Gamma-glutamyl transferase and cardiovascular events in patients with congenital heart disease.

INTRODUCTION: Serum gamma-glutamyl transferase activity (GGT) seems to predict cardiovascular events in different populations. However, no data exist on patients with congenital heart disease (CHD). METHODS: Observational, analytic, prospective cohort study design involving CHD patients and a control population to determine the effect of GGT levels on survival. RESULTS: A total of 589 CHD patients (58% males, 29 ± 14 years old) and 2745 matched control patients were followed up. A total of 69 (12%) CHD patients had a major acute cardiovascular event (MACE) during the follow-up time (6.1 [0.7-10.4] years). Patients with CHD and a GGT >60 U/L were significantly older, more hypertensive and dyslipidemic, had a worse NYHA functional class and a greater anatomical complexity than CHD patients with a GGT ≤60 U/L. The binary logistic regression analysis showed that age, a great CHD anatomical complexity, and having atrial fibrillation/flutter were the predictive factors of higher GGT levels (>60 U/L). The Kaplan-Meier analysis showed that patients with CHD and a GGT concentration above 60 UL showed the lowest probability of survival compared to that of CHD with GGT ≤60 U/L and controls irrespective of their GGT concentrations (p < .001). Similarly, the multivariable Cox regression analysis found an independent association between higher GGT levels (>60 U/L) and a worse prognosis (HR 2.44 [1.34-4.44], p = .003) among patients with CHD. CONCLUSION: Patients with CHD showed significant higher GGT levels than patients in the control group having those with higher GGT concentrations (>60 U/L) the worst survival.

Cardiovascular risk factors and arterial thrombotic events in congenital heart disease patients.

INTRODUCTION: As congenital patients get older, it can be hypothesised that cardiovascular risk factors increase. METHODS: Retrospective study of congenital heart disease (CHD) patients attended between January 2008 and September 2018. Cardiovascular risk factors, myocardial infarction, stroke, peripheral vascular disease, and analytical data such as serum glucose and lipid profile were determined. RESULTS: Eight hundred and eighteen CHD patients and 1955 control patients matched for age and sex were studied. CHD patients were distributed in simple (462 patients), moderate (228 patients) and great (128 patients) complexity. Median age in CHD patients was 33 (25-41) years old and 56% were male. CHD patients were significantly more hypertensive and diabetic but less dyslipidemic and smokers than patients in the control group. Twenty-seven (3.3%) CHD patients had an arterial thrombotic event: 3 coronary, 22 neurological and 2 peripheral vascular disease. No significant differences were seen in the incidence of myocardial infarction between the control and the CHD groups. However CHD patients had a significant higher incidence of arterial thrombotic events (coronary, neurological and peripheral vascular events) at the expense of strokes and transient ischaemic attacks (22 vs 2 events in CHD and control patients, respectively). Also, no significant differences were seen in age, sex, BMI, arterial hypertension, diabetes mellitus, dyslipidemia, smoking habit, serum glucose, total and LDL cholesterol, statin treatment, myocardial infarction and arterial thrombotic events according to CHD complexity. Being older and having arterial hypertension, diabetes mellitus, dyslipidemia and smoking habit were more frequent among CHD patients with arterial thrombosis. CONCLUSIONS: Congenital heart diseases are more hypertensive and diabetic but less dyslipemic and smokers than patients in the control group. CHD patients have a higher incidence of neurological events but not of myocardial infarction in relation to the control population.

Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke.

Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541-18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke.

Total antioxidant capacity is associated with mortality of patients with severe traumatic brain injury.

BACKGROUND: Previously, circulating total antioxidant capacity (TAC) in traumatic brain injury (TBI) patients has been scarcely studied and only in studies of small sample size (lower than 55 TBI patients). In one study were found higher serum TAC in non-survivor than in survivor TBI patients; however, an association between circulating TAC and mortality in patients with TBI has not been previously reported. Thus, the objective of this study was to determine whether there is an association between circulating TAC, peroxidation state and mortality in patients with severe TBI. METHODS: This was a multicenter, observational and prospective study was carried out in six Spanish Intensive Care Units. We included patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than 9. We excluded patients with Injury Severity Score (ISS) in non-cranial aspects higher than 9. We measured serum TAC on day 1 of TBI. The 30-day mortality was established as endpoint. RESULTS: Non-surviving TBI patients (N = 27) showed higher serum TAC (P < 0.001) than survivor ones (N = 73). Logistic regression analyses showed that serum TAC higher than 2.59 nmol/mL were associated with 30-day mortality controlling for APACHE-II and CT classification (OR = 4.40; 95% CI = 1.14-16.98; P = 0.03), controlling for GCS and age (OR = 5.88; 95% CI = 1.57-22.06; P = 0.009), and controlling for CT classification and admission abnormal pupils (OR = 3.89; 95% CI = 1.30-11.61; P = 0.02). There was an association between serum TAC and malondialdehyde (a biomarker of lipid peroxidation) levels (rho = 0.25; p = 0.01), APACHE-II score (rho = 0.23; p = 0.03) and GCS (rho = -0.21; p = 0.04). CONCLUSIONS: To our knowledge, our series is the largest reporting data on circulating TAC in patients with severe TBI. The most relevant and new findings of our study were that there is an association between circulating TAC and peroxidation state and mortality in patients with severe TBI.

