Technological process optimization and measurement of image quality of the electrically bifocal metalens.

This Letter describes the design procedure and process optimization of the electrically bifocal metalens. In our design, horizontal and vertical polarization is manipulated by applying a suitable voltage to a twisted nematic liquid crystal (TN-LC) cell. Each nanostructure is designed to be a rectangular prism, making different polarizations of light experience various phase delays, thus causing bi-focus. We selected lithographical methods to fabricate our metalens because of the minimum physical size, which can be as small as 50 nm, and the maximum aspect ratio, which is as high as 15. Furthermore, to increase the tolerance and make the sidewall vertical and smooth, we coated different characteristics of photoresist sensitivity to the upper and lower layers. After the development, the mushroom-type photoresist makes Ni easier to strip while in the lift-off process, thus increasing the quality of the whole metalens. Our experiment shows that the focal lengths and focusing efficiencies corresponding to the two polarizations are similar to the simulation results. The proposed electrically modulated bifocal metalens can be utilized in different applications and combined with other optical components.

Association of Serum Bilirubin with SYNTAX Score and Future Cardiovascular Events in Patients Undergoing Coronary Intervention.

BACKGROUND: Bilirubin has emerged as an important endogenous antioxidant molecule, and increasing evidence shows that bilirubin may protect against atherosclerosis. The SYNTAX score has been developed to assess the severity and complexity of coronary artery disease. The aim of this study was to evaluate whether serum bilirubin levels are associated with SYNTAX scores and whether they could be used to predict future cardiovascular events in patients undergoing coronary intervention. METHODS: Serum bilirubin levels and other blood parameters in patients with at least 12-h fasting states were determined. The primary endpoint was any composite cardiovascular event within 1 year, including death, nonfatal myocardial infarction, and target-vessel revascularization. RESULTS: In total, 250 consecutive patients with stable coronary artery disease (mean age 70 ± 13) who had received coronary intervention were enrolled. All study subjects were divided into two groups: group 1 was defined as high SYNTAX score (> 22), and group 2 was defined as low SYNTAX score (≤ 22). Total bilirubin levels were significantly lower in the high SYNTAX score group than in the low SYNTAX score group (0.51 ± 0.22 vs. 0.72 ± 0.29 mg/dl, p < 0.001). By multivariate analysis, serum total bilirubin levels were identified as an independent predictor for high SYNTAX score (adjusted odds ratio: 0.28, 95% confidence interval 0.04-0.42; p = 0.004). Use of the Kaplan-Meier analysis demonstrated a significant difference in 1-year cardiovascular events between high (> 0.8 mg/dl), medium (> 0.5, ≤ 0.8 mg/dl), and low (≤ 0.5 mg/dl) bilirubin levels (log-rank test p = 0.011). CONCLUSIONS: Serum bilirubin level is associated with SYNTAX score and predicts future cardiovascular events in patients undergoing coronary intervention.

The Association Between Insomnia and Increased Future Cardiovascular Events: A Nationwide Population-Based Study.

OBJECTIVES: Insomnia may increase the risk of cardiovascular disease (CVD), but the reported magnitude of the associations between sleep characteristics and CVD is inconsistent. We investigated the association between insomnia and the risk of developing acute myocardial infarction (AMI) and/or stroke by using a nationwide, population-based cohort database in Taiwan. METHODS: The analyses were conducted using information from a random sample of 1 million people enrolled in the nationally representative Taiwan National Health Insurance Research Database. A total of 44,080 individuals who were 20 years or older, including 22,040 people who had diagnosis of insomnia during the study period and an age-, sex-, comorbidity-matched group of 22,040 people without insomnia, were enrolled in our study. The study end points were the occurrence of cardiovascular events including AMI or stroke during follow-up. RESULTS: During a 10-year follow-up, 302 AMI events and 1049 stroke events were identified. The insomnia group had a higher incidence of AMI (2.25 versus 1.08 per 1000 person-years) and stroke (8.01 versus 3.69 per 1000 person-years, p < .001). Cox proportional hazard regression model analysis showed that insomnia was independently associated with a higher risk of future AMI (hazard ratio [HR] = 1.68, 95% confidence interval [CI] = 1.31-2.16, p < .001), stroke (HR = 1.85, 95% CI = 1.62-2.12, p < .001), and the composite event index (HR = 1.81, 95% CI = 1.61-2.05, p < .001), after adjusting for age, sex, and comorbidities. CONCLUSIONS: Insomnia is associated with an increased risk of future cardiovascular events.

