Outcome of a psychosocial health promotion intervention aimed at improving physical health and reducing alcohol use in patients with schizophrenia and psychotic disorders (MINT).

BACKGROUND: Life expectancy is reduced by 19 years in men and 17 in women with psychosis in Sweden, largely due to cardiovascular disease. AIM: Assess whether a psychosocial health promotion intervention improves cardiometabolic risk factors, quality of life, and severity of illness in patients with psychotic disorders more than treatment as usual. METHODS: A pragmatic intervention trial testing a manual-based multi-component health promotion intervention targeting patients with psychosis. The Swedish intervention was adapted from IMPaCT therapy, a health-promotion program based on motivational interviewing and cognitive behavioral therapy, designed to be incorporated into routine care. The intervention group consisted of 119 patients and the control group of 570 patients from specialized psychosis departments. Outcome variables were assessed 6 months before intervention during the run-in period, again at the start of intervention, and 12 months after the intervention began. The control group received treatment as usual. RESULTS: The intervention had no significant effect on any of the outcome variables. However, BMI, waist circumference, systolic BP, heart rate, HbA1c, general health, and Clinical Global Impressions Scale score improved significantly during the run-in period before the start of the active intervention (observer effect). The multi-component design meant that treatment effects could only be calculated for the intervention as a whole. CONCLUSION: The results of the intervention are similar to those of the U.K. IMPaCT study, in which the modular health-promotion intervention had little effect on cardiovascular risk indicators. However, in the current study, the run-in period had a positive effect on cardiometabolic risk factors.

Troponin T levels associated with genetic variants in NOTCH2 and MTNR1B in women with psychosis.

Psychosis patients have increased prevalence of metabolic disorders, which increase the risk for cardiovascular disease. Elevated troponin T level is an early biomarker of cardiovascular damage. We tested for association between troponin T levels and genetic risk variants of elevated blood glucose level in psychosis. Glucose and troponin T levels correlated positively. MTNR1B rs10830963 and NOTCH2 rs10923931 associated with troponin T levels in women, adjusted for glucose levels. These findings may indicate metabolic genetic influences on troponin T levels among women with psychosis.

Diabetes and glucose disturbances in patients with psychosis in Sweden.

OBJECTIVE: The objectives of this study were to (1) analyze the prevalence of diabetes, prediabetes, and antidiabetic medication in patients with psychosis compared with control subjects and (2) determine what factors in patients with psychosis were associated with antidiabetic medication. METHOD: We studied 977 patients with psychosis recruited from outpatient clinics in Stockholm County, Sweden, and they were compared with 3908 non-psychotic control subjects for fasting plasma glucose levels; prevalence of diabetes, prediabetes, antidiabetic treatment, and tobacco use; and blood pressure, weight, height, and waist circumference. Group differences were evaluated with analysis of variance and χ(2) test, and factors associated with antidiabetic treatment were evaluated with logistic regression. RESULTS: Diabetes was observed in 94 (10%) patients with psychosis, 2.7 times the prevalence observed in control subjects. Among patients with psychosis, 87 (10%) had prediabetes (fasting glucose, 6.1-6.9 mmol/L) compared with 149 (3.8%) control subjects. Most patients with psychosis (77%) who had prediabetes fulfilled criteria for metabolic syndrome. In patients with psychosis, both lipid-lowering medication and fasting glucose were significantly associated with antidiabetic treatment. There was no significant relation between antidiabetic treatment and lifestyle factors such as smoking or degree of psychiatric illness. CONCLUSIONS: The high prevalence of impaired fasting glucose and metabolic syndrome in patients with psychosis warrants further clinical research in preventing or delaying the onset of diabetes in these patients by pharmacotherapy and/or lifestyle intervention.

Genetic and Clinical Factors Affecting Plasma Clozapine Concentration.

OBJECTIVE: To assess (1) the variance of plasma clozapine levels; (2) the relative importance of sex, smoking habits, weight, age, and specific genetic variants of cytochrome P450 1A2 (CYP1A2), uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4), and multidrug resistance protein 1 (MDR1) on plasma levels of clozapine; and (3) the relation between plasma clozapine levels, fasting glucose levels, and waist circumference. METHOD: There were 113 patients on clozapine treatment recruited from psychosis outpatient clinics in Stockholm County, Sweden. Patients had genotype testing for single nucleotide polymorphisms: 2 in MDR1, 3 in CYP1A2, and 1 in UGT1A4. Multiple and logistic regression were used to analyze the relations. RESULTS: There was a wide variation in plasma concentrations of clozapine (mean = 1,615 nmol/L, SD = 1,354 nmol/L), with 37% of the samples within therapeutic range (1,100-2,100 nmol/L). Smokers had significantly lower plasma clozapine concentrations than nonsmokers (P ≤ .03). There was a significant association between the rs762551 A allele of CYP1A2 and lower plasma clozapine concentration (P ≤ .05). Increased fasting glucose level was 3.7-fold more frequent in CC and CA genotypes than AA genotype (odds ratio = 0.27; 95% confidence interval, 0.10-0.72). There was no significant relation between higher fasting glucose levels, larger waist circumference, and higher clozapine levels. CONCLUSIONS: It is difficult to predict plasma clozapine concentration, even when known individual and genetic factors are considered. Therefore, therapeutic drug monitoring is recommended in patients who are treated with clozapine.

