High left ventricular mass associated with increased risk of incident diabetes.

Evidence for the role of electrocardiography or echocardiography in determining left ventricular hypertrophy for the risk of diabetes is still controversial. We aimed to explore whether left ventricular mass, as measured by these methods, is associated with the risk of diabetes in a community population. We recruited 2696 participants aged 35 years or older without diabetes who had undergone screening with electrocardiography and echocardiography. Left ventricular mass index (LVMI) was calculated using a formula, and participants were divided into tertiles based on their LVMI tertiles. During a median follow-up period of median, 8.9 years, a total of 405 participants developed diabetes. The incidence and risk of diabetes significantly increased with higher LVMI tertiles. Multivariate Cox regression analysis demonstrated that individuals in the highest LVMI tertile had a greater likelihood of developing incident diabetes, with a hazard ratio of 1.40 (95% CI 1.06-1.91), even after adjusting related covariates. The highest risk of diabetes was observed in the presence of both the uppermost LVMI tertile and electrocardiographically determined left ventricular hypertrophy for the Chinese population. Left ventricular hypertrophy identified by either electrocardiography or echo may serve as a surrogate marker for identifying the risk of diabetes in clinical practice.

Associations between fibrinogen levels and the risk of cardiovascular disease and all-cause death: a cohort study from the Chin-Shan community in Taiwan.

OBJECTIVES: Although several studies have investigated the association between fibrinogen level and the risk of cardiovascular disease (CVD), few studies have been conducted in Asia. SETTING: We conducted a community-based prospective cohort study in the Chin-Shan community, Taiwan. PARTICIPANTS: A total of 2222 participants (54.6±11.9 years, 53.4% women, and 22.4 years of follow-up) who underwent plasma fibrinogen measurements and were without CVD at baseline were recruited, among which 735 participants with available C reactive protein (CRP) were included in the joint analysis of the association of fibrinogen and CRP levels with the risk of CVD. PRIMARY AND SECONDARY OUTCOME MEASURES: Fibrinogen and CRP levels were measured by clotting and high-sensitivity immunoturbidimetric assays, respectively. The study outcomes were CVD events and all-cause death. Our definition of CVD included both coronary artery disease (CAD) and stroke cases. Cox proportional hazards regression models were used to estimate the HRs and 95% CIs. RESULTS: Compared with the lowest quartile, participants with higher fibrinogen levels tended to have a higher risk of CAD (adjusted HR for the highest quartile=1.48 (95% CI 0.90 to 2.44); test for trend p=0.037) regardless of CRP level (adjusted HR=2.12 (95% CI 1.24 to 3.63) and 2.17 (95% CI 1.06 to 4.44) for high fibrinogen/low CRP and high fibrinogen/high CRP, respectively). The association was not observed for stroke (adjusted HR for the highest quartile=0.99 (95% CI 0.62 to 1.60); test for trend p=0.99) and was only observed for all-cause death among participants <65 years of age (adjusted HR for the highest quartile=1.47 (95% CI 1.11 to 1.95); test for trend p=0.004). CONCLUSIONS: Fibrinogen may be a potential risk factor for CAD but not for stroke. Further studies are necessary to clarify the differences in the role of fibrinogen levels on the risk of CVD between Asian and Western countries.

Urinary sodium excretion and the risk of CVD: a community-based cohort study in Taiwan.

