El-Wui Loh

CHADS2 Score, Statin Therapy, and Risks of Atrial Fibrillation

OBJECTIVE Little is known about the effectiveness of statins on primary prevention of atrial fibrillation in elderly patients. This study aimed to evaluate the efficacy of statin treatment for atrial fibrillation prevention in elderly patients with hypertension, and to determine if comorbidity or CHADS(2) (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or transient ischemic attack) score can predict the effectiveness of statin treatment. METHODS Patients aged ≥65 years with hypertension were identified from a National Health Insurance research database (a systemic sampling from 2000 to 2009 with a total of 1,000,000 subjects). Medical records of 27,002 patients were used in this study, in which 2400 (8.9%) were receiving statin therapy. Risk of new-onset atrial fibrillation in statin users and nonusers was analyzed. RESULTS During the 9-year follow-up period, 2241 patients experienced new-onset atrial fibrillation. Statin users were younger than nonusers (72.4 vs 73.4 years) but had a higher prevalence of ischemic heart disease, diabetes mellitus, stroke, and chronic renal disease. Overall, statin therapy reduced the risk of atrial fibrillation by 19% (adjusted hazard ratio 0.81; 95% confidence interval, 0.69-0.95; P=.009). Subgroup analysis showed that statin use was beneficial in patients with or without a particular comorbidity. The effectiveness of statins was significant in patients with CHADS(2) score ≥2 (adjusted hazard ratio 0.69; 95% confidence interval, 0.57-0.85; P <.001). However, statin therapy was not as beneficial in hypertensive patients without other cardiovascular comorbidities (CHADS(2) score =1). CONCLUSION Statin therapy in elderly patients with hypertension reduces the risk of new-onset atrial fibrillation. Statins are more beneficial in patients with CHADS(2) score ≥2 than in those with score of 1.

Panic Disorder and Risk of Stroke: A Population-Based Study

OBJECTIVE An estimate of the risk of stroke among patients with panic disorder was sought. METHOD A retrospective cohort study was conducted using data from the National Health Insurance Research Database in Taiwan. A total of 1725 patients who were newly diagnosed with panic disorder between 2001 and 2007 and had no other psychiatric disorders or history of stroke were included. We then selected our control group by excluding patients with past history of stroke or other mental disorder (n = 388,584). Each patient was tracked from his/her index ambulatory care visit until the end of 2009 to identify whether a stroke was diagnosed during the follow-up periods. The hazard ratios of strokes in panic disorder patients and control group during the observation periods were analyzed with multivariable Cox proportional-hazards models adjusted for age, sex, concurrent medical conditions, and medications. RESULTS In the control group, 19,060 patients (4.9%) had new-onset stroke whereas there were 88 patients (5.1%) in the panic disorder group during the follow-up periods. The risk of stroke was 1.38 times greater for patients with panic disorder than for patients in the control group; (hazard ratio [HR] = 1.38; 95% confidence interval [CI], 1.12-1.71, p = 0.0025). CONCLUSIONS Our findings demonstrated that patients with panic disorder had an increased risk of stroke in Taiwan. Further experimental studies are needed to identify the underlying mechanisms that could lead to early interventions. For panic disorder patients, treatment of their symptoms may be warranted to prevent possible stroke.

ADRA1A gene is associated with BMI in chronic schizophrenia patients exposed to antipsychotics

Noradrenaline and adrenaline are neurotransmitters of the sympathetic nervous system that interact with various adrenergic receptor (ADR) subtypes, and this regulates the basal metabolic rate, thermogenesis and efficiency of energy utilization. We examined a possible role of the gene coding for ADRA1A receptor in weight gain in schizophrenia subjects exposed to antipsychotics. A total of 401 schizophrenia in-patients treated with antipsychotics for >2 years were recruited and a final 394 DNA samples were genotyped. Their body mass indexes (BMIs) were recorded for 12 months and parameterized to be correlated in regression. Among the 58 single-nucleotide polymorphisms (SNPs) genotyped, 44 valid SNPs, which had minor allele frequency ⩾0.03, were analyzed in statistics. Linear regression model with age, gender, diabetes, use of typical antipsychotics and use of atypical antipsychotics as covariates, with or without gender interaction, showed evidence of associations between the ADRA1A gene and BMI. Most of the SNPs associated with BMI are located in the promoter and intron regions, and being female appeared to enhance the gene effect. Our study suggests that the ADRA1A gene is involved in weight gain among schizophrenia patients treated with antipsychotics. Further molecular dissection of the ADRA1A gene warrants better understanding on weight gain mechanisms in schizophrenia.

