Proinflammatory HLA-DRB1*01-haplotype predisposes to ST-elevation myocardial infarction

BackgroundMajor histocompatibility complex (MHC) gene region harbours haplotypes that associate with coronary artery disease (CAD). Their role in ST-elevation infarction (STEMI) or on the inflammatory level is not known.MethodsFour candidate MHC markers were analyzed by real-time quantitative PCR and constructed into haplotypes from patients with STEMI (n = 162), matched controls with no CAD (n = 319) and general population sample (n = 149). High sensitivity C-reactive protein (hsCRP) was assessed in a follow-up visit from patients (n = 86) and at inclusion from other study subjects.ResultsThe haplotype with one copy of HLA-DRB1*01, C4A, C4B but no HLA-B*35 doubled the risk of STEMI (OR = 2.15, 95%CI = 1.11–4.15, p = 0.020 for patients vs. controls, and OR = 2.26, 95%CI = 0.97–5.24, p = 0.052 for patients vs. population sample). The association between patients and controls persisted in multivariate analyses. The frequency of the haplotype was 5.86% (n = 19/324) in patients, 2.82% (n = 18/638) in controls and 2.68% (n = 8/298) in population sample. None of the individual MHC markers alone showed significant association with STEMI.In multivariate analyses, the haplotype carriers had higher hsCRP levels in patients (median 3.37 mg/L in carriers vs. 1.14 mg/L in non-carriers, p = 0.019) and in controls (median 2.90 mg/L vs. 1.21 mg/L, p = 0.009, respectively).ConclusionThe MHC haplotype associates with STEMI and elevated baseline hsCRP levels. The results are in concordance with previous data on non-STEMI patients, implying that a HLA-DRB1*01 – related haplotype increases the risk of CAD, possibly though increased inflammation.     

Contrasting Hemodynamic Mechanisms of Losartan- vs. Atenolol-Based Antihypertensive Treatment: A LIFE Study

BackgroundPharmaceutical differences in central hemodynamics might influence cardiac response to antihypertensive treatment despite similar lowering of brachial blood pressure (BP).MethodsData from all patients with at least two echocardiographic examinations in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) echocardiographic substudy (n = 801); high-risk patients on losartan- vs. atenolol-based antihypertensive therapy. Echocardiography was performed annually for 4 years to measure stroke index (SI), heart rate, cardiac index (CI), conduit artery stiffness assessed as pulse pressure/stroke index (PP/SI) and total peripheral resistance index (TPRI).ResultsAtenolol- and losartan-based therapy reduced BP similarly (cumulative difference in mean brachial blood pressure 0.3 mm Hg, P = 0.65). After 4 years the cumulative means of SI and heart rate were 1.8 ml/m(2) higher and 5.7 beats/min lower on atenolol-based treatment, respectively (both P < 0.001). This kept CI below baseline in atenolol-treated patients, whereas in the losartan group CI was unchanged from baseline throughout the study. TPRI was decreased more and remained lower in the losartan group (cumulative difference in mean TPRI 287 dynes/sec(-5)/cm/m(2), P < 0.001). These findings partly explained univariate differences in systolic- and diastolic function indices between the two treatments; fully adjusted losartan was only associated with a smaller left atrial diameter (cumulative mean difference 0.07 cm; 95% confidence intervals, -0.13 to -0.01, P = 0.03).ConclusionsContrasting hemodynamics impacted cardiac response to similar reductions in brachial BP on losartan- vs. atenolol-based therapy. The similar reduction of PP/SI suggests that the antihypertensive regimens used in the LIFE study had comparable effects on arterial stiffness (LIFE study; NCT00338260)American Journal of Hypertension, (2012); doi:10.1038/ajh.2012.81.     

Influence of physical activity on vertebral strength during late adolescence

Background contextReduced vertebral strength is a clear risk factor for vertebral fractures. Men and women with vertebral fractures often have reduced vertebral size and bone mineral density (BMD). Vertebral strength is controlled by both genetic and developmental factors. Malnutrition and low levels of physical activity are commonly considered to result in reduced bone size during growth. Several studies have also demonstrated the general relationship between BMD and physical activity in the appendicular skeleton.PurposeIn this study, we wanted to clarify the role of physical activity on vertebral bodies. Vertebral dimensions appear to generally be less pliant than long bones when lifetime changes occur. We wanted to explore the association between physical activity during late adolescence and vertebral strength parameters such as cross-sectional size and BMD.Study designThe association between physical activity and vertebral strength was explored by measuring vertebral strength parameters and defining the level of physical activity during adolescence.Patient sampleThe study population consisted of 6,928 males and females who, at 15 to 16 and 19 years of age, responded to a mailed questionnaire inquiring about their physical activity. A total of 558 individuals at the mean age of 21 years underwent magnetic resonance imaging (MRI) scans.MethodsWe measured the dimensions of the fourth lumbar vertebra from the MRI scans of the Northern Finland Birth Cohort 1986 and performed T2* relaxation time mapping, reflective of BMD. Vertebral strength was based on these two parameters. We analyzed the association of physical activity on vertebral strength using the analysis of variance.Results and conclusionsWe observed no association between the level of physical activity during late adolescence and vertebral strength at 21 years.     

