Does C-reactive Protein Add Prognostic Value to GRACE Score in Acute Coronary Syndromes?

Background

The incremental prognostic value of plasma levels of C-reactive protein (CRP) in relation to GRACE score has not been established in patients with acute coronary syndrome (ACS) with non-ST segment elevation.

Objective

To test the hypothesis that CRP measurements at admission increases the prognostic value of GRACE score in patients with ACS.

Methods

A total of 290 subjects, consecutively admitted for ACS, with plasma material obtained upon admission CRP measurement using a high-sensitivity method (nephelometry) were studied. Cardiovascular outcomes during hospitalization were defined by the combination of death, nonfatal myocardial infarction or nonfatal refractory angina.

Results

The incidence of cardiovascular events during hospitalization was 15% (18 deaths, 11 myocardial infarctions, 13 angina episodes) with CRP showing C-statistics of 0.60 (95% CI = 0.51-0.70, p = 0.034) in predicting these outcomes. After adjustment for the GRACE score, elevated CRP (defined as the best cutoff point) tended to be associated with hospital events (OR = 1.89, 95% CI = 0.92 to 3.88, p = 0.08). However, the addition of the variable elevated CRP in the GRACE model did not result in significant increase in C-statistics, which ranged from 0.705 to 0.718 (p = 0.46). Similarly, there was no significant reclassification of risk with the addition of CRP in the predictor model (net reclassification = 5.7 %, p = 0.15).

Conclusion

Although CRP is associated with hospital outcomes, this inflammatory marker does not increase the prognostic value of the GRACE score.     

A Comorbidity Index for Mortality Prediction in Chinese Patients with ESRD Receiving Hemodialysis

Background and objectives

Chinese patients with ESRD have different comorbidity patterns than white patients with ESRD and require a validated comorbidity index. The objective of this study was to develop a new index for mortality prediction in 2006–2009 Taiwanese incident hemodialysis patients.

Design, setting, participants, & measurements

Data were retrieved from 2005 to 2010 Taiwan National Health Insurance claim records, and follow-up was available until December 31, 2010. The same comorbid conditions as the US Renal Data System (USRDS) index that occurred during a 12-month period from 9 months before to 3 months after dialysis initiation were used to construct the index. Integer weight of the comorbid conditions was derived from coefficient estimates of Cox regression for all-cause mortality, and the index was internally validated. The performance of the index was assessed by discrimination, calibration, and reclassification.

Results

A total of 30,303 hemodialysis patients were included in this study. The weight for individual comorbid conditions of this index differed from that of the USRDS index. The performance of this index was similar to that of USRDS and Charlson indices in terms of model fit statistics, overall predictive ability, discrimination, and calibration. Hosmer–Lemeshow test showed that all three indices demonstrated significant differences between predicted and observed mortality rates. When patients were categorized by the predicted 2.5-year survival probabilities, the index achieved a net reclassification improvement of 4.71% (P<0.001), referenced to USRDS index.

Conclusions

Compared with USRDS index, this new index demonstrated better reclassification ability, but future studies should address the clinical significance.     

Uric Acid Levels and All-Cause and Cardiovascular Mortality in the Hemodialysis Population

Summary

Background and objectives

Hyperuricemia is associated with hypertension, coronary artery disease, and chronic kidney disease. However, there are no specific data on the relationship of uric acid to cardiovascular disease in the chronic hemodialysis setting.

Design, setting, participants, & measurements

Data from 5827 patients on chronic hemodialysis from six countries affiliated with the Dialysis Outcomes and Practice Patterns Study (DOPPS) were analyzed. All laboratory data were based upon the initial cross-section of patients in DOPPS I and II. Cox regression was used to calculate the hazard ratio (HR) of all-cause and cardiovascular (CV) mortality with adjustments for case-mix including 14 classes of comorbidity.

