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.

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.

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.

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.

Increased Rosuvastatin Dose versus Concomitant Fenofibrate and Rosuvastatin Therapy to Achieve Lipid Goal in Patients with Diabetes or Atherosclerosis with Metabolic Syndrome.

PUPOSE: We aimed to ascertain whether increased rosuvastatin dose is non-inferior to concomitant fenofibrate and rosuvastatin therapy in patients with diabetes or atherosclerosis with metabolic syndrome. METHODS: After treatment with rosuvastatin 5 mg/day for 12 weeks, 112 patients were randomly assigned to receive either 10 mg/day rosuvastatin (group A) or 80 mg/day supra-film coated fenofibrate plus 5 mg/day rosuvastatin (group B). The therapy effects were evaluated by measuring the serum lipid profile, liver and muscle enzymes, and renal function after the treatment period. RESULTS: After the treatment, the total cholesterol, high-density-lipoprotein cholesterol (HDL-C), non HDL-C, low-density-lipoprotein cholesterol (LDL-C), and triglyceride were comparable between the 2 groups. The change in the non-HDL-C were -7.39 ± 26.58 (-6.62%) and -0.68 ± 24.49 (-1.19%) mg/dl (p = 0.28); and the change in the triglyceride were -36.61 ± 62.51 (-14.00%) and -44.77 ± 77.35 (-23.17%) mg/dl (p = 0.64), respectively. While 41.37% of group A and 38.69% of group B achieved their LDL-C goal (< 100 mg/dl) (p = 0.79), 37.26% of group A and 42.31% of group B achieved their triglyceride goal (< 150 mg/dl) (p = 0.53), respectively. The changes in the serum transaminase and creatinine phosphokinase were similar between the 2 groups. CONCLUSIONS: After 5 mg/day of rosuvastatin, the lipid profile in patients with diabetes or atherosclerotic vascular diseases with metabolic syndrome could be improved by increasing rosuvastatin dose, and the resultant decrease of non-HDL and triglyceride were similar to those obtained with combination therapy. Both therapies were safe and feasible. KEY WORDS: Combination therapy; Diabetes; Fenofibrate; Metabolic syndrome; Monotherapy; Statin.

Electronegative low-density lipoprotein induces cardiomyocyte apoptosis indirectly through endothelial cell-released chemokines.

Cardiomyocyte apoptosis has a critical role in the pathogenesis of heart failure. L5, the most negatively charged subfraction of human plasma low-density lipoprotein (LDL), induces several atherogenic responses in endothelial cells (ECs), including apoptosis. We hypothesized that L5 also contributes to cardiomyocyte apoptosis and studied whether it does so indirectly by inducing the secretion of factors from ECs. We examined apoptosis of rat cardiomyocytes treated with culture-conditioned medium (CCM) of rat ECs that were exposed to L5 or L1 (the least negatively charged LDL subfraction). Apoptosis at early and late time points was twofold greater in cardiomyocytes treated with L5 CCM than in those treated with L1 CCM. The indirect effect of L5 on cardiomyocyte apoptosis was significantly reduced by pretreating ECs with inhibitors of phosphatidylinositol 3-kinase (PI3K) or CXC receptor 2 (CXCR2). Studies with cytokine protein arrays revealed that L5 CCM, but not L1 CCM, contained high levels of ELR(+) CXC chemokines, including lipopolysaccharide-induced chemokine (LIX) and interleukin (IL)-8. The L5-induced release of these chemokines from ECs was abolished by inhibiting the lectin-like oxidized LDL receptor-1 (LOX-1). Addition of recombinant LIX or IL-8 to CCM-free cardiomyocyte cultures increased apoptosis and enhanced production of tumor necrosis factor (TNF)-α and IL-1ß by increasing the translocation of NF-κB into the nucleus; these effects were attenuated by inhibiting PI3K and CXCR2. In conclusion, L5 may indirectly induce cardiomyocyte apoptosis by enhancing secretion of ELR(+) CXC chemokines from ECs, which in turn activate CXCR2/PI3K/NF-κB signaling to increase the release of TNF-α and IL-1ß.