Association of tamoxifen use and reduced cardiovascular events among asian females with breast cancer.

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.

Systemic sclerosis and risk of ischaemic stroke: a nationwide cohort study.

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.

Association between panic disorder and risk of atrial fibrillation:a nationwide study.

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-receptor blockers and risk of Alzheimer's disease in hypertension population--a nationwide cohort study.

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.

Decreased circulating endothelial progenitor cell levels in patients with heart failure with preserved ejection fraction.

OBJECTIVES: The purpose of this study was to explore the relationship between endothelial progenitor cell (EPC) levels, heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). METHODS: A total of 44 HFpEF patients, 40 HFrEF patients and 69 age-, gender- and comorbidity-matched controls were enrolled after evaluating their clinical manifestations and echocardiography findings. Flow cytometry with quantification of three EPC markers in peripheral blood samples was used to assess the number of circulating EPCs. RESULTS: HFpEF and HFrEF patients had significantly decreased circulating EPC levels compared to controls. Among heart failure patients, patients with New York Heart Association functional class (FC) IV had fewer circulating EPCs compared to those with FC II and FC III (p = 0.053). A simple linear regression analysis of data showed that high sensitivity C-reactive protein, left ventricular ejection fraction, left atrium diameter and the ratio of medial early filling to early diastolic mitral annular velocity all correlated with the EPC count. In multivariate Cox regression analyses, both HFpEF and HFrEF were found to be independent predictors of a decreased EPC number. CONCLUSIONS: HFpEF and HFrEF patients have decreased circulating EPC numbers, which is an indication of impaired endothelial turnover.

Primary Sjögren's Syndrome and the Risk of Acute Myocardial Infarction: A Nationwide Study.

BACKGROUND: Patients with autoimmune diseases have a high cardiovascular risk. However, few data are available on the risk of acute myocardial infarction (AMI) in patients diagnosed with primary Sjögren's syndrome (PSS). We conducted a large nationwide cohort study to investigate the possible association between PSS and the risk of AMI. METHODS: Between the years 2000-2006, a total of 5205 patients with newly diagnosed PSS and no history of AMI were identified from the Registry of Catastrophic Illness, a sub-dataset of the National Health Insurance Research Database in Taiwan. The control group, which consisted of subjects without systemic autoimmune disease or previous AMI, was matched by the date of enrollment, age, gender, history of coronary artery disease, diabetes, hypertension, chronic kidney disease, and hyperlipidemia. The study endpoints were the occurrence of AMI. RESULTS: Of the 5205 subjects with PSS and 5205 controls included in the study, 77 (35 PSS patients and 42 controls) developed AMI during the mean 3.7-year (interquartile range, 2.1-5.1 years) follow-up period. The incidence of AMI was similar in PSS patients and controls (1.91/1000 versus 2.25/1000 person-years). Multivariate analysis adjusted for baseline covariates demonstrated an insignificant association between PSS and AMI [adjusted hazard ratio, 0.86; 95% confidence interval (CI), 0.55-1.35; p = 0.506], suggesting that PSS does not increase the risk of AMI. CONCLUSIONS: PSS is not associated with a higher risk of subsequent AMI. KEY WORDS: Acute myocardial infarction; Atherosclerosis; Primary Sjögren's syndrome.

Niacin improves ischemia-induced neovascularization in diabetic mice by enhancement of endothelial progenitor cell functions independent of changes in plasma lipids.

Niacin was shown to inhibit acute vascular inflammation and improves endothelial dysfunction independent of changes in plasma lipids. Here, we investigated whether niacin can increase blood flow recovery after tissue ischemia by enhancing endothelial progenitor cell (EPC) functions in diabetic mice. Starting at 4 weeks after the onset of diabetes, vehicle or niacin (40 mg/kg/day) was administered daily by gavage to streptozotocin (STZ)-induced diabetic mice and diabetic endothelial nitric oxide synthase (eNOS)-deficient mice. Unilateral hindlimb ischemia surgery was conducted after 2 weeks of vehicle or niacin treatment. Compared to the control group, the niacin group had significantly increased ischemic/non-ischemic limb blood perfusion ratio and higher capillary density. These effects were markedly reduced in STZ-induced diabetic eNOS-deficient mice. Flow cytometry analysis showed impaired EPC-like cell (Sca-1(+)/Flk-1(+)) mobilization after ischemia surgery in diabetic mice but augmented mobilization in the mice treated with niacin. Diabetes was induced by administering STZ to FVB mice that received eGFP mouse bone marrow cells to evaluate effects of niacin on bone marrow-derived EPC homing and differentiation to endothelial cells. Differentiation of bone marrow-derived EPCs to endothelial cells in the ischemic tissue around vessels in diabetic mice that received niacin treatment, was significantly increased than that in control group. By in vitro studies, incubation with niacin in high-glucose medium reduced H(2)O(2) production, cell apoptosis, and improved high glucose-suppressed EPC functions by nitric oxide-related mechanisms. Our findings demonstrate that niacin increases blood flow recovery after tissue ischemia in diabetic mice through enhancing EPC mobilization and functions via nitric oxide-related pathways.

