Alanine aminotransferase decreases with age: the Rancho Bernardo Study

Background

Serum alanine aminotransferase (ALT) is a marker of liver injury. The 2005 American Gastroenterology Association Future Trends Committee report states that serum ALT levels remain constant with age. This study examines the association between serum ALT and age in a community-dwelling cohort in the United States.

Methods

A cross-sectional study of 2,364 (54% female) participants aged 30–93 years from the Rancho Bernardo Study cohort who attended a research clinic visit in 1984–87. Demographic, metabolic co-variates, ALT, bilirubin, gamma glutamyl transferase (GGT), albumin, and adiposity signaling biomarkers (leptin, IL-6, adiponectin, ghrelin) were measured. Participants were divided into four-groups based upon age quartile, and multivariable-adjusted least squares of means (LSM) were examined (p for trend <0.05).

Results

ALT decreased with increasing age, with mean ALT levels (IU/L) of 23, 21, 20, and 17 for those between quartile ages 30–62, 63–71, 72–77, and 78–93 years (p<0.0001). Trends of decreasing LSM ALT with age and the decreasing prevalence of categorically defined elevated serum ALT with age remained robust after adjusting for sex, alcohol use, metabolic syndrome components, and biomarkers of adiposity (p-value <0.0001), and was not materially changed after adjusting for bilirubin, GGT, and albumin.

Conclusions

ALT levels decrease with age in both men and women independent of metabolic syndrome components, adiposity signaling biomarkers, and other commonly used liver function tests. Further studies are needed to understand the mechanisms responsible for a decline in ALT with age, and to establish the optimal cut-point of normal ALT in the elderly.     

Interactions between Serum Vitamin D Levels and Vitamin D Receptor Gene FokI Polymorphisms for Renal Function in Patients with Type 2 Diabetes

Background

We aimed to examine associations among serum 25-hydroxyvitamin D (25OHD) levels, 1,25-dihyroxyvitamin D (1,25OHD) levels, vitamin D receptor (VDR) polymorphisms, and renal function based on estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.

Methods

In a cross-sectional study of 410 patients, chronic kidney disease (CKD) stage assessed by eGFR was compared with 25OHD, 1,25OHD, and VDR FokI (rs10735810) polymorphisms by an ordered logistic regression model adjusted for the following confounders: disease duration, calendar month, use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers or statins, and serum calcium, phosphate, and intact parathyroid hormone levels.

Results

1,25OHD levels, rather than 25OHD levels, showed seasonal oscillations; peak levels were seen from May to October and the lowest levels were seen from December to February. These findings were evident in patients with CKD stage 3∼5 but not stage 1∼2. eGFR was in direct proportion to both 25OHD and 1,25OHD levels (P<0.0001), but it had stronger linearity with 1,25OHD (r = 0.73) than 25OHD (r = 0.22) levels. Using multivariate analysis, 1,25OHD levels (P<0.001), but not 25OHD levels, were negatively associated with CKD stage. Although FokI polymorphisms by themselves showed no significant associations with CKD stage, a significant interaction between 1,25OHD and FokITT was observed (P = 0.008). The positive association between 1,25OHD and eGFR was steeper in FokICT and CC polymorphisms (r = 0.74) than FokITT polymorphisms (r = 0.65).

Conclusions

These results suggest that higher 1,25OHD levels may be associated with better CKD stages in patients with type 2 diabetes and that this association was modified by FokI polymorphisms.     

Effects of Clopidogrel on Mortality,Cardiovascular and Bleeding Outcomes in Patients with Chronic Kidney Disease - Data from Taiwan Acute Coronary Syndrome Full Spectrum Registry

Background

The efficacy of clopidogrel is inconclusive in the chronic kidney disease (CKD) population with acute coronary syndrome (ACS). Furthermore, CKD patients are prone to bleeding with antiplatelet therapy. We investigated the efficacy and safety of clopidogrel in patients with ACS and CKD.