Results

There were no clinically significant differences in baseline characteristics between those who had measured uric acid (n = 4637) and those who did not (n = 1190). Uric acid level was associated with lower all-cause mortality (HR: 0.95, 95% confidence interval [CI]: 0.90 to 1.00 per 1 mg/dl higher uric acid level) and CV mortality (HR: 0.92, 95% CI: 0.86 to 0.99). When analyzed as a dichotomous variable, the adjusted HR at uric acid ≤8.2 mg/dl compared with >8.2 mg/dl was 1.24 (95% CI: 1.03 to 1.49) for all-cause mortality and 1.54 (95% CI: 1.15 to 2.07) for CV mortality.

Conclusions

Higher uric acid levels were associated with lower risk of all-cause and CV mortality in the hemodialysis population. These results are in contrast to the association of hyperuricemia with higher cardiovascular risk in the general population and should be the subject of further research.     

Inverse relationship between the inflammatory marker pentraxin-3, fat body mass, and abdominal obesity in end-stage renal disease

Summary

Background and objectives

Pentraxin-3 (PTX3) belongs to the same pentraxin superfamily of acute-phase reactants as C-reactive protein (CRP). Abdominal fat accumulation in ESRD is considered a chronic inflammatory state, but the relationship of PTX3 to this phenomenon is unknown. This study assesses plausible associations between PTX3 and surrogates of fat mass deposits in dialysis patients.

Design, setting, participants, & measurements

Circulating levels of PTX3, CRP, and IL-6 were cross-sectionally analyzed in relation to anthropometric and nutritional surrogate markers of fat tissue in two cohorts comprising 156 prevalent hemodialysis (HD) and 216 incident dialysis patients.

Results

In both cohorts, PTX3 was negatively associated with body mass index (BMI) and fat body mass index (FBMI) derived from anthropometrics and leptin, whereas there was a positive association with adiponectin. In prevalent HD patients, those with larger waist circumference (above gender-specific median values) had lower PTX3, higher CRP, and higher IL-6 levels. This was also true in multivariate analyses. In both cohorts, multivariate regression analyses showed that PTX3 was negatively and CRP (or IL-6) was positively associated with FBMI.

Conclusions

Although CRP and IL-6 were directly associated with body fat, PTX3 levels showed negative correlations with surrogates of adipose tissue in two independent cohorts of ESRD patients. Understanding the underlying reasons behind these opposite associations may have clinical relevance given the survival advantage described for obese patients on dialysis.     

Associations of Self-Reported Physical Activity Types and Levels with Quality of Life,Depression Symptoms,and Mortality in Hemodialysis Patients: The DOPPS

Background and objectives

Physical activity has been associated with better health status in diverse populations, but the association in patients on maintenance hemodialysis is less established. Patient-reported physical activities and associations with mortality, health-related quality of life, and depression symptoms in patients on maintenance hemodialysis in 12 countries were examined.

Design, setting, participants, & measurements

In total, 5763 patients enrolled in phase 4 of the Dialysis Outcomes and Practice Patterns Study (2009–2011) were classified into five aerobic physical activity categories (never/rarely active to very active) and by muscle strength/flexibility activity using the Rapid Assessment of Physical Activity questionnaire. The Kidney Disease Quality of Life scale was used for health-related quality of life. The Center for Epidemiologic Studies Depression scale was used for depression symptoms. Linear regression was used for associations of physical activity with health-related quality of life and depression symptoms scores. Cox regression was used for association of physical activity with mortality.

Results

The median (interquartile range) of follow-up was 1.6 (0.9–2.5) years; 29% of patients were classified as never/rarely active, 20% of patients were classified as very active, and 20.5% of patients reported strength/flexibility activities. Percentages of very active patients were greater in clinics offering exercise programs. Aerobic activity, but not strength/flexibility activity, was associated positively with health-related quality of life and inversely with depression symptoms and mortality (adjusted hazard ratio of death for very active versus never/rarely active, 0.60; 95% confidence interval, 0.47 to 0.77). Similar associations with aerobic activity were observed in strata of age, sex, time on dialysis, and diabetes status.

