Hung-Ju Lin

Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-analysis

Objective To assess the effects of different classes of antihypertensive treatments, including monotherapy and combination therapy, on survival and major renal outcomes in patients with diabetes. Design Systematic review and bayesian network meta-analysis of randomised clinical trials. Data sources Electronic literature search of PubMed, Medline, Scopus, and the Cochrane Library for studies published up to December 2011. Study selection Randomised clinical trials of antihypertensive therapy (angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), α blockers, β blockers, calcium channel blockers, diuretics, and their combinations) in patients with diabetes with a follow-up of at least 12 months, reporting all cause mortality, requirement for dialysis, or doubling of serum creatinine levels. Data extraction Bayesian network meta-analysis combined direct and indirect evidence to estimate the relative effects between treatments as well as the probabilities of ranking for treatments based on their protective effects. Results 63 trials with 36 917 participants were identified, including 2400 deaths, 766 patients who required dialysis, and 1099 patients whose serum creatinine level had doubled. Compared with placebo, only ACE inhibitors significantly reduced the doubling of serum creatinine levels (odds ratio 0.58, 95% credible interval 0.32 to 0.90), and only β blockers showed a significant difference in mortality (odds ratio 7.13, 95% credible interval 1.37 to 41.39). Comparisons among all treatments showed no statistical significance in the outcome of dialysis. Although the beneficial effects of ACE inhibitors compared with ARBs did not reach statistical significance, ACE inhibitors consistently showed higher probabilities of being in the superior ranking positions among all three outcomes. Although the protective effect of an ACE inhibitor plus calcium channel blocker compared with placebo was not statistically significant, the treatment ranking identified this combination therapy to have the greatest probability (73.9%) for being the best treatment on reducing mortality, followed by ACE inhibitor plus diuretic (12.5%), ACE inhibitors (2.0%), calcium channel blockers (1.2%), and ARBs (0.4%). Conclusions Our analyses show the renoprotective effects and superiority of using ACE inhibitors in patients with diabetes, and available evidence is not able to show a better effect for ARBs compared with ACE inhibitors. Considering the cost of drugs, our findings support the use of ACE inhibitors as the first line antihypertensive agent in patients with diabetes. Calcium channel blockers might be the preferred treatment in combination with ACE inhibitors if adequate blood pressure control cannot be achieved by ACE inhibitors alone.

Neurocognitive Improvement After Carotid Artery Stenting in Patients With Chronic Internal Carotid Artery Occlusion and Cerebral Ischemia

Background and Purpose— Chronic cerebral hypoperfusion may lead to impairment in neurocognitive performance in patients with chronic internal carotid artery occlusion, and the effects of carotid artery stenting on neurocognitive function have been unclear. Methods— We prospectively enrolled 20 chronic internal carotid artery occlusion patients with objective ipsilateral hemisphere ischemia, in whom carotid artery stenting was attempted. Functional assessments, including the National Institutes of Health Stroke Scale, Barthel Index, and a battery of neuropsychological tests, including the Mini-Mental State Examination, Alzheimer Disease Assessment Scale–Cognitive Subtest, verbal fluency, and Color Trail Making A and B, were administered before and 3 months after intervention. Results— Successful recanalization was achieved in 12 of 20 patients (60%). There was no procedural or new cerebral ischemic event, except for 1 intracranial hemorrhage, which occurred during the procedure and had neurologic sequelae; this case was excluded from analysis. The demographics and baseline cognitive performance were similar between the group with a successful outcome (group 1, n=12) and patients who did not (group 2, n=7). Ten of 12 patients in group 1 had improvement in ipsilateral brain perfusion after the procedure, but none in group 2 had improvement. Significant improvement in the scores on the Alzheimer Disease Assessment Scale–Cognitive Subtest (before, 7.7±8.9 versus after, 5.7±7.1; P=0.024), Mini-Mental State Examination (before, 25.8±3.8 versus after, 27.7±2.7; P=0.015), and Color Trail Making A (before, 123.2±68.6 versus after, 99.3±51.5; P=0.017) were found in group 1 but not in group 2. Conclusions— Successful carotid artery stenting improves global cognitive function as well as attention and psychomotor processing speed in patients with chronic internal carotid artery occlusion.

A Prediction Model for the Risk of Incident Chronic Kidney Disease

BACKGROUND Chronic kidney disease is a health burden for the general population. We designed a cohort study to construct prediction models for chronic kidney disease in the Chinese population. METHODS A total of 5168 participants were followed up during a median of 2.2 (interquartile range, 1.5-2.9) years, and 190 individuals (3.7%) developed chronic kidney disease, defined by a glomerular filtration rate of less than 60 mL/min/1.73 m(2). RESULTS We developed a point system to estimate chronic kidney disease risk at 4 years using the following variables: age (8 points), body mass index (2 points), diastolic blood pressure (2 points), and history of type 2 diabetes (1 point) and stroke (4 points) for the clinical model, with the addition of uric acid (2 points), postprandial glucose (1 point), hemoglobin A1c (1 point), and proteinuria 100 mg/dL or greater (6 points) for the biochemical model. Similar discrimination measures were found between the clinical model (area under the receiver operating characteristic curve, 0.768; 95% confidence interval (CI), 0.738-0.798) and the biochemical model (area under the receiver operating characteristic curve, 0.765; 95% CI, 0.734-0.796). The area under the receiver operating characteristic curve of the clinical model was 0.667 (95% CI, 0.631-0.703) for the external validation data from community-based cohort participants. The optimal cutoff value for the clinical model was set as 7, with a sensitivity of 0.76 and a specificity of 0.66. CONCLUSION We constructed a clinical point-based model to predict the 4-year incidence of chronic kidney disease. This prediction tool may help to target Chinese subjects at risk of developing chronic kidney disease.

