because of HF.
Objectives. We evaluated C-reactive protein (CRP) alone and in conjunction with a rapid qualitative assay for cardiac-specific troponin T (cTnT) for predicting 14-day mortality in patients with unstable angina or non-Q wave myocardial infarction (NQMI).Background. Elevated CRP has been found to correlate with higher risk for cardiac events in patients with coronary disease.Methods. At enrollment into the Thrombolysis in Myocardial Infarction (TIMI) 11A trial, a dose-ranging trial of enoxaparin for unstable angina and NQMI, serum was obtained for CRP measurement and rapid cTnT assay.Results. Quantitative CRP and rapid cTnT assays were performed in all patients. CRP was higher among patients who died than in survivors (7.2 vs. 1.3 mg/dl, p = 0.0038). The probability of a positive rapid cTnT assay rose with increasing CRP concentration (p Conclusions. Elevated CRP at presentation in patients with unstable angina or NQMI is correlated with increased 14-day mortality, even in patients with a negative rapid cTnT assay. Quantitative CRP and a rapid cTnT assay provide complementary information for stratifying patients with regard to mortality risk.
Objectives: To test the hypothesis that intensive metabolic treatment with insulin-glucose infusion followed by multidose insulin treatment in patients with diabetes mellitus and acute myocardial infarction improves the prognosis.
Design: Patients with diabetes mellitus and acute myocardial infarction were randomly allocated standard treatment plus insulin-glucose infusion for at least 24 hours followed by multidose insulin treatment or standard treatment (controls).
Subjects: 620 patients were recruited, of whom 306 received intensive insulin treatment and 314 served as controls.
Main outcome measure: Long term all cause mortality.
Results: The mean (range) follow up was 3.4 (1.6-5.6) years. There were 102 (33%) deaths in the treatment group compared with 138 (44%) deaths in the control group (relative risk (95% confidence interval) 0.72 (0.55 to 0.92); P=0.011).The effect was most pronounced among the predefined group that included 272 patients without previous insulin treatment and at a low cardiovascular risk (0.49 (0.30 to 0.80); P=0.004).
Conclusion: Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infarction improves long term survival, and the effect seen at one year continues for at least 3.5 years, with an absolute reduction in mortality of 11%. This means that one life was saved for nine treated patients. The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk.
Key messages
Diabetes mellitus is common among patients with acute myocardial infarctionDiabetic patients with myocardial infarction have a poor short and long term prognosisPoor metabolic control is common among diabetic patients with myocardial infarctionImproved metabolic control by means of acute insulin-glucose infusion followed by long term intensive insulin treatment improves long term prognosis among these patients
Increased levels of certain hemostatic factors may play a part in the development of acute coronary syndromes and may be associated with an increased risk of coronary events in patients with angina pectoris.
We conducted a prospective multicenter study of 3043 patients with angina pectoris who underwent coronary angiography and were followed for two years. Base-line measurements included the concentrations of selected hemostatic factors indicative of a thrombophilic state or endothelial injury. The results were analyzed in relation to the subsequent incidence of myocardial infarction or sudden coronary death.
After adjustment for the extent of coronary artery disease and other risk factors, an increased incidence of myocardial infarction or sudden death was associated with higher base-line concentrations of fibrinogen (mean +/- SD, 3.28 +/- 0.74 g per liter in patients who subsequently had coronary events, as compared with 3.00 +/- 0.71 g per liter in those who did not; P = 0.01), von Willebrand factor antigen (138 +/- 49 percent vs. 125 +/- 49 percent, P = 0.05), and tissue plasminogen activator (t-PA) antigen (11.9 +/- 4.7 ng per milliliter vs. 10.0 +/- 4.2 ng per milliliter, P = 0.02). The concentration of C-reactive protein was also directly correlated with the incidence of coronary events (P = 0.05), except when we adjusted for the fibrinogen concentration. In patients with high serum cholesterol levels, the risk of coronary events rose with increasing levels of fibrinogen and C-reactive protein, but the risk remained low even given high serum cholesterol levels in the presence of low fibrinogen concentrations.
In patients with angina pectoris, the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent acute coronary syndromes. In addition, low fibrinogen concentrations characterize patients at low risk for coronary events despite increased serum cholesterol levels. Our data are consistent with a pathogenetic role of impaired fibrinolysis, endothelial-cell injury, and inflammatory activity in the progression of coronary artery disease.