Association between Mycoplasma pneumonia and increased risk of ischemic stroke: a nationwide study.

BACKGROUND AND PURPOSE: Infections have been hypothesized to play a role in vascular disease. The association between Mycoplasma pneumoniae (MP) infection and ischemic stroke remained undetermined. METHODS: A total of 1094 patients with MP infection were enrolled as the study group and compared with 5168 sex-, age-, and comorbidity-matched subjects without MP, to be followed up prospectively from January 2003 to December 2007 for development of ischemic stroke. RESULTS: During a maximum 5-year follow-up period, 49 patients with ischemic stroke were identified. Subjects with MP infection were significantly associated with increased risk of ischemic stroke compared with controls (1.10% versus 0.72%, respectively; P=0.01). The logrank test showed that patients with MP had significantly higher incidence of stroke development than did those without MP (P=0.046). After Cox model adjustment for risk factors and comorbidities, MP infection was still independently associated with increased risk of stroke (hazard ratio [HR], 2.07; 95% CI, 1.05-4.03). CONCLUSIONS: We conclude that MP infection is independently associated with risk of subsequent ischemic stroke development.

Increased Circulating Visfatin Is Associated With Progression of Kidney Disease in Non-Diabetic Hypertensive Patients.

BACKGROUD: Declining renal function is an independent risk factor for all-cause mortality in cardiovascular disease. Visfatin has been described as a marker of inflammation and endothelial dysfunction, but whether circulating visfatin levels are predictive to a subsequent decline in renal function remains unclear. METHODS: In total, 200 nondiabetic, non-proteinuric hypertensive outpatients with initial serum creatinine (Scr) ≤1.5 mg/dl were enrolled. Plasma visfatin concentration and endothelial function estimated by brachial artery flow-mediated dilatation (FMD) were determined in the study subjects. The primary endpoints were the occurrence of renal events including doubling of Scr, 25% loss of glomerular filtration rate (GFR) from baseline values, and the occurrence of end-stage renal disease during follow-up. RESULTS: The mean annual rate of GFR decline (ΔGFR/y) was -1.26±2.76 ml/min/1.73 m(2) per year during follow-up (8.6±2.5 years). At baseline, plasma visfatin was negatively correlated with estimated GFR. In longitudinal analysis, the ΔGFR/y was correlated with visfatin, baseline GFR, FMD, systolic blood pressure, and fasting blood glucose (FBG). Multivariate analysis indicated that increased visfatin (r = -0.331, P <0.001), baseline GFR (r = -0.234, P = 0.001), FMD (r = 0.163, P = 0.015), and FBG (r = -0.160, P = 0.015) are independent predictors of ΔeGFR/y. Cox regression model analysis showed that visfatin (hazard ratio (HR), 1.09; 95% confidence interval (CI), 1.05-1.13, P <0.001), FBG (HR, 1.01; 95% CI, 1.00-1.02, P = 0.020), and FMD (HR, 0.87; 95% CI, 0.76-1.00, P = 0.049) were independently associated with the risk of developing future renal events. CONCLUSIONS: Increased circulating visfatin are associated with subsequent decline in renal function in nondiabetic hypertensive patients.

The association between urinary calculi and increased risk of future cardiovascular events: A nationwide population-based study.

