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A retrospective cohort study was conducted using claims data from Taiwan's National Health Insurance program to assess the effect of diabetic pay-for-performance (P4P) program on major adverse limb events (MALE) and major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). This study included patients with T2DM who had completed or not completed a 1-year P4P program from 2002 to 2013. Propensity-score matching was used to balance the baseline characteristics between groups. The Cox proportional-hazard model and Fine and Gray subdistribution hazard model were used to examine the association between P4P and the risks of MALE, MACE, systemic thromboembolism (ST), heart failure (HF) hospitalization, and all-cause mortality. Patients who underwent the P4P program had a significantly decreased incidence of MALE (2.0% vs. 2.6%, subdistribution hazard ratio [SHR] 0.73, 95% CI 0.71-0.76). Regarding the individual components, the P4P group demonstrated lower risks for foot ulcer (1.1% vs 1.3%, SHR 0.80, 95% CI 0.77-0.84), gangrene (0.57% vs 0.93%, SHR 0.59, 95% CI 0.56-0.63), percutaneous transluminal angioplasty (0.61% vs 0.79%, SHR 0.72, 95% CI 0.68-0.77), and amputation (0.46% vs 0.75%, SHR 0.58, 95% CI 0.55-0.62). In addition, the risks of MACE, ST, HF hospitalization, and all-cause mortality were remarkably lower in the P4P group. The P4P program might significantly reduce critical events of MALE, MACE, ST, HF, and mortality in the diabetic population., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: This study assesses the mortality outcomes of non-vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF)., Methods: Medical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer-related death. Secondary outcomes were all-cause mortality, major bleeding, and gastrointestinal (GI) bleeding., Results: Among 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer-related death at one year (HR = 0.71, 95% CI = 0.54-0.93) and at the end of follow-ups (HR = 0.79, 95% CI = 0.64-0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all-cause mortality (HR = 0.81, 95% CI = 0.67-0.97), major bleeding (HR = 0.64, 95% CI = 0.47-0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39-0.84) at the end of follow-ups compared with rivaroxaban., Conclusion: Compared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer-related death and all-cause mortality., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Blood pressure (BP) is characterized by spontaneous oscillation over time, which is described as BP variability (BPV). The current study aimed to investigate whether short-term BPV was correlated with hypertensive nephropathy in Han Chinese individuals with hypertension. A single-center prospective cohort study of 300 Han Chinese participants with hypertension was conducted in Taiwan. Five different BPV parameters were derived from ambulatory BP monitoring (ABPM), including standard deviation (SD), weighted SD (wSD), coefficient of variation (CoV), successive variation (SV), and average real variability (ARV). Renal event was defined as > 50% reduction in baseline estimated glomerular filtration rate (eGFR). The average age of the participants was 63.5 years. The baseline eGFR was 84.5 mL/min/1.73 m 2 . The participants were divided into two groups according to the wSD of systolic BP (SBP). Survival was assessed via a Kaplan-Meier analysis. During the 4.2-year follow-up, the participants with the highest SBP wSD tertile had a greater number of renal events (6.0%) than their counterparts (0.5%) (log-rank test, p = .007). The Cox proportional hazard regression model was used to assess the independent effects of BPV, and results showed that 24-h SBP (HR = 1.105; 95% CI = 1.020-1.197, p = .015) and 24-h DBP (HR = 1.162; 95% CI = 1.004-1.344, p = .044) were independently associated with renal events. However, BPV parameters were only associated with renal events univariately, but not after adjusting for baseline characteristics, 24-h mean BP, and office BP. Therefore, the risk of hypertensive nephropathy was independently associated with 24-h mean BP, but not with ambulatory BPV, in Han Chinese participants with hypertension., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Increased sympathetic nervous system (SNS) activity leads to increased risk of cardiovascular morbidity and mortality. This study investigated whether there were sex differences in SNS activity among Chinese patients with hypertension. Ethnic Chinese non-diabetic hypertensive patients aged 20-50 years were enrolled in Taiwan. A total of 970 hypertensive patients (41.0 ± 7.2 years) completed the study, 664 men and 306 women. They received comprehensive evaluations including office blood pressure (BP) measurement, 24-h ambulatory BP monitoring, and 24-h urine sampling assayed for catecholamine excretion. Compared to women, men were younger, had higher body mass index (BMI), office systolic BP (SBP), office diastolic BP (DBP), 24-h ambulatory BP, and 24-h urine catecholamine excretion. In men, 24-h urine total catecholamine levels were correlated with 24-h SBP (r = 0.103, p = .008) and 24-h DBP (r = 0.083, p = .033). In women, however, there was no correlation between 24-h urine total catecholamine levels and 24-h ambulatory BP. Multivariate linear regression indicated that being male (β = 1.65, 95% confidence interval [CI] 0.01-3.29, p = .048) and 24-h urine total catecholamine (β = 5.03, 95% CI 0.62-9.44, p = .025) were both independently associated with 24-h SBP; being male was independently associated with 24-h DBP (β = 3.55, 95% CI 2.26-4.85, p < .001). In conclusion, Chinese men with hypertension had higher SNS activity than women, and SNS activity was independently associated with 24-h ambulatory BP in men rather than in women. These findings suggest that different hypertensive treatment strategies should be considered according to patient sex., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Atrial fibrillation (AF) is a major independent risk factor of stroke and anticoagulation therapy is needed in patients with AF after ischemic stroke. However, the detection rate of AF is low after ischemic stroke. Developing a prediction model for newly diagnosed AF after ischemic stroke will help to assess the subclinical AF.We identified 98,103 patients with diabetes mellitus (DM) and 261,893 patients without DM, who were not AF history and admitted for newly ischemic stroke from the National Health Insurance Research Database in Taiwan. The prediction model for 3-year incidence of AF after ischemic stroke was derived from multivariate logistic regression and also the accuracy rate of the prediction model was compared with CHA2DS2-VASC and CHADS2 scores as a reference.Four thousand nine hundred seventy six patients in the DM cohort and 16,127 patients in the non-DM cohort developed AF during 3 years of follow-up. The variables in the point-based prediction model for non-DM patients (range: -3-28), included age, heart failure, coronary artery disease, gout, obstructive pulmonary disease, hypertension, female, and statin use, while those for DM patients (range: -2-30) included age, heart failure, coronary artery disease, chronic kidney disease, hypertension, obstructive pulmonary disease, and statin use. Compared to the CHADS2 and CHA2DS2-VASc scoring systems, this scoring system was better at predicting 3-year risk of AF after ischemic stroke in both cohorts.This model might be useful in evaluating the benefit of insertable cardiac monitor implantation and anticoagulation agents in individual patients after ischemic stroke.