The pathogenesis of unstable angina is poorly understood, and predicting the prognosis at the time of hospital admission is problematic. Recent evidence suggests that there may be active inflammation, possibly in the coronary arteries, in this syndrome. We therefore studied the prognostic value of measurements of the circulating acute-phase reactants C-reactive protein and serum amyloid A protein, which are sensitive indicators of inflammation.
We measured C-reactive protein, serum amyloid A protein, creatine kinase, and cardiac troponin T in 32 patients with chronic stable angina, 31 patients with severe unstable angina, and 29 patients with acute myocardial infarction.
At the time of hospital admission, creatine kinase and cardiac troponin T levels were normal in all the patients, but the levels of C-reactive protein and serum amyloid A protein were > or = 0.3 mg per deciliter (exceeding the 90th percentile of the normal distribution) in 4 of the patients with stable angina (13 percent), 20 of the patients with unstable angina (65 percent), and 22 of the patients with acute myocardial infarction (76 percent). The 20 patients with unstable angina who had levels of C-reactive protein and serum amyloid A protein > or = 0.3 mg per deciliter had more ischemic episodes in the hospital than those with levels < 0.3 mg per deciliter (mean [+/- SD] number of episodes per patient, 4.8 +/- 2.5 vs. 1.8 +/- 2.4; P = 0.004); 5 patients subsequently had a myocardial infarction, 2 died, and 12 required immediate coronary revascularization. In contrast, no deaths or myocardial infarction occurred among the 11 patients with levels of C-reactive protein and serum amyloid A protein < 0.3 mg per deciliter, and only 2 of them required coronary revascularization. Among the patients admitted with a diagnosis of acute myocardial infarction, unstable angina preceded infarction in 14 of the 22 patients (64 percent) with levels of C-reactive protein and serum amyloid A protein > or = 0.3 mg per deciliter but in none of the 7 patients with levels < 0.3 mg per deciliter.
Elevation of the sensitive acute-phase proteins C-reactive protein and serum amyloid A protein at the time of hospital admission predicts a poor outcome in patients with unstable angina and may reflect an important inflammatory component in the pathogenesis of this condition.
The aim of the study was to investigate prospectively the prognostic value of blood glucose on admission in diabetic and non-diabetic patients with an acute myocardial infarction. Three hundred and thirty-three diabetic and 565 non-diabetic patients were admitted with acute myocardial infarction during the study period of 3.5 years. There was a significant association between mortality and blood glucose on admission in diabetic patients (regression coefficient, r = 0.92, 0.5 < p < 0.02) but not in non-diabetic individuals (r = 0.69, 0.2 < p < 0.5). Age- and sex-standardized mortality was higher in the diabetic group (12.2% vs 7.4%, p < 0.03), but was identical if standardized also for blood glucose on admission. We conclude that a high blood glucose on admission is a bad prognostic indicator in a diabetic patient with an acute myocardial infarction. The excess mortality in diabetic patients with acute myocardial infarction can be attributed to the higher proportion with hyperglycaemia.
To test the hypothesis that intensive metabolic treatment with insulin-glucose infusion followed by multidose insulin treatment in patients with diabetes mellitus and acute myocardial infarction improves the prognosis.
Patients with diabetes mellitus and acute myocardial infarction were randomly allocated standard treatment plus insulin-glucose infusion for at least 24 hours followed by multidose insulin treatment or standard treatment (controls).
620 patients were recruited, of whom 306 received intensive insulin treatment and 314 served as controls.
Long term all cause mortality.
The mean (range) follow up was 3.4 (1.6-5.6) years. There were 102 (33%) deaths in the treatment group compared with 138 (44%) deaths in the control group (relative risk (95% confidence interval) 0.72 (0.55 to 0.92); P = 0.011). The effect was most pronounced among the predefined group that included 272 patients without previous insulin treatment and at a low cardiovascular risk (0.49 (0.30 to 0.80); P = 0.004).
Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infarction improves long term survival, and the effect seen at one year continues for at least 3.5 years, with an absolute reduction in mortality of 11%. This means that one life was saved for nine treated patients. The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk.