Conclusions

The findings are consistent with the health benefits of aerobic physical activity for patients on maintenance hemodialysis. Greater physical activity was observed in facilities providing exercise programs, suggesting a possible opportunity for improving patient outcomes.     

Effect of angiotensin-converting enzyme inhibition on C-reactive protein levels: The Ramipril C-Reactive pRotein Randomized evaluation (4R) trial results

BACKGROUND:

Plasma levels of the inflammatory biomarker C-reactive protein (CRP) predict cardiovascular risk and may represent a target for treating and/or monitoring risk-reduction strategies. The effect of angiotensin-converting enzyme inhibitors on CRP levels has not been adequately studied.

METHODS:

A total of 264 men and women, with CRP levels of 2 mg/L or greater and no history of cardiovascular disease, were enrolled in a 12-week randomized, double-blind, placebo-controlled study. Participants were randomly assigned to receive 10 mg/day of ramipril (n=132) or placebo (n=132) for 12 weeks. The main outcome measure was the change in CRP levels from baseline to 12 weeks in the ramipril- versus placebo-treated patients.

RESULTS:

The mean (± SD) age was 53±9 years (60% men). Baseline demographics were similar between the volunteers allocated to receive either placebo or ramipril. The geometric mean CRP at baseline was 3.84 mg/L (95% CI 3.62 mg/L to 4.06 mg/L). The percentage change in geometric mean CRP values over 12 weeks was −13.2% (95% CI −22.3% to −3.2%) in the placebo group compared with −21.1% (95% CI −29.9% to −11.2%) in the ramipril group (P nonsignificant), indicating no significant reduction in the primary end point of the trial.

CONCLUSIONS:

A 12-week ramipril treatment protocol for healthy middle-aged volunteers did not lower CRP levels compared with placebo. However, because of the inherent variability of CRP levels, a much larger study is required to exclude a small treatment effect.     

Survival and Predictive Factors of Lethality in Hemodyalisis: D/I Polymorphism of The Angiotensin I-Converting Enzyme and of the Angiotensinogen M235T Genes

Background

End-stage kidney disease patients continue to have markedly increased cardiovascular disease morbidity and mortality. Analysis of genetic factors connected with the renin-angiotensin system that influences the survival of the patients with end-stage kidney disease supports the ongoing search for improved outcomes.

Objective

To assess survival and its association with the polymorphism of renin-angiotensin system genes: angiotensin I-converting enzyme insertion/deletion and angiotensinogen M235T in patients undergoing hemodialysis.

Methods

Our study was designed to examine the role of renin-angiotensin system genes. It was an observational study. We analyzed 473 chronic hemodialysis patients in four dialysis units in the state of Rio de Janeiro. Survival rates were calculated by the Kaplan-Meier method and the differences between the curves were evaluated by Tarone-Ware, Peto-Prentice, and log rank tests. We also used logistic regression analysis and the multinomial model. A p value ≤ 0.05 was considered to be statistically significant. The local medical ethics committee gave their approval to this study.

Results

The mean age of patients was 45.8 years old. The overall survival rate was 48% at 11 years. The major causes of death were cardiovascular diseases (34%) and infections (15%). Logistic regression analysis found statistical significance for the following variables: age (p = 0.000038), TT angiotensinogen (p = 0.08261), and family income greater than five times the minimum wage (p = 0.03089), the latter being a protective factor.

Conclusions

The survival of hemodialysis patients is likely to be influenced by the TT of the angiotensinogen M235T gene.     

Novel lipoprotein subfraction and size measurements in prediction of mortality in maintenance hemodialysis patients

Summary

Background and objectives

Conventional lipid profiles usually cannot predict cardiovascular outcomes in chronic disease states. We hypothesized that novel lipoprotein subfraction concentrations and LDL particle size measurements better predict mortality in maintenance hemodialysis (MHD) patients.

Design, setting, participants, & measurements

Mortality-predictability of LDL particle diameter and lipoprotein subfraction concentrations, measured by novel ion mobility, was examined in a cohort of 235 hemodialysis patients who were followed for up to 6 years using Cox models with adjustment for important covariables.