Urinary Na excretion is a potential risk factor for CVD. However, the underlying biological mechanisms and effects of salt sensitivity are unclear. The purpose of this study was to characterise the relative contribution of biological factors to the Na-CVD association. A total of 2112 participants were enrolled in this study. Structured questionnaires and blood and urine samples were obtained. Twenty-four-hour Na excretion was estimated using a single overnight urine sample. Hypertension, the metabolic syndrome and overweight status were considered to indicate salt sensitivity. Cox proportional hazard models were used to investigate the effects of salt sensitivity on urinary Na excretion and CVD risk. The traditional mediation approach was used to calculate the proportion of mediation. The mean age (sd) of the 2112 participants was 54·5 (sd 12·2) years, and they were followed up for a mean of 14·1 (sd 8·1) years. Compared with those in the lowest quartile, the highest baseline urinary Na excretion (>4·2 g/24 h) was associated with a 43 % higher CVD risk (hazard ratio, 1·43; 95 % CI 1·02, 1·99). Participants with high urinary Na excretion, hypertension or the metabolic syndrome had a significantly high risk of CVD. The carotid intima-media thickness had the largest mediating effect (accounting for 35 % of the Na-CVD association), followed by systolic blood pressure (BP) (33 %), left ventricular mass (28 %) and diastolic BP (14 %). Higher urinary Na excretion increased the risk of CVD, which was explained largely by carotid media-thickness and systolic BP.

Statin-induced microRNAome alterations modulating inflammation pathways of peripheral blood mononuclear cells in patients with hypercholesterolemia.

Statins inhibit cholesterol biogenesis and modulate atheroma inflammation to reduce cardiovascular risks. Promoted by immune and non-immune cells, serum C-reactive protein (CRP) might be a biomarker suboptimal to assess inflammation status. Although it has been reported that statins modulated inflammation via microRNAs (miRNAs), evidence remains lacking on comprehensive profiling of statin-induced miRNAome alterations in immune cells. We recruited 19 hypercholesterolemic patients receiving 2 mg/day pitavastatin and 15 ones receiving 10 mg/day atorvastatin treatment for 12 weeks, and performed microarray-based profiling of 1733 human mature miRNAs in peripheral blood mononuclear cells (PBMCs) before and after statin treatment. Differentially expressed miRNAs were determined if their fold changes were >1.50 or <0.67, after validated using quantitative polymerase chain reaction (qPCR). The miRSystem and miTALOS platforms were utilized for pathway analysis. Of the 34 patients aged 63.7 ± 6.2 years, 27 were male and 19 were with coronary artery disease. We discovered that statins induced differential expressions of miR-483-5p, miR-4667-5p, miR-1244, and miR-3609, with qPCR-validated fold changes of 1.74 (95% confidence interval, 1.33-2.15), 1.61 (1.25-1.98), 1.61 (1.01-2.21), and 1.68 (1.19-2.17), respectively. The fold changes of the four miRNAs were not correlated with changes of low-density-lipoprotein cholesterol or CRP, after sex, age, and statin type were adjusted. We also revealed that RhoA and transforming growth factor-ß signaling pathways might be regulated by the four miRNAs. Given our findings, miRNAs might be involved in statin-induced inflammation modulation in PBMCs, providing likelihood to assess and reduce inflammation in patients with atherosclerotic cardiovascular diseases.

Association of heart rate trajectories with the risk of adverse outcomes in a community-based cohort in Taiwan.

Heart rate trajectory patterns integrate information regarding multiple heart rate measurements and their changes with time. Different heart rate patterns may exist in one population, and these are associated with different outcomes. Our study investigated the association of adverse outcomes with heart rate trajectory patterns. This was a prospective cohort study based on the Chin-Shan Community Cardiovascular Cohort in Taiwan. A total of 3,015 Chinese community residents aged > 35 years were enrolled in a prospective investigation of cardiovascular risk factors and outcomes from 1990 to 2013.The primary outcome was all-cause mortality, and the secondary outcome was a composite of coronary artery disease and cerebrovascular accidents. The following trajectory patterns were identified: stable, 61%; decreased, 5%; mildly increased, 32%; and markedly increased, 2%. During follow-up (median, 13.9 years), 557 participants died and 217 experienced secondary outcomes. The adjusted hazard ratios of primary and secondary outcomes for participants with a markedly increased trajectory pattern were 1.80 (95% CI [1.18-2.76]) and 1.45 (95% CI [0.67-3.12]), respectively, compared to those for participants with a stable trajectory pattern. A markedly increased heart rate trajectory pattern may be associated with all-cause mortality risks. Heart rate trajectory patterns demonstrated the utility of repeated heart rate measurements for risk assessment.