Methods

In a Taiwan national-wide registry, 2819 ACS patients were enrolled. CKD is defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m². The primary endpoints are the combined outcomes of death, non-fatal myocardial infarction and stroke at 12 months.

Results

Overall 949 (33.7%) patients had CKD and 2660 (94.36%) patients received clopidogrel treatment. CKD is associated with increased risk of the primary endpoint at 12 months (HR 2.39, 95% CI 1.82 to 3.15, p<0.01). Clopidogrel use is associated with reduced risk of the primary endpoint at 12 months (HR 0.42, 95% CI: 0.29–0.60, p<0.01). Cox regression analysis showed that clopidogrel reduced death and primary endpoints for CKD population (HR 0.35, 95% CI: 0.21–0.61 and HR 0.48, 95% CI: 0.30–0.77, respectively, both p<0.01). Patients with clopidogrel(−)/CKD(−), clopidogrel(+)/CKD(+) and clopidogrel(−)/CKD(+) have 2.4, 3.0 and 10.4 fold risk to have primary endpoints compared with those receiving clopidogrel treatment without CKD (all p<0.01). Clopidogrel treatment was not associated with increased in-hospital Thrombolysis In Myocardial Infarction (TIMI) bleeding in CKD population.

Conclusion

Clopidogrel could decrease mortality and improve cardiovascular outcomes without increasing risk of bleeding in ACS patients with CKD.     

Serum early prostate cancer antigen (EPCA) level and its association with disease progression in prostate cancer in a Chinese population

Background

Early prostate cancer antigen (EPCA) has been shown a prostate cancer (PCa)-associated nuclear matrix protein, however, its serum status and prognostic power in PCa are unknown. The goals of this study are to measure serum EPCA levels in a cohort of patients with PCa prior to the treatment, and to evaluate the clinical value of serum EPCA.

Methods

Pretreatment serum EPCA levels were determined with an ELISA in 77 patients with clinically localized PCa who underwent radical prostatectomy and 51 patients with locally advanced or metastatic disease who received primary androgen deprivation therapy, and were correlated with clinicopathological variables and disease progression. Serum EPCA levels were also examined in 40 healthy controls.

Results

Pretreatment mean serum EPCA levels were significantly higher in PCa patients than in controls (16.84±7.60 ng/ml vs. 4.12±2.05 ng/ml, P<0.001). Patients with locally advanced and metastatic PCa had significantly higher serum EPCA level than those with clinically localized PCa (22.93±5.28 ng/ml and 29.41±8.47 ng/ml vs. 15.17±6.03 ng/ml, P = 0.014 and P<0.001, respectively). Significantly elevated EPCA level was also found in metastatic PCa compared with locally advanced disease (P<0.001). Increased serum EPCA levels were significantly and positively correlated with Gleason score and clinical stage, but not with PSA levels and age. On multivariate analysis, pretreatment serum EPCA level held the most significantly predictive value for the biochemical recurrence and androgen-independent progression among pretreatment variables (HR = 4.860, P<0.001 and HR = 5.418, P<0.001, respectively).

Conclusions

Serum EPCA level is markedly elevated in PCa. Pretreatment serum EPCA level correlates significantly with the poor prognosis, showing prediction potential for PCa progression.     

Serum fetuin-A associates with type 2 diabetes and insulin resistance in Chinese adults

Background

Previous studies have demonstrated that fetuin-A is related to insulin resistance among subjects with normal glucose tolerance but not patients with type 2 diabetes. There are limited data available concerning fetuin-A and insulin resistance in Chinese. We aimed to study the association of feuin-A with insulin resistance among participants with or without type 2 diabetes in a large sample size of adults aged 40 and older.