The prognostic influences of fibrinogen and C-reactive protein levels and their relations to myocardial damage in unstable coronary artery syndromes have not been well described.
Fibrinogen and C-reactive protein were determined at inclusion and related to outcome after 5 months in 965 patients with unstable angina or non-Q-wave myocardial infarction randomized to 5 weeks with low-molecular-weight heparin or placebo. The probabilities of death were 1.6%, 4.6%, and 6.9% (P=.005) and the probabilities of death and/or myocardial infarction were 9.3%, 14.2%, and 19.1% (P=.002), respectively, in patients stratified by tertiles of fibrinogen (< 3.38, 3.38 to 3.99, and > or = 4.0 g/L). The probabilities of death were 2.2%, 3.6%, and 7.5% (P=.003) after stratification of patient data by tertiles of C-reactive protein level (< 2, 2 to 10, and > 10 mg/L). In logistic multiple regression analysis, increased fibrinogen levels were independently associated with the incidence of death and/or myocardial infarction (P=.013), and elevated C-reactive protein level was associated with the incidence of death (P=.012). The increased relative risk of subsequent death or myocardial infarction in individuals with an elevated fibrinogen level was consistent in most subgroups evaluated; although significantly so only in patients with signs of myocardial damage.
Increased levels of both fibrinogen and C-reactive protein are associated with a worse outcome in patients with unstable coronary artery disease. The increased risk associated with elevated fibrinogen levels is independent of, and additive to, the prognostic influence of myocardial damage.
A large number of epidemiologic studies have reported on associations between various "inflammatory" factors and coronary heart disease (CHD).
To assess the associations of blood levels of fibrinogen, C-reactive protein (CRP), and albumin and leukocyte count with the subsequent risk of CHD.
Meta-analyses of any long-term prospective studies of CHD published before 1998 on any of these 4 factors. Studies were identified by MEDLINE searches, scanning of relevant reference lists, hand searching of cardiology, epidemiology, and other relevant journals, and discussions with authors of relevant reports.
All relevant studies identified were included.
The following information was abstracted from published reports (supplemented, in several cases, by the authors): size and type of cohort, mean age, mean duration of follow-up, assay methods, degree of adjustment for confounders, and relationship of CHD risk to the baseline assay results.
For fibrinogen, with 4018 CHD cases in 18 studies, comparison of individuals in the top third with those in the bottom third of the baseline measurements yielded a combined risk ratio of 1.8 (95% confidence interval [CI], 1.6-2.0) associated with a difference in long-term usual mean fibrinogen levels of 2.9 pmol/L (0.1 g/dL) between the top and bottom thirds (10.3 vs 7.4 pmol/L [0.35 vs 0.25 g/dL]). For CRP, with 1053 CHD cases in 7 studies, the combined risk ratio of 1.7 (95% CI, 1.4-2.1) was associated with a difference of 1.4 mg/L (2.4 vs 1.0 mg/L). For albumin, with 3770 CHD cases in 8 studies, the combined risk ratio of 1.5 (95% CI, 1.3-1.7) was associated with a difference of 4 g/L (38 vs 42 g/L, ie, an inverse association). For leukocyte count, with 5337 CHD cases in the 7 largest studies, the combined risk ratio of 1.4 (95% CI, 1.3-1.5) was associated with a difference of 2.8 x 10(9)/L (8.4 vs 5.6 x 10(9)/L). Each of these overall results was highly significant (P<.0001).
The published results from these prospective studies are remarkably consistent for each factor, indicating moderate but highly statistically significant associations with CHD. Hence, even though mechanisms that might account for these associations are not clear, further study of the relevance of these factors to the causation of CHD is warranted.
Circulating levels of C-reactive protein (CRP) may constitute an independent risk factor for cardiovascular disease. How CRP as a risk factor is involved in cardiovascular disease is still unclear.
By reviewing available studies, we discuss explanations for the associations between CRP and cardiovascular disease. CRP levels within the upper quartile/quintile of the normal range constitute an increased risk for cardiovascular events, both in apparently healthy persons and in persons with preexisting angina pectoris. High CRP responses after acute myocardial infarction indicate an unfavorable outcome, even after correction for other risk factors. This link between CRP and cardiovascular disease has been considered to reflect the response of the body to the inflammatory reactions in the atherosclerotic (coronary) vessels and adjacent myocardium. However, because CRP localizes in infarcted myocardium (with colocalization of activated complement), we hypothesize that CRP may directly interact with atherosclerotic vessels or ischemic myocardium by activation of the complement system, thereby promoting inflammation and thrombosis.
