A Nationwide Study on Outcomes for the Offspring of Renal Transplant Recipients in Taiwan.

OBJECTIVE: Hormonal changes, in either men or women experiencing chronic kidney disease, cause decreased libido, erectile dysfunction, dysmenorrhea, and ovarian dysfunction, all of which may contribute to infertility. Patients' endocrinal and sexual function could be rapidly restored after successful renal transplantation (RTx), which may assist in achieving a successful pregnancy. However, fetuses will be exposed to the immunosuppressive agents passed on from the female recipients, which may be another potential factor leading to a poor fetal outcome. This nationwide study examined the perinatal status of offspring from RTx recipients in Taiwan. METHODS: The National Health Insurance (NHI) program is a mandatory universal health insurance program in Taiwan which provides coverage for 99.6% of its population. Nationwide, births totaled 2,562,253 between 2001 and 2012. Of that total, 97 births were from mothers who had had a RTx prior to delivery. A total of 2,561,973 births from the general population was then determined by combining the NHI database with the National Birth Registry database. Offspring from the RTx recipients and the general population was at a ratio of 1:10 matched by both birth year and birth month, where 77 offspring were from RTx recipients, while 770 served as a control. RESULTS: The offspring from the RTx group displayed significant statistical differences from the general population regarding low birth weight (< 2500 g) (53.3% vs 9.9%, P < .001), premature delivery (< 37 weeks) (46.8% vs 10.7%, P < .001), and high cesarean section delivery rate (50.7% vs 38.2%, P = .033). Regarding the Apgar score, which was assessed 1 minute and 5 minutes after each birth, fewer than 7 disclosed rates of 21.3% and 6.7% respectively in offspring of the RTx group; the corresponding numbers were 5.1% (P < .001) and 2.3% (P = .028) respectively in the other group. CONCLUSION: Upon restoration of fertility after RTx, most female recipients wish to have their own child; therefore, we as doctors have the responsibility to provide the necessary information we possess regarding the outcomes of offspring of female surgery recipients of childbearing age. Consequently, as the outcomes may not be satisfactory, we will continue to require more studies on the long-term outcome of offspring from RTx recipients in order to provide a more rational conclusion.

C-reactive protein gene polymorphism predicts the risk of thromboembolic stroke in patients with atrial fibrillation: a more than 10-year prospective follow-up study.

Essentials We studied the C-reactive protein (CRP) gene on stroke risk in atrial fibrillation (AF) patients. 725 patients with CRP triallelic polymorphism genotype were followed-up for more than 10 years. Patients with the A-390/T-390 allele of the CRP gene were more likely to get ischemic stroke. The triallelic polymorphism of the CRP is related to ischemic stroke in AF patients. SUMMARY: Background Little evidence is available regarding the impact of genetic polymorphisms on the risk of thromboembolic stroke in patients with atrial fibrillation (AF). An increasing body of evidence is demonstrating that inflammatory responses play an important role in the pathophysiology of AF. Objectives To investigate the effect of genetic polymorphisms of the C-reactive protein (CRP) gene on the incidence of thromboembolic stroke in patients with AF. Methods A total of 725 AF patients were longitudinally followed up for > 10 years; this is the largest and longest AF follow-up cohort with genetic data. CRP promoter triallelic polymorphisms (C-390A and C-390T) were genotyped, and CRP levels were divided into four quartiles. Results Patients with higher CRP levels were more likely to develop thromboembolic stroke than those with lower CRP levels (P<0.001, log-rank test for comparison of four quartiles). After adjustment for conventional risk factors, patients with higher CRP levels were more likely to develop thromboembolic stroke than those in the lowest CRP quartile (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.08-4.81; the lowest CRP quartile was the reference group). Patients carrying the A-390 or T-390 allele had higher CRP levels (3.35 ± 2.71 mg L-1 versus 2.43 ± 2.00 mg L-1 ), and were more likely to develop thromboembolic stroke, even after adjustment for conventional risk factors (HR 2.07, 95% CI 1.23-3.48). Conclusion The CRP triallelic polymorphism and the CRP level are associated with the risk of incident thromboembolic stroke in patients with AF.