Results

Patients were 54 ± 14 years old (mean ± SD) and included 45% women with total, LDL and HDL cholesterol levels of 143 ± 42, 76 ± 29, and 37 ± 12 mg/dl, respectively. Over 6 years, 71 patients (31%) died. Conventional lipid profile was not associated with mortality. The death hazard ratio (HR, 95% confidence interval) of the highest versus lowest quartiles of very small and large LDL particle concentrations were 2.43 (1.03 to 5.72) and 0.38 (0.15 to 0.96), respectively. Across increasing quartiles of LDL particle diameter, death HRs were 1.00, 0.93 (0.46 to 1.87), 0.43 (0.21 to 0.89), and 0.45 (0.31 to 1.00), respectively.

Conclusions

Whereas conventional lipid profile cannot predict mortality in MHD patients, larger novel LDL particle diameter or higher large LDL particle concentrations appear predictive of greater survival, whereas higher very small LDL particle concentration is associated with higher death risk. Examining lipoprotein subfraction modulation in chronic diseases is indicated.     

Intradialytic Hypertension and the Association with Interdialytic Ambulatory Blood Pressure

Summary

Background and objectives

Increasing BP during maintenance hemodialysis or intradialytic hypertension is associated with increased morbidity and mortality. In hemodialysis patients, ambulatory BP measurements predict adverse cardiovascular outcomes better than in-center measurements. We hypothesized that patients with intradialytic hypertension have higher interdialytic ambulatory systolic BP than those without intradialytic hypertension.

Design, setting, participants, & measurements

We performed a case-control study in adult hemodialysis patients. Cases consisted of subjects with intradialytic-hypertension (systolic BP increase ≥10 mmHg from pre- to posthemodialysis in at least four of six treatments), and controls were subjects with ≥10 mmHg decreases from pre- to posthemodialysis in at least four of six treatments. The primary outcome was mean interdialytic 44-hour systolic ambulatory BP.

Results

Fifty subjects with a mean age of 54.5 years were enrolled (25 per group) among whom 80% were men, 86% diabetic, 62% Hispanic, and 38% African American. The mean prehemodialysis systolic BP for the intradialytic-hypertension and control groups were 144.0 and 155.5 mmHg, respectively. Mean posthemodialysis systolic BP was 159.0 and 128.1 mmHg, for the intradialytic-hypertension and control groups, respectively. The mean systolic ambulatory BP was 155.4 and 142.4 mmHg for the intradialytic-hypertension and control groups, respectively (P = 0.005). Both daytime and nocturnal systolic BP were higher among those with intradialytic hypertension as compared with controls. There was no difference in interdialytic weight gain between groups.

Conclusions

Time-integrated BP burden as measured by 44-hour ambulatory BP is higher in hemodialysis patients with intradialytic hypertension than those without intradialytic hypertension.     

Toward a Definition of Masked Hypertension and White-Coat Hypertension among Hemodialysis Patients

Summary

Background and objectives

Among people with essential hypertension, ambulatory BP measurement is superior to BP obtained in the clinic in predicting cardiovascular outcomes. In part, this is because it can detect white-coat hypertension and masked hypertension. Whether the same is true for hemodialysis patients is not known.

Design, setting, participants, & measurements

Using a threshold of 140/80 mmHg for median midweek dialysis-unit BP and 135/85 mmHg for 44-hour ambulatory BP, we defined four categories of BP: sustained normotension (SN), white-coat hypertension (WCH), masked hypertension (MHTN), and sustained hypertension (SHTN).