Background and Aims: Intracerebral hemorrhage (ICH) has a higher mortality than ischemic stroke. Statin is beneficial for stroke, but high potency statin treatment has been associated with the risk of hemorrhagic stroke. The aim of this study was to assess the impact of initiating statin therapy after ICH on cardiovascular outcomes., Methods: Dyslipidemic patients were retrieved from the ICH population from the National Health Insurance Research Database in Taiwan. We retrospectively compared patients prescribed with and without statin treatment after ICH. Outcomes of interest were mortality, myocardial infarction, ischemic stroke, and hemorrhagic stroke during 5 years of follow-up., Results: Of 17,980 adult patients with ICH and dyslipidemia, 8927 were eligible for analysis over the study period, including 1613 patients receiving statin therapy and 7314 patients not taking statins. After propensity score matching, the mean age was 61.2 ± 12.2 years in the statin group and 61.6 ± 13.0 years in the non-statin group. Hypertension was dominant, followed by diabetes mellitus, and the mean estimated NIHSS score was 12.9. The patients who received statin therapy were associated with lower risks of all-cause mortality (12.7% vs. 21.3%; hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.45-0.65), cardiovascular death (4.0% vs. 7.1%; HR, 0.54; 95% CI, 0.39-0.75) and ICH (5.4% vs. 8.5%; HR, 0.62; 95% CI, 0.46-0.83) compared to those who did not receive statins., Conclusions: Initiating statin therapy after ICH was associated with a decreased risk of recurrent ICH and mortality for dyslipidemia patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: High-dose steroids and intravenous immunoglobulin (IVIG) are controversial treatments for pediatric patients with acute myocarditis. This study aimed to investigate their efficacies in the Taiwanese pediatric population., Methods: This study evaluated 5563 acute myocarditis patients from the Taiwan's National Health Insurance Research Database and identified 1542 pediatric patients hospitalized for acute myocarditis between January 1, 2001 and December 31, 2011. The exclusion criteria were age of > 11 years, associated cardiovascular comorbidities, autoimmune disease, malignancy before the index hospitalization, extracorporeal membrane oxygenation, intra-aortic balloon pumping, and dual therapy using IVIG and high-dose steroids., Results: After 2:1 propensity score matching, we identified 208 subjects without steroid therapy and 104 subjects who received high-dose steroids. The mean age in that cohort was 2.6 ± 2.9 years, and high-dose steroid therapy had no significant effects on major in-hospital complications and post-discharge outcomes. After 2:1 propensity score matching, we identified 178 subjects without IVIG therapy and 89 subjects who received IVIG. The mean age in that cohort was 2.0 ± 2.1 years, and IVIG had no significant effects on the major outcomes., Conclusions: The present study revealed that high-dose steroid or IVIG therapy had no significant effects on major in-hospital complications, late heart failure hospitalization, and long-term mortality.

Background and Aims: Statins improve clinical outcomes in patients with ischemic stroke but there is no evidence of the effect of continuing long-term statin therapy in patients with intracerebral hemorrhage (ICH). The aim of this study was to evaluate the impact of continuing statin after ICH., Methods: Data on patients with ICH was retrieved from the National Health Insurance Research Database of Taiwan. The final population was separated into two groups according to those who continued and those who discontinued statin treatment. All-cause mortality and cardiovascular outcomes were analyzed after a 3 year follow-up after propensity score matching (PSM)., Results: Of the 114,101 patients with ICH, who were initially enrolled, 2468 patients with dyslipidemia and ICH were included. After PSM, the benefit of statin therapy on mortality appeared from 1 year to the end of the 3-year follow-up period after discharge (statin group versus non-statin group: 4.9% vs.12.3% at 1 year (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.26-0.57) and 12.9% vs. 25.3% at the end of the 3 year follow-up period (HR, 0.45; 95% CI, 0.35-0.58). Compared with the patients using lipophilic statins, those using hydrophilic statins had a significantly lower incidence of all-cause mortality (HR = 0.65, 95% CI = 0.43-0.99). There were no differences between those prescribed moderate-intensity statins and those prescribed high-intensity statins in terms of stroke and all-cause mortality (HR = 0.76; 95% CI = 0.40-1.46)., Conclusions: There was a lower risk of all-cause mortality following ICH in patients who continued statin treatment compared with those without statin treatment, especially in those treated with hydrophilic statins., (Copyright © 2018. Published by Elsevier B.V.)

Background: Although hepatitis C virus (HCV) is a known risk factor for cardiovascular disease, whether antiviral therapy (AVT) can reduce heart failure (HF) hospitalizations is unknown., Methods and results: In this population-based cohort study, we used data from the Taiwan National Health Insurance Research Database to evaluate the effect of interferon-based therapy (IBT) on cardiovascular events in patients with chronic HCV infection. Clinical outcomes evaluated included HF hospitalizations; a composite of acute myocardial infarction, ischemic stroke, and peripheral artery disease; all-cause death; and cardiovascular death. Of 83,229 eligible patients with chronic HCV infection, we compared 16,284 patients who received IBT with untreated subjects after propensity score matching. Patients who received IBT were less likely to be hospitalized for HF compared with untreated subjects (incidence density.ID, 0.9 vs. 1.5 events per 10 3 person-years; hazard ratio.HR, 0.58; 95% confidence interval.CI, 0.42-0.79; P=0.001). Compared with untreated subjects, the treated group had significantly lower risk of composite vascular events (ID, 3.7 vs. 5.0 events per 10 3 person-years; P<0.001), all-cause death (ID, 5.6 vs. 17.2 events per 10 3 person-years; P<0.001), and cardiovascular death (ID, 0.2 vs. 0.6 events per 10 3 person-years; P=0.001)., Conclusions: AVT for chronic HCV infection might offer protection against HF hospitalizations, critical vascular events, and cardiovascular death beyond known beneficial effects.

Background: The tendency for haemorrhagic stroke in patients with chronic HCV infection has emerged recently but the finding may be confounded by comorbidities. Proving the causality between HCV infection and haemorrhagic stroke is mandatory. Our study was designed to investigate the incidence of intracranial haemorrhage in HCV-infected patients with and without treatment., Methods: In the 11-year and population-based retrospective study, we acquired data from the Taiwan National Health Insurance Research Database. The patients with major comorbidities were excluded and 97,198 HCV-infected patients were included for analysis. Treated and untreated cohorts were matched with propensity score to make the confounding factors in two groups comparable. Cox proportional hazard regression analysis was performed to evaluate the hazard ratio of haemorrhagic stroke in the cohorts. We applied survival analysis to compare the cumulative incidence of outcome events between the two cohorts., Results: After matching, the incidence density (ID) of haemorrhagic stroke in the untreated cohort is significantly higher than in the treated cohort (ID: 1.0 versus 0.6 events per 1,000 person-years; P=0.0014). The adjusted hazard ratio (aHR) of haemorrhagic stroke is significantly reduced in the treated group (P<0.05). Cumulative incidence of haemorrhagic stroke is significantly lower in the treated group than in the untreated group (P=0.013)., Conclusions: The study demonstrates that antiviral therapy significantly reduces the events of intracranial haemorrhage in HCV-infected patients and consolidates the novel concept that chronic HCV infection is a risk factor for haemorrhagic stroke.

Background: Hepatitis C virus (HCV)-infected patients with chronic kidney disease (CKD) have rarely been studied because they rarely accept interferon-based therapy (IBT) and have been difficult to follow up. We investigated long-term outcomes of IBT on the population., Methods: This population-based cohort study used the Taiwan National Health Insurance Research Database as its data source. HCV patients diagnosed with CKD between Jan. 1, 2003, and Dec. 31, 2013, were selected. They were then divided into two groups based on whether they had undergone IBT. All-cause mortality, acute myocardial infarction (AMI), ischemic stroke (IS), hemorrhagic stroke, and new-onset dialysis were evaluated using a Cox proportional hazard regression analysis after propensity score matching., Results: We enrolled 9872 HCV patients with CKD: 1684 patients in the treated cohort and 8188 patients in the untreated cohort. The annual incidence of all-cause mortality (19.00 vs. 42.89 events per 1000 person-years; p < 0.001) and the incidences of hemorrhagic stroke (1.21 vs. 4.19 events per 1000 person-years; p = 0.006) were lower in the treated cohort. New-onset dialysis was also lower in the treated cohort (aHR: 0.31; 95% CI: 0.20-0.48; p < 0.001)., Conclusion: Antiviral therapy might provide protective benefits on all-cause mortality, hemorrhagic stroke, and new-onset dialysis in HCV-infected patients with CKD.