Long-Term Outcome of Liver Transplant Recipients After the Development of Renal Failure Requiring Dialysis: A Study Using the National Health Insurance Database in Taiwan.

BACKGROUND: The aims of this study were to identify the incidence of renal failure requiring dialysis and to investigate the long-term outcome after renal failure in liver transplantation (LT) patients. METHODS: The primary database used was the Taiwan National Health Insurance Research Database. Subjects with LT from 1997 to 2009 were included. Patients were grouped into the dialysis cohort if they once received hemodialysis owing to any pattern of renal failure during peri-transplantation periods or after LT. Otherwise, they were categorized into the nondialysis cohort. We conducted a retrospective observational study on the correlation of renal failure requiring dialysis and its effect on LT recipients. RESULTS: The analysis included data of 1,771 LT recipients with a mean follow-up time of 3.8 ± 2.9 years. The mean age was 43.2 ± 19.3 years, and 69.4% were male. Overall patient survival was 86.2% at 1 year, 82.2% at 3 years, and 80.5% at 5 years. Renal failure requiring dialysis had developed in the 323 patients (18.2%). Among them, 26 individuals (1.5%) had progressed to end-stage renal disease without renal recovery after perioperative hemodialysis. Individuals who developed renal failure requiring dialysis had a higher mortality compared with LT recipients never requiring dialysis (hazard ratio, 8.75; 95% confidence interval, 7.0-10.9). CONCLUSIONS: Renal failure requiring dialysis development after LT is common and carries high mortality in Chinese liver allograft recipients. Recognizing risk factors permits the timely institution of proper treatment, which is the key to reducing untoward outcomes.

The association between chronic obstructive pulmonary disease and dementia: a population-based retrospective cohort study.

BACKGROUND AND PURPOSE: Chronic obstructive pulmonary disease (COPD) is frequently associated with various comorbidities. However, the proportion of COPD patients with dementia has not been adequately examined. This retrospective cohort study investigated the association between COPD and dementia by using a nationwide population-based database in Taiwan. METHODS: Data were retrieved from the Taiwanese National Health Insurance Research Database and analyzed using multivariate Cox proportional hazards regression models to assess the effects of COPD on the risk of dementia after adjusting for demographic characteristics and comorbidities. RESULTS: The COPD cohort exhibited a higher prevalence of diabetes, hypertension, coronary artery disease, head injury and depression at baseline than did the non-COPD cohort (P < 0.0001). After adjusting for covariates, the COPD patients exhibited a 1.27-fold higher risk of developing dementia (hazard ratio 1.27, 95% confidence interval 1.20-1.36). The incidence rate was higher in patients with frequent acute exacerbations than in the non-COPD patients regardless of whether a hospital admission or emergency room visit was required (hazard ratio 196.8 vs. 41.7, 95% confidence intervals 145.9-265.5 and 22.3-78.0). CONCLUSION: This study shows that COPD is associated with a subsequent higher risk of dementia after adjusting for comorbidities. Specifically, the association between COPD and dementia is greater in patients with more frequent acute exacerbation events of COPD.

A nationwide population-based study of the risk of tuberculosis in different solid organ transplantations in Taiwan.

Advances in immunosuppressants for solid organ transplantation (SOT) have improved prevention and treatment of acute rejection as well as reduced the risk of chronic graft damage. However, SOT recipients are prone to developing opportunistic infections because of their long-term immunosuppressed status. Tuberculosis (TB) is a serious opportunistic infection that is associated with increased morbidity and mortality in SOT recipients. However, nationwide population-based research specifically focused on the associations between kidney transplantation (KTx), liver transplantation (LTx), and heart transplantation (HTx), and subsequent TB infection is lacking. This study was conducted using Taiwan's National Health Insurance Research Database, which provided claims data for SOT recipients from 2000 to 2009. Clinical features, treatment, and outcomes were analyzed to determine the risk for TB after SOT. In total, 153 (3.2%) RTx, 19 (1.1%) LTx, and 26 (2.8%) HTx recipients became infected with TB. Compared with non-TB patients, HTx recipients with TB had significantly higher prevalence of older age (P = .037), hypertension (P < .001), and coronary artery disease (CAD) (P = .002). There were also greater percentages of male sex (P = .018), diabetes (P = .029), hyperlipidemia (P = .016), CAD (P < .001), and chronic obstructive pulmonary disease (COPD) (P < .001) in RTx recipients with TB than in those without. In conclusion, posttransplantation TB is a serious problem worldwide, and a high index of suspicion is warranted to ensure early diagnosis and prompt initiation of treatment for TB among SOT patients. In this preliminary study, KTx recipients had a higher risk of TB infection than LTx and HTx recipients, and the high-risk factors were male sex, diabetes, hyperlipidemia, CAD, and COPD. The use of optimal immunosuppressive agents to minimize acute rejection, monitoring of high-risk recipients, prompt diagnosis, and appropriate treatment are required for the management of TB infection in endemic areas such as Taiwan.