CRP constitutes an independent cardiovascular risk factor. Unraveling the molecular background of this association may provide new directions for prevention of cardiovascular events.
"Stress" hyperglycemia may be associated with increased mortality and poor recovery in diabetic and nondiabetic patients after stroke. A systematic review and meta-analysis of the literature relating acute poststroke glucose levels to the subsequent course were done to summarize and quantify this relationship.
A comprehensive literature search was done for cohort studies reporting mortality and/or functional recovery after stroke in relation to admission glucose level. Relative risks in hyperglycemic compared with normoglycemic patients with and without diabetes were calculated and meta-analyzed when possible.
Thirty-two studies were identified; relative risks for prespecified outcomes were reported or could be calculated in 26 studies. After stroke of either subtype (ischemic or hemorrhagic), the unadjusted relative risk of in-hospital or 30-day mortality associated with admission glucose level >6 to 8 mmol/L (108 to 144 mg/dL) was 3.07 (95% CI, 2.50 to 3.79) in nondiabetic patients and 1.30 (95% CI, 0.49 to 3.43) in diabetic patients. After ischemic stroke, admission glucose level >6.1 to 7.0 mmol/L (110 to 126 mg/dL) was associated with increased risk of in-hospital or 30-day mortality in nondiabetic patients only (relative risk=3.28; 95% CI, 2.32 to 4.64). After hemorrhagic stroke, admission hyperglycemia was not associated with higher mortality in either diabetic or nondiabetic patients. Nondiabetic stroke survivors whose admission glucose level was >6.7 to 8 mmol/L (121 to 144 mg/dL) also had a greater risk of poor functional recovery (relative risk=1.41; 95% CI, 1.16 to 1.73).
Acute hyperglycemia predicts increased risk of in-hospital mortality after ischemic stroke in nondiabetic patients and increased risk of poor functional recovery in nondiabetic stroke survivors.
This two-part article provides an overview of the global burden of atherothrombotic cardiovascular disease. Part I initially discusses the epidemiologic transition which has resulted in a decrease in deaths in childhood due to infections, with a concomitant increase in cardiovascular and other chronic diseases; and then provides estimates of the burden of cardiovascular (CV) diseases with specific focus on the developing countries. Next, we summarize key information on risk factors for cardiovascular disease (CVD) and indicate that their importance may have been underestimated. Then, we describe overarching factors influencing variations in CVD by ethnicity and region and the influence of urbanization. Part II of this article describes the burden of CV disease by specific region or ethnic group, the risk factors of importance, and possible strategies for prevention.
Admission hyperglycemia has been associated with increased hospital mortality in critically ill patients; however, it is not known whether hyperglycemia in patients admitted to general hospital wards is associated with poor outcome. The aim of this study was to determine the prevalence of in-hospital hyperglycemia and determine the survival and functional outcome of patients with hyperglycemia with and without a history of diabetes. We reviewed the medical records of 2030 consecutive adult patients admitted to Georgia Baptist Medical Center, a community teaching hospital in downtown Atlanta, GA, from July 1, 1998, to October 20, 1998. New hyperglycemia was defined as an admission or in-hospital fasting glucose level of 126 mg/dl (7 mmol/liter) or more or a random blood glucose level of 200 mg/dl (11.1 mmol/liter) or more on 2 or more determinations. Hyperglycemia was present in 38% of patients admitted to the hospital, of whom 26% had a known history of diabetes, and 12% had no history of diabetes before the admission. Newly discovered hyperglycemia was associated with higher in-hospital mortality rate (16%) compared with those patients with a prior history of diabetes (3%) and subjects with normoglycemia (1.7%; both P < 0.01). In addition, new hyperglycemic patients had a longer length of hospital stay, a higher admission rate to an intensive care unit, and were less likely to be discharged to home, frequently requiring transfer to a transitional care unit or nursing home facility.