Association between Plasma N-6 Polyunsaturated Fatty Acids Levels and the Risk of Cardiovascular Disease in a Community-based Cohort Study.

Most studies support that saturated fatty acid replacement with polyunsaturated fatty acids (PUFAs) may reduce the risk of cardiovascular diseases (CVDs) and put emphasis on the effects of N-3 PUFAs. The reported relationships between N-6 PUFAs and CVD risks vary. We aimed to examine the associations between N-6 PUFA concentrations and CVD risks. In this community-based prospective cohort study on CVD-free patients at baseline (N = 1835, age: 60.6 ± 10.5 years, women: 44.5%), we measured the fatty acid concentrations in the blood using gas chromatography. Four hundred twenty-four participants developed CVDs during follow up. The total N-6 PUFA concentration was inversely associated with the CVD risk, with a 48% lower risk in the highest N-6 PUFA concentration quartile (hazard ratio = 0.52; P for trend <0.001). The estimated population attributable risk of N-6 PUFAs indicated that approximately 20.7% of CVD events would have been prevented if the plasma N-6 PUFA concentration had been higher than the median value. The total N-6 PUFA concentration presented the highest net reclassification improvement (NRI = 7.2%, P = 0.03) for predicting incident CVD. Further studies on N-6 PUFAs, diet habits, and their relationships with healthcare are warranted.

Differential effects of saturated fatty acids on the risk of metabolic syndrome: a matched case-control and meta-analysis study.

BACKGROUND: We investigated the association between plasma saturated fatty acids (SFAs) and the risk of metabolic syndrome among ethnic Chinese adults in Taiwan who attended a health check-up center. METHODS: A case-control study based on 1000 cases of metabolic syndrome and 1:1 matched control participants (mean age, 54.9 ±â€¯10.7 y; 36% females) were recruited. Metabolic syndrome was defined according to the criteria of the International Diabetes Federation. Gas chromatography was used to measure the distribution of fatty acids in plasma (% of total fatty acids). RESULTS: Even-chain SFAs, including 14:0, 16:0, and 18:0, were associated with metabolic syndrome; the adjusted odds ratio [OR] and 95% confidence interval [CI] per standard deviation [SD] difference was 3.32, [1.98-5.59]; however, very-long-chain SFAs, including 20:0, 21:0, 22:0, 23:0, and 24:0, were inversely associated with metabolic syndrome. The adjusted OR [95% CI] per SD difference was 0.67 [0.58-0.78]. The area under the receiver operative characteristic curve increased from 0.814 in the basic model to 0.815 (p = 0.54, compared with the basic model), 0.818 (p < 0.0001), and 0.820 (p < 0.0001) after adding odd-chain, even-chain, and very-long chain SFAs. A meta-analysis based on 12 studies showed that the summarized OR for type 2 diabetes mellitus was 1.16 [0.96-1.41] for the top versus bottom SFAs. CONCLUSIONS: Different carbon numbers of SFAs have been shown to have differential effects on the status of metabolic syndrome, implying that SFAs are not homogenous for the effects.

Association between plasma homocysteine concentration and the risk of all-cause death in adults with diastolic dysfunction in a community: A 13-year cohort study.