Cytomegalovirus disease after liver transplantation: a nationwide population-based study.

BACKGROUND: Cytomegalovirus (CMV) disease is a significant complication after liver transplantation. The estimated incidence varies among studies, which have been conducted in single regional centers and with small cohorts. In this study, we investigated the occurrence of CMV disease among liver transplant recipients in a national cohort in Taiwan. METHODS: This retrospective study used data from the Taiwan National Health Insurance Research Database. All liver transplant recipients in the catastrophic illness database from 2000 to 2009 were enrolled. Cases of CMV disease were identified from the admission database with the use of the ICD-9-CM code 078. RESULTS: The national cohort consisted of 1,721 liver transplant recipients (1,200 men and 521 women) with a mean age of 43.9 ± 8.9 years at the time of transplantation. The mean follow-up duration was 3.6 ± 2.7 years. The mortality rate was 14.9% at 1 year and 20.5% at 5 years. During the study period, 84 patients (4.9%) were diagnosed with CMV disease. The overall prevalence of CMV disease was 14.5 per 100 person-years. The cumulative incidences of post-transplantation CMV infection at 3 months, 6 months, 1 year, 2 years, 5 years, and 10 years were 1.2%, 2.7%, 3.8%, 4.2%, 4.8%, and 4.9%, respectively. The most common CMV-related diseases were colitis, hepatitis, and pneumonia. CONCLUSIONS: The risk of CMV disease was significantly elevated in the first 6 months after liver transplantation in the Taiwanese cohort.

Increased depression, diabetes and diabetic complications in Graves' disease patients in Asia.

BACKGROUND: This study aimed to evaluate the risk of depression and other cardiovascular comorbidities in Graves' disease (GD) patients in Asia. METHODS: The study patients were all newly diagnosed with GD [International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) 242.0] from January 1998 to December 2008. Patients aged <20 years or those with preexisting mental disorder (ICD-9-CM 290-319) were excluded from analyses. Control patients were randomly selected for the non-GD cohort, 1:4 frequency matched to the GD cohort according to sex, age and index year. The same exclusion criteria applied to the GD cohort were applied to the non-GD cohort. The GD cohort contained 4195 patients and the non-GD cohort contained 16 780 patients. RESULTS: The GD patients were more likely to have diabetes (8.03% vs. 4.48%, P < 0.0001), hypertension (18.1% vs. 13.5%, P < 0.0001), hyperlipidemia (11.9% vs. 9.09%, P < 0.0001) and coronary artery disease (10.3% vs. 5.86%, P < 0.0001) than the control patients were. The GD patients were also associated with significantly higher risk of depression than the control patients were (hazard ratio = 1.69, 95% confidence interval = 1.45-1.96). CONCLUSION: GD and GD treatment are associated with increased risk of depression diabetes and diabetic complications in Asian patients.

Outcome of lupus nephritis after entering into end-stage renal disease and comparison between different treatment modalities: a nationwide population-based cohort study in Taiwan.