Overexpression of cyclooxygenase-2 in oral cancer increases lymph node metastasis and is associated with a poor prognosis. The potential of celecoxib (CXB) use is reported in cancer treatment by inhibiting proliferation through apoptosis, but the effects on the epithelial-mesenchymal transition (EMT) and cancer cell mobility remain unclear. We performed a preclinical study and population-based study to evaluate CXB use in the prevention of oral cancer progression and occurrence. The in-vitro findings showed that CXB is involved in the inhibition of EMT and cell mobility through blocking transcription factors (Slug, Snail and ZEB1), cytoplasmic mediators (focal adhesion kinase (FAK), vimentin and β-catenin), cell adhesion molecules (cadherins and integrins), and surface receptors (AMFR and EGFR). The murine xenograft model showed a 65% inhibition in tumour growth after a 5-week treatment of CXB compared to placebo. Xenograft tumours in placebo-treated mice displayed a well-to-moderate/moderate differentiated SCC grade, while those from CXB-treated mice were well differentiated. The expression levels of membrane EGFR, and nuclear FAK, Slug and ZEB1 were decreased in the xenograft tumours of CXB-treated mice. A retrospective cohort study showed that increasing the daily dose and medication time of CXB was associated with oral cancer prevention. The findings provide an alternative prevention strategy for oral cancer development with CXB use.

We integrated genetic risk scores (GRS) and environmental factors for identifying high-risk subjects for oral squamous cell carcinoma (OSCC) occurrence by using case-control study. A total of 447 patients diagnosed with OSCC and 580 unrelated subjects were recruited from two medical centers in Taiwan. A multinomial logistic regression model was conducted to access interaction between GRS and betel quid (BQ) chewing. We employed ROC curve to compare the accuracy of OSCC occurrence. Four tag SNPs were found in NOTCH1, BRCA1, COL9A1 , and HSPA13 genes that were significantly associated with OSCC occurrence. GRS was calculated by the four tag SNP risk alleles. The higher GRS (scores = 4) remained independently associated with risk of OSCC after adjustment for age, the use of alcohol, BQ, and cigarette: adjusted OR = 4.42 [95% confidence interval (95% CI), 1.34-14.55]. The GRS and BQ chewing interaction showed an increased risk for OSCC occurrence with adjusting for other substance use and age (OR = 70.77; 95% CI, 8.70-575.73). The synergy index was 16.58 (95% CI, 2.27-70.56), suggesting a positive additive interaction between GRS and BQ chewing. The areas under the ROC curves (AUROC) were 0.91 for combined GRS and BQ chewing with sensitivity of 88.6% and specificity of 86.7%. The AUROC of GRS and BQ chewing is above 90%, which may be valuable in identifying high-risk subjects. Early screening can allow the clinician to provide the appropriate intervention and to reduce the OSCC occurrence. Cancer Prev Res; 10(6); 355-62. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: Metformin, an insulin-sensitizer, may correct several physiologic abnormalities owing to insulin resistance in patients with type 2 diabetes mellitus (DM). The effects of metformin on venous thrombosis in patient with type 2 DM have not been reported. Our study strived to explore the relationship of metformin therapy and the subsequent development of deep vein thrombosis (DVT) using a nationwide, population-based database., Methods: From 1997 to 2003, we identified a study cohort consisting of patients with type 2 DM using metformin 7154 cases in the National Health Insurance Research Database. A control cohort without metformin, matched for age, sex, comorbidities, and medications was selected for comparison., Results: Of the 14945 patients (7167 patients with metformin vs. 7778 control), 60 (0.40%) patients developed DVT during a mean follow-up period of 3.74 years, including 16 (0.21%) from the cohort with metformin and 44 (0.56%) from the control group. Subjects with metformin experienced a 0.427 fold (95% confidence interval 0.240-0.758; P = 0.004) changes of risk reduction in development of DVT, which was independent of age, sex and co-morbidities. Kaplan-Meier analysis also revealed metformin therapy is associated with lower occurrence of DVT (log-rank test, P = 0.001)., Conclusions: Metformin may have protective effect in patients with type 2 DM for DVT.

As the number of cardiac implantable electronic devices (CIEDs) is increasing annually, CIED-related complications are becoming increasingly important. The aim of the study was to assess the risks associated with CIEDs by a nationwide database. Patients were selected from the Taiwan National Health Insurance Database. Admissions for CIED implantation, replacement, and revision were evaluated and the evaluation period was 14 years. Endpoints included CIED-related infection, pneumothorax, and heart perforation. The study included 40,608 patients with a mean age of 71.8 ± 13.3 years. Regarding infection, the incidence rate was 2.45 per 1000 CIED-years. Male gender, younger age, device replacement, and previous infection were risks for infection while old age and high-volume centers (>200 per year) were protectors. The incidence of pneumothorax was 0.6%, with an increased risk in individuals who had chronic obstructive lung disease (COPD) and cardiac resynchronized therapy (CRT). The incidence of heart perforation was 0.09%, with an increased risk in individuals who had pre-operation temporal pacing and steroid use. High-volume center was found to decrease infection rate while male gender, young people, and individuals who underwent replacements were associated with an increased risk of infection. Additionally, pre-operation temporal pacing and steroid use should be avoided if possible. Furthermore, COPD patients or those who accept CRTs should be monitored closely.

Purpose: To investigate the incidence and risk factors for central serous chorioretinopathy (CSCR) in adults who use oral corticosteroids in Taiwan., Methods: This is a population-based nested case-control study between 2000 and 2008. From the Taiwan National Health Insurance Research Database, adults who were repetitively prescribed oral corticosteroids were included as the study cohort. Of those, newly diagnosed CSCR cases were identified and the CSCR incidence was calculated. Subjects matched for age, gender, and the enrollment time were randomly selected as the controls. Corticosteroids use was compared between the cases and controls. Poisson and conditional logistic regressions were used to analyze the potential risk factors for CSCR., Results: Among 142,035 oral corticosteroids users, 320 cases of CSCR were identified, and 1,554 matched controls were randomly selected. The incidence rate of CSCR was 44.4 (95% confidence interval, 39.5-49.3) cases per 100,000 person-years. Multivariate Poisson regression showed that male patients and those aged 35 years to 44 years had significantly higher incidence rates of CSCR. There were no differences in either median dosage or mean duration of systemic corticosteroid treatment between the cases and controls. After adjusting for other confounders, current use of oral corticosteroids was found to be significantly associated with the risk of CSCR (odds ratio, 2.40; 95% confidence interval, 1.49-3.89)., Conclusion: Male gender, middle age, and current use of oral corticosteroids were found to be the risk factors for CSCR. However, oral corticosteroids dosage and treatment duration were not associated with the CSCR risk.

