Wan-Leong Chan

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.

Angiotensin II Receptor Blockers and Risk of Cancer in Patients With Systemic Hypertension

Recently, concerns have been raised that angiotensin II receptor blockers (ARBs) may be associated with an increased risk for cancer development. However, the relation between ARBs and cancer is still unclear. Therefore, a nationwide population-based study was conducted to investigate the possible influence of ARBs on the occurrence of new cancers in patients with hypertension by using the Taiwan National Health Insurance database. A total of 109,002 patients with newly diagnosed hypertension were identified from a cohort database of 1 million individuals from January 1, 1998, to December 31, 2006. Among them, 40,124 (36.8%) had received ARBs for hypertension. The end point was the development of any type of cancer before the end of 2007. During an average of 5.7 ± 2.6 years of follow-up, a total of 9,067 cases of new cancer occurrence were observed. The log-rank test showed that the occurrence rate of newly diagnosed cancers in the subjects receiving ARBs was significantly lower than those receiving treatment without ARBs (ARBs vs controls 3,082 vs 5,985, p <0.001). After adjusting for age, gender, co-morbidities, and medications for hypertension control, ARB use was found to be independently associated with a decreased risk for cancer occurrence (hazard ratio 0.66, 95% confidence interval 0.63 to 0.68, p <0.001). In conclusion, long-term use of ARBs is associated with a lower incidence of cancer occurrence, thereby suggesting that ARBs may prevent cancer development.

Statin use in patients with asthma: a nationwide population-based study.

Eur J Clin Invest 2011; 41 (5): 507–512

Risk of Adverse Outcomes in Taiwan Associated With Concomitant Use of Clopidogrel and Proton Pump Inhibitors in Patients Who Received Percutaneous Coronary Intervention

Recent studies have suggested that proton pump inhibitors (PPIs) might reduce the inhibitory effect of clopidogrel on platelet aggregation, possibly through inhibition of the hepatic cytochrome P450 2C19 (CYP2C19) isoenzyme. The prevalence of CYP2C19 loss-of-function alleles is much greater among East Asians than among other populations. Thus, potential drug interactions might be more apparent. Therefore, we conducted a nationwide, population-based study using the Taiwan National Health Insurance database. We identified 3,278 patients (mean age 65.9 +/- 11.9 years, 71.9% men) with coronary artery disease who had taken clopidogrel after percutaneous coronary intervention from the 1 million sampling cohort data set since January 1, 2002. Of the 3,278 patients, 572 had received concomitant PPIs for underlying gastrointestinal disease and 2,706 had not used PPIs. To the end of 2007, 1,410 patients had been rehospitalized, 970 patients had undergone revascularization, and 499 patients had died. According to the Kaplan-Meier analysis, the incidence of rehospitalization (p = 0.001) and mortality (p <0.001) was significantly greater for the patients with concomitant PPI use than for those without concomitant PPI use. However, the incidence of revascularization was similar in the 2 groups. Multivariate analyses showed that concomitant PPI use was associated with an increased risk of rehospitalization (hazard ratio 1.23, 95% confidence interval 1.07 to 1.41, p = 0.003) and mortality (hazard ratio 1.65, 95% confidence interval 1.35 to 2.01, p <0.001). In conclusion, the concomitant use of clopidogrel and PPIs should be done with care to avoid adverse outcome in East Asians patients who have undergone percutaneous coronary intervention.

Prevalence and clinical characteristics of simple renal cyst.