The most negatively charged low-density lipoprotein L5 induces stress pathways in vascular endothelial cells.

BACKGROUND/AIMS: L5, the most negatively charged species of low-density lipoprotein (LDL), has been implicated in atherogenesis by inducing apoptosis of endothelial cells (ECs) and inhibiting the differentiation of endothelial progenitor cells. In this study, we compared the effects of LDL charge on cellular stress pathways leading to atherogenesis. METHODS: We isolated L5 and L1 (the least negatively charged LDL) from the plasma of patients with familial hypercholesterolemia and used JC-1 staining to examine the effects of L5 and L1 on the mitochondrial membrane potential (DCm) in human umbilical vein ECs (HUVECs). Additionally, we characterized the gene expression profiles of 7 proteins involved in various types of cellular stress. RESULTS: The DCm was severely compromised in HUVECs treated with L5. Furthermore, compared with L1, L5 induced a decrease in mRNA and protein expression of the endoplasmic reticulum (ER) chaperone proteins ORP150, Grp94, and Grp58, mitochondrial proteins Prdx3 and ATP synthase, and an increase in the expression of the pro-inflammatory protein hnRNP C1/C2. CONCLUSIONS: Our work suggests that L5, but not L1, may promote the destruction of ECs that occurs during atherogenesis by causing mitochondrial dysfunction and modulating the expression of key proteins to promote inflammation, ER dysfunction, oxidative stress, and apoptosis.

Differential effects of the changes of LDL cholesterol and systolic blood pressure on the risk of carotid artery atherosclerosis.

BACKGROUND: The effects of baseline and changes in blood pressure and low density lipoprotein (LDL) cholesterol on the carotid intima media thickness (IMT) have not been well documented. METHODS: A total of 2572 adults (mean age 53.8 years, 54.6% women) in a Taiwanese community undertook three blood pressure and LDL cholesterol examinations over 6 years. Latent growth curve modeling was used to investigate the effects of baseline and change in blood pressure and LDL cholesterol on IMT. RESULTS: Greater baseline LDL and blood pressure were associated with an increase in IMT (0.005 ± 0.002 mm per 1 mg/dL [p = 0.006] and 0.041 ± 0.004 mm mm Hg [p <0.0001], respectively. Change in blood pressure was associated with a significant increase in IMT (0.047 ± 0.016, P = 0.004), whilst the association between change in LDL and change in IMT was not statistically significant (0.008 ± 0.006, P = 0.20). CONCLUSIONS: Carotid IMT was associated with baseline blood pressure and LDL cholesterol, yet only changes of blood pressure, not LDL cholesterol, were related to carotid IMT during the 6-year observation.

Identification of the HDL-ApoCIII to VLDL-ApoCIII ratio as a predictor of coronary artery disease in the general population: the Chin-Shan Community Cardiovascular Cohort (CCCC) study in Taiwan.