Background: Pulse pressure (PP) is a risk factor for cardiovascular disease. It has been reported that ambulatory blood pressure (BP) and nighttime BP parameters are heritable traits. However, the genetic association of pulse pressure and its clinical impact remain undetermined., Method and Results: We conducted a genome-wide association study of PP using ambulatory BP monitoring in young-onset hypertensive patients and found a significant association between nighttime PP and SNP rs897876 (p = 0.009) at chromosome 2p14, which contains the predicted gene FLJ16124. Young-onset hypertension patients carrying TT genotypes at rs897876 had higher nighttime PP than those with CT and CC genotypes (TT, 41.6 ± 7.3 mm Hg; CT, 39.1 ± 6.0 mm Hg; CC, 38.9 ± 6.3 mm Hg; p<0.05,). The T risk allele resulted in a cumulative increase in nighttime PP (β = 1.036 mm Hg, se. = 0.298, p<0.001 per T allele). An independent community-based cohort containing 3325 Taiwanese individuals (mean age, 50.2 years) was studied to investigate the genetic impact of rs897876 polymorphisms in determining future cardiovascular events. After an average 7.79 ± 0.28 years of follow-up, the TT genotype of rs897876 was independently associated with an increased risk (in a recessive model) of coronary artery disease (HR, 2.20; 95% CI, 1.20-4.03; p = 0.01) and total cardiovascular events (HR, 1.99; 95% CI, 1.29-3.06; p = 0.002), suggesting that the TT genotype of rs897876C, which is associated with nighttime pulse pressure in young-onset hypertension patients, could be a genetic prognostic factor of cardiovascular events in the general cohort., Conclusion: The TT genotype of rs897876C at 2p14 identified in young-onset hypertensive had higher nighttime PP and could be a genetic prognostic factor of cardiovascular events in the general cohort in Taiwan.

Background: Tamoxifen is used for breast cancer treatment and has been reported to be beneficial for the cardiovascular system, but it is unclear whether tamoxifen exhibits a favorable cardiovascular effect in Asian patients., Methods and Results: From January, 1998 to December, 2006, a breast cancer cohort study was conducted using the Taiwan National Health Insurance database. Patients were divided according to whether tamoxifen was used. Study endpoints were occurrence of acute myocardial infarction (AMI), ischemic or hemorrhagic stroke and total cardiovascular events. A total of 3,690 female subjects were enrolled (mean age 50.1±11.3), 2,056 of whom received tamoxifen and 1,634 did not. During a mean follow-up of 6.9 years, the tamoxifen group had a significantly lower incidence of AMI (0.15% vs. 0.67%, P=0.008), ischemic stroke (1.99% vs. 3.30%, P=0.008), hemorrhagic stroke (0.15% vs. 0.55%, P=0.029), and total cardiovascular events (2.24% vs. 4.16%, P<0.001) than the non-exposed group. After adjusting for comorbidities, tamoxifen was independently associated with a reduced risk of myocardial infarction (hazard ratio [HR] 0.22; 95% confidence interval [CI] 0.07-0.70, ischemic stroke (HR 0.52; 95% CI 0.35-0.78), hemorrhagic stroke (HR 0.25; 95% CI 0.07-0.92), and total cardiovascular events (HR 0.54; 95% CI 0.37-0.78)., Conclusions: In Asian female breast cancer patients, tamoxifen use was associated with reduced risks of AMI, ischemic, hemorrhagic stroke and total cardiovascular events.

Purpose: Central serous chorioretinopathy (CSCR) mostly affects middle-aged men and has been associated with stress and hypercortisolism. We hypothesized that some factors prone to inducing CSCR could also have a harmful effect on erectile function. This study aimed to investigate the risk of subsequent erectile dysfunction after CSCR using Taiwan National Health Insurance Research Database., Methods: The study cohort (n = 1220) consisted of newly diagnosed CSCR men aged 19-64 years between 1999 and 2007, and men matched for age, monthly income and time of enrolment were randomly selected as the control group (n = 10870). Cox proportional hazard regressions were performed to calculate the hazard ratios (HR) of clinically diagnosed erectile dysfunction (including organic origin and/or psychogenic origin) for the two groups. Erectile dysfunction-free survival analysis was assessed using a Kaplan-Meier method., Results: Twenty-five patients (2.0%) from the CSCR cohort and 103 (0.9%) from the control group were diagnosed erectile dysfunction clinically during a mean observation period of 4.3 years. Patients with CSCR had a significantly higher incidence of erectile dysfunction diagnosis than those without CSCR (p < 0.001). After adjusting for age, geographic location, chronic comorbidities and medication habits, patients with CSCR were found to have a 2.22-fold [95% confidence interval (CI), 1.42-3.46] higher hazard ratio of a subsequent erectile dysfunction diagnosis than the matched controls. The adjusted HR for organic and psychogenic erectile dysfunction were 2.14 (95% CI: 1.34-3.44) and 3.83 (95% CI: 1.47-10.01), respectively., Conclusions: Central serous chorioretinopathy was independently associated with an increased risk of being diagnosed with erectile dysfunction., (© 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.)

Background: The beneficial effects of statins in patients undergoing hemodialysis are controversial. Our study aimed to investigate the use of statins and the subsequent risk of cardiovascular morbidity and mortality in patients undergoing hemodialysis., Methods: We conducted a cohort study using data from the Taiwan National Health Insurance Research Database. Cox regressions were performed to determine the hazard ratio (HR) of cardiovascular morbidity and mortality in the HD patients taking statins (statin cohort) compared with a propensity-matched comparison cohort., Results: The statin cohort included a total of 4074 patients who received statin treatment while also undergoing hemodialysis (mean age 53.3 ± 13.5 years, male 34.9%). The comparison cohort included 8148 propensity-matched hemodialysis patients who were not using statins. During the three years of follow-up, the statin cohort had lower incidence of ischemic stroke (p < 0.001), hospitalizations due to unstable angina (p < 0.001), deep vein thrombosis (p < 0.001), cardiovascular mortality (p < 0.001), and all-cause mortality (p < 0.001). After Cox regression analysis, statin use was independently associated with lower risk of future ischemic stroke (HR, 0.49; 95% confidence interval [CI], 0.39-0.63), hospitalization for unstable angina (HR, 0.57; 95% CI, 0.47-0.70), deep vein thrombosis (HR, 0.11; 95% CI, 0.05-0.27), cardiovascular mortality (HR, 0.29; 95% CI, 0.18-0.46), and all-cause mortality (HR, 0.49; 95% CI, 0.41-0.58)., Conclusion: Statin use was associated with a lower incidence of cardiovascular morbidity and mortality in patients undergoing hemodialysis., (© 2013.)