Hyperhomocysteinemia (HHCYS) has been associated with systolic heart failure. However, it is still unknown that serum homocycsteine level was useful in predicting the outcome in patients with diastolic dysfunction. We conducted a cohort study to determine if HHCYS was associated with poor prognosis in diastolic dysfunction patients. The Chin-Shan Community Cardiovascular Cohort (CCCC) study was designated to investigate the trends of cardiovascular morbidity and mortality in a community. Individuals who were 35 years and above were enrolled. Participants were categorized by homocysteine concentration quartiles. We used multivariate Cox proportional hazards models to calculate the hazard ratio (HR) of the 4th quartiles versus the 1st quartile. Area under the receiver-operating characteristic (ROC) curve was to compare prediction measures. A total of 2020 participants had completed the echocardiography examination, and 231 individuals were diagnosed as diastolic dysfunction. A total 75 participants had died during follow-up period. HHCYS was found to be significantly associated with poor prognosis. The adjusted HR for homocysteine level was 1.07 (95% confidence interval [CI], 1.01-1.14). Participants in the highest quartile had a 1.90 (95% CI, 0.88-4.12, P for trend, .026) fold risk for all cause death, compared with those in the lowest quartiles. The HR was 1.88 (95% CI, 1.07-3.29) using 11.11 µmol/L as cut point for hyperhomocysteine. HHCYS was significantly associated with poor prognosis in diastolic dysfunction participants in the community.

Association between type 2 diabetes and cancer incidence in Taiwan: data from a prospective community-based cohort study.

AIMS: Evidence of a role for type 2 diabetes in overall cancer risk and risk for specific types of cancer is limited in ethnic Chinese populations. We therefore investigated whether there is an association between diabetes and cancer incidence in Taiwan. METHODS: This study recruited a total of 3602 adults aged 35 years or over (average 54.9 ± 12.3 years, 52.8% women). Participants with fasting glucose ≥126 mg/dL, or taking hypoglycemic medications, were classed as having type 2 diabetes. Cancer incidence was established through regular follow-up interviews and medical records. Cox proportional hazard regression models were used to examine associations for diabetes with risk of all-cause and site-specific cancers. RESULTS: During a median of follow-up of 10.5 years, 275 individuals developed cancer, including 157 digestive cancers and 31 urinary cancers. Younger participants (aged < 55 years) with diabetes had a greater risk of all cancers [adjusted relative risk (RR) 3.42; 95% confidence interval (CI), 1.78-6.57], digestive cancers (adjusted RR 2.88; 95% CI 1.15-6.94) and urinary cancers (adjusted RR 13.4; 95% CI 2.70-66.3) compared with individuals in the same age group without diabetes. CONCLUSIONS: Our results clearly demonstrate that middle-aged individuals of Chinese ethnicity with diabetes have a greater risk of all-cause cancer and specific subtypes of cancer.

Carotid Atherosclerosis Progression and Risk of Cardiovascular Events in a Community in Taiwan.

The authors investigated the association between progression of carotid atherosclerosis and incidence of cardiovascular disease in a community cohort in Taiwan. Data has rarely been reported in Asian populations. Study subjects were 1,398 participants who underwent ultrasound measures of common carotid artery intima-media thickness (IMT) and extracranial carotid artery plaque score at both 1994-1995 and 1999-2000 surveys. Cox proportional hazards model was used to assess the risk of incident cardiovascular disease. During a median follow-up of 13 years (1999-2013), 71 strokes and 68 coronary events occurred. The 5-year individual IMT change was not associated with development of cardiovascular events in unadjusted and adjusted models. Among subjects without plaque in 1994-1995, we observed elevated risk associated with presence of new plaque (plaque score >0 in 1999-2000) in a dose-response manner in unadjusted and age- and sex- adjusted models. The associations attenuated and became statistically non-significant after controlling for cardiovascular risk factors (hazard ratio [95% confidence interval] for plaque score >2 vs. 0: stroke, 1.61 [0.79-3.27], coronary events, 1.13 [0.48-2.69]). This study suggested that carotid plaque formation measured by ultrasound is associated increased risk of developing cardiovascular disease, and cardiovascular risk factors explain the associations to a large extent.

Angiotensin receptor blockers (ARB) outperform angiotensin-converting enzyme (ACE) inhibitors on ischemic stroke prevention in patients with hypertension and diabetes - A real-world population study in Taiwan.