Results

Among 355 long-term hemodialysis patients, the prevalence of SN was 35%, WCH 15%, MHTN 15%, and SHTN 35%. Over a mean follow-up of 29.6 (SD 21.7) months, 102 patients died (29%), yielding a crude mortality rate of 121/1000 patient-years. Unadjusted and multivariate-adjusted analyses showed increasing all-cause mortality with increasing severity of hypertension (unadjusted hazard ratios from SN, WCH, MHTN, SHTN: 1, 1.12, 1.70, 1.80, respectively [P for trend < 0.01]; adjusted hazard ratios: 1, 1.30, 1.36, 1.87, respectively [P for trend 0.02]). When a predialysis BP threshold of 140/90 mmHg was used to classify patients into BP categories, the prevalence of SN was 24%, WCH 26%, MHTN 4%, and SHTN 47%. Hazard ratios for mortality were similar when compared with median midweek dialysis-unit BP.

Conclusions

As in the essential hypertension population, MHTN and WCH have prognostic significance. The prognostic value of BP obtained in the dialysis unit can be refined with ambulatory BP monitoring.     

Protective effect of silymarin during coronary artery bypass grafting surgery

BACKGROUND:

An inflammatory response and systemic oxidative stress are directly caused by coronary artery bypass grafting (CABG) surgery. Cytokines, such as interleukin (IL) 1β, IL-6 and tumour necrosis factor-α (TNF-α), can also be stimulated. Reducing the release of pro-inflammatory cytokines plays an important role in limiting the postoperative inflammatory response. Silymarin has strong anti-inflammatory, antioxidant and cytoprotective properties.

OBJECTIVE:

To investigate the protective anti-inflammatory and antioxidant properties of silymarin against the inflammation and oxidative stresss inherent to CABG surgery.

METHODS:

Of the 102 patients undergoing elective first-time CABG surgery that were recruited, 50 (49.02%) received silymarin treatment and 52 (50.9%) were controls. Plasma cytokine levels (IL-1β, IL-6 and TNF-α) were measured preoperatively, 6 h and 24 h after CABG surgery. C-reactive protein (CRP) levels, trolox equivalent antioxidant capacity (TEAC) and glutathione (GSH) and malondialdehyde (MDA) levels were analyzed.

RESULTS:

Postoperative cytokine levels in the silymarin group were significantly lower compared with preoperative levels, and were significantly lower compared with postoperative control group levels. The area under the curve for cytokines and CRP for the silymarin group were significantly lower compared with preoperative levels, and were significantly lower compared with postoperative control group levels. Postoperative levels of TEAC and MDA in the silymarin-treated group were significantly lower than in the control group. GSH levels were significantly elevated in the silymarin group compared with control. No side effects or mortality were associated with the use of silymarin.

CONCLUSION:

The anti-inflammatory and antioxidant effects of silymarin treatment provided protection against reperfusion injury and inflammation after CABG surgery.     

Why do mortality rates for nonvariceal upper gastrointestinal bleeding differ around the world? A systematic review of cohort studies

BACKGROUND:

Discrepancies exist in reported mortality rates of nonvariceal upper gastrointestinal bleeding (NVUGIB).

OBJECTIVE:

To perform a systematic review assessing possible reasons for these disparate findings and to more reliably compare them.

METHODS:

The MEDLINE, EMBASE and ISI Web of Knowledge databases were searched for studies reporting mortality rates in NVUGIB involving adults and published in English. To ensure robust and contemporary estimates, studies spanning 1996 to January 2011 that included more than 1000 patients were selected.

RESULTS:

Eighteen of 3077 studies were selected. Ten studies used administrative databases and the remaining eight used registries. The mortality rates reported in these studies ranged from 1.1% in Japan to 11% in Denmark. There were variations in reported mortality rates among countries and also within countries. Reasons for these disparities included a spectrum of quality in reporting as well as heterogeneous definitions of case ascertainment, differing patient populations with regard to severity of presentation and associated comorbidities, varying durations of follow-up and different health care system-related practices.

CONCLUSIONS:

Wide differences in reported NVUGIB mortality rates are attributable to differences in adopted methodologies and populations studied. More uniform standards in reporting are needed; only then can true observed variations enable a better understanding of causes of death and pave the way to improved patient outcomes.     