Methodology and Principal Findings

A community-based cross-sectional study was performed among 5,227 Chinese adults. The average age of our study was 61.5±9.9 years. Serum fetuin-A concentrations were not significantly different between male and female (296.9 vs. 292.9 mg/l, p = 0.11). Compared with the lowest quartile, the highest quartile of serum fetuin-A revealed a significant higher proportion of type 2 diabetic patients (34.8% vs. 27.3%, p<0.0001). In the multinomial logit models, the risk of type 2 diabetes was associated with each one quartile increase of serum fetuin-A concentrations when referenced not only to normal glucose tolerance (OR 1.24, 95% CI 1.07–1.43, p = 0.004) but also to impaired glucose regulation (OR 1.25, 95% CI 1.08–1.44, p = 0.003, respectively), after adjustment for age, sex, community, current smoking, and current drinking. The logistic regression analysis showed that fetuin-A were associated with elevated HOMA-IR and fasting serum insulin both among the participants with or without type 2 diabetes in the full adjusted analysis. There was no significant association between elevated serum fetuin-A concentrations and impaired glucose regulation (all p≥0.12).

Conclusions and Significance

Higher fetuin-A concentrations were associated with type 2 diabetes and insulin resistance in middle aged and elderly Chinese.     

The Relation between Serum Phosphorus Levels and Clinical Outcomes after Acute Myocardial Infarction

Background

Elevated serum phosphorus levels have been linked with cardiovascular disease and mortality with conflicting results, especially in the presence of normal renal function.

Methods

We studied the association between serum phosphorus levels and clinical outcomes in 1663 patients with acute myocardial infarction (AMI). Patients were categorized into 4 groups based on serum phosphorus levels (<2.50, 2.51–3.5, 3.51–4.50 and >4.50 mg/dL). Cox proportional-hazards models were used to examine the association between serum phosphorus and clinical outcomes after adjustment for potential confounders.

Results

The mean follow up was 45 months. The lowest mortality occurred in patients with serum phosphorus between 2.5–3.5 mg/dL, with a multivariable-adjusted hazard ratio of 1.24 (95% CI 0.85–1.80), 1.35 (95% CI 1.05–1.74), and 1.75 (95% CI 1.27–2.40) in patients with serum phosphorus of <2.50, 3.51–4.50 and >4.50 mg/dL, respectively. Higher phosphorus levels were also associated with increased risk of heart failure, but not the risk of myocardial infarction or stroke. The effect of elevated phosphorus was more pronounced in patients with chronic kidney disease (CKD). The hazard ratio for mortality in patients with serum phosphorus >4.5 mg/dL compared to patients with serum phosphorus 2.50–3.50 mg/dL was 2.34 (95% CI 1.55–3.54) with CKD and 1.53 (95% CI 0.87–2.69) without CKD.

Conclusion

We found a graded, independent association between serum phosphorus and all-cause mortality and heart failure in patients after AMI. The risk for mortality appears to increase with serum phosphorus levels within the normal range and is more prominent in the presence of CKD.     

A Decreased Level of Serum Soluble Klotho Is an Independent Biomarker Associated with Arterial Stiffness in Patients with Chronic Kidney Disease

Background

Klotho was originally identified in a mutant mouse strain unable to express the gene that consequently showed shortened life spans. In humans, low serum Klotho levels are related to the prevalence of cardiovascular diseases in community-dwelling adults. However, it is unclear whether the serum Klotho levels are associated with signs of vascular dysfunction such as arterial stiffness, a major determinant of prognosis, in human subjects with chronic kidney disease (CKD).

Methods

We determined the levels of serum soluble Klotho in 114 patients with CKD using ELISA and investigated the relationship between the level of Klotho and markers of CKD-mineral and bone disorder (CKD-MBD) and various types of vascular dysfunction, including flow-mediated dilatation, a marker of endothelial dysfunction, ankle-brachial pulse wave velocity (baPWV), a marker of arterial stiffness, intima-media thickness (IMT), a marker of atherosclerosis, and the aortic calcification index (ACI), a marker of vascular calcification.

