Inflammatory Markers and Outcomes in Cardiovascular Disease

In a commentary on two new research studies in PLoS Medicine, Leonard Kritharides discusses the role of inflammatory markers in predicting cardiovascular outcomes and patients' responses to treatment

Risk Prediction of Cardiovascular Disease in Type 2 Diabetes: A risk equation from the Swedish National Diabetes Register

OBJECTIVE—Risk prediction models obtained in samples from the general population do not perform well in type 2 diabetic patients. Recently, 5-year risk estimates were proposed as being more accurate than 10-year risk estimates. This study presents a diabetes-specific equation for estimation of the absolute 5-year risk of first incident fatal/nonfatal cardiovascular disease (CVD) in type 2 diabetic patients with use of A1C and clinical characteristics

A latent class model for competing risks

Survival data analysis becomes complex when the proportional hazards assumption is violated at population level or when crude hazard rates are no longer estimators of marginal ones. We develop a Bayesian survival analysis method to deal with these situations, on the basis of assuming that the complexities are induced by latent cohort or disease heterogeneity that is not captured by covariates and that proportional hazards hold at the level of individuals. This leads to a description from which risk-specific marginal hazard rates and survival functions are fully accessible, 'decontaminated' of the effects of informative censoring, and which includes Cox, random effects and latent class models as special cases. Simulated data confirm that our approach can map a cohort's substructure and remove heterogeneity-induced informative censoring effects. Application to data from the Uppsala Longitudinal Study of Adult Men cohort leads to plausible alternative explanations for previous counter-intuitive inferences on prostate cancer. The importance of managing cardiovascular disease as a comorbidity in women diagnosed with breast cancer is suggested on application to data from the Swedish Apolipoprotein Mortality Risk Study. Copyright © 2017 John Wiley & Sons, Ltd

Glycemic Control and Cardiovascular Disease in 7,454 Patients With Type 1 Diabetes: An observational study from the Swedish National Diabetes Register (NDR)

OBJECTIVE - We assessed the association between A1C and cardiovascular diseases (CVDs) in an observational study of patients with type 1 diabetes followed for 5 years. RESEARCH DESIGN AND METHODS - A total of 7,454 patients were studied from the Swedish National Diabetes Register (aged 20-65 years, diabetes duration 1-35 years, followed from 2002 to 2007). RESULTS - Hazard ratios (HRs) for fatal/nonfatal coronary heart disease (CHD) per 1% unit increase in baseline or updated mean A1C at Cox regression analysis were 1.31 and 1.34 and 1.26 and 1.32, respectively, for fatal/nonfatal CVD (all P < 0.001 after adjustment for age, sex, diabetes duration, blood pressure, total and LDL cholesterol, triglycerides, BMI, smoking, and history of CVD). HRs were only slightly lower for CHD (P = 0.002) and CVD (P = 0.002-0.007) after also adjusting for albuminuria. Adjusted 5-year event rates of CHD and CVD increased progressively with higher A1C, ranging from 5 to 12%, as well as when subgrouped by shorter (1-20 years) or longer (21-35 years) duration of diabetes. A group of 4,186 patients with A1C 5-7.9% (mean 7.2) at baseline showed risk reductions of 41% (95% confidence intervals: 15-60) (P = 0.005) for fatal/nonfatal CHD and 37% (12-55) (P = 0.008) for CVD, compared with 3,268 patients with A1C 8-11.9% (mean 9.0), fully adjusted also for albuminuria. CONCLUSIONS - This observational study of patients in modem everyday clinical practice demonstrates progressively increasing risks for CHD and CVD with higher A1C, independently of traditional risk factors, with no J-shaped risk curves. A baseline mean A1C of 7.2% showed considerably reduced risks of CHD and CVD compared with A1C 9.0%, emphasizing A1C as a strong independent risk factor in type 1 diabetes

Hyperglycemia and Stroke Mortality: Comparison between fasting and 2-h glucose criteria

OBJECTIVE—We investigated stroke mortality in individuals in different categories of glycemia and compared hazard ratios (HRs) corresponding to a 1-SD increase in 2-h plasma glucose and fasting plasma glucose (FPG) criteria

Cystatin C, a marker for successful aging and glomerular filtration rate, is not influenced by inflammation