Comparison of inflammatory response following coronary revascularization with or without cardiopulmonary bypass

BACKGROUND:

It is well known that conventional coronary revascularization is associated with a pronounced systemic inflammatory response due to the application of cardiopulmonary bypass (CPB).

OBJECTIVE:

To compare the effects of coronary artery bypass grafting (CABG) with (on-pump) or without (off-pump) extra-corporeal circulation observing certain inflammatory response parameters.

METHODS:

Twenty patients undergoing CABG with (CPB group: 10 patients) or without (off-pump coronary artery bypass grafting [OPCAB] group: 10 patients) CPB were enrolled in this prospective, randomized study. Blood samples were collected three times during the operation and on postoperative days 1, 2, 3 and 7. The plasma level of proinflammatory cytokine tumor necrosis factor (TNF)-alpha was measured by enzyme-linked immunosorbent assay method following stimulation, and the expression of adhesion molecules (CD11, CD18) of leukocytes were determined by flow cytometry. Furthermore, white blood cell (WBC) and neutrophil count were carried out.

RESULTS:

The WBC and neutrophil counts rose markedly in both groups following the operation and remained at this increased level during the observation period. There was a significant difference in WBC and neutrophil counts between the two groups of patients on postoperative day 7. A significant difference in the level of TNF-alpha was found between the two groups on postoperative day 2 (P<0.05). An intense increase was observed with CPB, which significantly exceeded the values of the OPCAB group without extracorporeal circulation in the early postoperative period. The CD11a and CD18 expression of leukocytes decreased during the operation and on postoperative day 1; thereafter, it increased markedly. There was a significant difference in adhesion molecule expression between the two groups on postoperative day 2.

CONCLUSION:

The investigation revealed that inflammatory response reactions following extracorporeal circulation could be reduced significantly using the off-pump technique.     

Prevalence of Cardiovascular Risk Factors in Hemodialysis Patients - The CORDIAL Study

Background

There are scarce epidemiological data on cardiovascular risk profile of chronic hemodialysis patients in Brazil.

Objective

The CORDIAL study was designed to evaluate cardiovascular risk factors and follow up a hemodialysis population in a Brazilian metropolitan city.

Methods

All patients undergoing regular hemodialysis for chronic renal failure in all fifteen nephrology centers of Porto Alegre were considered for inclusion in the baseline phase of the CORDIAL study. Clinical, laboratory and demographic data were obtained in medical records and in structured individual interviews performed in all patients by trained researchers.

Results

A total of 1215 patients were included (97.3% of all hemodialysis patients in the city of Porto Alegre). Their average age was 58.3 years old, 59.5% were male and 62.8% were white. The prevalence of cardiovascular risk factors observed was 87.5% for hypertension, 84.7% for dyslipidemia, 73.1% for sedentary lifestyle, 53.7% for tobacco use, and 35.8% for diabetes. In a multivariate adjusted analysis, we found that sedentary lifestyle (p = 0.032, PR 1.08 - 95%CI: 1.01-1.15), dyslipidemia (p = 0.019, PR 1.08 - 95%CI: 1.01-1.14), and obesity (p < 0.001, PR 1.96 - 95%CI: 1.45-2.63) were more frequent in women; and hypertension (p = 0.018, PR 1.06 - 95%CI: 1.01-1.11) and tobacco use (p = 0.006, PR 2.7 - 95%CI: 1.79-4.17) were more often found among patients under 65 years old. Sedentary lifestyle was independently associated with time in dialysis less than 12 months (p < 0.001, PR 1.23 - 95% CI: 1.14-1.33).

Conclusion

Hemodialysis patients in this southern metropolitan Brazilian city have a high prevalence of cardiovascular risk factors resembling many northern countries.     

Long-Term Viral Negativity After Interferon for Chronic Hepatitis C Virus Infection in Hemodialysis

Summary

Background and objectives

Interferon (IFN) and pegylated-IFN treatment of hepatitis C virus (HCV) infection in hemodialysis patients result in sustained virological response (SVR) rates of 45% and 37%, respectively. Although most nonhemodialysis patients who achieve SVR remain persistently viral negative, the durability of SVR in hemodialysis patients is unknown. We analyzed the rate of long-term virological negativity in hemodialysis patients who achieved SVR after IFN or pegylated-IFN through analysis of patient-level data.