Association of the ADRA1A gene and the severity of metabolic abnormalities in patients with schizophrenia

Patients with schizophrenia have a higher risk of developing metabolic abnormalities and their associated diseases. Some studies found that the accumulative number of metabolic syndrome components was associated with the severity of metabolic abnormalities. The purpose of this study was to examine the roles of the ADRA1A, ADRA2A, ADRB3, and 5HT2A genes in the risk of having more severe metabolic abnormalities among patients with schizophrenia. We studied a sample of 232 chronic inpatients with schizophrenia (120 males and 112 females) to explore the associations between the four candidate genes and the severity of metabolic syndrome by accumulative number of the components. Four single nucleotide polymorphisms in the candidate genes were genotyped, including the Arg347Cys in ADRA1A, the C1291G in ADRA2A, the Try64Arg in ADRB3, and the T102C in 5HT2A. An association between the accumulative number of metabolic syndrome components and the ADRA1A gene was found after adjusting age, sex, and other related variables (p-value=0.036). Presence of the Arg347 allele in the ADRA1A gene is a risk factor for having more severe metabolic abnormalities. These findings suggest a medical attention of closely monitoring metabolic risks for schizophrenia patients with high-risk genotypes.

Severity of psychosis syndrome and change of metabolic abnormality in chronic schizophrenia patients: Severe negative syndrome may be related to a distinct lipid pathophysiology

BACKGROUND Metabolic abnormality is common among schizophrenia patients. Some metabolic traits were found associated with subgroups of schizophrenia patients. OBJECTIVES We examined a possible relationship between metabolic abnormality and psychosis profile in schizophrenia patients. METHOD Three hundred and seventy-two chronic schizophrenia patients treated with antipsychotics for more than 2 years were assessed with the Positive and Negative Syndrome Scale. A set of metabolic traits was measured at scheduled checkpoints between October 2004 and September 2006. RESULTS Multiple regressions adjusted for sex showed negative correlations between body mass index (BMI) and total score and all subscales; triglycerides (TG) was negatively correlated with total score and negative syndrome, while HDLC was positively correlated with negative syndrome. When sex interaction was concerned, total score was negatively correlated with BMI but not with others; negative syndrome was negatively correlated with BMI and positively with HDLC. No metabolic traits were correlated with positive syndrome or general psychopathology. CONCLUSIONS Loss of body weight is a serious health problem in schizophrenia patients with severe psychosis syndrome, especially the negative syndrome. Schizophrenia patients with severe negative syndrome may have a distinct lipid pathophysiology in comparison with those who were less severe in the domain.

Newly diagnosed major depressive disorder and the risk of erectile dysfunction: A population-based cohort study in Taiwan

INTRODUCTION The primary aim of this study was to explore the incidence rate of erectile dysfunction (ED) among major depressive disorder (MDD) patients in an Asian country. The second aim was to compare the risk of ED in MDD patients that were treated using antidepressants with a high risk-ED, antidepressants with a low risk-ED, or without treatment. METHODS We identified 4339 male patients with newly diagnosed MDD using the National Health Database. Four matched controls per case were selected for the study. RESULTS The mean age of the participants was 42.3 ± 16.9. A higher crude HR of 3.6 (95% CI: 2.8-4.6) was seen in the male patients with MDD. After adjusting for obesity, monthly income, urbanization level, and comorbidity, the MDD patients had a 3.2-fold higher HR for an ED diagnosis than the controls. Patients with untreated depression had the highest risk of ED, compared to the control group (HR=3.9). Patients treated with IHiRA had a medium risk of developing ED (HR=3.6), and patients treated with ILoRA had the lowest risk of ED (HR: 2.5). CONCLUSION This prospective cohort study found an association between ED and prior MDD. Patients with untreated depression may have the highest risk of developing ED.