Results

The serum Klotho level significantly correlated with the 1,25-dihydroxyvitamin D level and inversely correlated with the parathyroid hormone level and the fractional excretion of phosphate. There were significant decreases in serum Klotho in patients with arterial stiffness defined as baPWV≥1400 cm/sec, atherosclerosis defined as maximum IMT≥1.1 mm and vascular calcification scores of ACI>0%. The serum Klotho level was a significant determinant of arterial stiffness, but not endothelial dysfunction, atherosclerosis or vascular calcification, in the multivariate analysis in either metabolic model, the CKD model or the CKD-MBD model. The adjusted odds ratio of serum Klotho for the baPWV was 0.60 (p = 0.0075).

Conclusions

Decreases in the serum soluble Klotho levels are independently associated with signs of vascular dysfunction such as arterial stiffness in patients with CKD. Further research exploring whether therapeutic approaches to maintain or elevate the Klotho level could improve arterial stiffness in CKD patients is warranted.     

Chronic hyper-hemolysis in sickle cell anemia: association of vascular complications and mortality with less frequent vasoocclusive pain

Background

Intravascular hemolysis in sickle cell anemia could contribute to complications associated with nitric oxide deficiency, advancing age, and increased mortality. We have previously reported that intense hemolysis is associated with increased risk of vascular complications in a small cohort of adults with sickle cell disease. These observations have not been validated in other populations.

Methods

The distribution of serum lactic dehydrogenase (LDH) values was used as a surrogate measure of intravascular hemolysis in a contemporaneous patient group and an historical adult population from the Cooperative Study of Sickle Cell Disease (CSSCD), all with sickle cell anemia. Chronic hyper-hemolysis was defined by the top LDH quartile and was compared to the lowest LDH quartile.

Results

Hyper-hemolysis subjects had higher systolic blood pressure, higher prevalence of leg ulcers (OR 3.27, 95% CI 1.92-5.53, P<0.0001), priapism (OR 2.62, 95% CI 1.13-6.90, P = 0.03) and pulmonary hypertension (OR 4.32, 95% CI 2.12-8.60, P<0.0001), while osteonecrosis (OR 0.32, 95% CI 0.19-0.54, P<0.0001) and pain (OR 0.23, 95% CI 0.09-0.55, P = 0.0004) were less prevalent. Hyper-hemolysis was influenced by fetal hemoglobin and α thalassemia, and was a risk factor for early death in the CSSCD population (Hazard Ratio = 1.97, P = 0.02).

Conclusions

Steady state LDH measurements can identify a chronic hyper-hemolysis phenotype which includes less frequent vasooclusive pain and earlier mortality. Clinicians should consider sickle cell specific therapies for these patients, as is done for those with more frequent acute pain. The findings also suggest that an important class of disease modifiers in sickle cell anemia affect the rate of hemolysis.     

Association of natural intake of dietary plant sterols with carotid intima-media thickness and blood lipids in Chinese adults: a cross-section study

Background

Many studies showed a moderate cholesterol-lowering effect of plant sterols (PS), but increased circulating PS might be atherogenic. We evaluated the associations between natural dietary intake of PS and carotid intima–media thickness (IMT) and serum lipids.

Methodology/Principal Findings

This community-based cross-sectional study included 1160 men and 2780 women aged 31–75 years. Dietary intakes were assessed using a food-frequency questionnaire. The IMTs at the common, bifurcation and internal carotid artery segments, and fasting serum total (TC), LDL (LDLc) and HDL (HDLc) cholesterol, and triglycerides (TG) were determined. After adjusting for potential covariates, multivariate analysis showed a dose-dependent inverse association of total PS intake with serum TC, LDLc, non-HDLc in women (P<0.001) and in men (P<0.05). As compared to the lowest quartile of PS intake (<206 mg/d), the multivariate-adjusted means of TC, LDLc and non-HDLc in the highest quartile of PS intake (447 mg/d) decreased by 5.0%, 6.2% and 6.5% in women (P<0.005), and by 6.4%, 7.1% and 6.7% (P>0.05) in men. Although the IMTs tended to be lower with greater intake of dietary PS, only small differences in the left internal IMT between the highest and lowest groups were observed among men (−7.6%) and women (−5.1%) (P<0.05). The multivariate analysis showed no significant mean differences among the PS groups in HDLc, TG and IMTs at other studied sites among men and women (all P>0.05).