Background: We investigated simple renal cysts to understand the prevalence in healthy individuals and evaluate their clinical characteristics to determine whether or not there are any risk factors associated with simple renal cysts. Methods: Abdominal sonography was performed in 577 individuals (317 men, 260 women; mean age, 48.84 years; age range, 20–94 years) who received health check‐up in January to February 2005. Data including age, sex, renal sonographic findings (cyst number, site, diameter, renal stones), values of serum cholesterol, glucose and creatinine, urine analysis (proteinuria, hematuria, pyuria), and smoking habit were analyzed. Results: The overall prevalence of simple renal cysts was 10.7%, ranging from 2.38% in the 2nd to 35.29% in the 7th or later decade of life. The prevalence increased with age (p < 0.001). The mean age of individuals with cysts was significantly older than those without cysts (57.65 ± 13.35 vs. 47.78 ± 12.40 years; p < 0.001). Male‐to‐female ratio was 2.81 (15.14% vs. 5.38%; p < 0.001). The majority of cysts were solitary (82.3%). Mean largest diameter of cysts was 20.89 ± 12.62 mm. The mean size of cysts in every age group was not statistically different. Factors significantly associated with simple renal cysts were age (odds ratio [OR], 4.37; p < 0.001), sex (OR, 0.32; p < 0.001), serum creatinine (OR, 11.77; p = 0.001), proteinuria (OR, 3.11; p = 0.004), renal stone (OR, 2.47; p = 0.006), and smoking (OR, 2.80; p < 0.001). However, in multivariate analysis, except proteinuria, all of the above factors were significantly related to the occurrence of simple renal cysts. Conclusion: The overall prevalence of simple renal cysts in healthy individuals was 10.7%. Age, sex, renal stone, serum creatinine, and smoking were found to be risk factors for the presence of simple renal cysts.

Nonpeptic Ulcer, Nonvariceal Gastrointestinal Bleeding in Hemodialysis Patients

OBJECTIVES Hemodialysis patients carry a higher risk of peptic ulcer bleeding. Whether hemodialysis patients also have a higher occurrence of nonpeptic ulcer, nonvariceal gastrointestinal bleeding needs further evaluation. METHODS Using Taiwans National Health Insurance research database, the occurrence of nonpeptic ulcer, nonvariceal gastrointestinal bleeding was compared among the hemodialysis patients, chronic kidney disease patients, and controls using log-rank test. Risk factors were identified by Cox regression analysis. RESULTS A total of 20,830 patients were enrolled, including 8210 hemodialysis and 4190 chronic kidney disease patients and 8430 age- and sex-matched controls in a 2:1:2 ratio. In the 7-year follow-up period, hemodialysis patients had a significantly higher cumulative hazard of nonpeptic ulcer, nonvariceal gastrointestinal bleeding than chronic kidney disease patients and controls (P <.001, by log-rank test). The hazard also was significantly higher in the chronic kidney disease patients than in controls. Cox regression analysis revealed that older age, the comorbidities of diabetes mellitus, cirrhosis, and chronic obstructive pulmonary disease, history of uncomplicated peptic ulcer disease, chronic kidney disease (hazard ratio 5.17), hemodialysis (hazard ratio 9.43), and use of selective serotonin reuptake inhibitors were independent risk factors for nonpeptic ulcer, nonvariceal gastrointestinal bleeding in all study patients. Old age, diabetes mellitus, cirrhosis, chronic obstructive pulmonary disease, history of uncomplicated peptic ulcer disease, and use of selective serotonin reuptake inhibitors were independent risk factors in hemodialysis patients. CONCLUSIONS There is a higher risk of developing nonpeptic ulcer, nonvariceal gastrointestinal bleeding in hemodialysis patients after adjustments for age, sex, underlying comorbidities, and ulcerogenic medication. The risk has increased since patients had chronic kidney disease.

Epidemiology of Idiopathic Central Serous Chorioretinopathy in Taiwan, 2001–2006: A Population-based Study

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.

Cirrhotic patients at increased risk of peptic ulcer bleeding: a nationwide population‐based cohort study

Few large population‐based studies have compared the occurrence of peptic ulcer bleeding (PUB) in cirrhotic and noncirrhotic patients.

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.

Chronic obstructive pulmonary disease: an independent risk factor for peptic ulcer bleeding: a nationwide population-based study

Peptic ulcer bleeding remains a major healthcare problem despite decreasing prevalence of peptic ulcer disease. The role of chronic obstructive pulmonary disease (COPD) in the risk of peptic ulcer bleeding has not yet been established.