BACKGROUND: Although accumulating evidence suggests urinary calculi may be associated with an increased risk of cardiovascular disease (CVD), the number of longitudinal studies linking urolithiasis to CVD events is limited. We investigated the association between urinary calculi and the risk of development of myocardial infarction (MI) and/or stroke in a nationwide, population-based cohort database in Taiwan. METHODS: Our analyses were conducted using information from a random sample of 1 million people enrolled in the nationally representative Taiwan National Health Insurance Research Database. A total of 81,546 subjects aged 18 years or above, including 40,773 subjects diagnosed with urinary calculi during the study period and a propensity score-matched 40,773 subjects without urinary calculi were enrolled in our study. RESULTS: During a 10-year follow-up period, 501 MI events and 1295 stroke events were identified. By comparison, the urinary calculi group had a higher incidence rate of MI occurrence (11.79 vs 8.94 per 10,000 person-years) and stroke (31.41 vs 22.45 per 10,000 person-years). Cox proportional hazard regression model analysis showed that development of urinary calculi was independently associated with higher risk of developing future MI (HR, 1.31; 95% CI, 1.09-1.56, p=0.003), stroke (HR, 1.39; 95% CI, 1.24-1.55, p<0.001), and total cardiovascular events (HR, 1.38; 95% CI, 1.25-1.51, p<0.001). CONCLUSIONS: Urinary calculi were associated with an increased risk of future cardiovascular events in the Asian population, which was consistent with the recent epidemiologic evidence in Western countries.

Sleep apnea and risk of aortic dissection: A nonrandomized, pair-matched cohort study.

BACKGROUND: Sleep apnea (SA) was associated with increased prevalence of aortic dissection (AD) in studies that were criticized for either their small sample size or lack of prospective observation. Using a considerably larger nationwide, population-based database and a long-term prospective cohort design, our study strived to explore the relationship between SA and the subsequent development of AD. METHODS: From 2000 to 2007, we gathered a study cohort consisting of 15,848 newly diagnosed cases of SA from Taiwan's National Health Insurance Research Database. For the control group, another 39,826 individuals without SA were matched for age, sex, and comorbidity. The two cohorts were followed-up to observe the occurrence of AD. RESULTS: During an average 3.59 ± 2.41 years of follow-up, we observed 33 cases of new AD occurrence [non-SA (22, 0.1%) vs. SA (11, 0.1%), p=0.669], and the incidence of AD was similar for both groups. After adjusting for age, sex, and comorbidity, only age [hazard ratio (HR) 1.03; 95% confidence interval (CI), 1.01-1.06; p=0.006], male gender (HR 2.49; 95% CI, 1.07-5.79; p=0.034), and hypertension (HR 6.28; 95% CI, 2.36-16.67; p<0.001) were independently associated with AD diagnosis. CONCLUSION: SA was not associated with an increased risk of AD using a large nationwide cohort database. Nonetheless, larger prospective studies or meta-analyses are recommended to confirm our findings.

Usefulness of Circulating Decoy Receptor 3 in Predicting Coronary Artery Disease Severity and Future Major Adverse Cardiovascular Events in Patients With Multivessel Coronary Artery Disease.

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an antiapoptotic soluble receptor considered to play an important role in immune modulation and has pro-inflammatory functions. This study was designed to test whether circulating DcR3 levels are associated with coronary artery disease (CAD) severity and predict future major adverse cardiovascular events (MACEs) in patients with CAD. Circulating DcR3 levels and the Syntax score (SXscore) were determined in patients with multivessel CAD. The primary end point was the MACE within 12 months. In total, 152 consecutive patients with angiographically confirmed multivessel CAD who had received percutaneous coronary intervention were enrolled and were divided into 3 groups according to CAD lesion severity. Group 1 was defined as low SXscore (≤13), group 2 as intermediate SXscore (>13 and ≤22), and group 3 as high SXscore (>22). DcR3 levels were significantly higher in the high SXscore group than the other 2 groups (13,602 ± 7,256 vs 8,025 ± 7,789 vs 4,637 ± 4,403 pg/ml, p <0.001). By multivariate analysis, circulating DcR3 levels were identified as an independent predictor for high SXscore (adjusted odds ratio 1.15, 95% confidence interval 1.09 to 1.21; p <0.001). The Kaplan-Meier analysis showed that increased circulating DcR3 levels are associated with enhanced 1-year MACE in patients with multivessel CAD (log-rank p <0.001). In conclusion, increased circulating DcR3 levels are associated with CAD severity and predict future MACE in patients with multivessel CAD.

Reduction of circulating endothelial progenitor cell level is associated with contrast-induced nephropathy in patients undergoing percutaneous coronary and peripheral interventions.