Conclusions

Greater PS consumption from natural diets is associated with lower serum total, LDL, non-HDL cholesterol and with thinner left internal IMT in women and men.     

Serum YKL-40 Independently Predicts Outcome after Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma

Background

Transcatheter arterial chemoembolization (TACE) is the most widely used treatment option for unresectable hepatocellular carcinoma (HCC). Elevated serum YKL-40 level has been shown to predict poor prognosis in HCC patients undergoing resection. This study was designed to validate the prognostic significance of serum YKL-40 in patients with HCC undergoing TACE treatment.

Methods

Serum YKL-40 level was determined by enzyme-linked immunosorbent assay. Overall survival (OS) was evaluated with the Kaplan-Meier method and compared by the log-rank test. Multivariate study with Cox proportional hazard model was used to evaluate independent prognostic variables of OS.

Results

The median pretreatment serum YKL-40 in HCC patients with was significantly higher than that in healthy controls (P<0.001). The YKL-40 could predict survival precisely either in a dichotomized or continuous fashion (P<0.001 and P = 0.001, respectively). Multivariate Cox regression analysis indicated that serum YKL-40 was an independent prognostic factor for OS in HCC patients (P = 0.001). In further stratified analyses, YKL-40 could discriminate the outcomes of patients with low and high alpha-fetoprotein (AFP) level (P = 0.006 and 0.016, respectively). Furthermore, the combination of serum YKL-40 and AFP had more capacity to predict patients’ outcomes.

Conclusions

Serum YKL-40 was demonstrated to be an independent prognostic biomarker in HCC patients treated with TACE. Our results need confirmation in an independent study.     

Total and high molecular weight adiponectin and hepatocellular carcinoma with HCV infection

Background

Adiponectin is shown to be inversely associated with development and progression of various cancers. We evaluated whether adiponectin level was associated with the prevalence and histological grade of hepatocellular carcinoma (HCC), and liver fibrosis in patients with hepatitis C virus (HCV) infection.

Methods

A case-control study was conducted on 97 HCC patients (cases) and 97 patients (controls) matched for sex, Child-Pugh grade and platelet count in patients with HCV infection. The serum total and high molecular weight (HMW) adiponectin levels were measured by enzyme-linked immunosorbent assays and examined in their association with the prevalence of HCC. In addition, the relationship between these adiponectin levels and body mass index (BMI), progression of liver fibrosis, and histological grade of HCC was also evaluated. Liver fibrosis was assessed using the aspartate aminotransferase to platelet ratio index (APRI).

Results

There were no significant differences in the serum total and HMW adiponectin levels between cases and controls. Moreover, there were no inverse associations between serum total and HMW adiponectin levels and BMI in both cases and controls. On the other hand, serum total and HMW adiponectin levels are positively correlated with APRI in both cases (r = 0.491, P<0.001 and r = 0.485, P<0.001, respectively) and controls (r = 0.482, P<0.001 and r = 0.476, P<0.001, respectively). Interestingly, lower serum total (OR 11.76, 95% CI: 2.97–46.66 [P<0.001]) and HMW (OR 10.24, CI: 2.80–37.40 [P<0.001] adiponectin levels were independent risk factors of worse histological grade of HCC.

Conclusions

Our results suggested that serum total and HMW adiponectin levels were predictors of liver fibrosis, but not prevalence of HCC in patients with HCV infection. Moreover, low these adiponectin levels were significantly associated with worse histological grades.     

Physical fitness and telomere length in patients with coronary heart disease: findings from the Heart and Soul Study

Background

Short telomere length (TL) is an independent predictor of mortality in patients with coronary heart disease (CHD). However, the relationship between physical fitness and TL has not been explored in these patients.

Methods

In a cross sectional study of 944 outpatients with stable CHD, we performed exercise treadmill testing, assessed self-reported physical activity, and measured leukocyte TL using a quantitative PCR assay. We used generalized linear models to calculate mean TL (T/S ratio), and logistic regression models to compare the proportion of patients with short TL (defined as the lowest quartile), among participants with low, medium and high physical fitness, based on metabolic equivalent tasks achieved (METs).