Design, setting, participants, & measurements

After performing a systematic literature review for IFN-based treatment of hemodialysis patients with chronic HCV infection, we extracted patient-level data on patients who achieved SVR. We performed life table analysis to estimate long-term virological negativity rates after SVR in patients who continued on hemodialysis or subsequently underwent kidney transplantation.

Results

Long-term HCV RNA outcomes following SVR were available for 121 hemodialysis patients (20 studies) and 45 patients who subsequently underwent transplantation (11 studies). The probability of remaining HCV RNA negative was 86% (95% confidence interval, 77% to 96%) for patients followed on hemodialysis 48 months after SVR and 95% (95% confidence interval, 89% to 100%) for kidney recipients followed 48 months after transplant.

Conclusions

Viral negativity from IFN-based HCV treatment in hemodialysis patient appears durable during extended follow-up, including after kidney transplantation. The certainty of the viral negativity estimate is limited by the small number with follow-up beyond 48 months or longer. Transplantation does not confer an increased risk of relapse. Future research should investigate whether IFN-based treatment improves clinical outcomes for hemodialysis patients.     

High-sensitivity C-reactive protein levels and treadmill exercise test responses in men and women without overt heart disease

BACKGROUND:

C-reactive protein (CRP) is a marker of systemic inflammatory activity and may be modulated by physical fitness. Treadmill exercise testing is used to evaluate cardiovascular health through different variables including exercise capacity, heart rate and blood pressure responses. It was hypothesized that CRP levels are associated with these variables in men and women without overt heart disease.

METHODS:

A total of 584 asymptomatic subjects (317 [54.3%] women and 267 [45.7%] men) were enrolled in the present study and underwent clinical evaluation. CRP levels in men and women were examined relative to clinical characteristics and to variables of treadmill exercise testing: peak heart rate, exercise systolic blood pressure, exercise time, chronotropic reserve and heart rate recovery at the first and second minutes after exercise. Multivariate analysis was performed using a log-linear regression model.

RESULTS:

In women, exercise time on the treadmill exercise test (P=0.009) and high-density lipoprotein cholesterol levels (P=0.002) were inversely associated with CRP levels. Body mass index (P<0.001) and total cholesterol levels (P=0.005) were positively associated with CRP levels. In men, exercise time on the treadmill exercise test was inversely associated with CRP levels (P=0.015). Body mass index (P=0.001) and leukocyte count (P=0.002) were positively associated with CRP levels. CRP levels were not associated with peak heart rate, chronotropic reserve, heart rate recovery at the first and second minutes, or exercise systolic blood pressure.

CONCLUSIONS:

These findings contribute to the evidence that CRP is lower in individuals with better exercise capacity and demonstrate that this relationship is also apparent in individuals without overt heart disease undergoing cardiovascular evaluation through the treadmill exercise test. Lowering inflammatory markers may be an additional reason to stimulate sedentary individuals with low exercise capacity in the treadmill exercise test to improve physical conditioning through regular exercise.     

Frequency and Genotype of Hepatitis D Virus Infection in Patients Infected with HIV and Those Undergoing Hemodialysis

Background

Hepatitis D virus (HDV) is a defective virus dependent on hepatitis B virus (HBV) for its replication. Due to HDV transmission routes, patients undergoing hemodialysis and those with HIV infection are at risk of acquiring HDV.

Objectives

This study was aimed to determine the frequency and genotype of HDV infection among patients with HIV infection and those undergoing hemodialysis.

Patients and Methods

720 cases including 120 patients undergoing hemodialysis, and 600 patients with HIV infection were studied. All cases with positive results for HBsAg were evaluated for the presence of anti-HDV antibodies. Samples with Anti-HDV positive results were subjected to nested PCR for HDV-RNA confirmation, and sequenced for HDV genotype determination.