Objectives: The epidemiology of idiopathic central serous chorioretinopathy (CSCR) is not well understood in an Asian population. The present study aimed to investigate the incidence and risk factors for corticosteroid-unrelated CSCR using Taiwan's National Health Insurance Research Database., Methods and Results: From 2001 to 2006, a total of 786 patients (500 [63.6%] males) who were newly diagnosed with CSCR, aged from 20 to 64 years and had no history of corticosteroid prescription were identified as incident cases of idiopathic CSCR. 3606 age-, gender-, and enrollment time-matched subjects were randomly selected as the control group. The mean annual incidence was 0.21‰ (0.27‰ for males, and 0.15‰ for females; P<0.001), with a male/female ratio of 1.74. The peak incidence was in the 35- to 39-year-old age group (0.30‰), followed by the 40- to 44-year-old age group (0.26‰). Males had a significantly higher mean annual incidence than female only in the middle age groups. Conditional logistic regression was used to estimate the odds ratios (ORs) for potential risk factors of idiopathic CSCR. Only exposure to anti-anxiety drugs (OR, 1.63; 95% confidence interval, 1.09-2.44) was found to be independently associated with idiopathic CSCR among males. No risk factors of idiopathic CSCR were found for females., Conclusions: This study provides the nationwide, population-based data on the incidence of idiopathic CSCR in adult Asians, and suggests that exposure to anti-anxiety drugs is an independent risk factor for idiopathic CSCR among males.

Background: High-sensitivity C-reactive protein (hs-CRP) is a sensitive inflammatory marker suggested for cardiovascular risk stratification. This study aimed to assess the potential genetic determinants for serum hs-CRP levels in a cohort with well-controlled nondiabetic hypertension., Materials and Methods: Ethnic Chinese nondiabetic hypertensive patients were enrolled in Taiwan. They received comprehensive evaluation including history taking, physical check-up, blood pressure (BP) measurement, 24-h ambulatory BP monitoring and blood sampling. Serum hs-CRP levels were determined. CRP genotyping was performed in two stages. In the first stage, 4 single-nucleotide polymorphisms (SNPs) of CRP including rs1572970, rs2794520, rs3093077 and rs2808630 were investigated in the 400 participants. In the second stage, only SNPs significant in the first stage were selected for complete genotyping in the whole population., Results: Total 915 consecutive patients (40·9 ± 7·3 years, 68·3% male) completed the study. Two of the 4 SNPs including rs1572970 and rs3093077 were correlated to hs-CRP levels in the whole population. Stepwise multiple linear regression indicated that age (P = 0·001), body mass index (P < 0·001), waist-hip ratio (P = 0·032), smoking habits (P = 0·001), night-time systolic BP (P = 0·040), total cholesterol (P = 0·005) and CRP rs3093077 polymorphism (P < 0·001) were independently associated with serum hs-CRP levels. Overall, genetic correlates explained 2·4%, BMI explained 11·9% and all other clinical correlates explained 4·8% of interindividual variability in serum hs-CRP level., Conclusion: C-reactive protein genotype contributed limitedly to serum hs-CRP levels in subjects with well-controlled hypertension, suggesting the impacts of clinical rather than genetic determinants to serum hs-CRP levels for cardiovascular risk stratification in this intermediate-risk Taiwanese cohort., (© 2013 The Authors. European Journal of Clinical Investigation © 2013 Stichting European Society for Clinical Investigation Journal Foundation.)

Both erectile dysfunction (ED) and herpes simplex virus (HSV) infections are related to cardiovascular events. However, the relationship between ED and HSV infections remains undetermined. The aim of our study was to investigate the possible influence of HSV infections on the development of ED using the Taiwan National Health Insurance database. We identified patients with HSV type 1 or type 2 infections from the 1 000 000 sampling cohort data set. Male patients of age 18 years or older who had been diagnosed as cases of HSV infection since January 1, 2001 were enroled. Patients with previous history of stroke, spinal cord injury or malignancy were excluded. A control group was selected, comprising male patients without HSV infection, stroke, spinal cord injury or malignancy. The age, time of enrolment and comorbidities were matched in the two groups. A total of 1 717 HSV subjects (mean age 43.29 ± 15.97 years) and 6 864 control subjects were enroled. During an average of 3.91 ± 1.93 years' follow-up, HSV-infected subjects experienced a higher incidence of ED than control subjects (1.7% vs. 0.7%, respectively). The log-rank test showed that patients with HSV infections had a significantly higher incidence of ED than those without HSV infections (p < 0.001). After Cox proportional hazard regression model analysis, HSV infections were independently associated with the increased risk of ED (hazard ratio, 2.90; 95% CI, 1.82-4.63, p < 0.001). In conclusion, HSV infections were associated with risk of ED in this cohort., (© 2012 American Society of Andrology and European Academy of Andrology.)

Osteoporotic fractures are associated with increased mortality risk. However, little data are available on the risk of acute myocardial infarction (AMI) after hip fracture. Therefore, we investigated whether hip fracture increased the risk of AMI in a large, nationwide cohort study. We obtained data from 8758 patients diagnosed with hip fracture from 2000 to 2009 and from 4 matched controls for each patient from the Longitudinal Health Insurance Database (LHID 2000), Taiwan. Controls were matched for age, sex, comorbid disorders, and enrollment date. All subjects were followed up from the date of enrollment until AMI, death, or the end of data collection (2009). Cox's regression model adjusted for age, sex, comorbid disorders, and medication was used to assess independent factors determining the risk of development of AMI. As expected, despite the matching, the hip fracture patients had more risk factors for AMI at baseline. A total of 8758 subjects with hip fractures and 35,032 controls were identified. Among these patients, 1183 (257 hip fracture patients and 926 controls) developed AMI during the median 3.2-year (interquartile range 1.4 to 5.8 years) follow-up period. Patients with hip fractures had a higher incidence of AMI occurrence when compared with controls (8.7/1000 person-years versus 6.82/1000 person-years). Multivariate analysis adjusted for baseline covariates indicated that hip fracture was associated with a greater risk for AMI development (hazard ratio [HR] = 1.29; 95% confidence interval [CI] 1.12-1.48; p < 0.001). We conclude that hip fracture is independently associated with a higher risk of subsequent AMI., (Copyright © 2013 American Society for Bone and Mineral Research.)

Objective: The aim of the present study was to investigate the association between panic disorder (PD) and atrial fibrillation (AF)., Methods: We used a nationwide population-based data set from Taiwan. A total of 3888 patients with PD and without a diagnosis of AF from a sampled cohort data set of 1,000,000 were included in the study group. Ten people without PD and AF were selected for every 1 patient in the study group, matched by propensity score matching according to time of enrollment, age, sex, and comorbidities. We performed log-rank tests to analyze differences in accumulated AF-free survival rates between the two groups. Cox proportional hazard regressions were performed to evaluate the independent factors determining the longitudinal hazard of AF., Results: During a maximal 7-year follow-up, 48 patients from the study group (1.2% of the patients with PD) and 358 from the control group (0.9% of the patients without PD) were newly diagnosed as having AF. Patients with PD had a significantly higher incidence of AF (hazard ratio [HR] = 1.54 [1.14-2.09]; log-rank test, p = .004). After Cox model adjustment for risk factors and comorbidities, PD (HR = 1.73, 95% confidence interval [CI] = 1.26-2.37), age (HR = 1.07, 95% CI = 1.06-1.08), male sex (HR = 1.26, 95% CI = 1.03-1.55), hypertension (HR = 2.00, 95% CI = 1.55-2.56), history of coronary artery disease (HR = 1.45, 95% CI = 1.15-1.82), congestive heart failure (HR = 2.46; 95% CI, 1.84-3.30), and valvular heart disease (HR = 2.83, 95% CI = 1.85-4.42) were independently associated with increased risk of AF., Conclusions: PD is independently associated with higher incidence of AF to be diagnosed in the future. Larger prospective studies or meta-analysis are suggested to confirm the findings.