Cholesterol Efflux Capacity In Vitro Predicts the Severity and Extent of Coronary Artery Disease in Patients with and without Type 2 Diabetes

Objective - To investigate the relation between severity and extent of coronary artery disease (CAD) and in vitro cholesterol efflux capacity. Design - This study consisted of 46 type 2 diabetic, and 42 nondiabetic men undergoing coronary angiography. Quantitative coronary angiography was used to estimate the severity, extent, and overall "atheroma burden" of CAD. The capacity of patient plasma to induce cholesterol efflux from cultured Fu5AH rat hepatoma cells was measured in vitro. Results - In the combined study population (n = 88), there was a significant inverse correlation between efflux and global atheroma burden (r = -0.23, p &lt; 0.05). In the diabetic group, the global atheroma burden index was independently associated both with cholesterol efflux and with LpA-I levels. However, in the nondiabetic CAD group this association was lost when efflux and LpA-I levels were included in the same model. Conclusion - The present study demonstrated that efflux capacity was inversely associated with the severity and extent of CAD. In the diabetic group this association was independent of LpA-I levels, suggesting impaired antiatherogenic potential of these particles in type 2 diabetic patients.     

Predictors of mortality following primary hip and knee replacement in the aged: A single-center analysis of 1,998 primary hip and knee replacements for primary osteoarthritis

Background and purpose High age is associated with increased postoperative mortality, but the factors that predict mortality in older hip and knee replacement recipients are not known.

Methods Preoperative clinical and operative data on 1,998 primary total hip and knee replacements performed for osteoarthritis in patients aged ≥ 75 years in a single institution were collected from a joint replacement database and compoared with mortality data. Average follow-up was 4.2 (2.2–7.6) years for the patients who survived. Factors associated with mortality were analyzed using Cox regression analysis, with adjustment for age, sex, operated joint, laterality, and anesthesiological risk score.

Results Mortality was 0.15% at 30 days, 0.35% at 90 days, 1.60% at 1 year, 7.6% at 3 years, and 16% at 5 years, and was similar following hip and knee replacement. Higher age, male sex, American Society of Anesthesiologists risk score of > 2, use of walking aids, preoperative walking restriction (inability to walk or ability to walk indoors only, compared to ability to walk > 1 km), poor clinical condition preoperatively (based on clinical hip and knee scores or clinical severity of osteoarthritis), preoperative anemia, severe renal insufficiency, and use of blood transfusions were associated with higher mortality. High body mass index had a protective effect in patients after hip replacement.

Interpretation Postoperative mortality is low in healthy old joint replacement recipients. Comorbidities and functional limitations preoperatively are associated with higher mortality and warrant careful consideration before proceeding with joint replacement surgery.     

Oxidative stress in schizophrenia patients treated with long-acting haloperidol decanoate

In this study the role of oxidative stress in schizophrenia was investigated by evaluating the relationship of oxidative stress markers with neurochemistry, psychopathology, and extrapyramidal symptoms. Antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and concentrations of malondialdehyde, protein carbonyls, nitrite, nitrate, glutathione, dopamine, noradrenaline, adrenaline, and serotonin were measured in 52 outpatients with DSM-IV diagnosis of schizophrenia treated with haloperidol decanoate. Psychopathology and extrapyramidal symptoms were assessed by positive and negative syndrome scale, global assessment of functioning, abnormal involuntary movement scale, Simpson Angus scale, and Barnes akathisia rating scale. Haloperidol dose was positively correlated with plasma protein carbonyls. Longer duration of illness was associated with decreased levels of glutathione peroxidase. Increased activity of superoxide dismutase was associated with increased levels of catalase, glutathione peroxidase, glutathione reductase and reduced glutathione, and decreased concentration of malondialdehyde, indicating joint action of various antioxidative systems. Increased levels of nitrite and noradrenaline were associated with decreased level of malondialdehyde. Akathisia was greater in patients with decreased catalase activity, indicating involvement of impaired antioxidant defense in developing extrapyramidal symptoms. These results confirm the hypothesis that oxidative stress is involved in pathophysiology of schizophrenia and severity of extrapyramidal symptoms.     

The joint contribution of physical activity,insomnia symptoms,and smoking to the cost of short‐term sickness absence

Physical inactivity has been associated with both insomnia symptoms and smoking. Further, they are all independently associated with increased sickness absence (SA) from work. However, joint contribution of either physical activity (PA) with insomnia symptoms or with smoking to SA and, especially, their direct cost for the employer is poorly understood. Therefore, we aimed to examine these joint associations with short‐term (<15 days) SA cost. The Helsinki Health Study is a cohort of midlife employees of the City of Helsinki, Finland (baseline n = 8960, response rate 67%). During 2000‐2002, the participants were mailed a survey questionnaire that gathered information on health behavior and sociodemographic characteristics. SA, salary, and time of employment were followed up through the employer's personnel register between 2002 and 2016 for those with a written consent to the use of their register data (78% of the participants). Individual salary data were used to calculate the direct cost of short‐term SA. Data were analyzed with a two‐part model. Inactive participants with frequent insomnia symptoms had 2526€ (95% CI 1736€‐3915€) higher cost of short‐term SA than vigorously active participants without insomnia symptoms. Furthermore, inactive smokers had 4166€ (95% CI 2737€‐5595€) higher cost for the employer over the follow‐up than vigorously active non‐smokers. In conclusion, this study showed that PA and insomnia symptoms as well as PA and smoking are jointly associated with short‐term SA cost. The results emphasize encouraging employers to improve work environments so that they promote active lifestyle, good sleep, and non‐smoking in order to reduce the cost of SA.