Our results indicate that in-hospital hyperglycemia is a common finding and represents an important marker of poor clinical outcome and mortality in patients with and without a history of diabetes. Patients with newly diagnosed hyperglycemia had a significantly higher mortality rate and a lower functional outcome than patients with a known history of diabetes or normoglycemia.
Glycometabolic state at hospital admission is an important risk marker for long-term mortality in patients with acute myocardial infarction, whether or not they have known diabetes mellitus. Our aim was to ascertain the prevalence of impaired glucose metabolism in patients without diagnosed diabetes but with myocardial infarction, and to assess whether such abnormalities can be identified in the early course of a myocardial infarction.
We did a prospective study, in which we enrolled 181 consecutive patients admitted to the coronary care units of two hospitals in Sweden with acute myocardial infarction, no diagnosis of diabetes, and a blood glucose concentration of less than 11.1 mmol/L. We recorded glucose concentrations during the hospital stay, and did standardised oral glucose tolerance tests with 75 g of glucose at discharge and again 3 months later.
The mean age of our cohort was 63.5 years (SD 9) and the mean blood glucose concentration at admission was 6.5 mmol/L (1.4). The mean 2-h postload blood glucose concentration was 9.2 mmol/L (2.9) at hospital discharge, and 9.0 mmol/L (3.0) 3 months later. 58 of 164 (35%, 95% CI 28-43) and 58 of 144 (40%, 32-48) individuals had impaired glucose tolerance at discharge and after 3 months, respectively, and 51 of 164 (31%, 24-38) and 36 of 144 (25%, 18-32) had previously undiagnosed diabetes mellitus. Independent predictors of abnormal glucose tolerance at 3 months were concentrations of HbA(1c) at admission (p=0.024) and fasting blood glucose concentrations on day 4 (p=0.044).
Previously undiagnosed diabetes and impaired glucose tolerance are common in patients with an acute myocardial infarction. These abnormalities can be detected early in the postinfarction period. Our results suggest that fasting and postchallenge hyperglycaemia in the early phase of an acute myocardial infarction could be used as early markers of high-risk individuals.
Abundant data link hypercholesterolaemia to atherogenesis. However, only recently have we appreciated that inflammatory mechanisms couple dyslipidaemia to atheroma formation. Leukocyte recruitment and expression of pro-inflammatory cytokines characterize early atherogenesis, and malfunction of inflammatory mediators mutes atheroma formation in mice. Moreover, inflammatory pathways promote thrombosis, a late and dreaded complication of atherosclerosis responsible for myocardial infarctions and most strokes. The new appreciation of the role of inflammation in atherosclerosis provides a mechanistic framework for understanding the clinical benefits of lipid-lowering therapies. Identifying the triggers for inflammation and unravelling the details of inflammatory pathways may eventually furnish new therapeutic targets.
We sought to evaluate C-reactive protein (CRP) and troponin T (TnT) as predictors of risk of the individual end points of mortality and myocardial infarction (MI) in a large cohort of patients with acute coronary syndrome (ACS).
Both CRP and TnT predict risk of future coronary events in patients with ACS. However, the relationships between the levels of the markers and the individual end points are still unclear.
Baseline levels of CRP and TnT were determined in 7,108 patients with ACS not undergoing early revascularization in the Global Use of Strategies To Open occluded arteries trial IV (GUSTO-IV) trial and related to outcome at 30 days.
Quartiles of TnT related to 30-day mortality, which was 1.1%, 3.7%, 3.7%, and 7.4% (p < 0.001) and to the rate of MI: 2.5%, 6.7%, 7.2%, and 5.6% (p < 0.001). Quartiles of CRP also related to 30-day mortality, which was 2.0%, 3.3%, 3.9%, and 6.3% (p < 0.001), whereas there was no relationship to the 30-day rate of MI: 5.6%, 4.7%, 5.2%, and 5.9% (p = 0.48). On multivariable analysis, both TnT and CRP were independent predictors of mortality, but only TnT was a predictor of MI. The combination of CRP and TnT provides an even better risk stratification of mortality, with 0.3% and 9.1% death rates, respectively, when both markers are in the bottom versus top quartiles.
In ACS, baseline levels of TnT and CRP are independently related to 30-day mortality. Any detectable elevation of TnT, but not of CRP, is also associated with an increased risk of subsequent MI. Regarding mortality, the combination of both markers provides a better risk stratification than either one alone.