Angiotensin-converting enzyme (ACE) has been implicated in multiple biological system, particularly cardiovascular diseases. However, findings associating ACE insertion/deletion polymorphism with hypertension or other related traits are inconsistent. Therefore, in a two-stage approach, we aimed to fine-map ACE in order to narrow-down the function-specific locations. We genotyped 31 single nucleotide polymorphisms (SNPs) of ACE from 1168 individuals from 305 young-onset (age ≤40) hypertension pedigrees, and found four linkage disequilibrium (LD) blocks. A tag-SNP, rs1800764 on LD block 2, upstream of and near the ACE promoter, was significantly associated with young-onset hypertension (p = 0.04). Tag-SNPs on all LD blocks were significantly associated with ACE activity (p-value: 10(-16) to <10(-33)). The two regions most associated with ACE activity were found between exon13 and intron18 and between intron 20 and 3'UTR, as revealed by measured haplotype analysis. These two major QTLs of ACE activity and the moderate effect variant upstream of ACE promoter for young-onset hypertension were replicated by another independent association study with 842 subjects.

Background: Although emerging evidence shows angiotensin-receptor blockers (ARBs) may have a beneficial effect against Alzheimer's disease (AD), the association is not consistent. We investigated the association between ARB use and the risk of development of AD using a nationwide, population-based cohort database in Taiwan., Methods and Results: In total, 16,426 newly diagnosed hypertensive patients who were administered ARB without a previous diagnosis of AD were identified from the Taiwan National Health Insurance database. The comparison group consisted of hypertensive patients who did not receive ARB, and were matched to exposed individuals using propensity score by enrolled time, age, sex, and comorbidities. During an average of 5.24 ± 2.01 years of follow-up, a total of 1,031 cases (3.13%) of new AD occurred. The log-rank test showed no significant difference in the AD occurrence rate between subjects exposed to ARBs and non-exposed controls [488 (2.97%) vs. 543 (3.29%), P=0.221]. After adjusting for age, sex, comorbidities, and medications, only advanced age [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.12-1.13, P<0.001), female sex (HR 1.18, 95% CI 1.04-1.33, P=0.011), diabetes (HR 1.53, 95% CI 1.31-1.79, P<0.001), but not ARB (HR 1.08, 95% CI 0.96-1.22, P=0.222) were independently associated with AD development., Conclusions: The use of ARB was not significantly associated with a reduction of risk of AD in Asian patients with essential hypertension.

Objective: To investigate whether SSc increases the risk of ischaemic stroke in a large, nationwide cohort study., Methods: From the Registry of Catastrophic Illness in Taiwan, we obtained data for 1280 patients with a diagnosis of SSc from 1997 to 2006. We also obtained data for 10 age-, gender-, comorbidity- and enrolment date-matched controls per SSc patient from the Longitudinal Health Insurance 2000. All study subjects were followed up from the date of enrolment until they developed ischaemic stroke, death or to the end of 2006, whichever was earlier. We used Cox's regression model with adjustment for age, gender and comorbid disorders to assess the independent factors in determining the risk of developing ischaemic stroke., Results: We identified 1238 SSc patients and 12 380 controls. Among these patients, 765 (86 SSc patients and 679 controls) had developed ischaemic stroke during the median 4.7 years (0.1-10.0 years) of follow-up. Patients with SSc had a significantly higher incidence of ischaemic stroke when compared with controls (16.5/1000 vs 11.5/1000 person-year). After multivariate analysis, SSc was associated with a 43% increase in ischaemic stroke risk (95% CI 12%, 83%; P = 0.004). Additionally, the medication usually being prescribed among SSc patients did not alter the risk of further ischaemic stroke., Conclusion: We conclude that SSc is independently associated with higher risk of ischaemic stroke development.

Background: Central serous chorioretinopathy (CSCR) is a common maculopathy that features choroidal circulatory disturbance. This population-based cohort study aimed to explore the relationship between CSCR and the future development of ischaemic stroke., Methods: Data were obtained from Taiwan's national health insurance research database. From 2000 to 2007, 1814 patients with newly diagnosed CSCR were eligible for inclusion in the study cohort. Using stratified random sampling, 9648 enrollees matched with the study subjects in terms of sex, age, monthly income, geographical location and time of enrolment were selected as the control group. Stroke-free survival analysis was assessed using a Kaplan-Meier method. Cox proportional hazard regressions were performed to calculate the HR of ischaemic stroke for the two groups after adjusting for possible confounding variables., Results: Of the sampled patients, 45 (2.5%) from the CSCR cohort and 157 (1.6%) from the control group developed ischaemic stroke during a mean follow-up period of 3.9 ± 2.2 years. CSCR patients had a significantly higher incidence of ischaemic stroke than those without a diagnosis of CSCR (p=0.003). After adjusting for age, sex and chronic comorbidities at baseline, CSCR patients were found to have a 1.56-fold (95% CI 1.11 to 2.18, p=0.010) greater risk of a subsequent ischaemic stroke than the matched controls., Conclusions: CSCR is an independent indicator for the increased risk of subsequent ischaemic stroke development.

The association between use of oral bisphosphonates and cancer development in elderly women is still uncertain, and previous studies have shown controversial results. We used a nationwide, population-based database to explore the relationship between the use of alendronate, an oral bisphosphonate agent used for the treatment of osteoporosis, and the risk of all malignancies in women with osteoporosis and age over 55 years. In the study group, we included 6906 women with osteoporosis (age, mean ± SD, 73.4 ± 8.4 years) taking oral alendronate, who were selected from a 1,000,000 sample cohort dataset collected between January 1998 and December 2009. Another 20,697 age- and comorbidity-matched women (73.5 ± 8.4 years) without bisphosphonates treatment were included in the control group. No subjects had any history of being diagnosed with cancer before inclusion. We used a log-rank test to analyze the differences in accumulated cancer-free survival rates between these two groups. A Cox proportional-hazard model, adjusted for confounding factors, was used to evaluate the association between alendronate use and the development of all cancer events in postmenopausal women with osteoporosis. During the mean follow-up period of 4.8 years, 821 patients from the study group and 2646 patients from the control group had new cancers. There was no significant difference in cancer incidence between alendronate users and controls (11.9% versus 12.8%, p = 0.054). The person-year incidence of newly-developed cancer in alendronate users and controls was 28.0 and 29.4 per 1000 person-years, respectively. Alendronate use was not associated with increased risk of cancer development in women with osteoporosis (adjusted hazard ratio, 1.05; 95% confidence interval [CI], 0.97-1.13; p = 0.237). However, due to the limited study size and underpowered results, further larger prospective studies or meta-analysis are suggested to further confirm our findings., (Copyright © 2012 American Society for Bone and Mineral Research.)