BACKGROUND: Combination therapy with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) has been stressed for its comprehensive blocking of the renin-angiotensin-aldosterone system, but the evidence for their respective safety and efficacy, in particular with stroke prevention, is still insufficient in population-based follow-up studies in the real world. METHODS: Using Taiwan's National Health Insurance claims data, we identified 5445 subjects aged 18years and older who had newly diagnosed hypertension in 1997-2010, from them diagnosed type 2 diabetes later. Among them, 2161 patients took ACEI, 1703 patients took ARB, 165 patients took both ACEI and ARB, and 1416 patients had neither. RESULTS: During the follow-up period, the stroke incidence density was the lowest (23.02 per 1000person-years) in ARB group, followed by the group with neither medication, the ACEI group, and ARB/ACEI combination group (24.06, 30.23, and 37.86 per 1000person-years, respectively). Compared with patients taking neither medication, the adjusted hazard ratios (HRs) were 1.27 (95% CI 1.02-1.58) for ACEI group, 0.95 (95% CI 0.74-1.22) for ARB group, and 1.56 (95% CI 0.99-2.47) for ARB/ACEI combined group. Greater reduction in risk of stroke was observed in patients with high dose ARB (adjusted HR=0·42, 95% CI 0·24-0·75). CONCLUSION: Our findings support the practice that ARBs could be used, from the perspective of stroke prevention, as a first-line antihypertensive drug for patients with both hypertension and diabetes. The group with ARB regimen reduces 26% of stroke in contrast to the group with ACEI regimen.

Total 25-hydroxyvitamin D concentration as a predictor for all-cause death and cardiovascular event risk among ethnic Chinese adults: a cohort study in a Taiwan community.

BACKGROUND: Evidence of an inverse association between serum 25-hydoroxyvitamin D [25(OH)D] and the risk of all-cause death and cardiovascular disease from prospective studies is inconsistent. We tested the relationship between 25(OH)D and the risk among adult ethnic Chinese in Taiwan. METHODS: We conducted a community-based cohort study of 1816 participants (age 60.2±10.2 yrs, 45.0% women) in the Chin-Shan Community Cardiovascular Cohort Study who were free of cardiovascular diseases at baseline and provided 25(OH)D measurements. RESULTS: During a median 9.6 (interquartile range, 8.8- 10.5) years' follow-up period, totally 263 cases developed cardiovascular death events and 559 participants were documented to death from any cause. As 25(OH)D concentration increased, the incidence rates of cardiovascular events and all-cause death decreased progressively. 25(OH)D was inversely associated with all-cause death: the adjusted hazard ratio was 0.49 (95% confidence interval [CI], 0.25-0.97) for the third quartile and a significant J-shape relationship was found. The performance measures by integrated discriminative improvement showed significant improvement after adding 25(OH)D information (0.14%, 95% CI, 0.03-0.31, P=0.050, for all-cause death and 0.32%, 95% CI, 0.02-0.62, P=0.018 for cardiovascular events). CONCLUSION: These findings suggested a modest inverse association between 25(OH)D and the risk of all-cause death among diabetic participants and a good predictive factor in the community. Further studies to investigate the mechanism of vitamin D role on health effect are warranted.

Urinary biomarkers of oxidative and nitrosative stress and the risk for incident stroke: a nested case-control study from a community-based cohort.

BACKGROUND: Oxidative and nitrosative stress has suggested to be involved in the pathophysiology of cardiovascular diseases, but has unclear relationship with the risk for incident stroke. METHODS: In this nested case-control study, cases consisted of 131 participants who were free of stroke at screening and experienced incident stroke during the follow-up period. Controls were 1:1 frequency-matched for age and sex. Baseline levels of urinary creatinine-indexed biomarkers were measured using liquid chromatography-tandem mass spectrometry, including 8-iso-prostaglandin F2α (8-iso-PGF2α), 4-hydroxynonenal conjugate with mercapturic acid, 8-hydroxydeoxyguanosine and 8-nitroguanine. RESULTS: The levels of urinary 8-iso-PGF2α in stroke cases were higher than in controls [median (interquartile range), 1.13 (2.23-4.36) µg/g creatinine versus 0.71 (1.34-3.02) µg/g creatinine, p=0.004]. After adjusting cardiovascular risk factors, the association remained that higher level of urinary 8-iso-PGF2α entailed the greater risk for incident stroke [per 1 standard deviation increase in log-transformed value, adjusted odds ratio, 1.40; 95% confidence interval (CI), 1.06-1.85; p=0.005] with a significant increasing trend across its quartiles (p for trend=0.016). After adding urinary 8-iso-PGF2α, the prediction model not only improved discrimination between participants with or without incident stroke (integrated discrimination improvement, 0.025; 95% CI, 0.006-0.045; p=0.005), but enhanced stroke risk stratification (net reclassification improvement, 19.8%; 95% CI, 4.6-35.1%; p=0.011). In contrast, the relationships were non-significant among the other three biomarkers. CONCLUSIONS: Our findings demonstrated that urinary 8-iso-PGF2α could be an independent biomarker of oxidative stress for prediction of the risk for incident stroke.