Results

229 participants had low physical fitness (<5 METS), 334 had moderate physical fitness (5–7 METS), and 381 had high physical fitness (>7 METS). Mean ± T/S ratio ranged from 0.86±0.21 (5349±3781 base pairs) in those with low physical fitness to 0.95±0.23 (5566±3829 base pairs) in those with high physical fitness (p<.001). This association remained strong after adjustment for numerous patient characteristics, including measures of cardiac disease severity and physical inactivity (p = 0.005). Compared with participants with high physical fitness, those with low physical fitness had 2-fold greater odds of having TL in the lowest quartile (OR 2.39, 95% CI 1.60–3.55; p<.001). This association was similar after multivariable adjustment (OR 1.94, 95%CI, 1.18–3.20; p = 0.009). Self-reported physical inactivity was associated with shorter TL in unadjusted analyses, but not after multivariable adjustment.

Conclusions

We found that worse objectively-assessed physical fitness is associated with shorter leukocyte telomere length in patients with CHD. The clinical implications of this association deserve further study.     

Planning and monitoring of patients for electrical cardioversion for atrial fibrillation

Objectives

This study evaluated the waiting list for elective electrical cardioversion (ECV) for persistent atrial fibrillation (AF), focusing on when and why procedures were postponed. We compared the effects of management of the waiting list conducted by physicians versus management by nurse practitioners (NPs) and we evaluated the safety of our anticoagulating policy by means of bleeding or thromboembolic complications during and after ECV.

Background

Not all patients selected for ECV receive their treatment at the first planned instance due to a variety of reasons. These reasons are still undocumented.

Methods

We evaluated 250 consecutive patients with persistent AF admitted to our clinic for elective ECV.

Results

Within 5 to 6 weeks, 186 of 242 patients (77%) received ECV. The main reason for postponing an ECV was an inadequate international normalised ratio (INR); other reasons included spontaneous sinus rhythm and switch to rate control. A total of 23 of the 147 patients (16%) managed by the research physician were postponed due to an inadequate INR at admission versus 4 out of 98 patients (4%) managed by NPs (p = 0.005)

Conclusion

An inadequate INR is the main reason for postponing an ECV. Management of ECV by NPs is safe and leads to less postponing on admission.     

Circulating fibroblast growth factor 21 levels are closely associated with hepatic fat content: a cross-sectional study

Background and Aims

Fibroblasts growth factor 21 (FGF21), a liver-secreted endocrine factor involved in regulating glucose and lipid metabolism, has been shown to be elevated in patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the quantitative correlation between serum FGF21 level and hepatic fat content.

Methods

A total of 138 subjects (72 male and 66 female) aged from 18 to 65 years with abnormal glucose metabolism and B-ultrasonography diagnosed fatty liver were enrolled in the study. Serum FGF21 levels were determined by an in-house chemiluminescence immunoassay and hepatic fat contents were measured by proton magnetic resonance spectroscopy.

Results

Serum FGF21 increased progressively with the increase of hepatic fat content, but when hepatic fat content increased to the fourth quartile, FGF21 tended to decline. Serum FGF21 concentrations were positively correlated with hepatic fat content especially in subjects with mild/moderate hepatic steatosis (r = 0.276, p = 0.009). Within the range of hepatic steatosis from the first to third quartile, FGF21 was superior to any other traditional clinical markers including ALT to reflect hepatic fat content. When the patients with severe hepatic steatosis (the fourth quartile) were included, the quantitative correlation between FGF21 and hepatic fat content was weakened.

Conclusions

Serum FGF21 was a potential biomarker to reflect the hepatic fat content in patients with mild or moderate NAFLD. In severe NAFLD patients, FGF21 concentration might decrease due to liver inflammation or injury.     