Introduction: Arterial stiffness may contribute to left ventricular hypertrophy (LVH). This study was conducted to evaluate the independent factor of LVH and the quantification of LVH by electrocardiogram (ECG) to predict the degree of aortic stiffness using brachial-ankle pulse wave velocity (baPWV) in subjects with hypertension., Materials and Methods: A total of 984 consecutive patients who were diagnosed as having essential hypertension were entered into the study. baPWV determination, ECG and blood sampling were performed after a 12-hour overnight fast. LVH was diagnosed using electrocardiography; Romhilt-Estes point score was subsequently calculated. Participants were separated into LVH and non-LVH groups. Additional factors associated with LVH were examined using multivariate analyses., Results: The non-LVH groups were younger (P = 0.001), had less men (P = 0.001), lower systolic and diastolic blood pressure and pulse pressure (P < 0.001 for each) and lower baPWV (P < 0.001). Stepwise multiple logistic regression analysis demonstrated that sex, age, systolic blood pressure and baPWV are independent factors. Using a baPWV value of 1825 cm/sec, the area under the receiver operating characteristic curve was 0.644 and the highest discriminating sensitivity and specificity were 60% and 65%, respectively., Conclusion: Aortic stiffness may be related to electrocardiographically determined LVH in patients with hypertension. Thus, stiffening of large arteries, together with increased systolic blood pressure, seems to significantly contribute to the pathogenesis of LVH. Quantification of LVH by ECG can also predict the degree of aortic stiffness.

Objective: Poor oral hygiene has been associated with an increased risk for cardiovascular disease. However, the association between preventive dentistry and cardiovascular risk reduction has remained undetermined. The aim of this study is to investigate the association between tooth scaling and the risk of cardiovascular events by using a nationwide, population-based study and a prospective cohort design., Methods: Our analyses were conducted using information from a random sample of 1 million persons enrolled in the nationally representative Taiwan National Health Insurance Research Database. Exposed individuals consisted of all subjects who were aged ≥ 50 years and who received at least 1 tooth scaling in 2000. The comparison group of non-exposed persons consisted of persons who did not undergo tooth scaling and were matched to exposed individuals using propensity score matching by the time of enrollment, age, gender, history of coronary artery disease, diabetes, hypertension, and hyperlipidemia., Results: During an average follow-up period of 7 years, 10,887 subjects who had ever received tooth scaling (exposed group) and 10,989 age-, gender-, and comorbidity-matched subjects who had not received tooth scaling (non-exposed group) were enrolled. The exposed group had a lower incidence of acute myocardial infarction (1.6% vs 2.2%, P<.001), stroke (8.9% vs 10%, P=.03), and total cardiovascular events (10% vs 11.6%, P<.001) when compared with the non-exposed group. After multivariate analysis, tooth scaling was an independent factor associated with less risk of developing future myocardial infarction (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.57-0.85), stroke (HR, 0.85; 95% CI, 0.78-0.93), and total cardiovascular events (HR, 0.84; 95% CI, 0.77-0.91). Furthermore, when compared with the non-exposed group, increasing frequency of tooth scaling correlated with a higher risk reduction of acute myocardial infarction, stroke, and total cardiovascular events (P for trend<.001)., Conclusion: Tooth scaling was associated with a decreased risk for future cardiovascular events., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: The effects of influenza vaccination on ischemic heart disease (IHD) patients remain controversial. The purpose of this study was to evaluate the effects of influenza vaccination on all-cause mortality and hospitalization for cardiovascular disease in elderly IHD patients., Methods: Elderly patients (>65 years old) with IHD, including ischemic heart failure and coronary artery disease between January 1997 and September 2002 were identified by using the Taiwan National Health Insurance Research Database. The association between influenza vaccination and all-cause mortality and hospitalization due to cardiovascular disease was analyzed., Results: We included 5048 patients. During the influenza season, influenza vaccination was associated with a reduced risk of all-cause mortality [hazard ratio (HR), 0.42; 95% confidence interval (CI) 0.35-0.49] and hospitalization for cardiovascular disease (HR, 0.84; 95% CI, 0.76-0.93). During the non-influenza season, vaccination was associated with a reduced risk of mortality (HR, 0.78; 95% CI, 0.68-0.90) in elderly IHD patients., Conclusion: Influenza vaccination was associated with a reduced risk of all-cause mortality in elderly IHD patients throughout the whole year, as well as a reduced risk of hospitalization during the influenza season., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: Precise mechanisms of atrial fibrillation (AF) are uncertain, but their association with esophageal disorders has been recently proposed. The association between gastroesophageal reflux disease (GERD), the most common gastroesophageal disorder, and AF remains undetermined. We therefore aimed to investigate the association between GERD and later development of AF., Methods and Results: Patients with GERD were identified from the 1,000,000-person cohort dataset sampled from the Taiwan National Health Insurance database. The study cohort comprised 29,688 newly diagnosed adult GERD patients; 29,597 randomly selected age-, gender-, comobidity-matched subjects comprised the comparison cohort. Cox proportional hazard regressions were performed as a means of comparing the AF-free survival rate for the two cohorts. During a maximum three years of follow-up, a total of 351 patients experienced AF, including 184 (0.62%) patients in the GERD cohort and 167 (0.56%) in the control group. The log-rank test showed that patients with GERD had significantly higher incidence of AF than those without GERD (p = 0.024). After Cox proportional hazard regression model analysis, GERD was independently associated with the increased risk of AF (hazard ratio, 1.31; 95% confidence interval, 1.06-1.61, p = 0.013)., Conclusion: GERD was independently associated with an increased risk of future AF in a nationwide population-based cohort.

Background: Systemic lupus erythematosus (SLE) has been reported to be associated with an increased risk of cardiovascular disease. However, most studies have been criticized for either a small sample size or the lack of a prospective control. Our study investigated the relationship of SLE and the subsequent development of ischemic stroke using a nationwide, population-based database in an Asian population., Methods: From 2000 to 2007, we identified a study cohort consisting of a total of 11,637 newly diagnosed SLE patients using the National Health Insurance Research Database in Taiwan. A control cohort of 58,185 subjects without SLE, matched for age, gender, and comorbidities were selected for comparison to observe the occurrence of ischemic stroke in these two groups., Results: During a follow-up period of up to 7 years, ischemic stroke developed in 258 (2.22%) of the patients with SLE and in 873 (1.5%) of patients in the comparison cohort. Kaplan-Meier analysis also revealed a tendency of SLE patients toward ischemic stroke development (log rank test, p = 0.001). After Cox model adjustment for patients' demographic characteristics and selected comorbidities, patients with SLE were found to have a 1.67-fold (95% CI, 1.45 to 1.91) higher risk of developing ischemic stroke., Conclusion: Patients with SLE have an increased risk of stroke.

This study analyzed the corrected QT dispersion (cQTd) before and at 24 hours after successful primary percutaneous coronary intervention (PCI) in 81 patients with single coronary artery disease and acute ST elevation myocardial infarction. Major cardiovascular events (MACE) at 1 year were defined as death, nonfatal myocardial infarction, life-threatening arrhythmias, and heart failure hospitalization. The cQTd before primary PCI was significantly longer in patients without MACE than in patients with MACE (73.1 ± 29.3 versus 56.3 ± 25.2 msec, P = 0.026). The cQTd at 24 hours after primary PCI was significantly shorter in patients without MACE than in patients with MACE (38.4 ± 20.8 versus 50.8 ± 28.7 msec, P = 0.045). Thus, the absolute cQTd change was significantly higher in patients without MACE compared to patients with MACE (P = 0.001). By multivariate analysis, absolute cQTd change was an independent predictor for the development of MACE, with an odds ratio of 1.498 for each 10-msec decrement in absolute cQTd change (95 percent confidence interval, 1.157 to 1.939, P = 0.002). In conclusion, the absolute cQTd change after primary PCI was an independent predictor of the development of MACE in patients with single vessel disease and acute ST elevation myocardial infarction.