OBJECTIVES: Reduced number and impaired function of circulating endothelial progenitor cells (EPCs) in patients with chronic kidney disease have been reported. However, there is little data about the association between circulating EPC levels and risk of contrast-induced nephropathy (CIN). The aim of this study was to investigate the relationship between circulating EPCs and CIN in patients after angiography. METHODS AND RESULTS: A total of 77 consecutive patients undergoing elective percutaneous coronary intervention (PCI) and percutaneous transluminal angioplasty (PTA) were enrolled. Flow cytometry with quantification of EPC markers (defined as CD34+, CD34+KDR+, and CD34+KDR+CD133+) in peripheral blood samples was used to assess EPC number before the procedure. CIN was defined as an absolute increase ≧0.5 mg/dl or a relative increase ≧25% in the serum creatinine level at 48 hours after the procedure. Eighteen (24%) of the study subjects developed CIN. Circulating EPC levels were significantly lower in patients who developed CIN than in those without CIN (CD34+KDR+, 4.11±2.59 vs. 9.25±6.30 cells/105 events, P<0.001). The incidence of CIN was significantly greater in patients in the lowest EPC tertile (CD34+KDR+; from lowest to highest, 52%, 15%, and 4%, P<0.001). Using univariate logistic regression, circulating EPC number (CD34+KDR+) was a significant negative predictor for development of CIN (odds ratio 0.69, 95% CI 0.54-0.87, P = 0.002). Over a two-year follow-up, patients with CIN had a higher incidence of major adverse cardiovascular events including myocardial infarction, stroke, revascularization of treated vessels, and death (66.7% vs. 25.4%, P = 0.004) than did patients without CIN. CONCLUSIONS: Decreased EPC level is associated with a greater risk of CIN, which may explain part of the pathophysiology of CIN and the poor prognosis in CIN patients.

Primary Sjögren's syndrome and risk of ischemic stroke: a nationwide study.

Few studies are available on the risk of ischemic stroke after a diagnosis of primary Sjögren's syndrome (PSS). This study investigated whether PSS increased the risk of ischemic stroke in a large, nationwide cohort. Data for 4,276 patients who were newly diagnosed with PSS from 2000 to 2006 and who did not have a stroke prior to diagnosis of PSS were obtained from the Registry of Catastrophic Illness in Taiwan. For each PSS patient, data for ten controls (matched by age, gender, comorbidities, and enrollment date) without systemic autoimmune disease or previous stroke were obtained from the Longitudinal Health Insurance 2000 database. All study subjects were followed up from the date of enrollment until they developed ischemic stroke, died, or until the end of 2006, whichever was earliest. To investigate if PSS was an independent factor in determining the risk of developing ischemic stroke, a Cox regression model was used with adjustment for age, gender, and comorbid disorders. Among 4,276 PSS patients and 42,760 controls, 669 subjects (51 PSS patients and 618 controls) developed ischemic stroke during the mean 3.7-year follow-up period (interquartile range 2.2-5.2 years). Patients with PSS and controls had a similar incidence of ischemic stroke occurrence (3.17/1,000 vs. 3.90/1,000 person years). Multivariate analysis adjusted for baseline covariates indicated that PSS did not increase the risk of ischemic stroke (adjusted hazard ratio: 0.84, 95 % confidence interval: 0.63-1.12, P = 0.244). PSS is not associated with an increased risk of ischemic stroke subsequent to diagnosis.

Diabetes mellitus and the risk of Alzheimer's disease: a nationwide population-based study.

OBJECTIVES: Possible association between diabetes mellitus (DM) and Alzheimer's disease (AD) has been controversial. This study used a nationwide population-based dataset to investigate the relationship between DM and subsequent AD incidence. METHODS: Data were collected from Taiwan's National Health Insurance Research Database, which released a cohort dataset of 1,000,000 randomly sampled people and confirmed it to be representative of the Taiwanese population. We identified 71,433 patients newly diagnosed with diabetes (age 58.74 ± 14.02 years) since January 1997. Using propensity score, we matched them with 71,311 non-diabetic subjects by time of enrollment, age, gender, hypertension, hyperlipidemia, and previous stroke history. All the patients were followed up to December 31, 2007. The endpoint of the study was occurrence of AD. RESULTS: Over a maximum 11 years of follow-up, diabetic patients experienced a higher incidence of AD than non-diabetic subjects (0.48% vs. 0.37%, p<0.001). After Cox proportional hazard regression model analysis, DM (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.50-2.07, p<0.001), age (HR, 1.11; 95% CI, 1.10-1.12, p<0.001), female gender (HR, 1.24; 95% CI, 1.06-1.46, p=0.008), hypertension (HR, 1.30; 95% CI, 1.07-1.59, p=0.01), previous stroke history (HR, 1.79; 95% CI, 1.28-2.50, p<0.001), and urbanization status (metropolis, HR, 1.32; 95% CI, 1.07-1.63, p=0.009) were independently associated with the increased risk of AD. Neither monotherapy nor combination therapy with oral antidiabetic medications were associated with the risk of AD after adjusting for underlying risk factors and the duration of DM since diagnosis. However, combination therapy with insulin was found to be associated with greater risk of AD (HR, 2.17; 95% CI, 1.04-4.52, p=0.039). CONCLUSION: Newly diagnosed DM was associated with increased risk of AD. Use of hypoglycemic agents did not ameliorate the risk.