BACKGROUND: Systemic lupus erythematosus (SLE) is not a rare disease among the Chinese and the incidence is higher in the female population. Lupus nephritis (LN) often develops in patients with SLE and may progress to end-stage renal disease (ESRD). Although there are studies that suggest postponement of the scheduling of kidney transplantation (KT) for these patients, there are still some other studies with conflicting results. Our study aimed to analyze the outcome of patients with LN after progression to ESRD and to try to elucidate whether deferral of KT is necessary in the Chinese population. METHODS: We used the National Health Insurance Research Database to perform this cohort study. The study cohort was observed between 1998 and 2009 after being diagnosed as having SLE. The cases of SLE and ESRD were identified according to the catastrophic illness database. RESULTS: In total, 1998 SLE patients with ESRD were identified. They received hemodialysis, peritoneal dialysis, or KT with the proportion of 82.1%, 9.8%, and 8.1%, respectively. The 1-year, 5-year, 10-year patient survival rates were best for those who underwent KT (100%, 98.1%, and 94.4%, respectively), followed by peritoneal dialysis (88.3%, 79.1%, and 76%, respectively), and hemodialysis (53.6%, 46.0%, and 41.6%, respectively). For those who underwent KT within 1 year after ESRD, no significant worse patient survival and graft survival were observed than those who underwent KT 1 year later. CONCLUSION: KT provides a better survival benefit for SLE patients with ESRD than hemodialysis and peritoneal dialysis. No obvious clinical benefit of KT deferral was observed in our study and the deferral may not be necessary for our population.

Trend of outcomes in renal transplant recipients with hepatitis B virus: a longitudinal analysis using a national database.

INTRODUCTION: Manifestations of hepatitis B virus (HBV) infection in renal transplant (RTx) recipients tend to be worse because of the higher viral load. RTx recipients with Asian heritage have a higher HBV infection rate and have unique characteristics. To date, no large-scale study on the outcomes of Asian RTx recipients has been conducted. Furthermore, there are few longitudinal studies comparing outcomes before and after availability of anti-HBV drugs. MATERIAL AND METHODS: We conducted a nationwide, population-based study to elucidate patient survival, graft survival, and hepatic outcome (incidence of hepatoma) in Asian RTx recipients. The study includes all RTx recipients in Taiwan from 1997 to 2006. Patients were divided into 2 groups according to HBV infection status to examine the effect of antiviral drug therapy. RESULTS: In all, 3826 RTx recipients were followed for a mean of 7.4 years, with a mean age of 43.7 years. There were no differences between the HBV and non-HBV groups in patient or graft survival rates. At 5 years after RTx, 89.2% of the patients were still alive and 84.5% RTx recipients were still dialysis free. In the era before anti-HBV drugs were available (1997-2001), patient survival in the HBV and non-HBV groups were similar (P = .614). This result can also be seen in the anti-HBV drug era, from 2002 to 2006 (P = .148). The unusual lack of a significant effect of drug anti-HBV administration on HBV-related mortality in RTx patients may be explained by the short duration of follow-up in the 2 eras. Another explanation may be the confounding effect of the different health status of RTx patients in the pre-anti-HBV drug era, when cardiovascular and infection-related mortality rates were considerably greater than HBV-related mortality rates. CONCLUSION: These results demonstrate that HBV is not a contraindication for RTx. Asian recipients with HBV can still achieve a similar graft outcome and survival rate compared with those of patients without HBV.

Comparison of tuberculosis infection rates in a national database of renal transplant patients with data from a single center in Taiwan.

Successful renal transplantation (RT) improves quality of life and patient survival. Advances in immunosuppressants for RT have improved the prevention and treatment of acute rejection as well as reduced the risk of chronic graft damage, but immunodeficiency may render patients vulnerable to opportunistic infections. We conducted this study to compare the difference in tuberculosis (TB) infection rates between a single institution and a national database of RT recipients in Taiwan. There were 153 patients with TB (3.2%) among 4,835 RT recipients in the database during the period 2000-2009, with a higher prevalence of men (P = .018) and diabetes patients (P = .029). In our institution's registry, 33 patients (2.7%) developed 35 episodes of TB infection among 1,209 RT recipients, but there were no significant differences in general characteristics among different subgroups. Interestingly, the use of cyclosporine was significantly more frequent in RT recipients with TB than in those without in both the national database and in our institution. In contrast, TB infection was negatively correlated with the use of tacrolimus (TAC) and mycophenolate (MPA). RT recipients with TB infection had poor survival (P = .0013) and low graft survival (P = .0003). Taken together, analyses of the national database and the RT patients in our institution revealed that the use of long-term cyclosporine-based immunosuppressive agents was associated with a greater risk of developing post-transplantation TB compared with that of other immunosuppressive agents, but the chronicity and accumulation effect of TAC and MPA should be observed despite the negative correlation found herein. In conclusion, post-transplantation TB is a serious health threat and one of the major causes of death among RT recipients, and a high index of suspicion to ensure early diagnosis and prompt initiation of treatment for TB is crucial. The use of optimal immunosuppressive agents to minimize acute rejection, monitoring of high-risk recipients, prompt diagnosis, and appropriate treatment are required to manage TB infection in endemic areas such as Taiwan.