Comparative assessment of the HAS-BLED score with other published bleeding risk scoring schemes, for intracranial haemorrhage risk in a non-atrial fibrillation population: The Chin-Shan Community Cohort Study

BACKGROUND The HAS-BLED score is a validated bleeding risk model for predicting major bleeding events in anticoagulated individuals with atrial fibrillation (AF). It remains uncertain whether the HAS-BLED score could identify non-AF individuals at risk of developing intracranial haemorrhage (ICH), which is the most intractable and devastating major bleeding complication. METHODS We assessed the predictive value of a modified HAS-BLED and other bleeding risk scoring models to predict the risk for ICH in the Chin-Shan Community Cohort, which followed 1899 women and 1703 men, aged >35 years, for a median of 15.9 years. ICH events (including haemorrhagic strokes) were ascertained according to questionnaires and the national register database. RESULTS Of 3524 individuals without baseline AF, 54 ICH events occurred during follow-up. The risk for ICH was raised with increasing HAS-BLED scores, and was significantly associated with uncontrolled hypertension and older age (Odds Ratios [95% confidence interval (CI)], 4.2[2.3-7.6] and 1.9[1.1-3.4], respectively). Among the five bleeding risk scoring schemes tested, HAS-BLED had highest general discrimination performance (c-statistic [95% CI], 0.72 [0.67-0.78]), and better ability to discriminate between those who were at risk for ICH and who were not (NRI, net reclassification improvement, all p<0.05, compared to other four scoring schemes). CONCLUSION The HAS-BLED score had the highest general discrimination performance and best ability to discriminate risk for ICH. This score may be of clinical use in predicting the risk for occurrence of ICH among non-AF individuals.

Postprandial Glucose Improves the Risk Prediction of Cardiovascular Death Beyond the Metabolic Syndrome in the Nondiabetic Population

OBJECTIVE With increasing evidence about the cardiovascular risk associated with postprandial nonfasting glucose and lipid dysmetabolism, it remains uncertain whether the postprandial glucose concentration increases the ability of metabolic syndrome to predict cardiovascular events. RESEARCH DESIGN AND METHODS This was an observational study of 15,145 individuals aged 35–75 years without diabetes or cardiovascular diseases. Postprandial glucose was obtained 2 h after a lunch meal. Metabolic syndrome was diagnosed using the criteria of the U.S. National Cholesterol Education Program Adult Treatment Panel III. Cardiovascular and all-cause deaths were primary outcomes. RESULTS During a median follow-up of 6.7 years, 410 individuals died, including 82 deaths from cardiovascular causes. In a Cox model adjusting for metabolic syndrome status as well as age, sex, smoking, systolic blood pressure, LDL, and HDL cholesterol levels, elevated 2-h postprandial glucose increased the risk of cardiovascular and all-cause death (per millimole per liter increase, hazard ratio 1.26 [95% CI 1.11–1.42] and 1.10 [1.04–1.16], respectively), with significant trends across the postprandial glucose quintiles. Including 2-h postprandial glucose into a metabolic syndrome–included multivariate risk prediction model conferred a discernible improvement of the model in discriminating between those who died of cardiovascular causes and who did not (integrated discrimination improvement 0.4, P = 0.005; net reclassification improvement 13.4%, P = 0.03); however, the improvement was only marginal for all-cause death. CONCLUSIONS Given the risk prediction based on metabolic syndrome and established cardiovascular risk factors, 2-h postprandial glucose improves the predictive ability to identity nondiabetic individuals at increased risk of cardiovascular death.

Cell therapy generates a favourable chemokine gradient for stem cell recruitment into the infarcted heart in rabbits

Stem cell recruitment into the heart is determined by a concentration gradient of stromal‐derived factor 1 (SDF‐1) from bone marrow to peripheral blood and from blood to injured myocardium. However, this gradient is decreased in chronic myocardial infarction (MI). This study evaluated the effect of cell therapy using bone marrow stromal cells (BMSCs) on an SDF‐1 gradient in post‐infarction rabbits.

Exercise training improves cardiac function in infarcted rabbits: involvement of autophagic function and fatty acid utilization.

To explore whether exercise can improve cardiac function in a post‐myocardial infarction (MI) rabbit model and to determine contributing factors in the left ventricle (LV).