Serum caspase-3 levels and mortality are associated in patients with severe traumatic brain injury.

BACKGROUND: Different apoptosis pathways activate caspase-3. In a study involving 27 patients with traumatic brain injury (TBI), higher caspase-3 levels were found in contusion brain tissue resected from non-survivors than from survivors. The objective of this study was to determine whether there is an association in TBI patients between serum caspase-3 levels (thus using an easier, quicker, less expensive and less invasive procedure) and mortality, in a larger series of patients. METHODS: We carried out a prospective, observational and multicenter study in six Spanish Hospital Intensive Care Units including 112 patients with severe TBI. All had Glasgow Coma Scale (GCS) scores lower than 9. Patients with an Injury Severity Score (ISS) in non-cranial aspects higher than 9 were excluded. Blood samples were collected on day 1 of TBI to measure serum caspas-3 levels. The endpoint was 30-day mortality. RESULTS: We found that non-surviving patients (n = 31) showed higher (p = 0.003) serum caspase-3 levels compared to survivors (n = 81). Kaplan-Meier survival analysis showed a higher risk of death in TBI patients with serum caspase-3 levels >0.20 ng/mL than in patients with lower concentrations (Hazard Ratio = 3.15; 95% CI = 1.40 to 7.08; P < 0.001). Multiple logistic regression analysis showed that serum caspase-3 levels > 0.20 ng/mL were associated with mortality at 30 days in TBI patients controlling for Marshall CT classification, age and GCS (Odds ratio = 7.99; 95% CI = 2.116 to 36.744; P = 0.001). CONCLUSIONS: The association between serum caspase-3 levels and mortality in TBI patients was the major novel finding of our study.

Association between red blood cell distribution width and mortality of COVID-19 patients.

PURPOSE: We have previously reported an association between high red blood cell distribution width (RDW) and mortality in septic and brain infarction patients. However, no association between RDW and mortality in coronavirus disease 2019 (COVID-19) patients has been reported so far; thus, the objective of this study was to determine if that association exists. METHODS: Prospective and observational study carried out in 8 Intensive Care Units from 6 hospitals of Canary Islands (Spain) including COVID-19 patients. We recorded RDW at ICU admission and 30-day survival. RESULTS: We found that patients who did not survive (n=25) compared to surviving patients (n=118) were older (p=0.004), showed higher RDW (p=0.001), urea (p<0.001), APACHE-II (p<0.001) and SOFA (p<0.001), and lower platelet count (p=0.007) and pH (p=0.008). Multiple binomial logistic regression analysis showed that RDW was associated with 30-day mortality after controlling for: SOFA and age (OR=1.659; 95% CI=1.130-2.434; p=0.01); APACHE-II and platelet count (OR=2.062; 95% CI=1.359-3.129; p=0.001); and pH and urea (OR=1.797; 95% CI=1.250-2.582; p=0.002). The area under the curve (AUC) of RDW for mortality prediction was of 71% (95% CI=63-78%; p<0.001). We did not find significant differences in the predictive capacity between RDW and SOFA (p=0.66) or between RDW and APACHE-II (p=0.12). CONCLUSIONS: Our study provides new information regarding the ability to predict mortality in patients with COVID-19. There is an association between high RDW and mortality. RDW has a good performance to predict 30-day mortality, similar to other severity scores (such as APACHE II and SOFA) but easier and faster to obtain.

Red blood cell distribution width in addition to N-terminal prohormone of B-type natriuretic peptide concentration improves assessment of risk of cardiovascular events in adult patients with congenital heart disease.

BACKGROUND: Red blood cell distribution width (RDW) is a predictor of adverse outcomes in patients with heart disease. AIM: To establish predictors of high RDW values in patients with congenital heart disease (CHD), and their relationship with cardiovascular events. METHODS: Overall, 561 patients with stable CHD who attended a single outpatient clinic and a matched control population of 2128 patients were studied. Exclusion criteria were renal failure, anaemia, receiving iron therapy and cyanosis. Blood tests included glucose, creatinine, iron, apoferritin, liver enzymes and a complete blood count. C-reactive protein and N-terminal prohormone of B-type natriuretic peptide (NT-pro-BNP) concentrations were also measured in patients with CHD. Major adverse cardiac events (MACE) were defined as cardiovascular/total mortality, arterial thrombotic events, arrhythmias, major bleedings, pulmonary embolism or heart failure needing hospital admission. RESULTS: The median age in patients with CHD was 23 (17-36) years and the median follow-up time was 5.8 (3.2-8.7) years; 103 (4.8%) controls and 40 (7.1%) patients with CHD had an RDW>15% (P=0.032). During follow-up, MACE were reported in 48 patients. CHD of great complexity, cardiovascular risk factors, low haemoglobin concentration and high NT-pro-BNP concentration were risk factors for an RDW>15%. Kaplan-Meier analysis showed a significantly worse cardiovascular outcome in patients with CHD with an RDW>15% (P<0.001). The multivariable survival analysis determined that age, CHD of great complexity, high NT-pro-BNP concentration and an RDW>15% were independent predictive factors for MACE. CONCLUSION: RDW and NT-pro-BNP concentration are independent analytical predictors of MACE in patients with CHD.

Mean platelet volume and major adverse cardiovascular events in congenital heart disease patients.

BACKGROUND: Platelet activation is linked with thrombosis, inflammation or heart failure. OBJECTIVE: To establish clinical and analytical factors that may favor high mean platelet volume (MPV) and to determine if MPV levels favor major adverse cardiovascular events (MACE). METHODS: Stable CHD patients and a control population matched for age, sex and cardiovascular factors. RESULTS: 658 CHD patients and 2092 controls were studied. Median age in CHD patients was 33 (25-41) year old with 56% of them being male. No significant differences were seen between MPV values and cardiac complexity (p = 0.308) nor between MPV values in the CHD and control groups (p = 0.911). CHD patients had significant lower platelet count and MPV levels than patients in the control group. In the binary logistic regression analysis NT-pro-BNP levels above 125 pg/ml, thrombocytopenia and having atrial fibrillation/flutter reached statistical significance as predictors of MPV levels above 11 fL. The Kaplan-Meier survival analysis showed no significance between MPV levels higher than 11 fL and MACE, cardiovascular mortality and thrombotic events in a median time follow-up of 6.7(1.5-10.6) years. CONCLUSIONS: Atrial fibrillation/flutter, heart failure and thrombocytopenia are predictors of high MPV levels. A MPV above 11 fL is not associated with MACE at a median follow-up time.

Risk factors for hyperuricemia in congenital heart disease patients and its relation to cardiovascular death.

INTRODUCTION: Hyperuricemia has been associated with cardiovascular risk factors but it remains controversial if uric acid is an independent predictor of cardiac mortality. METHODS: A total of 503 CHD patients (457 nonhypoxemic and 46 hypoxemic) and 772 control patients fulfilled inclusion criteria. Demographic, clinical, and analytical data [serum uric acid and 24h urine uric acid levels, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), and C-reactive-protein (CRP) concentrations] were studied. Survivals curves to determine cardiac death and arterial thrombosis in CHD patients were also examined. RESULTS: Noncyanotic and cyanotic CHD patients had significant higher serum uric acid concentration (5.2 ± 1.5 vs 4.9 ± 1.3mg/dL, P = .007 and 6.7 ± 2.1 vs 4.9 ± 1.3mg/dL, P < .001, respectively) and gout (1% vs 0%, P = .003 and 4% vs 0%, P < .01, respectively) than the control population. Among CHD patients, hyperuricemic patients were significant older and with overweight, used more diuretics, were more cyanotic and had higher serum creatinine, NT-pro-BNP and CRP concentrations than nonhyperuricemic. In the multivariable analysis, the body mass index (BMI) (OR 1.09; 95% CI 1.01-1.18), cyanosis (OR 6.2; 95 CI 1.5-24.6), serum creatinine concentration (OR 49; 95% CI 44-538), and being under diuretic treatment (OR 4.5; 95% CI 1.4-14.5) proved to be risk factors for hyperuricemia in CHD patients. The Kaplan-Meier events free survival curves, during a 5.2 ± 2.7 years follow-up of up time, showed that hyperuricemic CHD patients had significant higher cardiovascular death (P = .002). However, after applying the Cox regression analysis uric acid levels lost its statistical significance. No significant differences were seen in relation to thrombotic events between CHD patients with and without hyperuricemia. CONCLUSIONS: CHD patients, noncyanotic and cyanotic, have higher serum uric acid levels and gout than patients in the general population. BMI, renal insufficiency, cyanosis, and the use of diuretics were risk factor for hyperuricemia among CHD patients.