Abstract Background. The plasma level of cystatin C is a better marker than plasma creatinine for successful aging. It has been assumed that the advantage of cystatin C is not only due to it being a better marker for glomerular filtration rate (GFR) than creatinine, but also because an inflammatory state of a patient induces a raised cystatin C level. However, the observations of an association between cystatin C level and inflammation stem from large cohort studies. The present work concerns the cystatin C levels and degree of inflammation in longitudinal studies of individual subjects without inflammation, who undergo elective surgery. Methods. Cystatin C, creatinine, and the inflammatory markers CRP, serum amyloid A (SAA), haptoglobin and orosomucoid were measured in plasma samples from 35 patients the day before elective surgery and subsequently during seven consecutive days. Results. Twenty patients had CRP-levels below 1 mg/L before surgery and low levels of the additional inflammatory markers. Surgery caused marked inflammation with high peak values of CRP and SAA on the second day after the operation. The cystatin C level did not change significantly during the observation period and did not correlate significantly with the level of any of the four inflammatory markers. The creatinine level was significantly reduced on the first postoperative day but reached the preoperative level towards the end of the observation period. Conclusion. The inflammatory status of a patient does not influence the role of cystatin C as a marker of successful aging, nor of GFR

Serum levels of selenium and smoking habits at age 50 influence long term prostate cancer risk; a 34 year ULSAM follow-up

Background: Serum selenium level (s-Se) has been associated with prostate cancer (PrCa) risk. We investigated the relation between s-Se, smoking and non-screening detected PrCa and explored if polymorphisms in two DNA repair genes: OGG1 and MnSOD, influenced any effect of s-Se. Methods: ULSAM, a population based Swedish male cohort (n = 2322) investigated at age 50 for s-Se and s-Se influencing factors: serum cholesterol, erythrocyte sedimentation rate and smoking habits. At age 71 a subcohort, (n = 1005) was genotyped for OGG1 and MnSOD polymorphisms. Results: In a 34-year-follow-up, national registries identified 208 PrCa cases further confirmed in medical records. Participants with s-Se in the upper tertile had a non-significantly lower risk of PrCa. Smokers with s-Se in the two lower tertiles (&lt;= 80 mu g/L) experienced a higher cumulative incidence of PrCa than smokers in the high selenium tertile (Hazard Ratio 2.39; 95% CI: 1.09-5.25). A high tertile selenium level in combination with non-wt rs125701 of the OGG1 gene in combination with smoking status or rs4880 related variation of MnSOD gene appeared to protect from PrCa. Conclusions: S-Se levels and smoking habits influence long-term risk of PrCa. Smoking as a risk factor for PrCa in men with low s-Se is relevant to explore further. Exploratory analyses of variations in OGG1 and MnSOD genes indicate that hypotheses about patterns of exposure to selenium and smoking combined with data on genetic variation in genes involved in DNA repair can be valuable to pursue

Clinical and biochemical prediction of early fatal outcome following hip fracture in the elderly

Hip fracture, a moderate musculoskeletal trauma, is associated with a high postoperative mortality. Most patients are elderly, with comorbid conditions and often with heart disease. The objective of this study was to find out if clinical parameters and analyses of specific muscle enzymes could predict three month postoperative mortality. A total of 302 patients above 75 years of age with hip fracture were consecutively enrolled. Baseline information on age, sex and comorbidity assessed with the American Society of Anesthesiologists (ASA) score was obtained before surgery. Creatine kinase (CK), myocardium-specific creatine kinase (CK-MB) and troponin T (TnT) were analysed from venous blood, collected the day before surgery (−1) and postoperatively, within 24 hours (0) and on days one (+1) and four (+4). The overall three month mortality was 19.5%. Multivariate analyses showed that age, male sex and comorbidity (ASA) correlated with mortality (p = 0.027, p = 0.002, p < 0.001, respectively). Surgery induced a two- to threefold increase of CK and CK-MB but without any correlation with mortality. However, high TnT levels >0.04 μg/l correlated significantly with death (days −1, +1 and +4, p = 0.003, p = 0.005 and p = 0.003, respectively). Multivariate analyses, adjusted for age, sex and ASA category, confirmed this correlation (day +4, p = 0.008). Thus, in elderly patients with comorbidities undergoing hip fracture surgery information on sex, age, ASA category and postoperative laboratory analyses on TnT provide the clinicians with useful information on patients at risk of fatal outcome