Circulating endoglin concentration is not elevated in chronic kidney disease

Background

Soluble endoglin, a TGF-β receptor, plays a key role in cardiovascular physiology. Whether circulating concentrations of soluble endoglin are elevated in CKD or underlie the high risk of cardiovascular death associated with chronic kidney disease (CKD) is unknown.

Methods

Individuals with and without CKD were recruited at a single center. Estimated glomerular filtration rate (eGFR) was estimated using the modified MDRD study equation and the serum creatinine at the time of recruitment, and patients were assigned to specific CKD stage according to usual guidelines. Serum endoglin concentration was measured by ELISA and univariate and multivariable regression was used to analyze the association between eGFR or CKD stage and the concentration of soluble endoglin.

Results

Serum endoglin was measured in 216 patients including 118 with stage 3 or higher CKD and 9 individuals with end stage renal disease (ESRD). Serum endoglin concentration did not vary significantly with CKD stage (increase of 0.16 ng/mL per 1 stage increase in CKD, P = 0.09) or eGFR (decrease -0.06 ng/mL per 10 mL/min/1.73 m² increase in GFR, P = 0.12), and was not higher in individuals with ESRD than in individuals with preserved renal function (4.2±1.1 and 4.3±1.2 ng/mL, respectively). Endoglin concentration was also not significantly associated with urinary albumin excretion.

Conclusions

Renal function is not associated with the circulating concentration of soluble endoglin. Elevations in soluble endoglin concentration are unlikely to contribute to the progression of CKD or the predisposition of individuals with CKD to develop cardiovascular disease.     

Serum Gamma - Glutamyltransferase Is Associated with Albuminuria: A Population-Based Study

Background

Serum γ - glutamyltransferase (GGT) is implicated in the pathogenesis of endothelial dysfunction and atherosclerosis. Albuminuria is a marker of endothelial damage and correlated with structural and functional integrity of the vasculature. Our objective was to evaluate the association between serum GGT level and prevalence of albuminuria in a Chinese population.

Materials and Methods

We conducted a population-based cross-sectional study in 9,702 subjects aged 40 years or older. Increased urinary albumin excretion was defined according to the urinary albumin-to-creatinine ratio (ACR) ranges greater or equal than 30 mg/g. Low-grade albuminuria was defined according to the highest quartile of ACR in participants without increased urinary albumin excretion.

Results

The prevalence of low-grade albuminuria and increased urinary albumin excretion were respectively 23.4% and 6.6% in this population and gradually increased across the sex-specific serum GGT quartiles (all P for trend <0.05). In logistic regression analysis, compared with subjects in the lowest quartile of serum GGT level, the adjusted odds ratios (ORs) in the highest quartile was 1.22 [95% confidence interval (CI), 1.04–1.43] for low-grade albuminuria and 1.55 (95% CI, 1.18–2.04) for increased urinary albumin excretion. In subgroup analysis, significant relationship of serum GGT level with both low-grade albuminuria and increased urinary albumin excretion were detected in women, younger subjects, overweight subjects and in those with hypertension or glomerular filtration rate greater than 90 (all P <0.05).

Conclusion

Serum GGT level is associated with urinary albumin excretion in middle-aged and elderly Chinese.     

Chronic kidney disease itself is a causal risk factor for stroke beyond traditional cardiovascular risk factors: a nationwide cohort study in Taiwan

Background

Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in patients with chronic kidney disease (CKD). In Taiwan, CVD is dominated by strokes but there is no robust evidence for a causal relationship between CKD and stroke. This study aimed to explore such causal association.

Methods

We conducted a nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database from 2004 to 2007. Each patient identified was individually tracked for a full three years from the index admission to identify those in whom any type of stroke developed. The study cohort consisted of patients hospitalized with a principal diagnosis of CKD and no traditional cardiovascular risk factors at baseline (n = 1393) and an age-matched control cohort of patients hospitalized for appendectomies (n = 1393, a surrogate for the general population). Cox proportional hazard regression and propensity score model were used to compare the three-year stroke-free survival rate of the two cohorts after adjustment for possible confounding factors.