Increased risk of cancer for patients with ankylosing spondylitis: a nationwide population-based retrospective cohort study.

OBJECTIVES: Few studies have investigated the relationship between ankylosing spondylitis (AS) and other inflammatory spondyloarthritis and subsequent cancer. The aim of this study was to determine whether AS is associated with cancer risk. METHOD: We used data from the National Health Insurance (NHI) system of Taiwan to investigate this association. The AS cohort included 4133 patients, and each patient was randomly frequency matched with four persons without AS based on sex, age, and entry year (control cohort). We conducted a Cox proportional hazards regression analysis to estimate the influence of AS on cancer risk. RESULTS: Among patients with AS, the overall risk of developing cancer was 38% higher than that of people without AS, and the difference was significant [adjusted hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.18-1.60]. This phenomenon held true even when we analysed males and females separately. The risk of developing lung or head and neck cancer among patients with AS was significantly higher; and risks for liver, bladder, and uterus cancers were marginally significantly higher. CONCLUSIONS: This nationwide population-based cohort study shows that Taiwanese patients with AS have a higher risk of developing cancer, particularly lung or head and neck cancer.

Systemic lupus erythematosus increases the risks of deep vein thrombosis and pulmonary embolism: a nationwide cohort study.

BACKGROUND: Studies on the risks of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with systemic lupus erythematosus (SLE) are limited. We evaluated the effects of SLE on the risks of developing DVT and PE in a nationwide, population-based cohort study in Taiwan. METHODS: We randomly selected patients without SLE from the National Health Insurance database (N = 23.74 million), and frequency-matched four of them, on the basis of age, sex, and index year, to each SLE patient in the catastrophic illness registry of the NHI who was diagnosed with SLE between 1998 and 2008. Using a follow-up period ending in 2010, we analyzed the risks of DVT and PE with a Cox proportional-hazards regression analysis. RESULTS: The 13 084 SLE patients (87.9% women; mean age of 35.6 years) and 52 336 controls were followed for 90 237 and 379 185 person-years, respectively. After adjustment for age, sex, and comorbidities, the SLE patients' risks of developing DVT and PE were 12.8-fold and 19.7-fold higher, respectively, than those of the comparison cohort. The risks of DVT and PE increased in both study groups when the data were stratified on the basis of sex, age, and comorbidities. The SLE patients aged ≤ 35 years had the highest risks of developing DVT and PE. The multiplicative increased risks of DVT and PE were also significant in SLE patients with any comorbidity. CONCLUSION: The risks of DVT and PE are significantly higher in SLE patients than in the general population.

Bisphosphonate treatment may reduce osteoporosis risk in female cancer patients with morphine use: a population-based nested case-control study.