Results

HBsAg was found in 9 (7.5%) of 120 patients undergoing hemodialysis, and 9 (1.5%) of 600 patients with HIV infection. 3 (33.3%) of patients undergoing hemodialysis with positive results for HBsAg, and 5 (55.5%) of cases with HIV infection and positive results for HBsAg, had positive findings for anti-HDV which were then subjected to nested PCR. The amplification results confirmed that in 3 (37.5%) samples HDV-RNA was detected. Overall 2.5% of patients undergoing hemodialysis, and 0.8% of cases infected with HIV had positive results for anti-HDV and 1.7% and 0.2% of cases undergoing hemodialysis and patients infected with HIV had positive findings for HDV-RNA respectively. All of the HDV isolates were clustered in clade 1.

Conclusions

The survey showed that overall HDV frequency was not high in our high risk cases. Therefore, practitioners and health care managers should become aware of the risk of dual infection with HBV and HDV especially in high risk patients.     

HFE mutations in Caucasian participants of the Hemochromatosis and Iron Overload Screening study with serum ferritin level <1000 μg/L

BACKGROUND:

Many patients referred for an elevated serum ferritin level <1000 μg/L are advised that they likely have iron overload and hemochromatosis.

AIMS:

To determine the prevalence of HFE mutations in the hemochromatosis gene for 11 serum ferritin concentration intervals from 200 μg/L to 1000 μg/L in Caucasian participants in a primary care, population-based study.

METHODS:

The Hemochromatosis and Iron Overload Screening study screened 99,711 participants for serum ferritin levels, transferrin saturation and genetic testing for the C282Y and H63D mutations of the HFE gene. This analysis was confined to 17,160 male and 27,465 female Caucasian participants because the HFE C282Y mutation is rare in other races. Post-test likelihood was calculated for prediction of C282Y homozygosity from a ferritin interval. A subgroup analysis was performed in participants with both an elevated serum ferritin level and transferrin saturation.

RESULTS:

There were 3359 male and 2416 female participants with an elevated serum ferritin level (200 μg/L to 1000 μg/L for women, 300 μg/L to 1000 μg/L for men). There were 69 male (2.1%) and 87 female (3.6%) C282Y homozygotes, and the probability of being a homozygote increased as the ferritin level increased. Post-test likelihood values were 0.3% to 16% in men and 0.3% to 30.4% in women.

CONCLUSIONS:

Iron loading HFE mutations are unlikely to be the most common cause of an elevated serum ferritin level in patients with mild hyperferritinemia. Patients should be advised that there are many causes of an elevated serum ferritin level including iron overload.     

The relationship between serum ferritin levels and electrocardiogram characteristics in acutely ill patients

BACKGROUND:

Cardiac arrhythmias are common comorbidities among acutely ill patients admitted to hospitals. An abnormal iron metabolism may contribute to the abnormalities in the conduction and propagation of action potentials through myocardium.

OBJECTIVE:

To determine whether serum indexes of iron metabolism correlate with electrocardiogram (ECG) changes.

METHODS:

In the present retrospective, pilot chart review, serum levels of iron, ferritin, Na⁺, K⁺, Mg²⁺, Ca²⁺ and total iron-binding capacity in 77 hospitalized patients with acute illness were correlated with ECG variables.

RESULTS:

The serum ferritin level correlated strongly (r=0.49) with QT/QTs interval. There were three subjects with QT prolongation (longer than 450 ms) within the high serum ferritin (576 ng/mL or greater) group versus subjects with low ferritin. Multiple regression analysis showed that serum ferritin level and serum iron level contributed to the variance in the QT/QTs prolongation. No other correlation between the studied serum markers and ECG characteristics were found.

CONCLUSION:

The present study suggests that serum ferritin and iron levels affect the QT interval in a variety of medical conditions, possibly contributing to the emergence of fatal cardiac arrhythmias.