BACKGROUND: Apolipoprotein (Apo) levels are considered more reliable than plasma lipoprotein levels for predicting coronary artery disease (CAD). However, a unanimous Apo marker for CAD has not been identified. In the Chin-Shan Community Cardiovascular Cohort (CCCC), we sought to identify a common Apo marker for predicting CAD in the general population. METHODS: We examined the cross-sectional association between Apo markers and CAD in the CCCC from 1990 to 2001. Among 3,602 subjects, 90 had angiographically proven CAD (>50% stenosis in ≥1 vessel), and 200 did not have CAD. These subjects were divided into the following 4 groups for analysis: normolipidemic (total cholesterol [TC] <200 mg/dL, triglyceride [TG] <150 mg/dL), hypertriglyceridemic (TC <200 mg/dL, TG ≥150 mg/dL), hypercholesterolemic (TC ≥200 mg/dL, TG <150 mg/dL), and hyperlipidemic (TC ≥200 mg/dL, TG ≥150 mg/dL). RESULTS: Compatible with findings in other populations, our results showed that CAD patients in the CCCC had higher ApoB and lower high-density lipoprotein (HDL) cholesterol and ApoAI concentrations than non-CAD subjects, but the differences were not significant in all groups. Plasma concentrations of ApoE and lipoprotein (a) were not consistently correlated with CAD. In contrast, the ratio of HDL-ApoCIII to very-low-density lipoprotein (VLDL)-ApoCIII was the only universal determinant for CAD in the normolipidemic group (P=0.0018), the hypertriglyceridemic group (P=0.0001), the hypercholesterolemic group (P=0.0001), and the hyperlipidemic group (P=0.0001). Overall, a high HDL-ApoCIII/VLDL-ApoCIII ratio was observed in all CAD patients, including those with a normal lipid profile. In multivariate analyses, the HDL-ApoCIII/VLDL-ApoCIII ratio was the strongest predictor for CAD among all lipid factors investigated (odds ratio, 2.04; 95% confidence interval, 1.46-2.84; P<0.0001). CONCLUSIONS: A high HDL-ApoCIII to VLDL-ApoCIII ratio is a better marker for predicting CAD than are the conventional lipid markers or ApoAI and ApoB. High HDL-ApoCIII and low VLDL-ApoCIII values in CAD, irrespective of lipid variations, suggest that ApoCIII is markedly transported from VLDL to HDL in this disease. Measurement of plasma ApoCIII may improve CAD prediction in the general population.

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.

Lung cancer and incidence of stroke: a population-based cohort study.

BACKGROUND AND PURPOSE: Stroke is a known cerebrovascular complication in lung cancer patients; however, whether lung cancer patients are at elevated risk of developing stroke relative to the noncancer population remains unclear. METHODS: The present study used population-based claims data from the Taiwan National Health Insurance, which identified 52,089 patients with an initial diagnosis of lung cancer between 1999 and 2007, and 104,178 matched noncancer subjects from all insured subjects age 20 years and older. Subsequent occurrence of stroke was measured until 2008, and the association between lung cancer and the hazard of developing stroke was estimated using Cox proportional hazard models. RESULTS: The incidence of stroke was 1.5 times higher (25.9 versus 17.4 per 1000 person-years) in the lung cancer group compared with the comparison group. The multivariate-adjusted hazard ratio (HR) comparing lung cancer patients with the noncancer group was 1.47 (95% CI, 1.39-1.56) for stroke, 1.78 (95% CI, 1.54-2.05) for hemorrhagic stroke, and 1.43 (95% CI, 1.34-1.51) for ischemic stroke. The risk of stroke fell over time, decreasing after 1 year of follow-up for men and after 2 years of follow-up for women. Within the first year of follow-up, the risk of stroke peaked during the first 3 months for men and within 4 to 6 months for women. CONCLUSIONS: Lung cancer is associated with increased risk of subsequent stroke within 1 year after diagnosis for men and 2 years after diagnosis for women.

Iron-catalyzed oxidation of Trp residues in low-density lipoprotein.