Introduction: Accumulated evidence shows that erectile dysfunction (ED) may be a precursor of coronary artery disease (CAD)., Aims: The purpose of this study was to explore the differences in coronary phenotypes between patients with ED and patients with angina pectoris., Methods: The study enrolled 30 ED patients (study group) and 120 age-matched angina patients who had no ED (control group). All patients had angiographically documented CAD., Main Outcome Measures: The differences in demographic characteristics, biochemical profiles and coronary characteristics between the study and control groups were compared., Results: Diabetes mellitus (DM) and obesity defined by body mass index were more common in the study group than in the control group. The mean number of lesions and mean number of vessels with evidence of CAD were significantly different between the study and control groups (2.3 ± 0.1 vs. 2.2 ± 0.1, P < 0.001; 2.0 ± 0.2 vs. 1.8 ± 0.1, P < 0.001). The distribution of vessel involvement was similar between the groups, except for more common involvement of the ramus in the study group. There were no differences in distribution of lesion sites between the two groups. The control group had a higher percentage of type A stenotic lesions than the study group (16.3% vs. 2.9%, P = 0.004). Significant differences were also observed in type C lesions (52.9% in study group vs. 38.0% in control group, P = 0.026). Fewer calcified, irregular, and bifurcated lesions were present in the study group compared to control., Conclusions: This study documented coronary phenotypes in ED patients without symptomatic CAD. Although the artery size hypothesis and ED had well been thought to be a precursor of CAD, the severity of coronary lesions in these patients was not more benign than that observed in angina pectoris patients who have no ED., (© 2010 International Society for Sexual Medicine.)

Objectives: Obesity is a risk factor for all-cause mortality. The obesity incidence depends on different definitions. Among patients with high-risk coronary heart disease (HRCA), we have studied differences in obesity incidence, according to different anthropometric indices., Methods and Results: Based on the definitions of the International Guidelines Committees for body mass index (BMI), waist circumference (WCF), and waist-hip ratio (WHR), we have classified 487 CAD patients into 3 groups: normal (group 1), overweight (group 2), and obese patients (group 3). Among men, obesity criteria BMI, WCF and WHR were positive in 17.5%, 14.2%, and 66.4% of the subjects. Among male subjects < 65 years, the incidence of HRCA (%), for the 3 groups (normal, overweight, obese) were for BMI (2.4, 21.5, 28.9, P = 0.005); WCF (17.9, 12.1, 37.9, P = 0.012); WHR (0, 15.4, 30.4, P = 0.024). In male subjects > 65 years, for the HRCA incidence (%), only WHR showed a significant difference between the 3 groups (0, 15.4, 30.4, P = 0.024). Among women, 30.6%, 63.6%, and 87.6% were obese by the BMI, WCF, and WHR criteria, respectively. We did not find any significant differences in the HRCA distribution between age groups and degrees of obesity., Conclusions: HRCA distribution varied among obese male patients. According to the different methods of measurement, obesity percentages varied from 4- to 5-fold among men and 3-fold among women. In our view,WHR measurement is the method of choice for the determination of obesity among patients with CAD.

Previously, we observed that young-onset hypertension was independently associated with elevated plasma triglyceride(s) (TG) levels to a greater extent than other metabolic risk factors. Thus, focusing on the endophenotype--hypertension combined with elevated TG--we designed a family-based haplotype association study to explore its genetic connection with novel genetic variants of lipoprotein lipase gene (LPL), which encodes a major lipid metabolizing enzyme. Young-onset hypertension probands and their families were recruited, numbering 1,002 individuals from 345 families. Single-nucleotide polymorphism discovery for LPL, linkage disequilibrium (LD) analysis, transmission disequilibrium tests (TDT), bin construction, haplotype TDT association and logistic regression analysis were performed. We found that the CC- haplotype (i) spanning from intron 2 to intron 4 and the ACATT haplotype (ii) spanning from intron 5 to intron 6 were significantly associated with hypertension-related phenotypes: hypertension (ii, P=0.05), elevated TG (i, P=0.01), and hypertension combined with elevated TG (i, P=0.001; ii, P<0.0001), according to TDT. The risk of this hypertension subtype increased with the number of risk haplotypes in the two loci, using logistic regression model after adjusting within-family correlation. The relationships between LPL variants and hypertension-related disorders were also confirmed by an independent association study. Finally, we showed a trend that individuals with homozygous risk haplotypes had decreased LPL expression after a fatty meal, as opposed to those with protective haplotypes. In conclusion, this study strongly suggests that two LPL intronic variants may be associated with development of the hypertension endophenotype with elevated TG., (Copyright 2008 Wiley-Liss, Inc.)

Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP) quality, four SNPs from two SNP triplets with strong association signals (-log(10)(p)>7) and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (-log(10)(p)>8) were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene) and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population.

Objectives: Angiotensin converting enzyme (ACE) plays major roles in the pathogenesis of cardiovascular diseases (CVD). However, findings on the relations between ACE variants and CVD have not been consistent. The purpose of this study was to map quantitative trait loci (QTL) for serum ACE activity, a heritable endophenotype of cardiovascular diseases (estimated heritability = 0.58)., Methods: With 1,271 individuals from 373 young-onset (age

Previous studies have demonstrated improvement of regional wall motion and global left ventricular function after successful recanalization of chronic total occlusion in coronary artery. However, the difference of benefits of recanalization between infarct site and noninfarct site is unknown. This study assessed the changes in left ventricular ejection fraction, regional wall motion after successful angioplasty of chronic total occlusions with or without previous myocardial infarction. This study also evaluated the factors that influenced the outcome of left ventricular function. We retrospectively studied 75 patients with a successfully recanalized chronic total occlusion in native coronary artery. Left ventriculograms were obtained at baseline and after 6 months. Global and regional left ventricular function were determined. The patients were divided into two groups. Group 1 comprised patients without previous myocardial infarction in the territories of total occlusion vessel that was recanalized. Group 2 comprised patients with previous myocardial infarction in the territories of total occlusion vessel that was recanalized. Left ventricular ejection fraction increased from 53.2% +/- 16.3% at baseline to 57.3% +/- 20.1% at 6-month follow-up in the whole group (P = 0.001). In group 1 patients, the evolution of left ventricular (LV) ejection fraction increased from 59.5% +/- 13.7% to 67.3% +/- 14.6% (P < 0.001). In group 2 patients, the evolution of LV ejection fraction increased, but not significantly, from 48.9% +/- 16.2% to 50.5% +/- 16.9% (P = NS). The evolution of LV ejection fraction increased from 47.6% +/- 17.4% to 50.8% +/- 17.5% (P < 0.05) in the subgroup of recanalization in infarct-related vessel that had rich collateral circulation and had long-term patency. The regional wall motion all significantly improved in group 1 patients (P < 0.05). The regional wall motion did not change in group 2 patients (P = NS). The influence of recanalization of chronic coronary occlusions on the improvement of left ventricular global function was different between myocardial infarction and nonmyocardial infarction patients. The left ventricular function did not improve in myocardial infarction patient. Regional wall motion improved in patients without previous myocardial infarction. For reliable improvement of left ventricular function after recanalization of chronic total occlusions, evidence (not only by symptom or treadmill test) of viable myocardium in recanalized vessel is important. It is also important to keep patency of infarct-related vessel that has good collateral circulation for improving the left ventricular function., (Copyright 2003 Wiley-Liss, Inc.)