Results

There were 256 stroke patients, 156 (11.2%) in the study cohort and 100 (7.2%) in the control cohort. After adjusting for covariates, patients with primary CKD had a 1.94-fold greater risk for stroke (95% CI, 1.45–2.60; p<0.001) based on Cox regression and a 1.68-fold greater risk for stroke (95% CI, 1.25–2.25; p = 0.001) based on propensity score. This was still the case for two cohorts younger than 75 years old and without traditional cardiovascular risk factors.

Conclusions

This study of Taiwanese patients indicates that CKD itself is a causal risk factor for stroke beyond the traditional cardiovascular risk factors. Primary CKD patients have higher risk for stroke than the general population and all CKD patients, irrespective of the presence or severity of traditional cardiovascular risk factors, should be made aware of the stroke risk and monitored for stroke prevention.     

Measurement of warfarin in the oral fluid of patients undergoing anticoagulant oral therapy

Background

Patients on warfarin therapy undergo invasive and expensive checks for the coagulability of their blood. No information on coagulation levels is currently available between two controls.

Methodology

A method was developed to determine warfarin in oral fluid by HPLC and fluorimetric detection. The chromatographic separation was performed at room temperature on a C-18 reversed-phase column, 65% PBS and 35% methanol mobile phase, flow rate 0.7 mL/min, injection volume 25 µL, excitation wavelength 310 nm, emission wavelength 400 nm.

Findings

The method was free from interference and matrix effect, linear in the range 0.2–100 ng/mL, with a detection limit of 0.2 ng/mL. Its coefficient of variation was <3% for intra-day measurements and <5% for inter-day measurements. The average concentration of warfarin in the oral fluid of 50 patients was 2.5±1.6 ng/mL (range 0.8–7.6 ng/mL). Dosage was not correlated to INR (r = −0.03, p = 0.85) but positively correlated to warfarin concentration in the oral fluid (r = 0.39, p = 0.006). The correlation between warfarin concentration and pH in the oral fluid (r = 0.37, p = 0.009) confirmed the importance of pH in regulating the drug transfer from blood. A correlation between warfarin concentration in the oral fluid and INR was only found in samples with pH values ≥7.2 (r = 0.84, p = 0.004).

Conclusions

Warfarin diffuses from blood to oral fluid. The method allows to measure its concentration in this matrix and to analyze correlations with INR and other parameters.     

Prevalence and risk factors associated to chronic kidney disease in HIV-infected patients on HAART and undetectable viral load in Brazil

Background

To determine the prevalence and associated factors with chronic kidney disease (CKD) in a cohort of HIV-positive individuals with undetectable viral load on HAART.

Methods

From March, 2009 to September 2009, 213 individuals between 18-70 years, period on HAART ≥12 months, viral load < 50 copies/mm³, and CD4 ≥ 200 cells/mm³, were consecutively enrolled at the outpatient clinic of Hospital de Clínicas, Porto Alegre, Brazil. Exclusion criteria were obesity, malnourishment, amputee, paraplegic, previous history of renal disease, pregnancy and hepatic insufficiency. Renal function was determined by estimated glomerular filtration rate (eGFR) assessed by the modification of diet in renal disease. CKD was defined as an eGFR less or equal than 60 ml/min/1.73 m², for a period of at least 3 months. Poisson regression was used to determine factors associated with CKD.

Results

CKD was diagnosed in 8.4% of the population, and after adjustment, the risk factors were hypertension (RR = 3.88, 95%CI, 1.84 - 8.16), time on HAART (RR = 1.15, 95%CI,1.03–1.27) and tenofovir exposure (RR = 2.25, 95%CI, 1.04–4.95). Higher weight (RR = ,0.88 95%CI, 0.82–0.96) was associated to normal function.

Conclusions

CKD was a common finding in this cohort of patients and was related to hypertension, time on HAART and tenofovir exposure. We suggest a more frequent monitoring of renal function, especially for those with risk factors to early identify renal impairment.