The mechanisms of oxidation of low-density lipoproteins (LDLs) are not well defined, but epidemiological and experimental studies suggest that iron-catalyzed processes may contribute to atherogenesis. The aim of this study was to test the hypothesis that iron-catalyzed oxidations of LDLs in vitro produce diagnostic biomarkers of oxidation of the apolipoprotein that could be applied to studies in vivo. LDLs were oxidized in the presence of Fe2+, EDTA, and ascorbic acid for up to 40 h. Following delipidation and trypsin digestion, the peptides were separated by HPLC, with four peaks detected at 365 nm, whereas none were observed in peptides from unoxidized LDLs. The peptides were identified by MALDI-QTOF mass spectrometry as IVQILP(W+4) EQNEQVK, IYSL(W+4)EHSTK, FEGLQE(W+4)EGK, and YH(W+4)EHTGLTLR, with (W+4) rather than the W residues of the unoxidized protein. The mass gains (+4 increase in m/z in tryptophan, W) and absorbance at 365 nm indicate kynurenines, which were trypsin-releasable peptides that are on the surface of LDL particles. All four peptides thus characterized share the sequence of WE. The preferential oxidation of W residues in WE sequences suggest contributions from the C-proximate glutamate residues in chelation of the iron species, thereby influencing site selectivities of oxidation. These kynurenine-containing peptides might serve as biomarkers of iron-mediated oxidations in vivo.

Plasma fatty acids and the risk of metabolic syndrome in ethnic Chinese adults in Taiwan.

BACKGROUND: Evidence of predictive power of various fatty acids on the risk of metabolic syndrome was scanty. We evaluated the role of various fatty acids, including saturated fat, monounsaturated fat, transfat, n-6 fatty acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for the risk of the metabolic syndrome in Taiwan. RESULTS: A nested case-control study based on 1000 cases of metabolic syndrome and 1:1 matched control subjects. For saturated fat, monounsaturated fat and transfat, the higher the concentration the higher the risk for metabolic syndrome: participants in the highest quintile had a 2.22-fold (95% confidence interval [CI], 1.66 to 2.97) higher risk of metabolic syndrome. In addition, the participants in higher EPA quintiles were less likely to have the risk of metabolic syndrome (adjusted risk, 0.46 [0.34 to 0.61] for the fifth quintile). Participants in the highest risk group (low EPA and high transfat) had a 2.36-fold higher risk of metabolic syndrome (95% CI, 1.38 to 4.03), compared with those in the lowest risk group (high EPA and low transfat). For prediction power, the area under ROC curves increased from 0.926 in the baseline model to 0.928 after adding fatty acids. The net reclassification improvement for metabolic syndrome risk was substantial for saturated fat (2.1%, P = 0.05). CONCLUSIONS: Plasma fatty acid components improved the prediction of the metabolic syndrome risk in Taiwan.

Left atrial dimension and risk of stroke in women without atrial fibrillation: the Chin-Shan Community Cardiovascular Cohort study.

BACKGROUND: Evidence on the relationship between left atrial dimension and cardiovascular events is inconclusive. We explored the association between left atrial dimension and stroke and all-cause death in an ethnic Chinese population. METHODS: We recruited 1,937 subjects undertaking echocardiographic examination without prior atrial fibrillation/stroke in the Chin-Shan Community Cardiovascular Cohort study. Left atrial dimension indexed by body mass index was used as left atrial dimension index (LADI) for analysis. The end points were stroke and all-cause death. A multivariate Cox regression analysis was used to estimate the relative risks between participants stratified by tertile of LADI within each gender. RESULTS: During a median follow-up of 11.9 years, 21,733 person-years were accrued and 114 subjects with stroke and 364 all-cause deaths were identified. The adjusted relative risk of stroke was 2.44 (95% CI, 1.11 to 5.36, P for trend = 0.029) among women in the upper tertile of LADI compared with women in the lower tertile of LADI. Further adjusting for left ventricular mass index attenuated the relationship of LADI to stroke (adjusted relative risk 2.11, 95% CI, 0.88 to 5.02, P for trend = 0.09). In men, tertile of LADI was not associated with stroke. LADI was not associated with risk of all-cause death in both genders. CONCLUSIONS: We found an association between increased LADI and incident stroke in women but not in men in this ethnic Chinese population. LADI was not associated with all-cause death in both genders.

Constructing the prediction model for the risk of stroke in a Chinese population: report from a cohort study in Taiwan.

