Chia-Hung Chiang

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.

The severity of non-alcoholic fatty liver disease correlates with high sensitivity C-reactive protein value and is independently associated with increased cardiovascular risk in healthy population

OBJECTIVES We aimed to investigate the correlation between non-alcoholic fatty liver disease (NAFLD) and risk of cardiovascular disease (CVD). DESIGN AND METHODS We analyzed 724 subjects without CVD according to presence or absence of NAFLD. Logistic regression model was used to determine if NAFLD was an independent risk factor of CVD. RESULTS Subjects with NAFLD had increased percentage of 10-year cardiovascular risk ≧10% compared to those without NAFLD (p<0.001). The severity of NAFLD significantly correlated with increasing Framingham risk score and C-relative protein (CRP) value. After adjusting for conventional CVD risk factors, the presence of NAFLD was an independent predictor for future CVD risk ≧10% [odds ratio: 1.89, p=0.004]. Subgroup analysis showed the predictive value of NAFLD was significant among aged subjects and those with increased baseline hsCRP level. CONCLUSIONS NAFLD is independently associated with increased CVD risk, especially among elderly subjects and those with increased CRP level.

Decreased Circulating Endothelial Progenitor Cell Levels and Function in Patients with Nonalcoholic Fatty Liver Disease

Objectives Nonalcoholic fatty liver disease (NAFLD) is associated with advanced atherosclerosis and a higher risk of cardiovascular disease. Increasing evidence suggests that injured endothelial monolayer is regenerated by circulating bone marrow derived-endothelial progenitor cells (EPCs), and levels of circulating EPCs reflect vascular repair capacity. However, the relation between NAFLD and EPC remains unclear. Here, we tested the hypothesis that patients with nonalcoholic fatty liver disease (NAFLD) might have decreased endothelial progenitor cell (EPC) levels and attenuated EPC function. Methods and Results A total of 312 consecutive patients undergoing elective coronary angiography because of suspected coronary artery disease were screened and received examinations of abdominal ultrasonography between July 2009 and November 2010. Finally, 34 patients with an ultrasonographic diagnosis of NAFLD, and 68 age- and sex-matched controls without NAFLD 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 circulating EPC numbers. The adhesive function, and migration, and tube formation capacities of EPCs were also determined in NAFLD patients and controls. Patients with NAFLD had a significantly higher incidence of metabolic syndrome, previous myocardial infarction, hyperuricemia, and higher waist circumference, body mass index, fasting glucose and triglyceride levels. In addition, patients with NAFLD had significantly decreased circulating EPC levels (all P<0.05), attenuated EPC functions, and enhanced systemic inflammation compared to controls. Multivariate logistic regression analysis showed that circulating EPC level (CD34+KDR+ [cells/105 events]) was an independent reverse predictor of NAFLD (Odds ratio: 0.78; 95% confidence interval: 0.69–0.89, P<0.001). Conclusions NAFLD patients have decreased circulating EPC numbers and functions than those without NAFLD, which may be one of the mechanisms to explain atherosclerotic disease progression and enhanced cardiovascular risk in patients with NAFLD.

Hip fracture and risk of acute myocardial infarction: A nationwide study

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). Coxs 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.

The Association of Tooth Scaling and Decreased Cardiovascular Disease: A Nationwide Population-based Study

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.

Oral alendronate use and risk of cancer in postmenopausal women with osteoporosis: A nationwide study.

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.

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.

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 Coxs 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.

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 m2. The mean annual rate of GFR decline (△GFR/y) was −1.49±3.26 mL/min/1.73 m2 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.

Herpes simplex virus infection and risk of atrial fibrillation: A nationwide study

BACKGROUND Currently, precise mechanisms of atrial fibrillation (AF) are uncertain but proved to be associated with inflammation. There has been no specific study to evaluate the risk of AF after diagnosis of herpes simplex virus (HSV) infection. METHODS To investigate the relationship between HSV infection and the occurrence of AF, we used a nation-wide population-based dataset from Taiwan. A total of 15,180 patients with diagnosis of HSV infection were included in the study group from a 1,000,000 sampling cohort dataset between January 2000 and December 2003. Another 73,197 age-, gender-, and comorbidity-matched subjects without HSV infection were included in the control group. The log-rank test was performed to analyze the differences in accumulated AF-free survival rates between these 2 groups. Cox proportional hazard regressions were performed to evaluate the independent factor in determining the longitudinal hazard of AF. RESULTS During a 3-year follow-up period, 240 patients from the study group (1.6%) and 801 patients from the comparison group (1.1%) had newly developed AF. The log-rank test showed that patients with HSV had significantly higher incidence of AF development than those without HSV (p<0.001). After Cox model adjustment for risk factors and comorbidities, HSV infection was independently associated with increased risk of AF development (hazard ratios [HR], 1.39; 95% confidence interval [CI], 1.2-1.60; p<0.0001). CONCLUSION Our study concludes that HSV infection may be independently associated with an increased risk of future AF development.