Prolonged critical illness has a high morbidity and mortality. The acute and chronic phases of critical illness are associated with distinct endocrine alterations. The acute neuroendocrine response to critical illness involves an activated anterior pituitary function. In prolonged critical illness, however, a reduced pulsatile secretion of anterior pituitary hormones and the so-called "wasting syndrome" occur. The impaired pulsatile secretion of GH, thyrotropin and gonadotropin can be re-amplified by relevant combinations of releasing factors, which also substantially increase circulating levels of IGF-1, GH-dependent IGFBPs, thyroxin, tri-iodothyronine and testosterone. Anabolism is clearly re-initiated at the time GH secretagogues, thyrotropin-releasing hormone and gonadotropin-releasing hormone are coadministered but the effect on survival remains unknown. A lethal outcome of critical illness is predicted by a high serum concentration of IGFBP-1, pointing to impaired insulin effect rather than pituitary function, and survival was recently shown to be dramatically improved by strict normalization of glycemia with exogenous insulin. In addition to the illness-induced endocrine alterations, patients may have pre-existing central or peripheral endocrine diseases, either previously diagnosed or unknown. Hence, endocrine function testing in a critically ill patient represents a major challenge and the issue of treatment remains controversial. The recent progress in knowledge of the neuroendocrine response to critical illness and its interrelation with peripheral hormonal and metabolic alterations during stress, allows for potential new therapeutic perspectives to safely reverse the wasting syndrome and improve survival.
To associate the markers lipid profile, inflammatory profile (high-sensitivity C-reactive protein HSCRP and fibrinogen), and metabolic profile (glucose determination) with hospital and posthospital events in patients with acute ischemic syndrome (AIS) and to describe the predictors of mortality in this population.
A cohort study with 199 patients with AIS (unstable angina, acute myocardial infarction (AMI) with or without ST segment elevation) admitted to the intensive care unit (ICU) of a university cardiology Hospital, from March to November 2002. The previous diseases, the medication in use, and the coronary risk factors were recorded. The clinical events considered in the hospital were reinfarction, angina, heart failure (HF), ventricular fibrillation, and death; the posthospital events considered (30 days after hospital discharge) were reinfarction, angina, HF, death, and admittance for percutaneous procedures (PTCA) or for revascularization (MRS).
HSCRP and altered glycemia were significantly associated with hospital events (P = 0.03 and P < 0.01, respectively); however, they were not associated with posthospital events (P = 0.19 and P = 0.61, respectively). Lipid profile and fibrinogen did not have a statistically significant association in any of the times assessed. Using multiple logistic regression, age (P = 0.04), previous AMI (P = 0.04), myocardial infarction with ST segment elevation (P = 0.008) or without ST segment elevation (P = 0.048), and altered glycemia (P = 0.002) were predictors of hospital mortality.
Increased HSCRP and altered glycemia were associated with a greater number of hospital events, whereas age, previous AMI, AMI with or without ST segment elevation, and altered glycemia were predictors of hospital mortality.