Usefulness of plasma matrix metalloproteinase-9 level in predicting future coronary revascularization in patients after acute myocardial infarction.

OBJECTIVES: This study aims to determine whether plasma levels of matrix metalloproteinases (MMPs) and inflammatory markers can predict the long-term prognosis of coronary revascularization in patients after acute myocardial infarction (AMI). BACKGROUND: MMPs have been implicated in the development of atherosclerosis and plaque rupture in acute coronary syndrome. METHODS: Ninety-six consecutive patients (63±11 years) diagnosed with myocardial infarction were enrolled. All patients were followed up for 43±12 months. Plasma levels of MMP-2 and MMP-9 were determined from blood samples collected immediately after hospitalization. Coronary revascularization was defined as having received a percutaneous coronary intervention or a coronary artery bypass graft surgery. RESULTS: A total of 29 patients (30%) had undergone coronary revascularization during the follow-up period, including 27 percutaneous coronary intervention and two coronary artery bypass graft surgery. The baseline characteristics were similar between groups with or without revascularization. Patients with coronary revascularization had significantly higher MMP-9 levels (P=0.048), but not MMP-2 levels. In addition, a positive correlation was found between circulating MMP-9 level and total cholesterol (r=0.250, P=0.016) and low-density lipoprotein-cholesterol (r=0.284, P=0.009). All patients were divided into a high-MMP-9 group (highest tertile≥1.10 ng/ml) and a low-MMP-9 group (<1.10 ng/ml). The incidence of coronary revascularization was significantly increased in the high-MMP-9 group (P=0.034). In a multivariate Cox regression analysis that included MMP-9 and classical risk factors, the MMP-9 level was an independent predictor of coronary revascularization in patients after AMI (hazard ratio, 2.72; 95% confidence interval, 1.24-5.98; P=0.026). CONCLUSION: Increased plasma levels of MMP-9 but not MMP-2 or inflammatory markers predict future coronary revascularization, and a significant association was observed with MMP-9 and low-density lipoprotein-cholesterol. These findings suggest a pivotal role of MMP-9 in atherothrombosis in AMI patients.

Increased circulating endothelial apoptotic microparticle to endothelial progenitor cell ratio is associated with subsequent decline in glomerular filtration rate in hypertensive patients.

BACKGROUND: Recent research indicates hypertensive patients with microalbuminuria have decreased endothelial progenitor cells (EPCs) and increased levels of endothelial apoptotic microparticles (EMP). However, whether these changes are related to a subsequent decline in glomerular filtration rate (GFR) remains unclear. METHODS AND RESULTS: We enrolled totally 100 hypertensive out-patients with eGFR ≥ 30 mL/min/1.73 m(2). The mean annual rate of GFR decline (△GFR/y) was -1.49 ± 3.26 mL/min/1.73 m(2) per year during the follow-up period (34 ± 6 months). Flow cytometry was used to assess circulating EPC (CD34(+)/KDR(+)) and EMP levels (CD31(+)/annexin V(+)) in peripheral blood. The △GFR/y was correlated with the EMP to EPC ratio (r= -0.465, p<0.001), microalbuminuria (r= -0.329, p=0.001), and the Framingham risk score (r= -0.245, p=0.013). When we divided the patients into 4 groups according to the EMP to EPC ratio, there was an association between the EMP to EPC ratio and the ΔGFR/y (mean ΔGFR/y: 0.08 ± 3.04 vs. -0.50 ± 2.84 vs. -1.25 ± 2.49 vs. -4.42 ± 2.82, p<0.001). Multivariate analysis indicated that increased EMP to EPC ratio is an independent predictor of ΔeGFR/y. CONCLUSIONS: An increased circulating EMP to EPC ratio is associated with subsequent decline in GFR in hypertensive patients, which suggests endothelial damage with reduced vascular repair capacity may contribute to further deterioration of renal function in patients with hypertension.