Increased risk of cardiovascular events in patients with herpes zoster: a population-based study.

The association between herpes zoster and cardiovascular complications remains vague with limited study on the association between these two disorders. This study evaluated the risk of cardiovascular diseases in patients with herpes zoster. From insurance claims data of Taiwan, 19,483 patients with herpes zoster diagnosed in 1998-2008 and 77,932 subjects without herpes zoster were identified in this study. Both cohorts were followed up until the end of 2010 to measure the incidence of arrhythmia and coronary artery disease. The incidence rate ratio and adjusted hazard ratio (HR) of the cardiovascular complications with 95% confidence interval (CI) were estimated. The incidence of arrhythmia was 1.17-fold greater in the herpes zoster cohort than in the non-herpes zoster cohort (13.2 vs. 11.3 per 1,000 person-years), with an adjusted HR of 1.16 (P < 0.01). The coronary artery disease incidence in the herpes zoster cohort was 1.16-fold higher than that in the non-herpes zoster cohort (9.02 vs. 7.83 per 1,000 person-years), with an adjusted HR of 1.11 (P < 0.01). Over the stratified follow-up years, adjusted HRs were 1.22 (95% CI = 1.12-1.34) for arrhythmia and 1.14 (95% CI = 1.02-1.28) for coronary artery disease within 2 years after herpes zoster diagnosis. The risk measured for these disorders declined over time. Comorbidities of hypertension, diabetes, and hyperlipidemia also contributed to these cardiovascular disorders with greater extent. It is concluded that the contribution of herpes zoster to the risk of arrhythmia and cardiovascular diseases is less strong than that of hypertension, diabetes, and hyperlipidemia.

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.

Aspirin protects human coronary artery endothelial cells against atherogenic electronegative LDL via an epigenetic mechanism: a novel cytoprotective role of aspirin in acute myocardial infarction.

AIMS: L5 is the most negatively charged subfraction of human low-density lipoprotein (LDL) and is the only subfraction of LDL capable of inducing apoptosis in cultured vascular endothelial cells (ECs) by inhibiting fibroblast growth factor-2 (FGF2) transcription. We examined whether plasma L5 levels are elevated in patients with ST-segment elevation myocardial infarction (STEMI) and whether aspirin provides epigenetic protection of human coronary artery ECs (HCAECs) exposed to L5. METHODS AND RESULTS: Plasma L5 levels were compared between patients with STEMI (n = 10) and control subjects with chest pain syndrome but a normal coronary arteriogram (n = 5). L5 was isolated from the plasma of STEMI patients and control subjects, and apoptosis, FGF2 expression, and FGF2 promoter methylation were examined in HCAECs treated with L5 and aspirin. Plasma L5 levels were significantly higher in STEMI patients than in control subjects (P < 0.001). Treatment of HCAECs with L5 resulted in reduced survival and FGF2 expression and increased CpG methylation of the FGF2 promoter. Co-treatment of HCAECs with L5 and a physiologically relevant, low concentration of aspirin (0.2 mM) attenuated the adverse effects of L5 on HCAEC survival, FGF2 expression, and FGF2 promoter methylation. In contrast, high concentrations of aspirin (≥1.0 mM) accentuated the effects of L5. CONCLUSIONS: Our results show that L5 levels are significantly increased in STEMI patients. Furthermore, L5 impairs HCAEC function through CpG methylation of the FGF2 promoter, which is suppressed in the presence of low-concentration aspirin. Our results provide evidence of a novel mechanism of aspirin in the prevention of MI.