Relationship between metabolic syndrome and diagnoses of periodontal diseases among participants in a large Taiwanese cohort

OBJECTIVE Epidemiological studies suggested that individuals suffering from periodontitis present with greater prevalence of metabolic syndrome (MetS) and diabetes. We used a large health check-up data set in Taiwan to investigate this association. DESIGN AND METHODS Data from 33,740 individuals, who undertook comprehensive health check-up at a university hospital in Taipei, Taiwan, were analysed. The dental examinations were undertaken by experienced dentists, and the diagnosis of MetS was made according to the criteria defined by the Third Adult Treatment Panel of the National Cholesterol Education Program. RESULTS After adjusting for potential confounders, females and males in the periodontitis group had higher levels of blood pressure, blood glucose, triglyceride and body mass index, but lower high-density lipoprotein compared to controls. Females in the gingivitis and periodontitis group showed greater odds ratios [1.42 (95% CI: 1.30-1.56) and 1.52 (1.41-1.63) respectively] of being diagnosed with MetS, whereas males in the gingivitis and periodontitis group presented with odds ratios of being diagnosed with MetS of 1.06 (0.94-1.18) and 1.04 (0.96-1.12) respectively. CONCLUSIONS A small but statistically significant association between MetS and the diagnosis of periodontal diseases was found in Taiwanese women and a weaker association in Taiwanese men.

Comparison of predictive performance of various fatty acids for the risk of cardiovascular disease events and all-cause deaths in a community-based cohort

BACKGROUND The issue of whether saturated fats and trans fats are superior predictors of all-cause death and cardiovascular disease than n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), remains a matter of contention. Furthermore, few studies have examined the relationship between fatty acids and the outcomes of cardiovascular disease (CVD) in Asian populations. The aim of this study was to compare the effectiveness of various plasma fatty acids as predictors for all-cause death and CVD events in an ethnic Chinese population. METHODS This study assembled a community-based prospective cohort, comprising 1833 participants (60.6 ± 10.5 yrs, 44.5% women) who underwent a comprehensive evaluation of fatty acids in blood using gas chromatography. None of the subjects had a history of CVD at the time of recruitment. RESULTS A total of 568 individuals died and 275 individuals developed CVD during the follow-up period (median of 9.6 years; interquartile range of 8.9-10.5 years). Following adjustment for established cardiovascular risk factors, the relative risk of all-cause death in the highest quartile, compared with the lowest quartile, was 1.33 for saturated fats (95% confidence interval [CI], 1.01-1.75, test for trend, P = 0.015), 1.71 for trans fats (95% CI, 1.27-2.31, test for trend, P = 0.0003), 0.77 for EPA (95% CI, 0.59-1.00, test for trend, P = 0.048), and 0.89 for DHA (95% CI, 0.68-1.18, test for trend, P = 0.354). Similar patterns were observed for CVD events. Trans fats presented the largest area under the receiver operator characteristic curve (0.740, 95% CI, 0.716-0.766) for the prediction of all-cause death. A mutually adjusted two-marker model indicated that saturated fats and trans fats were significant predictors of all-cause death and CVD; however, the other fatty acids were not. In addition, trans fats presented the greatest improvement in net reclassification for all-cause death (7.7%, P = 0.003), followed by EPA (3.8%, P = 0.033). Saturated fats presented the greatest improvement in net reclassification for CVD events (5.6%, P = 0.039). CONCLUSIONS Our data provides strong evidence to support that plasma saturated fats and trans fats can predict all-cause death and CVD more effectively than other fatty acid markers.

Association of circulating matrix metalloproteinase-1, but not adiponectin, with advanced coronary artery disease

OBJECTIVE Recent evidence suggests that high tissue matrix metalloproteinase-1 (MMP-1) and low adiponectin may serve as biomarkers of atherosclerosis. Results on the associations of circulating MMP-1 and adiponectin concentrations are scarce. We hypothesized that patients with multivessel coronary artery disease (CAD) have elevated high-sensitivity C-reactive protein (hs-CRP), MMP-1 but low adiponectin levels, and concomitant measurements of these biomarkers could improve predictive strength for advanced CAD. RESEARCH DESIGN AND METHODS We analyzed concentrations of MMP-1, hs-CRP and adiponectin in 217 subjects with angiographically documented multivessel CAD (two-, or three-vessel disease by luminal stenosis >or=50%) and 81 controls. MMP-1 and hs-CRP were notably higher in patients with CAD; while adiponectin was not significantly different between two groups. Levels of hs-CRP positively correlated with body mass index and left ventricular dysfunction (R(2)=0.16, P<0.0001); while adiponectin was significantly associated with age, gender, and levels of cholesterol and triglyceride (R(2)=0.09, P<0.0001). On the contrary, MMP-1 was not associated with any clinical cardiovascular risk factors, and still an independent predictor (OR=1.49, P<0.0001) of multivessel CAD after the adjustment of clinical risk factors and hs-CRP. CONCLUSION Elevated MMP-1 and hs-CRP, but not low adiponectin concentrations, could predict the presence of advanced coronary atherosclerosis. In addition, MMP-1 may serve as a more specific marker for significant CAD independent of hs-CRP.