UNLABELLED: Chronic use of morphine is a risk factor for endocrinopathy and osteoporosis. Bisphosphonates accentuated the protective effect to develop osteoporosis in female patients with malignancy with morphine treatment. INTRODUCTION: This study investigates the risk of osteoporosis associated with morphine use by comparing the incidence of osteoporosis in female cancer patients treated with and without morphine. METHODS: A population-based nested case-control retrospective analysis was performed using the Longitudinal Health Insurance Database 2000 and Registry for Catastrophic Illness Patients of Taiwan. A malignancy cohort of 12,467 female patients without a history of osteoporosis during 1998-2010, and then 639 patients who subsequently developed osteoporosis as the osteoporosis group, were evaluated. Control-group patients were selected from the malignancy cohort without osteoporosis and frequency matched to each osteoporosis case 2:1 for age, year of cancer diagnosis, and index year. Logistic regression was used to estimate the odds ratios and 95% confidence intervals, and the multivariable model was applied to control for age. RESULTS: Female cancer patients who received morphine had a 10% lower risk of developing osteoporosis than non-morphine users, but this risk reduction was not significant. For patients treated with bisphosphonates, the morphine group had significantly lower odds in developing osteoporosis than the non-morphine group. CONCLUSION: Morphine treatment is not associated with the incidence of osteoporosis, and bisphosphonates accentuated the protective effect of morphine in the development of osteoporosis in female patients with malignancy in Taiwan.

A population-based cohort study in Taiwan--use of insulin sensitizers can decrease cancer risk in diabetic patients?

BACKGROUND: The purpose of the study was to explore the possible association between the use of insulin sensitizers (thiazolidinediones, TZDs) and the risk of cancer in Taiwanese diabetic patients. PATIENTS AND METHODS: From the National Health Insurance Research Database (NHIRD) of Taiwan, we identified 22 910 diabetic patients newly diagnosed from 2001 to 2009 and 91 636 non-diabetic comparisons frequency matched with age, sex, and calendar year, excluding those with cancer at the baseline. Among the diabetics, 4159 patients were treated with TZDs and the rest of 18 752 patients were on other anti-diabetic medications (non-TZDs). RESULTS: In comparison to the non-diabetes group, the non-TZDs group had an increased risk of developing cancer [the adjusted hazard ratio (HR): 1.20 and 95% confidence interval (CI) = 1.11-1.30]. The TZDs group had a HR of 1.18 (95% CI = 0.98-1.42). Analysis of site-specific cancer risks showed that both TZDs and non-TZDs groups with elevated risks of colorectal and pancreatic cancer. However, the non-TZDs group had an increased risk of liver cancer when comparing with TZD and non-diabetes groups. CONCLUSION: This study suggests that patients with diabetes are at an elevated risk of cancer (especially in colorectal and pancreatic cancers), and the use of TZDs might decrease the liver cancer risk in diabetic patients. Further investigation using large samples and rigorous methodology is warranted.

Risk of coronary artery disease is not linked to head and neck cancers: a population-based retrospective cohort study.

OBJECTIVES: To explore the possible association between the risk of coronary artery disease and head or neck cancer based on some possible shared risk factors and/or treatment-related complications. DESIGN AND SETTING: A population-based retrospective cohort study. PARTICIPANTS: All new 729 patients with head and neck cancer diagnosed between 2000 and 2003 were followed up till 2009, and the risk of subsequent coronary artery disease was calculated. For each patient, the risk was calculated in 4 age-and sex-matched population controls. Matching was not possible for factors including socio-economic group and smoking. MAIN OUTCOME MEASURES: Cox's proportional hazard regression analysis was conducted to estimate the relationship between head or neck cancer and risk of coronary artery disease. RESULTS: For patients with head or neck cancer, the overall risk for developing coronary artery disease was almost the same as that of the control group [adjusted hazard ratio (but without control for some lifestyle factors): 0.95; 95% confidence interval: 0.65-1.35]. Overall, we found no increased risk of coronary artery disease for patients with head or neck cancer when the data were categorised either by treatment methods or by cancer subsites. CONCLUSIONS: This population-based study indicated that patients with head or neck cancer were at no higher risk of developing coronary artery disease than was the general population over a 6- to 9-year period; however, we cannot exclude the risk over a longer period of time.

A functional variant in the promoter region regulates the C-reactive protein gene and is a potential candidate for increased risk of atrial fibrillation.

OBJECTIVES: In a large population-based cohort, the level of C-reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown. METHODS: A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association. RESULTS: Three polymorphisms (T-861C, A-821G and C-390A/C-390T) were found in the 1-kb promoter of CRP. A triallelic polymorphism (C-390A/C-390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The -390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L-type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts. CONCLUSION: A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis.