scholarly journals COL1A1 polymorphism and neurological complications in pediatric acute lymphoblastic leukemia patients and their associations with altered bone mineral density

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Alaa A. Omran ◽  
Rania S. Nageeb ◽  
Ghada S. Nageeb ◽  
Manal A. Yosif ◽  
Yassir A. Mohammad ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Risk Factor ◽  
Gene Polymorphism ◽  
Lymphoblastic Leukemia ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Neurological Complications ◽  
Mineral Density ◽  
Significant Decrement ◽  
Pediatric All

Abstract Background Osteoporosis and neurological complications are consequences of acute lymphoblastic leukemia (ALL). Collagen type I alpha 1 gene (COL1A1) polymorphism is associated with osteoporosis. This study aimed to detect the COL1A1 polymorphism and the neurological complications in ALL patients and their association with decreased lumbar spine bone mineral density (BMDLS). This study included 100 pediatric ALL patients and 100 controls. All participants were subjected to laboratory assessment and assessment of BMDLS at the start of the study and 3 years later. COLIA1 genotyping was done once for all participants. Results At the start of the study, there was a significant decrease in osteocalcin (OC), alkaline phosphatase (ALP), and BMDLS levels in the patients. G/T variants and “T” alleles were significantly more detected in the patients (34% and 35% respectively); also, significant differences were detected between patients with polymorphism (G/T and T/T) and those without polymorphism (G/G) regarding OC, ALP, and BMDLS. After 3 years, significant decrement in BMDLS, OC, and ALP was detected in the patients. Twenty-four patients had neurological complications and seven patients had bone fractures. Those patients had significant decrement in BMDLS, OC, and ALP levels. As regards COL1A1 gene polymorphism, the GT and TT variants were significantly detected in fractured patients, while there was no significant difference regarding GT and TT variants in the patients with neurological complications. T allele, neurological complications, high-risk stratification, and age were significantly associated with decreased BMDLS. T allele was the most significant risk factor. Conclusion COLIA1 gene polymorphism, decreased BMDLS, and neurological complications were significantly detected in pediatric ALL patients. COLIA1 gene polymorphism is a significant risk factor for decreased BMDLS in pediatric ALL patients. There is no significant relation between COLIA1 gene polymorphism and the development of neurologic complications.

Aggravated Bone Density Decline after Symptomatic Osteonecrosis in Children with Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2260-2260
Author(s):  
Marissa den Hoed ◽  
S.M.F. Pluijm ◽  
Mariël L. Te Winkel ◽  
Hester A. de Groot-Kruseman ◽  
Marta Fiocco ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Acute Lymphoblastic Leukemia ◽  
Side Effects ◽  
Bone Mineral ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Bone Destruction ◽  
Mineral Density ◽  
Pediatric All ◽  
Cessation Of Treatment

Abstract Background: Osteonecrosis (ON) and decline of bone mineral density (BMD) are serious side effects during and after treatment of childhood acute lymphoblastic leukemia (ALL). It is unknown whether ON and low BMD co-occur in the same patients, and whether these two osteogenic side effects can influence each other’s development during pediatric ALL treatment. Methods: BMD and the incidence of symptomatic ON were prospectively assessed in 466 patients with ALL (4-18 years of age) treated according to the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Symptomatic ON was defined as persistent pain in arms or legs not caused by vincristine administration, and confirmed by magnetic resonance imaging. Bone mineral density of the lumbar spine (BMDLS) (n=466) and of the total body (BMDTB) (n=106) were measured by dual X-ray absorptiometry at ALL diagnosis, after 32 weeks of treatment, at cessation of treatment (109 weeks) and 1 year after cessation of treatment. BMD was expressed as age-matched and gender-matched standard deviation scores (SDS; Z-score). Multivariate linear mixed models were adjusted for age at diagnosis. Results: Thirty patients (6.4%) suffered from ON. At cessation of treatment, mean BMDLS was -1.28 SDS (SD: 1.27, n=332; p<0.01) and BMDTB was -0.74 SDS (SD: 1.29, n=65; p<0.01) lower in ALL patients compared to their healthy peers. At baseline, BMDLS and BMDTB did not differ between patients who developed or who did not develop ON (mean BMDLS ON+: -0.90 vs. ON-: -1.14, p=0.36; mean BMDTB ON+: 0.07 vs. ON-: 0.25 p=0.65). At cessation of treatment, patients with ON seem to have a trend for a lower mean BMDLS (ON+: -1.68 vs. ON-: -1.31, p=0.18) and they have a lower mean BMDTB (ON+: -1.91 vs. ON-: -0.59, p=0.01) than patients without ON. Multivariate analyses showed that BMDTB change during follow-up was significantly different for patients with ON than without ON (interaction group time, p=0.04). Between BMD measurements before and after the diagnosis, patients with ON seemed to have a more rapid decline of BMDTB than in patients of the same age without ON (mean BMDTB difference -1.13 vs. -0.62, p=0.10). Conclusion: We conclude that symptomatic ON and low BMD during antileukemic treatment co-occur in pediatric ALL patients. BMD status at ALL diagnosis does not seem to precede ON. However, the development of ON seems to aggravate BMD decline during antileukemic treatment, most likely due to bone destruction and the advised physical immobilization. Disclosures No relevant conflicts of interest to declare.

scholarly journals Genetic Susceptibility Of Cytotoxic T Lymphocyte-Associated Antigen 4 Gene Polymorphism In The Onset Of Arthritis

2021 ◽  
Author(s):  
Maryam Mukhtar ◽  
Nadeem Sheikh ◽  
Saira Kainat Suqaina ◽  
Tayyaba Saleem ◽  
Rabia Mehmood ◽  
...  
Keyword(s):  
Risk Factor ◽  
Gene Polymorphism ◽  
T Lymphocyte ◽  
Large Scale ◽  
Cytotoxic T Lymphocyte ◽  
Disease Onset ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Polymorphic Site ◽  
Genotypic Frequency

ABSTRACTCytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene plays a vital role in the activation of T-cells as a down regulator. CTLA-4 gene polymorphisms have implicated a potential risk factor for autoimmune disorders like arthritis. Therefore the current study was designed to determine the association of CTLA-4 gene polymorphism in the onset of rheumatoid and osteoarthritis in Pakistani individuals. Genotyping was performed on 300 RA, 316 OA, and 412 control subjects by direct sequencing method as well as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. It was observed that allelic and genotypic frequency of rs5742909, rs231775, rs4553808, rs733618, and rs3087243 were significantly varied among patients and controls and considered as a significant risk factor in the onset of RA as well as OA. However, no mutation was identified on the rs11571317 polymorphic site. Haplotype CAGTCA and CAG TCG act as a protectant against disease onset whereas CAACCG was significant in disease onset. Mutation on rs231775 polymorphic site lead to the change of threonine into alanine It was concluded that CTLA-4 gene polymorphism is a significant risk factor in the onset of RA as well as OA. Large scale survey is required for the screening of the genetic markers for pre-diagnosis of the disease.SUMMARY STATEMENTThe study summarized that CTLA-4 gene polymorphism plays a key role in the arthritis onset in Pakistani population.

Clinical Utility of Next-Generation Sequencing-Based Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2611-2611
Author(s):  
Yuko Sekiya ◽  
Yusuke Okuno ◽  
Hideki Muramatsu ◽  
Atsushi Narita ◽  
Kyogo Suzuki ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Risk Factor ◽  
Clinical Utility ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Time Points ◽  
Generation Sequencing ◽  
Minimal Residual

Abstract Purpose Next-generation sequencing (NGS)-based monitoring of minimal residual disease (MRD) was developed to increase the sensitivity and specificity of standard MRD detection methods. However, few published studies have tested the clinical utility of this novel technique. We assessed the clinical utility of NGS-MRD in a uniformly treated cohort of patients with pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). PATIENTS AND METHODS We enrolled 79 unselected patients with pediatric BCP-ALL. Bone marrow samples were collected at the time of diagnosis, on days 33 and 80, at pre- and post-maintenance therapy time points (4-5 and 24 months, respectively), and upon relapse. Genomic DNA was extracted from frozen bone marrow mononuclear cells at each time point. We used diagnostic samples to define the immunoglobulin heavy chain (IGH), complementarity-determining region 3 (CDR3), and T-cell receptor gamma chain (TCRG) loci. From these samples, we detected leukemia-specific CDR3 sequences in >5.0% of all sequence reads. In addition, we performed a multiplex polymerase chain reaction (PCR) to determine the IGH, CDR3, and TCRG loci and subsequently assessed MRD using NGS. The result was considered positive for NGS-MRD if the leukemia-specific CDR3 sequence was detected. The resulting positive MRD values were categorized as "low positive" (<10−4) or "high positive" (≥10−4). RESULTS We detected leukemia-specific CDR3 sequences in 72 of 79 patients (91%). MRD was measured in 232 samples and we obtained positive results in 59 samples. MRD was detected in 51% (28/55) samples on day 33, and the frequencies of positive MRD decreased to 25% (16/65), 19% (11/58), and 7.4% (4/54) samples at day 80, 4-5 months, and 24 months, respectively. Each of the four patients with a positive MRD at 24 months relapsed shortly after detection. In a univariate analysis, the MRD values at day 80 {risk ratio [RR; 95% confidence interval (CI)] = 7.438 (2.561-21.6), p < 0.001}, 4-5 months [RR (95% CI) = 10.24 (3.374-31.06), p < 0.001], and 24 months [RR (95% CI) = 19.26 (4.974-74.59), p < 0.001] showed a statistically significant association with inferior leukemia-free survival (LFS). The classification of patients as either low or high positive for NGS-MRD at day 80 was a significant risk factor for poor LFS [low positive, RR (95% CI) = 6.63 (2.01-21.82), p = 0.002; high positive, RR (95% CI) = 9.40 (2.32-38.17), p = 0.002]. Furthermore, both low and high positivity for MRD at 4-5 months was also a significant risk factor for poor LFS [low positive, RR (95% CI) = 10.32 (3.07-34.70), p < 0.001; high positive, RR (95% CI) = 10.04 (2.00-50.34), p = 0.005]. In an assessment of three multivariate Cox proportional hazard models, we found that both low and high positive NGS-MRD values at day 80 [low positive, RR (95% CI) = 6.05 (1.80-20.39), p = 0.0037; high positive, RR (95% CI) = 8.20 (1.92-35.07), p = 0.002] and at 4-5 months [low positive, RR (95% CI) = 12.98 (3.49-48.28), p < 0.001; high positive, RR (95% CI) = 23.16 (3.28-163.7), p < 0.001] were independent covariates predictive of poor LFS. CONCLUSION We detected leukemia-specific CDR3 rearrangements in 91% of our cohorts, which was comparable with the frequencies detected using sensitive real-time quantitative (RQ)-PCR methods. In both univariate and multivariate analyses, low and high positive NGS-MRD results were significantly associated with poor LFS. In addition, we found that MRD positivity at later time points (4-5 and 24 months) was predictive of a high incidence of relapse and poor LFS. Therefore, NGS-MRD can identify a greater number of patients who are at a high risk of relapse and candidates for intensified chemotherapy or allogeneic HSCT. Our study demonstrates the potential superiority of NGS over the current standard method of MRD monitoring. However, standardization, quality control, and validation of this new technology are warranted prior to its use in routine practice. Disclosures No relevant conflicts of interest to declare.

Low Incidence of Osteonecrosis in Childhood Acute Lymphoblastic Leukemia Treated With ALL-97 and ALL-02 Study of Japan Association of Childhood Leukemia Study Group

2018 ◽  
Vol 36 (9) ◽  
pp. 900-907 ◽  
Author(s):  
Kenichi Sakamoto ◽  
Toshihiko Imamura ◽  
Kentaro Kihira ◽  
Koji Suzuki ◽  
Hisashi Ishida ◽  
...  
Keyword(s):  
Risk Factor ◽  
Acute Lymphoblastic Leukemia ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Significant Risk ◽  
Low Frequency ◽  
Concomitant Administration ◽  
Significant Risk Factor ◽  
Japanese Patients ◽  
Childhood Acute Lymphoblastic Leukemia

Purpose Osteonecrosis (ON) is a serious complication of the treatment of childhood acute lymphoblastic leukemia (ALL); however, data relating to ON in Asian pediatric patients with ALL are scarce. Therefore, we performed a retrospective analysis of cohorts of Japanese patients with ALL to clarify the incidence, clinical characteristics, and risk factors of ON. Patients and Methods The incidence and characteristics of ON were determined in patients with ALL (n = 1,662) enrolled in two studies from the Japan Association of Childhood Leukemia Study (JACLS) group (n = 635 and n = 1,027 patients treated with the ALL-97 and ALL-02 protocols, respectively). Results In total, 24 of 1,662 patients suffered from ON, of which 12 of 635 and 12 of 1,027 patients were treated with the ALL-97 and the ALL-02 protocol, respectively. Of the 24 patients, 23 were older than 10 years. In multivariate analysis, age (≥ 10 years) was the sole significant risk factor for ON ( P < .001). Separate evaluation of patients ≥ 10 years of age indicated a 5-year cumulative incidence of ON of 7.2% (95% CI, 4.0% to 12.6%) and 5.9% (95% CI, 3.3% to 10.4%) in the ALL-97 and the ALL-02 protocol, respectively, which was lower than reported previously, despite an administration of dexamethasone (DEX) similar to that in comparable studies; however, concomitant administration of DEX and l-asparaginase was reduced in the JACLS protocols. Conclusion We identified a low frequency of ON in the JACLS ALL-97 and ALL-02 studies. Although the sole risk factor for ON was age (≥ 10 years), even among high-risk patients, ON incidence was significantly lower than that reported in previous studies. These results suggest that, not only the total amount of DEX, but also how DEX and l-asparaginase are administered, which affects the clearance of DEX, may be associated with ON incidence in patients with ALL.

scholarly journals POS1109 MULTIVARIATE ANALYSIS OF RISK FACTORS FOR REDUCED BONE MINERAL DENSITY ASSESSED WITH RADIOFREQUENCY ECHOGRAPHIC MULTI SPECTROMETRY (REMS)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 835.1-835
Author(s):  
Z. Batalov ◽  
M. Nikolov ◽  
N. Nikolov
Keyword(s):  
Risk Factors ◽  
Bone Mineral Density ◽  
Risk Factor ◽  
Lumbar Spine ◽  
Femoral Neck ◽  
Body Fat ◽  
Significant Risk ◽  
Mineral Density ◽  
X Ray ◽  
T Score

Background:Radiofrequency echographic multi spectrometry (REMS) is an innovative radiation-free approach for the assessment of bone mineral density (BMD) at axial sites. The principle of this technology is based on the analysis of native raw unfiltered ultrasound signals, the so called radiofrequency ultrasound signals, acquired during an echographic scan of the lumbar spine and/or femoral neck. [1]. A previous published study showed a high degree of correlation between the T-score values provided by the two techniques-REMS and dual energy X-ray absorptiometry for both lumbar spine and femoral neck [2]. REMS software outputs information about BMD (g/cm2), T-scores, Z-scores [standard deviations (SD)], percentage of body fat and basal metabolic rate [BMR (kcal/daily)] [3].Objectives:The aim of the current study is to investigate the multivariate significant risk factors for reduced BMD through REMS technology.Methods:In this study, a total of 273 women with mean age 62 years (yrs.) ± 12 yrs. (range 25-88 yrs.) underwent REMS assessments. Subjects were divided into two groups after acquiring information about the spinal T-scores: 1st group with T-scores ≥-1 SD and 2nd group with T-scores <-1 SD. Age, weight, height, body mass index (BMI), basal metabolic rate (BMR), body fat and menopausal status were the risk factors included in the multivariate statistical analyses. Binary logistic regression was used to assess which are the significant risk factors for T-score <-1 SD. Youden’s indices were calculated for selecting the cut-off points for each risk factor.Results:273 women had mean weight of 70.5 kg. ± 15.7 kg. (range 39.4-127 kg.), mean height 157.1 cm. ± 8.8 cm. (range 100-182 cm.) and mean body mass index (BMI) 28.6 kg/cm2 ± 6.1 kg/cm2 (range 14.9-47.5 kg/cm2). The mean body fat of the subjects was 37.8% ± 8.8% (range 9-52%) and the mean BMR was 1274.01 kcal/daily ± 163.17 kcal/daily (range 929.7-1908.4 kcal/daily). 260 women (95.2%) were attributed to postmenopausal. Age (p=0.000), BMI (p=0.015), menopause (p=0.006) and BMR (p=0.000) were the multivariate significant risk factors for T-score <-1 SD. Odds ratio for the risk factor age was 1.16, so each added year of the women’s age increased the risk for T-score <-1 SD by 1.16%. Women over the age of 65 yrs. showed the highest risk for spinal T-score <-1 SD. The odds ratio of the menopause as a risk factor for spinal T-score <-1 SD was 9.54, so postmenopausal women showed about 9.5 times higher risk of T-score <-1 SD of the lumbar spine than women who still have their period. The increase of BMI by one kg/cm2 decreased the probability of spinal T-score <-1 SD by 0.15% and the increase of BMR by one kcal/daily decreased this probability by 0.02%. Women with BMI above 28.63 kg/cm2 and those with BMR >1331.75 kcal/daily were unlikely to develop spinal T-score <-1 SD.Conclusion:In the current study, multivariate regression analysis was used to develop a specific REMS-based risk prediction model for spinal BMD, corresponding to T-score <-1 SD. Postmenopausal women over age of 65 yrs. with BMI lower than 28.63 kg/cm2 and BMR <1331.75 kcal/daily were at the highest risk for T-score <-1 SD of the lumbar spine.References:[1]Pisani P, Renna MD, Conversano F, Casciaro E, Muratore M, et al. (2013) Screening and early diagnosis of osteoporosis through X-ray and ultrasound-based techniques. World J Radiol 5(11): 398-410.[2]Kirilov N. Analysis of dual-energy x-ray absorptiometry images using computer vision methods. (2020) Trakia Journal of Sciences, Vol. 18, Suppl. 1, pp 114-117.[3]Kirilova E, Kirilov N, Popov I, Vladeva S. (2019) Bone mineral density of lumbar spine and femoral neck assessed by novel echographic approach-Radiofrequency Echographic Multi Spectrometry (REMS). Clin. Cases Miner. Bone Metab., 16 (1), pp. 14-17.Disclosure of Interests:None declared.

scholarly journals PTHR1 Genetic Polymorphisms Are Associated with Osteoporosis among Postmenopausal Arab Women

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Saba Abdi ◽  
Abeer Abdulaziz Almiman ◽  
Mohammed Ghouse Ahmed Ansari ◽  
Abdullah M. Alnaami ◽  
Abdul Khader Mohammed ◽  
...  
Keyword(s):  
Risk Factor ◽  
Parathyroid Hormone ◽  
Inflammatory Markers ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Control Group ◽  
Arab Women ◽  
Mineral Density ◽  
25 Hydroxy Vitamin D ◽  
Turnover Markers

The parathyroid hormone 1 receptor (PTHR1) plays a crucial role in calcium homeostasis and bone metabolism. However, its genetic role in regulating bone turnover markers (BTMs) in postmenopausal osteoporosis (PMO) remains unclear. Herein, we explored parathyroid hormone (PTH) and PTHR gene variant susceptibility to osteoporosis and their association with various circulating BTM and inflammatory markers in postmenopausal women of Arab ethnicity. In total, 600 postmenopausal Arab women (300-PMO and 300-control) were genotyped for selected SNPs in PTH (rs1459015, rs307253, rs6054, rs307247, rs10500783 and rs10500784), PTHR1 (rs6442037, rs1138518, and rs724449 SNPs) and PTHR2 (rs9288393, rs10497900, and rs897083). Anthropometrics, BTMs, and inflammatory markers were measured. Bone mineral density (BMD) was measured at the lumbar spine L1–L4 and the femoral neck using dual-energy X-ray absorptiometry (DXA). PTHR1 rs1138518 genotype C/T was found to be a significant risk factor for PMO ( OR = 1.49 , 95% CI 1.0-2.1, P = 0.03 ). The genotypes C/T and T/T of PTHR1 rs1138518 were associated with 25-hydroxy-vitamin D (25(OH)D) regulation. In the PMO group, carriers of the C/T genotype had significantly lower 25(OH)D levels than carriers of the same genotypes in the control group (59.9 (36.7-92.4) nmol/l and 66.4 (43.5-87.8) nmol/l, respectively; P = 0.048 ]. Our study concludes that the PTHR1 rs1138518 genotype could be a potential risk factor for osteoporosis and 25(OH)D regulation in Arab women with PMO.

Physical Illness and Suicide Risk in Rural Residents of Contemporary China

Crisis ◽  
2014 ◽  
Vol 35 (5) ◽  
pp. 330-337 ◽  
Author(s):  
Cun-Xian Jia ◽  
Lin-Lin Wang ◽  
Ai-Qiang Xu ◽  
Ai-Ying Dai ◽  
Ping Qin
Keyword(s):  
Risk Factor ◽  
Family Income ◽  
Rural China ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Health Condition ◽  
Physical Illness ◽  
Rural Residents ◽  
Increased Risk ◽  
Study Population

Background: Physical illness is linked with an increased risk of suicide; however, evidence from China is limited. Aims: To assess the influence of physical illness on risk of suicide among rural residents of China, and to examine the differences in the characteristics of people completing suicide with physical illness from those without physical illness. Method: In all, 200 suicide cases and 200 control subjects, 1:1 pair-matched on sex and age, were included from 25 townships of three randomly selected counties in Shandong Province, China. One informant for each suicide or control subject was interviewed to collect data on the physical health condition and psychological and sociodemographic status. Results: The prevalence of physical illness in suicide cases (63.0%) was significantly higher than that in paired controls (41.0%; χ2 = 19.39, p < .001). Compared with suicide cases without physical illness, people who were physically ill and completed suicide were generally older, less educated, had lower family income, and reported a mental disorder less often. Physical illness denoted a significant risk factor for suicide with an associated odds ratio of 3.23 (95% CI: 1.85–5.62) after adjusted for important covariates. The elevated risk of suicide increased progressively with the number of comorbid illnesses. Cancer, stroke, and a group of illnesses comprising dementia, hemiplegia, and encephalatrophy had a particularly strong effect among the commonly reported diagnoses in this study population. Conclusion: Physical illness is an important risk factor for suicide in rural residents of China. Efforts for suicide prevention are needed and should be integrated with national strategies of health care in rural China.

scholarly journals Higher premature atrial complex burden from the Holter examination predicts poor cardiovascular outcome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ting-Chun Huang ◽  
Po-Tseng Lee ◽  
Mu-Shiang Huang ◽  
Pei-Fang Su ◽  
Ping-Yen Liu
Keyword(s):  
Risk Factor ◽  
Dose Response ◽  
Cox Model ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Cardiovascular Death ◽  
Specific Model ◽  
Distribution Model ◽  
All Cause Mortality ◽  
Quartile Group

AbstractPremature atrial complexes (PACs) have been suggested to increase the risk of adverse events. The distribution of PAC burden and its dose–response effects on all-cause mortality and cardiovascular death had not been elucidated clearly. We analyzed 15,893 patients in a medical referral center from July 1st, 2011, to December 31st, 2018. Multivariate regression driven by ln PAC (beats per 24 h plus 1) or quartiles of PAC burden were examined. Older group had higher PAC burden than younger group (p for trend < 0.001), and both genders shared similar PACs distribution. In Cox model, ln PAC remained an independent risk factor for all-cause mortality (hazard ratio (HR) = 1.09 per ln PAC increase, 95% CI = 1.06‒1.12, p < 0.001). PACs were a significant risk factor in cause-specific model (HR = 1.13, 95% CI = 1.05‒1.22, p = 0.001) or sub-distribution model (HR = 1.12, 95% CI = 1.04‒1.21, p = 0.004). In ordinal PAC model, 4th quartile group had significantly higher risk of all-cause mortality than those in 1st quartile group (HR = 1.47, 95% CI = 1.13‒1.94, p = 0.005), but no difference in cardiovascular death were found in competing risk analysis. In subgroup analysis, the risk of high PAC burden was consistently higher than in low-burden group across pre-specified subgroups. In conclusion, PAC burden has a dose response effect on all-cause mortality and cardiovascular death.

Sign in / Sign up

Export Citation Format

Share Document