Dosage of statin, cardiovascular comorbidities, and risk of atrial fibrillation: A nationwide population-based cohort study

BACKGROUND Statin has potential protective effects against atrial fibrillation. Clinically, there is a need to predict the atrial fibrillation protective effects in statin-treated patients. The purpose of this study was to investigate if cardiovascular co-morbidities or cumulative defined daily doses (cDDDs) of statin use could predict statin efficacy in atrial fibrillation prevention. METHODS Patients aged ≥ 50 years were identified from the Taiwan National Health Insurance Research Database. Medical records of 171,885 patients were used in this study, and 40,001 (23.3%) of the patients received statin therapy (≥ 28 cDDDs). Risk of new-onset atrial fibrillation in statin users and non-users (<28 cDDDs) was estimated. RESULTS During the 9-year follow-up period, 6049 patients experienced new-onset atrial fibrillation. Overall, statin therapy reduced the risk of atrial fibrillation by 28% (adjusted hazard ratio [HR] 0.72; 95% CI 0.68 to 0.77). There was a dose-response relationship between statin use and the risk of atrial fibrillation. The adjusted HRs for atrial fibrillation were 1.04, 0.85, and 0.50 when cDDDs ranged from 28 to 90, 91 to 365, and more than 365, respectively. Subgroup analysis showed that statin use was more beneficial in patients with higher CHADS2 and CHA2DS2VASc scores than those with a score of 0 (P value for interaction<0.001). The therapy provided no obvious beneficial effect in those with a CHADS2 score of 0, a CHA2DS2VASc score of 0, or cDDDs less than 91. CONCLUSIONS Statin therapy reduces the risk of new-onset atrial fibrillation in a dose-dependent manner, and is beneficial in patients with cardiovascular co-morbidities.

The quantitative detection of aripiprazole and its main metabolite by using capillary-electrophoresis

Background: We aimed to establish a feasible and reliable method to measure the level of aripiprazole and its main metabolite, dehydroaripiprazole, using a capillary‐electrophoresis (CE) machine. Methods: Two blood samples were obtained from psychiatric patients hospitalized in Yu‐Li Hospital who had been treated with aripiprazole for more than 4 weeks, at least 10 mg/d. Conditions for voltage, temperature and buffer concentration was optimized on a CE machine. Results: The most optimal conditions for CE were 80 mM 2–3% DMSO‐phosphate as a buffer under pH = 3.0, 15 KV, 20°C and a detection wavelength of 214 nm. The linear ranges of aripiprazole and dehydroaripiprazole concentration were from 0.5 to 50 ng/mL. Conclusion: CE method is a feasible method to measure aripiprazole level with relatively low price compared with other analytical techniques for clinical use.

Resistant Hypertension, Patient Characteristics, and Risk of Stroke

Background Little is known about the prognosis of resistant hypertension (RH) in Asian population. This study aimed to evaluate the impacts of RH in Taiwanese patients with hypertension, and to ascertain whether patient characteristics influence the association of RH with adverse outcomes. Methods and Results Patients aged ≥45 years with hypertension were identified from the National Health Insurance Research Database. Medical records of 111,986 patients were reviewed in this study, and 16,402 (14.6%) patients were recognized as having RH (continuously concomitant use of ≥3 anti-hypertensive medications, including a diuretic, for ≥2 years). Risk of major adverse cardiovascular events (MACE, a composite of all-cause mortality, acute coronary syndrome, and stroke [included both fatal and nonfatal events]) in patients with RH and non-RH was analyzed. A total of 11,856 patients experienced MACE in the follow-up period (average 7.1±3.0 years). There was a higher proportion of females in the RH group, they were older than the non-RH (63.1 vs. 60.5 years) patients, and had a higher prevalence of cardiovascular co-morbidities. Overall, patients with RH had higher risks of MACE (adjusted HR 1.17; 95%CI 1.09–1.26; p<0.001). Significantly elevated risks of stroke (10,211 events; adjusted HR 1.17; 95%CI 1.08–1.27; p<0.001), especially ischemic stroke (6,235 events; adjusted HR 1.34; 95%CI 1.20–1.48; p<0.001), but not all-cause mortality (4,594 events; adjusted HR 1.06; 95%CI 0.95–1.19; p = 0.312) or acute coronary syndrome (2,145 events; adjusted HR 1.17; 95%CI 0.99–1.39; p = 0.070) were noted in patients with RH compared to those with non-RH. Subgroup analysis showed that RH increased the risks of stroke in female and elderly patients. However, no significant influence was noted in young or male patients. Conclusions Patients with RH were associated with higher risks of MACE and stroke, especially ischemic stroke. The risks were greater in female and elderly patients than in male or young patients.

Correlation of antidepressive agents and the mortality of end‐stage renal disease

Aim:  Depression is one of the most common psychological disorders in end‐stage renal disease (ESRD) patients and is associated with impaired quality of life and increased mortality and rate of hospitalization. We aimed to examine the contributions of depression and the use of antidepressive agents in the mortality of ESRD patients.