Serum Malondialdehyde Levels and Mortality in Patients with Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: Oxidative stress has been associated with secondary brain injury after spontaneous intracerebral hemorrhage (SIH). Malondialdehyde (MDA) appears in blood during lipid oxidation. Higher serum MDA levels have been found in patients with SIH than in healthy controls; however, we have not found data indicating an association between elevated serum MDA and early mortality in this population. This was the main objective of our study. METHODS: MDA levels were measured in serum samples obtained from 100 patients at diagnosis of severe SIH (Glasgow Coma Scale score ≤8) and 80 healthy controls. The endpoint of the study was mortality at 30 days. RESULTS: Serum MDA levels were significantly higher in patients with severe SIH than in healthy controls (1.46 [1.18-2.2] vs. 1.11 [0.72-1.51]; P < 0.001), and in nonsurviving (n = 46) than in surviving (n = 54) patients (1.68 [1.23-4.02] vs. 1.37 [0.99-1.92]; P = 0.002). The area under the receiving operating characteristic curve of serum MDA levels to predict 30-day mortality was 0.68 (95% CI, 0.58-0.77; P < 0.001). Serum MDA levels were associated with 30-day mortality (OR, 6.279; 95% CI, 1.940-20.319; P = 0.002). CONCLUSIONS: The most important new finding of our study is that there is an association between serum MDA levels at diagnosis of severe SIH and early mortality.

Serum malondialdehyde levels in patients with malignant middle cerebral artery infarction are associated with mortality.

OBJECTIVE: Malondialdehyde (MDA) is an end-product formed during lipid peroxidation, due to degradation of cellular membrane phospholipids. MDA is released into extracellular space and finally into the blood; it has been used as an effective biomarker of lipid oxidation. High circulating levels of MDA have been previously described in patients with ischemic stoke than in controls, and an association between circulating MDA levels and neurological functional outcome in patients with ischemic stoke. However, an association between serum MDA levels and mortality in patients with ischemic stroke has not been previously reported, and that was the objective of this study. METHODS: Observational, prospective and multicenter study performed in six Intensive Care Units. We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as Glasgow Coma Scale (GCS) lower than 9. We measured serum MDA levels in 50 patients with severe MMCAI at the time of diagnosis and in 100 healthy subjects. Mortality at 30 days was the end point of the study. RESULTS: We found that patients with severe MMCAI showed higher serum MDA levels than healthy subjects (p<0.001). We found higher serum MDA levels (p<0.001) in non-surviving MMCAI patients (n=26) than in survivors (n=24). The area under the curve for prediction of 30-day mortality for serum MDA levels was 0.77 (95% CI = 0.63-0.88; p<0.001). Serum MDA levels >2.27 nmol/mL were associated with 30-day mortality (OR=7.23; 95% CI=1.84-28.73; p=0.005) controlling for GCS and age on multiple binomial logistic regression analysis. CONCLUSIONS: To our knowledge, this is the first study showing that serum malondialdehyde levels in patients with MMCAI are associated with early mortality.

Serum glucose and lipid levels in adult congenital heart disease patients.

Atherosclerosis has been correlated with known cardiovascular risk factors such as serum glucose or lipid levels. Because congenital heart disease patients tend to survive until adulthood, atherosclerosis has also become a matter of concern in these patients. One hundred fifty-eight congenital heart disease patients and 152 patients selected at random from the population were studied and compared to determine serum glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides levels. Both groups had similar socioeconomic status levels and the same environmental influences. Significant differences were seen between congenital heart disease patients and the control group, after sex, age, and body mass index adjustment, in fasting plasma glucose (97.7 [94.2-101.2] vs 86.9 [83.2-90.7], P < .001), total cholesterol (171.5 [165.7-177.3] vs 199.8 [90.7-206.0], P < .001), LDL cholesterol (103.9 [98.8-108.8] vs 123.8 [118.5-129.1], P < .001), and high-density lipoprotein cholesterol (48.1 [46.2-50.0] vs 54.2 [52.1-56.2], P < .001) levels. Nonsignificant differences were seen in triglycerides concentrations. Those patients with ventricular septal defect, coarctation of the aorta, and cyanosis had the lowest total cholesterol and LDL cholesterol concentrations. Congenital heart disease patients have lower plasma cholesterol concentrations and higher serum glucose levels than noncongenital ones.