Psychotic disorder is an independent risk factor for increased fasting glucose and waist circumference.

BACKGROUND: Psychosis is associated with excess cardiovascular morbidity and mortality. AIMS: To determine the prevalence of cardiovascular risk factors in patients with psychotic disorders compared with the population. METHODS: 731 consecutive patients with psychosis recruited from psychiatric outpatient clinics in Stockholm County, Sweden, were compared with 5580 individuals from a population study performed in the same area. The main outcome measures were waist circumference, body mass index (BMI) and fasting glucose. RESULTS: Mean waist circumference in patients vs. controls was for males 106 and 94 cm, respectively, and for females 97 and 85 cm, respectively (P < 0.001); mean fasting glucose in patients vs. controls was for males 5.8 and 5.2 mmol/l, respectively, and for females 5.6 and 4.8 mmol/l, respectively (P < 0.001). Comparisons were controlled for differences in age and family history of diabetes. Increased waist circumference was more common in psychotic patients compared with controls (OR = 3.99; 95% CI 3.09-5.15), controlling for fasting insulin, differences in gender, blood pressure, fasting glucose, family history of diabetes, age and tobacco use. Increased fasting blood glucose was also more common in psychotic patients (OR = 2.41; 95% CI 1.84-3.14) controlling for the same factors with the exception of fasting glucose and with the addition of increased waist circumference. CONCLUSION: Our study shows that the psychosis illness per se can be considered as a cardiovascular risk factor, independent of the traditional risk factors such as age and smoking.

Risk prediction in stable angina pectoris.

BACKGROUND: Although stable angina pectoris often carries a favourable prognosis, it remains important to identify patients with an increased risk of cardiovascular (CV) complications. Many new markers of disease activity and prognosis have been described. We evaluated whether common and easily accessible markers in everyday care provide sufficient prognostic information. MATERIALS AND METHODS: The Angina Pectoris Prognosis Study in Stockholm treated 809 patients (248 women) with stable angina pectoris with metoprolol or verapamil double blind during a median follow-up of 3·4 years, with a registry-based extended follow-up after 9·1 years. Clinical and mechanistic variables, including lipids and glucose, renal function, ambulatory and exercise-induced ischaemia, heart rate variability, cardiac and vascular ultrasonography, and psychosocial variables were included in an integrated analysis. Main outcome measures were nonfatal myocardial infarction (MI) and CV death combined. RESULTS: In all, 139 patients (18 women) suffered a main outcome. Independent predictive variables were (odds ratio [95% confidence intervals]), age (1·04 per year [1·00;1·08], P = 0·041), female sex (0·33 [0·16;0·69], P = 0·001), fasting blood glucose (1.29 per mM [1.14; 1.46], P < 0·001), serum creatinine (1·02 per µM [1·00;1·03], P < 0·001) and leucocyte counts (1·21 per 10(6)  cells/L [1·06;1·40], P = 0·008). Smoking habits, lipids and hypertension or a previous MI provided limited additional information. Impaired fasting glucose was as predictive as manifest diabetes and interacted adversely with serum creatinine. Sexual problems were predictive among men. CONCLUSIONS: Easily accessible clinical and demographic variables provide a good risk prediction in stable angina pectoris. Impaired glucose tolerance and an elevated serum creatinine are particularly important.

Vectorcardiography risk stratifies emergency department chest pain patients with left ventricular hypertrophy on the initial 12-lead ECG.

BACKGROUND: Vectorcardiographic (VCG) measurements of ST-vector magnitude (VM) and QRS-vector difference (VD) have been demonstrated to be independent predictors of adverse outcome (AO) and acute myocardial infarction (AMI) in emergency department (ED) chest pain patients with absence of bundle branch block or left ventricular hypertrophy (LVH) on the initial 12-lead electrocardiogram (ECG). The prognostic value of ST-VM and QRS-VD in ED chest pain patients with LVH on the initial 12-lead ECG has not been previously investigated. METHODS: A prospective observational study was performed in 196 consecutive ED chest pain patients with suspected AMI and presence of voltage criteria for LVH on initial ECG who underwent continuous VCG monitoring during the initial evaluation. The optimal baseline ST-VM value and 2-hour QRS-VD value were defined as the most accurate value on the receiver operator characteristic curve (value with lowest false-negative and false-positive rate). Thirty-day AO was defined as AMI, percutaneous coronary intervention, coronary artery bypass grafting (CABG), or cardiac death occurring within 30 days of initial ED visit. RESULTS: Fourteen patients (7.1%) were diagnosed as 24-hour AMI and 28 patients (14.3%) experienced 30-day AO. The optimal cut-off value for predicting 30-day AO was > 124 microV for ST-VM and > 21.7 microV for QRS-VD. Patients with either a positive ST-VM or a positive QRS-VD had 8.8 times increased odds of AMI (95% confidence interval, CI, 1.9-40.3; P = 0.003); 4.3 times increased odds of 30-day PTCA/CABG (95% CI 1.3-13.8; P = 0.019); and 3.8 times increased odds of 30-day AO (95% CI 1.6-9.3; P = 0.003). CONCLUSIONS: Baseline ST-VM and 2-hour QRS-VD risk stratifies ED chest pain patients with LVH voltage criteria on the initial 12-lead ECG.