BACKGROUND AND PURPOSE: Prediction rules for the risk of stroke have been proposed. However, most studies were conducted with whites or for secondary prevention, and it is not clear whether these models apply to the Chinese population. The purpose of this study was to construct a simple points-based clinical model for predicting incident stroke among Chinese adults in Taiwan. METHODS: We estimated the 10-year risk of stroke in a cohort study of middle-aged and elderly participants who were free from stroke at baseline. Multivariate Cox model-derived coefficients were used to construct the simple points-based clinical and biochemical model and the prediction measures using the area under the receive operating characteristic curve, net reclassification improvement, and integrated discrimination improvement statistics were applied. RESULTS: Of the 3513 participants without stroke at baseline, 240 incident cases of stroke were documented for a median 15.9-year follow-up. Age (8 points), gender (1 point), systolic blood pressure (3 points), diastolic blood pressure (2 points), family history of stroke (1 point), atrial fibrillation (3 points), and diabetes (1 point) were found to significantly predict stroke events. The estimated area under the receive operating characteristic curve for this clinical points-based model was 0.772 (95% CI, 0.744 to 0.799). The discrimination ability of this clinical model was similar to the coefficients-based models and better than available stroke models. CONCLUSIONS: We have constructed a model for predicting 15-year incidence of stroke in Chinese adults and this model may be useful in identifying individuals at high risk of stroke.

Red blood cell distribution width and risk of cardiovascular events and mortality in a community cohort in Taiwan.

The authors investigated whether red blood cell distribution width (RDW) was associated with the development of cardiovascular disease (CVD) events and mortality in a community cohort in Taiwan. The influence of anemia on the association was also assessed. RDW levels were measured in 3,226 participants aged 35 years or older who reported no CVD or cancer at baseline in 1990. During a median follow-up period of 15.9 years (1990-2007), 358 participants experienced stroke and/or coronary heart disease, and 810 participants died. The multivariate-adjusted hazard ratio for subjects in the highest RDW quartile as compared with the lowest quartile was 1.46 for both all-cause mortality (95% confidence interval: 1.17, 1.81) and non-CVD mortality (95% confidence interval: 1.13, 1.88) (P for trend < 0.01 for both) but was not significant for CVD morbidity and mortality. Further analyses showed that in comparison with participants with low RDW and no anemia, persons with high RDW but no anemia had elevated risks of all-cause mortality and non-CVD mortality. The authors conclude that elevated RDW values are associated with increased risk of mortality but not the development of CVD in the general population. RDW may precede anemia in predicting the risk of non-CVD death.

Habitual sleep duration and insomnia and the risk of cardiovascular events and all-cause death: report from a community-based cohort.

STUDY OBJECTIVES: To investigate the relationship between sleep duration and insomnia severity and the risk of all-cause death and cardiovascular disease (CVD) events. DESIGN: Prospective cohort study. SETTING: Community-based. PARTICIPANTS: A total of 3,430 adults aged 35 years or older. INTERVENTION: None. MEASUREMENTS AND RESULTS: During a median 15.9 year (interquartile range, 13.1 to 16.9) follow-up period, 420 cases developed cardiovascular disease and 901 cases died. A U-shape association between sleep duration and all-cause death was found: the age and gender-adjusted relative risks (95% confidence interval [CI]) of all-cause death (with 7 h of daily sleep being considered for the reference group) for individuals reporting < or = 5 h, 6 h, 8 h, and > or = 9 h were 1.15 (0.91-1.45), 1.02 (0.85-1.25), 1.05 (0.88-1.27), and 1.43 (1.16-1.75); P for trend, 0.019. However, the relationship between sleep duration and risk of CVD were linear. The multivariate-adjusted relative risk (95% CI) for all-cause death (using individuals without insomnia) were 1.02 (0.86-1.20) for occasional insomnia, 1.15 (0.92-1.42) for frequent insomnia, and 1.70 (1.16-2.49) for nearly everyday insomnia (P for trend, 0.028). The multivariate adjusted relative risk (95% CI) was 2.53 (1.71-3.76) for all-cause death and 2.07 (1.11-3.85) for CVD rate in participants sleeping > or = 9 h and for those with frequent insomnia. CONCLUSIONS: Sleep duration and insomnia severity were associated with all-cause death and CVD events among ethnic Chinese in Taiwan. Our data indicate that an optimal sleep duration (7-8 h) predicted fewer deaths.