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.

Total white blood cell count or neutrophil count predict ischemic stroke events among adult Taiwanese: report from a community-based cohort study.

BACKGROUND: Evidence about whether white blood cell (WBC) or its subtypes can act as a biomarker to predict the ischemic stroke events in the general population is scanty, particularly in Asian populations. The aim of this study is to establish the predictive ability of total WBC count or subtypes for long-term ischemic stroke events in the cohort population in Taiwan. METHODS: The Chin-Shan Community Cohort Study began from 1990 to 2007 by recruiting 1782 men and 1814 women of Chinese ethnicity. Following a total of 3416 participants free from ischemic stroke events at baseline for a median of 15.9 years; we documented 187 new incident cases. RESULTS: The multivariate relative risk for the comparison of the participants in the fifth and first WBC count quintiles was 1.67 (95% confidence interval [CI], 1.02-2.73; P for trend=0.03), and the corresponding relative risk for neutrophil count was 1.93 (95% CI, 1.13-3.29; P for trend=0.02). The discriminative ability by WBC and neutrophil counts were similar (area under the receiver operating characteristic curve, 0.600 for adding WBC, 0.610 for adding neutrophils, 0.595 for traditional risk factor model). In addition, the net reclassification improvement (NRI) values between the neutrophil and white blood cell count models were not significant (NRI, =-2.60%, P=0.35), indicating the similar discrimination performance for both WBC and neutrophil counts. CONCLUSIONS: WBC and neutrophil count had a similar ability to predict the long-term ischemic stroke events among Taiwanese.

Comparative assessment of published atrial fibrillation stroke risk stratification schemes for predicting stroke, in a non-atrial fibrillation population: the Chin-Shan Community Cohort Study.

BACKGROUND: In patients at high risk of stroke, such as atrial fibrillation (AF), there has been great interest in developing stroke risk prediction schemes for identifying those at high risk of stroke. Stroke risk prediction schemes have also been developed in non-AF populations, but are limited by lack of simplicity, which is more evident in schemes used in AF populations. We hypothesized that contemporary stroke risk stratification schemes used in assessing AF patients could predict stroke and thromboembolism in a non-AF community population, comparably to that seen in AF populations. METHODS: We tested the CHADS2 and CHA2DS2-VASc schemes, as well as the AF stroke risk stratification schemes from the Framingham study, Rietbrock et al., 2006 ACC/AHA/ESC guidelines, the 8th American College of Cardiology (ACCP) guidelines and NICE, for predicting stroke in a large community cohort of non-AF subjects, the Chin-Shan Community Cohort Study. RESULTS: The tested schemes had variable classification into low, moderate and high risk strata, with the proportion classified as low risk ranging from 5.4% (Rietbrock et al. to 59.0% (CHADS2 classical). Rates of stroke also varied in those classified as 'low risk' ranging from 1.1% (Rietbrock et al. to 3.5% (Framingham). All common risk schemes had broadly similar c-statistics, ranging from 0.658 (Framingham) to 0.728 (CHADS2 classical) when assessed as a continuous risk variable for predicting stroke in this population, with clear overlap between the 95% CIs. In an exploratory analysis amongst AF subjects in our population, the c-statistics were broadly similar to those seen in non-AF subjects. CONCLUSION: Contemporary stroke risk stratification schema used for AF can also be applied to non-AF populations with a similar (modest) predictive value. Given their simplicity (e.g. CHADS2 score), these scores could potentially be used for a 'quick' evaluation of stroke risk in non-AF populations, in a similar manner to AF populations.