Use of baseline ST-vector magnitude to identify electrocardiographic injury in patients with suspected acute myocardial infarction.

No information is currently available regarding optimal cut-off values of the ST-vector magnitude (ST-VM) for predicting acute myocardial infarction (AMI) in emergency department (ED) chest pain patients undergoing vectorcardiographic (VCG) monitoring. A prospective observational study was performed in 1,722 chest pain patients with suspected acute coronary syndrome and absence of bundle branch block (BBB) and left ventricular hypertrophy (LVH) on initial ECG who underwent continuous VCG ST-segment monitoring during the initial ED evaluation. Three cut-off values for baseline ST-VM are reported and represent the smallest values in which the positive likelihood ratio (+LR) for AMI is greater than 5, 10, and 20, respectively. AMI occurred in 158 of 1,722 patients (9.2%) without BBB or LVH on initial ECG. Optimal cut-off values at the predetermined +LR values of 5, 10, and 20, were 121 microV (sensitivity, 41.8%; specificity, 92.0%), 151 microV (sensitivity, 29.1%; specificity, 97.1%), and 175 microV (sensitivity, 25.9%; specificity, 98.7%), respectively. Combining the earlier-mentioned cut-off values with physician judgment of initial pretest probability (high, intermediate, or low, respectively) resulted in a relative increase in identification of injury of 37.5% as compared with the ED physician's interpretation of initial ECG (41.8% v 30.4%; P <.0001), and 65.2% as compared with the official ECG interpretation (41.8% v 25.3%; P <.0001). Increasing ST-VM results in increasing likelihood of AMI. Clinical studies need to be performed to determine if ST-VM cut-off values of 121, 151, and 175 microV in conjunction with physician pretest probability of AMI can be used as criterion for emergent reperfusion therapy in patients without LVH or BBB on the initial ECG.

Neurohormonal activation in heart failure after acute myocardial infarction treated with beta-receptor antagonists.

BACKGROUND: Few studies have described how neurohormonal activation is influenced by treatment with beta-receptor antagonists in patients with heart failure after acute myocardial infarction. The aims were to describe neurohormonal activity in relation to other variables and to investigate treatment effects of a beta(1) receptor-antagonist compared to a partial beta(1) receptor-agonist. METHODS: Double-blind, randomized comparison of metoprolol 50-100 mg b.i.d. (n=74), and xamoterol 100-200 mg b.i.d (n=67). Catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), renin activity, and N-terminal pro-atrial natriuretic factor (N-ANF) were measured in venous plasma before discharge and after 3 months. Clinical and echocardiographic variables were assessed. RESULTS: N-ANF showed the closest correlations to clinical and echocardiographic measures of heart failure severity, e.g. NYHA functional class, furosemide dose, exercise tolerance, systolic and diastolic function. Plasma norepinephrine, dopamine and renin activity decreased after 3 months on both treatments, in contrast to a small increase in NPY-LI which was greater (by 3.9 pmol/l, 95% CI 1.2-6.6) in the metoprolol group. N-ANF increased on metoprolol, and decreased on xamoterol (difference: 408 pmol/l, 95% CI 209-607). Increase above median of NPY-LI (>25.2 pmol/l, odds ratio 2.8, P=0.0050) and N-ANF (>1043 pmol/l, odds ratio 2.8, P=0.0055) were related to long term (mean follow-up 6.8 years) cardiovascular mortality. CONCLUSIONS: Decreased neurohormonal activity, reflecting both the sympathetic nervous system and the renin-angiotensin system, was found 3 months after an acute myocardial infarction with heart failure treated with beta-receptor antagonists. The small increase in NPY-LI may suggest increased sympathetic activity or reduced clearance from plasma. The observed changes of N-ANF may be explained by changes in cardiac preload, renal function, and differences in beta-receptor mediated inhibition of atrial release of N-ANF. NPY-LI, and N-ANF at discharge were related to long term cardiovascular mortality.