Homocysteine inhibits arterial endothelial cell growth through transcriptional downregulation of fibroblast growth factor-2 involving G protein and DNA methylation.

Homocysteine (Hcy) contributes to atherogenesis and angiostasis by altering the phenotype of arterial endothelial cells (ECs). The present study was aimed at elucidating potential mechanisms by which Hcy can slow EC proliferation and induce EC apoptosis, thereby disrupting endothelial integrity. Given the strong mitogenic and antiapoptotic properties of fibroblast growth factor (FGF)2, we examined whether Hcy can modulate its expression. In cultured human coronary and bovine aortic ECs, Hcy exerted time- and concentration-dependent (0 to 500 micromol/L) reduction of the mRNA and protein levels of FGF2, whereas vascular endothelial growth factor expression was not affected until Hcy reached a proapoptotic 500 micromol/L. By testing a panel of signal transduction inhibitors, we found that the Hcy-induced downregulation of FGF2 was specifically attenuated by pertussis toxin, an inhibitor of Gi protein signaling. Hcy induced cell cycle arrest at the G(1)/S transition and increased TUNEL-positive apoptotic cells in a graded manner. These effects were effectively counteracted by exogenous FGF2. Reporter gene assays showed that Hcy downregulated FGF2 by transcriptional repression of the gene promoter encompassed in a CpG dinucleotide-rich island. This region was heavily methylated at the cytosine residues by Hcy despite decreased methylation potential (S-adenosylmethionine to S-adenosylhomocysteine ratio). Normal levels of FGF2 transcription were restored to ECs simultaneously exposed to Hcy and 5-aza-deoxycytidine. We conclude that homocysteine disrupts the growth and survival of ECs through a G protein-mediated pathway associated with altered promoter DNA methylation and the transcriptional repression of FGF2.

Aortic root dimension as an independent predictor for all-cause death in adults <65 years of age (from the Chin-Shan Community Cardiovascular Cohort Study).

BACKGROUND: Evidence on aortic root dimension for predicting cardiovascular morbidity and mortality is inconclusive. This cohort study sought to characterize the predictive power of aortic root dimension on cardiovascular morbidity and mortality in an ethnic Chinese population. METHODS: We recruited 1,851 participants in the Chin-Shan Community Cardiovascular Cohort (CCCC) study who had received echocardiography without previous cardiovascular events. Aortic root dimension was measured by M-mode echocardiography and indexed by body surface area to obtain aortic root dimension index (AOI). The end points were all-cause death and incident cardiovascular events including coronary heart disease and stroke over a median follow-up of 11.9 years. RESULTS: Although tertiles of AOI was associated with an increased risk of cardiovascular events and all-cause death in univariate analysis, the significance diminished after adjusting for age variable (P for trend = 0.11 for cardiovascular events; P for trend = 0.23 for all-cause death). In subgroup analysis, we found a significant association between tertiles of AOI and risk of all-cause death in the final multivariate Cox regression model in adults <65 years. The adjusted relative risk was 1.88 (95% CI, 1.04 to 3.40) in participants in the upper tertile of AOI compared with participants in the lower tertile (P for trend = 0.037). In adults > or = 65 years, tertile of AOI was not associated with all-cause death (P for trend = 0.14). Tertiles of AOI was not associated with cardiovascular events throughout this study. CONCLUSION: Our study showed a significant association between AOI and all-cause death in adults <65 years in an ethnic Chinese population. (Echocardiography 2010;27:487-495).

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.