Municipal hospitals in large cities provide care for patients from immigrant and mixed ethnic communities that are at high risk for diabetes. Both diabetes and stress hyperglycemia increase the risk of adverse outcome after myocardial infarctions, and the impact of stress hyperglycemia on the outcome of myocardial infarctions in this particular setting has not been previously studied. We therefore undertook a retrospective cohort study to determine the prevalence of diabetes and stress hyperglycemia in patients presenting to a university-affiliated Bronx municipal hospital with myocardial infarction, and the relationship of these conditions to the extent of coronary disease and mortality. We obtained data on 106 consecutive patients from July 1998 to April 1999 with a diagnosis-related group diagnosis of either myocardial infarction or acute coronary syndrome, in which myocardial infarction was confirmed by serum enzymes or characteristic electrocardiographic changes. Patients were followed until March 30, 2001. Measurements of clinical parameters and results of catheterization were obtained for all patients. Death rates were determined by laboratory database, direct patient contact, or data from National Death Index. Eighty percent of the cohort had either a diagnosis of diabetes (n = 45, 42% of cohort) or evidence of stress hyperglycemia (defined as serum glucose greater than 126 mg/dL at the time of admission without prior diagnosis of diabetes, n = 40, 38%). In-hospital mortality for patients with diabetes, stress hyperglycemia, or normal glucose was 20%, 15%, and 14%, respectively. Eighty-three percent of the cohort received beta blockers, and 61% of hospital survivors had catheterization. Left main or triple vessel disease was common in both patients with diabetes (52%) and patients with stress hyperglycemia (32%). Mortality at follow up (maximum follow up 3 years; mean follow up 19.6 months) was much higher in patients with either diabetes (42%) or stress hyperglycemia (52%) than normal subjects (24%). Kaplan-Meier analysis of the difference in mortality between patients with high glucose on admission and normal subjects was borderline significant (P = 0.06). Multivariate regression demonstrated that age (P = 0.020), increase in admission serum creatinine (P = 0.001), and reduction in either ejection fraction (P = 0.016) or admission systolic blood pressure (P = 0.005) were significant predictors of mortality. Glycemic status and sex were not independently associated with death after controlling for these other factors. These results show that the prevalence of both diabetes and stress hyperglycemia on presentation with myocardial infarction is strikingly high in this immigrant, mixed ethnic, urban population. Patients with diabetes and stress hyperglycemia had advanced disease on presentation and much higher mortality at 2 to 3 years than those with normal blood glucose. The mortality difference is the result of older age and more advanced disease rather than hyperglycemia per se.
We aimed to study the relationship between C-reactive-protein (CRP), obtained within 12 to 24 h of symptoms onset, and long-term risk of death and heart failure (HF) in survivors of acute myocardial infarction (MI).
A robust inflammatory response is an integral component of the response to tissue injury during MI. The magnitude of the early inflammatory response to ischemic injury might be an important determinant of long-term outcome.
We prospectively studied 1,044 patients admitted with acute MI and discharged from hospital in stable condition.
During a median follow-up of 23 months (range, 6 to 42 months), 113 patients died and 112 developed HF. In a multivariable Cox regression model adjusting for clinical variables and predischarge ejection fraction, compared with patients in the first CRP quartile, the adjusted hazard ratios (HRs) for death progressively increased with higher quartiles of CRP (second quartile 1.4 [95% confidence interval (CI) 0.6 to 2.9]; third quartile 2.3 [95% CI 1.2 to 4.6]; fourth quartile 3.0 [95% CI 1.5 to 5.7]; for trend, p = 0.0002). Compared with patients in the first CRP quartile, the adjusted HRs for HF were: second quartile, 1.1 (95% CI 0.5 to 2.3); third quartile, 1.9 (95% CI 1.0 to 3.6); and fourth quartile, 2.1 (95% CI 1.2 to 3.9) (for trend, p = 0.005).
C-reactive-protein is a marker of long-term development of HF and mortality in patients with acute MI and provides prognostic information beyond that provided by conventional risk factors and the degree of left ventricular systolic dysfunction.
Acute phase hyperglycaemia has been associated with increased mortality in patients with acute coronary syndrome. We investigated whether the predictive value of admission hyperglycaemia for mortality differs between diabetics and non-diabetics with acute coronary syndrome.
Patients with acute coronary syndrome (n=1957) were followed up prospectively for 45 months. Patients were stratified into quartile groups defined by admission plasma glucose and hyperglycaemia was defined as plasma glucose of >9.4 mmol/l, which was the cut-off value for the 4th quartile. The relationship between admission hyperglycaemia and short-term (< or =30 day) and late (>30 day) mortality was analysed.
Of 1957 patients, 22% had a history of diabetes. Among patients without diabetes, those with hyperglycaemia had both a higher 30-day mortality rate (20.2% vs. 3.5%, p<0.0001) and late mortality rate (19.1% vs. 11.7%, p=0.007). Hyperglycaemic patients with diabetes had a higher late mortality rate than diabetic patients with plasma glucose of < or =9.4 mmol/l (29.3% vs. 14.9%, p=0.001). Of patients with hyperglycaemia at admission, those without diabetes had a higher 30-day mortality rate compared with those with diabetes (p=0.002).
Admission hyperglycaemia is a strong risk factor for mortality in patients with acute coronary syndrome and may be even stronger than a previous history of diabetes. Hyperglycaemic patients without recognised diabetes have a higher short-term mortality risk than hyperglycaemic patients with known diabetes.